Cardiology

Disorders of the Cardiovascular System PART 6
Section 1 Introduction to Cardiovascular .U -

Disorders
,
.
■ CARDIAC SYMPTOMS
231 Approach to the Patient
with Possible Cardiovascular T
, /
Disease , ,
.I ,
Joseph Loscalzo ’ ,
(Chap. 11),
.T
■ THE MAGNITUDE OF THE PROBLEM , (Chap. 37) -
C (Chap. 33). O ,
- ,
(Chap. 233). A - (Chap. 252). C ,
- — (Chap. 39), ,
U S , , (Chap. 18)—
.
, , .N , A , , , -
, ,
35% , 1 . .T , -
A - . I , , , (Chap. 33). S ,
, 80
, ~35% .T (Chap. 11). E , -
(Chap. 395), 2 (Chap. 396), ,
(Chap. 401), -
(Chap. 37). S
,
- . (Chap. 18). W
F ,
.I , (Chap. 234),
(43%)
(37%) (Chap. 391). I , (Chap. 235), , ,
(Chap. 236).
, . M
I , , 2 , .T , / -
.C , , ,
(CAD) ,
.E - .I , ,
- .
. M
■ NATURAL HISTORY
C , , ,
(ECG) .I
(Chap. 269), - CAD -
(Chap. 254) QT ,
(Chap. 247) - , ,
.H , C- , . S -
CAD — ,
. F , , —
-
.H , .
■ DIAGNOSIS
.S ,
A N Y H A (NYHA),
-
.T -
:
, ,
. 1. The underlying etiology. I , ,
P - , ?
, , - 2. The anatomic abnormalities. W ?A
, , ?W ?A
1650 TABLE 231-1 New York Heart Association Functional Classification ■ ASSESSMENT OF FUNCTIONAL IMPAIRMENT
Class I Class III W
No limitation o physical Marked limitation o physical
,
activity activity
No symptoms with ordinary Less than ordinary activity causes .T ,
PART 6
exertion symptoms . T
Class II Asymptomatic at rest
Slight limitation o physical activity Class IV
.I ,
Ordinary activity causes symptoms Inability to carry out any physical
.T -
Disorders of the Cardiovascular System
activity without discom ort

-
Symptoms at rest
-
Source: Data rom The Criteria Committee o the New York Heart Association. .T
’ .F ,
/ ?I ?H , ,
?
3. The physiologic disturbances. I ? I (Chap. 252) -
? .S ,
4. Functional disability. H
?T NYHA (Chap. 267)
(Table 231-1). .I ,
,
O , , 6
.I 1 .
,
.H , - ■ ELECTROCARDIOGRAM
(See also Chap. 235) A ECG
,
, , , , ,
, ,
- .T
, , , - ,
, . F , , , ,
. I ,
. .
T -
(Chap. 234). ■ ASSESSMENT OF THE PATIENT WITH A HEART
I , MURMUR
.T (Fig. 231-1) T
: (1) ECG (Chap. 235), :
(2) ( , - , , , , , , ,
, , , ,
, )
(Chap. 236), (3) ( . ., ,
C- ) ( . ., EVALUATION OF HEART MURMUR
[BNP] [Chap. 252]), (4) PRESENCE OF CARDIAC MURMUR
( . ., [Chap. 237]),
(5) ( . ., -
Systolic Murmur Diastolic or
[Chap. 254], M ’ [Chap. 406], Continuous Murmur
QT [Chap. 241]).
T . Grade I + II Grade III or >,
and midsystolic holosystolic,
or late systolic
■ FAMILY HISTORY
I -
, Asymptomatic and Other signs or
.F no associated findings symptoms of
. M - , cardiac disease
(Chap. 254), M ’ Echocardiography
(Chap. 406), QT
(Chap. 247). P , Normal ECG and Abnormal ECG
2 , ( chest X-ray or chest X-ray
CAD) .A
,
No further Cardiac consult
, . workup if appropriate
F
FIGURE 231-1 Approach to the evaluation o a heart murmur. ECG,
, electrocardiogram. (Reproduced with permission rom Primary Cardiology, 2nd ed,
. E Braunwald, L Goldman [eds]. Philadelphia, Saunders, 2003.)
, , .I - 1651
Chap. 234. , ’
T .
( I–II/VI). W 2. I
CHAPTER 232 Basic Biology of the Cardiovascular System

without
, (Chap. 267),
.B , - D
(Chap. 236) .
( ≥III/VI), , 3. A
. ,
6 12 , .
■ PITFALLS IN CARDIOVASCULAR MEDICINE E
I
, ,
.E : (Chap. 256).
1. F noncardiologist - 4. I CAD (Chap. 267),
.F , ( -
, , / , , -
, ). M
U S E E
R ’ .A - .T /
-
. .I ,
2. F cardiologist - CAD
.F ,
( . .,
, L CAD ).
.A
-
.F ,
3. O
,
.
,
.
232 Basic Biology of the
Cardiovascular System
C (Chap. 237) Joseph Loscalzo, Peter Libby, Calum A. MacRae
-
CAD.
A -
, supplement, DEVELOPMENTAL BIOLOGY OF THE
supplant, - CARDIOVASCULAR SYSTEM
.A T (Fig. 232-1),
, ,
. A .
E -
,
’ :
- .
. T ,
D , .C
, , ,
, .T , .
’ T ( . ., I -1) -
. ( . ., ),
■ DISEASE PREVENTION AND MANAGEMENT , -
T , CAD, .D
.
P , - .
, , , A ,
, , ,
, , (Chap. 396). ,
A .C
, .E
.S , -
: , “ ,”
, .S -
1. I , , ,
not ,
1652 Early heart-forming Neural folds Pericardial Foregut Forming heart -
regions coelom .O ,
( . ., )
.
T ,
PART 6
-
, -
. T
- -
A B ( ) ,
(SA) (AV)
First heart field Second heart field , - ( )
, H ,
, P .
P
SA ,
RA
LA AV -
AV
. S -
RV
AV
LV LV ,
RV
C D E
.E
.D
,
-
(W -P -W -
) (Chap. 241).
■ ORIGIN OF VASCULAR CELLS

F A , -
-
FIGURE 232-1 A. Schematic depiction o a transverse section through an early embryo depicts the bilateral regions . S - -
where early heart tubes orm. B. The bilateral heart tubes subsequently migrate to the midline and use to orm the -
linear heart tube. C. At the early cardiac crescent stage o embryonic development, cardiac precursors include a , - -
primary heart eld ated to orm the linear heart tube and a second heart eld ated to add myocardium to the infow -
and outfow poles o the heart. D. Second heart eld cells populate the pharyngeal region be ore subsequently
migrating to the maturing heart. E. Large portions o the right ventricle and outfow tract and some cells within the
atria derive rom the second heart eld. F. The aortic arch arteries orm as symmetric sets o vessels that then . B –
remodel under the infuence o the neural crest to orm the asymmetric mature vasculature. LA, le t atrium; LV, le t
ventricle; RA, right atrium; RV, right ventricle. . I
,
- -
.M - (Chaps. 92 and 473).
.
T THE BLOOD VESSEL
.M ■ VASCULAR ULTRASTRUCTURE
B
.T - .T —
, , —
.B , - , - -
, pericytes (Fig. 232-2A). A
(Fig. 232-2B–E). T intima -
.N A .T ,
, tunica media, - , ,
- (F . 232-2B). T
.T , adventitia, -
, , .L
. , vasa vasorum, .
C A
.E - (F . 232-2C). M - -
, , (F . 232-2D)
. .L
P - - ,
A. Capillary B. Vein C. Small muscular artery II), 1653
Pericyte NO.
N -
-

,
Vascular -
smooth-muscle cell
Endothelial cell ,
. T
D. Large muscular artery E. Large elastic artery
, -
Internal elastic
lamina
, -
-
External elastic . E
lamina -
. C -
Adventitia -
.T
- -
FIGURE 232-2 Schematics o the structures o various types o blood vessels. A. Capillaries consist o an , -
endothelial tube in contact with a discontinuous population o pericytes. B. Veins typically have thin medias and
thicker adventitias. C. A small muscular artery eatures a prominent tunica media. D. Larger muscular arteries have
a prominent media with smooth-muscle cells embedded in a complex extracellular matrix. E. Larger elastic arteries - .
have cylindrical layers o elastic tissue alternating with concentric rings o smooth-muscle cells. T
-
- (F . 232-2E). L .W -
, ,
. II, ,
,
■ VASCULAR CELL BIOLOGY 1 (PAI-1). T , ,
.I -
Endothelial Cell T
, - ,
.T .
, , E -
, , , . F ,
“ .” - ,
T
.E , - ,
, - , - .
(NO), (H2O2) - D -
(Table 232-1). I - .
NO -
.M - Vascular Smooth-Muscle Cell C
- -
(Fig. 232-3). E , -
.E ( ). V
, (O2–), . S -
- ( . .,
,
- ,
TABLE 232-1 Endothelial Functions in Health and Disease ,
HOMEOSTATIC PROPERTIES DYSFUNCTIONAL PROPERTIES . I
Optimize balance between Impaired dilation, vasoconstriction , -
vasodilation and vasoconstriction - -
Antithrombotic, pro ibrinolytic Prothrombotic, anti ibrinolytic - .
Anti-in lammatory Proin lammatory S -
Antiproli erative Proproli erative . E
Antioxidant Prooxidant ,
.I
Permselectivity Impaired barrier unction
, ,
1654 -
(Fig. 232-4). I - ,
- L-
.L ,
calcium sparks,
PART 6
( ).
O , -
.
2+
B [C ]
- C
4,5-
(DAG) 1,4,5- (IP3). T
C
2+
[C ]. I , IP3
(SR)
.
V -
,
.C
, -
ATP .M -
ATP
.O /
Control of Vascular Smooth-Muscle Cell Tone T -
- .A
-
.R -
: sympathetic,
; parasympathetic,
; nonadrenergic/noncholinergic,
— , NO,
, P, -
, - ,
- , (ATP).
E
2+
- C
, .N α
, α β ;
, α1
α2 ,
.M β2- -
- β
AMP– . A
- .N
FIGURE 232-3 Assessment o endothelial unction in vivo using blood pressure
NO, GMP– -
cu occlusion and release. Upon defation o the cu , an ultrasound probe – , -
monitors changes in diameter (A) and blood fow (B) o the brachial artery (C). . For the detailed molecular
(Reproduced with permission o J. Vita, MD.) physiology of the autonomic nervous system, see Chap. 432.
T -
. A (F . 232-2 232-3) ( ,
, , , .) ( ,
. , ). I
L , - ,
, .F - - .
, , -
■ VASCULAR REGENERATION
. G
Vascular Smooth-Muscle Cell Contraction V .G ,
- (VEGF)
Beta- 1655
NE, ET-1, Ang II NO ANP Agonist

VDCC K+ Ch Na-K ATPase
PIP2 PLC G pGC G AC
sGC GTP ATP
SR
RhoA
DAG cGMP cAMP
PKG PKA
IP3R Plb
RyrR ATPase
IP3
PKC Calcium
Rho
Kinase
MLCK
Caldesmon
Calponin
MLCP
FIGURE 232-4 Regulation o vascular smooth-muscle cell calcium concentration and actomyosin ATPase-dependent contraction. AC, adenylyl cyclase; Ang II,
angiotensin II; ANP, atrial natriuretic peptide; DAG, diacylglycerol; ET-1, endothelin-1; G, G protein; IP3, inositol 1,4,5-trisphosphate; MLCK, myosin light chain kinase;
MLCP, myosin light chain phosphatase; NE, norepinephrine; NO, nitric oxide; pGC, particular guanylyl cyclase; PIP2, phosphatidylinositol 4,5-bisphosphate; PKA, protein
kinase A; PKC, protein kinase C; PKG, protein kinase G; PLC, phospholipase C; sGC, soluble guanylyl cyclase; SR, sarcoplasmic reticulum; VDCC, voltage-dependent
calcium channel. (Modifed rom B Berk, in Vascular Medicine, 3rd ed. Philadelphia, Saunders, Elsevier, 2006, p. 23; with permission.)
(FGF), .T ,
, angiogenesis. , A ; 10 (100 Å)
G , , .T ,
, - , Z I A ;
.T ~5 (50 Å) 1.0 μ .T ,
, , ( )A , ( )I
- .O - -
.T , ,
, A ; ( ) .
,
(Chaps. 92 and 473).
■ THE CONTRACTILE PROCESS
T
CELLULAR BASIS OF CARDIAC
CONTRACTION .W ,
A .I , A
■ CARDIAC ULTRASTRUCTURE , I
M , Z .
60–140 μ 17–25 μ (Fig. 232-5A). E T myosin , -
500,000 D ; -
.T 150 (1500 Å) ( ) .T
, -
, , ATP .I , ~300 -
, SR. , -
T sarcomere, , , ,
Z ,
.T Z (Fig. 232-5B).
Actin 47,000 D . T -
1.6 2.2 μ . A
(1.5 μ ), A , , .A
, I , .T — C, I, T— -
, , (Fig. 232-6). I ,
1656
PART 6
Myofiber
A Myocyte 10 µm
Ca2+
enters
Na + Ca2+
Exchange T tubule
Pump
Ca2+
Myofibril “trigger”
Ca2+
te
Myocy
leaves
Free
Ca2+ SR
Myofibril
Mitochondrion Contract Relax
B Systole
Myofibril
C Diastole
Actin
Head
Titin
Myosin
M
43 nm
Z
D
FIGURE 232-5 A shows the branching myocytes making up the cardiac myo bers. B illustrates the critical role played by the changing [Ca2+] in the myocardial cytosol.
Ca2+ ions are schematically shown as entering through the calcium channel that opens in response to the wave o depolarization that travels along the sarcolemma.
These Ca2+ ions “trigger” the release o more calcium rom the sarcoplasmic reticulum (SR) and thereby initiate a contraction-relaxation cycle. Eventually the small
quantity o Ca2+ that has entered the cell leaves predominantly through an Na +/Ca2+ exchanger, with a lesser role or the sarcolemmal Ca2+ pump. The varying actin-
myosin overlap is shown or (B) systole, when [Ca2+] is maximal, and (C) diastole, when [Ca 2+] is minimal. D. The myosin heads, attached to the thick laments,
interact with the thin actin laments. (From LH Opie: Heart Physiology: From Cell to Circulation, 4th ed. Philadelphia, Lippincott, Williams & Wilkins, 2004. Reprinted with
permission. Copyright LH Opie, 2004.)
, ATP (F . 232-6). R
2+
C .C ATP , cross-bridge cycling,
ATP (F . 232-6). T , /
ATP - - .T ATP -
, . - .I ATP (F . 232-6),
I , . Titin (F . C 2+
2+
232-5D) , , , ; [C ] ,
Z ; . - -
D , (Fig. 232-7).
, - I [C 2+]
- .M
.M ( ), β- -
2+
, [C ], -
. .I
2+
D ,C - , β
C, , G- - ,
- ,
1657
ADP
ATP
Pi
1. ATP hydrolysis

Relaxed Relaxed, energized
4. Dissociation of Actin Actin 2. Formation of

actin and myosin active complex
ATP Pi
ADP
ADP
3. Product
dissociation
Rigor complex Active complex
FIGURE 232-6 Four steps in cardiac muscle contraction and relaxation. In relaxed muscle (upper le t), ATP bound to the myosin cross-bridge dissociates the thick and
thin laments. Step 1: Hydrolysis o myosin-bound ATP by the ATPase site on the myosin head trans ers the chemical energy o the nucleotide to the activated cross-
bridge (upper right). When cytosolic Ca2+ concentration is low, as in relaxed muscle, the reaction cannot proceed because tropomyosin and the troponin complex on the
thin lament do not allow the active sites on actin to interact with the cross-bridges. There ore, even though the cross-bridges are energized, they cannot interact with
actin. Step 2: When Ca2+ binding to troponin C has exposed active sites on the thin lament, actin interacts with the myosin cross-bridges to orm an active complex
(lower right) in which the energy derived rom ATP is retained in the actin-bound cross-bridge, whose orientation has not yet shi ted. Step 3: The muscle contracts
when ADP dissociates rom the cross-bridge. This step leads to the ormation o the low-energy rigor complex (lower le t) in which the chemical energy derived rom
ATP hydrolysis has been expended to per orm mechanical work (the “rowing” motion o the cross-bridge). Step 4: The muscle returns to its resting state, and the cycle
ends when a new molecule o ATP binds to the rigor complex and dissociates the cross-bridge rom the thin lament. This cycle continues until calcium is dissociated
rom troponin C in the thin lament, which causes the contractile proteins to return to the resting state with the cross-bridge in the energized state. ADP, adenosine
diphosphate; ATP, adenosine triphosphate; ATPase, adenosine triphosphatase. (From AM Katz: Heart ailure: Cardiac unction and dys unction, in Atlas o Heart Diseases,
3rd ed, WS Colucci [ed]. Philadelphia, Current Medicine, 2002. Reprinted with permission.)
2+
AMP ATP (F . 232-7). T C SR
C AMP A (PKA), - C (F . 232-7), ’ -
2+
C , C 2+ , .D ,
. SR C 2+ ATP (SERCA2A) C 2+
T SR (Fig. 232-8), - SR
2+
, .T , T - , calsequestrin. T C ATP
, SR, , ( )- [C 2+]
.
2+
Z , . ., . T C N + (F . 232-8), -
2+
[C
]. A -
■ CARDIAC ACTIVATION AMP– PKA
I , ; . ., - SR phospholamban, SERCA2A ,
, - SR C 2+ , , SR
–80 –100
V (Chap. 238). T , C 2+ , .
N +, N +- T , , ,
K+- ATP N +
, SR,
.I , [K+] C 2+
,
[N +] ; , [N +] .G ,
[K+] .A , , [C 2+
] , .
[C 2+].
T (see Fig. 238-1B). D CONTROL OF CARDIAC PERFORMANCE
( 2), - AND OUTPUT
L- C 2+ (F . 232-8). D - T , ,
, , :
T .T (1) , . ., ;
2+
C T - (2) , . .,
. H , C 2+ , ; (3) , . .,
Ca2+-induced Ca 2+ release, C 2+ . Table 232-2
SR, . , , .
2+
C SR C 2+ ,
(R R2). S , ■ THE ROLE OF MUSCLE LENGTH (PRELOAD)
calstabin 2, R R2 SR C 2+ .I P .C -
(~2.2 μ )
2+ 2+
SR C , , C , -
. .T
1658
Ca2+
β - Adrenergic agonist
PART 6
β
γ Adenyl
αs P
cyclase SL
Ca2+
+
β GTP
Receptor
+
cAMP SR
Via protein kinase A +
Metabolic
• glycolysis Ca2+
• lipolysis
• citrate cycle ADP + Pi
+
+
ATP Troponin C cAMP
Myosin + 2 via Tnl
ATPase
ADP + Pi +
cAMP
1 via PL
Increased
1. rate of contraction +
β 2. peak force 3
3. rate of relaxation Control
Force
Time
Pattern of contraction
FIGURE 232-7 Signal systems involved in positive inotropic and lusitropic (enhanced relaxation) e ects o a-adrenergic stimulation. When the β-adrenergic agonist
interacts with the β receptor, a series o G protein–mediated changes leads to activation o adenylyl cyclase and the ormation o cyclic adenosine monophosphate
(cAMP). The latter acts via protein kinase A to stimulate metabolism (le t) and phosphorylate the Ca 2+ channel protein (right). The result is an enhanced opening
probability o the Ca2+ channel, thereby increasing the inward movement o Ca2+ ions through the sarcolemma (SL) o the T tubule. These Ca 2+ ions release more
calcium rom the sarcoplasmic reticulum (SR) to increase cytosolic Ca2+ and activate troponin C. Ca 2+ ions also increase the rate o breakdown o adenosine
triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate (Pi). Enhanced myosin ATPase activity explains the increased rate o contraction, with
increased activation o troponin C explaining increased peak orce development. An increased rate o relaxation results rom the ability o cAMP to activate as well the
protein phospholamban, situated on the membrane o the SR, that controls the rate o uptake o calcium into the SR. The latter e ect explains enhanced relaxation
(lusitropic e ect). P, phosphorylation; PL, phospholamban; TnI, troponin I. (Modifed rom LH Opie: Heart Physiology: From Cell to Circulation, 4th ed. Philadelphia,
Lippincott, Williams & Wilkins, 2004. Reprinted with permission. Copyright LH Opie, 2004.)
■ VENTRICULAR AFTERLOAD
S ’ , , I , ,
-
; , . .,
- . .I ,
.A
■ CARDIAC PERFORMANCE -
V - “ ” .L ’
- .I - , -
- ( - .T ,
) ( ), ,
— . ., — - . C ,
- ,
.T - .A -
( ) ,
,
.A .
( V
- , - (Fig. 232-10). A ,
), ,
(Fig. 232-9). .T
1659
Na + Na+/Ca2+ Plasma membrane
pump exchanger Ca2+ pump . U , ,
B1 B2 ,

Extracellular Plasma
T tubule membrane , , -
. U ,
Plasma Intracellular -
(cytosol)
membrane Cisterna
Ca2+ , -
channel .
Sarcoplasmic reticulum
Ca2+-
A release channel ■ EXERCISE
('foot' protein) T
Sarcotubular network
A1 G : , , (F .
Calsequestrin 232-9). H ,
Sarcoplasmic reticulum , -
Ca2+ pump Mitochondria
C D (T 232-2). S -
H
,
, -
,
(F . 232-9,
E F 1 2),
,
-
(F . 232-9, A B). V
,
Z-line Troponin C Thin Thick Contractile
-
filament filament proteins
.T -
FIGURE 232-8 The Ca2+ uxes and key structures involved in cardiac excitation-contraction coupling.
The arrows denote the direction o Ca2+ fuxes. The thickness o each arrow indicates the magnitude
o the calcium fux. Two Ca2+ cycles regulate excitation-contraction coupling and relaxation. The larger
cycle is entirely intracellular and involves Ca2+ fuxes into and out o the sarcoplasmic reticulum, as well .
as Ca2+ binding to and release rom troponin C. The smaller extracellular Ca 2+ cycle occurs when this
cation moves into and out o the cell. The action potential opens plasma membrane Ca2+ channels to ASSESSMENT OF CARDIAC
allow passive entry o Ca2+ into the cell rom the extracellular fuid (arrow A). Only a small portion o FUNCTION
the Ca2+ that enters the cell directly activates the contractile proteins (arrow A1). The extracellular cycle S
is completed when Ca2+ is actively transported back out to the extracellular fuid by way o two plasma
membrane fuxes mediated by the sodium-calcium exchanger (arrow B1) and the plasma membrane
. C
calcium pump (arrow B2). In the intracellular Ca2+ cycle, passive Ca2+ release occurs through channels in
the cisternae (arrow C) and initiates contraction; active Ca2+ uptake by the Ca2+ pump o the sarcotubular ,
network (arrow D) relaxes the heart. Di usion o Ca2+ within the sarcoplasmic reticulum (arrow G) , .A
returns this activator cation to the cisternae, where it is stored in a complex with calsequestrin and , . .,
other calcium-binding proteins. Ca2+ released rom the sarcoplasmic reticulum initiates systole when - (
it binds to troponin C (arrow E). Lowering o cytosolic [Ca 2+] by the sarcoplasmic reticulum (SR) causes
this ion to dissociate rom troponin (arrow F) and relaxes the heart. Ca 2+ also may move between
= 67 ± 8%),
mitochondria and cytoplasm (H). (Adapted rom AM Katz: Physiology o the Heart, 4th ed. Philadelphia,
Lippincott, Williams & Wilkins, 2005, with permission.) .A , -
- ( = 75 ± 20
L/ 2) - ( = 25 ±
2
.A 7 L/ ) .
, , , N , , -
, . (MRI)
W , (Chap. 236)
(L ’ ) . I . T - -
, , ,
.T ( )
, .T -
, ,
O2 .T - .
; , S
(Chap. 252). , ,
U , - . T ,
, ,
(F . 232-10). I , .
.F T - -
,
1660 TABLE 232-2 Determinants of Stroke Volume
I. Ventricular Preload
Venous
Preload
A. Blood volume return
B. Distribution o blood volume
PART 6
1. Body position Contractility Stroke volume

Cardiac
2. Intrathoracic pressure output
3. Intrapericardial pressure Afterload Heart rate Arterial
4. Venous tone pressure
Peripheral
5. Pumping action o skeletal muscles resistance
C. Atrial contraction
II. Ventricular A terload
Medullary Carotid and
A. Systemic vascular resistance vasomotor aortic
B. Elasticity o arterial tree and cardiac baroreceptors
centers
C. Arterial blood volume
D. Ventricular wall tension
1. Ventricular radius Higher
2. Ventricular wall thickness nervous
centers
III. Myocardial Contractilitya
A. Intramyocardial [Ca2+] ↑↓ FIGURE 232-10 Interactions in the intact circulation o preload, contractility,
and a terload in producing stroke volume. Stroke volume combined with heart
B. Cardiac adrenergic nerve activity ↑↓ b rate determines cardiac output, which, when combined with peripheral vascular
C. Circulating catecholamines ↑↓ b resistance, determines arterial pressure or tissue per usion. The characteristics
D. Cardiac rate ↑↓b o the arterial system also contribute to a terload, an increase that reduces
E. Exogenous inotropic agents ↑ stroke volume. The interaction o these components with carotid and aortic
arch baroreceptors provides a eedback mechanism to higher medullary and
F. Myocardial ischemia ↓
vasomotor cardiac centers and to higher levels in the central nervous system
G. Myocardial cell death (necrosis, apoptosis, autophagy) ↓ to e ect a modulating infuence on heart rate, peripheral vascular resistance,
H. Alterations o sarcomeric and cytoskeletal proteins ↓ venous return, and contractility. (From MR Starling: Physiology o myocardial
1. Genetic contraction, in Atlas o Heart Failure: Cardiac Function and Dys unction, 3rd ed, WS
2. Hemodynamic overload Colucci and E Braunwald [eds]. Philadelphia: Current Medicine, 2002, pp 19–35.)
I. Myocardial ibrosis ↓
J. Chronic overexpression o neurohormones ↓ (Fig. 232-11). A
K. Ventricular remodeling ↓ , -
L. Chronic and/or excessive myocardial hypertrophy ↓ - ; , -
a
Arrows indicate directional e ects o determinants o contractility. Contractility b ( - ) .M -
rises initially but later becomes depressed. - -
,
,
Maximal activity 2 C Normal-exercise , .
1 ■ DIASTOLIC FUNCTION
Normal-rest
Ventricular performance
V
2+
, C SR;
,
Contractile state of myocardium 2+
ATP C SR (
). T
Walking 3
.V
B
3′ Exercise , ,
D Heart failure ( . ., ) (Fig. 232-12).
Rest
A
V
E D .N ,
Fatal myocardial
4 ;
depression
,
, .W ,
Dyspnea Pulmonary edema “ - ,”
Ventricular EDV .
Stretching of myocardium
■ CARDIAC METABOLISM
FIGURE 232-9 The interrelations among in uences on ventricular end-diastolic
volume (EDV) through stretching o the myocardium and the contractile state
T (ATP)
o the myocardium. Levels o ventricular EDV associated with lling pressures , -
that result in dyspnea and pulmonary edema are shown on the abscissa. Levels .T , -
o ventricular per ormance required when the subject is at rest, while walking, ,
and during maximal activity are designated on the ordinate. The broken lines ’ , O2 ~15%
are the descending limbs o the ventricular-per ormance curves, which are rarely .
seen during li e but show the level o ventricular per ormance i end-diastolic
volume could be elevated to very high levels. For urther explanation, see text.
M ATP -
(Modifed rom WS Colucci and E Braunwald: Pathophysiology o heart ailure, in (FFA ). FFA
Braunwald’s Heart Disease, 7th ed, DP Zipes et al [eds]. Philadelphia: Elsevier, FFA , ,
2005, pp 509–538.) ’
Normal I , , FFA - 1661
contractility ,
Contractility
ESPVR ’ -C A (~70%).
I ,

Contractility , FFA
afterload
. I , ,
LV pressure
LV pressure
,
preload ,
,
2 2 ( ). B , β- ,
,
1 1
FFA .S -
3 3 ,
,
( ),
. A
LV volume LV volume
ATP .
FIGURE 232-11 The responses o the le t ventricle to increased a terload, increased preload, H FFA ,
and increased and reduced contractility are shown in the pressure-volume plane. Left. E ects
o increases in preload and a terload on the pressure-volume loop. Because there has been no
change in contractility, the end-systolic pressure-volume relationship (ESPVR) is unchanged. With an ,
increase in a terload, stroke volume alls (1 → 2); with an increase in preload, stroke volume rises ATP ; ATP
(1 → 3). Right. With increased myocardial contractility and constant le t ventricular end-diastolic .I , FFA -
volume, the ESPVR moves to the le t o the normal line (lower end-systolic volume at any end-systolic
pressure) and stroke volume rises (1 → 3). With reduced myocardial contractility, the ESPVR moves .
to the right; end-systolic volume is increased, and stroke volume alls (1 → 2).
M
(CP), ATP,
’ ( ). T .I , CP
A .C , , ,
.G - ,
, , , 2+
[C ] .W -
- , -C A, ,
. FFA -C A - ,
C A .A -C A (K ) ATP
ATP ; ATP , .
.I -
(ADP), ATP , ■ REGENERATING CARDIAC TISSUE
ATP . U ,
. E
Abnormal relaxation Pericardial restraint

.C -
-
.T
(Chap. 473).
Acknowledgment
Left ventricular pressure
The authors wish to thank Jonathan Epstein for his contribution to the prior
version of this chapter.
■ FURTHER READING
Bautch VL, Caron KM: B .C
Increased chamber Chamber
stiffness dilation
S H P B 7(3): 008268, 2015.
Dejana E :T .N
C 8:14361, 2017.
Green DJ : V :R
.P R 97:495, 2017.
MacLeod KT: R
. F1000R 5(F1000 F R ):1770, 2016.
Mann D, ( ): Braunwald’s Heart Disease: A Textbook of Cardiovas-
cular Medicine, 10 .P ,E , 2015.
Page E ( ): Handbook of Physiology: A Critical Comprehensive
Left ventricular volume Presentation of Physiological Knowledge and Concepts. Section 2: The Car-
diovascular System, Volume I: The Heart. N Y , O U
FIGURE 232-12 Mechanisms that cause diastolic dys unction re ected in P , 2002.
the pressure-volume relation. The bottom hal o the pressure-volume loop is
depicted. Solid lines represent normal subjects; broken lines represent patients Spinale FG: A —B
with diastolic dys unction. (From JD Carroll et al: The di erential e ects o positive .C P 5:1911, 2015.
inotropic and vasodilator therapy on diastolic properties in patients with congestive Srivastava D: M :F -
cardiomyopathy. Circulation 74:815, 1986; with permission.) . C 126:1037, 2006.
1662 , . CHD ,
35 65% CVD. T ,
233 Epidemiology of
Cardiovascular Disease D
CHD
,
2:1 3:1.
50.
R 35% ’ .
PART 6
Thomas A. Gaziano, J. Michael Gaziano I age of delayed degenerative diseases, CVD

, CVD 40%
.H , - CVD ,
C (CVD) ( ,
), ,
.B 1900,
, CVD <10% . , . CHD,
I 2015, CVD ~17.9 (32%), , CVD.
34% - A 15% ’
32% - - .
.
THE EPIDEMIOLOGIC TRANSITION I ,
T CVD - .T -
age of inactivity and
.K , obesity. R 2 , , -
, , - , .
I , - CVD
, , .T .
: , ,
- , .A ■ PATTERNS IN THE EPIDEMIOLOGIC TRANSITION
, , - U -
(Table 233-1). .H -
T age of pestilence and famine , CVD 50–60% 60 ,
, CVD 15% 20
.T , , , , - - .H ,
30 . CVD, , U S
<10% , .T 1900,
. A - .I
10% ’ . B 1930 ,
. .T -
P age of
receding pandemics , . L
, CVD
.I - , ~390 100,000. B 1930 1965,
, CVD 10 35% - .I -
.R , , 50 100,000 ,
(CHD), CVD. A CVD
40% ’ . , , -
T age of degenerative and man-made diseases - . T
— CVD— 1965 2000. N , ,
. C ,
TABLE 233-1 Five Stages of the Epidemiologic Transition

DEATHS RELATED
STAGE DESCRIPTION TO CVD, % PREDOMINANT CVD TYPE
Pestilence and Predominance o malnutrition and in ectious diseases as causes <10 Rheumatic heart disease,
amine o death; high rates o in ant and child mortality; low mean li e cardiomyopathies caused by in ection and
expectancy malnutrition
Receding Improvements in nutrition and public health lead to decrease in 10–35 Rheumatic valvular disease, hypertension,
pandemics rates o deaths related to malnutrition and in ection; precipitous CHD, and stroke (predominantly
decline in in ant and child mortality rates hemorrhagic)
Degenerative Increased at and caloric intake and decrease in physical activity 35–65 CHD and stroke (ischemic and
and man-made lead to emergence o hypertension and atherosclerosis; with increase hemorrhagic)
diseases in li e expectancy, mortality rom chronic, noncommunicable diseases
exceeds mortality rom malnutrition and in ectious disease
Delayed CVD and cancer are the major causes o morbidity and mortality; 40–50 CHD, stroke, and congestive heart ailure
degenerative better treatment and prevention e orts help avoid deaths among
diseases those with disease and delay primary events; age-adjusted CVD
morality declines; CVD a ecting older and older individuals
Inactivity and Overweight and obesity increase at alarming rate; diabetes and 38 CHD, stroke, and congestive heart ailure,
obesity hypertension increase; decline in smoking rates levels o ; a peripheral vascular disease
minority o the population meets physical activity recommendations
Abbreviations: CHD, coronary heart disease; CVD, cardiovascular disease.
Source: Data rom AR Omran: The epidemiologic transition: A theory o the epidemiology o population change. Milbank Mem Fund Q 49:509, 1971; and SJ Olshansky,
AB Ault: The ourth stage o the epidemiologic transition: The age o delayed degenerative diseases. Milbank Q 64:355, 1986.
- H , CVD , 1663
CVD . ,
C , U S (Fig. 233-2). T E A P
.T - CVD 3% .
CHAPTER 233 Epidemiology of Cardiovascular Disease

1970 1980 1990 2%. H - CVD C , J ,
, CVD 3–5% CHD .V
.C . C , ,
O , , .T M E N A
, ,
. CVD
O , HIC . I ,L A
. ,
M - (HIC )— .
15% — - T E E C A , ,
U S . , CVD
CHD CVD , (~66%) .I , CHD
- .H , -
. W N A , A , .S A — ,I ,
E HIC ’ —
CVD , E .T
.M , E W , CHD CVD. H ,
( . ., A , B , G )
( . ., F ,S , .A S A , -
D , N ). C P ,S , J CVD -S A ,
U S .
,
CHD 200 100,000, .T M LMIC . F ,
W
E / .
CVD, ( . ., S , .
F ,I , S ) M T , -
( . ., F ,S , I ). J HIC , CVD. I ,
.A , - -
, CHD .
J .H ,J
, . ■ GLOBAL TRENDS IN CARDIOVASCULAR DISEASE
P - - (LMIC ; CVD 32% ,
<$12,736) , , , . I 2015, CHD 16.7%
, , (10%)
.A (YLL ) - - (DALY ) (7%). T
, CVD (11.9% ),
LMIC . W 85% ’ - YLL DALY . T ,
, LMIC CHD -
CVD (Fig. 233-1). I LMIC , / .T LMIC . T
CHD, , , . DALY
LMIC HIC .
W 81% ’ -
Global deaths by cause, 2015 , LMIC
CVD . M
14 (14.2) CVD
INJ
LMIC 2015, 3.7
8.5%
HIC . G ,
CMNN
20.2% Low- and /
middle- ; 1990 2015, -
income CVD 42%,
countries High- -
CVD
32.1% income 27.3% . A -
countries , ,
- -
- -
(Fig. 233-3). P
-
ONC
39.2% -
- . A
FIGURE 233-1 Global deaths by cause, 2015. CMNN, communicable, maternal, neonatal, and nutritional disorders;
- ,
CVD, cardiovascular diseases; INJ, injuries; ONC, other noncommunicable diseases. (Based on data rom Global CVD . H -
Burden o Disease Study 2015. Global Burden o Disease Study 2015 [GBD 2015] Results. Seattle, United States: , -
Institute or Health Metrics and Evaluation [IHME], 2016.) ,
1664 Latin America and the Caribbean Middle East and North Africa Europe and Central Asia
29.3% 38.2% 46.2%
(636 million) (471 million) (409 million)
PART 6
High-income
33.9%
(984 million)
South Asia
28.1%
(1698 million)
Sub-Saharan Africa
East Asia and Pacific
13.4% 36.9%
(937 million) (2033 million)
FIGURE 233-2 Cardiovascular disease deaths as a percentage o total deaths and total population in seven economic regions o the world defned by the World
Bank. (Based on data rom Global Burden o Disease Study 2015. Global Burden o Disease Study 2015 [GBD 2015] Results. Seattle, United States: Institute or Health
Metrics and Evaluation [IHME], 2016.)
- . C
CVD 25 CVD .F ,
(Fig. 233-4). E E C A 0.7%
A HIC 2014, 1.4% S A .
LMIC , HIC CVD .E
’ .T CVD CVD , , I
HIC , S A , 35 64
.H , CVD 30 , -
CVD, - .I
. C , 9 CVD
S LMIC 2030— 2.4 2002—
, 35 64 .
500
450
400
CVD deaths per 100,000
350
300
250
200
150
World bank high income
100 World bank low income
World bank lower middle income
50 World bank upper middle income
Global
0
1990 1995 2000 2005 2010 2015
Year
FIGURE 233-3 Age-standardized cardiovascular diseases (CVD) death rate per 100,000 rom 1990 to 2015, by World Bank income. (Based on data rom Global
Burden o Disease Study 2015. Global Burden o Disease Study 2015 [GBD 2015] Results. Seattle, United States: Institute or Health Metrics and Evaluation [IHME],
2016.)
20 1665
Number of CVD deaths in millions

18
16
CHAPTER 233 Epidemiology of Cardiovascular Disease

14
12
10
8
6 World bank high income
World bank low income
4
World bank lower middle income
2 World bank upper middle income
Global
0
1990 1995 2000 2005 2010 2015
Year
FIGURE 233-4 Number o cardiovascular diseases (CVD) deaths rom 1990 to 2015, by World Bank income. (Based on data rom Global Burden o Disease Study
2015. Global Burden o Disease Study 2015 [GBD 2015] Results. Seattle, United States: Institute or Health Metrics and Evaluation [IHME], 2016.)
■ RISK FACTORS ,
T CVD - .
.E
CVD ■ METABOLIC RISK FACTORS
E
— , , — - CVD .H
— , , , —
. G B D , I , R F
S (GBD 2015). T GBD
Behavioral Risk Factors • TOBACCO O 1.3 187 1990 2015.
,
1.6 2030. T 6.4
Lipid Levels W ,
56% 18% ,
(11.5% ), ~2.4
4.3 .A
CVD- .I ,
10 2030.
,
A HIC , -
1980 2008 0.08 /L
LMIC .S
0.07 /L . I 2008, -
E A P .A
4.64 /L (179.4 / L)
LMIC
4.76 /L (184.2 / L) . L
-
A ,N A , W E (0.19–0.21 /L).
.I S A ,
C E A P
>0.08 /L .S
. S -
-
- CHD,
886,000 2015. A
.T
- ,
—
.
— . I HIC , , -
DIET T . ,
W CVD, LMIC .
,
trans ,
Hypertension E
.W , ~62% 49% CHD
- .F -
(>115 H ) ,
<20% C I , <30% J ,
>7 .R -
30% U S .C
,
HIC . I U S , 1971 2010,
<140 H , -
.B
13 11%.
1980 2008, - -
PHYSICAL INACTIVITY T
, .T
- - - .R
. I U S , - - .
- , F , I 25%,
51.6% 10 15% .O -
.P LMIC , ,
.T , ,
.I C , , - CHD
- - .T A ,
1666 , 786 -
.G , , 5.4 .L 377:568, 2011.
(0.8 H Gaziano T, Gaziano JM: G ,
; 1.0 H ). Heart Disease: A Textbook of Cardiovascular Medicine, 11 ,EB
( ). P ,E , 2018; .
PART 6
Obesity A CHD, Lozano R :G 235

CVD
20 1990 2010: A
, , , G B D S 2010. L 380:2095, 2012.
.A GBD , 1.46 Roth G :G
( [BMI] ≥25 / 2) 2008,
1990 2013. C 132:1667, 2015.
~508 (BMI ≥30 / 2). O

, ,
-
.I LMIC , -
.A .C ,1 Section 2 Diagnosis of Cardiovascular Disorders
10 ,
.W ,
Diabetes Mellitus A
36 LMIC .
, , -
234 Physical Examination of
the Cardiovascular System
BMI ,
Patrick T. O’Gara, Joseph Loscalzo
— 2 — .A
GBD ,
1980 2008. A -
346 .T I T -
D F 522 -
2030, ’ .T
.N 50% , ,
80% LMIC . T -
M E N A , 12.5% .T
.F , -
, LMIC S A - , -
S A . T .C
. F , .
S A I D ,
E . ; ,
SUMMARY . L
A CVD HIC , .O
.T
,
, ,
. .P
T . -
F , CVD -
- , .T -
, , . , - ,
S , - D
, - - .
, T
.S , - , , , -
“ ,” , ,
, .T , , , .F ,
.F , ,
, , (MR)
- ,
. . O -
I , HIC -
, .T
.T -
(JVP) (S3).
CVD .T - - A
.F ,
CVD. - .
■ FURTHER READING ■ THE GENERAL PHYSICAL EXAMINATION

Danaei G :N , , A
1980: S , , , ,
.I , - .A - 1667
?D
,
? A .B
CHAPTER 234 Physical Examination of the Cardiovascular System

, H
- , , - ?S . R
, , , , - -
. A - ;
- (W ’) - .
, .V ,
, , Chest M , ,
21, M , H -O .H /
,
.K -
- - - .A
.M , , . I
.
,
Skin C - - . T
,
. P , .T (“ ”) -
, (“ ”). O
, , , , -
, ; , .T
β- α- . , , -
D
- (AR). S
(PDA) - -
.H (MVP) .I
, , , O -W - ,
R ( ), , .
- - T
. M , , ,
(MS) .A .L
, , .
.J , Abdomen I -
, , , .
, T
- .S -
P2Y12 . V (TR). S
,
, .A
.S - , ,
.P , .T
III .P - JVP .I ,
, , .T
, -
( )
.E .B
— , C ’ ,
, .C - .T -
- ,
- .
, , ,
. Extremities T ,
, ,
Head and Neck D . C
- - ,
.A - M .I
.B ,
L -D , ,
T . T ,
.M - .
, - , P H -O , “ -
.B .A ” , M
- “ ”(
.T ) “ ”(
,
, , .A ) .T J
1668 , ,
O ’ , A
.S
C V
-
,
PART 6
. X Y
L JVP
IV I II
.L A
-
.O V
, , -
, ,
( ), A
( ). P
Severe
.AH ’ ( V
) A C Y
.M Mild X
A C V Y
. Normal
X Y
■ CARDIOVASCULAR EXAMINATION
Jugular Venous Pressure and Waveform T JVP I II III
B
-
.T
.N ,
P
ECG
(CVP) , ,
. P
A
V
.V JVP V X
( L ). A >4.5
30° . H ,
- L -
Y
(30°, 45°, 60°). T
CVP,
I II K
CVP. T C
.V
FIGURE 234-1 A. Jugular venous pulse wave tracing (top) with heart sounds
, - (bottom). The A wave represents right atrial presystolic contraction and occurs
10 .T just a ter the electrocardiographic P wave and just be ore the rst heart sound
, (I). In this example, the A wave is accentuated and larger than normal due to
, decreased right ventricular compliance, as also suggested by the right-sided S4
.I (IV). The C wave may refect the carotid pulsation in the neck and/or an early
systolic increase in right atrial pressure as the right ventricle pushes the closed
CVP , -
tricuspid valve into the right atrium. The x descent ollows the A wave just as atrial
pressure continues to all. The V wave represents atrial lling during ventricular
(1.36 H2O = 1.0 H ). systole and peaks at the second heart sound (II). The y descent corresponds to
T the all in right atrial pressure a ter tricuspid valve opening. B. Jugular venous
, .N , wave orms in mild (middle) and severe (top) tricuspid regurgitation, compared
, - with normal, with phonocardiographic representation o the corresponding heart
(Fig. 234-1). T sounds below. With increasing degrees o tricuspid regurgitation, the wave orm
becomes “ventricularized.” C. Electrocardiogram (ECG) (top), jugular venous
; wave orm (JVP) (middle), and heart sounds (bottom) in pericardial constriction.
, Note the prominent and rapid y descent, corresponding in timing to the pericardial
; knock (K). (From J Abrams: Synopsis o Cardiac Physical Diagnosis, 2nd ed. Boston,
( - Butterworth Heinemann, 2001, pp 25–35.)
).
T .T a .T a .
T x
P , (S1). a .T c ,
A a , -
; a (AV) - x .T v
.I ( )
, .T v -
a
- 1669
.I TR, v ,
(y ) .W , , .S -
TR, v c , 20 H -

“ .” T y .G –
, v , AR
, .T - (
.N , /
3 H .K ’ )
JVP - - .
, T
, - . “W -
, , ” -
(LV) .I , >140/90 H - -
<140/90 H -
. .I
V - ,
.W . M
, - -
. ,
A .H
, 24-
, >15 . A -
>3 JVP .
T 10 .
O
.P >20 H >10 H -
V - .P 3 .
T ,
>15 H . ,
A JVP , P ’ .O
.I /
, .I
>10 H ( ) , , ,
88% , , / .
>22 H .I , JVP -
Arterial Pulse T
LV .T JVP . T
, .P
, , . , -
, , , , , ,
Assessment of Blood Pressure M .I
,
.A - .A
, , , , , 10% , .
, , .I , - T A ’
- ,
- .B .T , ,
, , , .I ,
, ,
5–10 .W , . S
- .
T 80 . T
40% ’ , .A .L
, -
, .T
, . T
30 H - ,
2–3 H /.S -
K , .I ,
.V ( 0 H ) , ,
, AR , .T
“ - .” I ,
IV VK .B , ,
, .
, , .I , T
- (Fig. 234-2). A (pulsus parvus et tardus)
.B (AS). S AS
, <10 H .A , , ( )
1670 . W
S4 P2 S4 P2 T- ,
S1 A2 S1 A2 .
A
.A -
PART 6
.F /
A Dicrotic notch B Dicrotic notch -
.
T -
S4 S4
(Fig. 234-3). F ,
P2 P2
S1 A2 S1 A2 ,
, -
.A -
, , ,
C Dicrotic notch D Dicrotic notch .H , -
.A
;
S4 P2
S1 A2 .I ,
.A
.
T
, ,
E Dicrotic notch , .
FIGURE 234-2 Schematic diagrams o the confgurational changes in carotid A ( >2%
pulse and their di erential diagnoses. Heart sounds are also illustrated. )
A. Normal. S 4, ourth heart sound; S1, rst heart sound; A2, aortic component o
second heart sound; P2, pulmonic component o second heart sound. B. Aortic - .
stenosis. Anacrotic pulse with slow upstroke to a reduced peak. C. Bis eriens
pulse with two peaks in systole. This pulse is rarely appreciated in patients
with severe aortic regurgitation. D. Bis eriens pulse in hypertrophic obstructive
Inspection and Palpation of the Heart T LV
cardiomyopathy. There is a rapid upstroke to the rst peak (percussion wave)
and a slower rise to the second peak (tidal wave). E. Dicrotic pulse with peaks in - . V
systole and diastole. This wave orm may be seen in patients with sepsis or during .T
intraaortic balloon counterpulsation with infation just a ter the dicrotic notch. .A
(From K Chatterjee, W Parmley [eds]: Cardiology: An Illustrated Text/Re erence. ,
Philadelphia, Gower Medical Publishers, 1991.)
.I ,
.W AR, , ,
- (C ’ - ). .
S AR , P
.A 30°
.T LV <2
(HOCM), .A ;
, .C -
(IABP), . , ,
Pulsus paradoxus >10 H .
E LV
, .A
, , . ,
P AS .A
K (S4)
( ) K LV -
, .A (S3), -
.B , K ,
.T .A LV
.I - ,
, , . HOCM
.A S4
.
15 H .T R
. .S TR (cv ) /
Pulsus alternans, , - - ( P 2)
.I IK .T -
, .A
- LV
.P LV
.S
Posterior tibial artery pressure 1671

Anterior superior
iliac spine Posterior tibial a.
Inguinal ligament
External iliac a.
Symphysis pubis
Doppler
Deep femoral a.
Palpatation of Blood pressure
popliteal artery pulse cuff
Femoral a.
Dorsalis pedis artery pressure

Popliteal a.
Doppler
Anterior tibial a. Femoral a.
Popliteal a.
Posterior Anterior tibial a. Extensor tendon
tibial a.
Dorsalis pedis a.
Dorsalis pedis a.
A Major arteries of the lower limb B Measurement of ankle systolic pressure

FIGURE 234-3 A. Anatomy o the major arteries o the leg. B. Measurement o the ankle systolic pressure. (From NA Khan et al: JAMA 295:536, 2006.)
- .T ,
. (ASD). R
,
■ CARDIAC AUSCULTATION , -
, AS, HOCM, .W
Heart Sounds V , S2
(S1) (S2) (Fig. 234-4). T , ,
(S1) .N -
. P2 A2
, . ,
T S1 - ( ),
, S2 .T
, LV , PR . S1 A2 P2 (PS),
MS - .I , S2 .
PR . S1
MS , - Systolic Sounds A -
β- , PR , .
LV .T , , I
; ,
, -
, , , , .T
.
A .T
(S2). W , A2–P2 PS
.T - .I , -
.E -
MR .A .N ( ),
S2 , MVP
.F S 2, A2–P2 .T .T
1672 EXPIRATION INSPIRATION .N
,
A2 A2
A Normal P2 P2
.T , , ,
S1 S2 S1 S2 , ,
PART 6
A2 P2 A2 P , ,
2
B Atrial septal .T
defect S1 S2 S1 S2 1 6; 4 .
O
, , .
A2 P A2 A
C Expiratory splitting 2 P2
,
with inspiratory S1 S2 S1 S2
increase (RBBB,
-
idiopathic dilatation PA)
.
S , , ,
D Reversed splitting P2 A2 P2 A2 (Fig. 234-5). A MR
(LBBB, aortic ,
stenosis) S1 S2 S1 S2 LV
.
S MR
P2 A2 P2
A2 ,
E Close fixed AS. MR
splitting S1 S2 S1 S2 .W TR
(pulmonary
, -
hypertension)
,
FIGURE 234-4 Heart sounds. A. Normal. S1, rst heart sound; S2, second heart cv .
sound; A2, aortic component o the second heart sound; P2, pulmonic component A S1 S2 ; -
o the second heart sound. B. Atrial septal de ect with xed splitting o S2.
C. Physiologic but wide splitting o S2 with right bundle branch block (RBBB).
- . AS
PA, pulmonary artery. D. Reversed or paradoxical splitting o S2 with le t bundle . I
branch block (LBBB). E. Narrow splitting o S2 with pulmonary hypertension. (From
NO Fowler: Diagnosis o Heart Disease. New York, Springer-Verlag, 1991, p 31.)
A B
-
, . O ECG ECG
, S1.
LVP LVP AOP
Diastolic Sounds T - (OS) MS
.T A2–
OS – LAP
. T S1
OS MS HSM
EDM
. T (PK) -
OS, S1 S2 S1 A2
y
.A ECG ECG
LVP
- LVP
.I AOP
. LAP
T (S3)
.I , ,
; , , . MSM
PSM MDM
A - S3 - LV .A
- S3 S1 A2 S1 S2
.A - S3
FIGURE 234-5 A. Top. Graphic representation o the systolic pressure di erence
(green shaded area) between le t ventricle and le t atrium with phonocardiographic
.I , S3 recording o a holosystolic murmur (HSM) indicative o mitral regurgitation. ECG,
LV . electrocardiogram; LAP, le t atrial pressure; LVP, le t ventricular pressure; S1, rst
T (S4) heart sound; S2, second heart sound. Bottom. Graphic representation o the
LV . A S4 systolic pressure gradient (green shaded area) between le t ventricle and aorta
in patient with aortic stenosis. A midsystolic murmur (MSM) with a crescendo-
decrescendo con guration is recorded. AOP, aortic pressure. B. Top. Graphic
, LV representation o the diastolic pressure di erence between the aorta and le t
. A S4 ventricle (blue shaded area) in a patient with aortic regurgitation, resulting in a
. decrescendo, early diastolic murmur (EDM) beginning with A 2. Bottom. Graphic
representation o the diastolic le t atrial–le t ventricular gradient (blue areas)
Cardiac Murmurs H in a patient with mitral stenosis with a mid-diastolic murmur (MDM) and late
presystolic murmurs (PSM).
, TR , 1673
(C ’ ),
.E - cv , ,
AS parvus et .

tardus , - 3
, A2 , LV , S4. I Diastolic Murmurs I , -
(F . 234-5).
.T T , AR
LV
. T -LV .
D 2.5 / .P I , AR
2 3 - ,
AS. O .
( W AR,
), HOCM, .T -
ASD - - , .T
, .I
, , , , /
. . S2 .T
T HOCM LV - /
MR, - .A PR -
.T HOCM F .I
, - ,
, V , , / -
.I , LV ( .
LV ) , - MS - ,
LV , -
.A , HOCM , OS
V .P
.T
.T AS .I
.T
, HOCM - ,
.T PS MS.
.T “F ”
ASD -
.
A , ,
MVP. A ,
Impedance
. D ,
, - Ao
.
T -
LV
HOCM V Contractility
/ (Fig. 234-6). T -
MVP -
.
H -
-
Volume
MR,
(VSD),
TR. I MR, MR
C S2 C S2
S1 M S1 M
. T
MR
. T
FIGURE 234-6 Behavior o the click (C) and murmur (M) o mitral valve prolapse with changes in loading
LV ,
(volume, impedance) and contractility. S 1, rst heart sound; S2, second heart sound. With standing (le t
.T VSD side o gure), volume and impedance decrease, as a result o which the click and murmur move closer to
( ) S1. With squatting (right), the click and murmur move away rom S 1 due to the increases in le t ventricular
- volume and impedance (a terload). Ao, aorta; LV, le t ventricle. (Adapted rom RA O’Rourke, MH Craw ord:
, . T Curr Prob Cardiol 1:9, 1976.)
1674 - (100% , 88% ). A ,
, - MR, VSD, AR
, MR, TR, ASD - LV ,
- .T A F AR .T
- - .S
PART 6
MS. T A F LV ,
, .I MVP,
MS OS
. .
U - , W , ,
, . -
.T HOCM ,
Continuous Murmur A
(95% , 85% )
(95% , 84% ).
. T
A
, (S2),
.T
AS MR,
-
AS
.T
(G ). O , ,
PDA,
HOCM .
.O
T LV
V
LV
– , -
( )
,
LV .I , ,
.T
LV (
.T
) .I ,
.I
MR ,
,
LV
.T
.B
, ,
.T -
.M -
.
Dynamic Auscultation D V .T MVP
HOCM .T V
(Table 234-1). E
, - .
; -
Prosthetic Heart Valves T
TABLE 234-1 Effects of Physiologic and Pharmacologic Interventions
on the Intensity of Heart Murmurs and Sounds
Respiration .T
Right-sided murmurs and sounds generally increase with inspiration, except or .A
the PES. Le t-sided murmurs and sounds are usually louder during expiration. 2 3
Valsalva Maneuver (
Most murmurs decrease in length and intensity. Two exceptions are the LV ) -
systolic murmur o HOCM, which usually becomes much louder, and that o LV .T
MVP, which becomes longer and o ten louder. A ter release o the Valsalva .A -
maneuver, right-sided murmurs tend to return to control intensity earlier than MR
do le t-sided murmurs. / -
A ter VPB or AF , .
Murmurs originating at normal or stenotic semilunar valves increase in the C
cardiac cycle a ter a VPB or in the cycle a ter a long cycle length in AF. By .A
contrast, systolic murmurs due to AV valve regurgitation do not change,
diminish (papillary muscle dys unction), or become shorter (MVP). 2 3
Positional Changes .A AR
With standing, most murmurs diminish, with two exceptions being the murmur
.M
o HOCM, which becomes louder, and that o MVP, which lengthens and o ten
is intensi ied. With squatting, most murmurs become louder, but those o .A -
HOCM and MVP usually so ten and may disappear. Passive leg raising usually
produces the same results.
Exercise .P
Murmurs due to blood low across normal or obstructed valves (e.g., PS, , , .
MS) become louder with both isotonic and submaximal isometric (hand grip)
exercise. Murmurs o MR, VSD, and AR also increase with hand grip exercise. Pericardial Disease A 100%
However, the murmur o HOCM o ten decreases with nearly maximum hand ,
grip exercise. Le t-sided S4 and S3 sounds are o ten accentuated by exercise, ,
particularly when due to ischemic heart disease. .T
Abbreviations: AF, atrial ibrillation; AR, aortic regurgitation; HOCM, hypertrophic - -
obstructive cardiomyopathy; MR, mitral regurgitation; MS, mitral stenosis; MVP, , . C , -
mitral valve prolapse; PES, pulmonic ejection sound; PR, pulmonic regurgitation;
PS, pulmonic stenosis; TR, tricuspid regurgitation; TS, tricuspid stenosis; VPB, , ,
ventricular premature beat; VSD, ventricular septal de ect. .
I .A 1675
12- .
T
.P
CHAPTER 235 Electrocardiography

98%, 83%, 5.9 (95% - Sinoatrial (SA) LA
2.4–14) 12 H node Ventricular
. AV junction RA myocardium
T - AV node
- His bundle LV
.T Purkinje
RV fibers
.E
,
.
Left bundle
branch
■ FURTHER READING
Right bundle branch
Drazner MH :V
: T ESCAPE .C H F 1:170, 2008. Ventricular septum
Fanaroff AC : D FIGURE 235-1 Schematic o the cardiac conduction system.
?T R C E S
R . JAMA 314:1955, 2015. .S -
Fang JC, O’Gara PT: T . A ,
- , Braunwald’s Heart Disease. A Textbook of .
Cardiovascular Medicine, 10 , DL M ( ). P ,
E /S , 2015, 95–113.
Marcus GM :A
■ ECG WAVEFORMS AND INTERVALS
T ECG ,
-
P , (Fig. 235-2). T
. JAMA 293:2238, 2005.
QRS , ST-T-U
(ST , T , U )
.T J QRS
Electrocardiography ST .A
235 (ST-T ) ,
Ary L. Goldberger , , AV
.
T QRS-T ECG
A electrocardiogram (ECG EKG) -
action potentials,
.T ,
(Chap. 239). T ( 0)
, -
QRS. T ( 2)
electrocardiograph. ECG ( )
ST , ( 3) -
differences
T .F
.T ECG
0 N + ( . .,
, , -
) QRS .C
.I
2 3( , ) QT
, -
.I , ( . ., , )
QT.
(see also Chaps. 299 and 401).
■ ELECTROPHYSIOLOGIC BACKGROUND QRS

D -
.T
: ,
, .T ECG -
( ) ( ) -
“ ” (see also
Chaps. 239 and 241). T
P
T U
ST
sinoatrial (SA) node (Fig. 235-1), -
.S
.N , J
(AV) PR interval
H - ; , AV .
T H , QRS interval
,
P .T QT interval
.T FIGURE 235-2 Basic ECG wave orms and intervals. Not shown is the RR interval,
, , the time between consecutive QRS complexes.
1676 2
T ECG 1-
. W 25 /,
Left
(1 ) 0.04 (40 ), axi
ion s
0.20 (200 ). V , ECG iat de
d ev via
(1 V = 10 - is –90° ti
ax
on
–60°
PART 6
–120° –aVF
me
; –III
–II
tre
). T ECG :
Ex
RR, PR, QRS, QT/QT (F . 235-2). T –150° –30°
( ) (RR) +aVR +aVL
(0.20 )
R 300 (0.04 ) 1500. T

PR ( 120–200 ) 180° 0°
, –I +I
AV .T QRS -
( 100–110 ) +150° +30°
Rig
. T QT - – aVL –aVR
ht
( )
ax
is
.A - (“ ”) QT , QT , -
is
+60°
ax
+120°
de
QT/√RR ≤0.44 . S QT +II
al
+III +90°
v
0.45 0.46 .A ia
tio +aVF rm
- , . n No
■ ECG LEADS
T 12 ECG :
FIGURE 235-4 The rontal plane (limb or extremity) leads are represented on a
( ) ( ) .T hexaxial diagram. Each ECG lead has a speci c spatial orientation and polarity.
frontal plane (Fig. 235-3A); The positive pole o each lead axis (solid line) and the negative pole (hatched
horizontal plane (Fig. 235-3B). line) are designated by their angular position relative to the positive pole o lead
T I (0°). The mean electrical axis o the QRS complex is measured with respect to
(Fig. 235-4). T this display.
Fig. 235-5.
E
“ ” — VR, P II
— .T 12- ECG VR. B , -
. AV
F , V 3R V 6R P ( II,
. B VR). T P V1
ECG (H ) ,
2
.T ECG (<1 ) .
( ) -
■ QRS COMPLEX
,
N , -
.I
. T
mean
,
, ( ) -
(Fig. 235-6). T -
.
GENESIS OF THE NORMAL ECG ( 1). T
; -
■ P WAVE , 2
T . T , (V1)
’ ,
.S ( )
II (S ). A , , V6 ,
(
A B Posterior
) -
Superior
(R ). I
R- ( R- -
) S- -
. T
– – – R S
aVR Right – – Left
+ aVL – transition zone ( V3 V 4)
+ –
– (Fig. 235-7).
– – +V
6
+ I T QRS -
– +V
– 5
+ electrical axis QRS,
Right + + Left +V
+V 4 QRS
III aVF II +V +V 3
1 2 .N , QRS
−30° +100° (F . 235-4). A
Inferior Anterior –30° left axis deviation,
FIGURE 235-3 The six rontal plane (A) and six horizontal plane (B) leads provide a three- +90 +100° right axis devia-
dimensional representation o cardiac electrical activity. tion. L
, 1677
( -
), .R
(

),
,
( ), , , ,
.
■ T WAVE AND U WAVE

N , T-
V1 V2 QRS ( 45° ). S -
,
V3R V3 QRS–T-
V4 V5 V6 ( . .,
V4R
). T U
, (≤1 ) T
T .A U-
( . ., , ,
FIGURE 235-5 The horizontal plane (chest or precordial) leads are obtained
, ) .V U
with electrodes in the locations shown. Additional posterior leads are sometimes torsades de pointes (Chap. 241).
placed on the same horizontal plane as V4 to acilitate detection o acute
posterolateral in arction (V7, midaxillary line; V8, posterior axillary line; and V9,
posterior scapular line). Right chest leads (V3R–V6R) may enhance detection o
MAJOR ECG ABNORMALITIES
right ventricular involvement in the context o in erior in arction.
■ CARDIAC ENLARGEMENT AND HYPERTROPHY
R ( )
P- (≥2.5 ) (Fig. 235-8),
“P- .” L
P V1 (≥120 ),
P (F . 235-8). T
, “P- ,”
,
left atrial abnormality.
r LV R ,
V1 RV V6 ( . .,
q
1 )
R V1 (R ≥ S ),
A (Fig. 235-9); , R V1 V3R. ST
T- - -
.T ,
“ ,”
.P S
V1 R . R
– ,
r LV
RV ,
V1 V6 -
2
q QRS .
Acute cor pulmonale (Chap. 273),
B S , ECG -
.S ,
, , .
T QRS ,
- S1Q3T3 ( S I
–– –
–
– 2 Q III, T- III). A -
– + R-
1 V6
ST-T V1 V4 .
+ A .
V5
+
Chronic cor pulmonale (Chap. 252)
+ V4 ECG
+ + V3
C V1 V2 . I R ,
FIGURE 235-6 Ventricular depolarization can be divided into two major phases, R
each represented by a vector. A. The rst phase (arrow 1) denotes depolarization - - ( R- )
o the ventricular septum, beginning on the le t side and spreading to the right. .L -
This process is represented by a small “septal” r wave in lead V1 and a small , .
septal q wave in lead V6. B. Simultaneous depolarization o the le t and right M left ventricular hypertrophy (F . 235-9)
ventricles (LV and RV) constitutes the second phase. Vector 2 is oriented to the
le t and posteriorly, refecting the electrical predominance o the LV. C. Vectors
(arrows) representing these two phases are shown in re erence to the horizontal R S ( . ., SV1 + [RV5 RV6]
plane leads. (A ter AL Goldberger et al: Goldberger’s Clinical Electrocardiography: A >35 ). R (ST T-
Simplifed Approach, 9h ed. Philadelphia, Elsevier/Saunders, 2017.) , “ ” )
1678
I aVR V1 V4
PART 6
II aVL V2 V5
III aVF V3 V6
FIGURE 235-7 Normal electrocardiogram rom a healthy subject. Sinus rhythm is present with a heart rate o 75 beats per minute. PR interval is 0.16 s; QRS interval
(duration) is 0.08 s; QT interval is 0.36 s; QTc is 0.40 s; the mean QRS axis is about +70°. The precordial leads show normal R-wave progression with the transition
zone (R wave = S wave) in lead V3.
R .H , ■ BUNDLE BRANCH BLOCKS AND RELATED PATTERNS

, - I
.L ( ) -
( . ., QRS .W ,
R VL + SV3 >20 >28 ). T QRS ≥120 ; ,
QRS 110 120 .T QRS
.L
(Fig. 235-10). T ,
.T - , QRS
( SR′ V1 RS V6, ). L
. ECG .T
QRS .I , -
, . H , - -
- - , ECG
.M
(Chap. 236). QRS in hypertrophy Main QRS vector
V1 V6
V6
V1
Normal
LA
RA
V1
Normal Right Left LVH
RA
RA LA LA RA LA
II
RA or or
RA
RA RVH
V1
LA LA
LA
FIGURE 235-8 Right atrial (RA) overload may cause tall, peaked P waves FIGURE 235-9 Le t ventricular hypertrophy (LVH) increases the amplitude o
in the limb or precordial leads. Le t atrial (LA) abnormality may cause broad, electrical orces directed to the le t and posteriorly. In addition, repolarization
o ten notched P waves in the limb leads and a biphasic P wave in lead V1 with abnormalities may cause ST-segment depression and T-wave inversion in leads
a prominent negative component representing delayed depolarization o the LA. with a prominent R wave. Right ventricular hypertrophy (RVH) may shi t the QRS
(A ter MK Park, WG Guntheroth: How to Read Pediatric ECGs, 4th ed. St. Louis, vector to the right; this e ect usually is associated with an R, RS, or qR complex
Mosby/Elsevier, 2006.) in lead V1. T-wave inversions may be present in right precordial leads.
V1 V6 QRS - 1679
Normal ( . .,
),
.I , ,

ST–T- .
P T- . F ,
R′ R T-
r
.
RBBB A
ST- B
T (Chap. 250).
q P ( “ ”)
S
S ( )
QRS
LBBB QRS ( , ). L
(QRS –45°) -
.
I , (QRS
+110–120°)
-
.I
T ( ) , -
( . ., 1 , -
FIGURE 235-10 Comparison o typical QRS-T patterns in right bundle branch , ). P QRS
block (RBBB) and le t bundle branch block (LBBB) with the normal pattern in preexcitation
leads V1 and V6. Note the secondary T-wave inversions (arrows) in leads with an
, W -P -W (WPW)
rSR′ complex with RBBB and in leads with a wide R wave with LBBB.
(Chap. 244) .
.A ,
, (QS) ■ MYOCARDIAL ISCHEMIA AND INFARCTION
V1 (R) V 6. A - (See also Chap 269) T ECG
, .I -
, .S ,
.
B .I .S
, .A ,
.R .T
, ( . ., ECG ST (Fig. 235-11). W
) ( . ., , ). L transmural, ST
( ) , ST ,
: - , , -
( ), T .W
, , . subendocardium, ST -
B .A , ( . ., )
- ; , ST- ( ST VR).
. M ST .
B P ST
(QRS) .F ,
secondary repolarization ST- -ST
(ST-T) .W , T - (
QRS (F . 235-10). ) ;
T QRS–T- -ST MI
- (see Chap. 268). T
.I , primary repolarization STEMI -STEMI (Chap. 266).
A B
ST
ST
V5
V5
ST
ST
FIGURE 235-11 Acute ischemia causes a current o injury. With predominant subendocardial ischemia (A), the resultant ST vector will be directed toward the
inner layer o the a ected ventricle and the ventricular cavity. Overlying leads there ore will record ST depression. With ischemia involving the outer ventricular layer
(B) (transmural or epicardial injury), the ST vector will be directed outward. Overlying leads will record ST elevation.
1680 V1 V2 V3 V4 V5 V6
PART 6
FIGURE 235-12 Severe anterior wall ischemia (with or without in arction) may cause prominent T-wave inversions in the precordial leads and in leads I and aVL. This
pattern (sometimes re erred to as Wellens T waves) is usually associated with a high-grade stenosis o the le t anterior descending coronary artery.
T ECG ST Q .H , ECG-
-ST .F , -
( ) Q ( )
ST T- Q .T , -
(V1–V6) I VL. I “Q- ”
II, III, VF. “P ” “ -Q- ” (Chap. A7). L
( ) - R-
reciprocal ST V1 V3 ( V1 V2 Q
ST “ ” ). . (A V7-V9
R ST - .) I , ECG
(F . 235-5). W ST .C ECG
, Q- ,
T- . I , ST-
Q .R - Q-
, , ,
(P ’ ) ST- - .
Q .D T ECG
, ST .A
T- . ECG ,
P T- ECG throughout .
( . ., V1–V4, I, VL) P ECG
(Fig. 235-12). (Chap. 11). F ,

W , (QRS)
(ST-T) . N - , , W -
R- Q P -W .H , -
( ) ST-
(Fig. 235-13). A Q ; T- ; , T ;
, Q not ( ).
A ECG sequence with anterior Q-wave infarction

I II III aVR aVL aVF V2 V4 V6
Early
Evolving
B ECG sequence with inferior Q-wave infarction

I II III aVR aVL aVF V2 V4 V6
Early
Evolving
FIGURE 235-13 Sequence o depolarization and repolarization changes with (A) acute anterior and (B) acute in erior wall Q-wave in arctions. With anterior in arcts,
ST elevation in leads I and aVL and the precordial leads may be accompanied by reciprocal ST depressions in leads II, III, and aVF. Conversely, acute in erior (or
posterolateral) in arcts may be associated with reciprocal ST depressions in leads V1 to V3. (A ter AL Goldberger et al: Goldberger’s Clinical Electrocardiography: A
Simplifed Approach, 9th ed. Philadelphia, Elsevier/Saunders, 2017.)
TABLE 235-1 Differential Diagnosis of ST-Segment Elevations , , ( - 1681
Ischemia/myocardial in arction ), .
Nonin arction, transmural ischemia (Prinzmetal’s angina, and probably Tako- ■ METABOLIC FACTORS AND DRUG EFFECTS
tsubo syndrome, which may also exactly simulate classical acute in arction)

A
Acute myocardial in arction ECG , , (ST-T-U)
Postmyocardial in arction (ventricular aneurysm pattern) QRS .C -
Acute pericarditis ECG.
Normal variants (including benign “early repolarization” patterns) Hyperkalemia (Fig. 235-14),
Le t ventricular hypertrophy/le t bundle branch blocka ( ) T .
Other (rarer) F K+ AV -
Acute pulmonary embolisma , P- , QRS
. S
Brugada patterns (right bundle branch block–like pattern with ST elevations
in right precordial leads)a (“ - ” )
Class 1C antiarrhythmic drugsa
. Hypokalemia (Fig. 235-15) -
, U .P QT
DC cardioversion
Hypercalcemiaa
: 1A
Hyperkalemiaa ( . ., , , , ,
Hypothermia (J [Osborn] waves) ) III ( . ., [F . 235-15],
Nonischemic myocardial injury , , ). S hypothermia (F . 235-15)
Myocarditis ,
Tumor invading le t ventricle J (O ). M QT ,
Trauma to ventricles , T- ,
a
, (“CVA T- ” )
Usually localized to V1–V2 or V3.
(F . 235-15). Hypocalcemia QT (ST
Source: Modi ied rom AL Goldberger et al: Goldberger’s Clinical
Electrocardiography: A Simpli ied Approach, 9th ed. Philadelphia, Elsevier/ ), hypercalcemia (Fig. 235-16). D -
Saunders, 2017. QT , “ -
” ST–T- (digitalis effect).
F , ST- ■ NON-SPECIFIC ST-T CHANGES AND LOW QRS
, ( VOLTAGE
“ ” ), M ECG ,
(Table 235-1). S , T - . T- ,
T- , ST- (“
, , , . ST–T- ”)
ST- , T - - , ,
V1 V2 , , , -
.T , , ,
Q , - ( . ., ).
, , L QRS - - QRS -
, .D , - ≤5 / ≤10 .
, , M .A
ST- . (Fig. 235-17) , -
P T- , , , .
Hyperkalemia
Mild-Moderate Moderate-Severe Very Severe
T Lead I
V1 V1
P
Lead II
V2
V2
P
1mV
1s
FIGURE 235-14 The earliest ECG change with hyperkalemia is usually peaking (“tenting”) o the T waves. With urther increases in the serum potassium concentration,
the QRS complexes widen, the P waves decrease in amplitude and may disappear, and nally a sine-wave pattern leads to asystole unless emergency therapy is given.
(A ter AL Goldberger et al: Goldberger’s Clinical Electrocardiography: A Simplifed Approach, 9th ed. Philadelphia, Elsevier/Saunders, 2017.)
1682 Hypokalemia Hypothermia Amiodarone
II V3 V5 V4
T
U
PART 6
Tricyclic overdose Subarachnoid hemorrhage
V2
I III V3
FIGURE 235-15 A variety o metabolic derangements, drug e ects, and other actors may prolong ventricular repolarization with QT prolongation or prominent U
waves. Prominent repolarization prolongation, particularly i due to hypokalemia, inherited “channelopathies,” or certain pharmacologic agents, indicates increased
susceptibility to torsades des pointes ventricular tachycardia (Chap. 249). Marked systemic hypothermia is associated with a distinctive convex “hump” at the J point
(Osborn wave, arrow) due to altered ventricular action potential characteristics. Note QRS and QT prolongation along with sinus tachycardia in the case o tricyclic
antidepressant overdose.
Hypocalcemia Normal Hypercalcemia

I I I
II II II
QT 0.48 s QT 0.36 s QT 0.26 s

QTc 0.52 QTc 0.41 QTc 0.36
FIGURE 235-16 Prolongation o the Q-T interval (ST-segment portion) is typical o hypocalcemia. Hypercalcemia may cause abbreviation o the ST segment and
shortening o the QT interval.
FIGURE 235-17 Classic triad o fndings or pericardial e usion with cardiac tamponade: (1) sinus tachycardia; (2) low QRS voltages; and (3) electrical alternans (best
seen in leads V3 and V4 in this case; arrows). This triad is highly speci c or pericardial e usion, usually with tamponade physiology, but o limited sensitivity. (Adapted
rom LA Nathanson et al: ECG Wave-Maven. http://ecg.bidmc.harvard.edu.)
■ ELECTRICAL ALTERNANS 1683
E — - - - Noninvasive Cardiac Imaging:
ECG — 236
- Echocardiography, Nuclear
CHAPTER 236 Noninvasive Cardiac Imaging: Echocardiography, Nuclear Cardiology, and Magnetic Resonance/ComputedTomography Imaging
.T (P-QRS-T)
,
Cardiology, and Magnetic
(F . 235-17). I , (ST-T Resonance/Computed
U )
. Tomography Imaging
Marcelo F. Di Carli, Raymond Y. Kwong,
■ CLINICAL INTEPRERATION OF THE ECG Scott D. Solomon
A ECG . T
’ , ,
.M ECG .
T
T , .T 14
ECG: (1) ( -
(ECG). C
) ( ),
, -
(2) , (3) , (4) PR /AV , (5) QRS
,
, (6) QT/QT , (7) QRS , (8) P ,
.M
(9) QRS , (10) R- , (11)
( ),
Q , (12) ST , (13) T , (14) U .C -
(PET) ,
ECG .
(MRI), (CT).
T , ,
■ COMPUTERIZED ELECTROCARDIOGRAPHY
C .I , -
ECG .C ECG
, , - .
.
PRINCIPLES OF MULTIMODALITY CARDIAC
■ FURTHER READING IMAGING
Goldberger AL, Goldberger ZD, Shvilkin A: Goldberger’s Clinical
Electrocardiography: Simplified Approach, 9 .P ,E , ■ ECHOCARDIOGRAPHY
2017. E - ( )
Kligfield P :R S I - , ,
E : P I: T E . T -
I T AS S A H A - ,
E A C , C
C C ; A C C F - . E “M- ”
; H R S E I
S C E . J A C C (Fig. 236-1, left panel). M
49:1109, 2007.
Mirvis DM, Goldberger AL: E , Braunwald’s 512 . T
Heart Disease: A Textbook of Cardiovascular Medicine, 11 , JL J .A“
( ). P ,E , 2017. ”
Nathanson LA : ECG W -M . S -A P (Fig. 236-1, right panel). T
S P . https://ecg.bidmc.harvard.edu/maven/ “ ”
mavenmain.asp. L M 8, 2017. 30 ,
Rautaharju PM :R 100 .T -
. P IV: T ST ,T ;
U .JA C C 53:982, 2009. , ,
Surawicz B, Knilans T: Chou’s Electrocardiography in Clinical Practice: , .T -
Adult and Pediatric, 6 .P ,S , 2008. ,
Surawicz B :R - .A M-
. P III: I - - (2D) ,
.C 119: 235, 2009.
Wagner GS . AHA/ACCF/HRS R S - .
I E : P VI: T -
A I /I :AS S A :
H A E A C , ,
C C C ; A C C .I
F ; H R S E I - .H
S C E . JA C C -
53:1003, 2009.
Zimetbaum PJ, Josephson ME: U ,
.NE J M 348:933, 2003. .
T - -
.T -
1684
Image Generation in M-Mode and 2D Echocardiography
Phased array Processing and scan conversion

transducer
PART 6
time
Piezoelectric
elements
Echoes
Ultrasound Time
Distance (depth)
pulses
Heart
M-mode image 2-D image
FIGURE 236-1 Principle o image generation in two-dimensional (2D) echocardiography. An electronically steerable phased-array transducer emits ultrasound rom
piezoelectric elements, and returning echoes are used to generate a 2D image (right) using a scan converter. Early echocardiography machines used a single
ultrasound beam to generate an “M-mode” echocardiogram (see text), although modern equipment generates M-mode echocardiograms digitally rom the 2D data.
LV, le t ventricle.
,
2D (Fig. 236-2). .
I 2D T D
, : D ,
D D ,
D .W - D .B D
,
, .P D
;
.T , .
D , C D - ,
.T
.A .B -
B ,
,
p = 4v2 .C
p= v= D D
,
.T 2D , -
.T D
,
3D matrix array (Fig. 236-3). A -
transducer 2D
D .
T
Matrix array
elements .T ,
,
, , .B ,
,
I L -
3D
, .T
, -
, ,
,
,
3D scan .T -
FIGURE 236-2 Three-dimensional (3D) probe and 3D image. , ,
1685
A B C
FIGURE 236-3 Three types o Doppler ultrasound. A and B. Pulsed and continuous wave Doppler wave orms with time on horizontal axis and velocity o blood fow on
vertical axis. C. Color fow Doppler, where velocities are encoded by colors according to scale on right side o screen and superimposed on a two-dimensional grayscale
image.
, / .R -
, , - .
.P - T -
( - [SPECT]
.T PET) ,
. .L CT MRI,
S ( - ) .
.S -
Radiopharmaceuticals Used in Clinical Imaging
T 236-1 -
, SPECT PET .
( Protocols for Stress Myocardial Perfusion Imaging B
). -
W , , . E
, -
( . ., , ST- , -
(Fig. 236-4). T - , ). H ,
- - ,
- CAD. I
.A , ,
, .P
, , , . ,
, , , β1- ,
■ RADIONUCLIDE IMAGING .F ,
R - -
.D β1-
(CAD), , ,
.T .I -
(Table 236-1), ,
.D
.
Myocardial Perfusion and Viability Imaging
Protocols I -
, ’
, , ,
.
F SPECT , -99 (99 T )-
(Fig. 236-5).
S ( - , -, 2- )
.A -
99
, T- -
(1–2 ). A ,
-
99
FIGURE 236-4 Two examples o hand-held ultrasound equipment: V-Scan (General Electric, le t) .T T
and Sonosite (right).
1686 TABLE 236-1 Radiopharmaceuticals for Clinical Nuclear Cardiology
RADIOPHARMACEUTICAL IMAGING TECHNIQUE PHYSICAL HALF-LIFE APPLICATION
Technetium-99m sestamibi SPECT 6h Myocardial per usion imaging
Technetium-99m tetro osmin SPECT 6h Myocardial per usion imaging
PART 6
Thalium-201 SPECT 72 h Myocardial per usion imaging

Iodine-123 metaiodobenzylguanidine SPECT 13 h Cardiac sympathetic innervation
(MIBG)
Rubidium-82 PET 76 s Myocardial per usion imaging
13
N-ammonia PET 10 min Myocardial per usion imaging
18
F- luorodeoxyglucose PET 110 min Myocardial viability and in lammation
imaging
Abbreviations: PET, positron emission tomography; SPECT, single-photon emission computed tomography.
, ( . ., ) (Fig. 236-6). C
. I , PET SPECT CT ( -
hybrid PET/CT SPECT/CT). CT
( ). W ( -
, -201 attenuation correction). H ,
(CAC) / CT -
. ( ).
PET SPECT F
, ( SPECT PET)
(T 236-1). T - - PET ( . ., -
( . ., -82) [FDG] PET). I PET ,
, -201 SPECT .
. H ,
( . ., 13N- ). PET ■ CARDIAC COMPUTED TOMOGRAPHY
SPECT, .I CT -
SPECT, PET - .T - -
( L/
), ’ . T
.T -
, , , ,
Short axis Total perfusion deficit

Perfusion Defect blackout map
506.0 100.0%
LAD
LCX
RCA
Horizontal long axis Vertical long axis 0.0 0.0%
Perfusion Defect blackout map
145.0 100.0%
LAD
LCX
RCA
0.0 0.0%
Gated perfusion images Perfusion Defect blackout map
50.0% 100.0%
12 13 14 15 16 17 LAD
LCX
18 19 20 21 22 23
RCA
0.0% 0.0%
24 25 26 27 28 29
FIGURE 236-5 Tomographic stress (top o each pair) and rest myocardial per usion images with technetium-99m sestamibi single-photon emission computed
tomography imaging demonstrating a large per usion de ect throughout the anterior and anteroseptal walls. The right panel demonstrates the quantitative extent o
the per usion abnormality at stress (top bull’s-eye), at rest (middle bull’s-eye), and the extent o de ect reversibility (lower bull’s-eye). The lower le t panel demonstrates
electrocardiogram-gated myocardial per usion images rom which one can determine the presence o regional wall motion abnormalities and calculate le t ventricular
volumes and ejection raction.
1687
Myocardial perfusion images
23 31 36
Gated perfusion images
GStrCTAC
Frame: 1 of 8 Mid-HLA
19 21 23 25 27
29 31 33 35 37
23 31 36
39 41 43 45 47
Stress time activity curves Mid-VLA

900
Total perfusion images
800
Stress Rest 700
600
(kBq/ml)
500
400
300
200
100
0
5 10 15 20 25 30 35
Frame index
Quantitative myocardial blood flow and flow reserve Rest time activity curves
600
Flow (ml/min/g)
500
Region Stress Rest Reserve
400
LAD 2.32 1.09 2.12 (kBq/ml)
300
LCX 2.29 1.08 2.12
RCA 2.30 0.99 2.33 200
TOT 2.30 1.06 2.18 100
0
5 10 15 20 25 30 35
Frame index
FIGURE 236-6 Multidimensional cardiac imaging protocol with positron emission tomography. The le t upper panel demonstrates stress and rest short-axis images
o the le t and right ventricles demonstrating normal regional myocardial per usion. The middle panel demonstrates the quantitative bull’s-eye display to evaluate the
extent and severity o per usion de ects. The lower right panel illustrates the time-activity curves or quanti cation o myocardial blood fow. The right upper panel
demonstrates electrocardiogram-gated myocardial per usion images rom which one can determine the presence o regional wall motion abnormalities and calculate
le t ventricular volumes and ejection raction. LAD, le t anterior descending artery; LCX, le t circumfex artery; RCA, right coronary artery; TOT, total le t ventricle.
H . I Mixed
A B
CT , , , RCA
.
H , PA
,
. Ao
C CT
.W CT ,
- LAD
5–15 . Ao
CT Calcium Scoring CT
CT C D Noncalcified
Calcified
.T -
Ao
.
C ( . ., A )
(0–10), (10–100), -
(100–400), (>400) (Fig. 236-7). CAC LAD
. P - -
CT .W , FIGURE 236-7 Examples o non-contrast- and contrast-enhanced coronary imaging with

computed tomography (CT). A. Calci ed coronary plaques in the distal le t main and proximal
CAC le t anterior descending coronary artery (LAD) in a noncontrast cardiac CT scan. Calcium deposits
(~1–2 S ). are dense and present as bright white structures on CT, even without contrast enhancement. B,
C, and D. Di erent types o atherosclerotic plaques on contrast-enhanced CT scans. Importantly,
CT Coronary Angiography C CT - noncalci ed plaques are evident only on contrast-enhanced CT scans. AO, aorta; PA, pulmonary
(CTA) artery; RCA, right coronary artery.
1688 . I ASSESSMENT OF CARDIAC STRUCTURE AND
CT FUNCTION
.R E , CMR, CT
- , , -
’ , 60 / , .
PART 6
- . R
W CTA, .E
.I - , .
- -
T -
.I .L
ECG .T 2D
- , . T
(F . 236-7). .M ,
.I , -
■ CARDIAC MAGNETIC RESONANCE CMR CT
C (CMR) .T - (3D)
, ,
.W MRI - .H , 3D -
, , -
, .
.A - L -
(RF) . F ,
.
O RF , , .A
- ’ , ,
K- , - . T
.T ( )
RF .
D
. I CMR, T1- CMR ( [LGE])
, , - (
. T2- T2*- , ). CMR
, , LGE
, . V ECG- (Video 236-1).
- - M
, . H , , .I , -
ECG- - , .P
.A CMR
Table 236-2. ( . .,
). A ,
TABLE 236-2 Clinical Cardiac Magnetic Resonance Pulse Sequences
and Their Application ,
PULSE SEQUENCE KEY IMAGING INTERESTS .B
Cardiac Morphology
,
Still rame imaging (black or bright Cardiac structures
.A
blood)
, CMR
Cardiac Function .
Cine imaging Le t ventricular volume and unction L -
Cine myocardial tagging Le t ventricular de ormation (strain) .T -
Blood Flow Imaging ,
Velocity-encoded phase contrast Cardiac and great vessel low , ,
, ;
Stress Testing
;
Myocardial per usion imaging Regional myocardial blood low , .T
Cine imaging Regional wall motion .A
Myocardial Tissue Characterization ,
Late gadolinium enhancement Myocardial in arction and in iltrative “ ”
disease .I
T2-weighted imaging Myocardial edema , -
Iron content imaging Myocardial iron in iltration ,
Magnetic Resonance Angiography .
V
Aorta, peripheral and coronary Luminal stenosis and vessel wall
CMR. A
arteries remodeling
CT
, . - 1689
A .E (
, , TAPSE)
, .
- A
.A CMR
-
. .I
RV ,
■ ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC ,
FUNCTION ,
A , .R
, .L -
-
- - .A .A
.
(LVEF). A , I ,
( . ., CMR, CT, )
- .I
. A LVEF 55% ,
, LVEF 50–55% - .
N , .I -
- ,
, , , ,
CMR, MC , -
.A
.A .T
,
.
/ .I A
, .F ,
, - -
- - , .A -
D - .I
CMR .T
LVEF. , .T
-
■ ASSESSMENT OF LEFT VENTRICULAR DIASTOLIC
, ,
FUNCTION
E
.R
.R D
-
.M -
.
, E′,
I
, , .
,
D , E,
.E
E/E′,
.T
; ,
E A
“ A1 ” ,
.M
- -
(<150 ),
. R
. S
-
.
, D - ,
D , (Fig. 236-8). D
, PATIENT SAFETY CONSIDERATIONS
.
■ RADIATION EXPOSURE
■ ASSESSMENT OF RIGHT VENTRICULAR FUNCTION B CT
R - .S
,
, CMR, CT, . CMR .T effective dose
( S ). H ,
(Video 236-2). -
A ,
, .T
. H , SPECT ~4 11 S ,
, .T
(FAC = [ – ]/ ), PET , ~2.5–4 S . R
1690
Normal diastolic Mild diastolic Moderate diastolic Severe diastolic dysfunction
function dysfunction dysfunction
Reversible Fixed
Impaired relaxation Pseudonormal
restrictive restrictive
PART 6
0.75< E/A<1.5 E/A≤0.75 0.75 <E/A<1.5 E/A≥1.5 E/A>1.5

DT >140 ms DT>140 ms DT<140 ms DT<140 ms
2.0
Velocity, m/s
E
Mitral inflow A
0
Adur
∆E/A<0.5 ∆E/A<0.5 ∆E/A≥0.5 ∆E/A≥0.5 ∆E/A≥0.5

2.0
Velocity, m/s
Mitral inflow at
peak valsalva E
maneuver A
0
Velocity, m/s
E/e’<10 E/e’<10 E/e’≥10 E/e’≥10 E/e’≥10

Doppler tissue 0
imaging of mitral
annular motion a’
0.15 e’
S≥D S>D S<D or S<D or S<D or

ARdur<Adur ARdur<Adur ARdur>Adur+30 ms ARdur>Adur+30 ms ARdur>Adur+30 ms
2.0
Velocity, m/s
Pulmonary
venous flow ARdur
0
Time, ms Time, ms Time, ms Time, ms Time, ms
Vp
Flow propagation
velocity (Vp) on
color M-mode
>50 cm/s >45 cm/s >45 cm/s >45 cm/s >45 cm/s
E/Vp <1.5 E/Vp <1.5 E/Vp >2.5 E/Vp >2.5 E/Vp <2.5
Left ventricular relaxation Normal Impaired Impaired Impaired Impaired

Left ventricular compliance Normal Normal to
Atrial pressure Normal Normal
FIGURE 236-8 Stages o diastolic unction based on various parameters, including mitral infow (with and without Valsalva maneuver), Doppler tissue imaging,
pulmonary venous fow, and fow propagation. (Adapted with permission rom MM Redfeld et al: JAMA 289:194, 2003.)
CT , , T – -
.A
CT , .T
( . ., - , ECG
) .T - - - .I ,
CTA 5 15 S ,
, 1 S .I ( -
ALARA ( ) - )
.B , - .B
~7 S, , ,
U S ~3 -
S . .T
■ SAFETY CONSIDERATIONS OF CMR IN PATIENTS 1691
.I “ ” - WITH PACEMAKERS AND DEFIBRILLATORS
. A MRI
,
■ CONTRAST AGENTS ( ),
C CT, CMR, - ,
.A , “ ’ .” B ,
, CMR
. .
T I ,
CT .T (AICD)
CMR
. T FDA .
0.4–3% .
M - .T
- (CIN)
PATIENT-CENTERED APPLICATIONS OF
( [ GFR] >60 L/ CARDIAC IMAGING
) .I , CIN - , ■ CORONARY ARTERY DISEASE
7–10 , T
.H , GFR CAD
<60 L/ , .I , -
- . ( . ., ). I ,
T - (GBCA ) CAD
CMR .T ( , , ),
GBCA U S , - , , .I
.M GBCA ~1% , ,
. A GBCA CAD. I ( . ., ECG
.T ),
GBCA - -
.A .R ,
(NSF),
CAD
.R .
NSF - Table 236-3
2
( GFR <30 L/ 1.73 ), , GFR CAD.
2
<15 L/ 1.73 , , I -
/ .W
- , - NSF CAD , , - ,
.M CMR ,
GBCA NSF. CAD (>50–60%). M -
C .I -
, ,
“ ” .A .
,
, Stress Echocardiography T
.T U.S. F D A (FDA)
- (Video 236-3). S -
. . S
T - -
, . T .I -
, , , , ,
.
TABLE 236-3 Comparative Diagnostic Accuracy of Cardiac Imaging Approaches to Coronary Artery Disease
IMAGING MODALITY PUBLISHED DATA SENSITIVITY SPECIFICITY
Exercise echocardiography 15 studies (n = 1849 patients) 84% 82%
Dobutamine echocardiography 28 studies (n = 2246 patients) 80% 84%
SPECT MPI 113 studies (n = 11,212 patients) 88% 76%
Myocardial per usion PET 9 studies (n = 650 patients) 93% 81%
CMR per usion 37 studies (n = 2841 patients) 91% 81%
CMR wall motion 14 studies (n = 754 patients) 83% 86%
Coronary CTA 18 studies (n = 1286 patients) 99% 89%
Note: In these studies, the diagnosis o coronary artery disease was based on the presence o a >50% or >70% stenosis on invasive coronary angiography.
Abbreviations: CMR, cardiac magnetic resonance; CTA, computed tomography angiography; MPI, myocardial per usion imaging; PET, positron emission tomography;
SPECT, single-photon emission computed tomography.
1692
. , CAD.
T - D
, - CAD ,
, ,
PART 6
.L (1) .C ,
CAD,
, (2) .T
PET
( - , ), (3) - . I - “ ”
CAD, -
, (4)
, (5) (Fig. 236-10). C ,
-
85% .N - CAD. T
-
, ,
. .
A , HYBRID CT AND NUCLEAR PERFUSION IMAGING B
CAD. A CT
- ,
, .C , CAC
- (SPECT/CT PET/CT) (Fig. 236-11). T
.
Stress Radionuclide Imaging SPECT .C , CAC -

CAD
.T -
.T
(Fig. 236-9, left panel), , CAD.
(Fig. 236-9, right
panel). A , PET SPECT, Cardiac CT V ,
, , - .
. I , CAC -
N CAD,
CAD,
, , ( . ., A >400). H ,
( . ., ). O CAC CAD,
-
.I , -
SPECT PET .C , CAC <400, -
<1% .I , - CAD,
, CAD,
Reversible perfusion defect Fixed perfusion defect

(Fig. 236-12).
A ,
Stress CT
Rest CTA. T
CAD ( )
Stress (T 236-3). I
( . ., >400), ,
Rest .
G CTA,
Stress
CAD -
.A ,
-
Rest .H ,
-
FIGURE 236-9 Selected technetium-99m sestamibi myocardial per usion single-photon emission ,
computed tomography images o two di erent patients demonstrating a reversible per usion
de ect involving the anterior and septal le t ventricular wall, refecting ischemia in the le t anterior
.
descending coronary territory (arrows in le t panel), and a xed per usion de ect involving the in erior T
and in erolateral walls consistent with myocardial scar in the right coronary territory (arrow in right CT (
panel ). CMR) (Fig. 236-13, top panel)
21 22 23 24 25 26 27 28 29 30 31 1693
Stress
LAD
23 24 25 26 27 28 29 30 31 32 33
Rest
35 36 37 38 39 40 41 42 43 44 45
LM Stress
37 38 39 40 41 42 43 44 45 46 47
Rest
67 66 65 64 63 62 63 64 65 66
LCX Stress
67 66 65 64 63 62 63 64 65 66
Rest
Stress Rest
Ant
Sep Lat
RCA
Inf
FIGURE 236-10 Coronary angiographic (left panel) and rubidium-82 myocardial per usion positron emission tomography images (right panel) in an 85-year-old
emale with diabetes presenting with chest pain. The coronary angiogram demonstrates signi cant stenoses o the le t main and circumfex coronary arteries.
However, the per usion images demonstrate only a reversible lateral wall de ect. Quanti cation o stress and rest myocardial blood fow demonstrated a signi cant,
global reduction on coronary fow reserve (estimated at 1.2, normal value >2.0), refecting extensive myocardium risk that was underestimated by the semiquantitative
estimates o myocardial per usion. LAD, le t anterior descending artery; LCX, le t circumfex artery; LM, le t main artery; RCA, right coronary artery.
ANT
SEP LAT
Stress
INF
STRESS(G)
PA
ANT
Rest SEP LAT

aAo
INF
REST(G)
Stress
Rest
dAo
Stress
Calcium score: 1330

Rest
FIGURE 236-11 Stress and rest rubidium-82 myocardial per usion positron emission tomography (PET) images (left) and noncontrast gated computed tomography
(CT) images (right) delineating the extent and severity o coronary artery calci cations obtained with integrated PET/CT imaging. The images demonstrate extensive
atherosclerosis (Agatston coronary calcium score = 1330) without fow-limiting disease based on the normal per usion study. aAo, ascending aorta; dAo, descending
aorta; PA, pulmonary artery.
1694 23 24 25 26 27 28 29 30 31 32 33
Stress
24 25 26 27 28 29 30 31 32 33 34
PART 6
Rest
64 65 66 67 68 64 63 62 61 60
Stress
65 66 67 68 69 64 63 62 61 60
Rest
LM
LAD
FIGURE 236-12 Stress and rest rubidium-82 myocardial per usion positron emission tomography images (top), noncontrast gated computed tomography images
(lower right), and selected coronary angiographic images obtained on a 59-year-old male patient with atypical angina. Despite the absence o signi cant coronary
calci cations (Agatston calcium score = 0), the per usion images demonstrated a dense and reversible per usion de ect involving the anterior and anteroseptal walls
(arrows), refecting signi cant obstructive disease in the le t anterior descending coronary artery (LAD), con rmed on angiography. LM, le t main artery.
FFRCT
0.9
LAD
0.8
0.7
FFR 0.57
FFRCT0.64
FIGURE 236-13 Examples o novel approaches to the assessment o ow-limiting coronary artery disease (CAD) with cardiac computed tomography (CT). In the
top panel, representative views o a coronary CT angiogram (CTA; le t), coronary angiogram (middle), and stress myocardial per usion CT (right) images in a patient with
CAD and prior stenting o the le t anterior descending coronary artery (LAD) are presented. On the CTA, the stent (arrows) is totally occluded as evidenced by the loss
o contrast enhancement distal to the stent. The coronary angiogram demonstrates a concordant total occlusion o the LAD. On the per usion CT images, there is a
black rim (arrows) involving the anterior and anterolateral walls, indicating the lack o contrast opaci cation during stress consistent with myocardial ischemia. (Images
courtesy o CORE 320 investigators.) The lower panel illustrates an example o ractional fow reserve (FFR) estimates with coronary CTA (le t) compared to the re erence
standard o invasive FFR. The FFR refects the pressure di erential between a coronary segment distal to a stenosis and the aorta. In normal coronary arteries, there
is no gradient, and FFR is 1. An FFR <0.80 is consistent with a hemodynamically signi cant stenosis. (Images courtesy o Dr. James Min, Cornell University, New York.)
( - FFRCT) 1695
(Fig. 236-13, lower panel), - SPECT. A
.H , , CMR .
. A CMR -
A , <1%
CAD CTA .A .
1- -
CTA. F CAD, Selecting a Testing Strategy in Patients without Known
CAD A ,
CAD. T CAD .
- T
. : (1) D CAD? (2) W
A CTA , - - ? (3) D -
?
CT (<3 F CAD
ECG ,
) . A C C /A H A -
(ETT)
CMR Imaging CMR CAD - .T
ETT ( . ., >10
, . [METS] ECG ) -
S CMR - , - ETT ( . .,
.M GBCA >2 ST- ,
ST , , -
.R ) .
( ) T
(Video 236-4). S GBCA , LGE ,
( ), CAD
.C ,
(Fig. 236-14).
W , .I , ETT -
CMR -
CAD, ( - microvascular disease). I ,
(T 236-3). H - - , -
(~1%), ,
.T .T
CMR SPECT CAD
.H , WOMEN
, - ,
ETT
.I , 2- -
, ETT-
48% .
P - ETT ( . .,
, , / ST- -
) ,
CTA, .M
-
.I ,
SPECT
-
ETT (Fig. 236-15). F
- ETT -
ETT -
.
A
/ -
ECG ( . ., ,
). I ,
-
CAD ( . ., , )
CAD -
FIGURE 236-14 The image shows the late gadolinium enhancement image o a
mid short-axis view. There is no evidence o in arction in the anterior wall, which
.I ,
would be seen as bright white areas, indicating that the stress per usion de ect .
primarily represents myocardial ischemia. This patient had a signi cant stenosis F , CTA
o the le t anterior descending coronary artery. CAD
1696 Exercise SPECT Exercise Echo
12 11
Event rate (%/year)

Normal 10 Normal
10 Mild 8.9 9.1 Single VD
Severe 7.8 Multi VD
8 6.7
6.4
6 5.7
PART 6
4 3.6 3.6
2.9 2.7
1.8 1.5 1.7
2 0.7
0.3 0.4
0
Low Intermediate High Low Intermediate High
Duke treadmill score Duke treadmill score

FIGURE 236-15 Incremental risk stratifcation o stress imaging over Duke treadmill score in patients with suspected coronary artery disease. Stress imaging is
most valuable in the intermediate-risk group. SPECT, single-photon emission computed tomography; VD, vessel disease. (Part A reproduced with permission rom R
Hachamovitch et al: Circulation 93:905, 1996. Part B data rom TH Marwick et al: Circulation 103:2566, 2001.)
, , . T
.
B .T -
, , CTA ,
- ,
.I , -
- -
(Fig. 236-16). CAD. W
T SPECT PET
- CMR, .
-
- .I , Selecting a Testing Strategy in Patients with Known
- CAD U
- CAD ( . ., , -
. P , )
CAD. A ETT -
- , ECG
(
). T ECG -
.I ,
,
. C ,
CAD.
T -
. A
, CTA
.W CTA -
Stress ,
CTA. L ,
Rest CTA
-
.I ,
.
Stress S
CAD.
A CAD,
Rest CAD
- .I
,
Stress
.I ,
,
.A CAD,
Rest
.
FIGURE 236-16 Selected views rom coronary computed tomography angiographic (CTA)
images (top panel) and stress and rest rubidium-82 myocardial per usion positron emission Testing Strategy Considerations in Patients
tomography images (lower panel) obtained on a 64-year-old male patient with atypical angina. Presenting with Chest Pain to the Emergency
The CTA images demonstrate dense ocal calci cations in the le t main (LM) and le t anterior
descending (LAD) coronary arteries and a signi cant noncalci ed plaque in the mid right coronary Department A -
artery (RCA; arrow). The myocardial per usion images demonstrated no evidence o fow-limiting -
stenosis. LCx, le t circumfex artery; OM, obtuse marginal branch. (ED),
A , CTA 1697
CAD
(Fig. 236-18). F -
, ,
CTA ED (
). P
.O , -
.L ,
ED -
.T
CTA, .A
- , ,
CTA (6.3%
8.4%, ) (2.6% 4.6%, ).
T -
CTA
.
T ,
.
P ( -
- ) .T
-
, - .
■ VALVULAR HEART DISEASE

FIGURE 236-17 A our-chamber long-axis late gadolinium enhancement (LGE) A
image o a patient with acute myocarditis. Note that the LGE primarily involved , , .
the epicardial aspect o the myocardium (arrows), sparing the endocardium, which E , CMR, CT
is a eature that distinguishes myocarditis rom myocardial in arction, which ,
a ects the endocardium. Also note the multiple oci o LGE in this case a ecting
the lateral wall o the le t ventricle. Viral myocarditis o ten presents with this
pattern. .I , -
. I , CMR
(ACS). S
, ,
( . .,
), (ETT),
.
.I
E
ACS
. T
CAD.
-
T
,
U S
, ,
ACS ECG .I
.A
,
-
.S
.
.M CMR -
(Video 236-5). D Assessment of Aortic Stenosis A ,
, , ,
LGE , CMR -
ACS ( . ., , .A
, ) (Fig. 236-17). ,
A B C
RCA
FIGURE 236-18 Representative coronary computed tomography angiographic (CTA) images o two patients presenting to the emergency department with chest
pain and negative biomarkers. The patient in A had angiographically normal coronary arteries; the panel shows a representative view o the right coronary artery (RCA).
B and C show a corresponding signi cant stenosis in the mid portion o the RCA on both the CTA (B) and invasive angiographic view (C). (Images used with permission
rom Dr. Quynh Truong, Massachusetts General Hospital, Boston, MA.)
1698
A B C
PART 6
FIGURE 236-19 Normal aortic valve in the parasternal long-axis view (A) and short-axis view (B), and bicuspid aortic valve showing typical 10 o’clock to 4 o’clock
leafet orientation (C).
CMR - ,
.E , - . CT
.T (CTA
, , )
, ; ; , ,
. .C CT
T : .T
, , .A –
, ,
, , ( . ., , -
(Fig. 236-19). T – ). E -
, - - .
,
( ). B , Assessment of Aortic Regurgitation A
, -
. .A
T , .
.P A ,
-
3.0 / , 4.0 /, - .C ,
36 64 H , . , .D
B - ,
, ,
-
.H , .A
- - - , ,
.I , - (Fig. 236-20).
B -
- . ,
2
A <1.0 ,
2 .P
<0.6 .B
- 5.5 LVEF
, ,
.
, . Q
S .S
. H - D .T
, -
.S .S ,
,
, A B
,
, -
.S ,
, .
T
FIGURE 236-20 Aortic regurgitation visualized by color ow Doppler in the parasternal long-axis view (A) and
. I the parasternal short-axis view (B).
700 .S - - 1699
600
-
,
500 ,
Flow (ml/s)
400 .
Forward flow volume 123 mL T
300
,
200 .K
Regurgitant volume 67 mL
100
.M ,
0 .
200 400 600 800 1000 1200
–100 V
.I
–200 ,
Time (ms)
-
FIGURE 236-21 The resultant ow curve generated rom phase contrast , .T ,
imaging demonstrates a orward fow o 123 mL and a regurgitant volume o 67 55% -
mL, yielding a regurgitant raction o 54% indicating severe aortic regurgitation.
.
CMR
, . CMR
, -
.O D -
- , .
, ,
.T - Assessment of Mitral Stenosis R
,
, . .
CMR R
. CMR - -
, –
.I , CMR (Fig. 236-24). N
,
. CMR ,
3D .W
,
(Fig. 236-21 and Video 236-6). ( ),
, ,
Assessment of Mitral Regurgitation T .A
-
(Fig. 236-22). T .
.
■ MYOCARDIAL INFARCTION AND HEART FAILURE
M ,
, , Role of Imaging after Myocardial Infarction I
(Fig. 236-23). - -
M , .A , LGE
, CMR
, - .I , LGE
,
. R 99 94%, .I ,
D .T ( - )
.T
- , - (Fig. 236-25). B LGE
, .
D (F . 236-23). V D W -
,
- , – ,
.F , . I ,
,
. T , -
(PISA) - .I , -
.T
, ,
(Fig. 236-26).
. E
A , .
. T
A ,
, , , .A
1700
PART 6
FIGURE 236-22 Normal mitral valve in two-dimensional views (le t) and with three-dimensional imaging (right).
A B C
FIGURE 236-23 A. Mitral valve prolapse with posterior leafet visualized prolapsing behind the plane o the anterior leafet (arrow). B. Color fow Doppler showing mitral
regurgitation in a patient with mitral valve prolapse. C. Severe unctional mitral regurgitation in a patient with a dilated le t ventricle.
A B
FIGURE 236-24 A. Rheumatic mitral stenosis showing pliable leafets tethered at the tips (arrow). Note the characteristically enlarged le t atrium. B. Mitral stenosis
visualized rom a three-dimensional echocardiogram.
. 1701
T , PET,
, -
. I ,
.T
CMR
.
Role of Imaging in New-Onset Heart Failure E -

- -
.A ,
. I ,
,
, .
A
, -
CAD .I ,
CAD
, -
CAD
.T ,
FIGURE 236-25 Example o a patient who presented with in erior ST segment , -
elevation myocardial in arction a ter several days o intermittent chest pain. -
The MRI con rmed an in erior MI by the location o LGE (red arrows). In addition, .S
there is a central area o microvascular obstruction (dark region surrounded by
the bright LGE, white arrow). RV: right ventricle, LV: le t ventricle.
.M CMR -
.A
. W , , CMR
, , , - .T LGE -
. (
T - )
( -
. ) (Fig. 236-28). I ,
S ( . ., )
, ,
.A .I
- , 1 6 (
.T - ). CMR
( . ., - (F . 236-28).
- H -
). ,
I , - LGE (Fig. 236-29).
/ CMR
, - (Video 236-7).
(Fig. 236-27). A PET
,
/
.I , -
, PET
(Fig. 236-30). I ,
PET
(F . 236-26).
■ ASSESSING CARDIAC FUNCTION IN PATIENTS

UNDERGOING CANCER TREATMENT
T
.A ,
-
/ . T ,
,
FIGURE 236-26 Acute le t anterior descending artery distribution myocardial .E -
in arction at end systole showing akinetic region (arrows).
1702
Contrast-enhanced MRI
PART 6
Positron emission tomography
Perfusion
Metabolism
Perfusion
Metabolism
FIGURE 236-27 Examples o myocardial viability patterns obtained with cardiac magnetic resonance imaging (MRI) and positron emission tomography (PET)
in three di erent patients with coronary artery disease. The top panel demonstrates extensive late gadolinium enhancement (bright white areas) involving the
anterior, anteroseptal, and apical le t ventricular walls (arrows), consistent with myocardial scar and nonviable myocardium. The lower le t panel demonstrates
rubidium-82 myocardial per usion and 18F-fuorodeoxyglucose (FDG) images showing a large and severe per usion de ect in the anterior, anterolateral, and apical walls,
indicating preserved glucose metabolism (so-called per usion-metabolic mismatch) consistent with viable myocardium. The right lower panel shows similar PET images
demonstrating concordant reduction in per usion and metabolism (so-called per usion-metabolic match) in the lateral wall, consistent with nonviable myocardium.
, , ,
. .
T E
>5% LVEF <55% , (Fig. 236-31). M , -
, >10% LVEF <55% -
.T , ,
. T , ,
.R
.H , . P
.
R , , , .T
CMR. T .C
.I , ,
- - ,
( . ., -
), . I ,
- .H , , -
. ,
. I
■ PERICARDIAL DISEASE , ,
T , .T
, , , ,
.T ~1 , .E -
. A ,
’ . , D
I , D
, pericardial effusion, .D -
, CMR, CT. O , -
, , , , ’
.T ,
, , .
1703
FIGURE 236-28 Di erentiation o various cardiomyopathies by CMR. The le t upper panel shows the short-axis late gadolinium enhancement (LGE) imaging o
a patient who su ered an acute myocardial in arction. Note LGE o the endocardial myocardium in the in erior wall extending rom the septum to the lateral wall
associated with myocardial thinning (arrows). The right upper panel shows the long-axis LGE imaging o a patient who has cardiac amyloidosis. Note the di use LGE
throughout le t ventricular myocardium, the le t atrium, and the interatrial septum (arrows). In addition, the blood pool is characteristically dark in signal indicating
sequestration o gadolinium contrast out o the blood pool a ter injection due to a high burden o amyloidosis in other organs. The le t lower panel shows a cine
diastolic long-axis image o a patient with a non-ischemic dilated cardiomyopathy. Note that there is extensive sponge-like non-compacted myocardium o the LV as
well as dilatation o all our cardiac chambers. This patient has a non-ischemic dilated cardiomyopathy secondary to LV non-compaction. The right lower panel shows a
22-year-old emale patient with a recent episode o acute chest pain and troponins elevation. Note the multiple mid-wall oci o LGE which suggests acute myocarditis
(arrows). LA, le t atrium; LV, le t ventricle; RA, right atrium; RV, right ventricle.
RV
LV
FIGURE 236-29 This fgure demonstrates three pulse sequence techniques by cardiac magnetic resonance that are o ten used to assess patients with hypertrophic
cardiomyopathy, all displayed in the mid short-axis scan plane. The center panel demonstrates that the le t ventricle (LV) was markedly thickened in its wall thickness
especially in the LV septum (red arrows). This nding was matched by marked regions o late gadolinium enhancement (LGE), which was consistent with brosis in
these segments (right panel, white arrows). The le t panel was cine myocardial tagging in the same slice plane. Myocardial tagging is used to assess the normal
intramyocardial strain by assessing distortion o the myocardial grids during systole. In this case, despite normal-appearing systolic radial wall thickening, the
myocardial strain as assessed by the distortion o grids was markedly reduced (le t panel, white arrows). This nding is consistent with substantial myo bril disarray in
the anterior and anteroseptal segments in this patient. RV, right ventricle.
1704
PART 6
RV RV
LV LV
Ant 21 22 23 24 25 26 27 28 29 30 31
Sep Lat
Perfusion
Inf
24 25 26 27 28 29 30 31 32 33 34 35
Metabolism
34 35 36 37 38 39 40 41 42 43 44 45
Perfusion
38 39 40 41 42 43 44 45 46 47 48 49
Metabolism
FIGURE 236-30 Representative cardiac magnetic resonance (CMR; top panel) and positron emission tomography (PET; lower panel) images rom a 45-year-old
male presenting with complete heart block. The CMR images demonstrate extensive late gadolinium enhancement in the subepicardial le t ventricular (LV) anterior
and anteroseptal walls and also in the right ventricular (RV) ree wall (arrows). The PET images demonstrate extensive fuorodeoxyglucose uptake in the same areas,
most consistent with active infammation due to sarcoidosis.
C , , -
, - . CT CMR , -
.I
, - ( , ,
. ) (Fig. 236-32 and Video 236-8). CMR
A ,
.T , -
, ’
. P
D
FIGURE 236-31 Pericardial e usion with tamponade physiology. The right FIGURE 236-32 A emale patient developed pericardial constriction and right
ventricle (arrow) is small and collapsing in end diastole due to increased heart ailure, secondary to radiation therapy or breast cancer. Note the multiple
pericardial pressure. pericardial adhesions (red arrows).
1705
LGE ( . .,
,
V ).
■ CARDIAC THROMBUS AND MASS
E
, , -
.G
- , CMR CT -
. C CT, CMR
, ,
-
.G
-
.
S (1)
, E , C , -
, , (2) *
“ ,” , -
, , -
, / .C FIGURE 236-34 Late gadolinium enhancement image o a massive anterior
(Fig. 236-33) in arction complicated by a dyskinetic le t ventricular LV aneurysm and
, intracavitary thrombus (red asterisk).
, -
. CMR
T
, .
, LGE , .F M ( . .,
, - LGE ), ( . ., ),
- ( . ., ). P -
.I , , , ,
- “ ” (Fig. 236-35). A
( ) LGE - (75%), (20%),
, - (5%). T -
(Fig. 236-34). C -
-
( . ., ) .P
.L , , , ,
, .
.C CT
■ ROLE OF IMAGING IN INFECTIOUS AND
INFLAMMATORY DISEASE
P
.
.
V
.T
,
.E
-
,
(Fig. 236-36).
T
.A , -
,
.
V
,
. I ,
(F . 236-36). V -
FIGURE 236-33 Cardiac thrombus (arrow) in an apical aneurysmal region
ollowing acute myocardial in arction. .
1706
PART 6
*
FIGURE 236-35 A case o a cardiac fbroma. A patient presented with shortness o breath and was ound to have a large myocardial mass on echocardiography.
Cine cardiac magnetic resonance imaging con rmed the large myocardial mass involving the anterolateral wall. Shortly a ter gadolinium contrast was injected, the
myocardial mass demonstrated intense accumulation o contrast on LGE imaging (right panel, asterisk). This is a case o cardiac broma. The patient also has gingival
hyperplasia and bi d thoracic ribs, a part o the rare Gorlin’s syndrome.
LA
LV
LV
LA
FIGURE 236-36 Vegetation on native mitral valve (le t panel, arrow). Le t atrium (LA) and le t ventricle (LV) are indicated. Middle panel shows a vegetation on a
mechanical prosthesis (St. Jude) indicated by an arrow; right panel shows vegetation on prosthesis a ter excision.
CT FDG PET PET/CT fusion

A
Before R L
treatment
After
treatment
FIGURE 236-37 Representative cross-sectional computed tomography (CT; left), uorodeoxyglucose (FDG) positron emission tomography (PET; middle), and
used CT and PET (right) images be ore and a ter antibiotic treatment in a patient with ever and suspected in ection o the stent placed in the descending portion
o the aortic arch (arrow) or treatment o aortic coarctation. The FDG images be ore treatment demonstrate intense glucose uptake within the stent, consistent with
infammation/in ection. The lower panel demonstrates signi cant attenuation o the FDG signal a ter treatment. (Images used with permission rom Dr. Sharmila Dorbala,
Brigham and Women’s Hospital.)
1707
CTA PET PET/CT fusion
Ao Ao
Ao LV LV
LV
FIGURE 236-38 Representative coronal computed tomography (CT) angiographic (CTA; left panel), uorodeoxyglucose (FDG) positron emission tomography (PET;
middle panel), and used CT and PET (right panel) images in a patient with suspected aortitis. The CTA images demonstrate thickening o the ascending aorta (Ao),
which correlates with intense, ocal FDG uptake consistent with active infammation. LV, le t ventricle.
PET , D PFO. I , -
( ) PFO
, , / , . S
/ .I ,
. T
- .B PFO - ,
18
F-FDG PET (Fig. 236-37). L , FDG PET .E V
- .
(Fig. 236-38). A
, - (Fig. 236-39). A
■ EVALUATION OF COMMON CONGENITAL .C D

ABNORMALITIES IN THE ADULT - ,
W
, .
, V
. A D - -
- .I , D
.P (PFO) 25% .T
.I PFO, - -
, .D
.
.H , - - PFO I , -
, - -
. .S
T PFO
, PFO , Q /Q .S
.B -
- PFO CMR (Fig. 236-40).
FIGURE 236-39 Large secundum-type atrial septal de ect (arrow) noted in the subcostal view with color fow Doppler showing fow through the de ect (right).
1708
PART 6
A B
Flow volume
ms
0 10 20 30 40 50 60 70 80 90 100
800
750
700
650
Main pulmonary artery
600
Ascending aorta
550
500
450
400
350
300
250
200
150
100
50
0
–50
0 50 100 150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900 950
C Time |ms |
FIGURE 236-40 A and B are phase contrast images that display blood fow (phase images on A) and anatomy (structural images on B) o the aorta (red) and pulmonary
artery (green). C demonstrates the fow curves o the aorta (red) and the pulmonary artery (green). Note that the total fow (area under the curve) was substantially
higher in the pulmonary artery than the aorta, indicative o a marked elevated pulmonary-to-systemic shunt ratio, as a result o the partial anomalous pulmonary venous
return that drained into the superior vena cava.
■ FURTHER READING VIDEO 236-2 This is cine cardiac magnetic resonance (CMR) imaging o a
patient in the long-axis our-chamber view. Note that the basal aspect o the
Di Carli MF :T .C
right ventricular (RV) ree wall is thickened, aneurysmal, and akinetic (red arrows).
133:2640, 2016. The global RV systolic unction is mildly reduced, and the RV is dilated. CMR can
Johnson NP :I FFR CFR image the RV using tomographic views and can quanti y the RV volumes and
:W ?JA C C 67:2772, 2016. ejection raction volumetrically. This is a patient who presented with syncopal
Naoum C : C - spells and inducible ventricular tachycardia on subsequent workup. He was
: diagnosed to have arrhythmogenic right ventricular dysplasia.
I .C C I
10: : 005331, 2017. VIDEO 236-3 Exercise echocardiogram showing rest images on le t and
poststress images on right, with parasternal long-axis, upper panel, and apical
Solomon SD : Essential Echocardiography, a Companion to our-chamber, lower panel, end-systolic rames. Following exercise, the distal
Braunwald’s Heart Disease, E , 2018. septal/apical region becomes akinetic. A = upper le t (UL); B = upper right (UR);
Steel KE, Kwong RY: A - C = lower le t (LL); D = lower right (LR).
.C H F R 5:128, 2008.
Vandoorne K, Nahrendorf M: M VIDEO 236-4 The VIDEO shows cardiac magnetic resonance (CMR) myocardial
.C C I 10: : 005613, 2017. per usion imaging during vasodilating stress, in three parallel-short-axis views.
A bolus o gadolinium contrast was injected intravenously while rapid imaging
VIDEO 236-1 Cine steady-state ree precession (SSFP) imaging (left) in short acquisition occurred. The contrast enhances the right ventricle rst, then travels
axis in a patient who had a large anterior myocardial in arction. Only one cut o through the pulmonary circulation, enters the le t ventricle (LV), and then per uses
a stack o short axis is shown. This method allows quanti cation o le t ventricular the LV myocardium. Myocardial per usion de ects with this technique show as
(LV) and right ventricular (RV) volumes in diastole and systole and calculation black subendocardial rims, refecting lack o contrast accumulation due to
o the LV ejection raction, stroke volumes, and cardiac output (a product o ischemia and/or scar. In this case, the anterior wall has a severe per usion de ect
LV stroke volume and heart rate). Note that in this case there is anterior and (red arrow). Figure 236-14 shows the late gadolinium enhancement (LGE) image
anteroseptal akinesia (lack o systolic wall thickening, as shown by the le t cine o a mid short-axis view. There is no evidence o in arction in the anterior wall,
movie, red arrows) matching by a near-transmural myocardial in arction as seen which would be seen as bright white areas, indicating that the stress per usion
by the matching late gadolinium enhancement (LGE) image (right picture, white de ect primarily represents myocardial ischemia. This patient had a signi cant
arrows). stenosis o the le t anterior descending coronary artery.
VIDEO 236-5 A 60-year-old emale presented with intermittent chest pain o CARDIAC CATHETERIZATION 1709
3 days in duration but was pain- ree at the time o assessment in the emergency
room. Admission electrocardiogram (ECG) demonstrated T-wave inversion ■ INDICATIONS, RISKS, AND PREPROCEDURE
in the anterior precordial lead, but cardiac enzymes were normal. A resting
cardiac magnetic resonance (CMR) study reviewed a large area o anteroseptal
MANAGEMENT
CHAPTER 237 Diagnostic Cardiac Catheterization and Coronary Angiography

hypokinesia (le t picture, region o hypokinesia shown by the red arrows), matching C -
with a large resting per usion de ect (middle picture, per usion de ect shown by the
blue arrows). Late gadolinium enhancement (LGE) imaging (right picture), however, , , -
did not show any enhancement to indicate any in arction in the anteroseptal wall, (Table 237-1). T -
suggesting that the hypocontractile and hypoper used anteroseptal wall was
viable. Urgent coronary angiography demonstrated an acute thrombus in the
mid le t anterior descending coronary artery, which required coronary stenting.
-
This case represents an example o acute coronary syndrome with hibernating .C
but viable myocardium in the anteroseptal wall. The anteroseptal wall recovered
contractile unction when reassessed 6 months later.
,
.
VIDEO 236-6 A patient with severe aortic regurgitation quantifed by cardiac T -
magnetic resonance (CMR). Notice the dark fow jet during diastolic across the
, <0.1% ,
aortic valve. For quantitation o the aortic regurgitation severity, a cross-sectional
cut was made just below the aortic valve, perpendicular to the aortic regurgitation
jet, using phase contrast fow imaging. Apart rom aortic regurgitation raction and
volume, CMR also can volumetrically quanti y ventricular sizes and dimensions TABLE 237-1 Indications for Cardiac Catheterization and Coronary
o the aorta, which are use ul in monitoring patients with aortic valve diseases. Angiography
CORONARY ARTERY DISEASE
Asymptomatic or Symptomatic
VIDEO 236-7 These are T2* images o the heart (left panel) and the liver (right High risk or adverse outcome based on noninvasive testing
panel) o a patient who has hemochromatosis. Note that iron and the liver are
markedly darkened in these movies, indicating high load o iron in the heart Sudden cardiac death
muscle and liver. The rate o signal reduction (decay) in the myocardium and Sustained (>30 s) monomorphic ventricular tachycardia
liver can be calculated as T2* value expressed in milliseconds. In this case, Nonsustained (<30 s) polymorphic ventricular tachycardia
the T2* was at 10 ms. T2* <20 ms in patients with cardiomyopathy has been
shown to indicate iron toxicity as the etiology o the cardiomyopathy, and it carries Symptomatic
prognostic valve or such patients at risk o cardiac iron toxicity. Canadian Cardiology Society Class II, III, or IV stable angina on medical
therapy
Acute coronary syndrome (unstable angina and non-ST-segment elevation
VIDEO 236-8 This video shows the heart in long and short axis. Note the large myocardial in arction)
atria, thickened pericardium, and extensive pericardial adhesions. Given the Chest-pain syndrome o unclear etiology and equivocal indings on noninvasive
extensive pericardial adhesions, there is little shearing motion o the ventricles tests
against the parietal pericardium.
ST-Segment Elevation Acute Myocardial In arction
Reper usion with primary percutaneous coronary intervention
Persistent or recurrent ischemia
Pulmonary edema and/or reduced ejection raction
Cardiogenic shock or hemodynamic instability
Risk strati ication or positive stress test a ter acute myocardial in arction
237 Diagnostic Cardiac
Catheterization and
Mechanical complications—mitral regurgitation, ventricular septal de ect
Valvular Heart Disease
Coronary Angiography Suspected severe valve disease in symptomatic patients—dyspnea, angina,
heart ailure, syncope
Jane A. Leopold, David P. Faxon In ective endocarditis with need or cardiac surgery
Asymptomatic patients with aortic regurgitation and cardiac enlargement or
↓ ejection raction
D Prior to cardiac surgery in patients with suspected coronary artery disease
Congestive Heart Failure
. I 1929, New onset with angina or suspected undiagnosed coronary artery disease
F New-onset cardiomyopathy o uncertain cause or suspected to be due to
coronary artery disease
’ Congenital Heart Disease
- .I 1940 , C R
Prior to surgical correction, when symptoms or noninvasive testing suggests
. coronary disease
T N P 1956. I 1958,
Suspicion or congenital coronary anomalies
S -
Pericardial Disease
, , - 40 L Symptomatic patients with suspected cardiac tamponade or constrictive
.T pericarditis
, Cardiac Transplantation
.S , Preoperative and postsurgical evaluation
J , Other Conditions
Hypertrophic cardiomyopathy with angina
.I U S ,
Diseases o the aorta when knowledge o coronary artery involvement is
, 1.5 necessary or management
.
1710 0.01% , 0.1% .T (INR) <1.7 - .T
, 24–48 .
.A C ,
- - .
,
PART 6
, ■ TECHNIQUE
, - - C
.O , -
, 1.5–2.0% , . T ’
- - . ,
I .
,
- - Vascular Access C -
. R , , ;
; ; , ,
, ; ; , .A
; ; - ,
, ,
; / .T ( )
; / /
- , , ;
; ; -
. .U -
C - - .A
, - A ’ B
.A <5% , .T
( ,
I E ) 0.1–0.2%
.M , , , .
, -
, .P Right Heart Catheterization T -
.R -
24 ,
(H1- H 2- ) ,
, - , , , /
. , ,
C - , .R
>0.5 / L 25% 48–72 -
, ~2–7% , , ,
20–30% - , ( ) -
, , , , ; ,
.D 0.3–0.7%
- .F , - .
0.9%
(1.0–1.5 L/ ) 3–12 6–24 Left Heart Catheterization T
- . .W
P N- (M ) ,
- , -
, . D . I -
24 , ,
48
.O -
(3 L/ ) .O
1 6 ; - - , .
; <50 L T .H
.
C . F -
6 ,
.A (0.75 / , 1.75 / -
325 .I ) (350 μ / , 15 μ / -
- ) .
, :
(600- 75 ) (60- ■ HEMODYNAMICS
10 ), (180- 90 A -
). P -
.W 2–3 (Table 237-2). T
TABLE 237-2 Normal Values for Hemodynamic Measurements - 1711
.W ,
Pressures (mmHg)
; ,
Right atrium

Mean 0–5 ( ) (Fig. 237-2). H -
a wave 1–7
v wave 1–7
Right ventricle -
Peak systolic/end diastolic 17–32/1–7 .T
Pulmonary artery -
Peak systolic/end diastolic 17–32/1–7 ;
Mean 9–19
,
Pulmonary capillary wedge (mean) 4–12
.H
Le t atrium
B -B : -
Mean 4–12 , – -
a wave 4–15 .
v wave 4–15 T .
Le t ventricle R ( )
Peak systolic/end diastolic 90–130/5–12 “ ” .I -
Aorta , -
Peak systolic/end diastolic 90–130/60–85 , v (
Mean 70–100 ). S
-
(Resistances [dyn-s]/cm5)
,
Systemic vascular resistance 900–1400 - .
Pulmonary vascular resistance 40–120 H
Oxygen Consumption Index ([L-min]/m2) 115–140 , , -
Arteriovenous oxygen di erence (vol %) 3.5–4.8 (Table 237-3). I ,
Cardiac index ([L-min]/m2) 2.8–4.2 “ ” ,
, -
.I ,
“ ” , -
; .A
Fig. 237-1. I , “ ,”
“ ” ; -
, ;
, (
“ .” T
) .T
.R -
ECG -
( >60 H ),
50
>5 H (
), -
RA RV PA PCWP
( ).
Cardiac Output C
25 F -
. T , F
-
, F -
-
. T F
0
mmHg
FIGURE 237-1 Normal hemodynamic wave orms recorded during right heart catheterization. Atrial pressure (
tracings have a characteristic “a” wave that refects atrial contraction and a “v” wave that refects pressure )
changes in the atrium during ventricular systole. Ventricular pressure tracings have a low-pressure diastolic lling
period and a sharp rise in pressure that occurs during ventricular systole. d, diastole; PA, pulmonary artery; ( ) -
PCWP, pulmonary capillary wedge pressure; RA, right atrium; RV, right ventricle; s, systole.
1712 ECG Vascular Resistance R -
ECG
O ’
( ). T ,
PART 6
([ −
200 50 ]/ ) 80
−5
W -- .
LV
S , ([
−
Aortic
gradient ]/ ) × 80. P
PCW
, ,
, ,
100 25 ;
Ao
.
Valve Area H
Mitral
LV gradient G
0 0
mmHg mmHg . T
: A = (
FIGURE 237-2 Severe aortic and mitral stenosis. Simultaneous recording o le t ventricular (LV) 3
[ / ]/[ -
and aortic (Ao) pressure tracings demonstrates a 62-mmHg mean systolic gradient (shaded area)
that corresponds to an aortic valve area o 0.6 cm2 (le t). Simultaneous recording o LV and ][ ])/44.3 C ×
pulmonary capillary wedge (PCW) pressure tracings reveals a 14-mmHg mean diastolic gradient , C = 1
2
(shaded area) that is consistent with critical mitral stenosis (mitral valve area = 0.5 cm2). 0.85 . A <1.0
d, diastole; e, end diastole; s, systole. >40 H
2
, <1.5
( - ). >5–10 H - -
T , F : ;
>1.5 2, >15 H ,
C (L/ )=( >60 H , >25 H
[ L/ ])/( - [ L/L]) .
O 125 L / × T H
, - .T
( (L/ ) . A -
[ /100 L] × 1.36 [ L / ] × 10) G -
.T , , ,
. I ,
. M - . I
- - ,
10 L
- . .
TABLE 237-3 Hemodynamic Findings in Tamponade, Constrictive Pericarditis, and Restrictive Cardiomyopathy
EFFUSIVE-CONSTRICTIVE
CARDIAC TAMPONADE CONSTRICTIVE PERICARDITIS PERICARDITIS RESTRICTIVE CARDIOMYOPATHY
Pericardial pressure ↑ ↑ ↑ Normal
Right atrium pressure ↑ ↑ ↑ (Fails to decrease by ↑
50% or to <10 mmHg a ter
pericardiocentesis)
Right atrium pressure Prominent “x” descent Prominent “x” descent Prominent “x” descent Prominent “y” descent
wave orm Diminished or absent “y” Prominent “y” descent “y” descent less prominent
descent than expected
Right ventricle systolic <50 mmHg <50 mmHg <50 mmHg >60 mmHg
pressure
Right ventricle end- >1/3 right ventricular systolic >1/3 right ventricular systolic <1/3 right ventricular systolic
diastolic pressure pressure pressure pressure
Equals le t ventricular end- Equals le t ventricular end-diastolic Equals le t ventricular end- Less than le t ventricular end-
diastolic pressure within pressure within 5 mmHg diastolic pressure within diastolic pressure by ≥5 mmHg
5 mmHg 5 mmHg
Right ventricle Dip and plateau or “square root” sign Dip and plateau or “square Dip and plateau or “square root”
pressure wave orm root” sign sign
Right ventricle–le t Discordant Discordant Discordant Concordant
ventricle systolic
pressure relationship
with inspiration
DIASTOLE SYSTOLE . M 1713
-
1+ ,

-
4+
. V
-
.C
-
.
A -
-
,
.A
-
,
,
1+−4+
.
FIGURE 237-3 Le t ventriculogram at end diastole (left) and end systole (right). In patients with normal le t
ventricular unction, the ventriculogram reveals symmetric contraction o all walls (top). Patients with coronary artery
■ CINEFLUOROSCOPY OF
disease may have wall motion abnormalities on ventriculography as seen in this 60-year-old male ollowing a large PROSTHETIC
anterior myocardial in arction. In systole, the anterior, apical, and in erior walls are akinetic (white arrows) (bottom). MECHANICAL VALVES
P
-
Intracardiac Shunts I , (Fig. 237-4). T -
, , - 0.1–6.0% -
. A , , -
, .P
.A“ ”
- - “ ” - I N R (INR), -
- .T , , , ,
5–7% . T , ,
. C
(Q ) (Q ), Q /Q = ([ , , -
− ]/ - , .
− ). F P en face 90°
, 1.5
.W .E -
, ≥2.0
. .
■ VENTRICULOGRAPHY AND AORTOGRAPHY

V DIASTOLE SYSTOLE
. A -
30–45 L
-
.T *
.N -
; ,
,
(Fig. 237-3). V
FIGURE 237-4 Cine uoroscopic detection o mechanical valve lea et
, , - dys unction. Images o a bileafet mechanical valve in the aortic position taken
during diastole (le t) and systole (right) show that one leafet opens normally
.T during systole while the other leafet (below asterisk) remains immobile and xed
consistent with valve leafet thrombosis.
1714 CORONARY ANGIOGRAPHY
S
.S
PART 6
A
.H
“ ”
( ). B - B
- C
, D
.
T -
, , ,
— , ,
(Fig. 237-5). W -
, ,
, ; A B C D
~85% .W
~5% , -
.T ~10%
.I ,
; FIGURE 237-6 Coronary stenoses on cine angiogram and intravascular
.C 1–2% , ultrasound. Signi cant stenoses in the coronary artery are seen as narrowings
(black arrows) o the vessel. Intravascular ultrasound shows a normal segment
o artery (A), areas with eccentric plaque (B, C), and near total obliteration o
(0.41%). the lumen at the site o the signi cant stenosis (D). Note that the intravascular
C - ultrasound catheter is present in the images as a black circle.
. T
(TIMI) ,
“ ”; >50% , -
(Fig. 237-6). O ,
TIMI 1( ) 2( )
.T .
,
, ; ■ INTRAVASCULAR ULTRASOUND, OPTICAL
COHERENCE TOMOGRAPHY, AND FRACTIONAL FLOW
- RESERVE
.T D , (40–70%), -
“ ” ,
.C ’ .I ,
.C (IVUS)
-
. T (F . 237-6). IVUS
LAD
D
RCA
LCx LM LAD
OM
PDA
A B C
FIGURE 237-5 Normal coronary artery anatomy. A. Coronary angiogram showing the le t circumfex (LCx) artery and its obtuse marginal (OM) branches. The le t
anterior descending (LAD) artery is also seen but may be oreshortened in this view. B. The LAD and its diagonal (D) branches are best seen in cranial views. In this
angiogram, the le t main (LM) coronary artery is also seen. C. The right coronary artery (RCA) gives o the posterior descending artery (PDA), so this is a right dominant
circulation.
Fibrous Lipid plaque Thrombus Stent 1715

A B C D E
FIGURE 237-7 Optical coherence tomography imaging. A. The optical coherence tomography (OCT) catheter (*) in the lumen o a coronary artery with limited
neointima ormation. The intima is seen with high de nition, but unlike intravascular ultrasound imaging, the vessel media and adventitia are not well visualized. B. A
brous plaque (arrow) is characterized by a bright signal. C. A large, eccentric, lipid-rich plaque obscures part o the vessel lumen. Because lipid in the plaque absorbs
light, the lipid-rich plaque appears as a dark area with irregular borders (arrow). The plaque is covered by a thin brous cap (arrowhead) typical o a vulnerable plaque.
D. A thrombus (arrow) adherent to a ruptured plaque that is protruding into the vessel lumen. E. A coronary stent is that is well opposed to the vessel wall. The stent
struts appear as short bright lines with dropout behind the struts (arrow).
40- H .S
.D IVUS .
, -
, ; - ■ POSTPROCEDURE CARE
O , .
.O (OCT) I , -
- -
IVUS (12–18 / , , .
150–200 ); , . T ( 6
T OCT IVUS 2–4 ) ,
( , )
, , - .W - ,
(Fig. 237-7). 2 .W
M ,
- -
.T ,
,
- .O -
.F ,
– - ,
(Fig. 237-8). A .H -
<0.80
.U , .P >2 G
FIGURE 237-8. Fractional ow reserve. The ractional fow reserve is measured using a coronary pressure-sensor guidewire that measures the ratio o the pressure in
the coronary artery distal to the stenosis (Pd, green) divided by the pressure in the artery proximal to the stenosis (Pa, red) at maximal hyperemia ollowing the injection
o adenosine. A ractional fow reserve o <0.80 indicates that revascularization would be bene cial.
1716 .F P ECG (see Fig. 235-2). T
(>5 G ), - 1
. AV. T AVN
PR ECG. T AVN -
■ FURTHER READING .
PART 6
Bashore TM : 2012 A C C F / T AVN

S C A I H -P , H ,
, P , -
:A A C C F .I ,
T F E C - - -
S T S S V P ,
M .JA C C 59:2221, 2012. QRS (see Fig. 235-2). R
Berr C :F -
:R - .T
.E H J 36:3155, 2015.
Bezerra HG : I : A ,
. JACC C I 2:1035, 2009. T QRS .
Lim MJ ( ): Hemodynamic Rounds: Interpretation of Cardiac Patho- T
physiology from Pressure Waveform Analysis, 3 . H , J
W S , 2009. ECG QT (see Fig. 235-2).
Maehara A :A :C .C - C -
I 2:482, 2009. (200–400 )
Moscucci M ( ): Grossman & Baim’s Cardiac Catheterization, Angiog- (1–5 ). T
raphy, and Intervention, 8 .P ,L W & - -
W , 2014. (Fig. 238-1A). T -
( ),
( , ), -
Section 3 Disorders of Rhythm ( ).
A .T
238 Principles of
Electrophysiology
.F ,
,
David D. Spragg, Gordon F. Tomaselli (F . 238-1A).

I , -
,
■ HISTORY AND INTRODUCTION , (
T - G – ),
(ECG) E (Fig. 238-2). O
.S - .I
ECG
.I 1960 , .
, ,H T
, - ( . ., -
+ 2+
.A (RF) N C ) electrogenic
1990 .
. T
T - .S
, , - .F , , -
.T ( . ., K )
- ( . ., N C ). S ,
, , -
, , ,
.O ( . ., N P ). T , -
, (
- . ) : -
I , (S4), ,
, ,
.F ,
. - (α )
( . ., β ) (F . 238-2).
■ DESCRIPTIVE PHYSIOLOGY N C
T ;
(SA) K ,
(see Fig. 235-1). T (Fig. 238-1B).
, T plateau phase ,
(AVN),
Ventricular AP 1717
Atrial AP
Current GENE (Protein)
1
Depolarizing
INa SCN5A (Nav1.5) INa
CHAPTER 238 Principles of Electrophysiology

2
ICa-L CACNA1C (Cav1.2) ICa-L
0
INCX SLC8A1 (NCX1.1) 3
2 4
voltage voltage
1 3
0 time time
4 K+ K+
K+ outward
IK1 KCNJ2 (Kir2.1) IK1

Repolarizing
inward
Ito Ito Ca2+

KCND3/KCNIP2 (Kv4.3/KChIP2)
IKr KCNH2/KCNE2 (HERG/MiRP-1) IKr

IKs IKs Na +
KCNQ1/KCNE1 (KVLQT1/minK)
KCNA5 (Kv1.5) IKur
A B
FIGURE 238-1 A. Cellular atrial and ventricular action potentials. Phases 0–4 are the rapid upstroke, early repolarization, plateau, late repolarization, and diastole,
respectively. The ionic currents and their respective genes are shown above and below the action potentials. The major currents that underlie the action potentials vary
in atrial and ventricular myocytes. B. A ventricular action potential with a schematic o the ionic currents fowing during the phases o the action potential. Potassium
current (IK1) is the principal current during phase 4 and determines the resting membrane potential o the myocyte. Sodium current generates the upstroke o the
action potential (phase 0); activation o Ito with inactivation o the Na current inscribes early repolarization (phase 1). The plateau (phase 2) is generated by a balance
o repolarizing potassium currents and depolarizing calcium current. Inactivation o the calcium current with persistent activation o potassium currents (predominantly
IKr and IKs) causes phase 3 repolarization.
.M - , G βγ
(IKAC ) .T K+
QT - ,
,B , , 4 . C ,
, .
, α- β- .T
■ MECHANISMS OF CARDIAC ARRHYTHMIAS β1- ,
C L- C (IC -L) I,
, , .B 4. E
SA SA ,
, >200 / .B ,
, AVN, - P , -
H -P .T >120 / .
, ( - N
, , ), .H
( N , K-ATP , -
, 3 4 4 .T
), ( -
). A - .M
,
(Table 238-1). .A [K+] ,
,
Alterations in Impulse Initiation: Automaticity S - .
( 4) N
SA -
(AV) , H -P , , - .S
+
.P 4 N ([N +] ), N +
+ 2+ N , K-ATP -
, K ,C , -
N , K-ATP , N -C , - , 4 .A
, (I ); , , [N +] , N , K-ATP , -
. -
T 4 , , .O - -
.P - , , .
4 .T - A (entrance
block)
- .
1718 K channels ,
N .
α Subunits β Subunits
Afterdepolarizations and Triggered Automaticity
T
(Fig. 238-3). A
PART 6
( -
C , EAD ) ( , DAD )
N
.
C T DAD -
2+
C -
.D , ,
2+
X4 C DAD . A
Extracellular N +
K+
2+
C DAD
N .C
, “ ”
.
EAD
.T , EAD
-
,
-
EAD . C
.T , , L- C
, -
Intracellular EAD . I
2+
DAD . T [C ], EAD ,
DAD
Pore Na channels ( . ., [CHF])
N
segments N , –
.
EAD- . I ,
+ + + +
EAD
β1 + + + + β2
.I ,
+ + + +
EAD QT .
H , , , , ,
C C EAD ,
P
N P C
PP Inactivation LA .A
P
P binding IA III ( ) QT -
.
N , ,
Ca channels
EAD- . D
α2 [K+] ( -
S
, IK ) ,
δ
γ α1 S
EAD . I ,
QT (LQTS) - QT
QT .
β EAD-
,
FIGURE 238-2 Topology and subunit composition o the voltage-dependent ion , LQTS.
channels. Potassium channels are ormed by the tetramerization o α or pore- S , ,
orming subunits and one or more β subunits; only single β subunits are shown ( - -
or clarity. Sodium and calcium channels are composed o α subunits with our
homologous domains and one or more ancillary subunits. In all channel types,
) -
the loop o protein between the th and sixth membrane-spanning repeat in each .T
subunit or domain orms the ion-selective pore. In the case o the sodium channel,
the channel is a target or phosphorylation, the linker between the third and ourth .
homologous domain is critical to inactivation, and the sixth membrane-spanning
repeat in the ourth domain is important in local anesthetic antiarrhythmic drug Abnormal Impulse Conduction: Reentry T
binding. The Ca channel is a multisubunit protein complex with the α1 subunit
containing the pore and major drug binding domain.
. T
A , -
, , - (Fig. 238-4). R
.I ( . ., ),
TABLE 238-1 Arrhythmia Mechanisms 1719
ELECTROPHYSIOLOGIC
PROPERTY MOLECULAR COMPONENTS MECHANISM PROTOTYPIC ARRHYTHMIAS

Cellular
Impulse Initiation
Automaticity I , I Ca-L, I Ca-T, IK, IK1 Suppression/acceleration o phase 4 Sinus bradycardia, sinus tachycardia
Triggered automaticity Calcium overload, ITI DADs Digitalis toxicity, reper usion VT
ICa-L, IK, INa EADs Torsades des pointes, congenital and acquired
Excitation INa Suppression o phase 0 Ischemic VF
IK-ATP AP shortening, inexcitability
ICa-L Suppression AV block
Repolarization INa, ICa-L, IK, IK1, Ca2+ homeostasis AP prolongation, EADs, DADs Polymorphic VT (HF, LVH)
ICa-L, K channels, Ca2+ homeostasis AP shortening Atrial ibrillation
Multicellular
Cellular Coupling Connexins (Cx43), INa, IK-ATP Decreased coupling Ischemic VT/VF
Tissue Structure Extracellular matrix, collagen Excitable gap and unctional reentry Monomorphic VT, atrial ibrillation
Abbreviations: AP, action potential; AV, atrioventricular; DADs, delayed a terdepolarizations; EADs, early a terdepolarizations; HF, heart ailure; LVH, le t ventricular
hypertrophy; VF, ventricular ibrillation; VT, ventricular tachyarrhythmia.
.T , ,
anatomic reentry excitable gap reentry ( ), .T -
,
.C - ,
, , .
- C - -
.S -
,
(λ = × ) .F ,
, (C III) -
.W λ - λ
, - .C -
.A , ( . .,
- ,
, AV , , ). D
, . ,
R ( . .,
) .
. I , S
.
; leading circle reentry, C
( ( 43)
). U , . T
, , , -
. .
F , T ,
A B C D
Slow
0 mV Block Gap
EAD
Reactivation
of L-type Ca
current DAD
50 mV
Reentrant Initiation of Sustained Termination of

circuit reentry reentry reentry
Intracellular
Ca2+ overload FIGURE 238-4 Schematic diagram o reentry. A. The circuit contains two limbs,
one with slow conduction. B. A premature impulse blocks in the ast pathway
0.5 s and conducts over the slow pathway, allowing the ast pathway to recover so
FIGURE 238-3 Schematic action potentials with early a terdepolarizations that the activation wave can reenter the ast pathway rom the retrograde
(EADs) and delayed a terdepolarizations (DADs). A terdepolarizations are direction. C. During sustained reentry utilizing such a circuit, a gap (excitable gap)
spontaneous depolarizations in cardiac myocytes. EADs occur be ore the end exists between the activating head o the wave and the recovering tail. D. One
o the action potential (phases 2 and 3), interrupting repolarization. DADs occur mechanism o termination o reentry occurs when the conduction and recovery
during phase 4 o the action potential a ter completion o repolarization. The characteristics o the circuit change and the activating head o the wave collides
cellular mechanisms o EADs and DADs di er (see text). with the tail, extinguishing the tachycardia.
1720 , -
.
(CAD). A - V , ,
, - ,
, ,
PART 6
. . S
, AV
E ’ .E
APPROACH TO THE PATIENT
Cardiac Arrhythmias . I ,
,
T
; , — ,
ECG— . .
P H - (HUT)
ECG
.I , - . T
, HUT ; , -
.L
.E
, - .T HUT
,
- .O
.T - HUT
. HUT
. ,
T ,
.I
. T , HUT
, , , ( . ., , -
.I , , , ) . HUT
,
.I , , ,
. .I , HUT
T CAD
, , ,
ECG, ,
. U ( . ., ).
E
ECG, W -P -W . I , ,
(WPW) , QT , , -
ST- B , .T
. : ;
V ECG - ;
.H - ( . .,
, , , ). T
ECG ,
.H - ( ) ,
, .A
- -
( . ., ). -
A .
( . ., -
), , -
,
. I - TREATMENT
.I -
Cardiac Arrhythmias
ANTIARRHYTHMIC DRUG THERAPY
T
.A
, .
E
; ,
.C , -
QT
.T
.
ECG
T -
.C
: ;
TABLE 238-2 Antiarrhythmic Drug Actions 1721
CLASS ACTIONS +
MISCELLANEOUS N ; I ( , )
DRUG I II III IV ACTION ;

Quinidine ++ ++ α-Adrenergic I ( , )
blockade ; I ( , )
Procainamide ++ ++ Ganglionic .T
blockade V -W
Flecainide +++ + , -
Propa enone ++ + ,
Ranolazine ++ ++ Late Na + current .
blockade CATHETER ABLATION
Eleclazine ++ Late Na + current T
blockade
Sotalol ++ +++ .
Do etilide +++ D
Amiodarone ++ ++ +++ + α-Adrenergic .T RF -
blockade .T DC
Dronedarone ++ + +++ ++ HCN4 blockade 1980 S .B
Ibutilide +++ Na+ channel 1990 , RF -
activator (Fig. 238-5).
T RF (300–30,000 H )
, -
- .E
, ; ,
;
.B . A ,
, -
.S (915 MH 2450 MH ), , ,
1970 V -W - ( ). O ,
S H .T ,
+
I, N ; AVN. A 32°C, -
II, β- , ,
; III, K+ - , -
; IV, ( )—
(Table 238-2). C I .T
A
FIGURE 238-5 Catheter ablation o cardiac arrhythmias. A. A schematic o the catheter system and generator in a patient undergoing radio requency catheter ablation
(RFCA); the circuit involves the catheter in the heart and a dispersive patch placed on the body sur ace (usually the back). The inset shows a diagram o the heart with
a catheter located at the AV valve ring or ablation o an accessory pathway. B. A right anterior oblique fuoroscopic image o the catheter position or ablation o a
le t-sided accessory pathway. A catheter is placed in the atrial side o the mitral valve ring (abl) via a transseptal puncture. Other catheters are placed in the coronary
sinus (CS), in the right atrium (RA), and in the right ventricular (RV) apex to record local electrical activation. C. Body sur ace electrocardiogram recordings (I, II, V1) and
endocardial electrograms (HRA, high right atrium; HISp, proximal His bundle electrogram; CS 7, 8, recordings rom poles 7 and 8 o a decapolar catheter placed in the
coronary sinus) during RFCA o a le t-sided accessory pathway in a patient with Wol -Parkinson-White syndrome. The QRS narrows at the ourth complex; the arrow
shows the His bundle electrogram, which becomes apparent with elimination o ventricular preexcitation over the accessory pathway.
1722
PART 6
FIGURE 238-5 (Continued)
.C
,
WPW
AVN
,
AV
239 The Bradyarrhythmias:
Disorders of the
.A
, ,
Sinoatrial Node
. David D. Spragg, Gordon F. Tomaselli
DEVICE THERAPY
B E
AV - (SA) , .O
.C (AV) , ,
SA
.T ,
Chaps. 239 and 240. , ,
V , .
- S -
, .
A Chap. 238,
. I , .T
- (ICD)
.I CHF - (Fig. 239-1). T
, ICD,
, - . E
. I ( 4), -
CHF, .
.T T ( 0)
ICD ,
. .C SA AV
■ FURTHER READING .C SA
Josephson ME: Clinical Cardiac Electrophysiology: Techniques and Inter- 4
pretations, 5 .P ,W K , 2016. .
Priori SG, Napolitano C: G B
, Hurst’s The Heart, 13 ,VF ( ). N . F
Y ,M G -H , 2011. 4
Saksena S, Camm AJ ( ): Electrophysiological Disorders of the Heart, (Fig. 239-2),
2 .P ,E C L , 2012. .P , -
Zipes DP, Jalife J ( ): Cardiac Electrophysiology: From Cell to Bedside, 4
6 .P ,E , 2014. (SA ) .F
.C -
( . ., )
.
SA AV -
. SA
,
120 (IN ) L- 1723
ECa + 120 mV
(IC -L); 4 -
ENa + 70 mV
Voltage, mV
1
.P ,
2 L- T- (IC -T) ,
CHAPTER 239 The Bradyarrhythmias: Disorders of the Sinoatrial Node

0 mV
( - , I) -
0 0 - - ,
ECI –30 mV
3 - -
4
–100 EK –90 mV (IK ) - (IKAC ) .
Ventricular Atrial Nodal 200 ms
IC -L, IC -T, I β-
FIGURE 239-1 Action potential profles recorded in cells isolated rom sinoatrial or IKAC ,
atrioventricular nodal tissue compared with those o cells rom atrial or ventricular myocardium. -
Nodal cell action potentials exhibit more depolarized resting membrane potentials, slower phase
.T SA
0 upstrokes, and phase 4 diastolic depolarization.
IN -
,
. SA .
T
, , . ,
P .
, , , (Table 239-1). ■ ETIOLOGY OF SA NODAL DISEASE

A 50% 160,000 SA .T
U S 20–30% E -
SA .
(T 239-1). T SA
■ STRUCTURE AND PHYSIOLOGY OF THE SA NODE
T SA - / .O
– , ,
, SA . , ,
T SA ,
TABLE 239-1 Etiologies of SA Node Dysfunction
, , EXTRINSIC INTRINSIC
, T- .C Autonomic Sick-sinus syndrome (SSS)
SA
Carotid sinus hypersensitivity Coronary artery disease (chronic and
.T SA acute MI)
Vasovagal (cardioinhibitory)
55–60% 40–45% .T SA stimulation In lammatory
Drugs Pericarditis
.
Beta blockers Myocarditis (including viral)
I SA
Calcium channel blockers Rheumatic heart disease
SA .T SA - Digoxin Collagen vascular diseases
(F . 239-1) Ivabradine Lyme disease
−40 −60 V, 0 , 4 - Antiarrhythmics (class I and III) Senile amyloidosis
Adenosine Congenital heart disease
.T Clonidine (other sympatholytics) TGA/Mustard and Fontan repairs
(IK1) ; Lithium carbonate Iatrogenic
0 Cimetidine Radiation therapy
Amitriptyline Postsurgical
Control Acetylcholine Phenothiazines Chest trauma
0 mV Narcotics (methadone) Familial
Pentamidine SSS2, AD, OMIM #163800
Hypothyroidism (15q24-25)
Sleep apnea SSS1, AR OMIM #608567 (3p21)
Hypoxia SSS3, AD, OMIM #614090
Phase 4 (14q11.2)
Endotracheal suctioning (vagal
maneuvers) SA node disease with myopia,
–50 mV
OMIM #182190
Hypothermia
Kearns-Sayre syndrome, OMIM
Increased intracranial pressure
#530000
ΙCa-T, Ι F, ΙCa-L
Depolarizing currents Myotonic dystrophy
Repolarizing currents ΙK , Ι K1, Ι K ACh Type 1, OMIM #160900
(19q13.2-13.3)
FIGURE 239-2 Schematics o nodal action potentials and the currents that Type 2, OMIM #602668
contribute to phase 4 depolarization. Relative increases in depolarizing L- (ICa-L) (3q13.3-q24)
and T- (ICa-T) type calcium and pacemaker currents (I ) along with a reduction in
repolarizing inward recti er (IK1) and delayed recti er (IK) potassium currents Friedreich’s ataxia, OMIM #229300
result in depolarization. Activation o ACh-gated (I KACh) potassium current and beta (9q13, 9p23-p11)
blockade slow the rate o phase 4 and decrease the pacing rate. (Modifed rom Abbreviations: AD, autosomal dominant; AR, autosomal recessive; MI, myocardial
J Jali e et al: Basic Cardiac Electrophysiology or the Clinician, Blackwell Publishing, in arction; OMIM, Online Mendelian Inheritance in Man (database); TGA,
1999.) transposition o the great arteries.
1724 (C ’ ), - , those at greatest risk,
. ≥65 , -
I - , , ,
SA .U -
.A SA AV ,
PART 6
(CAD) SA , -
(MI; ), AV .
. I SA T SA
, .P , .
, S SA ,
SA , , .
C (SLE), - .T
(RA), (MCTD ) .
SA .S
; ■ ELECTROCARDIOGRAPHY OF SA NODE DISEASE
SA T SA
.S SA , , , ,
SA . ( SSS), .I -
R , .
.A B , SA
<60 / ;
( . ., - - [SSS2]) .R <60 /
(I ) .A
HCN4 15. A SSS1 <40 / -
P .S
(ECG) SA ,
, SCN5A, 3. V P ECG (Fig. 239-3). S
6 (MYH6) SSS (SSS3). SA 3 ,
.I -
.T , SA .
K -S ( , T
, ) - AV (Chap. 240). P
SA . ECG; - SA
SSS SA
SA .T SSS .
, CAD, , , T I - SA -
. SA
■ CLINICAL FEATURES OF SA NODE DISEASE .S - SA ECG -

SA P (Fig. 239-4). I II - SA
ECG ; ; , SA .
, , C - SA P ECG.
.S SA , T -
- , .A ,
.F , , ,
, , , .C
, , , , -
.I SSS, SA .
.I , SA - ■ DIAGNOSTIC TESTING
.A SA -
SSS . S ECG
. SA , -
O - -
SA -
, -
. T II II
SA
, ,
, , - V V
, .
R ,
-
-
FIGURE 239-3 Sinus slowing and pauses on the electrocardiogram (ECG). The ECG is recorded during sleep in
, a young patient without heart disease. The heart rate be ore the pause is slow, and the PR interval is prolonged,
.P consistent with an increase in vagal tone. The P waves have a morphology consistent with sinus rhythm. The
- SSS, recording is rom a two-lead telemetry system in which the tracing labeled II mimics rontal lead II and V represents
, Modi ed Central Lead 1, which mimics lead V 1 o the standard 12-lead ECG.
1725
SAN EG
CHAPTER 239 The Bradyarrhythmias: Disorders of the Sinoatrial Node

VI
FIGURE 239-4 Mobitz type I SA nodal exit block. A theoretical SA node electrogram (SAN EG) is shown. Note that there is grouped beating producing a regularly
irregular heart rhythm. The SA node EG rate is constant with progressive delay in exit rom the node and activation o the atria, inscribing the P wave. This produces
subtly decreasing P-P intervals be ore the pause, and the pause is less than twice the cycle length o the last sinus interval.
.S , -
SA
SA . .C -
E .S SA
SA .D ; , , SNRT
ECG, - H SA .I -
. IV . T
M
ECG . - -
I ECG - (12–18 ) , -
. , ,
F .C ,
chronotropic incompetence. T SA .I
85% <50 >30 / H
>100 / , - -
- .E -
.
. I ,
A . S
; >3 MI
.D
(IHR) SA .I SA
.T IHR
0.2 / 0.04 / , , SA
117.2 − (0.53 × ) / ; IHR SA . .
E S -
SA
, .I . C
,
, -
AV .T SA . S
.T (SNRT), -
, .A -
SA ( : <1500 ,
, <550 ), (SACT), ,
- - .
( <125 ). T SNRT, PERMANENT PACEMAKERS

SACT, IHR Nomenclature and Complications T -
SA . SA . S
1950 ,
,
TREATMENT , , -
Sinoatrial Node Dysfunction .T ,
.
S SA - P - .
, .E - T () (O, ; A,
SA ; V, ; D, ; S, ), ()
(O, ; A, ; V, ; D, ;
. P S, ), (O, ; I,
SA . ; T, ; D, + ),
P (R, ),
SA .A -
SA (O, ; P, ; S, ; D, + ).
(T 239-1). B A
SNRT SA ,
I III SA .I : , , QT .T
1726 - - TABLE 239-2 Summary of Guidelines for Pacemaker Implantation in
VVIR DDDR, , SA Node Dysfunction
. Class I
A ,
1. SA node dys unction with symptomatic bradycardia or sinus pause
PART 6
2. Symptomatic SA node dys unction as a result o essential long-term drug

. I , therapy with no acceptable alternatives
–
3. Symptomatic chronotropic incompetence
.R , , -
4. Atrial ibrillation with bradycardia and pauses >5 s
,
, , , / Class IIa
, . L 1. SA node dys unction with heart rates <40 beats/min without a clear and
, , , consistent relationship between bradycardia and symptoms
2. SA node dys unction with heart rates <40 beats/min on an essential long-
’ . term drug therapy with no acceptable alternatives, without a clear and
R consistent relationship between bradycardia and symptoms
, , 3. Syncope o unknown origin when major abnormalities o SA node
dys unction are discovered or provoked by electrophysiologic testing
“ ’ ,”
. Class IIb
T 1. Mildly symptomatic patients with waking chronic heart rates <40 beats/min
. T Class III
“A ” . E 1. SA node dys unction in asymptomatic patients, even those with heart rates
<40 beats/min
2. SA node dys unction in which symptoms suggestive o bradycardia are not
. T “ ” - associated with a slow heart rate
3. SA node dys unction with symptomatic bradycardia due to nonessential
( ) (see Chap. 240). drug therapy
C Source: Data rom AE Epstein et al: J Am Coll Cardiol 51:e1, 2008 and CM
AV / - Tracy et al: J Am Coll Cardiol 61:e6, 2013.
.P AV
,
,
, , , , , - (Table 239-2).
, , , , T
A , , , SA .A , -
, .R .T
, AV -
, - - SA -
, .I ,
.M AV AV .
.S I - -
- - ,
( ) AV
- - .P AV
.
.B
Pacemaker Therapy in SA Node Dysfunction P SA AV , SA -
. C - - .
A H A Pacemaker Therapy in Carotid Sinus Hypersensitivity and Vaso-
(AHA)/A C C /H R S vagal Syncope C ,
(ACC/HRS) , .
.C I - I ,
- .T -
.I II ,
; II , - -
; II , - .S
. -
I III , ,
.
C I SA .A -
, – , , ,
- ,
.C II .
SA - ■ FURTHER READING
.M Epstein AE : ACC/AHA/HRS 2008 G D -B
<40 / II .P T C R A :A A
SA C C /A H A T F
P G ( C R ACC/AHA/ , 1727
NASPE 2002 G U I C P - - .
A D ) S , , -
A A T S S T AV .T AV (~1 × 3 × 5 )
CHAPTER 240 The Bradyarrhythmias: Disorders of the Atrioventricular Node

S .JA C C 51: , 2008. K ,
Epstein AE : ACC/AHA/NASPE 2008 G - ,
.JA C C , T .T AV
51:21, 2008. AV
Epstein AE : 2012 ACCF/AHA/HRS F U I - , ,
ACCF/AHA/HRS 2008 G D -B ; ,
T C R A :A A .T AV
C C F /A H A T
F P G H R S -
A A T H . T (RBB) AV
S S T S . JA C C ( ). I
61: 6, 2013. , (LBB)
Goldschlager N :S , Electrophysiological .T P
Disorders of the Heart, 2 ,SS , AJ C ( ). P , RBB LBB
E C L , 2012. , .
Josephson ME: Clinical Cardiac Electrophysiology: Techniques and Inter- T AV AV
pretations, 5 .P ,W K , 2016. -
Vijayaraman P, Ellenbogen KA: B , .T
Hurst’s The Heart, 13 ,VF ( ). N Y , M G -
H , 2011. .T AV
-
.T H
.
T AV
240 The Bradyarrhythmias:
Disorders of the
.I
(see Fig. 239-1). A

,
Atrioventricular Node decremental conduction,

.F
David D. Spragg, Gordon F. Tomaselli AV ,
-
AV
I (SA) .M
- ( ~–60 V)
(AV) .A Chap. 239, , 0 (<10 V/ ),
4 ; - ; -
.C AV - [K+]. T
. AV
, (IK1) -
4 , 0 ( - (IN ); L- (IC -L) 0;
) 4 -
( ). — (I ), IC -L, T- (IC -T),
B AV (INCX)—
, , — (IK ) - (IKAC ) -
, , , ( .E AV -
) .I -
AV , SA ( -40) .
, T H -
. T AV .T
. T
10% .A ( 0), ( 2),
AV ( 4 ). G , -
, 200 -40, ,
.I , , .
, , AV
. ■ ETIOLOGY OF AV CONDUCTION DISEASE
A SA - C
, , AV
AV .A 50% 160,000 .T
U S 70–80% , SA
E AV . .T
AV
■ STRUCTURE AND PHYSIOLOGY OF THE AV NODE AV . Table 240-1
T AV , AV . T ( , -
AV .U SA , AV / , - ) .M
1728 TABLE 240-1 Etiologies of Atrioventricular Block I
Autonomic
AV .A
-
Carotid sinus hypersensitivity Vasovagal
, ,
Metabolic/Endocrine “ .” T
PART 6
Hyperkalemia Hypothyroidism
Hypermagnesemia Adrenal insu iciency , , .A
Drug-Related
(SCN5A)
Beta blockers Adenosine
1 19.
Calcium channel blockers Antiarrhythmics (class I and III)

AV -
Digitalis Lithium , ,
In ectious K -S (Chap. 441),
Endocarditis Tuberculosis .C AV
Lyme disease Diphtheria (Chap. 264),
Chagas’ disease Toxoplasmosis ,
Syphilis (ASD ), (VSD ),
, - .C AV
Heritable/Congenital
Congenital heart disease Facioscapulohumeral MD, OMIM SLE. I AV
Maternal SLE #158900 (4q35)
, ,
Kearns-Sayre syndrome, OMIM Emery-Drei uss MD, OMIM #310300 . AV -
#530000 (Xq28)
VSD ASD
Myotonic dystrophy Progressive amilial heart block, type
.
IA OMIM #113900 (3p21)
Type 1, OMIM #160900 C AV
(19q13.2-13.3) Progressive amilial heart block, type
IB, OMIM #604559 (19q13.32) .I , ,
Type 2, OMIM #602668 , AV .
(3q13.3-q24) Progressive amilial heart block, type
II, OMIM %140400 (1q32) I (MI), AV
10–25% ; , - - AV
In ammatory
, (CHB) .S -
SLE MCTD - AV
Rheumatoid arthritis Scleroderma MI; , MI
Infltrative AV , .I
Amyloidosis Hemochromatosis , MI AV
Sarcoidosis ,H ,
,
Neoplastic/Traumatic
.
Lymphoma Radiation
Mesothelioma Catheter ablation ■ ELECTROCARDIOGRAPHY AND
Melanoma ELECTROPHYSIOLOGY OF AV CONDUCTION BLOCK
Degenerative AV ,
Lev’s disease Lenègre’s disease
. AV -
Coronary Artery Disease
Acute MI , , -
Abbreviations: MCTD, mixed connective tissue disease; MI, myocardial in arction; .F - AV (PR >200 ) -
OMIM, Online Mendelian Inheritance in Man (database; designations: AV (Fig. 240-1). T
#, phenotypic description, molecular basis known; %, phenotypic description);
SLE, systemic lupus erythematosus. AV , H , H -P
.A QRS -
, QRS AV ,
, , , H .I - AV
AV .H
- .S - AV M I
AV .C , (W ) M II. T
, M I PR
SA AV .T , RR ,
RR
AV . (ECG). T ECG PR
S (Fig. 240-2). T ECG -
.L 50% ; 10%
L AV , AV .
. I I II - AV
C ’ , L A , -
AV .S - .T II - AV
AV , P
(SLE), , PR RR .W AV 2:1, -
, , ( I II . T II - AV
), , ; -H ,
AV . ( . .,
1729
I 200 ms

II
V1
V6
137 msec
HIS A V A V
H H
RV
FIGURE 240-1 First-degree AV block with slowing o conduction in the AV node as indicated by the prolonged atrial-to-His bundle electrogram (AH) interval, in this
case 157 ms. The His bundle-to-earliest ventricular activation on the sur ace ECG (HV) interval is normal. The normal HV interval suggests normal conduction below
the AV node to the ventricle. I and V1 are sur ace ECG leads, and HIS is the recording o the endocavitary electrogram at the His bundle position. A, H, and V are labels
or the atrial, His bundle, and right ventricular electrograms, respectively.
), AV AV
I - AV .S - AV ( -
II) P , .C ,
paroxysmal AV block (Fig. 240-3), , ,
. AV .I
C CHB QRS , ;
- AV . AV , CHB, QRS,
- .
AV , CHB, AV A , -
.I , AV , , -
QRS AV .T
.I , -
QRS (Fig. 240-4B) H .E -
; , QRS
AV H AV AV
AV (Fig. 240-4A). N QRS .R
QRS H
AV .
AV .A
■ DIAGNOSTIC TESTING H , H ,
D AV ;
, , , , AV
, (F . 240-1).
AV .V , , , T
H H (AH interval)
.O AV <130 .T
AV , H QRS
II
A 1 sec
AV 0.32 0.30 0.53 0.40
V
FIGURE 240-2 Mobitz type I second-degree AV block. The PR interval prolongs be ore the pause, as shown in the ladder diagram. The ECG pattern results rom slowing
o conduction in the AV node.
1730
II
PART 6
V1
III
FIGURE 240-3 Paroxysmal AV block. Multiple nonconducted P waves a ter a period o sinus bradycardia with a normal PR interval. This implies signi cant conduction
system disease, requiring permanent pacemaker implantation.
ECG (HV interval) H - HV HV -

P ≤55 . >100 , AV
R AV . 10%, .I CHB,
M I - AV , ,
.H , >500 .
(<120 / ) , .
T , I - AV -
AH ,
AV . AH TREATMENT
( , , ) Management of AV Conduction Block
.A ; , AH
AV , - T -
AV .T II - AV .
, H -P . B H , AV
HV H
(Fig. 240-5) .C
.I ,
- AV , AV
2:1 ; , H - .A
. AV .S
I - , -
H -P ( . ., HV .T
) ,
.I ( )
, HV ( ). A ,
,
AV .P HV -
.I
- AV .T ,
P P P P P P P P P P P P
V1
P P P P P P P P P P P P
V1
B
FIGURE 240-4 High-grade AV block. A. Multiple nonconducted P waves with a regular narrow complex QRS escape rhythm probably emanating rom the AV junction.
B. A wide complex QRS escape and a single premature ventricular contraction. In both cases, there is no consistent temporal relationship between the P waves and
QRS complexes.
1731
I

II
III
V1
HRA
HI Sd H H H H H
A H A A A A A
HI Sp
RVA
FIGURE 240-5 High-grade AV block below the His. The AH interval is normal and is not changing be ore the block. Atrial and His bundle electrograms are recorded
consistent with block below the distal AV junction. I, II, III, and V1 are sur ace ECG leads. HISp, HISd, and RVA are the proximal HIS, distal HIS, and right ventricular apical
electrical recordings, respectively. A, H, and V represent the atrial, His, and ventricular electrograms on the His bundle recording, respectively. (Used with permission
rom Dr. Joseph Marine.)
.T , K -
, S .
, .I
, , PACEMAKER THERAPY IN MYOCARDIAL INFARCTION
AV . AV MI ,
PACEMAKERS IN AV CONDUCTION DISEASE .T
T MI - - AV ,
AV , - , - - AV -
AV - AV - (Table 240-3). P
.T AV AV -
(Table 240-2). P - AV
.F MI
- - AV , AV
.S (T 240-3 Table 240-4).
, , PACEMAKER THERAPY IN BIFASCICULAR AND TRIFASCICULAR

.P AV BLOCK
; D AV
CHB, . P -
; ; ,
≤40 / .P - AV ,
. P
- -H
QRS .P - , II - AV
, - .I
AV AV , HV
, H -
AV ( - AV , .P
)
, (T 240-4).
1732 TABLE 240-2 Guideline Summary for Pacemaker Implantation in TABLE 240-4 Indications for Pacemaker Implantation in Chronic
Acquired AV Block Bifascicular and Trifascicular Block
Class I Class I
1. Third-degree or high-grade AV block at any anatomic level associated with: 1. Intermittent third-degree AV block
PART 6
a. Symptomatic bradycardia 2. Type II second-degree AV block

b. Essential drug therapy that produces symptomatic bradycardia 3. Alternating bundle branch block
c. Periods o asystole >3 s or any escape rate <40 beats/min while Class IIa
awake, or an escape rhythm originating below the AV node
1. Syncope not demonstrated to be due to AV block when other likely causes
d. Postoperative AV block not expected to resolve (e.g., ventricular tachycardia) have been excluded
e. Catheter ablation o the AV junction 2. Incidental inding at electrophysiologic study o a markedly prolonged HV
. Neuromuscular diseases such as myotonic dystrophy, Kearns-Sayre interval (>100 ms) in asymptomatic patients
syndrome, Erb dystrophy, and peroneal muscular atrophy, regardless o 3. Incidental inding at electrophysiologic study o pacing-induced in ra-His
the presence o symptoms block that is not physiologic
2. Second-degree AV block with symptomatic bradycardia Class IIb
3. Type II second-degree AV block with a wide QRS complex with or without
1. Neuromuscular diseases such as myotonic dystrophy, Kearns-Sayre
symptoms
syndrome, Erb dystrophy, and peroneal muscular atrophy with any degree
4. Exercise-induced second- or third-degree AV block in the absence o o ascicular block regardless o the presence o symptoms, because there
ischemia may be unpredictable progression o AV conduction disease
5. Atrial ibrillation with bradycardia and pauses >5 s Class III
Class IIa 1. Fascicular block without AV block or symptoms
1. Asymptomatic third-degree AV block regardless o level 2. Fascicular block with irst-degree AV block without symptoms
2. Asymptomatic type II second-degree AV block with a narrow QRS complex
Source: Data rom AE Epstein et al: J Am Coll Cardiol 51:e1, 2008.
3. Asymptomatic type II second-degree AV block with block within or below the
His at electrophysiologic study
4. First- or second-degree AV block with symptoms similar to pacemaker SELECTION OF PACING MODE
syndrome I , AV
Class IIb -
1. AV block in the setting o drug use/toxicity, when the block is expected to - .T
recur even with drug discontinuation ; - ,
2. Neuromuscular diseases such as myotonic dystrophy, Kearns-Sayre , .T -
syndrome, Erb dystrophy, and peroneal muscular atrophy with any degree o
AV block regardless o the presence o symptoms ,
Class III AV . S
1. Asymptomatic irst-degree AV block
2. Asymptomatic type I second-degree AV block at the AV node level AV -(VVI)
3. AV block that is expected to resolve or is unlikely to recur (Lyme disease,
-(DDD) .I
drug toxicity) ,
. I
Source: Data rom AE Epstein et al: J Am Coll Cardiol 51:e1, 2008.
AV ,
-
- .
■ FURTHER READING
TABLE 240-3 Guideline Summary for Pacemaker Implantation in AV Epstein AE : ACC/AHA/HRS 2008 G D -B
Conduction Block in Acute Myocardial Infarction (AMI) T C R A :A A
Class I C C /A H A T F
1. Persistent second-degree AV block in the His-Purkinje system with bilateral P G ( C R ACC/AHA/
bundle branch block or third-degree block within or below the His a ter AMI NASPE 2002 G U I C P -
2. Transient advanced (second- or third-degree) in ranodal AV block and A D )
associated bundle branch block. I the site o block is uncertain, an A A T S S T
electrophysiologic study may be necessary S . JA C C 51: , 2008.
3. Persistent and symptomatic second- or third-degree AV block Epstein AE : 2012 ACCF/AHA/HRS F U I -
Class IIb I ACCF/AHA/HRS 2008 G D -B
1. Persistent second- or third-degree AV block at the AV node level T C R A :A A
C C F /A H A T
Class III
F P G H R S -
1. Transient AV block in the absence o intraventricular conduction de ects A A T
2. Transient AV block in the presence o isolated le t anterior ascicular block S S T S . JA C C
3. Acquired le t anterior ascicular block in the absence o AV block 61: 6, 2013.
4. Persistent irst-degree AV block in the presence o bundle branch block that Goldschlager N :A , Electrophysiological
is old or age-indeterminate Disorders of the Heart, 2 ,SS , AJ C ( ). P ,
Source: Data rom AE Epstein et al: J Am Coll Cardiol 51:e1, 2008. E C L , 2012.
TABLE 241-1 Supraventricular Tachycardia 1733
I. Physiologic sinus tachycardia
241 Approach to Supraventricular
Tachyarrhythmias De ining eature: normal sinus mechanism precipitated by exertion, stress,
concurrent illness (Table 242-1)
CHAPTER 241 Approach to Supraventricular Tachyarrhythmias

II. Pathologic supraventricular tachycardia
Gregory F. Michaud, William G. Stevenson
A. Tachycardias originating rom the atrium
De ining eature: tachycardia may continue despite beats that ail to
conduct to the ventricles, indicating that the AV node is not participating in
S the tachycardia circuit
(AV) 1. Inappropriate sinus tachycardia
.M QRS- (QRS De ining eature: tachycardia rom the normal sinus node area that occurs
<120 ) without an identi iable precipitating actor as a result o dys unctional
P .C autonomic regulation
2. Focal atrial tachycardia (AT)
QRS De ining eature: Regular atrial tachycardia with de ined p wave; may be
(Chap. 249). M sustained, nonsustained, paroxysmal, or incessant. Frequent sites o
origin occur along the valve annuli o le t or right atrium, pulmonary veins,
(Table 241-1). P coronary sinus musculature, superior vena cava
- 3. Atrial flutter—macroreentrant atrial tachycardia
AV ( . ., AV De ining eature: organized reentry creates organized atrial activity,
), ( . ., commonly seen as sawtooth lutter waves at rates typically aster than
200 beats/min
)
(see Figs. 243-3 and 245-1). T a. Common atrial lutter
- i. Right atrial reentry parallel to the tricuspid annulus and
dependent on conduction through the isthmus between the
.
in erior vena cava and tricuspid annulus
S ,
1. Counterclockwise (as viewed rom the ventricular aspect)
nonsustained, ,
2. Clockwise
, .E -
b. Atypical atrial lutter
. Paroxysmal supraventricular tachycardia (PSVT) i. Usually due to reentry in le t or right atrium associated with
AV , AV scars usually rom prior surgery or catheter ablation or atrial
ibrillation, but may be idiopathic
, .
4. Atrial fibrillation
■ CLINICAL PRESENTATION De ining eature: chaotic rapid atrial electrical activity with variable
S ventricular rate; the most common sustained cardiac arrhythmia in older
, , , adults
, , , , 5. Multifocal atrial tachycardia
. R , - De ining eature: multiple discrete p waves o ten seen in patients with
W -P -W - pulmonary disease during acute exacerbations o pulmonary insu iciency
, . B. AV nodal reentry tachycardia (AVNRT)
De ining eature: paroxsymal regular tachycardia with P waves visible
Initial Evaluation D - at the end o the QRS complex or not visible at all; the most common
(ECG) . W paroxysmal sustained tachycardia in healthy young adults; more common
, ECG in women
(Figs. 241-1 241-3 Table 241-2). T C. Tachycardias associated with accessory atrioventricular pathways
.F - 1. Orthodromic AV reentry tachycardia (AVRT)
, ECG .E - De ining eature: paroxysmal sustained tachycardia similar to AV nodal
- .O reentry; during sinus rhythm, evidence o ventricular preexcitation may be
present (Wol -Parkinson-White syndrome) or absent (concealed accessory
, , , . pathway)
P 2. Preexcited tachycardia
. De ining eature: wide QRS tachycardia with QRS morphology similar
O , , to VT
.A a. Antidromic AV reentry—regular paroxysmal tachycardia
.A b. Atrial ibrillation with preexcitation—irregular wide complex, or
. intermittently wide complex tachycardia, some with dangerously rapid
rates aster than 250/min
T
, , c. Atrial tachycardia or lutter with preexcitation
.T - Abbreviations: AV, atrioventricular; VT, ventricular tachycardia.
.
(Chap. 242). T .I .A
, - , , ,
, .
1734
NARROW COMPLEX TACHYCARDIA – OBTAIN FULL
12-LEAD ECG WITH LONG RHYTHM STRIP
Irregular atrial
Regular
and ventricular
atrial rate
rates
PART 6
1:1 AV AV block: more VA block: more Multifocal atrial

Atrial fibrillation
response A’s than V’s V’s than A’s tachycardia
• AVNRT • Atrial • Junctional

•O R T flutter tachycardia
• AT • Atrial
• R arely tachycardia
atrial flutter • R arely
AVNRT with
2:1 block
below the
His bundle
FIGURE 241-1 Diagnostic possibilities based on the appearance o the 12-lead ECG recorded during an episode o SVT. AVNRT, AV nodal reentry tachycardia;
ORT, orthodromic AV reentry tachycardia; AT, ocal atrial tachycardia.
AV NODAL BLOCKADE
AVNRT Orthodromic AV Atrial Atrial flutter
reentry (ORT) tachycardia (AT)
Terminates Terminates Increased AV Increased AV

tachycardia tachycardia block with block with
continuation continuation of
of AT. May atrial flutter
terminate exposes
tachcyardia underlying
flutter waves
FIGURE 241-2 Diagnostic e ect o increasing AV node blockade with vagal maneuvers, adenosine, verapamil or beta blockers.
FIGURE 241-3 12-lead ECG o ORT due to an accessory pathway between the le t ventricle and le t atrium. The ECG is rom an otherwise healthy young woman who had
recurrent episodes o tachycardia, sometimes terminating with vagal maneuvers and always terminated by administration o adenosine. Termination with AV node blocking
agents make atrial futter and atrial tachycardia unlikely and are consistent with mechanisms dependent on AV nodal conduction, such as ORT or AVNRT. The 12-lead ECG
shows a narrow complex tachycardia with a regular atrial rate and 1:1 atrioventricular response. Using the algorithm shown in Fig. 241-2, the most likely mechanisms are
AVNRT or ORT. The P wave can be seen in the ST segment (arrows) and appears to be positive in lead III and negative in leads I and aVL, which suggests a le t ree wall
origin. Ablation o the le t ree wall accessory pathway eliminated urther episodes o SVT. (See Chap. 244 or urther discussion o ORT and accessory pathways).
TABLE 241-2 Usual Relation of P-wave to QRS in Paroxysmal TABLE 242-1 Common Causes of Physiologic Sinus Tachycardia 1735
Supraventricular Tachycardias (see also Fig. 241-3) 1. Exercise
Regular tachycardia with 1:1 AV conduction: 2. Acute illness with ever, in ection, pain
– AVNRT either has no discernible p-waves because they are synchronous with
CHAPTER 242 Physiologic and Nonphysiologic SinusTachycardia

3. Hypovolemia, anemia
the QRS, or p-waves that are negative in II, III, aVF immediately ollowing the
QRS (re erred to as short R-P tachycardia). Atypical orms may have a longer 4. Hyperthyroidism
R-P interval. 5. Pulmonary insu iciency
– ORT has p-waves ollowing the QRS, although they may be di icult to de ine 6. Drugs that have sympathomimetic, vagolytic, or vasodilator properties, e.g.,
when simultaneous with the T-wave. (See example in Fig. 241-3.) albuterol, theophylline, tricyclic antidepressants, ni edipine, hydralazine
– AT typically has p-waves preceding the QRS (R-P) interval > P-R interval. P
7. Pheochromocytoma
wave morphology depends on the ocus location and is di erent compared
to sinus rhythm unless the ocus is near the sinus node.
Note: Further analysis o SVT with a regular ventricular rate may allow
discrimination among the three most common orms: atrioventricular nodal
(Fig. 242-1). S -
reentry tachycardia (AVNRT), orthodromic reentrant tachycardia (ORT), or atrial ,
tachycardia (AT). II, III, VF; VR;
V1. N
60–100 / . S
■ FURTHER READING (>100 / ) -
Appelboam A : P V , -
(REVERT): A .L 386:1747, 2015. -

Page RL : 2015 ACC/AHA/HRS G M ,
A P S T :AR .
A C C /A H A T S 60 / ; ,
F C P G H R S . .
C 133: 506, 2016. S
, , .S
( )
.A ( )
,
.T
242 Physiologic and
Nonphysiologic Sinus .T
ECG
Tachycardia (Table 242-1),

.
Gregory F. Michaud, William G. Stevenson Nonphysiologic Sinus Tachycardia Inappropriate sinus tachy-
cardia
-
Physiologic Sinus Tachycardia T -
.A
.F , ,
, .A
A B Crista terminalis
II, III, aVF

SVC
Pectinate
Sinus
muscles
node
V1
Compact TVA
AVN
FO
CS Os
aVR Eustachian
ridge
IVC
Triangle of Koch
FIGURE 242-1 Right atrial anatomy pertinent to normal sinus rhythm and supraventricular tachycardia. A. Typical P-wave morphology during normal sinus rhythm
based on standard 12-lead electrocardiogram. There is a positive P wave in leads II, III, and aVF; biphasic, initially positive P wave in V1; and negative P wave in aVR.
B. Right atrial anatomy seen rom a right lateral perspective with the lateral wall opened to view the septum. AVN, atrioventricular node; CS Os, coronary sinus ostium;
FO, ossa ovalis; IVC, in erior vena cava; SVC, superior vena cava; TVA, tricuspid valve annulus.
1736 , , .I AT
. AT AV .
. T S AT -
- (SVT ). I AT -
.T . .
PART 6
C / AT 1:1 AV AV
.C W ( . ., 2:1 3:1). B
.I , I AV , AT
, U S AV , , -
, - AT AV – SVT , AV
.C AV ( ). A
, - , - -
. AT AV – SVT,
Postural orthostatic tachycardia syndrome (POTS) .P
, ,
.T 30 / AT ( )
>120 / 10
.S .W 1:1 ,
. POTS P-R
R-P (Fig. 243-1), particularly when sympathetic
3–12 .V , tone produces rapid AV nodal conduction. I
, , α- , P- ,
, .E .F AT
. ,
, , ,
( , ,
■ FURTHER READING ) (Fig. 243-2),
George SA : T POTS : E P- . AT
. P- . AT
H R 13:943, 2016. , P V1
Nwazue VC :P P I VL
: R . AT ,
. JA H A 3: 000700, 2014. ,
Salazar Adum JP, Arora R: T - II, III, VF, AT
.A JT 24: 574, 2017. , ,
Sheldon RS : 2015 H R S P .W
, , ,
, , . .A
H R 12: 41–63, 2015. AT .D , P
T , 2:1 ,
QRS. M AV ,
,V , AV
– , , AV
(Fig. 243-3).
243 Focal Atrial Tachycardia Gregory F. Michaud,

A -
PSVT (Chaps. 241 and 244),
,
, AT
.F
-
William G. Stevenson AT ,
AV .
S AT ,
F (AT) , .C
, , ,
, .B -
, .I , , , AV
.F AT ~10% PSVT , ,
.N AT 24- .P -
ECG , .I .U
, AT .
. F , ,
T , AT ,
, , , , -
AT. ,
AT (Tables 243-1, 243-2, and 243-3).
, C AT 80%
.A AT
AT -
. S .
1737
A B
N o P-w av e v isible
CHAPTER 243 Focal Atrial Tachycardia

AT •AV no de r
eentry
AVNRT
RP < PR •AV no de reentry

•AV reentry using an
AVRT accesso ry p athw ay
RP > PR • Fo cal atrial tachycar

dia
•AV r eentry using an
accesso ry p athw ay
•AV no de r eentry
unco m m o n fo rm
FIGURE 243-1 Common mechanisms underlying paroxysmal supraventricular tachycardia along with typical R-P relationships. A. Schematic showing a our-chamber
view o the heart with atrioventricular node in green and an accessory pathway between the le t atrium and le t ventricle in blue. Atrial tachycardia (AT; red circuit)
is con ned completely to atrial tissue. Atrioventricular nodal reentry tachycardia (AVNRT; blue circuit) uses atrioventricular (AV) nodal and perinodal atrial tissue.
Atrioventricular reentry tachycardia (AVRT; black circuit) uses atrial and ventricular tissue, accessory pathway, AV node, and specialized conduction bers (His-Purkinje)
as part o the reentry circuit. B. Typical relation o the P wave to QRS, commonly described as the R-P to P-R relationships or the di erent tachycardia mechanisms.
V1 SVC aVL
RS L AA
V V
LS
A
Lateral left atrium

RA
Left atrium
LIV II, III, aVF
Right atrium RIV
IVC Posterior septum

narrow P-wave
FIGURE 243-2 Location o ocal atrial tachycardia ocus estimated by P-wave morphology. LAA, le t atrial appendage; LIV, le t in erior pulmonary vein; LSV, le t superior
pulmonary vein; RAA, right atrial appendage; RIV, right in erior pulmonary vein; RSV, right superior pulmonary vein; SVC, superior vena cava.
VI
VI
B
FIGURE 243-3 Atrial tachycardia (AT) with 1:1 and 2:1 atrioventricular (AV) conduction. Arrows indicate P waves. A. AT with 1:1 AV relationship and R-P > P-R. B.
Same AT with 2:1 AV relationship a ter AV nodal–blocking agent administered. (Adapted rom F Marchlinski: The tachyarrhythmias in DL Longo et al [eds]: Harrison’s
Principles o Internal Medicine, 18th ed. New York, McGraw-Hill, 2012, pp 1878–1900.)
1738 TABLE 243-1 Commonly Used Antiarrhythmic Agents—Intravenous Dose Range/Primary Indication
DRUG LOADING MAINTENANCE PRIMARY INDICATION CLASS a
Adenosine 6–18 mg (rapid bolus) N/A Terminate reentrant SVT involving AV node —
Amiodarone 15 mg/min or 10 min, 1 mg/min or 6 h 0.5–1 mg/min AF, AFL, SVT, VT/VF III
Digoxin 0.25 mg q2h until 1 mg total 0.125–0.25 mg/d AF/AFL rate control —
PART 6
Diltiazem 0.25 mg/kg over 3–5 min (max 20 mg) 5–15 mg/h SVT, AF/AFL rate control IV
Esmolol 500 μg/kg over 1 min 50 μg/kg per min AF/AFL rate control II
Ibutilide 1 mg over 10 min i over 60 kg N/A Terminate AF/AFL III
Lidocaine 1–3 mg/kg at 20–50 mg/min 1–4 mg/min VT IB
Metoprolol 5 mg over 3–5 min × 3 doses 1.25–5 mg q6h SVT, AF rate control; exercise-induced VT; long QT II
Procainamide 15 mg/kg over 60 min 1–4 mg/min Convert/prevent AF/VT IA
Quinidine 6–10 mg/kg at 0.3–0.5 mg/kg per min N/A Convert/prevent AF/VT IA
Verapamil 5–10 mg over 3–5 min 2.5–10 mg/h SVT, AF rate control IV
a
Classi ication o antiarrhythmic drugs: class I—agents that primarily block inward sodium current; class IA agents also prolong action potential duration; class II—
antisympathetic agents; class III—agents that primarily prolong action potential duration; class IV—calcium channel–blocking agents.
Abbreviations: AF, atrial ibrillation; AFL, atrial lutter; AV, atrioventricular; SVT, supraventricular tachycardia; VF, ventricular ibrillation; VT, ventricular tachycardia.
TABLE 243-2 Commonly Used Antiarrhythmic Agents: Chronic Oral Dosing/Primary Indications
DOSING ORAL, mg, PRIMARY ROUTE(S) OF
DRUG MAINTENANCE HALF-LIFE, h METABOLISM/ELIMINATION MOST COMMON INDICATION CLASSa
Acebutolol 200–400 q12h 6–7 Renal/hepatic AF rate control/SVT II
Long QT/RVOT VT
Amiodarone 100–400 qd 40–55 d Hepatic AF/VT prevention III b
Atenolol 25–100 per d 6–9 Renal AF rate control/SVT II
Long QT/RVOT VT
Digoxin 0.125–0.25 qd 38–48 Renal AF rate control —
Diltiazem 30–60 q6h 3–4.5 Hepatic AF rate control/SVT IV
Disopyramide 100–300 q6–8h 4–10 Renal 50%/hepatic AF/SVT prevention Ia
Do etilide 0.125–0.5 q12h 10 Renal AF prevention III
Dronedarone 400 q12h 13–19 Hepatic AF prevention IIIb
Flecainide 50–200 q12h 7–22 Hepatic 75%/renal AF/SVT/VT prevention Ic
Metoprolol 25–100 q6h 3–8 Hepatic AF rate control/SVT II
Long QT/RVOT VT
Mexiletine 150–300 q8–12h 10–14 Hepatic VT prevention Ib
Nadolol 40–240 per d 10–24 Renal Same as metoprolol II
Propa enone 150–300 q8h 2–8 Hepatic AF/SVT/VT prevention Ic
Quinidine 300–600 q6h 6–8 Hepatic 75%/renal AF/SVT/VT prevention Ia
Sotalol 80–160 q12h 12 Renal AF/VT prevention III
Verapamil 80–120 q6–8h 4.5–12 Hepatic/renal AF rate control/RVOT VT IV
Idiopathic LV VT
a
Classi ication o antiarrhythmic drugs: class I—agents that primarily block inward sodium current; class II—antisympathetic agents; class III—agents that primarily prolong action
potential duration; class IV—calcium channel-blocking agents. bAmiodarone and dronedarone both are grouped in class III, but both also have class I, II, and IV properties.
Abbreviations: AF, atrial ibrillation; LV, le t ventricular; RVOT, right ventricular out low tract; SVT, supraventricular tachycardia; VT, ventricular tachycardia.
TABLE 243-3 Common and Proarrhythmic Toxicities of Antiarrhythmic Agents

DRUG POTENTIAL PROARRHYTHMIC TOXICITIES COMMON TOXICITIES
Amiodarone Sinus bradycardia, AV block, increase in de ibrillation threshold. Rare: Tremor, peripheral neuropathy, pulmonary ibrosis or
long QT and torsades des pointes, incessant slow VT in heart disease in lammation, hypo- and hyperthyroidism, hepatitis,
photosensitivity
Adenosine Transient pro ound pauses, atrial ibrillation Cough, lushing, chest pain, anxiety
Digoxin AV block, ascicular tachycardia, accelerated junctional rhythm, atrial Anorexia, nausea, vomiting, visual changes
tachycardia with AV block
Disopyramide Long QT and torsades des pointes, 1:1 ventricular response to atrial Anticholinergic e ects, acute urinary retention (males), negative
lutter inotropy
Do etilide Long QT and torsades des pointes Nausea
Dronedarone Bradyarrhythmias and AV block, long QT and torsades des pointes (rare) Gastrointestinal intolerance, exacerbation o heart ailure
Flecainide 1:1 Ventricular response to atrial lutter; increased risk o ventricular Dizziness, nausea, headache, decreased myocardial contractility
tachycardias in patients with structural heart disease; sinus bradycardia
Ibutilide Long QT and torsades des pointes Nausea
Lidocaine Slow VT in some patients with structural heart disease Dizziness, con usion, delirium, seizures, coma
Mexiletine Slow VT in patients with structural heart disease Ataxia, tremor, gait disturbances, rash, nausea
Procainamide Long QT and torsades des pointes, accelerated ventricular rate in AF or lutter Lupus erythematosus–like syndrome (more common in slow
acetylators), anorexia, nausea, neutropenia
Propa enone 1:1 Ventricular response to atrial lutter; increased risk ventricular Taste disturbance, dyspepsia, nausea, vomiting
tachycardias in patients with structural heart disease; sinus bradycardia
Quinidine Long QT and torsades des pointes, accelerated ventricular rate in AF or lutter Diarrhea, nausea, vomiting, cinchonism, thrombocytopenia
Sotalol Long QT and torsades des pointes Hypotension, bronchospasm rom β-blocking e ect
Abbreviations: AF, atrial ibrillation; AV, atrioventricular; VT, ventricular tachycardia.
■ FURTHER READING AV 1739
Link MS: C .E - H ,
.NE JM
367:1438, 2012.
Liu CF :U .T P , ,
CHAPTER 244 Paroxysmal SupraventricularTachycardias

.C A E 9: : 004028, 2016. QRS .O P
Page RL : 2015 ACC/AHA/HRS G M QRS -′ V1
A P S T :AR -S II, III, VF (Fig. 244-1A). M
A C C /A H A T AVNRT P , QRS
F C P G H R S . , P
C 133: 506, 2016. Fig. 244-2 P
T .T .S
.E
Paroxysmal Supraventricular
244 Tachycardias -
AV
.I AT ,
.
-
Gregory F. Michaud, William G. Stevenson A PSVT (

). W
.R
V
Atrioventricular Nodal Reentry Tachycardia AV .A ,
(AVNRT) -
,
(PSVT), ~60%
.C -
.I .C
, .I ,
AV -
, , , -
, -
, , .I , .C >95%
. . T (AV)
T AV
, <1% .
,
AV - Junctional Tachycardia J (JET)
(Fig. 244-1). M AVNRT AV .I -
AV ( ) ,
AV H , .I
. QRS , (VA) ,
T AV . JET
AV -
AV .T , .
- I AVNRT.
.M AVNRT Accelerated junctional rhythm
AV 50 100 / . I
, , , ,
.I , , -
. VA ,
A B P-
AVNRT
II .I
-
. I
.
Inferior AV node
P waves extension:
Slow pathway
■ ACCESSORY PATHWAYS
V1
AND THE WOLFF-PARKINSON-
WHITE SYNDROME
Compact AV node:
A (AP ) 1
Fast pathway
1500–2000
- PSVT, -
, , , .
M
, AP
E ’
CS Tricuspid -
valve PRKAG2 ,
D ’ , F ’ .
FIGURE 244-1 Atrioventricular (AV) node reentry. A. Leads II and V1 are shown. P waves are visible at the end o the
QRS complex and are negative in lead II, and may give the impression o S waves in the in erior limb leads II, III, and AP
aVF and an R’ in lead V1. B. Stylized version o the AV nodal reentry circuit within the triangle o Koch (see Fig. 242-1)
that involves AV node and its extensions along with perinodal atrial tissue. AV
1740
I
II
PART 6
III
aVr
aVL
aVF
V1
V2
V3
V4
V5
V6
A B
FIGURE 244-2 Comparison o 12-lead ECG tracings showing SVT (Panel A) and normal sinus rhythm (Panel B). The P wave is observed at the end o the T wave and
morphology can be in erred rom comparing to sinus rhythm. P waves are inverted in the in erior limb leads (II, III, and aVF), positive in V1, I, and aVL consistent with
conduction retrogradely through the AV junction. In typical orms o AVNRT, the P wave is not visible or is seen at the end o the QRS complex.
(Fig. 244-3). T - H
AV .T ,
AV , .A ,
, M , AV H -
, , . I P
AP
( ) AV H .
, ,
ECG P-R (<0.12 ), AV Reentry Tachycardia T
QRS ( ), QRS AP PSVT orthodromic AV reentry. T
AP (Fig. 244-3A). T QRS AV H -P

AP (Fig. 244-4) AP (Fig. 244-3B). T QRS
AV ,
AP. R - .B
, – AV AP , AV
VA -
V 1, .D ,
AP (F . 244-4). L - (F . 244-3A). M -
, R-P P-R -
– V1 AVNRT (see Fig. 242-1). U AVNRT,
VL, P QRS
(F . 244-4). QRS
B AP .
AP , 12- T P ,
ECG. P AP ST
, , .T P AP II, III,
III VF, VF, AV , P-
(F . 244-4). P AV (F . 244-4).
AV Figure 241-3 P
. I VL AP
W -P -W (WPW) .
QRS PSVT. T O , AP
AP , / - , R-P ,
.C AP , AT . T
, , SVT P II, III, VF. S AP
. O AP . F , ,
A Left lateral Right free wall 1741
aVL V1
CHAPTER 244 Paroxysmal SupraventricularTachycardias

PV
AV
TV
MV
B
Coronary
sinus (CS)
Postero-septal
II aVF III
FIGURE 244-4 Potential locations or accessory pathways in patients with

C
Wol -Parkinson-White Syndrome and typical QRS appearance o delta waves
Sinus rhythm— Orthodomic AV Antidromic AV that can mimic underlying structural heart disease such as myocardial in raction
antegrade reentry—retrograde reentry—antegrade o bundle branch block. AV, aortic valve; MV, mitral valve; PV, pulmonary valve;
AP conduction AP conduction AP conduction
TV, tricuspid valve.
AP
-
H -P .T -
.T
.
P AP -
Delta-wave p p AT, ,
(AF) (Fig. 244-5), AV ,
AP . AF
AP . A
25% AP R- -R
FIGURE 244-3 Wol -Parkinson-White (WPW) syndrome. A. A 12-lead electro- <250 AF
cardiogram in sinus rhythm (SR) o a patient with WPW demonstrating short P-R .P AF
interval, delta waves, and widened QRS complex. This patient had an anteroseptal - , .D AF,
location o the AP. B. Orthodromic AV reentry in a patient with WPW syndrome using AP AV .T
a posteroseptal AP. Note the P waves in the ST segment (arrows) seen in lead III and
QRS - -
normal appearance o QRS complex. C. Three most common rhythms associated
with WPW syndrome: sinus rhythm demonstrating antegrade conduction over the
AP and AV node; orthodromic AVRT using retrograde conduction over the AP and AV AP,
antegrade conduction over the AV node; and antidromic AVRT using retrograde AP (F . 244-5). V P
conduction over the AV node and antegrade conduction over the AP. AP, accessory AP
pathway; AV, atrioventricular; AVRT, atrioventricular reentry tachycardia; WPW, AP. S AV
Wol -Parkinson-White.
AP AP
.A AV –
permanent junctional reciprocating tachycardia (PJRT). T - , , -
.W - , , -
, AF. R
AV AV AT.
,
Preexcited Tachycardias P .
AP
(Fig. 244-3C). T antidromic AV reentry Management of Patients with APs A
AP AV PSVT. P
H -P WPW - -
AV ( AP). T QRS AV , AV ,
1742
PART 6
FIGURE 244-5 Preexcited atrial fbrillation (AF) due to conduction over a le t ree wall accessory pathway (AP). The electrocardiogram shows rapid irregular QRS
complexes that represent usion between conduction over the atrioventricular node and le t ree wall AP. Shortest R-R intervals between preexcited QRS complexes o
<250 ms, as in this case, indicate a risk o sudden death with this arrhythmia.
, ,
. , , ,
I .R -
, - .C , ~2 1000
.E - .
.A E ’
AP . TREATMENT
P Paroxysmal Supraventricular Tachycardia
AF AP
.T A QRS PSVT
2 1000 .A .C ECG
12- ECG ,
AF , .I
.C , QRS-
- ,
, , (F . 244-5). E ,
95% AP. S - ( ). F ,
3% , AV , PSVT AV
, , , (AV AV )
.P <1 1000 .A - -
AP (Fig. 244-6). A , ECG
; ,
( ) . AV
, .G AP P , AT
.
AV . C
F AP - AP ,
AV , .AV
.V , , ,
, , .I
.C ,
. PSVT
A AV .A , -
1 1000 - .E - , .I
.I
1743
Hemodynamically stable
Hemodynamically stable
regular,
regular,narrow
NarrowQRS
QRStachycardia
tachyca
Common Atrial Flutter,
245 Macroreentrant, and
CHAPTER 245 Common Atrial Flutter, Macroreentrant, and Multifocal Atrial Tachycardias
Vagal
Vagal maneuvers
maneuvers Multifocal Atrial Tachycardias
IV
i.v.adenosine
adenosine Termination
Termination
IV
i.v.verapamil/diltiazem
verapamil/diltiazem Gregory F. Michaud, William G. Stevenson
No
No termination
termination
Macroreentrant atrial tachycardia ,
. Common or typical right atrial
IV
i.v.ibutilide
Ibutilide++AV
AVnodal–blocking
nodal blocking agent
agent flutter
IV
i.v.procainamide
procainamide++AV AVnodal–blocking
nodal blocking agent , -
Cardioversion
cardioversion .T
,
FIGURE 244-6 Treatment algorithm or patients presenting with hemodynamically -E ,
stable paroxysmal supraventricular tachycardia. AV, atrioventricular. .T ,
cavotricuspid isthmus-dependent atrial flutter. T
( -
),
.A AF, -
, 15% , II, III, VF P V1 (Fig. 245-1). W
WPW AF - , P-
.I .T 240–300 /
( ) .
I 2:1 AV ,
.T 150 / , P
- .M AV
V . , .
T - C
(Chap. 247), PSVT
, ( ). I - .S -
, , , , ,
.I ,
, .V .
- AF M AT
( ) , - atypical atrial flutters. T
, . I PSVT
, .L
, PSVT
. I , ECG .T
, , P- (Fig 245-2). T
. AT, , -
.
■ FURTHER READING
Al-Khatib SM :R TREATMENT
- :A 2015 Atrial Flutter
ACC/AHA/HRS G M A P
S T :AR A C I
C /A H A T F C , .E
P G H R S . C .
133: 575, 2016. O , AV
Appelboam A : P V – ,
.T
(REVERT): A .L 386:1747, 2015. .A
Gupta S, Figueredo VM: T : 48
P , , .I
JC 172:40, 2014. CHA2DS2-VAS (Table 245-1).
Link MS: C .E - F ,
.NE J M 367:1438, 2012. . F -
Page RL : 2015 ACC/AHA/HRS G M , , ,
A P S T :AR , , >70%
A C C /A H A T .F
F C P G H R S . ,
C 133: 506, 2016. >90% -
,
1744
VI II
PART 6
A
Counterclockwise flutter
Tricuspid
valve
B
FIGURE 245-1 A. Common right atrial futter, also known as cavotricuspid isthmus futter, showing positive P waves in lead V 1 and negative “sawtooth” pattern in
lead II typical o counterclockwise rotation relative to the tricuspid valve annulus. (Adapted rom F Marchlinski: The tachyarrhythmias in DL Longo et al [eds]: Harrison’s
Principles o Internal Medicine, 18th ed. New York, McGraw-Hill, 2012, pp 1878–1900.) B. A right atrial map o common counterclockwise futter is shown. Colors indicate
activation time, progressing rom red to yellow to green, blue, and purple. The reentry path parallels the tricuspid annulus.
I aVR V1 V4
II aVL V2 V5
III aVF V3 V6
VI
V5
FIGURE 245-2 Atrial utter in a 52-year-old man that occurred one year a ter extensive le t atrial ablation or persistent atrial fbrillation. In contrast to common
futter the P waves in V1 and in erior limb leads (II, III, and aVF) have the same polarity (positive in this case). Also, lead aVL shows a predominant negative P wave
consistent with a le t atrial ocus, however P-wave morphology used to diagnose arrhythmia mechanism and location is unreliable in the setting o advanced atrial
brosis, such as a ter extensive catheter ablation.
TABLE 245-1 CHA2DS 2-VASc Risk Assessment and Oral Anticoagulants 1745
RISK FACTORS POINTS CHA2DS2-VASc SCORE ESTIMATED ANNUAL STROKE RATEa

C—congestive heart ailure 1 0 0
CHAPTER 245 Common Atrial Flutter, Macroreentrant, and Multifocal Atrial Tachycardias
H—hypertension 1 1 1.3%
A—age ≥75 y 2 2 2.2%
D—diabetes mellitus 1 3 3.2%
S—stroke or TIA, embolus 2 4 4.0%
V—vascular disease 1 5 6.7%
A—age 65–75 y 1 6–9 >9%
Sex— emale 1
ANTICOAGULANTS MECHANISM EXCRETION DOSING CONSIDERATIONS RISK/BENEFIT
War arin Vitamin K Liver Adjusted to INR 2–3 Major hemorrhage: 1% per year
antagonist Days to therapeutic e ect Intracranial hemorrhage: 0.1–0.6% per
Multiple drug/ ood interactions (e.g., year
amiodarone) Risk o bleeding increases with INR >3.5
Inexpensive
Dabigatranb Thrombin inhibitor Kidney
CCr >30 mL/min 150 mg bid Onset o action within hours
CCr 15–30 mL/min 75 mg bid No reversal agent or bleeding
P-glycoprotein substrate (inducers—
ri ampin, reduce concentration)
(inhibitors—amiodarone, verapamil,
dronedarone, quinidine)
Proton pump inhibitors may reduce
absorption
Rivaroxaban Xa inhibitor Kidney P-glycoprotein substrate No reversal agent or bleeding
CCr ≥50 mL/min 20 mg daily
CCr 15–50 mL/min 15 mg daily
Apixaban Xa inhibitor Kidney and liver P-glycoprotein substrate No reversal agent or bleeding
Any 2 o : 5 mg bid
Cr >1.5 mg/dL, age 2.5 mg bid
>80 yrs,
or wt <60 kg
a
Modi ied rom GY Lip et al: Lancet 379:648, 2012. bU.S. Food and Drug Administration recommended dosing; other regimens are available outside the United States.
Abbreviations: CCr, creatinine clearance; Cr, creatinine; INR, international normalized ratio; TIA, transient ischemic attack; wt, weight.
.A 50% .I
5 ,
.
. T MAT
. E
■ MULTIFOCAL ATRIAL TACHYCARDIA .T
M AT (MAT) .P
P- 100 . MAT
150 / . U , , -
P (Fig. 245-3) .T , .
FIGURE 245-3 Multi ocal atrial tachycardia. Rhythm strip obtained rom a patient with severe pulmonary disease during an acute illness. Arrows note three distinct
P-wave morphologies.
1746 ■ FURTHER READING - —
Page RL : 2015 ACC/AHA/HRS G M AF. AF
A P S T :AR 25% .I
A C C /A H A T MRI. S AF
F C P G H R S . ,
PART 6
C 133: 506, 2016. , AF

Rahman F :A :C - .
F H S .H R 13:233, 2016. AF
, ,
. AF
30% ,
246 Atrial Fibrillation
Gregory F. Michaud, William G. Stevenson
T
.
AF
(F . 246-1). P AF -
7 .P AF
A (AF) , , (PV). C
AF,
AV .T -PV
(Fig. 246-1). I , -
, 120 160 / , .P AF , 7 ,
, 200 / .P , ,
AV . . C
AF .A AF,
. P , >95% PV , -PV ,
AF >60 .T 80 ~10%. (SVC)
T AF 40 ~25%. AF AF . I ,
AF -
.R AF ,
, - , .I -
, , , . AF AF (>1 ),
1.5- 1.9- - .S
. AF AF. A
.T , AF
AF.
C AF -
, ,
. P
.R
Types of AF Triggers
Paroxysmal AF Ectopic foci
, ,
.E -
.O ,
AF
(Fig. 246-2). D -
Persistent AF Electrophysiologic
requires cardioversion remodeling fibrosis ( 100–110 )
,
-
.T -
.
T AF ’ -
Long-standing persistent Chronic substrate
, AF, AF,
or permanent AF fibrosis . New-onset
AF , ,
QRS
FIGURE 246-1 A rhythm strip o atrial fbrillation (AF) showing absence o distinct P-waves 200 J, -
and an irregularly irregular ventricular response. Diagram depicts atrial brillation types.
.G
Paroxysmal AF is initiated by premature beats, as shown in the rhythm strip (arrow) a ter two
sinus beats. Triggering oci are o ten an important cause o this arrhythmia. Persistent AF is AF.
associated with atrial structural and electrophysiologic remodeling, as well as with triggering A
oci in many patients. Long-standing persistent AF is associated with greater structural AF
remodeling with atrial brosis and electrophysiologic remodeling. ,
1747
CHAPTER 246 Atrial Fibrillation

Post trigger Recorded: 02/24/2013 @ 12:44 AM (CT) 25 mm/sec, 32 mm/mV Continues->
7.2 seconds
Recorded: 02/24/2013 @ 12:44 AM (CT) 25 mm/sec, 32 mm/mV Continues->
Recorded: 02/24/2013 @ 12:44 AM (CT) 25 mm/sec, 32 mm/mV Continues->
FIGURE 246-2 A continuous rhythm strip is shown rom a patient with tachy-brady syndrome. Atrial brillation is present at the top and abruptly terminates in the
second tracing, with atrial and ventricular standstill or 7.2 s until resumption o sinus rhythm. The patient experienced syncope.
QT LV T .
P .I , O 3
, 4 .A
. C - .I -
, ,
AF, 4
. I .I , AF
.I AF , .
>48 , L -
.A - AF ’ ,
.I , CHA2DS2-VAS .
, ■ RATE CONTROL
. A /
■ CARDIOVERSION AND ANTICOAGULATION , -

T AF .D , , -
,
.F - .D ,
AF , - AF,
, .I AV –
.W AF >48 .I
, .T ,
, 100/ ,
.T - .
,
. ■ CHRONIC RATE CONTROL
C within 48 h of the onset of AF F AF ,
,
, - . β-A
, .D
. T - - .E -
AF AF .R
48 . .T
If the duration of AF exceeds 48 h or is unknown, <80 / <100 / ,
, .I
(CHA2DS2-VAS 0 1[ ]) . , 110 /
1748 -
, .
- . T
I AF , - , X , , ,
( ). C K .A -
PART 6
AV .I - AF,
64% 37% -
AV , . .P AF
R ,
. .T ,
B H , , ,
. ,
0.4–0.7%
■ STROKE PREVENTION IN ATRIAL FIBRILLATION , , , -
T , . W
. T ,
.A
, ,
.P .W
AF. T CHA2DS2-VAS (Table 246-1) (
.A - [PT]/ [INR] >2),
≥2 1. T PT/INR , ,
AF .T
AF. I
AF . D , ,
.A AF ,
.T (C C <15 L/ ),
TABLE 246-1 CHA2DS 2-VASc Risk Assessment and Oral Anticoagulants

RISK FACTORS POINTS CHA2DS2-VASc SCORE ESTIMATED ANNUAL STROKE RATE a
C—congestive heart ailure 1 0 0
H—hypertension 1 1 1.3%
A—age ≥75 y 2 2 2.2%
D—diabetes mellitus 1 3 3.2%
S—stroke or TIA, embolus 2 4 4.0%
V—vascular disease 1 5 6.7%
A—age 65–75 y 1 6–9 >9%
Sex— emale 1
ANTICOAGULANTS MECHANISM EXCRETION DOSING CONSIDERATIONS RISK/BENEFIT
War arin Vitamin K antagonist Liver Adjusted to INR 2–3 Major hemorrhage: 1% per year
Days to therapeutic e ect Intracranial hemorrhage: 0.1–0.6% per
Multiple drug/ ood interactions year
(e.g., amiodarone) Risk o bleeding increases with INR >3.5
Inexpensive
Dabigatranb Thrombin inhibitor Kidney
CCr >30 mL/min 150 mg bid Onset o action within hours
CCr 15–30 mL/min 75 mg bid Reversal agent available
P-glycoprotein substrate
(inducers—ri ampin, reduce
concentration)
(inhibitors—amiodarone, verapamil,
dronedarone, quinidine),
Proton pump inhibitors may reduce
absorption
Rivaroxaban Xa inhibitor Kidney P-glycoprotein substrate Reversal agent or bleeding in
development
CCr ≥50 mL/min 20 mg daily
CCr 15–50 mL/min 15 mg daily
Apixaban Xa inhibitor Kidney and liver P-glycoprotein substrate Reversal agent or bleeding in
Any 2 o Cr>1.5 mg/dl, 5 mg bid development
age > 80 yrs or 2.5 mg bid
wt < 60 kg.
Edoxaban Xa inhibitor Kidney and Liver P-glycoprotein substrate
CCr> 60 <95 mL/min 60 mg
CCr 15–60 mL/min 30 mg
a
Modi ied rom GY Lip et al: Lancet 379:648, 2012. bU.S. Food and Drug Administration recommended dosing; other regimens are available outside the United States.
Abbreviations: CCr, creatinine clearance; Cr, creatinine; INR, international normalized ratio; TIA, transient ischemic attack.
, , Pharmacologic Therapy for Maintaining Sinus Rhythm 1749
.E T
P- .W AF. R
K. A .D
CHAPTER 246 Atrial Fibrillation

( )
X ( . β-A -
). F , X , ,
, - - , AF .
12 , C I – ( . ., , ,
. )
T - ,
AF . .T
C III
, ~3%
. QT .
B .M - D ECG ,
~1% .D -
.D . A
AF,
.R ~30–50% .A ,
>65–75 , , , - - .I
, - . .O 40%
I ( . ., - -
) , - .
.T ■ CATHETER AND SURGICAL ABLATION FOR ATRIAL

AF - FIBRILLATION
. S
C .F
.B AF, -
, ,
,
, - AF .L -
.P AF AF,
, - - .
- C , ( )
, . ,
PV,
■ RHYTHM CONTROL AF,
AF , , .E
.A ,
AF . PV 20–50%
T - .
( I AF,
“ ”) >1 ~60% ;
70–80% . M
. I , PV
AF. T .A
AF .I AF, - AF,
, - .
- M ,
, .
D .T
PV
.T .A AF
, .A
- .O
AF, AF, AF , ,
, AF AF. M
.A
- AF.
.E C 2–7% - -
, - , (0.5–1%), (1%),
CHA2DS2-VAS , ,
AF .F , 1–3 .I
AF, AV – , -
, , .A PV PV , -
. I , .
. T
1750 , Premature ventricular beats ( -
contraction or PVC)
( < 0.1%) (Fig. 247-1). PVC -
10 3 .E QRS
(Fig. 247-1A). PVC
PART 6
.D CT QRS
IV .E (Fig. 247-1B). T
/ .D .
- Ventricular tachycardia (VT)
. 100 / .T
S AF (Fig. 247-1C). VT
30 non-sustained
- .H , AF, - (Fig. 247-2) VT >30
- - , -
.R , ,
.S .
, Monomorphic VT QRS , -
. ,
(Fig. 247-3A). T
■ FURTHER READING
Calkins H : 2012 HRS/EHRA/ECAS .T , QRS PVC
:R - VT
, , - (Fig. 247-4). T
- , , , . .A -
H R 9:632. 21, 2012.
Cox JL: E - ,
.A M 47:278, 2015. S- V1 – -
Douketis JD :P .A
.NE JM 373:823, 2015. V1,
Freedman B : S . L – V1. T
388:806, 2016. QRS .A ,
January CT : 2014 AHA/ACC/HRS - R II, III, AVF,
:E :A ,
A C C /A H A ( S II, III, AVF)
T F H R S .C - .
130:2071, 2014. V VT ,
Kirchhof P : 2016 ESC G ventricular flutter,
EACTS. E H J QRS T (Fig. 247-3B). R sinusoidal
37:2893, 2016. VT QRS
Masoudi FA : 2015 ACC/HRS/SCAI - (Fig. 247-3C). H ,
.H R 12: 122, 2015. ( . ., , ,
Nair KK :A :A . J A F ) .
8:1331, 2015. Polymorphic VT QRS -
Nyong J : E - . P VT
. C D S R
11:CD012088, 2016. QT QRS
Voskoboinik A :A :A . “ ” T
JA C C 68:2567, 2016. P (Fig. 247-3D).
Ventricular fibrillation (VF)
QRS (Fig. 247-3E). M -
VT VF .
T idiopathic ventricular arrhythmias PVC
VT
.
247 Approach to Ventricular
Arrhythmias ■ CLINICAL MANIFESTATIONS
C ,
Roy M. John, William G. Stevenson , , ,
.V
-
■ TYPES OF VENTRICULAR ARRHYTHMIAS , ECG,
V ECG .
P , , S ,
P . VT ,
T
. C .A , -
( ) ,
P .H , QRS ,
, >0.12 . VT. W
A 1751
1000 ms
I
CHAPTER 247 Approach toVentricular Arrhythmias

Art. Pr.
FIGURE 247-1 A. Uni ocal premature ventricular contractions (PVCs) at bigeminal requency. Trace shows ECG lead 1 and arterial pressure (Art. Pr.). Sinus rhythm
beats are ollowed by normal arterial wave orm. The arterial pressure ollowing premature beats is attenuated (arrows) and imperceptible to palpation. The pulse in
this patient is registered at hal the heart rate. B. Multi ocal PVCs. The two PVCs shown have di erent morphologies. C. Example o accelerated idio-ventricular rhythm
(see text or details).
II aVR V1 V4
aVL V2
V5
III
V3
aVF V6
V1
II
FIGURE 247-2 Repetitive monomorphic non-sustained ventricular tachycardia (VT) o right ventricular out ow tract origin. The VT has a le t bundle branch block
pattern with in erior axis with tall QRS complexes in the in erior leads.
1752 A -
.S , -
,
.F ,
PART 6
.T
.
T
B
ECG,
ICD, ,
(Table 247-1). A 12
ECG
( ). F
’
. T
C
Chap. 249. T VT
Chap. 299. O
Evaluation of the Patient with Arrhythmia Symptoms

W ,
,
.S -
D
.S
,
, - -
.A .A
.M QT
VT (see Chap. 250). A
.
F -
, , , -
E
.F
-
.D .S
“ ”
.
T
,
.S -
.
FIGURE 247-3 A. Monomorphic ventricular tachycardia (VT) with dissociated P
waves (short arrows). B. Ventricular futter. C. Sinusoidal VT due to electrolyte A 12- ECG
disturbance or drug e ects. D. Polymorphic VT resulting rom prolongation o QT .O -
interval (torsade de Pointes VT). E. Ventricular brillation (see text or details). .P
ECG .A
, ECG . P
. Q- ,
S VT QRS , ,
- .A
(see Chap. 241) ECG
,
.S VT VF, QT ,B , QT
.M VT (see Chap. 250).
I ,
(ICD). I ICD, VT - .T
, .
ICD ( ). D
,
■ EVALUATION OF PATIENTS WITH DOCUMENTED OR , ,
SUSPECTED VENTRICULAR ARRHYTHMIAS .V -
T .C MRI
. F , ,
, 1753
II , -
VT
(Fig. 247-5). T
CHAPTER 247 Approach toVentricular Arrhythmias

.E -
-
III ,
.
■ TREATMENT OPTIONS FOR

VENTRICULAR ARRHYTHMIAS
II, III AVF = Inferior axis T
superior origin .F ,
( . .,
) .F -
V1 , ICD
“ - ”
RV LV
- VT VF, -
V1 = LBBB V1 = RBBB , .
Septal or RV origin LV origin W ,
II
.
Antiarrhythmic Drugs U
III .E
-
. A -
II, III AVF = Superior axis ,
inferior origin
.C , ,
FIGURE 247-4 Site o ventricular tachycardia (VT) origin based on QRS morphology (see text or “ - ”
details).
.A
.A -
TABLE 247-1 Diagnostic Tests for Ventricular Arrhythmias ,
12-Lead ECG , .
Event recorder
Non-looping, patient activated recorder Beta-adrenergic Blockers M
• R ecords only w hen the patient pu ts the device in contact w ith the chest , -
wall and activates it
• Usefu l for episodes that are infreq u ent bu t last for m ore than several - .T -
minutes .T
Looping event recorders -
• Continu ou sly recording, storing only segm ents triggered by the patient or ,
with a heart rate outside set parameters .B
• Usefu l for interm ittent, infreq u ent sym ptom atic and asym ptom atic .
arrhythmias
Continuous ambulatory recording Calcium Channel Blockers T - -
Holter monitor—typically used or 24–48 h
• R ecords all arrhythm ias du ring the recording period VT . T - ,
• Usefu l for very freq u ent arrhythm ias (daily) or w hen q u antitation of an
arrhythmia is needed (e.g., quantitation o premature ventricular contraction .
[PVCs] potentially contributing to depressed ventricular unction)
Implanted loop recorders Sodium Channel Blocking Agents D
• A llow continu ou s recording for >1 year , -
, , , ,
• Usefu l for captu ring rare events su ch as rare syncopal episodes
.B
Exercise Testing
C I .A -
• Usefu l for evalu ation of exercise indu ced sym ptom s; arrhythm ias u su ally
emerge during the early recovery phase a ter exercise
.C
• QT interval response to exercise m ay be abnorm al in long QT syndrom e
QRS .L , ,
Electrophysiologic study .Q , ,
• Invasive test that attem pts to initiate ventricu lar arrhythm ias in a
controlled setting
QT (C III )
• Usefu l for assessing arrhythm ia risk w hen there is concern for a risk of su dden . T
death, but a su icient diagnosis to guide therapy has not been achieved
- , ,
• Usefu l for distingu ishing betw een w ide com plex tachycardia du e to ventricu lar
tachycardia (VT) versus supraventricular tachycardia with aberrancy
1754
PART 6
FIGURE 247-5 Imaging studies o the le t ventricle (LV) used to assist ablation or VT. Le t panel is an MRI image o a longitudinal section demonstrating thinning o
the anterior wall and late gadolinium enhancement in a sub-endocardial scar (white arrows). The middle panel shows a 2-D image o the LV in long axis corresponding
to the sector through the mid LV (arrow in fgure on right panel) obtained by an intra-cardiac echo probe positioned in the RV. An electro-anatomic 3-D map o the LV
in the le t anterior oblique projection is displayed in the right panel. The purple areas depict areas o normal voltage (>1.5 mV). Blue, green, and yellow represent
progressively lower voltages with the red areas indicating scar (<0.5 mV). Channel o viable myocardium with slow conduction within the scar are identi ed with the
light blue dots. Areas o ablation delivered to regions involved in re-entrant VT are indicated by maroon dots.
.L - - ( ATP )
,
ICD . ICD . ICD
ICD,
Potassium Channel Blocking Agents S . T
IK , - ICD
(QT ) .D
, C III .S ~1% .
- - .I ICD
ICD .I ICD
.P VT torsade
de pointes QT 3–5% .T -
.B , - -
. T , QRS
-
, QT , ICD (Fig. 247-6C).
. D VT VF ICD,
Amiodarone and Dronedarone A
. I .O VT VF
. ,
I - . , . R ,
D , , .A -
.I ICD , ,
.A -
ICD. B VT
.V - , ICD’
, torsade de pointes VT .N - .
T ICD
- .H
.P - - (F . 247-6C). T ICD
~1% .P , , -
.S , .A ICD
.W
, , .I ,
>24 - .A ICD
.D -
.E -
. .
Implantable Cardioverter Defibrillators (ICD) ICD Catheter Ablation for VT C

VT, , (RF)
. VF .A
RV ICD .M VT
VT, ,
- (ATP) (Fig. 247-6A). I ATP .T
, VT VF, ,
(Fig. 247-6B). S . .W
ICD VT VF - , ,
.T ICD .L
A 1755
CHAPTER 248 PrematureVentricular Beats, Non-SustainedVentricularTachycardia, and Idioventricular Rhythm

Antitachycardia Pacing
B C
Atrial ICD
lead
ICD Shock
LV
lead
RV
lead
FIGURE 247-6 Implantable cardioverter defbrillator (ICD) and therapies or ventricular arrhythmias. A. A monomorphic ventricular tachycardia (VT) is terminated by
a burst o pacing impulses at a rate aster than VT (anti-tachycardia pacing). B. A rapid VT is converted with a high voltage shock (arrow). The chest x-ray in Panel C
shows the components o an ICD capable o biventricular pacing. ICD generator in the subcutaneous tissue o the le t upper chest, pacing leads in the right atrium
and the LV branch o the coronary sinus (LV lead) and a pacing/de brillating lead in the right ventricle (RV lead) are shown.
, - V A P S C
, , D E S C (ESC). E :
.I A E P C C
- VT , (AEPC). E H J 36:2793, 2015.
.B
,
(F . 247-5).
C
,
248 Premature Ventricular
Beats, Non-Sustained
- 0.5–3%. O Ventricular Tachycardia, and
VT Idioventricular Rhythm
- .A Roy M. John, William G. Stevenson
VT.
I VT PVC
,
■ PREMATURE VENTRICULAR CONTRACTIONS AND
(see Chaps. 248 and 249). NON-SUSTAINED VT
P (see Fig. 247-1A)
(see Chap. A9). T -
■ ARRHYTHMIA SURGERY ,
W , , , ,
, , - , .D
, VT , PVC
VT VF.
.F T ECG
. . PVC -
QRS
■ FURTHER READING
Pedersen CT : EHRA/HRS/APHRS - QRS . T QRS
.E 16:1257, 2014.
Priori SG : 2015 ESC G (see Fig. 247-4). PVC S- V1,
- –
: T T F M P .T R-
1756 V1 .A ( - -
II, III, AVF) , QT -
( ), ,B , ARVC,
( II, III, AVF) (F . 248-1). A -
.T , , .
PART 6
. M C
– . PVC RBBB VT (see Fig. 247-5). E

. M - -
PVC ( PVC ) .
(see Fig. 247-1B). I ,

( - VT) ■ TREATMENT OF IDIOPATHIC ARRHYTHMIAS
. F PVC - VT
, ,
■ PVCs AND NON-SUSTAINED VT DURING ACUTE
ILLNESS PVC ( ). R -
T
, ,
.W . A ,
, , .I ,
, - -
, , ( ) .I
.U .
. A , , ,
■ PVCs AND NON-SUSTAINED VT IN PATIENTS , -
WITHOUT HEART DISEASE .C
T 80% .F
, PVC VT -
– , - , ,
(see Fig. 247-2). .
H , QRS
. N - VT - ■ PVCs AND NON-SUSTAINED VT ASSOCIATED WITH
<200 / <8 (see ACUTE CORONARY SYNDROMES
Fig. 247-2). N - VT , , D (MI), PVC
T- (“ - - VT
”) VF. T -
. -
A VF. R
, -
, QT - PVC - VT,
(ARVC) ( ). A VT VF ,
12- ECG (Fig. 248-1). R .
F MI,
PVC ( >10 PVC / ), PVC
, - VT
,
V1 V1
.A -
,
.T ,
-
V2
.B -
V2 ,
.
F MI,
(ICD)
- :
V3
>40 MI
≤0.30,
V3 <0.35 -
( C II III);
A B >5 MI
, VT,
FIGURE 248-1 Precordial chest leads V1–V3 showing typical abnormalities o arrhythmogenic right
ventricular cardiomyopathy (ARVC) (A) and Brugada syndrome (B). In ARVC, there is T inversion and VT VF -
delayed ventricular activation mani est as Epsilon waves (arrows). Panel B shows ST elevation in V1 and . ICD
V2 typical o the Brugada syndrome. MI,
1757
. Sustained Ventricular
■ PVCs AND NON-SUSTAINED VT ASSOCIATED WITH
249 Tachycardia
CHAPTER 249 SustainedVentricularTachycardia

DEPRESSED VENTRICULAR FUNCTION AND HEART
FAILURE Roy M. John, William G. Stevenson
P - VT
,
, - S (VT)
QRS QRS
.T -
( , , (see Fig. 247-3A). VT
, , ) .I ,
- , ,
.T
, . A (see Fig. 247-5). L , VT
P .I VT
. ICD
P .
LV <0.35 NYHA II III , T
36 29%, 5 . , ,
.W VT, >200 / ,
■ PVC AND NON-SUSTAINED VT ASSOCIATED WITH ,
OTHER CARDIAC DISEASES VT,
V (LV) ,
hypertrophic cardiomyopathy (Chap. 254) congenital heart VT 150 / .M VT
disease .I -
, (VF),
. P .
. ICD -
. ■ DIAGNOSIS
S VT
■ PVC-INDUCED VENTRICULAR DYSFUNCTION QRS . T
V - VT (see -
Fig. 247-2) , ,
. (Chap. 241),
D PVC . I
>15 20% 24- .O PVC VT QRS .
, - H VT. A
ECG -
.T PVC- - VT. T AV -
VT (Fig. 249-1), P-
. A P- QRS
VT 1:1 .A -
- R R AVR V1 V6
, , .
VT versus Supraventricular Tachycardia
■ IDIOVENTRICULAR RHYTHMS with Aberrancy
T 100 /
(see Fig. 247-1C). A
.I Yes
AV dissociation VT
MI .O ,
, No
.A
.T Yes AVR AVR
AVR = R or Rs VT
.I
, -
.T No
.S -
V1 V2 V3 V4 V5 V6
. Yes
No rS or Rs in VT
any of V1 to V6
■ FURTHER READING
Katritsis DG :N - .JA C No V1 V2 V3 V4 V5 V6
C 60:1993, 2012.
Pedersen CT : EHRA/HRS/APHRS - Possible SVT with aberrancy
.E 16:1257, 2014. VT still possible
FIGURE 249-1 Algorithm or di erentiation o ventricular tachycardia rom
supraventricular tachycardia with aberration.
1758 R S VT (F . 249-1). TABLE 249-1 Ventricular Arrhythmias Associated with Different
A QRS , Forms of Heart Disease
, 1. Idiopathic ventricular tachycardia (VT) without structural heart disease
.I , A. Out low tract origin
QRS a. Right ventricular (RV) out low tract: le t bundle branch block pattern
PART 6
VT, - with in erior axis (tall QRS in in erior leads) and late transition in the
.A precordial leads
. O , b. Le t ventricular (LV) out low tract: prominent “r” in V1
VT; B. Le t posterior ascicular VT
.
Right bundle branch block pattern with le t axis deviation (most

W LV common)
, - - 2. Ischemic cardiomyopathy
VT. S Q- • M onom orphic VT is com m on w ith prior large m yocardial infarction
ECG, -
• P olym orphic VT and ventricu lar fibrillation (VF) shou ld prom pt ischem ia
, evaluation
MR (see Fig. 247-5). 3. Nonischemic cardiomyopathy
■ TREATMENT AND PROGNOSIS • P olym orphic VT and VF m ore com m on bu t fibrotic scars can cau se
I A C L S (ACLS) monomorphic VT especially with sarcoidosis, Chagas disease, Lamin
A/C genetic cardiomyopathy
(Chap. 299). I , , -
4. Arrhythmogenic Right Ventricular Cardiomyopathy
, QRS
, . • M onom orphic VT u su ally of right ventricu lar origin (left bu ndle branch
morphology)
F ,
(Chap. 241). • P olym orphic VT and VF can occu r independently or throu gh degeneration
o monomorphic VT
I .
5. Repaired Tetralogy o Fallot
F ,
.A • M onom orphic VT of right ventricu lar origin (u su ally left bu ndle branch
morphology)
(MI) ,
6. Hypertrophic Cardiomyopathy
MI VT,
CK-MB - • P olym orphic VT or ventricu lar fibrillation
• Less com m only, m onom orphic VT associated w ith m yocardial scars
VT. S 7. Genetic Arrhythmia Syndromes:
VT. I VT , A. Long QT syndrome
, • Torsade de Pointes VT
.M - B. Brugada syndrome
VT , . • Ventricu lar fibrillation
I (ICD ) C. Catecholaminergic polymorphic VT
VT . • P olym orphic VT or bidirectional VT
■ SUSTAINED MONOMORPHIC VT IN SPECIFIC D. Short QT syndrome
DISEASES • Ventricu lar fibrillation
E. Early repolarization syndrome
Coronary Artery Disease P
8. Polymorphic VT or VF
VT
MI
Nonischemic Dilated Cardiomyopathy S -
.E MI, - VT
MI - .T , -
VT. I VT .O MR -
70% 2 . ,
S - -
, - MI. S VT
VT, .A -
.D , VT, ,
, .I C , L A/C
ICD VT (Table 249-1). A ICD
VT .C - VT.
ICD 12.3 8.8%
50% ■ MONOMORPHIC VT IN ARRHYTHMOGENIC RIGHT
VT .C - VENTRICULAR (RV) CARDIOMYOPATHY (ARVC)
, ARVC (Chap. 254)
ICD . .A -
F ICD , , 50%
, VT, 5- .A ,
30%. A - N
, - C . P
, , - ,
. P VT VT, VT .
. F -
, VT Left ventricular intrafascicular VT VT 1759
– , - – .I
VT. .T
T ECG >85% ,
CHAPTER 250 PolymorphicVentricularTachycardia andVentricular Fibrillation

T- V1-V3 (see Fig. 248-1). D P .
QRS (>110 )
S- ■ MANAGEMENT OF IDIOPATHIC VT
, QRS T
“E ” (see Fig. 248-1). C . B -
, - .N -
MRI. ( ) .C
L -
.H .E
, VT,
VT . A ICD .W VT -
, - - .F
.S . .
C VT 70% , L VT
. , -
.C
Tetralogy of Fallot V 3–14% -
F , 2% .
.M VT
RV (T 249-1). F ■ FURTHER READING
VT >5 , Alzand BS, Crijns HJ: D QRS
- , VT :D .E 13:465, 2011.
, RV , QRS John RM, Stevenson WG: O -
>180 . A ICD - :T -
VT, ICD .C E C 8:545, 2016.
.C - - Pedersen CT : EHRA/HRS/APHRS E -
. .E 16:1257, 2014.
■ BUNDLE BRANCH REENTRY VT

R P ~5%
VT . T
,
.C
VT 250 Polymorphic Ventricular
Tachycardia and Ventricular
VT. B Fibrillation
. O -
VT ICD Roy M. John, William G. Stevenson
.
■ IDIOPATHIC MONOMORPHIC VT ■ POLYMORPHIC VENTRICULAR TACHYCARDIA (VT)

I VT
S VT
, , -
.H , VT, -
,
VT
.T QRS
. R ,
( ). T ECG .C -
-
(Chap. A9). S VT
.O
(VF). P VT -
VT, .
(MI),
S .
,
Outflow Tract VTs , -
(see Table 249-1).
.T
VT, - VT PVC Polymorphic VT Associated with Acute Myocardial
.R - VT, Infarction/Ischemia A MI
, VT VT -
— - .A 10% MI VT
.M VF,
, VT .T MI. F -
V1 A C L S (ACLS) ,
, R- II, III, AVF (see Fig. 247-2). I MI (Chap. 269). B - ,
VT , -
. LV . R VT
V1 V2 R- (T 249-1). A MI -
QRS VT, .P VT VF 48
, ARVC, PVC VT MI - ,
.E .
1760 .L - - - CONGENITAL LONG QT SYNDROME T QT
(LV) (LQTS) -
(ICD) - .T QT (QT )
(LV) (LV <0.35). >440 460 .
S torsades des pointes VT (F . 250-1). S
PART 6
Repolarization Abnormalities and Genetic Arrhythmia LQTS ,

Syndromes • ACQUIRED LONG QT A LQT-1, LQT-2 LQT-3 90%
QT VT torsades des pointes .T , LQTS 1 2,
(Fig. 250-1). T VT ,
, (LQTS-3)
QT T- (T 250-1).
(PVC) T , -
VT. T “ - . I LQTS-1, , -
” (F . 250-1). C QT . I LQTS-2,
, , . I LQTS-3,
, .A
, , , - ECG. G
- , , - .
, , , (Table 250-1). C -
I .I LQT-1 LQT-2,
. - ( - -
P - , , ) .
.S VF . M QT 0.5 ,
PVC - VT VT. , .R
I 1–2 , - -
. I , ICD. A QT
, LQTS ,
100–120 / PVC , QT .
VT .T
SHORT QT SYNDROME S QT
( )
(T 250-1). LQTS. T QT 0.36, 0.3 . T
D -
. P VT (IK ) .T
QT - , VT, .
, - BRUGADA SYNDROME B -
QT . >0.2 V ST ST
I aVR V1 V4
II aVL V2 V5
III aVF V3 V6
QT = 680 ms
V1
II II
Sinus
beat PVC
V1 V1
Long interval
Short Initiating beat of
B interval polymorphic VT
FIGURE 250-1 Torsades des pointes VT in patient with bradycardia and marked QT prolongation. A.12-lead ECG showing 2:1 AV block (P waves marked by blue arrows)
with heart rate o 40 bpm and QT interval o 680 ms and corrected QT o 550 ms. B. The bottom panel shows a telemetry rhythm strip with periods o sel -limiting
torsades des pointes polymorphic VT. Following a normally conducted sinus beat, a premature ventricular contraction (PVC) causes a compensatory pause leading to a
long RR interval. A PVC a ter the next sinus beat initiates VT. This is the classic “pause dependent” mode o initiation o torsades des pointes VT with long–short intervals.
VT, ventricular tachycardia.
TABLE 250-1 Causes of QT Prolongation and Torsade de Pointes T- (V1–V3) 1761
Ventricular Tachycardia (VT) (see Fig. 248-1)
1. Congenital long QT syndromes (see text or details) VT . C
Long QT syndrome type 1: Reduced repolarizing current IKs due to .M
CHAPTER 250 PolymorphicVentricularTachycardia andVentricular Fibrillation

mutation in KCNQ1 gene .M -
Long QT syndrome type 2: Reduced repolarizing current IKr due to ~25% .D
mutation in KCNH2 gene ST ,
Long QT syndrome type 3: Delayed inactivation o the I Na due to , MI , ,
mutations in SCN5A gene -
Others: Several other types o Long QT syndromes have been described; (ARVC) .F ,
long QT types 1, 2, and 3 account or 80–90% o cases ST-
2. Acquired Prolongation o QT Interval . A
Electrolyte abnormalities: , ,
Hypokalemia ST . A ICD
Hypomagnesemia
Hypocalcemia
. Q
(RV)
Drugs:
VT.
Antiarrhythmic drugs
Class IA: Quinidine, disopyramide, procainamide EARLY REPOLARIZATION SYNDROME P VF
Class III: Sotalol, amiodarone (QT prolongation common but torsade VT
is rare), ibutilide, do etilide, almokalant J-
Antibiotics QRS. A , -
Macrolides: Erythromycin, clarithromycin, azithromycin
. J-
B
Fluroquinolones: Levo loxacin, moxi loxacin, gati loxacin,
. A ICD
Trimethoprim-sul amethoxazole
.I J- -
Clindamycin
Pentamidine , .
Chloroquine
CATECHOLAMINERGIC POLYMORPHIC VT T
Anti ungals: Ketoconazole, itraconazole
,
Antivirals: Amantadine
, 2. T -
Antipsychotics -
Haloperidol, phenothiazines, thioridazine, tri luoperazine, sertindole,
zimeldine, ziprasidone .T VT QRS
Tricyclic and tetracyclic antidepressants VT. P
Antihistamines (histamine 1-receptor antagonists) , ,
Ter enadine, astemizole, diphenhydramine, hydroxyzine .B - ( . ., )
Cholinergic antagonists: Cisapride, organophosphates .V
Citrate (massive blood trans usions)
Cocaine VT .
Methadone HYPERTROPHIC CARDIOMYOPATHY (HCM) HCM
Fluoxetine (in conjunction with other drugs that prolong QT) 1 500
Cardiac conditions 35 (Chap. 254).
Myocardial ischemia and in arction S VT/VF. R
Myocarditis VT .R -
Marked bradycardia , -
Stress cardiomyopathy
VT, , (
6 ) , >3 ,
Endocrine disorders
LV . A ICD
Hypothyroidism
- , ICD -
Hyperparathyroidism .S ,
Pheochromocytoma <1%
Hyperaldosteronism .T VT
Intracranial disorders -
Subarachnoid hemorrhage 1 5%.
Thalamic hematoma GENETIC DILATED CARDIOMYOPATHIES G -
Cerebrovascular accident 30–40% -
Encephalitis . S .A
Head injury , , X- ,
Nutritional disorders .M
Anorexia nervosa (L A/C) SCN5A
Starvation -
Liquid protein diets . T VT
Gastroplasty and ileojejunal bypass VT. ICD
VT
Celiac disease
(LV
1762 ≤0.35 ) -
. .L
-
■ VENTRICULAR FIBRILLATION .
VF - C PVC
PART 6
QRS (see Fig. 247-3E). S .R ,

. .
S VT VF O ,
.T VT VF ( ).
ACLS .I -
, ■ INCESSANT VT
, VT VT
VT , ,
VF. I MI (Fig. 251-1). T , VT . R ,
, ICD VT ICD
.C .I -
ICD . ,
. VT
■ FURTHER READING -
Adler A, Gollob M: A .C .H
O C 30:8, 2015. .U
Priori SG : HRS/EHRA/APHRS E .
.H R 10:1932, 2013. ■ MANAGEMENT OF PATIENTS PRESENTING WITH

ICD SHOCKS
A ICD
ICD,
.A ,
251 Electrical Storm and
Incessant VT
,
ICD ,
,
.I ICD
Roy M. John, William G. Stevenson
.A -
■ ELECTRICAL STORM ,
E (VT) ,
VT -
(VF) 24 . T .H ,
. ICD
E 4% ,
(ICD) 20% .
VT . S ,
,
■ MANAGEMENT OF THE PATIENT WITH ELECTRICAL .
STORM T , , -
P .R VT/ ,
VF - .
, , I ICD VT VF,
.R
ECG ICD .P
VT VT
.I -
VT VF . , VT
I QT torsades des pointes (see Fig. 247-6). S
. I .I -
QT B , ICD .
/ - S
VT/VF .I , >70% VT , VT .M ICD
VT Anti-tachycardia pacing
terminates VT Spontaneous recurrence of VT
II
FIGURE 251-1 Example o incessant monomorphic VT. In the initial portion o this ECG tracing, monomorphic VT is present. A train o antitachycardia pacing (area
bracketed by arrows) that is initiated at the 4th VT complex results in ventricular capture with usion by the 8th beat and termination o VT at cessation o pacing. The
patient has underlying atrial brillation. Multi ocal PVCs are present. VT similar in morphology to the initial VT restarts spontaneously toward the latter part o the trace
(arrow). VT, ventricular tachycardia.
- .T HF 1763
.I , .A - -
. HF
.F ICD - (LV) (EF); ,
CHAPTER 252 Heart Failure: Pathophysiology and Diagnosis

, VF >220 / -
.L HF EF (EF ≥50%).
VT A , “ ” “ ” HF
. , HF HF
R VT VF - EF (HF EF; systolic failure) HF -
EF (HR EF; diastolic failure). P LV EF
Chaps. 247–250. B 40 50%
.A - EF. A ,
. .
I VT/VF -
, ■ ETIOLOGY
. A Table 252-1,
M LV HF.
ICD , A HF EF
. C EF, -
VT. .I
, (CAD)
■ FURTHER READING 60–75% HF.
Deneke T :C .E R C - H HF 75% ,
T 9:1051, 2011. CAD. B CAD -
John RM, Stevenson WG: V HF, .
.T C M 22:169, I 20–30% HF EF,
2012. .T -
, ,
(Chap. 254). P ( . .,
) .M -
Section 4 Disorders of the Heart ,
,
.M
.
Heart Failure: M ( ,
252 Pathophysiology and , ) ( )
Diagnosis
TABLE 252-1 Etiologies of Heart Failure
Douglas L. Mann, Murali Chakinala
Depressed Ejection Fraction (<40%)
Coronary artery disease Nonischemic dilated cardiomyopathy
Myocardial in arctiona Familial/genetic disorders
HEART FAILURE Myocardial ischemia a In iltrative disordersa
■ DEFINITION Chronic pressure overload Toxic/drug-induced damage
D Hypertensiona Metabolic disordera
(HF), Obstructive valvular diseasea Viral
.T - Chronic volume overload Chagas’ disease
A C C F (ACCF)/A Regurgitant valvular disease Disorders o rate and rhythm
H A (AHA) HF Intracardiac (le t-to-right) shunting Chronic bradyarrhythmias
Extracardiac shunting Chronic tachyarrhythmias
,
Chronic lung disease
HF,
Cor pulmonale
.B
, “ ” Pulmonary vascular disorders
“ .” Preserved Ejection Fraction (>40–50%)
Pathologic hypertrophy Restrictive cardiomyopathy
■ EPIDEMIOLOGY Primary (hypertrophic In iltrative disorders (amyloidosis,
HF , >20 cardiomyopathies) sarcoidosis)
. T HF Secondary (hypertension) Storage diseases
2%. HF - Aging (hemochromatosis)
, , 6–10% Endomyocardial disorders Fibrosis
>65. A HF
High-Output States
, - HF
.I N A E , Metabolic disorders Excessive blood low requirements
HF Thyrotoxicosis Systemic arteriovenous shunting
40- - .T HF , Nutritional disorders (beriberi) Chronic anemia
, - a
Indicates conditions that can also lead to heart ailure with a preserved ejection
(MI), , , raction.
1764 . D Inde
D ’, B ’, - . C - x ev Compensatory
ent
( . ., , mechanisms
) HF
; , , 60%
PART 6
HF.
Ejection fraction
■ GLOBAL CONSIDERATIONS
R HF A
A , .H -
Secondary
HF A A -A - damage
.C ’ HF S A .N
, HF
. A
, HF 20%
W E N A , CAD Time, years
HF. A -
HF , Asymptomatic Symptomatic
. FIGURE 252-1 Pathogenesis o heart ailure with a depressed ejection raction.
Heart ailure begins a ter an index event produces an initial decline in the
heart’s pumping capacity. A ter this initial decline in pumping capacity, a variety
■ PROGNOSIS o compensatory mechanisms are activated, including the adrenergic nervous
D HF, system, the renin-angiotensin-aldosterone system, and the cytokine system. In
HF .C - - the short term, these systems are able to restore cardiovascular unction to a
30–40% 1 normal homeostatic range with the result that the patient remains asymptomatic.
60–70% 5 , HF However, sustained activation o these systems leads to secondary end-organ
( ). A - damage within the ventricle, with worsening le t ventricular remodeling and
subsequent cardiac decompensation. (From D Mann: Circulation 100:999, 1999.)
,
(N Y H A [NYHA] IV) 30–70%
, .I , -
(NYHA II) 5–10%. T ,
(Table 252-2).
.
■ PATHOGENESIS A LV
Figure 252-1 ,
HF EF. HF
index event , / LV
, , , LV .T
, -
. T (1) - - (RAAS)
, MI; , , ,
,
; , (Fig. 252-2) (2) .I -
. R , ,
, (ANP BNP),
, (PGE2 PGI2), (NO),
. M
,
TABLE 252-2 New York Heart Association Classification
, , -
FUNCTIONAL .T LV
CAPACITY OBJECTIVE ASSESSMENT
/
Class I Patients with cardiac disease but without resulting .T ,
limitation o physical activity. Ordinary physical activity does
not cause undue atigue, palpitations, dyspnea, or anginal
pain. ; , -
Class II Patients with cardiac disease resulting in slight limitation ,
o physical activity. They are com ortable at rest. Ordinary . A
physical activity results in atigue, palpitation, dyspnea, or , ,
anginal pain. HF -
Class III Patients with cardiac disease resulting in marked limitation , ,
o physical activity. They are com ortable at rest. Less than LV
ordinary activity causes atigue, palpitation, dyspnea, or remodeling.
anginal pain.
I HF
Class IV Patients with cardiac disease resulting in inability to carry EF,
on any physical activity without discom ort. Symptoms o
heart ailure or the anginal syndrome may be present even HF EF .T ,
at rest. I any physical activity is undertaken, discom ort is ( )
increased. HF
Source: Adapted rom New York Heart Association, Inc., Diseases o the Heart
EF, -
and Blood Vessels: Nomenclature and Criteria or Diagnosis, 6th ed. Boston, Little ,
Brown, 1964, p. 114. .
1765
Baroreceptor
dysfunction - -
↓ Afferent (see Figs. 232-6 and
inhibitory signals
232-7). T -

Vasomotor
Vasomo
Va
asomo
omo
oto
ttor
o center
cente
nter
nte
er 2+
(SR) C
(SERCA2A),
SR,
,
↑ Sympathetic nervous ↑ Vasopressin
SR. T -
↑ Angiotensin II
system activity secretion
α- -
β- , -
↑ Renin secretion
,
.C ,
-
↓ Limb
mb
bbblood
lo
oo flow LV
↓ Renal
na
al blood
bloodd fflflo
flow HF.
↑ Aldosterone
dosster
terone
t rone
tero
onne
e secretion
se M -
↑ Sodium
dium reabso
reabsorption (ATP)-
↑ Water reabsorption
SR SERCA2A -
FIGURE 252-2 Activation o neurohormonal systems in heart ailure. The decreased cardiac output in heart (see Fig. 232-7).
ailure (HF) patients results in an “unloading” o high-pressure baroreceptors (circles) in the le t ventricle, A , ATP -
carotid sinus, and aortic arch. This unloading o the peripheral baroreceptors leads to a loss o inhibitory , ,
parasympathetic tone to the central nervous system (CNS), with a resultant generalized increase in e erent
-
sympathetic tone, and nonosmotic release o arginine vasopressin (AVP) rom the pituitary. AVP (or antidiuretic
hormone [ADH]) is a power ul vasoconstrictor that increases the permeability o the renal collecting ducts, .A , LV
leading to the reabsorption o ree water. These a erent signals to the CNS also activate e erent sympathetic LV
nervous system pathways that innervate the heart, kidney, peripheral vasculature, and skeletal muscles. ( . ., ), LV
Sympathetic stimulation o the kidney leads to the release o renin, with a resultant increase in the circulating
levels o angiotensin II and aldosterone. The activation o the renin-angiotensin-aldosterone system promotes (see Fig. 232-11). A
salt and water retention and leads to vasoconstriction o the peripheral vasculature, myocyte hypertrophy,
myocyte cell death, and myocardial brosis. Although these neurohormonal mechanisms acilitate short-
term adaptation by maintaining blood pressure, these same neurohormonal mechanisms result in end-organ ,
changes in the heart and the circulation, as well as to the excessive salt and water retention in advanced HF. LV ,
(Modifed rom A Nohria et al: Atlas o Heart Failure: Cardiac Function and Dys unction, 4th ed, WS Colucci [ed]. . E LV -
Philadelphia, Current Medicine Group, 2002, p. 104 and J Hartupee, DL Mann: Nat Rev Cardiol 14:30, 2017.)
,
■ BASIC MECHANISMS OF HF -
. I ,
HF with a Reduced Ejection Fraction LV -
TABLE 252-3 Overview of Left Ventricular Remodeling
(Table 252-3). T (1)
; (2) - Alterations in Myocyte Biology
; (3) , , Excitation-contraction coupling
; (4) β- ; (5) Myosin heavy chain ( etal) gene expression
; (6) β-Adrenergic desensitization
- Hypertrophy
Myocytolysis
Cytoskeletal proteins
.T
Myocardial Changes
, ( . .,
, II), ( . ., Myocyte loss
[TNF]), ( . ., - Necrosis
), ( . ., ). T Apoptosis
Autophagy
HF Alterations in extracellular matrix
.I , Matrix degradation
Myocardial ibrosis
( . ., - [ACE] , Alterations in Le t Ventricular Chamber Geometry
- [ARNI ] )
Le t ventricular (LV) dilation
HF (Chap. 253).
T Increased LV sphericity
LV HF, LV wall thinning
Mitral valve incompetence
(Chap. 232). S Source: Adapted rom D. Mann: Pathophysiology o heart ailure, in Braunwald’s
Heart Disease, 8th ed, PL Libby et al (eds). Philadelphia, Elsevier, 2008, p. 550.
1766 . Cardiac asthma
.I - PND,
, ,
HF. .
CHEYNE-STOKES RESPIRATION A
PART 6
Left Ventricular Remodeling Ventricular remodeling

LV , , ,C -S 40%
/ HF
. LV HF .C -S
Pco2 .
LV. I LV T , Po2
- , LV Pco2 .T
.T , , ,
LV , afterload mis- .
match .M - ACUTE PULMONARY EDEMA See Chap. 298.
, - (1)
, LV Other Symptoms P HF -
; (2) , .A , ,
( . ., TNF
1β); (3) / .C -
.I LV -
.C , ,
,
.T HF,
, LV - .N HF
HF. R .
LV
LV ■ PHYSICAL EXAMINATION
HF EF. I , A
HF / LV . HF, HF,
.
■ CLINICAL MANIFESTATIONS General Appearance and Vital Signs I
HF,
Symptoms T HF
.A .
HF, - I HF, ,
,
( . ., )
.I HF, .S HF,
; , , HF LV -
.T ,
, .T -
HF (Chap. 33). T .S
. P
- , J -
.
, ,
.O - Jugular Veins (See also Chap. 234) E
, .T
, / , . ,
D 45°. T
(RV) . ( ≤8 )
ORTHOPNEA O ,
, HF - 5 .I HF,
.I -
(~15 ) ( ).
, . G v .
N - Pulmonary Examination P ( -
HF. O )
.A - .I ,
HF,
( ). W -
. , HF. I ,
PAROXYSMAL NOCTURNAL DYSPNEA (PND) T - HF, LV
,
, 1–3 .P
. PND , -
- .S
, ,
.W .A
- HF, ,
, PND .
Cardiac Examination E , - D , LV 1767
, - /
HF. I , ( MI). T
(PMI) / LV ,

, LV -
.S LV PMI. I D , HF EF. T
, (S3) . 2-D /D RV
P , -
- ( ). M
. A S3 ( protodiastolic gallop) (MRI)
, LV -
.A . MRI
(S4) HF HF, LV
.T - HF ( . ., , -
HF. , ).
T LV EF (
Abdomen and Extremities H - ). B EF
HF. W , ,
- .U , EF -
.A , , , -
.J , / . N ,
HF, , EF (≥50%), -
, EF (<30–40%),
. .M
P HF, -
LV EF .
.P
HF Biomarkers C -
.I ,
(presacral edema) .L - HF. B B- (BNP) N- -BNP
. (NT- BNP), ,
HF EF;
Cardiac Cachexia W HF, HF EF,
. A . I ,
, .W , BNP NT- BNP -
. HF,
■ DIAGNOSIS . M , BNP NT- BNP
T HF HF
HF; ,
HF .A , . H ,
, - ,
- .W , HF
HF, . . BNP ARNI . L
.O , ST-2
Routine Laboratory Testing P - HF -3,
HF - HF .
, , ,
, , .S Exercise Testing T -
( HF,
), ( ), HF
( - ). (Chap. 255). A ( 2
) <14 L/ -
.P 2
<14 L/
Electrocardiogram (ECG) A 12- ECG - , ,
.T ECG .
LV MI (
Q- ) QRS ■ DIFFERENTIAL DIAGNOSIS
( HF (1)
). A ECG LV .
Chest X-Ray A -
( . ., ), (2)
, -
( . ., ). I
, ’ .
HF,
A HF -
.H ,
, , / ,
-
HF .T
(Chap. 33). I , ,
HF -
, , - .
/ .
A BNP NT- BNP
Assessment of LV Function N .A
(Chap. 236) , , , , , . W
HF. T - (2-D) / HF EF,
1768 HF ,
/ . ,
, -
COR PULMONALE .
PART 6
■ DEFINITION ■ PATHOPHYSIOLOGY AND BASIC MECHANISMS

C , pulmonary heart disease, A , -
RV /
RV RV ( . .,
.A RV ) . N ,
HF EF HF EF, . ~15 H
, -
■ ETIOLOGY AND EPIDEMIOLOGY
C .B , , -
, , ( ) ,
, , ,
(Table 252-4). T .A , RV
.F , , (T 252-4). T -
, .
S , - .A , RV
- , -
. H , 2-D /D . T ,
(BNP) . RV .
O , T RV
, .A - .A
(COPD) ( . .,
~50% N A (Chap. 286), ), RV RV
(Chap. 277) - (Chap. 273). C , ,
(T 252-4). P , RV
, RV .O , RV
RV .
A
TABLE 252-4 Etiology of Chronic Cor Pulmonale
.T
Diseases o the Lung Parenchyma ( . ., ), ( . ., COPD),
Chronic obstructive pulmonary disease , , ,
Emphysema
Chronic bronchitis RV .
Interstitial lung diseases
Idiopathic interstitial pneumonias (e.g., IPF, UIP) ■ CLINICAL MANIFESTATIONS
Secondary interstitial diseases Symptoms T
Sarcoidosis .D , -
Combined pulmonary ibrosis and emphysema ,
Bronchiectasis ( -
Cystic ibrosis ), ( . ., - COPD),
Pulmonary Langerhans cell histiocytosis ( . ., ).
Lymphangioleiomyomatosis D
Developmental lung disorders . L -
Disorders o Chronic (Alveolar) Hypoxia
, RV
Alveolar hypoventilation syndromes , -
Obesity hypoventilation syndrome , .
Central hypoventilation syndrome
Neuromuscular respiratory ailure
Signs A
(Chap. 33),
Chest wall disorders
.I ,
Kyphoscoliosis
, S3 RV
Chronic exposure to high altitude .B
Diseases o the Pulmonary Vasculature -
Pulmonary arterial hypertension (PAH) -
Idiopathic PAH v , , -
Heritable PAH , , - .C
Drug and toxin-induced
Associated PAH
( . ., ), , .
Venoocclusive disease
■ DIAGNOSIS
Chronic thromboembolic pulmonary hypertension
I LV -
Pulmonary tumor thrombotic microangiopathy - HF. T ECG
Mediastinal disorders a ecting central pulmonary vasculature P , , RV -
Abbreviations: IPF, idiopathic pulmonary ibrosis; UIP, usual interstitial pneumonitis. .R
.S HEART FAILURE WITH PRESERVED EJECTION 1769
/ FRACTION
-
; ■ GENERAL PRINCIPLES
CHAPTER 253 Heart Failure: Management

.A - (CT) T HF EF , -
- ,
.C CT .A , -
; , - ,
chronic thromboembolic disease (Chap. 273). , ,
T - RV .E
.T
RV - .
, RV LV.
D ■ CLINICAL TRIALS IN HFpEF
.T RV T C H F —A M M -
RV , (CHARM) P
.C - -
RV ( . ., HF EF
[TAPSE], RV , RV , (ARB), .S , I H F
T I ) . MRI P S F (I-PRESERVE)
RV ,
2-D .A D I
.C G (DIG) HF EF.
- I S E N I O
( LV - R S H F (SENIORS)
) - HF. BNP N- , ,
BNP HF EF
RV . - .M -
-
■ FURTHER READING (ACEI)
Braunwald E: H . JACC H F 1:1, 2013. , 6- , ,
Hartupee J, Mann DL: N , .
.N R C 14:30, 2017.
Pengo V :I - ■ NOVEL TARGETS
.NE J M 350:2257, 2004. A -5 silden-
Reddy YN, Borlaug BA: H . afil
C P C 41:145, 2016. HF EF .T
II ,P -5 I
I C -
S E C D H F (RELAX),
HF EF ( [LVEF] >50%) N
Y H A (NYHA) II III ,
Heart Failure: Management 20 3 ,
253 Mandeep R. Mehra
60
T
3 ,
,
.
(QOL),
. C
HF EF, - A A
D T A P E F C H
.T F (TOPCAT) .T
(HF EF) , -
(HF EF), - HF , , ,
(ADHF), . E , .H ,
- A -
HF EF - - R B D H F (ALDO-DHF)
(RAAS)– , , - spironolactone
, , , , QOL
- . H , .O , ,
HF EF ADHF, , ,
, N ’ E A T
.I , H F P E F (NEAT-HF EF)
HF EF, .I QOL -
- - ,
, , .A ARB with an
endopeptidase inhibitor, LCZ696,
3′,5′- , ,
. S .T
– (Chap. 255). I ,
-
, HF EF. T
( ). (PARAGON-HF).
1770 ■ CLINICAL PEARLS , , -
E HF EF , , , (
.A - ), .A -
- , ,
.E .W ,
PART 6
.S - -
HF EF
- .A
, -
(Fig. 253-1). . T
ACUTE DECOMPENSATED HEART FAILURE -

■ GENERAL PRINCIPLES .A -
ADHF :
>43 / L( /L, 0.357),
, , <115 H , >2.75 / L(
.A ADHF - μ /L, 88.4), I .
, A
6 , ADHF
- (5% - ) - Fig. 253-2.
(20% 1 ). I , -
, , - ■ VOLUME MANAGEMENT
, , ,
50% 12 .T Intravenous Diuretic Agents I -
.W
- ( ). ,
T
. I . R - -
- , ADHF, ,
Heart Failure with Preserved Ejection Fraction: Management
Pathology Risk markers

Hypertension
Hypertrophy
Aging
Fibrosis/altered collagen
Atherosclerosis
Infarction/ischemia Diabetes
General Therapeutic Principles Specific Therapy Targets

(beyond general management)
• Reduce the congestive state • Renin-angiotensin-aldosterone–directed therapy

– Caution to not reduce preload excessively – ACEIs and ARBs ineffective (except in “prevention”)
– Aldosterone antagonists (may be beneficial)
• Control blood pressure
– Central aortic blood pressure control may be more relevant • Digoxin
– Ineffective (may reduce hospitalizations)
• Maintain atrial contraction and prevent tachycardia
• Beta blockers and calcium channel blockers
– Efforts to maintain sinus rhythm in atrial fibrilation may be beneficial
– Ineffective (useful in preventing tachycardia)
• Treat and prevent myocardial ischemia • Phosphodiesterase-5 inhibitors
– May mimic HF as an “angina equivalent” – Sildenafil ineffective
• Detect and treat sleep apnea • Novel Therapy

– Common co-morbidity causing systemic hypertension, pulmonary – ARNIs show early promise
hypertension and right heart dysfunction (adaptive servo-ventilation – Isosorbide Mononitrate ineffective (reduces activity tolerance)
ineffective)
• Chronotropic insufficiency
– ? Targeted pacing (unproven)
FIGURE 253-1 Pathophysiologic correlations, general therapeutic principles, and results o speci c “directed” therapy in heart ailure (HF) with preserved ejection
raction. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor.
1771
Heterogeneity of ADHF: Management Principles
Hypertensive Normotensive

Acute Decompensation
“Typical” (usually not volume overloaded) (usually volume overloaded)
High-Risk Features
Vasodilators Diuretics
Renal insufficiency
Biomarkers of injury
Acute coronary syndrome, arrhythmia, hypoxia, pulmonary embolism, infection
Severe Pulmonary Congestion with Hypoxia

Acute Decompensation New onset arrhythmia
“Pulmonary edema” Valvular heart disease
Opiates Inflammatory heart disease O2 and noninvasive ventilation
Myocardial ischemia
CNS injury
Vasodilators Drug toxicity Diuretics
Hypoperfusion with End-Organ Dysfunction

Low pulse pressure Inotropic therapy
Acute Decompensation
Cool extremities (if low blood pressure or
“Low output”
Vasodilators Cardio-renal syndrome diuretic refractoriness)
Hepatic congestion
Hemodynamic monitoring
(suboptimal initial therapeutic response)
Hypotension, Low Cardiac Output, and End-Organ Failure
Acute Decompensation Extreme distress

“Cardiogenic shock” Inotropic therapy Pulmonary congestion Mechanical circulatory support
(usually catecholamines) Renal failure (IABP, percutaneous VAD,
ultrafiltration)
FIGURE 253-2 The distinctive phenotypes o acute decompensated heart ailure (ADHF), their presentations, and suggested therapeutic routes. (Unique causes o
ADHF, such as isolated right heart ailure and pericardial disease, and rare causes, such as aortic and coronary dissection or ruptured valve structures or sinuses o
Valsalva, are not delineated and are covered elsewhere.) IABP, intraaortic balloon pump; VAD, ventricular assist device.
.A .I
, -
-
.C -
,
, .
.
I
Ultrafiltration U (UF)
.P , .P
, UF ,
, . T
.
The Cardiorenal Syndrome T – .I
ADHF. M - UF ,
, -
, UF; ,
,
.A .I C R S A D H
30% ADHF - F (CARRESS-HF) , 188 ADHF
, UF.
.H , T
, - ( ) 96 . A
, - , ; (~5.5 ),
- UF .D
.I ,
, - UF , , ,
, “ ” - .T
UF ADHF
.C .W UF
- ,
- .
1772 ■ VASCULAR THERAPY ,
V intravenous nitrates, nitroprusside, nesiritide - 180
( - ) .T
ADHF. T -
- .
PART 6
A , omecamtiv
. E mecarbil, -
.D , ,
.T - , .A
, - , A S - , COSMIC-HF (C O
C E N D H F S M A I C H F )
(ASCEND-HF) 2011 448 -
7141 ADHF 24–168 - , 20 ,
.N ,
.O
. R -
, . A T I A
, . (Table 253-1 , ,
. Recombinant human ADHF.)
relaxin-2, ,
ADHF . ■ NEUROHORMONAL ANTAGONISTS
I R A H F (RELAX-AHF) , O
1161 ADHF. T P -C R S
ADHF, , S A1 A R A R
>125 H .S , - P H A D H F
, V O A T E C R
HF. E 6 F (PROTECT)
.A E V A H F O S
.R , T (EVEREST) -2
(TRUE-AHF) ADHF ADHF .
In patients who fail to respond adequately to medical therapy,
, mechanical assist devices may be required. This is covered in more
6 .U detail in Chap. 255.
.
HEART FAILURE WITH REDUCED EJECTION
FRACTION
■ INOTROPIC THERAPY T 50
I ADHF, HF EF. T
( ) ( , -
, ) -
( ) -3 .I , RAAS
( ), , . -
T .I
- , , QOL,
, . A - ,
, - (Fig. 253-3).
■ NEUROHORMONAL ANTAGONISM
.S M - 23% 35% -
β1 - , -
. ACEI . P
S - 35% -
.H , - ACEI .I
ADHF , , HF EF
.I ACEI -
( - ,
) - , .T ACEI
. (NYHA III –IV).
N H ,
. Levosimendan
, -3 . S ACEI
.T - .
.
T , R M E I - Class Effect and Sequence of Administration ACEI
L E (REVIVE II) S P HF EF ; ,
A H F N I I S .
(SURVIVE), ADHF. SURVIVE B ( )
, , ,
B- . O , HF EF
TABLE 253-1 Intravenous Therapy in Acute Decompensated Heart Failure 1773
DRUG CLASS GENERIC DRUG USUAL DOSING SPECIAL CAUTION COMMENTS

Inotropic Use in hypotension, end-organ hypoper usion, or shock states
therapy

Dobutamine 2–20 μg/kg per min Increased myocardial oxygen Short acting, an advantage; variable e icacy in presence o beta
demand, arrhythmia blockers (requires higher doses); clinical tolerance to prolonged
in usions; concerns with hypersensitivity carditis (rare)
Milrinone 0.375–0.75 μg/kg Hypotension, arrhythmia Decrease dose in renal insu iciency; avoid initial bolus;
per min e ectiveness retained in presence o beta blockers
Levosimendan 0.1 μg/kg per min, Hypotension, arrhythmia Long acting; should not be used in presence o low blood
range, 0.05–0.2 μg/ pressure; similar e ectiveness as dobutamine but e ectiveness
kg per min retained in presence o beta blockers
*
Omecamtiv Mecarbil N/A In trials Increases contractility without increasing myocardial oxygen
demand; in con irmatory trials
Vasodilators Use in presence o pulmonary congestion or rapid relie o
dyspnea, in presence o a preserved blood pressure
Nitroglycerine 10–20 μg/min, Headache, lushing, tolerance Most common vasodilator but o ten underdosed; e ective in
increase up to higher doses
200 μg/min
Nesiritide Bolus 2 μg/kg Hypotension Decrease in blood pressure may reduce renal per usion pressure;
and in usion at bolus may be avoided since it increases hypotension predilection
0.01 μg/kg per min
Nitroprusside 0.3 μg/kg per min Thiocyanate toxicity in renal Requires arterial line placement or titration or precise blood
titrated to 5 μg/kg insu iciency (>72 h) pressure management and prevention o hypotension
per min
Serelaxin N/A (tested at Baseline blood pressure Not widely commercially available; ine ective in con irmatory trials
30 μg/kg per d) should be >125 mmHg
Ularitide 15 ng/kg/min (48 h) Baseline blood pressure Excess hypotension and increase serum creatinine
>116 mmHg
Diuretics First line o therapy in volume overload with congestion; may use
bolus or continuous dosing; initial low dose (1 × home dose) or
high dose (2.5 × home dose) equally e ective with higher risk o
renal worsening with higher dose
Furosemide 20–240 mg daily Monitor or electrolyte loss In severe congestion, use intravenously and consider continuous
in usion (not trial supported)
Torsemide 10–100 mg daily Monitor or electrolyte loss High bioavailability, can be given orally; anecdotally more e ective
in advanced heart ailure states i urosemide less bioavailable
(due to gut congestion)
Bumetanide 0.5–5 mg daily Monitor or electrolyte loss Can be used orally; intermediate bioavailability
Adjuvant diuretics n/a Metolazone, chlorthalidone, Acetazolamide is use ul in presence o alkalosis; metolazone
or augmentation spironolactone, acetazolamide given in 2.5- to 10-mg doses; causes severe electrolyte
imbalance; spironolactone is use ul in presence o severe
hypokalemia and normal renal unction
, , (SCD). H -
— ,
. W ACEI ,
C I B S (CIBIS) III, .
.
T , ; ■ RAAS THERAPY AND NEUROHORMONAL “ESCAPE”
ACEI - N “ ” HF EF
. II -
Dose and Outcome A - ACEI . ARB -
ACEI AT1 .M -
. B - 24 ARB
- ACEI
. C , - -
( ), ACEI . T V H F T (V -H FT)
- 2 -
. ACEI
.S ,
■ MINERALOCORTICOID ANTAGONISTS
A
NYHA II IV HF EF. E -
HF EF , .T ,
, - (ACEI ;
.T ( NYHA , ACEI ARB; ACEI , ARB
II – ) - ). I (NYHA II–IV),
( NYHA III IV , -
) , .
1774 Limits of Pharmacologic Therapy in HFrEF
Placebo (Diu retics and dig oxin)

PART 6
Ineffective Potentially effective

ACE inhibitors • EPO for anem ia • Fis h oil(PUFA)
orARBs • Warfarin for • Ivabradine
(ARNIs ins tead • Irons u pplem entation(?)
Mortality reduction
throm boem bolis m

ofACEI m ore
effective) • SSRI for depres s ion

• Statins for HF
β-Block ers
(except bu cindolol) Moxonidine
X am oterol
Mineralocorticoid receptor *Hydralazine-nitrates
antag onis ts
Endothelin
antag onis ts
Om apatrilat Etanercept
Incremental benefit
FIGURE 253-3 Progressive decline in mortality with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) or angiotensin receptor
neprilysin inhibitors (ARNIs), beta blockers, mineralocorticoid receptor antagonists, and balanced vasodilators (*selected populations such as A rican Americans);
urther stack-on neurohormonal therapy is ine ective or results in worse outcome; management o comorbidity is o unclear e cacy. EPO, erythropoietin; HF, heart
ailure; HFrEF, heart ailure with reduced ejection raction; PUFA, polyunsaturated atty acid; SSRI, selective serotonin reuptake inhibitor.
A A T A H F .T ACEI
O (ASTRONAUT) , , ,
, - O V E R T U R
HF EF. N E (OVERTURE) .T
6 12 -
.A .T
, - ACEI .
, , M , LCZ696, ARB ( )
.T ( ),
RAAS . ARB .T ,
– (ARNI) ( E ),
■ ARTERIOVENOUS VASODILATION PARADIGM-HF
T ACEI
HF EF. H ACEI .M -
ACEI -
;
, - .
- .T Table 253-2 -
, ACEI HF EF.
ARB . H , HF EF RAAS-
,
- .A ■ HEART RATE MODIFICATION
- A A , A -A I , I ,
H F T (A-H ), .T S H F
HF EF T I C P T (SHIFT)
.T II III HF EF, >70 / ,
.
.A - I -
. - .T
N A
■ NOVEL NEUROHORMONAL ANTAGONISM HF EF , ,
D -
40% .A
RAAS , 90% , .W
.A , ,
- .I
HF EF - 2012 E S C
. S , , ,I
- ACEI , ,
TABLE 253-2 Pharmacologic Therapy and Target Doses in Heart Failure with Reduced Ejection Fraction 1775
MEAN DAILY DOSE IN

DRUG CLASS GENERIC DRUG CLINICAL TRIALS (mg) INITIATION (mg) TARGET DOSE (mg)

Angiotensin-Converting Enzyme Inhibitors
Lisinopril 4.5–33 2.5–5 qd 20–35 qd
Enalapril 17 2.5 bid 10–20 bid
Captopril 123 6.25 tid 50 tid
Trandolapril N/A 0.5–1 qd 4 qd
Angiotensin Receptor Blockers
Losartan 129 50 qd 150 qd
Valsartan 254 40 bid 160 bid
Candesartan 24 4–8 qd 32 qd
Aldosterone Antagonists
Eplerenone 42.6 25 qd 50 qd
Spironolactone 26 12.5–25 qd 25–50 qd
Beta Blockers
Metoprolol succinate CR/XL 159 12.5–25 qd 200 qd
Carvedilol 37 3.125 bid 25–50 bid
Bisoprolol 8.6 1.25 qd 10 qd
Arteriovenous Vasodilators
Hydralazine isosorbide 270/136 37.5/20 tid 75/40 tid
dinitrate
Fixed-dose hydralazine/ 143/76 37.5/20 qid 75/40 qid
isosorbide dinitrate
Angiotensin Receptor Neprilysin Inhibitor
Sacubitril-valsartan 375 100 bid 200 bid
■ INFLAMMATION
>70 / .A T α
. (TNF-α)
.U
■ DIGOXIN
D , .N -
, - .T A C
, , - H F C A I M T
.T DIG (ACCLAIM-HF) -
( -
) -
QOL. I , . T
.I -
- .T
, , (
.A -
, ) .
.G ,
■ STATINS
. P -
■ ORAL DIURETICS – -
N . .O ,
L
, .T ,C R -
.I , M T H F (CORONA) G
, I S S ’I C
.T , - (GISSI-HF), - HF EF
. .I
I ,
. , .
H ,
■ CALCIUM CHANNEL ANTAGONISTS .
A , - –
, HF EF ■ ANTICOAGULATION AND ANTIPLATELET THERAPY
, , QOL. T - , HF EF
, , , ,
.T .A - -
. ,
1776 , - - ,
.A
.I , - -
W A R C E F
(WARCEF) , - – .W
PART 6
- 6 . A
LVEF ,
-
.A .T
. , LVEF,
A ACEI- , 6- .H ,
.C - .
. A , -
HF EF
■ FISH OIL .
T - -3 (ω-3 Anemia , -
PUFA ) QOL,
HF EF. T .A
GISSI-HF ω-3 PUFA , HF EF,
3 .T - , A A . T
ω-3 PUFA (EPA) , ,
(DHA). L EPA . I
HF EF. (F C A
P I D C H F [FAIR-HF]
■ MICRONUTRIENTS )
A .A , CONFIRM-HF,
. R ( <100 / L 100–300 / L
. <20%)
T -
, , QOL. O
.S .
HF EF E -
.T .T R E
ADHF .D D A H F (RED-HF)
, -
. .
Depression HF EF,
■ ENHANCED EXTERNAL COUNTERPULSATION (EECP) , QOL,
P , -
1- 35 .H , HF EF,
(7 ) - S A D H D C H
- F (SADHART-CHF) ,
. T P E E ,
E C C H F (PEECH)
- .
- - . T - Atrial arrhythmias, ,
, QOL, NYHA .
W ,
.A .R
. ,
■ EXERCISE . A
T H F :AC T I O E - ,
T (HF-ACTION) - (3- ) -
- (12- ) .T A T D M - -S
HF EF. E , C H F E M D (ANDROM-
’ - , - EDA) -
.M 6- - .
3 C
12 . -
T ,
. .
Diabetes mellitus - .P
MANAGEMENT OF SELECTED ( -
COMORBIDITY ) .
Sleep-disordered breathing HF G - 1 (GLP-1)
HF EF. A - -
, , C -S .R ,
. F EMPA-REG
. TABLE 253-3 Principles of ICD Implantation for Primary Prevention 1777
T , – 2 (SGLT2), of Sudden Death
.T PRINCIPLE COMMENT
. Arrhythmia–sudden death Sudden death in heart ailure patients is

mismatch generally due to progressive LVD, not a ocal
■ NEUROMODULATION USING DEVICE THERAPY arrhythmia substrate (except in patients with
A post-MI HF)
- Diminishing returns with Intervention at early stages o HF most
.B , advanced disease success ul since sudden death diminishes as
, , , - cause o death with advanced HF
, Timing o bene its LVEF should be evaluated on optimal medical
.W - therapy or a ter revascularization be ore ICD
, - , , therapy is employed; no bene it to ICD implant
.T INOVATE-HF within 40 days o an MI (unless or secondary
prevention)
HF. V
Estimation o bene its and Patients and clinicians o ten overestimate
prognosis bene its o ICDs; an ICD discharge is not
HF. H , QOL equivalent to an episode o sudden death (some
. ventricular arrhythmias terminate spontaneously);
appropriate ICD discharges are associated with a
CARDIAC RESYNCHRONIZATION THERAPY worse near-term prognosis
N Abbreviations: HF, heart ailure; ICD, implantable cardioverter-de ibrillator; LVD,
( ) ( - le t ventricular disease; LVEF, le t ventricular ejection raction; MI, myocardial
in arction.
) ,
, .M -
LVEF <35%,
.T , ICD . I
QRS -
, . LVEF ≤30% ( ),
W ICD .A D
, (CRT) ICD
-
.E - -
, , - .I , <60 .I
.T C R H F S (CARE-HF) <6
- - NYHA IV -
CRT HF EF ,
- - NYHA ICD .I
III IV .M QRS CRT, CRT ICD
- CRT (Table 253-3).
HF EF, R –D
A H F T (RAFT) M A SURGICAL THERAPY IN HEART FAILURE
D I T C R T - Coronary artery bypass grafting (CABG)
(MADIT-CRT), CRT
.M . T ,
HF EF QRS
>149 .A ,
CRT CABG
- .R -
. I , .R
, QRS -
.U .T S T I H F (STICH)
CRT ADHF, - ≤35%
, , CABG
, CRT . H , CABG
.
10
SUDDEN CARDIAC DEATH PREVENTION IN .A
HEART FAILURE
SCD - -
- ,
HF EF . .
P SCD Surgical ventricular restoration (SVR), -
-
(ICD). A ,
, . H ,
(≤35%) 1000- HF EF CABG
( – ) CABG SVR, SVR CABG -
. H ,
.C , NYHA II III ,
1778 ,
.O , -
- .H ,
, , .I
. -
PART 6
Mitral regurgitation (MR) , ,

HF EF .A -
,
, MR. I 39% ( C MEMS H S A M P -
- I O NYHA C III H F P
, . I MR ( [CHAMPION] ). O ,
- MR)
-
.N - -
MR - .A ,
MR . , , -
, QOL,
CELLULAR AND GENE-BASED THERAPY .E
T
, – .
. I – W ,
- , -
- ICD ,
.M , , - QOL .
.T
.I , - – GLOBAL CONSIDERATIONS
CABG S
.I , - .T -
.T CRT ICD U S
E .C , U S ,
.T , E .V -
, -
, ( . I HF EF,
), , - - E
. N A -
T , .T
, HF EF. A .I ,
.A ,
SERCA2 HF EF. P TOPCAT,
- US R
, CUPID (E .W
S S G T E R T . ADHF,
A H F ) .T - E E ,
- 1 SERCA2 . P S
, A , -
, , .I , N A
.H ,
. .G -
More advanced therapies for late-stage heart failure such as left ,
ventricular assist devices and cardiac transplantation are covered in U S W E .
detail in Chap. 255.
■ FURTHER READING
DISEASE MANAGEMENT AND SUPPORTIVE Braunwald E: H . JACC H F 1:1, 2013.
CARE Braunwald E: T :T L .L
D , 385:812, 2015.
, Cowie MR :A -
6 .R .NE J M 373:1095, 2015.
Kusumoto FM : HRS/ACC/AHA
, - -
.T .C -
130:94, 2014.
- McMurray JJ : PARADIGM-HF I C .
, , A - .
, - . E NE J M . 371:993, 2014.
- , - , Ramani GV :C :C
– .M C P 85:180, 2010.
2 .A Redfield MM : NHLBI H F C R N .
, I -
. I .NE J M 373:2314, 2015.
Shah SJ :P - - , 1779
:A .C 134:73, “ .” A
2016. ,
Velazquez EJ : STICHES I .C -
CHAPTER 254 Cardiomyopathy andMyocarditis

. N E J M .A ,
374:1511, 2016. , -
Zinman B : EMPA-REG OUTCOME .E ,
, 2 .NE J .T congestive heart failure
M 373:2117, 2015. ,
.A -
(AV) ,
, -
Cardiomyopathy and , (T 254-1). I
254 Myocarditis ,
,
(Table 254-2).
,
Neal K. Lakdawala, Lynne Warner Stevenson,

■ GENETIC CAUSES OF CARDIOMYOPATHY
Joseph Loscalzo
E -
,
.W - -
■ DEFINITION AND CLASSIFICATION , 30%
C . I (DCM) .C
5–10%
5–6 U S .T , ,
“ ,”
, , ,
, ; , , .
ischemic cardiomyopathy M
, , X-
nonischemic cardiomyopathy (Table 254-3). M -
.A 2013, “ - .E
, , . M
.” It was further specified that many cardiomyopathies ( ) ( )
will be attributable to genetic disease.1 -
T ( ). D
, , ,
. D .
M -
; , - ( ),
( ). A
, “ ” ,
.R ,
, .
- G -
.R , .T
, , , .
(Table 254-1). R same
E
. , , -
I , .S
- ,
( ) - .C -
.T , 3–5%
, .I , . H ,
,
, ; ,
.A .C ,
, . H ,
. ,
F ’ G .
GENERAL PRESENTATION
F , ■ GENES AND PATHWAYS IN CARDIOMYOPATHY
, M , -
. T , . W
,
1
F EA : JA C C 62:2046, 2013. DCM,
1780 TABLE 254-1 Presentation with Symptomatic Cardiomyopathy
DILATED RESTRICTIVE HYPERTROPHIC
Ejection raction (normal >55%) Usually <30% when symptoms severe 25–50% >60%
Le t ventricular diastolic ≥60 mm <60 mm (may be decreased) O ten decreased
dimension (normal <55 mm)
PART 6
Le t ventricular wall thickness Normal or decreased Normal or increased Markedly increased

Atrial size Increased, may also be primarily a ected Increased; may be massive Increased; related to
elevated illing pressures
Valvular regurgitation Related to annular dilation; mitral appears Related to endocardial involvement; requent Related to valve-septum
earlier during decompensation; tricuspid mitral and tricuspid regurgitation, rarely severe interaction; mitral
regurgitation with right ventricular dys unction regurgitation
Common irst symptoms Exertional intolerance Exertional intolerance, luid retention early, may Exertional intolerance; may
have dominant right-sided symptoms have chest pain
Congestive symptomsa Le t be ore right, except right prominent in Right o ten dominates Le t-sided congestion at
young adults rest may develop late
Arrhythmias Ventricular tachyarrhythmia; conduction block Ventricular uncommon except in sarcoidosis, Ventricular
in Chagas’ disease, and some amilies. Atrial conduction block in sarcoidosis and tachyarrhythmias; atrial
ibrillation. amyloidosis. Atrial ibrillation. ibrillation
a
Le t-sided symptoms o pulmonary congestion: dyspnea on exertion, orthopnea, paroxysmal nocturnal dyspnea. Right-sided symptoms o systemic venous congestion:
hepatic and abdominal distention, discom ort on bending, peripheral edema.
TABLE 254-2 Initial Evaluation of Cardiomyopathy . T

DCM
Clinical Evaluation
, TTN,
Thorough history and physical examination to identi y cardiac and noncardiac .
disordersa
A , -
Detailed amily history o heart ailure, cardiomyopathy, skeletal myopathy,
, ,
conduction disorders, tachyarrhythmias, and sudden death
, (Fig. 254-1).
History o alcohol, illicit drugs, chemotherapy or radiation therapya
F ,
Assessment o ability to per orm routine and desired activitiesa
, Z- ,
Assessment o volume status, orthostatic blood pressure, body mass indexa .D
Laboratory Evaluation
Electrocardiograma .
Chest radiographa D
Two-dimensional and Doppler echocardiograma DCM. T , X
Magnetic resonance imaging or evidence o myocardial in lammation and DMD, D ’ B ’
ibrosis . (I ,
Chemistry: .)
Serum sodium,a potassium,a calcium,a magnesiuma T
Fasting glucose (glycohemoglobin in diabetes mellitus) .T
Creatinine,a blood urea nitrogena .
Albumin,a total protein,a liver unction testsa
D -
, , DCM.
Lipid pro ile
D (channelopathies) -
Thyroid-stimulating hormonea
, SCN5A,
Serum iron, trans errin saturation
B QT ,
Urinalysis DCM .
Creatine kinase iso orms N
Cardiac troponin levels ( A/C) X- ( ) .
Hematology: T -
Hemoglobin/hematocrita ,
White blood cell count with di erential,a including eosinophils .
Erythrocyte sedimentation rate I ,
Initial Evaluation When Specifc Diagnoses Are Suspected -
DNA sequencing or genetic disease, panel selection based on phenotype
. M
,
Titers or in ection in the setting o clinical suspicion:
,
Acute viral (coxsackie, echovirus, in luenza)
.T
Human immunode iciency virus .A
Chagas’ (Trypanosoma cruzi), Lyme (Borrelia burgdor eri), toxoplasmosis ( ),
Catheterization with coronary angiography in patients with angina who are “
candidates or interventiona .”
Serologies or active rheumatologic disease A ,
Endomyocardial biopsy including sample or electron microscopy when
suspecting speci ic diagnosis with therapeutic implications . I ,
Screening or sleep-disordered breathing
a .C ,
Level I recommendations rom ACC/AHA Practice Guidelines or Chronic Heart
Failure in the Adult.
TABLE 254-3 Selected Genetic Defects Associated with Cardiomyopathy 1781
CARDIAC ISOLATED CARDIAC

GENE PRODUCT INHERITANCE PHENOTYPE PHENOTYPE a EXTRACARDIAC MANIFESTATIONS
Sarcomere AD HCM, DCM, LVNC Yes Skeletal myopathy

MYH7 (β myosin heavy chain)
MYBPC3 (myosin binding protein C) AD HCM Yes
TNNT2 (cardiac troponin T) AD HCM, DCM, LVNC Yes
TNNI3 (cardiac troponin I) AD, AR HCM, DCM, RCM Yes
TTN (Titin) AD DCM Yes
TPM1 (α-tropomyosin) AD HCM, DCM Yes
TNNC1 (cardiac troponin C) AD DCM Yes
MYL2 (myosin regulatory light chain) AD HCM Yes Skeletal myopathy
MYL3 (myosin essential light chain) AD HCM Yes
Z-disk and DES (Desmin) AD DCM, RCM Yes Skeletal myopathy
Cytoskeleton
ANKRD1 (CARP) AD HCM, (DCM) Yes
CSRP3 (MLP) AD DCM, (HCM) Yes
ACTN2 (α-actinin-2) AD DCM Yes
CRYAB (αB-crystallin) AD DCM Yes
FLNC (Filamin C) AD DCM Yes Skeletal myopathy
Nuclear LMNA (Lamin A/C) AD, AR CDDC Yes Skeletal myopathy
Membrane
EMD (Emerin) X-linked CDDC No Skeletal myopathy, contractures
Excitation- PLN (Phospholamban) AD DCM Yes
Contraction
Coupling
SCN5A (NAV 1.5) AD CDDC Yes Note other mutations associated
with Brugada syndrome
RYR2 (cardiac ryanodine receptor) AD ARVC Yes
CASQ2 (calsequestrin 2) AR ARVC Yes
Cellular PRKAG2 (γ-subunit o AMP kinase) AD HCM+ Yes
Metabolism
LAMP2 (lysosomal associated X-linked HCM+ No a Danon’s disease: skeletal myopathy,
membrane protein) cognitive impairment
TAZ (Ta azzin) X-linked DCM, LVNC No Barth’s syndrome: skeletal
myopathy, cognitive impairment,
neutropenia
FXN (Frataxin) AR HCM No Friedreich’s ataxia: ataxia, diabetes
mellitus type 2
TMEM43 (transmembrane protein 43) AD ARVC Yes
GLA (α-galactosidase-A) X-linked HCM+ Yes Fabry’s disease: renal ailure,
angiokeratomas and pain ul
neuropathy
Mitochondria Mitochondrial DNA Maternal DCM, HCM No MELAS, MERRF, Kearns-Sayre
transmission syndrome, ocular myopathy
Sarcolemmal DMD (Dystrophin) X-linked DCM No a Duchenne’s and Becker’s muscular
Membrane dystrophy
DMPK (dystrophica myotonica protein AD DCM No Myotonic dystrophy type 1
kinase)
SGCD (δ-sarcoglycan) AD DCM Yes
Desmosome DSP (Desmoplakin) JUP (Plakoglobin) AD, AR ARVC Yes Carvajal syndrome (AR), Naxos
syndrome (AR), “woolly hair” and
hyperkeratosis o palms and soles
DSG2 (Desmoglein 2) DSC2 AD ARVC Yes
(Desmocollin 2) PKP2 (Plakophilin 2)
Other Examples RBM20 (RNA binding moti 20) AD DCM Yes
PSEN1 (Presenilin-1,2) AD DCM Yes Dementia
BAG3 (BCL2-associated athanogene 3) AD DCM Yes
ALPK3 (Alpha-kinase 3) AR HCM Yes
a
Indicates that the usual clinical presentation is o isolated cardiomyopathy, however occasionally present extra cardiac mani estations are also provided. aIndicates that
isolated cardiac phenotype can occur in women with the X-linked de ects.
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; ARVC, arrhythmogenic right ventricular cardiomyopathy; CDDC, conduction disease with dilated
cardiomyopathy; DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; HCM+, HCM with preexcitation; HCMc, HCM with conduction disease; LVNC, le t
ventricular noncompaction; MELAS, (mitochondrial) myopathy, encephalopathy, lactic acidosis, and strokelike episodes syndrome; MERRF, myoclonic epilepsy with ragged
red ibers; RCM, restrictive cardiomyopathy.
1782
PART 6
FIGURE 254-1 Drawing o myocyte indicating multiple sites o abnormal gene products associated with cardiomyopathy. Major unctional groups include the
sarcomeric proteins (actin, myosin, tropomyosin, and the associated regulatory proteins), the dystrophin complex stabilizing and connecting the cell membrane to
intracellular structures, the desmosome complexes associated with cell-cell connections and stability, and multiple cytoskeletal proteins that integrate and stabilize
the myocyte. ATP, adenosine triphosphate. (Figure adapted rom Je rey A. Towbin, MD, University o Tennessee Health Science Center, with permission.)
, ( ),
- A (F ’ ). A .L
DNA ( ) -
, .D -
.T .
M
.H , .
, - M “ ”
. .D
F , ,
-
. S
(ECG). T .
.T R , -
, . A
. -
.E - ,
DILATED CARDIOMYOPATHY -
A , β-
DCM (Figs. 254-2, - . F
254-3, and 254-4). Systolic failure -
.A DCM - , -
(Table 254-4),
.W , .I
, “ ”
1783

FIGURE 254-4 Dilated cardiomyopathy. Microscopic specimen o a dilated
cardiomyopathy showing the nonspeci c changes o interstitial brosis and
myocyte hypertrophy characterized by increased myocyte size and enlarged,
irregular nuclei. Hematoxylin and eosin–stained section, 100× original
magni cation. (Image courtesy o Robert Padera, MD, PhD, Department o
Pathology, Brigham and Women’s Hospital, Boston.)
.T
DCM
FIGURE 254-2 Dilated cardiomyopathy. This gross specimen o a heart removed (Chap. 252),
at the time o transplantation shows massive le t ventricular dilation and .
moderate right ventricular dilation. Although the le t ventricular wall in particular
appears thinned, there is signi cant hypertrophy o this heart, which weighs ■ MYOCARDITIS
>800 g (upper limit o normal = 360 g). A de brillator lead is seen traversing the
tricuspid valve into the right ventricular apex. (Image courtesy o Robert Padera, M ( )
MD, PhD, Department o Pathology, Brigham and Women’s Hospital, Boston.)
, -
, .
M -
,
-
.I
Trypanosoma cruzi.
■ INFECTIVE MYOCARDITIS
T
.A -
, ,
- .V
LV .F ,
2A
,
.A
RV ,
.
T
, T -
.C , -
T- B- .
LA
T ,
RA
.H ,
,
.
T
FIGURE 254-3 Dilated cardiomyopathy. This echocardiogram o a young man with T-
dilated cardiomyopathy shows massive global dilation and thinning o the walls o .I ,
the le t ventricle (LV). The le t atrium (LA) is also enlarged compared to normal.
Note that the echocardiographic and pathologic images are vertically opposite, .O
such that the LV is by convention on the top right in the echocardiographic image
and bottom right in the pathologic images. RA, right atrium; RV, right ventricle. , .
(Image courtesy o Justina Wu, MD, Brigham and Women’s Hospital, Boston.) S - .
1784 TABLE 254-4 Major Causes of Dilated Cardiomyopathy S -
(with Common Examples) ,
In ammatory Myocarditis β- , , N +/K+ ATP ,
-
In ective
.
Viral (coxsackie,a adenovirus,a HIV, hepatitis C)
PART 6
I ,
Parasitic (T. cruzi—Chagas’ disease, trypanosomiasis, toxoplasmosis) -
Bacterial (diphtheria) , .
Spirochetal (Borrelia burgdor eri—Lyme disease) G
Rickettsial (Q ever) DCM, -
Fungal (with systemic in ection)

Nonin ective ( ). F
Granulomatous in lammatory disease , ,
Sarcoidosis
Giant cell myocarditis
(Fig. 254-5).
Eosinophilic myocarditis
Polymyositis, dermatomyositis
Clinical Presentation of Viral Myocarditis Acute viral
myocarditis .
Collagen vascular disease
S
Checkpoint inhibitor chemotherapy . O , -
Transplant rejection ,
Toxic . E
Alcohol
Catecholamines: amphetamines, cocaine .T -
Chemotherapeutic agents (anthracyclines, trastuzumab)
-
Inter eron
.
Other therapeutic agents (hydroxychloroquine, chloroquine) A ,
Drugs o misuse (emetine, anabolic steroids)
Heavy metals: lead, mercury -
Occupational exposure: hydrocarbons, arsenicals , , , .T
Metabolic a
Nutritional de iciencies: thiamine, selenium, carnitine
, -
Electrolyte de iciencies: calcium, phosphate, magnesium
.P
Endocrinopathy
- -
Thyroid disease .R
Pheochromocytoma -
Diabetes , -
Obesity .T
Hemochromatosis - , -
Inherited Metabolic Pathway De ectsa .
Chronic viral myocarditis , ,
Familiala (See Table 254-3)
DCM .H ,
Skeletal and cardiac myopathy “ ”
Dystrophin-related dystrophy (Duchenne’s, Becker’s)
Mitochondrial myopathies (e.g., Kearns-Sayre syndrome) .T , DCM
Arrhythmogenic ventricular cardiomyopathy .
Hemochromatosis
Associated with other systemic diseases Laboratory Evaluation for Myocarditis T
ECG, ,
Susceptibility to immune-mediated myocarditis
.M -
Overlap with Nondilated Cardiomyopathy -
“Minimally dilated cardiomyopathy” ,
Hemochromatosisa (Fig. 254-6),
Amyloidosisa - ( ).
Hypertrophic cardiomyopathya (“burned-out”) Endomyocardial biopsy
“Idiopathic”a
.T
Miscellaneous (Shared Elements o Above Etiologies)
, ,
Peripartum cardiomyopathy - - .
Le t ventricular noncompactiona W , D C
Tachycardia-related cardiomyopathy (Fig. 254-7)
Supraventricular arrhythmias with uncontrolled rate 80–90% .N
Very requent nonsustained ventricular tachycardia or high premature D C -
ventricular complex burden , -
a
Some speci ic cases can be linked now to speci ic genetic mutation in a amilial
- .R
cardiomyopathy; others with similar phenotypes that appear to be acquired or
idiopathic may represent genetic actors not yet identi ied. , Cytomegalovirus.
Immune Responses 1785
,
Lymphocytes Antibodies ,
Antibodies Against pathogen . W
Infection

Against Against surface antigens
pathogen Against myocyte proteins
CK-MB
, -
Cytokines
. (3)
Chronic dilated Definite myocarditis
Entry into myocytes cardiomyopathy
Viral replication
(
Viremia and protein expression Persistent or latent ) -
Delayed apoptosis infection .T
Myocyte lysis MRI.
■ SPECIFIC VIRUSES IMPLICATED IN

MYOCARDITIS
I ,
. F -
Extracellular RNA ,
Matrix
, , ,
.I , RNA ,
FIGURE 254-5 Schematic diagram demonstrating the possible progression rom in ection through direct,
secondary, and autoimmune responses to dilated cardiomyopathy. Most o the supporting evidence or this .O
sequence is derived rom animal models. It is not known to what degree persistent in ection and/or ongoing DNA , , ( -
immune responses contribute to ongoing myocardial injury in the chronic phase. ), (
, , E -B ,
6 [HHV6]) -
I
.P (PCR)
HLA - DCM,
, “ ” .M B19
. HHV6, , ,
A - .H ,
,
.T .
- , , Human immunodeficiency virus (HIV) -
, DCM 1–2%; ,
. (HAART), HIV -
P .C HIV
. (1) Possible subclinical acute ,
myocarditis
, ,
ECG , -
. (2) Probable acute myocarditis
FIGURE 254-7 Acute myocarditis. Microscopic image o an endomyocardial

biopsy showing massive in ltration with mononuclear cells and occasional
eosinophils associated with clear myocyte damage. The myocyte nuclei are
enlarged and reactive. Such extensive involvement o the myocardium would lead
FIGURE 254-6 Magnetic resonance image o myocarditis showing the typical mid- to extensive replacement brosis even i the infammatory response could be
wall location (arrow) or late gadolinium enhancement rom cardiac infammation suppressed. Hematoxylin and eosin–stained section, 200× original magni cation.
and scarring. (Image courtesy o Ron Blankstein, MD, and Marcelo Di Carli, MD, (Image courtesy o Robert Padera, MD, PhD, Department o Pathology, Brigham and
Division o Nuclear Medicine, Brigham and Women’s Hospital, Boston.) Women’s Hospital, Boston.)
1786 C, HIV . ,
A HIV , AV .A -
.T .S
. , . T
T , , -
PART 6
.X ,
, . , .T I G -
Hepatitis C , - ,
G A .C .
.A - T
, , -
. The effect of new treatments for hepatitis C , . T
on cardiac function has not yet been well-studied. I
B , T. cruzi .B
( ). , ,
A , .M , -
mumps, respiratory syncytial virus, arboviruses (dengue fever and yellow C ’ ,
fever), arenaviruses (Lassa fever). H , , , .S
<30% 5 .P
, . -
,
■ THERAPY .
T African trypanosomiasis
.D , - A .T W A
, Trypanosoma brucei gambiense
.T E A T. brucei rhodesiense
. T (
) . , . T
T , ,
. . A
L D C – (
.T ).
- Toxoplasmosis
- , , , -
- , - .I
. H , - ,
.U 40% HIV .
T ,
, , , ,
DCM. , .T
I M I G
Parasitic Myocarditis Chagas’ disease .A -
I G -
.T T. cruzi ,
, S C A . .F
T , - . C
, , .W .
Trichinellosis Trichinella spiralis
16 <10 S A , - .L -
W ( G P ). , , .P -
M . T .A
.S , ,
, .
T
.M DNA . T -
.F - ( , )
.
.A , C Echinococcus ,
.
(F . 254-5). A
C ’ Bacterial Infections M
. ,
T C ’ .M ,
, 5% , . Diphtheria -
, - , -
.I .
, T
>10–30
.F C ’ .T
1787
.T
, .O
brucellosis,

chlamydophila, legionella, meningococcus, mycoplasma, psittacosis,
salmonellosis,
.
Clostridial infections
.G , -
. Streptococ-
cal infection β-
.
Tuberculosis
,
. Whipple’s disease Tropheryma whipplei. T
, ,
FIGURE 254-8 Sarcoidosis. Microscopic image o an endomyocardial biopsy
, , - showing a noncaseating granuloma and associated interstitial brosis typical
.M , o sarcoidosis. No microorganisms were present on special stains, and no
. oreign material was identi ed. Hematoxylin and eosin–stained section, 200×
original magni cation. (Image courtesy o Robert Padera, MD, PhD, Department o
Other Infections Spirochetal myocarditis Pathology, Brigham and Women’s Hospital, Boston.)
Borrelia burgdorferi
Lyme disease. L
1–2 ,
, . Fungal myo- . S
carditis . C
, , -
, , , , , . M (
, .H , [PET])
. T rickettsial .M (MRI)
infections, Q fever, Rocky Mountain spotted fever, and scrub typhus - .T ,
ECG , ,
. .B
. T
■ NONINFECTIVE MYOCARDITIS
M - (Fig. 254-8).
.T - I -
, ,
, .P
-
, ,
. . P -
T - -
, , .B
.S , Chap. 360, -
. A , -
A -A ,
, - .
C .P Giant cell myocarditis ,
, 10–20% - . G -
.R
.D
-
. , .A -
T , , , , ,
. , . G
P -
, , , .T -
, .
, .T A
.W ,
-
, .
. Eosinophilic myocarditis
D , - , W -
.T , M A ,
1788 .I .T
C -S - , .P
. Hypersensitivity myocarditis , -
- -
.M , . S
PART 6
, ,
, , , .T -
.O -
.A ( 4 ) 5–10 ,
, . M
.H - -
.T
.A
( -
). .A
M - (“ ”) .M
, polymyositis dermatomyositis, -
.A .W
, .E
, 3–6
, , , , .I
- ,
. .W ,
.
■ PERIPARTUM CARDIOMYOPATHY Cocaine, amphetamines,
P (PPCM) -
6 , 1:2000 . P
1:4000 U S .R , .
, , , , Chemotherapy
, .J
.S - ,
(VEGF) .
, FLT1 ( FLT1). R Anthracyclines ( . ., )
. G
PPCM, -
.A .R -
, , ,
; - , ,
. .A
H , PPCM. H , -
N , - 1
. D
, - , -
.I W , .T ,
.T 30–40%,
-
- - .T
. - β-
A , “ ” ,
, .
PPCM - O ,
.B ,
- (PACM). - ,
B PPCM PACM .T
DCM. A DCM, ,
TTN 15% PPCM
.P , , .
- Trastuzumab (H )
. 2 (HER2)
.T -
■ TOXIC CARDIOMYOPATHY
C . A , -
.O ,
, - . A
, ,
. -
Alcohol DCM. . T
E 10% -HER2 ( . ., )
, .
C cyclophosphamide and ifosfamide C 1789
. 5-F , , - ,
.H ,
.A

interferon-α .C -
.D
. “ ” , , ,
M - tyrosine kinase inhibitors VEGF .
.A T obesity
“ ” , - .I ,
, ,
“ - ”
~2.7- . , , ,
R .F
-
( , , ) .I -
.T
( ,
) ( ), .I -
.
Proteasome inhibitors ,
.T , - . P -
, . , ,
I checkpoint inhibitors, , .
Nutritional deficiencies DCM
( . ., , , , ) W . Beri-beri heart
. H , - disease
-
, AV , ,
.T .T
.
Other therapeutic drugs ; -
, , , .A carnitine
. , .D
Toxic exposures selenium (K ’
. C ).
, , , , . Calcium - . C
,
■ METABOLIC CAUSES OF CARDIOMYOPATHY ( ) (
Endocrine disorders , . ),
Hyperthyroidism and hypothyroidism
, . Phosphate -
.C , .
. Hypophosphatemia
H - , .
Magnesium -
.T - (ATP ), -
, - .
.H Hemochromatosis
- (Chap. 407). I -
.H , DCM. T
, - HFE .W 10%
, , ,
. 1 500. T
Pheochromocytoma , ,
,
(Chap. 380). P .H
. I .E
α- , ,
.V , .
, D -
, >60% >45–50%
, - . MRI ,
. (Fig. 254-9),
C diabetes obesity -
.M . I ,
, .F
. , ( )
1790 .T -
MRI. B
,
“
” .I -
PART 6
.T
, , .
Left ventricular noncompaction
.
T
, “ ”
, -
.N
,
TAZ ( ). T
,
.T
, ,
FIGURE 254-9 Hemochromatosis. Microscopic image o an endomyocardial
biopsy showing extensive iron deposition within the cardiac myocytes with the
.T
Prussian blue stain (400× original magni cation). (Image courtesy o Robert
Padera, MD, PhD, Department o Pathology, Brigham and Women’s Hospital, Boston.) ,
.
S - .
T ,
.
- , .
I DCM,
S -
-
.
(T 254-4).
P DCM
.I
■ FAMILIAL DCM , ,
T ,
“G E C .” T .T
DCM 30%. M , .H -
TTN, , - ,
DCM, 25% .O , , -
, TTN .
, .M
~8% DCM ■ TAKOTSUBO CARDIOMYOPATHY
. T , - ,
T
muscular dystrophies. B D - . T
’ B ’ , -
X- .S - (takotsubo) J . O
J , -
(T 254-3),
. .P , ,
P / - ECG .T
-
.W .A
; -
-
LV
-
.
A
-
- RV
(Fig. 254-10). O
(
[ARVC]), A B
( )
FIGURE 254-10 Arrhythmogenic right ventricular cardiomyopathy. A. Cross-sectional slice o a pathology
.P specimen removed at transplantation, showing severe dilation and thinning o the right ventricle (RV)
. G - with extensive atty replacement o right ventricular myocardium. B. The remarkably thin right ventricular
ree wall is revealed by transillumination. LV, le t ventricle. (Images courtesy o Gayle Winters, MD, and
, Richard Mitchell, MD, PhD, Division o Pathology, Brigham and Women’s Hospital, Boston.)
1791
-
, , /
.C

.N
,
, ,
-
, QT -
.A
. W
, 10% .
■ IDIOPATHIC DCM
Idiopathic DCM ,
.A - -
; ,
.C -
FIGURE 254-11 Fabry’s disease. Transmission electron micrograph o a right
-
ventricular endomyocardial biopsy specimen at high magni cation showing the
’ . characteristic concentric lamellar inclusions o glycosphingolipids accumulating
as a result o de ciency o the lysosomal enzyme alpha-galactosidase A. Image
OVERLAPPING TYPES OF CARDIOMYOPATHY taken at 15,000× original magni cation. (Image courtesy o Robert Padera, MD,
T PhD, Department o Pathology, Brigham and Women’s Hospital, Boston.)
. C .W , ,
DCM, “ ,
,” .
. F , - C - -
.E . M
. ,
P “ - ” DCM, .F
, , -
.O - .D ,
,
(F . 254-4). .
T
■ DISORDERS OF METABOLIC PATHWAYS -
M - .M -2 -
, - (AMP)-
, , (PRKAG2) -
( T 254-3, 254-4). H , AV
.S
“ ,” X- - (LAMP2). T
PR .T -
, DCM .M , -
. , ,
Fabry’s disease Danon’s disease. E ,
- A 160 , -
GLA. T X- - .E -
.G
- .
, , .E
- RESTRICTIVE CARDIOMYOPATHY
(Fig. 254-11). D R -
/ GLA ,
( >30–50%). B , .
.T M ,
- , - <6 .E -
>$100,000 .E - ,
G ’ , - .S
-
- .C - , .T
. - , , ,
G - , .T
, DCM
glycogen storage disease type III, .A -
.T >10 mucopolysaccharidoses, - ,
X- . J Y
, , ( K ’ ).
1792 TABLE 254-5 Causes of Restrictive Cardiomyopathies
Infltrative (Between Myocytes)
Amyloidosis
Primary (light chain amyloid)
PART 6
Familial (abnormal transthyretin)a

Senile (normal transthyretin or atrial peptides)
Inherited metabolic de ectsa
Storage (Within Myocytes)
Hemochromatosis (iron)a
Inherited metabolic de ectsa
Fabry’s disease
Glycogen storage disease (II, III)
Fibrotic
Radiation
Scleroderma
Endomyocardial
Possibly related ibrotic diseases
Tropical endomyocardial ibrosis
Hypereosinophilic syndrome (Lö ler’s endocarditis)
Carcinoid syndrome
Radiation
Drugs: e.g., serotonin, ergotamine
Overlap with Other Cardiomyopathies
Hypertrophic cardiomyopathy/“pseudohypertrophic”a
“Minimally dilated” cardiomyopathy
FIGURE 254-12 Restrictive cardiomyopathy—amyloidosis. Gross specimen o a
Early-stage dilated cardiomyopathy heart with amyloidosis. The heart is rm and rubbery with a waxy cut sur ace. The
Partial recovery rom dilated cardiomyopathy atria are markedly dilated, and the le t atrial endocardium, normally smooth, has
Sarcoidosis yellow-brown amyloid deposits that give texture to the sur ace. (Image courtesy o
Robert Padera, MD, PhD, Department o Pathology, Brigham and Women’s Hospital,
Idiopathica
Boston.)
a
Can be amilial.
M
,
, (Table 254-5). T -
,
- .
Pacing Pericardial
■ INFILTRATIVE DISEASE lead in effusion
Amyloidosis RV
(Figs. 254-12, 254-13, and 254-14). S -
- ,
.T -
LV Lateral
Chap. 108. I , RV
wall of
( ) ( Septum LV
). T >100
13, V122I
~4% A A
50% .H , -
RA
V122I LA
70 .
O
,
-
FIGURE 254-13 Restrictive cardiomyopathy—amyloidosis. Echocardiogram
.I ,
showing thickened walls o both ventricles without major chamber dilation. The
, 10% atria are markedly dilated, consistent with chronically elevated ventricular lling
>80 >90 - pressures. In this example, there is a characteristic hyperre ractile “glittering” o
.M the myocardium typical o amyloid in ltration, which is a non-speci c nding with
contemporary echocardiography. The mitral and tricuspid valves are thickened.
.T A pacing lead is visible in the right ventricle (RV), and a pericardial e usion is
evident. Note that the echocardiographic and pathologic images are vertically
.
opposite, such that the le t ventricle (LV) is by convention on the top right in
C the echocardiographic image and bottom right in the pathologic images. LA, le t
ECG .H , atrium; RA, right atrium. (Image courtesy o Justina Wu, MD, Brigham and Women’s
Hospital, Boston.)
, 1793
-
. Scleroderma
,

. T
-
■ ENDOMYOCARDIAL DISEASE
T
FIGURE 254-14 Amyloidosis—microscopic images o amyloid involving the myocardium. The le t , -

panel (hematoxylin and eosin stain) shows glassy, grey-pink amorphous material in ltrating between .F -
cardiomyocytes, which stain a darker pink. The right panel shows a sul ated blue stain that highlights the , ,
amyloid green and stains the cardiac myocytes yellow. (The Congo red stain can also be used to highlight -
amyloid; under polarized light, amyloid will have an apple-green bire ringence when stained with Congo (Löffler’s endocarditis),
red.) Images at 100× original magni cation. (Image courtesy o Robert Padera, MD, PhD, Department o
.I ,
Pathology, Brigham and Women’s Hospital, Boston.)
>1500 /μL
6 -
AL .A (
, ), .T
.B , , ,
- , , .I
.A
MRI. T - .I -
TTR ,
AL .T AV .T
, , .
, W , -
, Lö ’
, .
(F . 254-14). D I , -
endomyocardial fibrosis, .T -
, .
T
, . ; ,
D , .P
, .T Lö ’ .F -
, , ,
A -A .W
-
.T ,
. .G -
T , .
6–12 , - M
.I , .F
, . A -
. . A
I - , .S
- ,
, . .
A - T carcinoid
- , -
.S - - , .V
.N RNA . S .
TTR . L
■ FIBROTIC RESTRICTIVE CARDIOMYOPATHY .

P
.T , HYPERTROPHIC CARDIOMYOPATHY
, H -
. P radiation cardiomyopathy ,
, - , ,
. C , , (Figs. 254-15 and 254-16). I
hypertrophic obstructive cardiomyopathy (HOCM), asymmetric
1794 septal hypertrophy (ASH), idiopathic hypertrophic subaortic stenosis
Mitral valve Tricuspid valve (IHSS). H ,
. P N
A ,A , A 1:500. I
.
PART 6
A -
,
.
T
~55 .
E -
RV free .I -
wall -
.A ~60% -
LV free
wall .M
>1400 -
RV Chamber , ~80% MYH7
LV Chamber IVS MYBPC3 (T 254-3).
H -
FIGURE 254-15 Hypertrophic cardiomyopathy. Gross specimen o a heart with .T
hypertrophic cardiomyopathy removed at the time o transplantation, showing
asymmetric septal hypertrophy (septum much thicker than le t ventricular ree
.
wall) with the septum bulging into the le t ventricular outfow tract causing A ,
obstruction. The orceps are retracting the anterior leafet o the mitral valve, . I MYBPC3 , -
demonstrating the characteristic plaque o systolic anterior motion, mani est as 40 , 30%
endocardial brosis on the interventricular septum in a mirror-image pattern to 70 .R same
the valve leafet. There is patchy replacement brosis, and small thick-walled ( . .,
arterioles can be appreciated grossly, especially in the interventricular septum.
IVS, interventricular septum; LV, le t ventricle; RV, right ventricle. (Image courtesy
), ,
o Robert Padera, MD, PhD, Department o Pathology, Brigham and Women’s ( . ., , ).
Hospital, Boston.) A , -
, ,
ATP .C
.S -
, .
H
(Fig. 254-17),
.A
,
.I
.I
LV ,
MRI. T “ ”
. I
Septum
MV
LA
FIGURE 254-16 Hypertrophic cardiomyopathy. This echocardiogram o

hypertrophic cardiomyopathy shows asymmetric hypertrophy o the septum
compared to the lateral wall o the le t ventricle (LV). The mitral valve (MV) is FIGURE 254-17 Hypertrophic cardiomyopathy. Microscopic image o hypertrophic
moving anteriorly toward the hypertrophied septum in systole. The le t atrium cardiomyopathy showing the characteristic disarrayed myocyte architecture with
(LA) is enlarged. Note that the echocardiographic and pathologic images are swirling and branching rather than the usual parallel arrangement o myocyte
vertically opposite, such that the LV is by convention on the top right in the bers. Myocyte nuclei vary markedly in size and interstitial brosis is present.
echocardiographic image and bottom right in the pathologic images. (Image (Image courtesy o Robert Padera, MD, PhD, Department o Pathology, Brigham and
courtesy o Justina Wu, MD, Brigham and Women’s Hospital, Boston.) Women’s Hospital, Boston.)
DIAGNOSIS 1795
T
.M - .P
.

M , ( ) ,
(F . 254-15). T , .A ,
, . C
. (F . 254-16)
H ( ECG -
) .T -
, ~15%. L - ,
-
, , DNA .B
, -
.O .R ( ’ )
~30%
~30%. S , .U -
, ’
.M ,
, . I (VO2 >50 L/ ), ,
, .
,
.S
.C TREATMENT
, , , - Hypertrophic Cardiomyopathy
, - . T
M
(Fig. 254-18). L
, .
V . β-A L-
Hypertrophic Cardiomyopathy
In all pts, evaluate No

risk for sudden death Symptomatic?
Yes
Evidence of Titrate beta blocker

If high, If low follow with fluid retention? and/or calcium
consider ICD serial evaluation Yes channel blocker
Use diuretics with caution

to avoid hypovolemia, Persistent
particularly in presence of symptoms
outflow gradient
Outflow
No gradient? Yes
Evidence of severe Try disopyramide

progressive LV dysfunction?
No Yes
Reevaluate cause Rarely, consider Refractory

of symptoms cardiac transplantation severe symptoms
Consider procedure
Septal ablation Mitral surgery
FIGURE 254-18 Treatment algorithm or hypertrophic cardiomyopathy depending on the presence and severity o symptoms and the presence o an intraventricular
gradient with obstruction to outfow. Note that all patients with hypertrophic cardiomyopathy should be evaluated or atrial brillation and risk o sudden death, whether
or not they require treatment or symptoms. ICD, implantable cardioverter-de brillator; LV, le t ventricular.
1796 ( . ., ) - A -
, ,
.P .R
. β-A
, - L- AV
PART 6
. ; ,
P .S
.S AV
~5% , .D
.D 50 , ,
.A
. .
I ,
- PROGNOSIS
. M - T
. F
.A , -
- .T <1% ; ,
, - 1 20
(“
.U - ” - ). T -
, -
.N
.W .
,
. H , GLOBAL PERSPECTIVES
C
. ,
P , , -
. .D /
V . G B D 51%
F 1990 2013 -
0.5% Table 254-6. A 12.6% -
, 4%. F ,
- , 26.5
55% .D C ’ -
.N , 12.7 10.6 ,
, 51.7% - 100,000 -
.L - - 0.2,
- , S C A .B ,
.R C ’ 300,000
U S , .I
MRI . -
.
H -
TABLE 254-6 Risk Factors for Sudden Death in Hypertrophic .D
Cardiomyopathy .H ,
SCREENING <50 100 ,
MAJOR RISK FACTOR TECHNIQUE R .W -
History o cardiac History HIV
arrest or spontaneous - . I
sustained ventricular
tachycardiaa
Syncope Nonvagal, o ten with or History
a ter exertion
. F ,
-
Family history o sudden Family history
cardiac death
, P ,J ,
Spontaneous >3 beats at rate >120 Exercise or 24- to 48-h
nonsustained ventricular ambulatory recording A -C .
b
tachycardia
■ FURTHER READING
LV thickness >30 mm Present in <10% o Echocardiography
patients Arbustini E : T MOGE(S) -
:E W
Abnormal blood Systolic blood pressure Maximal upright exercise
pressure response to all or ailure to increase testing H F .JA C C 62:2046, 2013.
b Bozkurt BJ : C
exercise at peak exercise
a
:A
Implantable cardioverter-de ibrillator advised or patients with prior arrest or
sustained ventricular tachycardia regardless o other risk actors. b Prognostic A H A .C 134: 579, 2016.
value most applicable to patients <40 years old. Cooper LT :T
Abbreviation: LV, le t ventricle. .C 116:2216, 2007.
Gilmore JD :N - TABLE 255-1 Principles for Listing Candidates for Cardiac 1797
.C 133:2404, 2016. Transplantation
Ho CY: G .P PRINCIPLE COMMENT
C D 54:456, 2012. Advanced Disease Re ractory heart ailure with a VO2 o <14 mL/kg/
CHAPTER 255 CardiacTransplantationand Prolonged Assisted Circulation

Morillo CA : R Severity min (<12, i on beta blockers) or percent predicted
C ’ .NE J M 373:1295, 2015. VO2 <50%; combination o intolerance to disease
Sagar S :M .L 379:738, 2011. modi ying therapy, cardiorenal syndrome, use o
Ware JS :S inotropic therapy to maintain stability or need or a
.NE J M 374:233, 2016. le t ventricular assist system.
Zamorano JL : 2016 ESC P P Co-Morbidity Age is not an absolute contraindication, but railty
should be considered a relative contraindication; a
ESC
BMI > 35 kg/m2 should require weight loss; cancer
C P G .E H J 37:2768, 2016. should be dealt with on an individual basis (e.g., low-
grade prostate cancer may not be a contraindication);
poorly controlled diabetes mellitus or end-organ
damage may be a contraindication; eGFR <30 mL/
min/1.73 m2 is a relative contraindication; severe
cerebrovascular disease or peripheral vascular
255 Cardiac Transplantation

and Prolonged Assisted Donor-Recipient
disease (which will limit rehabilitation or unction) is
also a relative contraindication.
Sensitized individuals with circulating antibodies
Circulation Matching should have a prospective or virtual cross match;
pulmonary vascular resistance with a transpulmonary
gradient >15, PVR >3 Wood Units and absolute PA
Mandeep R. Mehra systolic pressure >50 mmHg provided the systolic
BP is >85 mmHg is a relative contraindication unless
reactive.
A , , Psychosocial Issues Tobacco use in any orm limits posttransplant
- survival and should be stopped or at least
6-months; substance abuse, including marijuana,
, should be a contraindication i the individual cannot
, . demonstrate control and cessation; patients with
S - severe cognitive-behavioral disabilities or dementia
, , (inability to ever understand and cooperate with
, medical care) have the potential or sel -harm and
. should not receive a transplant.
I , Abbreviations: BMI, body mass index; eGFR, estimated glomerular iltration rate;
PA, pulmonary artery; PVR, pulmonary vascular resistance; VO2, peak oxygen
consumption.
.M , -
- . ■ PRINCIPLES OF DONOR RECOVERY AND

ALLOCATION
CARDIAC TRANSPLANTATION A
A N S - , -
,C .T
B ( ) , ( )
D 3, 1967. N ,5 , , () .T , -
-
. G , >150,000
1 >80% ,
11 .T .T
-
, “
, ,” 4 .T
, . ABO .
D
■ CANDIDATES FOR CARDIAC TRANSPLANTATION ,
T .I
.H , , ,
HLA .I
.S , ( -
.H , - ),
.O
- . I 2006, I S H L
T . - , (
T 2016 55 )
,
, ( - ( )
), ( C ’ , - .I ,
). S (
Table 255-1. )
1798 .I ( ) ( -
, - )
.T
.T -
; , -
PART 6
. Table 255-2
- .
. A (ACR) -
(AMR)
. ACR -
■ SURGERY FOR CARDIAC TRANSPLANTATION

T “ - 6 .T
” T –
.I , - .I
- ,
.T .I
ACR, ,
.T - , ,
, ,
, .T . S ACR
.T ,
.I ,
, -
.C , AMR
.D ,
- - -
.O ,
-
,
.
-
. AMR - -
■ CARDIAC ALLOGRAFT REJECTION AND , ,
IMMUNOSUPPRESSION .C , AMR
T , ,
ACR. I
- ,
. T ,
( ), - ( CD20
( , ) , ( )
, ) . ( ). T
T
, - -
, .I
( , ) (CMV), ,
( ), .
TABLE 255-2 Immunoprophylaxis Drugs in Cardiac Transplantation

DRUG CLASS GENERIC DRUG CELLULAR TARGET MAJOR SIDE EFFECTS
Calcineurin Inhibitors Cyclosporine Binds to cyclophilin which then inhibits calcineurin Hypertension, dyslipidemia, gum hypertrophy,
hypertrichosis
Tacrolimus Binds to immunophilin FK506 binding protein which inhibits Hypertension, dyslipidemia, alopecia, diabetes
calcineurin mellitus
Anti-Thymocyte Rabbit ATG T-cell depletion in blood and peripheral lymphoid tissues Cytokine release syndrome, leukopenia,
Globulin (ATG) through complement-dependent lysis and T-cell activation thrombocytopenia, serum sickness
and apoptosis
Horse ATG Same as above Same as above
Interleukin-2 Basiliximab Inhibition o CD-25 o IL-2 receptor Well tolerated; rare hypersensitivity; increased
receptor antagonists in ection risk
Anti-metabolites Azathioprine Imidazolyl derivative and prodrug o 6-mercaptopurine (cell cycle Bone marrow suppression, pancreatitis, hepatitis
inhibitor)
Mycophenolate Inhibits inosine monophosphate dehydrogenase, which controls Leukopenia, gastrointestinal toxicity
Mo etil guanine monophosphate in the de novo pathway o purine
synthesis (inhibits T and B cell proli eration)
Proli eration-Signal Sirolimus Binds with FKBP12 and complex inhibits the mechanistic Delayed wound healing, non-speci ic
Inhibitors Target o Rapamycin (mTOR) pneumonia, pericardial e usion, hyperlipidemia
(hypertriglyceridemia)
Everolimus Binds to FKBP12, which inhibits mTORC1 (and not mTORC2) Dyslipidemia, stomatitis, pericardial e usions and
pancytopenia
■ LATE COMPLICATIONS AFTER CARDIAC PROLONGED ASSISTED CIRCULATION 1799
TRANSPLANTATION T
T - -
- - (LVAS). I -

,
.O (“ -
”). T LVAS
, -
(CAV). T - , “ ”(
,
, ).
. C ,
, , ■ LEFT VENTRICULAR ASSIST SYSTEMS AND CLINICAL
TRIALS
.E A , REMATCH, 2001,
. ,
S , , -CMV -
CAV. A - LVAS. T -
48% .
- H , LVAS -
. H , “ ” 5 .
CAV (Fig. 255-1). F , , ,
A .O ,
, - -
- ,
. P , - . A
E -B , LVAS
, , - LVAS, H M II, -
- .S ( - - ,
CD20) .S .A
( LVAS, H W HVAD,
), - . F .A ,
, - , H M 3 LVAS .U
, , - H M II LVAS, ,
.
CARDIAC ALLOGRAFT VASCULOPATHY
NON-IMMUNOLOGICAL IMMUNOLOGICAL
FACTORS FACTORS
Angiogram IMMUNE ACTIVATION Pathology

RELATED
INFLAMMATION
IVUS
VASCULOPATHY
Severe, diffuse, mid to distal luminal loss Severe fibrotic intimal proliferation leading to luminal loss
FIGURE 255-1 Cardiac allogra t vasculopathy is initiated and propagated by the combined infuence o immunological and non-immunological insults on the allogra t
vasculature. An infammatory milieu determines the development o di use, aggressive luminal blockages that in early orms exhibit intimal thickening and brosis.
IVUS, Intravascular Ultrasound (can be used to diagnose early orms o intimal thickening).
1800
CONTINUOUS FLOW LEFT VENTRICULAR ASSIST SYSTEMS
Axial Flow Centrifugal Flow

PART 6
LOW PULSE PRESSURE
HeartMate II HeartMate 3
Mechanical Bearing Magnetically Levitated
Intra-thoracic and Abdominal Intra-thoracic
Restrictive Blood Paths Wide Blood paths
No Intrinsic Pulse Intrinsic Pulse @30 bpm
CLINICAL IMPROVEMENT
Current New
Incremental device durability

Absence of pump thrombosis
FIGURE 255-2 Continuous ow le t ventricular assist systems (LVAS), their types and mechanisms. The mechanical bearing axial fow HeartMate II pump is prone to
thrombosis, while the rictionless magnetically levitated centri ugal fow HeartMate 3 does not induce hemolysis or pump thrombosis.
(Fig. 255-2). R .C -
>70% 2- LVAS
LVAS, ,
- 5–10 . .
T LVAS H -
( ), -
.C , , -
(Fig. 255-3). A 81–325
<12 L/ / ; INR 2–3
, LVAS -
, .C , .O ,
LVAS “ ” ( )
.S 8%
- . H M II LVAS 29% H W HVAD
, 2 .O
■ MANAGEMENT OF LVAS AND THEIR ; ,
COMPLICATIONS
C LVAS .A -
.A , .T
. D 6–12% LVAS , ( 6 ),
- , H M II LVAS. T
D ( , LVAS
) .P ,
.T “ ”
<90 H . L -
RAAS .A - (LDH) ( - ) -
, .T .P
(LVAD)
LVAD
W 6- 48%, VAD
.T ( -
, - ). R ( ) 6.5% -
. 65% 2- .
T I , ( -
. W )
- , 1 5 LVAS .S
LVAS - -
, -
.I
1801
LEFT VENTRICULAR ASSIST SYSTEMS

HEMOCOMPATIBILITY RELATED ADVERSE EVENTS
PUMP THROMBOSIS results in need for reoperation and 01

occurs with a high rate with the HeartMate II (10–14%) and PUMP
01 HeartWare HVAD (6–8%) LVAS; No Hemolysis or Pump
Thrombosis is seen with the HeartMate 3 LVAS
THROMBOSIS
GASTROINTESTINAL BLEEDING is associated with

diminished pulsatility, defects in von Willebrand factor,
02 development of AV Malformations and anti-platelet and
anticoagulation intensity
CEREBROVASCULAR DISEASE includes strokes

(ischemic and bleeds), TIA and seizures; occurrence
03 correlated with blood pressure control and antiplatelet
therapy
03 02
CEREBROVASCULAR GASTROINTESTINAL
DISEASE BLEEDING
FIGURE 255-3 Hemocompatibility-related adverse events with LVAS are o ten interrelated and typically result in cerebrovascular, gastrointestinal, or pump mal unction
events.
- ■ GLOBAL CONSIDERATIONS
, . W LVAS , -
.I U S , -
■ NOVEL DEVICES
T H M 3 , , E
LVAS. .C -
T , ,
, (UK), -
( 2 ). T - .N ,
MOMENTUM 3 ,
6 LVAS ,
H M II . I - LVAS.
,
W ■ FURTHER READING
. L - Mehra MR: C
LVAS .A JT 6:1248, 2006.
- - Mehra MR :I S H L T -
, , .
-2010. J H L T 29:717, 2010.
■ TOTAL ARTIFICIAL HEART Mehra MR :T 2016 I S H L T -
N LVAS, : A 10- .
- - JH L T 35:1, 2016.
LVAS ( , - Mehra MR : MOMENTUM 3 I .A
, ). I , .NE JM
376:440, 2017.
.T S C - Nair N :C -
, .JH L T 30:612, 2011.
, . Nair N :L - -
T :W ?JH L T
.T 33:461, 2014.
.T Rogers JG : I
- .NE J M 376:451, 2017.
Shah SP, Mehra MR: D
.A , :P .
I H J 68:S45, 2016.
.S Stehlik J :O :I
ISHLT I R H L T .J
.N H L T 33:975, 2014.
, Stewart GC, Mehra MR: A
. .H F C 10:S1, 2014.
1802 14
All valve disease
Aortic Valve Disease 12 Mitral valve disease
256 Patrick T. O’Gara, Joseph Loscalzo
Aertic valve disease
10
PART 6
8
GLOBAL BURDEN OF VALVULAR HEART
DISEASE 6
P
, , , , 4
.N ,
.R
(Chap. 352) -
2
- .I
1 100,000 - C R
150 100,000 C (Fig. 256-1). R 0
12–65% FIGURE 256-2 The burden o moderate or severe mitral and aortic valve disease
2–10% . in the United States. Prevalence estimates are derived rom three population-
based studies comprising a total o 11,911 individuals: The Coronary Artery Risk
P
Development in Young Adults (CARDIA), the Atherosclerosis Risk in Communities
(ARIC), and the Cardiovascular Health Study (CHS). (From VT Nkomo et al: Lancet
- 368:1005, 2006.)
A . I
, (
I S A ), C A , 12–13% >75 (Fig. 256-2). S
M E , (AS) 3.5% >75 .I
- U S , 85,000
<20 .T 2010,
- (
.A 15–20 ).
, 300,000 T (Chap. 123)
233,000 , ,
S A (~7.6 100,000). I U , -
S , 20,000 - - ,
2010 3281 2014. . T
A 2007
N A , - -
.I
, , .T .R
. I - U.S. 2000 2010.
Change in age-
standardized prevalence
(1990–2013)
>20% decrease
11–20% decrease
5–10% decrease
<5% decrease
<5% increase
5–10% increase
5–20% increase
>20% increase
No data available
Number of prevalent
case (2013)
<50,000
<100,000
<500,000
<1,000,000
<2,500,000
<5,000,000
<8,000,000
<8,000,000
FIGURE 256-1 The global burden o rheumatic heart disease. This world map provides a snapshot o both the change in prevalence o rheumatic heart disease cases
between 1990 and 2013 (upper right legend) and the estimated number o rheumatic heart disease cases per country (lower right legend). Regions in which the
disease is highly prevalent include sub-Saharan A rica, India, China, and Southeast Asia. (From JR Carapetis et al: Nat Rev Dis Primers 2:15084, 2016.)
B (BAV) 0.5–1.4% 1803
, . R AS
.A (AR).
M , , -
CHAPTER 256 AorticValve Disease

.T AS.
.
A , ■ BICUSPID AORTIC VALVE DISEASE
A (BAV)
, - 0.5–1.4% 2–4:1
- - .M - - .T
, , , ,
X-
. BAV T ’ .T
T BAV -
Chaps. 38 and 234; ~10%. A
(ECG) Chap. 235; , NOTCH1
Chap. 236; .A
Chap. 237. NKX2.5 .M -
AORTIC STENOSIS BAV ;

A (AS) - .P BAV
; ~80% - .T -
, AS . ,
■ ETIOLOGY AND PATHOGENESIS .F ,

(Table 256-1) AS
- , .P
(BAV), ( ) , BAV / .
.A A BAV
AS 53% - , S ’
4% .T .
, -
, , ■ OTHER FORMS OF OBSTRUCTION TO LEFT
, , , VENTRICULAR OUTFLOW
(Fig. 256-3). E , I AS,
LV : hypertrophic obstructive cardiomyopathy
(Chap. 254), discrete fibromuscular/membranous subaortic stenosis,
supravalvular AS (Chap. 264). T LV
. G - D
D , .
, 10, E4
AS, ■ PATHOPHYSIOLOGY
F .S - T LV
LV .W -
AS, - (LDL) , LV
, (L [ ]), , , . H , ,
, .T /
( , LV
) LV .I , -
(MI)
>65. A 30% >65 , L (S = Pr/h,
.R S= ,P= ,r= , h= ).
( ) . A
Rheumatic disease of the aortic leaflets , (CO) LV
- .T , . U , , -
, , LV ,
, , .B , -
(LV) , .
, A >40 H CO
2 2 2
~<1 ( ~<0.6 /
- )— . ., -
TABLE 256-1 Major Causes of Aortic Stenosis —
VALVE LESION ETIOLOGIES LV . T LV -
Aortic stenosis Congenital (bicuspid, unicuspid) AS
Degenerative calci ic (EF)
Rheumatic ever
LV. A CO
AS,
Radiation
.L , ,
1804 Lipid infiltration Inflammation Fibro-calcific response
Radiation
Mechanical stress
Lipid-derived species
Cytokines
PART 6
Lipids
Lp(a) LDL
Calcium
hydroxyapatite
NOS
uncoupling Blood
ROS Angiotensin I
vessel
VEGF
Chymase ACE LDL
Ox-LDL
Ox-PL MMPs Osteoprogenitor
Lp-PLA2 TNF
VEGF Angiotensin II cell
IL-1β
ATX IysoPC inflammation
IysoPA RANKL
IL-6 TNF
ATX WNT3a
sPLA2 TGFβ Collagen Apoptosis
LPAR BMP2 RUNX2 Osteogenic transition
ENPP1 MSX2 Fibrosis
A2AR
VIC NT5E
AA Monocyte Macrophage
Mineralization
ATP AMP Adenosine Mastocyte Calcifying
5-LO COX2
+PPi +Pi microvesicles
ALP T cell
Leukotrienes Prostaglandins
Pi
Time
FIGURE 256-3 Pathogenesis o calcifc aortic stenosis. Lipid and infammatory cell in ltration occurs across damaged endothelium. A cascade o events ollows that
leads eventually to ormation o disorganized collagen ( brosis) and calcium hydroxyapatite (bone) deposition. Valvular interstitial cells (VIC) are critical participants in
this active process. AA, arachidonic acid; ACE, angiotensin-converting enzyme; ALP, alkaline phosphatase; ApoB, apolipoprotein B; AMP, adenosine monophosphate;
ATP, adenosine triphosphate; ATX, autotaxin; A2AR, adenosine A2A receptor; BMP, bone morphogenetic protein; COX2, cyclo-oxygenase2; ENPP, ectonucleotide
pyrophosphatase/phosphodiesterase; IL, interleukin; 5-LO, 5-lipoxygenase; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); LPAR, lysophosphatidic acid receptor;
Lp-PLA2, lipoprotein-associated phospholipase A2; lysoPA, lysophosphatidic acid; lysoPC, lysophosphatidylcholine; MMP, matrix metalloproteinase; NOS, nitric oxide
synthase; Ox-PL, oxidized phospholipid; Ox-LDL, oxidized LDL; RANKL, receptor activator o nuclear actor-κB ligand; ROS, reactive oxygen species; RUNX2, runt-related
transcription actor 2; sPLA2, secreted PLA2; TGFβ, trans orming growth actor-β; TNF, tumor necrosis actor; VEGF, vascular endothelial growth actor; VIC, valvular
interstitial cell. (From B Lindman et al: Nat Rev Dis Primers 2:16006, 2016.)
(AF) , M AS -
.L ,
, CO LV– .A BAV , ,
, (LA),
(PA), (RV) . LV .E , ,
.O , -
(CAD). S ( CO)
LV . Dyspnea
EF. L - , - AS (
LV ) . LV
T LV LV . Angina pectoris
. I , CAD,
. CAD
.C , AS
, , >65. Exertional syncope
LV - - -
.T CO,
. CO .
B CO
■ SYMPTOMS , , , , ,
AS CO -
2
~1 .E AS . O ,
LV , , . ., LV ,
.S
.O , . RV ,
, AF, (TR) .E - 1805
AS. . TEE
W AS (MS) , ,
(CO) MS AS. T

, , D
2
AS. T .S AS <1 , -
AR . AS 1–1.5 2 AS
2
1.5–2 .A , ,
■ PHYSICAL FINDINGS <2.5 / ( <25 H ). LV
T ; , LV .T
AF .
H AS. I LV ,
, , , EF .D
.T .
(pulsus parvus et tardus). A E
“ ” , , AS LV
.I , ,
.I , a . T -
.T BAV . D
RV , AS
. LV ( - , - , AS
T LV EF), AS
2
.A ( S 4) . P AS ( . ., <1 ) -
, (<40 H ) EF ( - ,
.A - , AS EF) ,
. D .T
.W
Auscultation A AS
, , BAV . CO,
T (CT) .T
. A AS , LV CT
.I -
, - (TAVR).
, ,
S2 (Chap. 234). T Chest X-Ray T - -
AS .H
,
.F , S4 .A -
LV LV - ; S3
, LV .A
. ,
T AS ( ) ; -
S 1, AS
, not .I , LV ,
.I - , LV ,
, , , LA, PA, -
.I .
.O
, Catheterization R - -
(MR) (G ). I AS -
CO, III/
VI. I . C
CO , LV
, , .C
. : (1) patients with multivalvular disease,
; (2) young, asymptomatic patients with

■ LABORATORY EXAMINATION noncalcific congenital AS, LV -
ECG I AS, LV .I ,
, ST- T- (LV (PABV) AS ,
“ ”) I VL ; (3) patients in whom it is suspected that
.H , ECG the obstruction to LV outflow may not be at the level of the aortic valve
, ECG - .
LV .S - C CAD -
. AS
.T CAD
Echocardiogram T TTE , -
, LV (SAVR) 50% .
1806 TABLE 256-2 Mortality Rates after Aortic Valve Surgerya , 1.5–2 . M , >80%
UNADJUSTED OPERATIVE
AS, <4 .A
OPERATION NUMBER MORTALITY (%) AS, ,
AVR (isolated) 21,921 2.2 , 10–20%; ,
.
AVR + CAB 13,000 4.0
PART 6
S AS
AVR + MVR 1349 8.0
(~1% ) .C AS -
a 2
Data are or the irst three quarters o calendar year 2015 during which 1033 , 0.1
sites reported a total o 210,421 procedures. Data (accessed March 9, 2017)
are available rom the Society o Thoracic Surgeons at http://www.sts.org/sites/
0.3 / 7 H , (Table 256-2).
de ault/ iles/documents/2015Harvest4_ExecutiveSummary.pd .
Abbreviations: AVR, aortic valve replacement; CAB, coronary artery bypass;
MVR, mitral valve replacement.
TREATMENT
■ NATURAL HISTORY Aortic Stenosis (Fig. 256-4)
D AS
. B - MEDICAL TREATMENT
2
, I AS ( <1 ),
,
: ,3 ; ,3 ; ,2 ; .C
Abnormal Aortic Valve with Class I

Reduced Systolic Opening
Class IIa
Class IIb
Severe AS
Vmax 3 m/s –3.9 m/s
Vmax ≥4 m/s
∆Pmean 20–39 mmHg
∆Pmean ≥40 mmHg
Symptomatic Asymptomatic Asymptomatic

Symptomatic
(stage D1) (stage C) (stage B)
LVEF <50% LVEF <50%

(stage C2)
Yes No Other cardiac
surgery
Other cardiac surgery
DSE with AVA ≤1 cm2
Vmax ≥5 m/s AVA ≤1 cm2 and and
∆Pmean ≥60 mmHg Vmax ≥4 m/s LVEF ≥50%
low surgical risk (stage D2) (stage D3*)
Abnormal ETT As likely cause of

symptoms
∆Vmax >0.3 m/s/y
low surgical risk
AVR AVR AVR AVR

(I) (IIa) (IIb) (IIa)
FIGURE 256-4 Management strategy or patients with aortic stenosis. Preoperative coronary angiography should be per ormed routinely as determined by age,
symptoms, and coronary risk actors. Cardiac catheterization and angiography may also be help ul when there is a discrepancy between clinical and noninvasive
ndings. Patients who do not meet criteria or intervention should be monitored periodically with clinical and echocardiographic ollow-up. The class designations
re er to the American Heart Association/American College o Cardiology methodology or treatment recommendations. Class I recommendations should be per ormed
or are indicated; Class IIa recommendations are considered reasonable to per orm; Class IIb recommendations may be considered. The stages re er to the stages
o progression o the disease. At disease stage A, risk actors are present or the development o valve dys unction; stage B re ers to progressive, mild-moderate,
asymptomatic valve disease; stage C disease is severe in nature but clinically asymptomatic; stage C1 characterizes asymptomatic patients with severe valve disease
but compensated ventricular unction; stage C2 re ers to asymptomatic, severe disease with ventricular decompensation; stage D re ers to severe, symptomatic valve
disease. With aortic stenosis, stage D1 re ers to symptomatic patients with severe aortic stenosis and a high valve gradient (>40 mmHg mean gradient); stage D2
comprises patients with symptomatic, severe, low-fow, low-gradient aortic stenosis and low le t ventricular ejection raction; and stage D3 characterizes patients with
symptomatic, severe, low-fow, low-gradient aortic stenosis and preserved le t ventricular ejection raction (paradoxical, low-fow, low-gradient severe aortic stenosis).
AS, aortic stenosis; AVA; aortic valve area; AVR, aortic valve replacement; DSE, dobutamine stress echocardiography; ETT, exercise treadmill test; LVEF, le t ventricular
ejection raction; ΔPmean, mean pressure gradient; Vmax, maximum velocity. (Adapted rom RA Nishimura et al: J Am Coll Cardiol 70:252, 2017.)
CO. M - 1807
CAD, (T 256-2).
- (ACE) - B AS ,
, , ,

LV . N AVR . A
CAD. R SAVR AS. T
AS HMG-C A ’
(“ ”) .A
. . T
H , - AS
/
- .T , , , ,
, .T 10-
AVR ~60%. R -
(ASCVD) . ACE ( )
AS- .T - /
AS .
. B >65 .S -
.A -
SURGICAL TREATMENT 30%
A AS 10 , - ,
-
LV - K
.O AS ( .H AVR
2 2 2
<1 0.6 / ) , .
LV (EF <50%), T R
BAV (
>5.5 ). O - .I -
(4.5–5.0 ) U S
(>0.5 / ). P AR. T
AS .
AVR. I
, SAVR ( AS PERCUTANEOUS AORTIC BALLOON VALVULOPLASTY (PABV)
AR) ~2% (T 256-2) T
, AS (Chap. 264). I
.T SAVR
, AS (80% 1 )
.R , ,
“ ”
; AS, LV .I
; TAVR ( ).
AS, >5 /
>60 H ; LV TRANSCATHETER AORTIC VALVE REPLACEMENT
. E TAVR AS -
, - -, -, -
.A , -
(RCT) SAVR - , -
AS . (Fig. 256-5). N
O (1–3 ) . N 25,000 U.S.
. I - , - TAVR 2015 415 . TAVR
AS LVEF, , -LV ,
(15–20%), , , .
.L - - A RV
LV .N , .
P 90%. A
, AS ( . .,
, ), 1- 2- TAVR
( ( PABV) (Fig. 256-6). O -
≥20% ). 2- - -
P TAVR, TAVR SAVR (Fig. 256-7). L , 2-
( ), RCT .
T - , - AS TAVR SAVR
LVEF .O (Fig. 256-8). TAVR
- , AR,
“ ” - AS, 2 .T
.I (~10%)
AS CAD , AS TAVR. V
1808
B
PART 6
V
A B
FIGURE 256-5 Balloon-expandable (A) and sel -expanding (B) valves or transcatheter aortic valve replacement (TAVR). B, infated balloon; N, nose cone; V, valve. (Part
A, courtesy o Edwards Li esciences, Irvine, CA; with permission. NovaFlex+ is a trademark o Edwards Li esciences Corporation. Part B, © Medtronic, Inc. 2015. Medtronic
CoreValve Transcatheter Aortic Valve. CoreValve is a registered trademark o Medtronic, Inc.)
5 ; - , .T
5 .O - .T
AVR (“ - - ”),
. N - , .P , BAV
, TAVR.
100 TAVR group

SAVR group
90
100
Hazard ratio, 0.56 (95% CI, 0.43–0.73)
80
Death from any cause (%)
90 P<0.001
80 HR 1–04, 95% CI 0–86–1.24; p = 0.76
70
Probability (%)
70 68.0
Standard therapy 60
60
50 43.3 50
40
40
30 TAVR
20 30
10 20
0
0 6 12 18 24 10
Months since randomization 0
No. at Risk 0 12 24 36 48 60
TAVR No. at Risk
179 138 124 110 83
Standard 179 121 85 62 42 TAVR group 348 262 228 191 154 61
therapy SAVR group 351 236 210 174 131 62
FIGURE 256-6 Twenty- our-month outcomes ollowing transcatheter aortic valve FIGURE 256-7 Five-year mortality rates ollowing transcatheter (TAVR) or
replacement (TAVR) or inoperable patients in the PARTNER I trial (cohort B). CI, surgical aortic valve replacement (SAVR) or high-surgical-risk patients (cohort
con dence interval. (Adapted rom RR Makkar et al: N Engl J Med 366:1696, A) in the PARTNER I trial. Mortality rates in this AS patient cohort are similar or
2012; with permission.) TAVR and SAVR. CI, con dence interval. (Adapted rom MJ Mack et al: Lancet
2015; 385:2477–2484.)
50 1809
Hazard ratio, 0.79 (95% CI, 0.62–1.00)
100 P = 0.05
40
CHAPTER 257 Aortic Regurgitation

90
80 40
or disabling stroke (%)

Death from any cause
70 20.4
20
15.9
60 Surgery
16.8
50 10 12.3
40 TAVR
0
40 0 3 6 9 12 15 18 21 24
20
10
0
0 3 6 9 12 15 18 21 24
Months since procedure
FIGURE 256-8 Rates o death rom any cause or disabling stroke or intermediate surgical risk as patients undergoing surgical aortic valve replacement (SAVR) or
trans emoral transcatheter aortic valve replacement (TAVR). In this intention-to-treat analysis, trans emoral TAVR proved superior to SAVR. (Adapted rom MB Leon
et al: N Engl J Med 374:1609, 2016.)
■ FURTHER READING
Carapetis JR :A . AR. P , AR,
N R D P 2:15084, 2016. ~15% (Chap. 264),
Lindman B :C .N R D P 2:16006,
2016. /
Nishimura RA : 2014 AHA/ACC G .
:A A C AR (IE),
C /A H A T F P ,
G .JA C C 63: 57, 2014. , , -
Nishimura RA : 2017 AHA/ACC F U 2014 .T
AHA/ACC G M P V -
H D :AR A C C / AR
A H A T F C P G - .A -
. JA C C 70:252, 2017. AR,
. T AS
AR AR
TABLE 257-1 Major Causes of Aortic Valve Disease

VALVE LESION ETIOLOGIES
257 Aortic Regurgitation
Aortic regurgitation Valvular
Congenital (bicuspid)
Endocarditis
Rheumatic ever
■ ETIOLOGY Myxomatous (prolapse)
(Table 257-1) A (AR) Traumatic
, . Syphilis
Primary Valve Disease R - Ankylosing spondylitis
, , , Root disease
Aortic dissection
.A Cystic medial degeneration
AR Mar an syndrome
.P (BAV) Bicuspid aortic valve
AR, ~20% Nonsyndromic amilial aneurysm
10 40 .C - Aortitis
AR. M
Hypertension
1810 AR. I ,
AR , .T
. , -
, (CAD).
Primary Aortic Root Disease AR
PART 6
, . ., , - ■ HISTORY
; A - -
AR ;
AR (Chap. 274). M , AR .A -
IE
M ; ; - , -
; ; , .
AR. O I acute severe AR, IE, ,
AR , LV -
.S , , LV
, LA PA .P /
, , .
, .I Chronic severe AR ,
(Chap. 177), , 10–15 .U -
, , ,
.T ’ .S , ,
AR. -
.T
■ PATHOPHYSIOLOGY ,
T (LV) ( . ., .T
, , -
LV) AR. I .A CAD
AR, AR, .A
.I MR, .N
LV - , -
(LA), AR LV - .T
, .A LV - ( .
) AR. S ,
T LV , .
-
.T , AR ■ PHYSICAL FINDINGS
LV I AR,
(LVEF, [ ] / - ,
), LV - .
.H , L ’ , LV T
LV AR, , IE, M ,
.C AR , , LV .
.U ,
. A LV , - Arterial Pulse A “ - ” ,
EF .D LV
.C (C ’ ), ,
LV AR, ,
, (Q ’ ),
>1000 . AR. A “ - ”
T LV, (T ’ ), - -
(D ’ )
AR , , -
.
.E
T
LV
.T -
AR, .I
AR, LV
. LV , LV
.H ,
, >40 H . T LV
K ( IV) -
LA ,
.A
.
LV - ,
I AR,
,
(CO) ,
LV - .F
.A LV
, AR -
EF. I ,
.S
LA, (PA) , PA, -
CO.
(RV) CO .
Myocardial ischemia AR Palpation I AR, LV
LV , , - .T
LV , . .A
A , - ,
Chest X-Ray I AR, - 1811
.T .I
, LV
(AS). I AR .W AR ,
CHAPTER 257 Aortic Regurgitation

AS AR, , . ., ,
(see Fig. 234-2D). . E ,
MRI, CT -
Auscultation I AR,
.
(A2) .A
BAV , S4 . Cardiac Catheterization and Angiography W ,
T AR - , , - -
,
(see Fig. 234-5B). I AR, LV .C -
, , .
, .W ,
, ,
TREATMENT
.I AR Aortic Regurgitation
,
.H , ACUTE AORTIC REGURGITATION (FIG. 257-1)
, AR P AR
. “C ” ( ),
. - .I
A - .B
AR. I CO ,
.T - LV. S
.A 24 .
AR Austin Flint murmur, , - ,
CHRONIC AORTIC REGURGITATION
- - .I
AR E -
- ; (A
.T AR [ACE] , ,
, . ) .S
I AR, LV - . T
, S 1, AR
, , , AR. LV -
. S
■ LABORATORY EXAMINATION ( <140 H ) AR,
ECG I AR, ECG LV - .I

(Chap. 235). I , AR. C
ST- T- I, VL,
V5, V6 (“LV ”). L - / QRS AR .
, A -
, .
Echocardiogram LV AR , .P
(Chap. 177). B
, (EF) (ARB) -
- .A , -
M . A
.T
. W ARB
AR, , -
(see Fig. 236-5, ). W
( . ., BAV ,T ’
AR, D
) .B
65% LV , ≥60 L/ ,
AR
≥50%,
.T - D
.O ,
AR
,
AR, LV .S -
AR. B -
(TTE)
-
AR .T
LV / .F TTE
.P
LV
AR, ,
, (CMR)
.
. T
.T - SURGICAL TREATMENT
(TEE) , I -
, .T , : (1)
3D LV . AR after
1812
Class
Class II
Aortic
AorticRegurgitation
regurgitation Class
Class IIa
IIa
PART 6
Class
Class IIb
IIb
Severe AR
(stages C and D) Progressive AR
Progressive AR
Vena contracta >0.6 cm (stage B)
(stages B)
Holodiastolic aortic flow reversal Vena

vena contracta ≤ 0.6 cm
>0.6
Rvol ≥60 mL/beat <60 mL/beat
RVol≥60%
Rvol mL/beat
RF ≥50% RF
RF <50%
≥50%
ERO ≥0.3 cm2 ERO
ERO <0.3 cm22
≥0.3 cm
LV dilation
Other
Other cardiac
cardiac
surgery
surgery
Symptomatic Asymptomatic
(stage D) (stage C)
No Yes
LVEF
LVEF ≥50%
≥50% LVEF
LVEF ≥50%
≥50% LVEF
LVEF ≥50%
≥50%
LVEF
LVEF <50%
<50% Other
Other cardiac
cardiac LVESD
LVESD >50
>50 mm
mm LVEDD
LVESD >65 mm mm LVESD
LVESD ≤50
≤50 mm
mm
(stage
(stage C2)
C2) surgery
surgery (stage
(stage C2)
C2) low
low surgical
surgical risk
risk LVEDD
LVEDD ≤65
≤65 mm
mm
AVR
AVR AVR
AVR AVR
AVR AVR
AVR
Periodic Monitoring
(I)
(I) (IIa)
(IIa) (IIb)
(IIb) (IIa)
(IIa)
FIGURE 257-1 Management o patients with aortic regurgitation. See legend or Fig. 256-4 or explanation o treatment recommendations (Class I, IIa, and IIb) and
disease stages (B, C1, C2, and D). Preoperative coronary angiography should be per ormed routinely as determined by age, symptoms, and coronary risk actors.
Cardiac catheterization and angiography may also be help ul when there is a discrepancy between clinical and noninvasive ndings. Patients who do not meet criteria
or intervention should be monitored periodically with clinical and echocardiographic ollow-up. AR, aortic regurgitation; AVR, aortic valve replacement (valve repair may
be appropriate in selected patients); ERO, e ective regurgitant ori ce; LV, le t ventricular; LVEDD, le t ventricular end-diastolic dimension; LVEF, le t ventricular ejection
raction; LVESD, le t ventricular end-systolic dimension; RF, regurgitant raction; RVol, regurgitant volume. (Adapted rom RA Nishimura et al: 2014 AHA/ACC Guideline
or the Management o Patients with Valvular Heart Disease. J Am Coll Cardiol 63:e57-185, 2014, with permission.)
; (2)
( >1 LV ), AR
LV - .R ,
.T , AR, IE
- ~6- , .W AR
12-
, . ., after LV prior to ,
.E
.O .
E , -
LV .
A (AVR)
AR LV . (Fig. 257-2). R
I , ~50%
AR LV AR A .I
LVEF <50%, LV - >50 , LV , ,
>65 .S - ,
,
LV LV - .T
.P AR AVR.
A , -
6–12 .
S -
. AVR . T AVR
1813
CHAPTER 258 Mitral Stenosis

B
FIGURE 257-2 Valve-sparing aortic root reconstruction (David procedure). Aortic root and proximal ascending aorta (A) are resected (B) with sinuses o Valsalva and
mobilized coronary artery buttons remaining. Subannular sutures (C) are placed, commissural posts are drawn up inside the valve and the annular sutures are passed
through the proximal end o the gra t. The annular sutures are tied (D), the valve is re-implanted inside the gra t, aortic continuity is re-established with another gra t o
appropriate size and the coronary buttons are attached to the side o the gra t. (From P Steltzer et al [eds]: Valvular Heart Disease: A Companion to Braunwald’s Heart
Disease, 3rd ed, Fig 12-27, p. 200.)
( AS AR) ~2% (Table 257-2). H - ■ FURTHER READING

, AR, , Lacro RV :A
LV ~10% M ’ .NE J M 371:2061, 2014.
~5% LV - Malaisrie SC, McCarthy PM: S
.N , , Valvular Heart Disease: A Compan-
, ion to Braunwald’s Heart Disease, 4 . CM O , RO B ( ).
LV . P ,E S , 2014, 199–218.
P AR (24–48 ) Nishimura RA : 2014 AHA/ACC
, . .JA C C 63: 57, 2014.
TABLE 257-2 Mortality Rates After Aortic Valve Surgerya

OPERATION
AVR (isolated)
NUMBER
14,795
MORTALITY (%)
2.3
258 Mitral Stenosis
AVR + CAB 9158 4.2
AVR + MVR 876 8.8
Abbreviations: AVR, aortic valve replacement; CAB, coronary artery bypass; MVR, T
mitral valve replacement.
Chaps. 38 and 234; -
a
Data are or the irst two quarters o calendar year 2013, during which (ECG) Chap. 235;
1004 sites reported a total o 135,666 procedures. Data are available rom
the Society o Thoracic Surgeons at http://www.sts.org/sites/de ault/ iles/ Chap. 236; -
documents/2013_3rdHarvestExecutiveSummary.pd . Chap. 237.
1814 MITRAL STENOSIS v
(y ). I MS
■ ETIOLOGY AND PATHOLOGY , PA (PAP)
R (MS) (Table 258-1; ,
see also Chap. 352). O (RV) - .
PART 6
, ,
, Cardiac Output I MS (
2
, , , 1–1.5 ), CO ,
2
. P .I MS ( <1 ),
MS ~40%
(Chap. 352). I , CO
, MS - .
(MR) .W
Pulmonary Hypertension T
, -
MS PAP.
, MS
P : (1) -
.H , -
LA ; (2)
, .
( - “ ”), LA
I MS,
( -
); (3) ;
. T ,
(4) , -
, , -
.S RV ,
-
(TR),
(“ - ”) .A
(PR), - .
,
.C - ■ SYMPTOMS
I ,
.T (
, )
(AF), (LA), MS ;
LA . .S
■ PATHOPHYSIOLOGY MS , -
2
I , 4–6 .I 2–5 .
, . ., I
2
<~2 , LA LA ,
(LV) -
, MS. W , , CO,
2
<1.5 , “ ” MS, , , , , , ,
LA ~25 H AF , , ,
(CO). T . A MS , -
(PA) , , ,
.T . T -
AF ’
, LA ( ).
T , . Hemoptysis (Chap. 35)
-
(Chap. 237). T CO .I
, .A LA
. Recurrent pulmonary emboli (Chap. 273),
.T , CO, , ,
AF, MS. Pulmonary infections, . ., ,
LA .S , ,
(TS). MS, .
T LV (EF)
MS. I MS , LA PA Pulmonary Changes I
(a ) ,
MS. T
, , ,
TABLE 258-1 Major Causes of Mitral Stenosis (Chap. 279). P
Etiologies
Rheumatic ever .
Congenital (parachute valve, cor triatriatum) Thrombi and Emboli Thrombi , -
Severe mitral annular calci ication with lea let involvement MS.
SLE, RA S , 10–20%,
Myxoma AF, >65 ,
IE with large vegetations CO. H ,
Abbreviations: IE, in ective endocarditis; RA, rheumatoid arthritis; SLE, systemic
lupus erythematosus. MS.
■ PHYSICAL FINDINGS TTE 1815
(See also Chaps. 38 and 234) . TEE
LA PMBV. T
Inspection and Palpation I MS, TTE

.I PAP MS
TS,
a .
.T
.A RV. A Chest X-Ray T
, , PA , -
. ,
LA. K B , ,
Auscultation T (S1) ,
. T -
(P2) LA
PAP , ~20 H .
(S2) .T (OS)
, , . ■ DIFFERENTIAL DIAGNOSIS
T (A2) L MS, MR -
0.05–0.12 . T A2 OS ,
MS. T OS - , , MR,
, MS, -
(see Fig. 234-5); LV . A OS P2 , S1
( . ., - ) . .A III/VI
I , S3 MR. S ,
CO. I - AR (Austin Flint murmur)
, MS,
( ). S , I II/VI -
. TS,
.H , , MS, MS -
, , , ; , TS
MS RV . y .
Atrial septal defect (Chap. 264) MS;
Associated Lesions W , , , ECG, - RV
TR .H ,
.T - LA K B -
(C ’ ). W S2 II III -
CO MS, ,
, ( MS. A - -
MS), .T Graham TS .
Steell murmur PR, - , , Left atrial myxoma (Chap. 266) LA ,
, - , ,
MS. H , LA -
.T - , , , -
, , I G 6 (IL-6)
(AR), .T
P 2. .T
- LA TTE.
■ LABORATORY EXAMINATION
ECG I MS , P LA ■ CARDIAC CATHETERIZATION
(see Fig. 235-8). I II L
V1 TS ,
MS (RA) .T QRS TEE -
.H , - .C ,
, RV . AS AR. C
- <65
Echocardiogram (See also Chap. 236) T -
(TTE) D - TTE. I >40 , >45
, , ,
(E ) (A , -
) ,
,
MR, , .C (CTCA)
,
(PMBV; (CAD)
). I , TTE LV RV - CAD. C -
, , PA PMBV
, MS,
, ,
(AS) / .T (TEE) () .
1816 INR. I
TREATMENT
, -
Mitral Stenosis (Fig. 258-1) TEE LA
.C -
P A β- - MS,
PART 6
(Chap. 352) LA AF
- MS. R 1 .
- MITRAL VALVOTOMY
, - U ,
.I , (N Y H A [NYHA] F
.B C II–IV) MS,
, ( . ., - ( ) < ~1 2/ 2 , <1.5 2 -
), .M -
AF. W . I PMBV (Figs. 258-2 and 258-3),
(INR) 2–3 - LA ,
MS AF .I
.T
LA ( >5.5 ) .I , -
.A , LA .
, ( . ., , ) T - -
MS. , -
I AF MS .E -
PMBV , - (<45 ) ,
- 80–90% 3–7 .T , PMBV
. U ,
3 - .
Class I
Rheumatic MS
Class IIa
Class IIb
Very severe MS Severe MS Progressive MS

MVA ≤1 cm2 MVA ≤1.5 cm2 MVA >1.5 cm 2
T½ ≥220 ms T½ ≥150 ms T½ <150 ms
Asymptomatic Symptomatic Asymptomatic Symptomatic with

(stage C) (stage D) (stage C) no other cause
Favorable valve Favorable valve

morphology morphology New-onset AF
No LA clot No LA clot PCWP >25 mmHg
No or mild MR No or mild MR No with exercise
Yes
Yes No
No Yes Favorable valve

NYHA class III-IV
morphology
symptoms with Yes No
No LA clot
high surgical risk
No or mild MR
No Yes Yes No
Periodic PBMC PBMC MVR PBMC Periodic PBMC Periodic

monitoring (IIa) (I) (I) (IIb) monitoring (IIb) monitoring
FIGURE 258-1 Management o rheumatic mitral stenosis. See legend or Fig. 256-4 or explanation o treatment recommendations (class I, IIa, IIb) and disease
stages (C, D). Preoperative coronary angiography should be per ormed routinely as determined by age, symptoms, and coronary risk actors. Cardiac catheterization
and angiography may also be help ul when there is a discrepancy between clinical and noninvasive ndings. AF, atrial brillation; LA, le t atrial; MR, mitral regurgitation;
MS, mitral stenosis; MVA, mitral valve area; MVR, mitral valve surgery (repair or replacement); NYHA, New York Heart Association; PCWP, pulmonary capillary wedge
pressure; PMBC, percutaneous mitral balloon commissurotomy; and T ½, pressure hal -time. (Adapted rom RA Nishimura et al: 2014 AHA/ACC Guideline or the
Management o Patients with Valvular Heart Disease. J Am Coll Cardiol 63:e57-185, 2014, with permission.)
1817
TABLE 258-2 Mortality Rates after Mitral Valve Surgerya
Guide UNADJUSTED OPERATIVE
wire OPERATION NUMBER MORTALITY (%)

MVR (isolated) 3448 4.6
MVR + CAB 1321 10.0
Stiffening MVRp 4284 1.2
cannula MVRp + CAB 2051 4.8
a
Data are or the irst two quarters o calendar year 2015, during which
the Society o Thoracic Surgeons at http://www.sts.org/sites/de ault/ iles/
documents/2015Harvest3_ExecutiveSummary.pd .
Abbreviations: CAB, coronary artery bypass; MVR, mitral valve replacement;
MVRp, mitral valve repair.
A B
I PMBV ,
, “ ”
.I
,
;
,
; .T
~2%.
S 50%
.S -
, ,
-
.H ,
C D .T ,
FIGURE 258-2 Inoue balloon technique or percutaneous mitral balloon (PA
valvotomy. A. A ter transseptal puncture, the defated balloon catheter is >50 H >60 H ), not -
advanced across the interatrial septum, then across the mitral valve and into /
the le t ventricle. B–D. The balloon is infated stepwise within the mitral ori ce. 2
). W
( >1.5
,
TTE - , MR, -
; TEE LA .A
MR .A
“ ” - . 10 .I MS,
T , , -
, .A . PMBV
PMBV. TEE - .
M (MVR) MS
MR,
-
PREDILATATION POSTDILATATION ,
ECG ECG . MVR
LV . P
LV LV MVR , LV , CAD,
.T 5%
40 40 >65
(Table 258-2). B
Pressure (mmHg)
- ,
MVR
LA MS— . .,
2
20 20 ≤1.5 — NYHA C III, . .,
LA .T
10- ~70%. L -
>65 -
CO .P
RV
0 0
.
Mean mitral gradient 15 mmHg Mean mitral gradient 3 mmHg
Cardiac output 3 L/min Cardiac output 3.8 L/min
Mitral valve area 0.6 cm2 Mitral valve area 1.8 cm 2 ■ FURTHER READING
FIGURE 258-3 Simultaneous le t atrial (LA) and le t ventricular (LV) pressure Nishimura RA : 2014 AHA/ACC
be ore and a ter percutaneous mitral balloon valvotomy (PMBV) in a patient .JA C C 63:357, 2014.
with severe mitral stenosis. ECG, electrocardiogram. (Courtesy o Raymond G. Nishimura RA :M –C
McKay, MD; with permission.) .L 387:1324, 2016.
1818 , , ,
. MR
259 Mitral Regurgitation
Patrick T. O’Gara, Joseph Loscalzo (Chap. 264),
. MR
( ). A
PART 6
.R
T , , , -
Chaps. 38 and 234; - .C MR
(ECG) Chap. 235;
, , ,
Chap. 236; -
Chap. 237. , MI( )
. S
MR
■ ETIOLOGY
M (MR)
LV - 6 . T MR
(HOCM)
( , , ,
, ) (Table 259-1). A
LV .P
MR (MI)
- , (AF)
(Chap. 269),
MR. A
, (IE)
MR
.W MI,
-
>65
.T ,
.I ,
MR
MR ,
.R “ - -
(LA) ,
MR”
-
.
.S , LV , , ,
C MR (T 259-1).
LA LV , ;
D MR, -
, “MR MR.”
/
, ( ) MR,
■ PATHOPHYSIOLOGY
T LV (LV )
(LV) ,
MR. A , LV LA
, , .
, LV ,
P , , - -
LV . T
MR. M -
MR LV .H , LV
(MVP) Chap. 260. T
, ,
LV .T LV
(CO). LV
, , LV
TABLE 259-1 Major Causes of Mitral Regurgitation .T
Etiologies LV ;
Acute , , LV -
IE .B (EF) MR
Papillary muscle rupture (post-MI) LV , (<60%)
Chordal rupture/lea let lail (MVP, IE) .
Blunt trauma D , LA , -
y MS. A ,
Chronic
LA-LV (
Primary (a ecting lea lets, chordae)
[S3] - MS)
Myxomatous (MVP, Barlow’s, orme ruste)
, MR
Rheumatic ever - .
IE (healed) M LV (LVEF), CO, -
Congenital (cle t, AV canal) (PA) , ,
Radiation (RF),
Secondary (lea lets, chordae are “innocent bystanders”) D .T
Ischemic cardiomyopathy (CMR)
Dilated cardiomyopathy , .L
HOCM (with SAM)
Chronic AF with LA enlargement and annular dilatation
. C , MR
2
≥60 L/ , RF ≥50%, ≥0.40 .
Mitral annular calci icationa
I MR, MR
a
Mitral annular calci ication may include elements o both primary and secondary ,
MR as the disease process may encroach on the lea lets, impair the normal
sphincteric unction o the annulus, or both. .
Abbreviations: AF, atrial ibrillation; AV, atrioventricular; IE, in ective endocarditis; LA Compliance I MR,
HOCM, hypertrophic obstructive cardiomyopathy; LA, le t atrial; LV, le t ventricular;
MI, myocardial in arction; MVP, mitral valve prolapse; SAM, systolic anterior - LA .
motion. A , LA LA .
T v LA , LA T MR MVP 1819
, ( )
.B LA V LV
, MR .
CHAPTER 259 Mitral Regurgitation

S2,
LV-LA . LV - ■ LABORATORY EXAMINATION
MR , , ,
.
ECG I , LA -
, (RA)
P MR, ,
RV .
LA increased LA
C MR AF. I ,
LA LA .
- ECG .I
T LA v .T MR
, LV .
,
- LV-LA .T Echocardiogram T (TTE) -
MR -
CO, . LV LV - -
; AF EF. O
LA . , , LA LV , ,
LV .D
■ SYMPTOMS MR LA,
P - - , MR D ,
. T LV . , ,
F , , , RF,
MR. P - .I , PA (PAP )
AF. R - , TR . TTE
, , , , MR
(TR), .T (TEE)
MR TTE (see Fig. 236-5). E
.A TTE
MR. MR , PA , -
■ PHYSICAL FINDINGS , -
I MR, - .
, , - Chest X-Ray T LA LV
CO. A MR. L , LA
, LV - .P
- (S3), , , K B .
. M
I MR, - , MR MS. C
, ,
, .P MR -
,
. .
Auscultation S1 , , -
, MR. I MR, TREATMENT
,
S2. A - S3 0.12–0.17 Mitral Regurgitation
, . ., -
LV, MEDICAL TREATMENT (FIG. 259-1)
, , . I T MR
, , - , .A
MS. I , ( . ., , ) AF ,
, (S3) . CHA2DS2-VAS .T -
A acute MR ;
.A -
MR. .C
A III/VI , AF , LA .I
MR. I , , -
(see Fig. 234-5A), , , -
- - MR. T MR LV in the absence of
MR systemic hypertension. T MR
.H , -
,
, , , , - (ACE) , ,
LA .I , - ( [CRT])
, , .A
AS. I IE MR IE. A -
, “ ” , MR LV
. .
1820
Mitral Regurgitation Class I

Class IIa
Class IIb
PART 6
Primary MR Secondary MR
Severe MR Progressive MR CAD Rx

Vena contracta ≥0.7 cm (stage B) HF Rx
RVol ≥60% mL Vena contracta <0.7 cm Consider CRT
RF ≥50% RVol <60 mL
ERO ≥0.4 cm2 RF <50%
LV dilation ERO <0.4 cm2
Symptomatic Asymptomatic Progressive

Symptomatic Asymptomatic severe MR severe MR MR
(stage D) (stage C) (stage D) (stage C) (stage B)
LVEF 30 to ≤60% LVEF >60% and New onset AF or

LVEF >30% LVESD <40 mm PASP >50 mmHg
Persistent NYHA
LVESD ≥40 mm
(stage C1) (stage C1)
class III-IV
(stage C2)
symptoms
Progressive increase Likelihood of successful

No Yes in LVESD or repair >95% and
decrease in EF expected mortality <1%
Yes No
MV surgery* MV surgery* MV surgery MV repair MV surgery*

Periodic monitoring Periodic monitoring
(IIb) (I) (IIa) (IIa) (IIb)
*MV repair is preferred over MV replacement when possible.
FIGURE 259-1 Management o mitral regurgitation. See legend or Fig. 256-4 or explanation o treatment recommendations (class I, IIa, IIb) and disease stages
(B, C1, C2, D). Preoperative coronary angiography should be per ormed routinely as determined by age, symptoms, and coronary risk actors. Cardiac catheterization
and angiography may also be help ul when there is a discrepancy between clinical and noninvasive ndings. AF, atrial brillation; CAD, coronary artery disease; CRT,
cardiac resynchronization therapy; EF, ejection raction; ERO, e ective regurgitant ori ce; HF, heart ailure; LV, le t ventricular; LVEF, le t ventricular ejection raction;
LVESD, le t ventricular end-systolic dimension; MR, mitral regurgitation, MV, mitral valve; MVR, mitral valve replacement; NYHA, New York Heart Association; PASP,
pulmonary artery systolic pressure; RF, regurgitant raction; RVol, regurgitant volume; and Rx, therapy. (Adapted rom RA Nishimura et al: 2017 Focused Update o
the 2014 AHA/ACC Guideline or the Management o Patients with Valvular Heart Disease. J Am Coll Cardiol. Available at www.onlinejacc.org/lookup/doi/10.1016/j.
jacc.2017.03.011.)
P MR LV
.D , ( - EF <60% LV -
), (LV ESD) >40 .O -
-MI (1)
MR. - AF ( <3 ); (2)
SURGICAL TREATMENT ( PA ≥50 H ≥60 H
); (3) LV EF
I , , MR -
LV ESD .T
,
-
- -
.T
(Table 259-2). R TABLE 259-2 Mortality Rates after Mitral Valve Surgerya
.R OPERATION NUMBER MORTALITY (%)
- , MVR (isolated) 3448 4.6
MVR + CAB 1321 10.0
MVRp 4284 1.2
.I ,
MVRp + CAB 2051 4.8
,
a
, , Data are or the irst two quarters o calendar year 2015, during which
LV the Society o Thoracic Surgeons at http://www.sts.org/sites/de ault/ iles/
. documents/2015Harvest3_ExecutiveSummary.pd .
S MR - Abbreviations: CAB, coronary artery bypass; MVR, mitral valve replacement; MVRp,
, (F . 259-1). S mitral valve repair.
LV 1821
- .I , MR ( . ., -
, ) <75 LV
CHAPTER 260 Mitral Valve Prolapse

(CAD)
<1% .T
, , ~1%. R 95%
-
.R
, , ,
.L - ;
~1% 10 .F
AF, ,
AF.
T MR
. S MR FIGURE 259-2 Clip used to grasp the ree edges o the anterior and posterior
. C lea ets in their midsections during transcatheter repair o selected patients
, with mitral regurgitation. (Courtesy o Abbott Vascular. © 2014 Abbott Laboratories.
All rights reserved.)
-
MR. V MR
.C
MR
TEE
.I MR LV
.I
(EF <30%), ,
,
LV , - .
.
R
-
CRT, .T ■ FURTHER READING
MR Carabello BA: T .A
- .C 127:1567, 2013.
. P Maisano F :T :
MR - C . .E
, H J 36:1651, 2015.
Nishimura RA :M .C
. .L 387:1324, 2016.
Nishimura RA : 2017 F U 2014 AHA/ACC
W ,
G M P V H D -
may -
.JA C C 2017. A www.onlinejacc.org/lookup/
MR -
doi/ 10.1016/j.jacc.2017.03.011.
TTE
Otto CM, Verrier ED: M —W
TEE CMR. C
?NE J M 364:1462, 2011.
.
Rugueiro A :T :
TRANSCATHETER MITRAL VALVE REPAIR AND REPLACEMENT . JA C C
A 69:2175, 2017.
MR
.T
.O
- (
A2-P2; Fig. 259-2). T
.T
- -
.I
,
U S 260 Mitral Valve Prolapse
, ( ) MR. T - -
U S
, LVEF, , T
MR - . O Chaps. 38 and 234; -
(ECG) Chap. 235;
Chap. 236; -
Chap. 237.
.V -
MITRAL VALVE PROLAPSE
.A M (MVP), systolic click-
- murmur syndrome, Barlow’s syndrome (Fig. 260-1), floppy-valve syndrome,
LV and billowing mitral leaflet syndrome,
1822 ,
B
, -
. ECG ( )
MVP
A
PART 6
■ CLINICAL FEATURES
MVP -
15 30 ;
. MVP
C (>50 ) , , MR
.
T
,
. MVP
,
MR
.T
.I ,
; ,
.
FIGURE 260-1 Congenital or developmental mitral valve prolapse. Myxomatous thickening and M
prolapse o the mitral valve can occur in isolation in 2–3% o the general population, or may be
associated with heritable collagen-vascular disorders and aortic root dilatation, such as in Mar an . H , N A -
syndrome. Myxomatous degeneration o the valve predisposes to severe regurgitation and chordal , MVP
rupture, and is a requent indication or mitral valve repair or replacement. Prolapse can a ect only one MR .A ,
or both leafets, to varying degrees. A. Three-dimensional transesophageal echocardiogram showing -
a myxomatous mitral valve rom the le t atrial en ace aspect. There is billowing and prolapse o the -
entire middle scallop o the posterior leafet. (Figure courtesy o Douglas C. Shook, MD, Department , (AF),
o Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital). B. The posterior
leafet o the mitral valve demonstrates marked prolapse and hooding in all segments and severe , -
redundancy in this photograph taken rom the vantage point o the le t atrium. C. Opening the le t , .S
heart reveals prominent mitral leafet hooding (arrows). The chordae are ocally thickened, but are not
used as would be the case in rheumatic valve disease. (Used with permission rom JC Wu, RF Padera: MR (LV)
Clinicopathologic correlates, in Atlas o Echocardiography, 2nd ed, SD Solomon [ed], E Braunwald , -
[series ed]. Philadelphia, Current Medicine Group LLC, 2008. p 363.)
LV .T
.M
- ; ,
.A , ,
, .T
.I
. MVP MR / .
(MR) (see Chap. 259). Auscultation A - -( )
I MVP, , , , 0.14 S1
.A ,
III , .
. S - ,
MVP - – ,
, M (Chap. 406), - “ ” “ ” .R
, E -D . MVP .W
, MR -
M , - .W ,
, - MR
.O .T ,
, , , . V ,
I MVP, LV ( ),
, .C , ,
.T LV , MVP; -
, .I , S 1, .S
, , , - ;
. .S .
MVP ,
, , LABORATORY EXAMINATION
20% . T ECG
MVP , , T- II, III, VF,
, .T (TTE)
.R -
.A
■ FURTHER READING 1823
Grover FL : 2016 A R S T
S /A C C T V
T R .JA C C 69:1215, 2017.
CHAPTER 261 TricuspidValve Disease

Nishimura RA :M .C
.L 387:1324, 2016.
Nishimura RA : 2017 F U 2014 AHA/ACC
G M P V H D .
JA C C 70:252, 2017.
FIGURE 260-2. Barlow’s valve with classic mitral valve prolapse, as seen on
transthoracic echocardiogram in parasternal long-axis windows. Le t: parasternal
long-axis window, showing both myxomatous leafets billowing into the le t atrium
in late systole. Right: same window with color Doppler showing signi cant mitral
regurgitation (yellow jet) in systole. (Courtesy o Justina Wu, MD, PhD.)
MVP ( )
261 Tricuspid Valve Disease
2
(LA) .T
(Fig. 260-2). C
D MR TRICUSPID STENOSIS
. T MR T (TS), -
MVP , - (MS) N A W E ,
.B - , (Table 261-1). I
LV .T MS. H TS 5–10%
(TEE) MS; TS
(TR). N TS .
.E
.I ■ PATHOPHYSIOLOGY
TTE LV - A (RA)
(RV) , MR (RV) TS. I
.I .
A 4 H
. RA
. U
, ,
TREATMENT , , .I ,
Mitral Valve Prolapse RA a
RV .T y .T -
I (CO) , .
.B T CO
.D (LA), (PA), RV
AF CHA2DS2-VAS
.I -
MR, (see Fig. 259-1). TABLE 261-1 Causes of Tricuspid Valve Diseases
O MVP MR
VALVE LESION ETIOLOGIES
LV ,
, AF. M Tricuspid stenosis Rheumatic
MVP Congenital
(see Table 258-2); Tricuspid regurgitation Primary (organic)
, Rheumatic
.R - Endocarditis
, Myxomatous (TVP)
( . ., , ,B ’ ) Carcinoid
.C - TEE - Radiation
Congenital (Ebstein’s)
.T - -
Trauma
Papillary muscle injury (post-MI)
MR MVP (see Fig. 259-2). M , MR Secondary ( unctional)
.N , RV and tricuspid annular dilatation due to
LV multiple causes o RV enlargement (e.g., long-
standing pulmonary HTN, remodeling post-RV MI,
, >200
le t-sided valve disease, cardiomyopathy, AF)
U S .R -
Chronic RV apical pacing
~2%. O
U S (see Chap. 259). Abbreviations: AF, atrial ibrillation; HTN, hypertension; MI, myocardial in arction;
RV, right ventricular; TVP , tricuspid valve prolapse.
1824 2
MS. T , TS - <1.5–2 . TS -
MS. TR. O
.I -
■ SYMPTOMS , .M -
B MS TS,
PART 6
. .M
C , TS -
, , .P
.H , CO TS TR .
, ,
TS / TR. I , TS -
- TRICUSPID REGURGITATION
. M 80% TR -
( )
■ PHYSICAL FINDINGS RV
B TS ( ), (MI)
, .S (T 261-1). S TR
TS ,
, , , , .C - PA (PA >55 H ),
, , - ( . ., )
. T , ( . ., ). I
, a .T v PA .S TR
, RA RV
, y .I ; , RV
, TV . TR
. (AF), .R
O , (OS) TR, TS. T
~0.06 . T , , , ,
TS MS, , TR.
TS MS, L , TR -
.H , , ,
, E ’ (Chap. 264).
.T -
TS , ■ PATHOPHYSIOLOGY
V T
, . RV RA,
( . ., RV ) .
■ LABORATORY EXAMINATION T TR PA -
T (ECG) RA (see Fig. 235-8) ( RV ),
, P II, , , -
P V 1. T absence ECG RV RV , RA . RV -
(RVH) - .F CO .
MS .T S TR RA
- TS MS - RA c-v
RA .P TR “ ”
PA RA (see Fig. 234-1B). S TR
MS; RV (RV ) -
.O (TTE) ,
, PA
; .
D .S TS
2
≤1 - ≥190 . T RA ■ SYMPTOMS
(IVC) . TTE M TR
TR, .B TR
, (LV) RV , PA . - , LV , / PA
C TS. ,
. F
CO , TR. A
TREATMENT RV , -
Tricuspid Stenosis , / , ,
,
P TS - .
; , ,
. S ■ PHYSICAL FINDINGS
T TR -
, , c-v y ( TS). TR
.S TS ,
.O
(MVR) , , , , , -
TS ~4 H .A RV
TR. 1825
, T - TR
(C ’ ) RV .
V , .T
CHAPTER 261 TricuspidValve Disease

TR (MR)
TREATMENT
RV . AF Tricuspid Regurgitation (Fig. 261-1)
.
D TR
■ LABORATORY EXAMINATION .A
T ECG
TR, . ., Q- MI RV MI, RVH, .T PA -
- / , -
E ’ . ECG RA - ,
; AF .T PA TR. T
- RA RV , - TR -
TR. TTE -
RA RV , , , TR -
/ ; (>40 ),
TR D , PA .O
(see Fig. 236-8). S TR
.C D TR .S
PA , , TR
TR
RA .A TR , PA , RV RV .R
TTE
.R - - ( ) (~8–9%)
(CMR)
, . I -
TR, CO , RA RV .I
x .I
c-v y .T RA RV
.
- .E
Class I
Tricuspid Regurgitation
Class IIa
Class IIb
Progressive functional TR Asymptomatic severe TR Symptomatic severe TR

(stage B) (stage C) (stage D)
Mild Moderate Functional Primary Reoperation Functional Primary
At time of left-sided Preserved RV

At time of left-sided Progressive RV At time of left-
valve surgery function
valve surgery dysfunction sided valve surgery
PHTN not severe
TA dilation* PHTN without

TA dilation
TV repair or TV repair or
TV repair TV repair TV repair or TVR TV repair or TVR
TVR TVR
(IIa) (IIb) (I) (IIb)
(I) (IIa)
FIGURE 261-1 Management o tricuspid regurgitation. See legend or Fig. 256-4 or explanation o treatment recommendations (Class I, IIa, IIb) and disease stages
(B, C, D). Preoperative coronary angiography should be per ormed routinely as determined by age, symptoms, and coronary risk actors. Cardiac catheterization and
angiography may also be help ul when there is a discrepancy between clinical and noninvasive ndings. PHTN, pulmonary hypertension; RV, right ventricular; TA,
tricuspid annular; TTE, transthoracic echocardiogram; TR, tricuspid regurgitation; TV, tricuspid valve; TVR, tricuspid valve replacement. TA dilation is de ned by >40 mm
on TTE (>21 mm/m2) or >70 mm on direct intraoperative measurement. (Adapted rom RA Nishimura et al: 2014 AHA/ACC Guideline or the Management o Patients
with Valvular Heart Disease. J Am Coll Cardiol 63:e57-185, 2014, with permission.)
1826 ■ FURTHER READING ■ SYMPTOMS
Dreyfus GD :F .JA C C P PS
65:2331, 2015. ( -
Hahn RT :E ) .W PS,
.JA C C 69:1795, 2017. - .A
PART 6
Nishimura RA : 2014 AHA/ACC RV -

.JA C C 63: 59, 2014. ,
Rodés-Cabau J, Taramasso M, O’Gara PT: D , , , , .
:C .L
388:2431, 2016. ■ PHYSICAL FINDINGS
Rodés-Cabau J : T T PS - , -
. JA C C 67:1829, 2016. – , -
, ( )
. T
- .
T
RV - ( a ) .T
Pulmonic Valve Disease .W
262 PS,
Patrick T. O’Gara, Joseph Loscalzo .A -
.T
(A2). P
, (P2)
PULMONIC STENOSIS .A a ,
P (PS) RV, -
(Table 262-1). W PS, . D - .A RV -
N .S , , ,
(Chap. 275), 12. M PTPN1 , .
N .
M ■ LABORATORY EXAMINATION
.T T (ECG) , RVH,
. RA PS. C -
PA -
■ PATHOPHYSIOLOGY RV
PS .I RVH,
(RV) (PA). RV - . T RA .
(RVH) RV T (TTE)
, .C , -
LV , RV , PA ( ),
(AS), RV .T
PS , RV (TEE)
.W - RV (RVOT) -
(CO), PS . C
>50 H ; PS , ,
30–50 H . PS
<30 H , .T
. D
T RA a - - - . T
, RV. A RA v D .
(TR) RV .
T CO .
TREATMENT
TABLE 262-1 Causes of Pulmonic Valve Disease Pulmonic Stenosis
VALVE LESION ETIOLOGIES D
Pulmonic stenosis Congenital .P
Carcinoid (PR),
Tumor
Endocarditis >50 H ( >30 H ) -
Pulmonic regurgitation Primary valve disease >60 H (
Congenital >40 H ). S
Postvalvotomy ( N ’ ).
Endocarditis A
.
Carcinoid
Annular enlargement
Pulmonary hypertension PULMONIC REGURGITATION
Idiopathic dilation PR ,
, ; RVOT
Mar an syndrome
F ;
(T 262-1). C - ■ FURTHER READING 1827
PR PS. Ansari MM :P .JA
L - PA C C 66:2246, 2015.
PR. Baumgartner H : ESC -
CHAPTER 263 Multiple andMixedValvular Heart Disease

.E H J 31:2915, 2010.
■ PATHOPHYSIOLOGY Warnes CA : 2008 ACC/AHA
S PR RV - .JA C C 52: 143, 2008.
.A (AR), PR
.T
PA RV, PR, -
. A RV ,
. T CO
.A
,
RV
263 Multiple and Mixed
Valvular Heart Disease
.I ,
RV RA Patrick T. O’Gara, Joseph Loscalzo
.
■ SYMPTOMS M
M PR , , / .F , -
.O , PA , ( [MS],
.W PR RV , [MR], MS MR), ( [AS],
, , / , [AR], AS AR), (
. [TS], [TR], TS TR) ,
.T TR
■ PHYSICAL FINDINGS
Chap. 261. S
T PR - , -
(G S ) (
) (
AR. T G S
). P AS LV
P2 RV , MR
(AVR). C
PA .S
AS. A (IE)
F PS/
RV-PA
“ -
. PA
”
PR RV . .M , , -
, .
■ LABORATORY EXAMINATION C
D PR, ECG .E ,
RVH RA .O - , RV RA ,
.P / .P M
D . PA AR MR
.C (MVP). M -
(CMR) , - ( , , )
, - .B
RV .C -
.T
. .
■ PATHOPHYSIOLOGY
TREATMENT I ,
Pulmonic Regurgitation .
I PR PA F , ,
, PA (CO) -
.S /
/ / , ( , ,
PA ( . ., PA , - ). A , (AF) -
). D - MS
.S , .T -
, , , ,
.T “ ,”
PR . A CO
F ,
.T - .
. O
TR .
1828 F TR - , , LV
; (PA) .T .I ,
.P - -
TR AVR. C LV
.T TR ; AR ( MR)
PART 6
(RA) , c-v , ,
RA .T c-v RA .N
. T RA
“ ” , .
TR PA . CO
.F ■ SYMPTOMS
( . ., , ) - C , - ,
. P -
.
TR, TS, .W TS, y RA S
. , CO, .P -
A , AF -
, - ,
MS AR. I MS, (LV) . C
/
.W AR, , LV / -
- . S
.B CO ( / , )
MS, , .
(AR, AS, ). A ,
AF .T ■ PHYSICAL FINDINGS
AF CO, M
LA LV , ,
. .T , AS AR -
S ( ) MR , - ,
AS. T
.I LV - , .M
( ) AR -
LV .R / , AS .T -
AVR , , AS AR
MR. P
MR AVR (PDA) V .W
.I , ,
MR AVR , (S2). T
.M - - PDA .
MR AVR. S T V -
MR .A
AVR. ,
I AS AR, , ,
.B AS AR. A , -
CO
AR LV , LV- D - .I
- MS MR, ,
- ( )
. U , G , .A
CO ( ) AF. F TS TR
, - MS MR,
.S .T
.T D - AS AR;
E ( 0) MR .S
Chaps. 38 and 261.
(LA) MS.
W AR MR ■ LABORATORY EXAMINATION
, , LV .W AS T (ECG) -
MS , LV .I / . ECG -
-
, PA / -
.T AF
- .
P AS, LV , - .T -
, / -
, , , IE ,
AVR (TAVR) . . T
T LV PA
/ K B , AS AR, 1829
LA .A
RA .R AS (Chap. 256). I ,
, ,
CHAPTER 264 Congenital Heart Disease in the Adult

. ,
T (TTE) , , ,
PA .I ,
/ - /
.T (TEE)
.
( , ) IE C -
. TTE
, - ,
, , , PA .D
, , ( )
, PA, .E ( -
) - ,
-
TTE .A .I ,
TTE
( ) .T
- .N ( . ., ).
. T
C (CMR) - ( ) TR - -
,
, (>40 ). T ,
.C (CT) ,
IE. I . R (
.C ) TR -
CT - , ,
.R
. MR AVR AS
I - .
T MR -
MS
.I - (PMBV). L , AR
- - AS
.M PA (PABV). TAVR
(PVR) - , AS AR. T
, - AS ( TAVR) MR (
.I - - ) .F -
.A .
CO .C (
) .C - ■ FURTHER READING
. Bolling SF: T .JA C
C 64:2643, 2014.
Egbe AC : O . J A C
TREATMENT C 167:2321, 2016.
Multiple and Mixed Valve Disease Magne J : P . JACC:
C I 8:83, 2015.
M
.A ,
- (Chaps. 256–262),
.F , AF
.
, 264 Congenital Heart Disease
in the Adult
M -
Anne Marie Valente, Michael J. Landzberg
AF. B –
,
- , ■ PREVALENCE
. P T (CHD)
PVR . U S 1.4 ,
T CHD. T
/ CHD , -
.W , CHD .L -
1830
Normal Heart
PV
SVC
Pulmonary
artery IVC
PART 6
RA LA
Aorta Tricuspid Mitral
valve valve
Right RV LV
pulmonary Left
veins Left pulmonary
atrium veins Pulmonary Aortic
Superior valve valve
vena cava Right Mitral
atrium valve
PA Ao
Pulmonary Left
valve ventricle
Right
ventricle
Inferior
vena cava
Tricuspid valve Aortic valve
FIGURE 264-1 Normal heart. Understanding o congenital cardiac anatomy and physiology is acilitated by use o box diagrams, displaying passage o blood fow
between blood vessels and cardiac chambers. Labeling (e.g., structure names, arrows to denote direction o fow, coloring to represent oxygen saturation, connections
or obstructions, chamber or vascular pressures, oxygen saturations) can aid in representation. Ao, aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA,
pulmonary artery; PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava.
, , .I ,
(ACHD) . I , -
ACHD, ACHD , .
CHD .T
CHD
Non-Cardiac Surgery N CHD -
.L , CHD A( ) .
.T , A , CHD
,
,
(Fig. 264-1). . C , -
■ THE CHANGING LANDSCAPE OF ADULT CHD CHD. Table 264-1 -
A Relatively New Subspecialty in Cardiovascular Disease CHD .A

O , CHD (ACHD) ,
, , -
.T A C C ,
A H A
CHD, 2008. T
, - TABLE 264-1 Multi-Organ Considerations in ACHD Patients
, ACHD .T Neurologic Increased incidence o occult or clinically
ACHD evident strokes
’ Decreased level o executive unctioning skills
2015 ACHD Anxiety, post-traumatic stress disorder,
A B M S , depression
2- ACHD Psychosocial disorders
, A C G M E .I Lungs Restrictive lung disease
, A C H A (ACHA)
Pulmonary vascular disease
ACHD
Renal Decreased per usion
ACHD. Hepatic Liver ibrosis
Peripheral Vasculature Increased chronic venous insu iciency
■ SPECIAL CONSIDERATIONS FOR THE ACHD PATIENT Lymphatic Impaired reabsorption
A CHD Orthopedic Scoliosis
, ; Kyphosis
, Hematologic Anemia
. ACHD , ,
Coagulopathies
, ,
, 1831
, - . . T
Pregnancy W CHD ,
,

CHD - , ,
.P , ,
’ , , .W
. Table 264-2 W H O -
C - .A
; 18 22
CHD. A , CHD
.N CHD .
, , ■ CONGENITAL TERMINOLOGY, DEVELOPMENT,
CHD. W AND GENETICS
CHD, (PA)
, , - Congenital Nomenclature O
, . CHD
P - .S -
. A (ACE) , M A ,M L ,
, , - - J E , S
, - R V P R A .I ,
, .T , .T
FDA (A, B, C, D, .T
X) ; D 2014, , , ,
FDA P L L R ,
( ). I , (RV) -
, - - ,
(LV) - - -
TABLE 264-2 Modified WHO Classification of Heart Disease .I : ,
in Pregnancy .F ,
WHO I
(RA) RV LV .F , -
,
• Uncom plicated, sm all or m ild pu lm onary stenosis, patent du ctu s arteriosu s, , .F ,
mitral valve prolapse
PA RV ( -
• Su ccessfu lly repaired sim ple lesions (atrial or ventricu lar septal defect,
), LV -
patent ductus arteriosus, partially anomalous pulmonary venous
drainage). ( ). A
• Isolated atrial or ventricu lar ectopic beats
, .
WHO II (i otherwise well and uncomplicated) Cardiac Development T
• Unoperated atrial or ventricu lar septal defect , 8 ’ .M -
• R epaired tetralogy of Fallot (
) ,
• M ost arrhythm ias
WHO II-III (depending on individual) .C
• M ild left ventricu lar im pairm ent -
• Hypertrophic cardiom yopathy , , RV, .A -
• Native or tissu e valvu lar heart disease not considered W HO I or IV ,
• M arfan syndrom e w ithou t aortic dissection 5 –6 ,
• A orta < 45 m m in bicu spid aortic valve , . O
• R epaired coarctation ,
.T
WHO III
( ),
• M echanical valve (D- ). F -
• System ic right ventricle - ( )
• Fontan circu lation ,
• Cyanotic heart disease (u nrepaired) .F
• O ther com plex congenital heart disease ,
• A ortic dilation 40– 45 m m in M arfan syndrom e .F
• A ortic dilation 45– 50 m m in bicu spid aortic valve RV,
. W ,
WHO IV (pregnancy contraindicated)
.
• P u lm onary arterial hypertension S ,
• Severe system ic ventricu lar dysfu nction (LVEF <3 0% , NYHA class > II) , , ,
• P reviou s peripartu m cardiom yopathy w ith any residu al im pairm ent of left
ventricular unction , LV -
• Severe m itral stenosis, severe sym ptom atic aortic stenosis PA RV.
• M arfan syndrom e w ith aorta dilated >45 m m
• A ortic dilation >50 m m in bicu spid aortic valve
Genetic Considerations CHD
; ,
• Native severe aortic coarctation
. C T 21
1832 50% CHD, - .I
.C ASD .R
, , ,
22 11 (D G ). E ASD -
, ,
PART 6
. M ( ). T -
DG - , ASD ,
.T , ASD .P -
.P N 10% ASD, E
.S (ES) ( ). M
N , ASD
PTPN11. A W (7 11.23 ) ACHD .
, Figure 264-2B ASD . T
“ - ” .T ASD ASD, ,
- CHD. , .
T (PFO),
■ SPECIFIC CHD LESIONS (
- ) 25%
Dilated Right Heart T .S ASD
(Table 264-3). T .H ,
( E ), , , -
RV ( RV , ,
U ’ ), .A ASD
.C AV ; ASD
, - AV , -
. .A
Atrial Septal Defect O
(ASD, Fig. 264-2A). .A ,
I , , -
, , .P ( ) , ,
ASD ; , ASD - .
.T ASD - S ASD , ,
“ - - ” ( , .
, , , Partial Anomalous Pulmonary Venous Return P
). T - - (PAPVR) -
, -
.A , (Fig. 264-3). T
, , , - ,
, -
- - .I
.T , ,
, RV .C
PA , , , , . S ,
.T (ECG) PAPVR
.S , , , ,
, , , , .
Ebstein Anomaly E (Fig. 264-4)
TABLE 264-3 Congenital Etiologies of Right Heart Dilation , “ ,”
Congenital tricuspid valve disease ,
Tricuspid valve dysplasia with regurgitation .T
Ebstein anomaly , -
Congenital pulmonary valve regurgitation , “ ”
Pulmonary arterial hypertension RV, , ,
.T
Myocardial abnormalities
, .T -
Arrhythmogenic RV cardiomyopathy
E
Uhl’s anomaly , ,
Shunt lesions (TR), ,
Partial anomalous pulmonary venous return .T E
Primum ASD .I
Secundum ASD ,
Sinus venosus de ect (
Coronary sinus septal de ect , -
Gerbode de ect (LV-RA shunt) ). P TR “ ”
Coronary artery istula to the RA, CS ; ,
Postoperative residual shunts . T ECG ,
.U 20%
Atrial Septal Defect PV 1833
SVC
ASD
IVC x x+y

RA y LA
Ao PA
Right x+y x
PVs SVC x Sinus ASD 1°
x Left venosus
x+y PVs RV LV
ASD defect
y LA x+y x
RA x
x+y x
x+y x
x+y LV PA Ao
RV
ASD 2°
IVC
A B
FIGURE 264-2 A. Atrial septal de ect. In the presence o an atrial septal de ect, the di erence in compliance between the (RA+ RV) as compared to the (LA+LV), combined
with the size o the de ect itsel , allows or a “shunt” o fow (“y”) o “red” (oxygenated) blood rom the le t side o the heart to the right side (deoxygenated). Systemic
venous return o pure deoxygenated blood (“x”) is increased by the oxygenated shunted blood (“y”) to increase volume o blood (“x + y”) in the RA, RV, and total blood fow
to the lungs. I the volume or the sequelae o the shunted blood is su cient, RA and RV can dilate (hashed lines), and arrhythmias or shortness o breath (and occasionally
pulmonary hypertension) can ensue. Ao, aorta; ASD, atrial septal de ect; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary artery; PV, pulmonary veins;
RA, right atrium; RV, right ventricle; SVC, superior vena cava. B. Diagrammatic representation o the location o various atrial septal de ects. ASD 1, primum atrial septal
de ect; ASD 2, secundum atrial septal de ect. (Part B used with permission rom Emily Flynn McIntosh, illustrator.)
- (W -P W ). S 10% CHD ,
, VSD .L VSD
, . ,
.S VSD .
Shunt Lesions Causing Left Heart Dilation I Figure 264-5B VSD ;
( -
.T , ). M
, -
(VSD, Fig. 264-5A) (PDA,
.A ,
Fig. 264-6). ,
Ventricular Septal Defects VSD - .S
, , , ,
Partial Anomalous
Pulmonary Venous Return
APV PV
SVC APV
y
x IVC x+y x
y
Ao PA RA LA
Right x+y x
PVs x
SVC x+y Left
LA PVs
RV LV
x x+y x
RA
x+y
x+y x
x
LV
x+y PA Ao
RV
IVC
FIGURE 264-3 Partial anomalous pulmonary venous return. In the presence o an anomalously draining pulmonary vein (typically to a systemic vein such as the le t
innominate vein, SVC, or rarely IVC), an obligate “shunt” o fow (“y”) o “red” (oxygenated) blood rom the a ected pulmonary vein to the right heart (deoxygenated)
ensues. Systemic venous return o pure deoxygenated blood (“x”) is increased by the oxygenated shunted blood (“y”) to increase volume o blood (“x + y”) in the SVC,
RA, RV, and total blood fow to the lungs. I the volume or the sequelae o the shunted blood is su cient, RA and RV can dilate (hashed lines), or shortness o breath
can ensue. Ao, aorta; APV, anomalous pulmonary vein; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries; PV, pulmonary veins; RA, right
atrium; RV, right ventricle; SVC, superior vena cava.
1834 Ebstein Malformation
PV
SVC PFO
IVC x x
PART 6
Ao PA
Right RA z LA
PVs x+z
SVC x Left x+y x+z
x LA PVs
*
PFO y
LV
z x+z RV x+z
RA x+y
x+y
x+z x x+z
y
LV
RV PA Ao
x+y
IVC
FIGURE 264-4 Ebstein mal ormation. In the presence o Ebstein anomaly, the tricuspid valve leafets can be redundant, enestrated and sail-like (typically seen in the
anterior leafet *), or adherent to the underlying myocardium with apical displacement o the non-adherent components (typically the septal and posterior leafets).
Location and degree o leafet coaptation are variable and account or varying degrees o tricuspid regurgitation, shi t o the unctional tricuspid valve anterior rom
the anatomic annulus into the right ventricle, “atrialization” o the right ventricle, and most commonly angulation o the tricuspid valve into the RV outfow tract. RA
and RV dilation (hashed lines) can occur due to the e ects o combined volume rom systemic venous return (“x”) and tricuspid regurgitant fow (“y”). PFO is requent;
worsening compliance and elevation o pressure in the RA as compared to the LA can lead to increasing “right-to-le t” (deoxygenated to oxygenated) shunt and
cyanosis. RV myocardial unction may be abnormal. Ao, aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries; PFO, patent oramen
ovale; PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava; *, anterior tricuspid valve leafet.
.T ( - - ). L PDA
VSD -
. , ES.
Patent Ductus Arteriosus A PDA ■ MODERATE AND COMPLEX CHD
.S
PDA , Tetralogy of Fallot T F (TOF)
.T CHD, 0.5 1000 .I
, -
, (RVOT) , VSD,
Ventricular Septal Defect

PV
SVC
IVC x x+y
Ao PA RA LA
Right x x+y Subpulmonary
PVs
SVC x x+y Left
x RV LV Membranous
LA PVs
x x+y
x+y y
RA
x VSD
x+y x AV canal
type
y
x+y
x LV PA Ao
RV
IVC Muscular
B
A
FIGURE 264-5 A. Ventricular septal de ect. In the presence o a ventricular septal de ect, the di erence in pressure and outfow resistance in systole (and the
di erence in compliance in diastole) between the RV and LV, combined with the size o the de ect itsel , allow or a “shunt” o fow (“y”) o “red” (oxygenated) blood
rom the le t side o the heart to the right side (deoxygenated). Systemic venous return o pure deoxygenated blood (“x”) is increased by the oxygenated shunted blood
(“y”) to increase volume o blood (“x + y”) through the outfow o the RV into the lungs, and in the le t atrium and le t ventricle. I the volume or the sequelae o the
shunted blood is su cient, LA and LV can dilate (hashed lines), and arrhythmias or shortness o breath (and occasionally pulmonary hypertension) can ensue. Ao,
aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries; PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava;
VSD, ventricular septal de ect. B. Diagrammatic representation o the location o various ventricular septal de ects. AV, atrioventricular. (Part B used with permission
rom Emily Flynn McIntosh, illustrator.)
1835
Patent Ductus Arteriosus PV
SVC
PDA

IVC x x+y
y
RA LA
Ao x+y x x+y
Right
PVs x
SVC Left
x RV LV
PVs
LA x x+y
x+y
x x+y
RA
y
x+y PDA x
x x+y
x LV PA Ao
RV
IVC
FIGURE 264-6 Patent ductus arteriosus. In the presence o a patent ductus arteriosus, the di erence in pressure and resistance in both systole and diastole between
the pulmonary arteries and the aorta, combined with the size o the ductus itsel , allow or a “shunt” o fow (“y”) o “red” (oxygenated) blood rom the aorta to the
pulmonary arteries (deoxygenated). Systemic venous return o pure deoxygenated blood (“x”) is increased by the oxygenated shunted blood (“y”) to increase volume
o blood (“x + y”) in the lungs, the le t atrium, the le t ventricle, and out the aortic valve. I the volume or the sequelae o the shunted blood is su cient, LA and LV can
dilate (hashed lines), and arrhythmias or shortness o breath (and occasionally pulmonary hypertension) can ensue. Ao, aorta; IVC, in erior vena cava; LA, le t atrium;
LV, le t ventricle; PA, pulmonary arteries; PDA, patent ductus arteriosus; PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava.
(Fig. 264-7A, B). T .A PVR

TOF, ,
,
(TOF/PA). C .T , PVR
(Fig. 264-7C); , - ; ,
(B -T ,P ,W )
.T .
VSD. U 7% TOF P TOF -
, , VSD , / RVOT
. , .P
P TOF/PA .
RV- -PA . Transposition of the Great Arteries T
A TOF (TGA)
- (Table 264-4). P ; ,
TOF - RV PA LV. T TGA,
RV .A RV , , D- TGA,
TOF, RV - ,
, , (Fig. 264-8A)
.P RVOT .T
, , - .P
, , . TGA (
C - VSD).
.L T D- TGA .I
20% TOF, 1950 1970 , (M ,
, , S ) (Fig. 264-8B). T
RV .
A TOF, RV. D - ,
. A QRS - -
ECG 180 .T -
. .T
I - 144 TOF,
72% 40 , 25% RV .L -
.T - ( - .
, PVR), , A D- TGA, VSD, PS
. R .T
T - TOF RV- -PA LV VSD,
PVR. H , PVR LV.
1836 Conal Anatomy
PV Tetralogy of Fallot (unrepaired)
SVC
IVC x x-y
PART 6
RA LA
x x-y Ao PA
Right
PVs
RV LV SVC x-y Left
x x-y x PVs
y LA
RVH #
* x-y
VSD
x-y
* VSD
RA 1
x 1
x-y x *
y LV
x
x-y
PA Ao RV
x
IVC #
Tetralogy of Fallot (repaired) PV

SVC
IVC x x
RA LA
Ao PA x+y x
Right
PVs x
SVC x Left
x x x+y RV LV
PVs x+y x
LA
x VSD
RA VSD patch
patch x+y x
y
x
x
LV PA Ao
x+y
RV
IVC
C
FIGURE 264-7 A. Tetralogy o Fallot involves anterior and superior malalignment o a bar o tissue (conal septum) (see * in Fig. 264-7B, which presents a cut-away view
through the anterior sur ace o the RV, into the RV outfow), partially obstructing the right ventricular outfow (under the pulmonary valve, i.e., “subpulmonary stenosis”-
labeled as 1), and leaving a gap in the interventricular septum (VSD). The pulmonary valve annulus is typically hypoplastic. Outfow obstruction prevents regression o
right ventricular hypertrophy #, which was present in utero. The di erence in pressure and outfow resistance in systole (and the di erence in compliance in diastole)
between the obstructed RV and the LV allow or a “shunt” o fow (“y”) o “blue” (deoxygenated) blood rom the right side o the heart to the le t side (oxygenated).
Systemic venous return o pure deoxygenated blood (“x”) is decreased by the shunted blood (“y”) leading to a total decrease in the volume o blood (“x – y”) passing
beyond into the lungs. The deoxygenated shunted blood (“y”) mixes with ully oxygenated blood in the LV, contributing to systemic arterial cyanosis. C. Tetralogy o
Fallot—repaired. A ter modern repair o tetralogy o Fallot, VSD has been patched closed, and outfow tract obstruction has been surgically removed, requently at the
expense o a patch enlarging the pulmonary valve annulus at the expense o sacri cing the integrity o the pulmonary valve (causing pulmonary regurgitation). Volume
o pulmonary regurgitant volume (“y”) is added to systemic venous return (“x”), contributing to RV chamber enlargement (hashed lines), and may be associated with
tricuspid annular dilation and valve regurgitation resulting in RA enlargement. Ao, aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries;
PV, pulmonary veins; RA, right atrium; RV, right ventricle; RVH, right ventricular hypertrophy; SVC, superior vena cava; VSD, ventricular septal de ect.
I 1980 , (ASO, Fig. 264-8C) T TGA, L- TGA ( -

D- TGA. T TGA, Fig. 264-9), ,
, TGA. L- TGA
RV, (RA
- LV, ,
.A .T
- . RV) - ( LV
T - PA, RV ). T ,
D- TGA Table 264-5. RV .P L- TGA
TABLE 264-4 Potential Sequelae of Repaired Tetralogy of Fallot PA; 1837
Right atrial dilation .O ,
Right ventricular dilation
( , )
, .A

Right ventricular dys unction
, -
Right ventricular out low tract obstruction
.S -
Pulmonary regurgitation , LV
Branch pulmonary artery stenosis , ,
Tricuspid regurgitation .B (
Residual ventricular septal de ect - ) .I
Le t ventricular dys unction , , , ,
Aortic root dilation T
Atrial arrhythmias , ,
Ventricular arrhythmias .P
Sudden cardiac death ; ,
, -
, LV , , ,
.
, , ASD ,
, .C - Single Ventricle Physiology T , “
, 30% ,” , , -
.T
, , - . C
, . , LV,
.M -
Coarctation of the Aorta A F
(Fig. 264-10) - (Fig. 264-11A, B). S
1971, ,
D-loop Transposition PV
SVC ASD
IVC
RA LA
Right Ao PA
PVs
SVC Left
LA PVs
RV LV
RA
Ao PA
LV
RV
IVC
A
FIGURE 264-8 A. Transposition o the great arteries. When the great arteries are transposed, the aorta arises rom the RV, and the pulmonary artery arises rom the
LV, leaving deoxygenated blood circulating rom systemic veins to systemic arteries in separated ashion rom oxygenated blood, which circulates rom pulmonary veins to
pulmonary arteries. Without interchamber or intravascular communications, this circulation is incompatible with li e. Presence o an atrial septal de ect (ASD), depicted
here, ventricular septal de ect (VSD), or patent ductus arteriosus (PDA), allow or some interchamber or intravascular mixing, and, at best, partial relie o cyanosis
and sustenance o li e, at the expense o increased pulmonary blood fow. B. Atrial switch. Atrial level switch procedures (“Mustard” and “Senning”) were the rst
standardized surgeries to alter the natural course o complex congenital heart disease, utilizing intracardiac re-routing via a “ba fe” to re-direct blood fow. The atrial
switch simulates inverted trousers, with each “pants-leg” * attaching to either the SVC or the IVC, transporting deoxygenated blood through the interior o the trousers
to the “waist o the trousers” and directing blood through the mitral valve to the LV and out the PA. Surgical removal o the atrial septum allows pulmonary venous return
to traverse rom posterior le t atrium through the space between the pants legs o the ba fe, through the tricuspid valve to the RV (serving as the “systemic ventricle,”
i.e., that pumps to the systemic arterial circulation) and out the aorta. Non-in requent sequelae include sinus node dys unction, atrial arrhythmias, systolic dys unction
o the RV, tricuspid regurgitation ( rom RV to LA), leaks in the ba fe material allowing shunting o blood, and obstruction o the systemic or pulmonary venous ba fes.
C. Arterial switch. The arterial switch operation allowed both anatomic and physiologic correction or D-loop transposition o the great arteries. Success ul surgical
switching o the PA and the Ao above the level o the native roots (hashed lines) necessitated ability to trans er coronary artery origins contained within a button o
tissue * back to the neo-aorta (now supported by the LV). Deoxygenated blood fow rom SVC and IVC pass rom RA to RV to PA, and oxygenated blood passes rom
PV to LA to LV to Ao. Uncommon sequelae include obstruction at any o the surgical sites (supravalvar PA or Ao stenosis, coronary ori ce obstruction), or more distal
obstructions due to tension placed on the PA, Ao or coronary arteries. Ao, aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries;
PV, pulmonary veins; RA, right atrium; RV, right ventricle; SVC, superior vena cava.
1838
Atrial Switch PV
PART 6
SVC LA
Ao PA IVC
Right
PVs
SVC Left
LA PVs RV LV
RA
Ao PA
LV
RV
IVC
B
Arterial Switch PV
SVC
IVC
RA LA
neo
Right Ao neo
PVs PA
SVC Left
LA PVs RV LV
oo
RA oo *
*
neo neo
LV PA Ao
RV
IVC
C
, “ ”
. T F
( ) .P F
, -
TABLE 264-5 Long-Term Sequelae of D-loop TGA Surgery , , ,
ATRIAL SWITCH ARTERIAL SWITCH RASTELLI PROCEDURE .
Systemic venous ba le Arterial anastomosis Subaortic stenosis
stenosis ■ UNREPAIRED CYANOTIC CHD
Pulmonary venous ba le Branch PA stenosis RV-PA conduit Eisenmenger Syndrome ES
obstruction - - -
RV (systemic) Neo-aortic root dilation Pulmonary regurgitation
dys unction
Tricuspid regurgitation Neo-aortic regurgitation Ventricular dys unction , - - . ES
Ba le leaks Coronary artery stenosis - CHD
LVOT obstruction (PS) LV dys unction - - .T ES ,
Abbreviations: LV, le t ventricle; LVOT, le t ventricular out low tract; PA, pulmonary , , ES
artery; RV, right ventricle.
1839
Congenitally (L-loop transposition)
Corrected TGA PV
SVC

IVC
RA LA
PA Ao
Right
PVs
SVC Left
LA PVs LV RV
RA
PA Ao
RV
LV
IVC
FIGURE 264-9 Congenitally corrected transposition o the great arteries. Physiologically corrected transposition o the great arteries (also known as congenitally
corrected transposition o the great arteries) is characterized by atrioventricular discordance and ventriculoarterial discordance. Systemic venous blood passes rom
the right atrium (RA) through the mitral valve into the morphologic le t ventricle (LV) to the pulmonary artery (PA). Oxygenated blood then returns to the lungs to the le t
atrium (LA) through the tricuspid valve into the morphologic right ventricle (RV) and then out the aorta (Ao). IVC, in erior vena cava; PV, pulmonary veins; SVC, superior
vena cava.
.M
, - ,
, . R
( ES .
, - A
). E
ES. C ES -
, ,
Coarctation of the Aorta:
Sequelae/Associations .P
.
6
R
, , ES.
3 S – -
PA , .
*
Global Considerations A
2 ,
Ao LA ;
, ,
1 , .A ,
RA
CHD .C
5 CHD ACHD
LV .H -
, CHD
4 ACHD
RV ,
.U ,
CHD
, ,
FIGURE 264-10 Aortic coarctation (*). Bicuspid aortic valve (1) is most common ,
concomitant lesion. Sequelae rom aortic coarctation (unrepaired or repaired) , .I
include systemic arterial hypertension, ascending (2) or descending (3) aortic ACHD ACHD
enlargement or aneurysm ormation, le t ventricular hypertrophy (4), LV diastolic
and systolic heart ailure, accelerated coronary (5) or cerebral (6) atherosclerosis,
,
cerebral aneurysm ormation, and recurrence o coarctation a ter repair. Ao, aorta; , , ,
LV, le t ventricle; PA, pulmonary arteries. , .
1840
Fontan PV
SVC
Extracardiac conduit
IVC
PART 6
LA
PA
Ao * *
LV
RA
SVC LA
RA
*
LV PA Ao
RV
IVC
Classic fontan Atriopulmonary

fontan
Lateral tunnel Extracardiac

fontan fontan
B
FIGURE 264-11 A. Fontan surgery creates a unique circulation in which deoxygenated blood is directed to the PAs rom the SVC and IVC in a ashion that bypasses
any pumping chamber. The SVC and IVC are connected * via either an internal “tunnel” or an extracardiac conduit that guides fow to the PA. Pulmonary venous
(oxygenated) return courses rom PV to LA to LV to aorta. In contrast to physiology in normal adults (where pressure is generated by an RV to propel blood fow rom
a lower pressure RA to a higher pressure LA), in Fontan circulation, by de nition, due to the absence o a pumping chamber to the PA, RA pressure is greater than
LA pressure, permitting fow through the lungs. Ao, aorta; IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; PA, pulmonary arteries; PV, pulmonary veins; SVC,
superior vena cava, * Fontan ba fe. B. Diagrammatic representation o the location o various types o Fontan operations. (Part B used with permission rom Emily
Flynn McIntosh, illustrator.)
■ FURTHER READING TABLE 265-1 Classification of Pericarditis 1841
Gilboa SM : C H D U S : Clinical Classifcation
E 2010.
I. Acute pericarditis (<6 weeks)
C 134:101, 2016.
CHAPTER 265 Pericardial Disease

Gurvitz M :E R D A C A. Fibrinous
H D :A NHLBI/ACHA W G . B. E usive (serous or sanguineous)
JA C C 67:1956, 2016. II. Subacute pericarditis (6 weeks to 6 months)
Regitz-Zagrosek V : ESC - A. E usive-constrictive
:T T F M - B. Constrictive
C D P E III. Chronic pericarditis (>6 months)
S C (ESC). E H J 32:3147, 2011. A. Constrictive
Warnes CA : ACC/AHA 2008 B. Adhesive (nonconstrictive)
:A A
Etiologic Classifcation
C C /A H A T F
P G ( I. In ectious pericarditis
). C A. Viral (coxsackievirus A and B, echovirus, herpesviruses, mumps,
118: 714, 2008. adenovirus, hepatitis, HIV)
Webb G : S . B. Pyogenic (pneumococcus, Streptococcus, Staphylococcus, Neisseria,
C 129:1795, 2014. Legionella, Chlamydia)
Webb G :T C. Tuberculous
: C : A D. Fungal (histoplasmosis, coccidioidomycosis, Candida, blastomycosis)
I S A C H E. Other in ections (syphilitic, protozoal, parasitic)
D (ISACHD). I J C 195:326, 2015. II. Nonin ectious pericarditis
A. Acute idiopathic
B. Renal ailure
C. Neoplasia
1. Primary tumors (benign or malignant, mesothelioma)
265 Pericardial DiseaseEugene Braunwald

2. Tumors metastatic to pericardium (lung and breast cancer,
lymphoma, leukemia)
D. Trauma (penetrating chest wall, nonpenetrating)
E. Aortic dissection (with leakage into pericardial sac)
F. Acute myocardial in arction
■ NORMAL FUNCTIONS OF THE PERICARDIUM G. Postirradiation
T - ; - H. Familial Mediterranean ever
I. Familial pericarditis
(15–50 L) , 1. Mulibrey nanisma
.T , ,
J. Metabolic (myxedema, cholesterol)
,
III. Pericarditis presumably related to hypersensitivity or autoimmunity
, .I
, A. Rheumatic ever
. B. Collagen vascular disease (systemic lupus erythematosus, rheumatoid
N , total , arthritis, ankylosing spondylitis, scleroderma, acute rheumatic ever,
granulomatosis with polyangiitis [Wegener’s])
, . I partial
, C. Drug-induced (e.g., procainamide, hydralazine, phenytoin, isoniazid,
minoxidil, anticoagulants, methysergide)
; , -
D. Postcardiac injury
.
1. Postpericardiotomy
ACUTE PERICARDITIS 2. Posttraumatic
A , 3. Postmyocardial in arction (Dressler’s syndrome)
(Table 265-1), a
An autosomal recessive syndrome characterized by growth ailure, muscle
: hypotonia, hepatomegaly, ocular changes, enlarged cerebral ventricles, mental
retardation, ventricular hypertrophy, and chronic constrictive pericarditis.
1. Chest pain
, -
, ( ). T - ( - )
, / , .H , , ,
, , .F , AMI,
( . ., ST- .T
), , .
, , 2. A pericardial friction rub
; , 85% ,
(AMI) .C , , , ,
, (Chap. 234). I
(Chap. 11). P - .
, , , . 3. T electrocardiogram (ECG)
T AMI -
, , (Fig. 265-1A). I .
-MB , I 1, ST ,
,
1842
I aVR V1 V4
PR ST
ST
PART 6
PR
II aVL V2 V5
III aVF V3 V6
I aVR V1 V4
II aVL V2 V5
III aVF V3 V6
II
B
FIGURE 265-1 A. Acute pericarditis. There are di use ST-segment elevations in leads I, II, aVF, and V2–V6). There is PR-segment depression due to a concomitant atrial
injury current. B. Electrical alternans. This tracing was obtained rom a patient with a large pericardial e usion with cardiac tamponade.
V2–V6, VR Diagnosis Echocardiography (Chap. 236)

V 1. A , PR TP - .I , , , ,
, .U ,
QRS , .T
( ). A , ST -
( 2), , , T -
( 3). W /
, ECG ( 4). I ,
AMI, ST , (Fig. 265-2).
; T
.Q , R- (CT) (MRI).
, T- ; T
before ST , , -
(Chaps. 268 and 269). . MRI
4. Pericardial effusion / ECG (Fig. 265-3).
,
(Fig. 265-1B). P
TREATMENT
( ). D Acute Pericarditis
,
. T T ,
.T - (2–4 / ),
, Ewart’s - (NSAID ), -
sign, (600–800 ) (25–50 ),
.T ( . .,
, “ ” , 20 / ). I ,
. 1–2 .I ,
■ CARDIAC TAMPONADE 1843
T -
.T

.T
, ,
, , ,
.
T (Beck’s triad) -
, ,
x( ) y( )
.T -
. T
200 L
>2000 L
.
A
FIGURE 265-2 Two-dimensional echocardiogram in lateral view in a patient with a
large pericardial e usion. Ao, aorta; LV, le t ventricle; pe, pericardial e usion; RV, ,
right ventricle. (From M Imazio: Curr Opin Cardiol 27:308, 2012.)
, ,
.T
(0.5 [<70 ] 0.5 [>70 ]), QRS , electrical alternans P, QRS,
3 . C T (F . 265-1).
NSAID . Table 265-2 -
T .
, Paradoxical Pulse T
, - (10 H )
.G ( . ., 1 / ) .W
NSAID - ,
.H , , .
- 2–4 B , . .,
.A ,
. ,
I , , ; , -
2 , .P -
NSAID - ( ),
, , ( IL-1β ) , ,
. R , . R (Chap. 269)
,
. , y , ,
T , (T 265-2).
- . H ,
( , , ) - Diagnosis B
, ( >38°C, , ,
, ) , - , . W
. , D
,
AO
LA
RV
LV
LV
* *
*
A B
FIGURE 265-3 Pericardial in ammation by cardiac magnetic resonance imaging. A. Short axis view. The pericardium is thickened and enhanced on T2 magnetic
images. Note thickened white line denoted by arrow. B. Long axis view. Late gadolinium enhancement o thickened, infamed pericardium. AO, aorta; LA, le t atrium;
LV, le t ventricle; RV, right ventricle. (From RY Kwong: Cardiovascular magnetic resonance imaging, in Braunwald’s Heart Disease, 10th ed, Mann DL et al [eds]. Philadelphia:
Elsevier, 2015, pp 320–40.)
1844 TABLE 265-2 Features That Distinguish Cardiac Tamponade from Constrictive Pericarditis and Similar Clinical Disorders
EFFUSIVE
CONSTRICTIVE RESTRICTIVE CONSTRICTIVE
CHARACTERISTIC TAMPONADE PERICARDITIS CARDIOMYOPATHY RVMI PERICARDITIS
Clinical
PART 6
Pulsus paradoxus +++ + + + +++

Jugular veins
Prominent y descent – ++ + + –
Prominent x descent +++ ++ +++ + +++
Kussmaul’s sign – +++ + +++ ++

Third heart sound – – + + +
Pericardial knock – ++ – – –
Electrocardiogram
Low ECG voltage ++ ++ + – +
Electrical alternans ++ – – – +
Echocardiogram
Thickened pericardium – +++ – – ++
Pericardial calci ication – ++ – – _
Pericardial e usion +++ – – – ++
RV size Usually small Usually normal Usually normal Enlarged Usually normal
Exaggerated respiratory +++ +++ – +++ +
variation in low velocity
CT/MRI
Thickened pericardium – +++ – ++
Equalization o diastolic +++ +++ – ++ ++
pressures
Abbreviations: +++, always present; ++, usually present; +, rare; –, absent; DC, diastolic collapse; ECG, electrocardiogram; RV, right ventricle; RVMI, right ventricular
myocardial in arction.
Source: Adapted rom GM Brockington et al: Cardiol Clin 8:645, 1990, with permission.
, , ( . I , ,
, ) (Fig. 265-4). I , HIV , / .
( ) T
.T , CT, .C .
MRI - T DNA Mycobacterium tuberculosis
.
(Chap. 173).
TREATMENT
Cardiac Tamponade ■ VIRAL OR IDIOPATHIC ACUTE PERICARDITIS
I ,
P
.I , - .T
Inspiration Expiration
.
E Septum Septum
PERICARDIOCENTESIS A E
A
I ,
, , , , TV MV TV MV
, RV LV
Doppler
.W , transvalvular
.I inflow patterns
, Thickened
.I , - pericardium
, RA
Pulmonary
. LA vein
A ,
- DIASTOLE DIASTOLE
.S IVC and hepatic veins
( ) Apical 4-chamber views
, /
FIGURE 265-4 Constrictive pericarditis. Doppler schema o respirophasic
.
changes in mitral and tricuspid infow. Reciprocal patterns o ventricular lling
P are assessed on pulsed Doppler examination o mitral valve (MV) and tricuspid
. I , valve (TV) infow. IVC, in erior vena cava; LA, le t atrium; LV, le t ventricle; RA, right
, , atrium; RV, right ventricle. (Courtesy o Bernard E. Bulwer, MD; with permission.)
, . I 1845
.I A B , , ,
, , , , , - HIV .I
, / , , ,

. .T
F , , idiopathic .I -
acute pericarditis . .
V Pericarditis of renal failure (uremic pericarditis) -
, , -
.T (dialysis-
, 10–12 associated pericarditis). T
, .A -
AMI, .T - , .T
, NSAID .
.T O , .W
4 .E C- , -
.T ST- ECG .
1 , T P neoplastic diseases -
(
.A - , , , ) -
, .T , ,
, , . .D
T ( ) , . Mediastinal irradiation
- - / .
.I , . U ,
( , , , ),
Postcardiac Injury Syndrome A ( , , ,
—
) (T 265-1).
.T
( ■ CHRONIC PERICARDIAL EFFUSIONS
), (Chap. S8), C
; , AMI. .T
T . per se,
T , . Tuberculosis
1–4 .R .N , SLE, ,
2 .F , - , ,
, ,
1 2 .T - .A
, , .P
. ECG .G
.T - , ,
() , .P -
/ . ,
O . . I
W - .
, NSAID, , ,
, .
CHRONIC CONSTRICTIVE PERICARDITIS
■ DIFFERENTIAL DIAGNOSIS T -
B acute idiopathic pericarditis, -
.C ,
.A - .T
, .I ,
AMI . ,
P N A W E .C -
.I
, , - , ,
, AMI, . , , , -
I pericarditis due to collagen vascular dis- , ( , ,
ease .M - ), , SLE,
.I ,
(SLE; Chap. 349) - ( ) ,
.W - , ,
, SLE .
.A - T -
rheumatoid arthritis, scleroderma, polyarteritis nodosa,
. , .V
Pyogenic (purulent) pericarditis
, , ,
, , .I
1846 , - MRI ,
- - .
, ,
( . ., 5 H ). D ■ DIFFERENTIAL DIAGNOSIS
, L , (Chap. 252)
PART 6
.H , , - , -
, ,
, .H , ,
. falls -
I , ( . ., K ’ ). Tricuspid stenosis (Chap. 261)
M- , x y .T
y , , , , , .H ,
;
.T y .
, B , -
.T
, (Chap. 254), ( . ., -
.I , ). T -
“ ” T 265-2. W , ,
.T , ,
, D
(Chap. 254, Table 254-2). (F . 265-4) MRI CT
,
■ CLINICAL AND LABORATORY FINDINGS .
W , , , ,
, .T - TREATMENT
, , , ,
. E , Constrictive Pericarditis
, .T
P
.D
,
-
(Kussmaul’s sign). T
.C
, , -
>50
.
.T -
T .A .T
- .C - -
; ,
.P , /
.T , ’ .O
(Broadbent’s sign). T 5–10% ;
; ( . ., ) , ,
.T , , ,
. .
T ECG QRS
T .A
Subacute Effusive-Constrictive Pericarditis T
- .T chest roentgenogram
.P
-
.P , - .A ,
, ,
. .I ( ),
I ( - , ,
, ) , , , . T
, , - , .A
- ,
.T .F ,
.
T echocardiogram , , .T -
, .W
, .
.
T D Tuberculous Pericardial Disease T
(F . 265-4). D , - ,
HIV .
; T ,
.D ,
( ). T ,
.I
. H , , HIV,
; CT , , ,
.I TABLE 266-1 Imaging Modalities and Their Utility in the Evaluation 1847
- of Cardiac Tumors
, , , MODALITY UTILITY IN CARDIAC TUMOR EVALUATION
.I - Transthoracic Assessment o tumor location and size, and
CHAPTER 266 Atrial Myxoma and Other CardiacTumors

, echocardiography (TTE) its impact on adjacent structures (e.g., valves,
(Chap. 173) . (including 2-D, 3-D, and pericardium).
I contrast)
2–4 , - Transesophageal Improved tumor characterization and spatial
.T echocardiography (TEE) resolution compared with TTE. May aid in
determining surgical approach.
. Cardiac MRI with Improved tissue characterization, de inition
gadolinium contrast o tumor size and identi ication o local
■ FURTHER READING invasion when compared with TTE or TEE. May
Adler Y : 2015 ESC di erentiate tumor rom thrombus.
.E H J 36:2921, 2015. Gated cardiac CT Provides anatomic assessment and tissue
characterization o the tumor. Use ul when
Alraies MC :U -
patients cannot tolerate MRI or when MRI is
. A J C not easible (e.g., patients with implantable
115:542, 2015. cardiac devices). Allows or better assessment o
Cremer PC :C :U calci ied lesions and evaluation o extra-cardiac
.JA C tumor involvement.
C 68:2311, 2016. Nuclear Imaging (including De inition o extra-cardiac disease. May be
18
Garcia MJ: C - F- luorodeoxyglucose use ul in diagnosis o certain cardiac tumors
?JA C C 67:2061, 2016. positron emission (e.g., neuroendocrine tumors) but assessment
tomography [FDG-PET]) o smaller tumors may be limited by surrounding
Imazio M :E - myocardial FDG uptake.
(CORP-2); , - ,
- , .L 383:2232, 2014.
LeWinter MM: A .NE J M 371:2410, 2014.
Lotan D :U
.A JC 117:861, 2016. , -
Vistarini N :P .A ,
T S 100:107, 2015. , , (CHF), , ,
,
. A ,
.
Myxoma M
, - - -
Atrial Myxoma and Other , -
266 Cardiac Tumors .T
,
,
.A 90%
Eric H. Awtry ;
.T
(C ) (1) ( -
, , / ), (2) / ,
C (3) (
- C ’ , , / -
.P ). C
.O , NAME (n , a
, ,m , e ) LAMB
20% (l ,a m , b ),
- .W C .T
, ; ,
- PRKAR1A,
. S A I-α ,
~70% C .
, , .E P ,
; , .
M ,
( ),
(Table 266-1). .I ,
■ PRIMARY TUMORS ,
P .A - , ,
, . .
M , , 25% M .
.A , T -
, - .M :
; , . - -
.V
Clinical Presentation C .T
.T , ,
1848
PART 6
A B
FIGURE 266-1 Transthoracic echocardiogram demonstrating a large atrial myxoma. The myxoma (Myx) lls the entire le t atrium in systole (A) and prolapses across
the mitral valve and into the le t ventricle (LV) during diastole (B). RA, right atrium; RV, right ventricle. (Courtesy o Dr. Michael Tsang; with permission.)
.A - - ,
, “ ,” -
- , , . Papillary fibroelastomas
.M -
. R
( - ,
) , .
, , , , , , - A ,
, R ’ .L , , , ,
, , , , - .I ,
, C- , ,
, . T - , - . Rhabdomyomas fibromas
, , ,
. , , CHF,
T - - / , .
R ,
- 90% ,
,
(Fig. 266-1). C -
(CT) (MRI)
, , ,
(Fig. 266-2).
A
, -
( . ., )
.A ,
.B
, -
,
.
TREATMENT
Myxoma
S -
, . M
12–22% 1–2% .T
FIGURE 266-2 Cardiac magnetic resonance imaging demonstrating a rounded

Other Benign Tumors C lipomas, - mass (M) within the le t atrium (LA). Pathologic evaluation at the time o surgery
, ; - revealed it to be an atrial myxoma. LV, le t ventricle; RA, right atrium; RV, right
, 15 , ventricle.
■ TUMORS METASTATIC TO THE HEART 1849
T
,
CHAPTER 266 Atrial Myxoma and Other CardiacTumors

-
.A
RA ,
, , -
(Fig. 266-4). I ,
RV
T T , .
LV C
T ,
T .N , -
.
C
.T ,
FIGURE 266-3 Transthoracic echocardiogram revealing multiple tumors (T) ; ,
consistent with rhabdomyomas in a 1-day-old in ant. The largest tumor (arrows)
.T
was located in the le t AV groove and measured 2 cm × 2 cm. LV; le t ventricle;
RA, right atrium; RV, right ventricle. , ,
, .
C ~10% ,
(Fig. 266-3). T ’ ,
; - .T
.F , , .A ,
, -
, . .W ,
Paragangliomas - , , -
.M , , , ,
CT MRI, CHF. I ,
131-I- .T - , , -
, - ,
.E . Hemangiomas
mesotheliomas , - .
, (AV) E (ECG)
QRS -
AV .O .
teratoma, chemodectoma, neurilemoma, granular cell O - ,
myoblastoma, paraganglioma. .E
Sarcoma A -
; , , CT
.S .C MRI
;
- .P
.I ,
’
, ,
.A -
, . S
, ,
,
.S
.
Met
TREATMENT RV
LV
Sarcoma
T LA
; ,
, -
.A
/ ,
.
T , FIGURE 266-4 Large metastatic lesion (Met) in the le t ventricle (LV) o a
- . patient with di usely metastatic bladder cancer. The mass arose rom the
interventricular septum and prolapsed into the aortic outfow tract during systole.
1850 .A ,
. IHD,
.
O , , 2 -
TREATMENT IHD. T
PART 6
Tumors Metastatic to the Heart

’ . W
M , -
; , - - W .A ,
.S IHD IHD
- ,
.P (3–5 ) , -
( . ., ) .P
, S A , I M E .I
IHD ,
.G , IHD
2020.
.
■ PATHOPHYSIOLOGY
■ FURTHER READING C
Buckley O :C , 1: I - .I
. AJR A J R 197:W837, 2011. , , -
Buckley O :C , 2: K - - -
. AJR 1 A J R 97:W842, 2011.
Bussani R :C .JC P 60:27, 2007. .T
Shapira O :T , Sabiston and Spenser Surgery of (MVO2) , ,
the Chest, 9 , FW S ( ). P ,E , 2016, ( ). A
1849–1857. -
Tamin SS :P - ( , ,
.JA C C 65:2420, 2015. ) -
.B
, .A 75%
:
(1) (R 1 = R1), (2)
(R2), (3) (R3). I
Section 5 Coronary and Peripheral - , R1
; R2
Vascular Disease R3 (Fig. 267-1). T
’ . T
( ,
Ischemic Heart Disease , )
267 .N , -
Elliott M. Antman, Joseph Loscalzo (R2
R3 ). F ,
Ischemic heart disease (IHD) -

; (metabolic regulation). T
.T (autoregulation).
B ,
( )
, .W
. Chapter 291e ( 19 , .
Harrison’s) - C ( P ’
.T Chap. 268), , , ,
IHD. T IHD. .C
■ EPIDEMIOLOGY AND GLOBAL TRENDS

IHD , .
. M
IHD , , , -
U S , 15.5 IHD, , (LVH)
3.4 ≥40 .A .T -
, 4% -
. G , - - , (Chap. 256). A
, - ,
IHD. I U S W E , IHD ,
- ,
. D .
1851
Macrocirculation Microcirculation
Segment Epicardial arteries >400 µm Small arteries <400 µm Arterioles <100 µm Capillaries <10 µm
and size
CHAPTER 267 Ischemic Heart Disease

Main stimulus
for vasomotion Flow Pressure Metabolites
Main
Transport Regulation Exchange
function
Percentage of
total resistance
to flow
FIGURE 267-1 Macrocirculation and microcirculation across segments and sizes o the arteries. The location and size o the arteries supplying blood to the heart
is shown at the top. Vasomotion o the arterial segments occurs in response to the stimuli shown. The main unction o each o the arterial segments is shown next,
ollowed by a depiction o the relative resistance to antegrade fow. (Modifed rom B De Bruyne et al: J Am Coll Cardiol 67:1170, 2016.)
N , , S -
LVH ,
.A .U ,
. : (1)
W , microvascular , (2) -
angina. , .A
CORONARY ATHEROSCLEROSIS ,
E - .
.T ( T -
- [LDL], -
[HDL], , , . T , ,
.T , , .C
, -
.T , -
, , . W ,
, ,
. F .
, W
, , , ( )
.R .A -
, ,
( ; - .W , -
LDL , , , W
, VII, ). T - .I , ,
“ ” “ ” ST- ,
.T
. , , / .C
A
- , ( -
- , . ., . T ), (P ’ ), -
, .
.W
50%, ■ EFFECTS OF ISCHEMIA
.W ~80%, D -
, ,
, ,
. (Fig. 267-2). C
1852
Repetitive/progressive manifestations of ischemia Systolic dysfunction

PART 6
Regional wall motion
Decreased segmental perfusion

Diastolic dysfunction
Micro-infarction/myocardial fibrosis
Altered metabolism/abnormal ST segment
Decreased subendocardial perfusion
Endothelial and microvascular dysfunction
Near term Prolonged

Exposure time of mismatch in myocardial oxygen supply/demand
FIGURE 267-2 Cascade o mechanisms and mani estations o ischemia. (Modifed rom LJ Shaw et al: J Am Coll Cardiol 54:1561, 2009. Original fgure illustration by
Rob Flewell.)
.D - ■ ASYMPTOMATIC VERSUS SYMPTOMATIC IHD

, A ,
, , , , ( ), W
. 20
T , . E
, -
.T , . ., - ECG
;
( ).
I - (Chap. 237). C (CAC) CT
(LV) , , , CAC ,
.W , IHD. H ,
; ,
. (S
(Chap. 269). .) P
A , ,
.T
,
.W , .A , ~25%
, ; H
, - , . ., ,
ATP .I -
(Chap. 269). S
.T IHD (Chap. 299).
- P IHD
(≤20 LV
) , ;
(>20 ). ischemic cardiomyopathy. I
I IHD,
(ECG) ,
T , , ST (Chap. 269). H ,
(Chap. 235). T T- - , -
, ; ST- , .
; ST-
.A STABLE ANGINA PECTORIS
, T -
- .V -
(Chaps. 249 and 250). M
IHD - Chap. 11. M ~70%
(Chap. 299). <50 .I , ,
TABLE 267-1 Cardiovascular Disease Classification Chart 1853
( ).
NEW YORK HEART CANADIAN CARDIOVASCULAR
ASSOCIATION FUNCTIONAL SOCIETY FUNCTIONAL
■ HISTORY CLASS CLASSIFICATION CLASSIFICATION

T >50
I Patients have cardiac disease Ordinary physical activity, such
>60 , but without the resulting as walking and climbing stairs,
, , , , limitations o physical activity. does not cause angina. Angina
.W Ordinary physical activity does present with strenuous or rapid
, , - not cause undue atigue, or prolonged exertion at work or
, , , palpitation, dyspnea, or recreation.
anginal pain.
(L ’ ). A -
, 2–5 , II Patients have cardiac disease Slight limitation o ordinary
resulting in slight limitation activity. Walking or climbing
( ). o physical activity. They are stairs rapidly, walking uphill,
I , , com ortable at rest. Ordinary walking or stair climbing a ter
, , , .A physical activity results in meals, in cold, or when under
.A atigue, palpitation, dyspnea, emotional stress or only during
or anginal pain. the ew hours a ter awakening.
; Walking more than two blocks
on the level and climbing more
. than one light o stairs at a
A ( . ., normal pace and in normal
, , ) ( . ., , , conditions.
, ) , III Patients have cardiac disease Marked limitation o ordinary
(Chap. 268) ( ). resulting in marked limitation physical activity. Walking one
T o physical activity. They are to two blocks on the level and
.N , com ortable at rest. Less climbing more than one light o
than ordinary physical activity stairs in normal conditions.
causes atigue, palpitation,
, dyspnea, or anginal pain.
; ( - IV Patients have cardiac Inability to carry on any physical
), , disease resulting in inability activity without discom ort—
LV . to carry on any physical anginal syndrome may be
T activity without discom ort. present at rest.
.M Symptoms o cardiac
, , insu iciency or o the anginal
syndrome may be present
.I , - even at rest. I any physical
, activity is undertaken,
; discom ort is increased.
.I , Source: Modi ied rom L Goldman et al: Circulation 64:1227, 1981.
.I , ,
, , (Chap. 419). I
.A IHD (<55 -
<65 )
( -
, , , ,
) -
.
.A ,
T
, , .
IHD .T ,
E 1–5
, ,
-
-
( ). I , -
.A -
.T
-
C
- .T
C S (Table 267-1). I
.P
’ N Y
( -
H A (T 267-1).
S , , , , )
.H , . T
, - , ,
.I , , , , -
, , .I (ACE) .A -
, .
.A “ ”
.T , , , ■ PHYSICAL EXAMINATION
. T
S IHD - . H ,
IHD /
, ,
, , .S - , ,
, . T
,
( [Chap. 275]), .
1854 E - ECG, .E -
- ,
( - , , , ,
). E ST- >0.2 V (2 ), -
.T >10 H , .
PART 6
, , T ,
. ECG ,
P .T ST-
(LV ). A - ST -
, / , , >0.1 V ( . ., PR )
, 0.08 (F . 267-2). U ST-

.T
. .A T- , ,
A , (Chap. 256), -
(Chap. 277), (Chap. 254) , .N
, (85% )
.E - .
, LV I ECG ,
/ , , (CAD) ( . .,
, .T , ) . O , -
, - - .H ,
CAD 98%
.A >50
.T
. / .
T -
■ LABORATORY EXAMINATION IHD,
A IHD <40 -
, .I ,
.T ,
( - , ST- T- -
) .S , , , .
O
( — , LDL, HDL— ), ( - -
A1C), , , , 12- ECG.
, .A - S
IHD, . ., , ~75%, CAD,
, .T - - CAD .
IHD . A .
E - C- I ,
(CRP) ( , 0 3 / L) ST- ,
IHD - ( ),
.T , . ., – .
- CRP IHD T ST- -
“ ” . ECG .B
—
■ ELECTROCARDIOGRAM 10,000 —
A 12- ECG - . M ( – - )
, 6
(Chap. 235). A , . ., (T 267-2). C
ST- T- , LVH 48 , ,
IHD, , , ,
, , - , .
, , , T
, , , .T .F
LVH
IHD. O , LVH , -
IHD, LV . T /
(>0.2 V) ST- , . .,
IHD II B , / ST- -
. D ST- T- >5
. IHD
.
■ STRESS TESTING
Cardiac Imaging (See also Chap. 236) W ECG
Electrocardiographic T ( . ., , >1 ST-
IHD , ,
12- ECG , , , ),
(Fig. 267-3). T - -
(Table 267-2) , -201 99 -
( ) . C , , .I , 1855
(PET) ( .
) N-13 -82 F , -
.I “ ”

.A -
, -
. MVO2. A
A (F . 267-3). T -
-201
99 - .
Evaluation of the patient with known or suspected IHD
Possible indications for stress testing of patient:

1. Dx of IHD uncertain
2. Assess functional capacity of patient
3. Assess adequacy of treatment program for IHD
4. Markedly abnormal calcium score on EBCT
Can patient exercise adequately?
Yes No
Are confounding features

present on resting ECG?
No Yes
Perform treadmill An imaging study

exercise test should be performed
Nuclear Cardiac Cardiac

2-D perfusion MR PET
Echo scan scan scan
ECG ECHO MIBI CMR PET
A
FIGURE 267-3 Evaluation o the patient with known or suspected ischemic heart disease. On the le t o the gure is an algorithm or identi ying patients who
should be re erred or stress testing and the decision pathway or determining whether a standard treadmill exercise with electrocardiogram (ECG) monitoring alone is
adequate. A specialized imaging study is necessary i the patient cannot exercise adequately (pharmacologic challenge is given) or i there are con ounding eatures on
the resting ECG (symptom-limited treadmill exercise may be used to stress the coronary circulation). Panels B–E on the next page are examples o the data obtained
with ECG monitoring and specialized imaging procedures. CMR, cardiac magnetic resonance; EBCT, electron beam computed tomography; ECHO, echocardiography;
IHD, ischemic heart disease; MIBI, methoxyisobutyl isonitrite; MR, magnetic resonance; PET, positron emission tomography. A. Lead V 4 at rest (top panel) and a ter
4.5 min o exercise (bottom panel). There is 3 mm (0.3 mV) o horizontal ST-segment depression, indicating a positive test or ischemia. (Modifed rom BR Chaitman,
in E Braunwald et al [eds]: Heart Disease, 8th ed, Philadelphia, Saunders, 2008.) B. A 45-year-old avid jogger who began experiencing classic substernal chest pressure
underwent an exercise echo study. With exercise the patient’s heart rate increased rom 52 to 153 beats/min. The le t ventricular chamber dilated with exercise,
and the septal and apical portions became akinetic to dyskinetic (red arrow). These ndings are strongly suggestive o a signi cant fow-limiting stenosis in the
proximal le t anterior descending artery, which was con rmed at coronary angiography. (Modifed rom SD Solomon, in E. Braunwald et al [eds]: Primary Cardiology,
2nd ed, Philadelphia, Saunders, 2003.) C. Stress and rest myocardial per usion single-photon emission computed tomography images obtained with 99m-technetium
sestamibi in a patient with chest pain and dyspnea on exertion. The images demonstrate a medium-size and severe stress per usion de ect involving the in erolateral
and basal in erior walls, showing nearly complete reversibility, consistent with moderate ischemia in the right coronary artery territory (red arrows). (Images provided
by Dr. Marcello Di Carli, Nuclear Medicine Division, Brigham and Women’s Hospital, Boston, MA.) D. A patient with a prior myocardial in arction presented with recurrent
chest discom ort. On cardiac magnetic resonance (CMR) cine imaging, a large area o anterior akinesia was noted (marked by the arrows in the top le t and right
images, systolic rame only). This area o akinesia was matched by a larger extent o late gadolinium-DTPA enhancements consistent with a large transmural myocardial
in arction (marked by arrows in the middle le t and right images). Resting (bottom le t) and adenosine vasodilating stress (bottom right) rst-pass per usion images
revealed reversible per usion abnormality that extended to the in erior septum. This patient was ound to have an occluded proximal le t anterior descending coronary
artery with extensive collateral ormation. This case illustrates the utility o di erent modalities in a CMR examination in characterizing ischemic and in arcted
myocardium. DTPA, diethylenetriamine penta-acetic acid. (Images provided by Dr. Raymond Kwong, Cardiovascular Division, Brigham and Women’s Hospital, Boston,
MA.) E. Stress and rest myocardial per usion PET images obtained with rubidium-82 in a patient with chest pain on exertion. The images demonstrate a large and
severe stress per usion de ect involving the mid and apical anterior, anterolateral, and anteroseptal walls and the le t ventricular apex, showing complete reversibility,
consistent with extensive and severe ischemia in the mid-le t anterior descending coronary artery territory (red arrows). (Images provided by Dr. Marcello Di Carli, Nuclear
Medicine Division, Brigham and Women’s Hospital, Boston, MA.)
1856
PART 6 Disorders of the Cardiovascular System
TABLE 267-2 Relation of Metabolic Equivalent Tasks (METs) to Stages in Various Testing Protocols 1857
FUNCTIONAL O2 COST
CLASS CLINICAL STATUS mL/kg/min METs TREADMILL PROTOCOLS
BRUCE Modi ied 3 min Stages BRUCE 3 min Stages

MPH %GR MPH %GR
6.0 22 6.0 22
HEALTHY, DEPENDENT ON AGE, ACTIVITY 5.5 20 5.2 20
5.0 18 5.0 18
56.0 16
NORMAL 52.5 15
AND 49.0 14
I 45.5 13 4.2 16 4.2 16
42.0 12
38.5 11 3.4 14 3.4 14
SEDENTARY HEALTHY
35.0 10
31.5 9
28.0 8
24.5 7 2.5 12 2.5 12
21.0 6
LIMITED
SYMPTOMATIC
II
17.5 5 1.7 10 1.7 10
14.0 4
III 10.5 3 1.7 5
7.0 2 1.7 0
IV 3.5 1
Note: The standard Bruce treadmill protocol (right hand column) begins at 1.7 MPH and 10% gradient (GR) and progresses every 3 min to a higher speed
and elevation. The corresponding oxygen consumption and clinical status o the patient are shown in the center and le t hand columns.
Abbreviations: GR, grade; MPH, miles per hour.
Source: Modi ied rom GF Fletcher et al: Circulation 104:1694, 2001.
E LV ,
- ,
, Q ,
. T - , —
.L ,
. S ( ) .
. S , Indications C (1)
, -
IHD. C -
(CMR) , . ., (PCI)
, PET, . CMR (CABG); (2)
, IHD; (3)
. CMR ; (4)
(MRI) .
A , ; (5)
.F -
, ,
.T - ( ).
(CT) E
( [EBCT] :
[MDCT] ). C
A , 1. P
. A -
( , ,
90–94%; , 95–97%; , 93–99%), , , .
.T , CT, EBCT, 2. P
MDCT IHD (Chaps. 268 and 269),
.
CAD .
■ CORONARY ARTERIOGRAPHY 3. P ( . ., ,
(See also Chap. 237) T , )
.H , - .
, 4. P
.O , IHD.
1858 5. M >45 >55 , . T
,
. ( ), (Chap. 268)
6. P , .
W CAD,
PART 6
, - LV ; , LV ,
, . -
7. P , , - .T ,
( ( -
). ECG, , -
8. P , ), LV (
( . ., ,K - ),
) . (
). T
N
, -
CT CMR (Chap. 236). A
.R
-
, , , ,
.I , ,
- ( . ., ).
CT - T
CMR ( [>75 ], , ,
, . , , / -
, ),
■ PROGNOSIS .E CRP
T IHD , CT (
, , () ), -
, .
.A , (Chap. 268),
,
, TREATMENT
Stable Angina Pectoris
.T
, , O IHD ,
, - -
( ) , , , -
(<0.40) .
M , - .T
:
6 , . ., II (B ) ; .T -
: (1)
(≥0.1 V ST- II, ≥0.2 V , (2)
ST- , ST- >5 , (3)
, >10 H , (4)
, , (5)
); , (6) .
; LV EXPLANATION AND REASSURANCE

. P IHD
C , III B
. O
.T ST-
ECG ( ) . A
. ,
O , LV - ,
.
LV
. P LV IDENTIFICATION AND TREATMENT OF AGGRAVATING
. O - CONDITIONS
(>50% ) A
-
IHD. LVH, ,
. A . O , ,
.T -
, , .D -
, , ,
.T ( . ., , ,
/ ) -
( . ., ). C , - - 1859
, . IHD. I
ADAPTATION OF ACTIVITY
.

M Cigarette smoking
, -
.M , , . I ,
,
.M - . S
.P .N -
( )
, , .T ’
.O , -
. (Chap. 448).
P Hypertension (Chap. 271)
.
A .I , LVH -
’ - .T -
80%
.B (Chap. 271).
, Diabetes mellitus (Chap. 396)
(MET )
(T 267-2) , ,
.A ( LDL
(Table 267-3). <70 / L) (
TREATMENT OF RISK FACTORS 120/80 H )
, .
A family history IHD
DYSLIPIDEMIA
, , . Obesity T -
, , -
.I , .T
: , , trans-
.T , , .N ,
. HMG-C A ( )
A trans- LDL (25–50%), HDL (5–9%),
TABLE 267-3 Energy Requirements for Some Common Activities

LESS THAN 3 METs 3–5 METs 5–7 METs 7–9 METs MORE THAN 9 METs
Sel -Care
Washing/shaving Cleaning windows Easy digging in garden Heavy shoveling Carrying loads up stairs
Dressing Raking Level hand lawn mowing Carrying objects (60–90 lb) (objects more than 90 lb)
Light housekeeping Power lawn mowing Carrying objects (30–60 lb) Climbing stairs (quickly)
Desk work Bed making/stripping Shoveling heavy snow
Driving auto Carrying objects (15–30 lb)
Occupational
Sitting (clerical/assembly) Stocking shelves (light objects) Carpentry (exterior) Digging ditches (pick and Heavy labor
Desk work Light welding/carpentry Shoveling dirt shovel)
Standing (store clerk) Sawing wood
Recreational
Gol (cart) Dancing (social) Tennis (singles) Canoeing Squash
Knitting Gol (walking) Snow skiing (downhill) Mountain climbing Ski touring
Sailing Light backpacking Vigorous basketball
Tennis (doubles) Basketball
Stream ishing
Physical Conditioning
Walking (2 mph) Level walking (3–4 mph) Level walking (4.5–5.0 mph) Level jogging (5 mph) Running more than 6 mph
Stationary bike Level biking (6–8 mph) Bicycling (9–10 mph) Swimming (crawl stroke) Bicycling (more than 13 mph)
Very light calisthenics Light calisthenics Swimming, breast stroke Rowing machine Rope jumping
Heavy calisthenics Walking uphill (5 mph)
Bicycling (12 mph)
Abbreviation: METs, metabolic equivalent tasks.
Source: Modi ied rom WL Haskell: Rehabilitation o the coronary patient, in NK Wenger, HK Hellerstein (eds): Design and Implementation o Cardiac Conditioning
Program. New York, Churchill Livingstone, 1978.
1860 (5–30%). A - TABLE 267-5 Properties of Beta Blockers in Clinical Use for Ischemic
, IHD, - Heart Disease
LDL .F PARTIAL
HDL (Chap. 400). C AGONIST USUAL DOSE FOR
- DRUGS SELECTIVITY ACTIVITY ANGINA
PART 6
, , , , . Acebutolol β1 Yes 200–600 mg twice daily

I PCSK9 Atenolol β1 No 50–200 mg/d
LDL Betaxolol β1 No 10–20 mg/d
.
Bisoprolol β1 No 10 mg/d
C -
, - Esmolol β1 No 50–300 μg/kg/min

(intravenous) a
. M
Labetalolb None Yes 200–600 mg twice daily
.I Metoprolol β1 No 50–200 mg twice daily
, - Nadolol None No 40–80 mg/d
, , Nebivolol β1 (at low doses) No 5–40 mg/d
. Pindolol None Yes 2.5–7.5 mg 3 times daily
RISK REDUCTION IN WOMEN WITH IHD Propranolol None No 80–120 mg twice daily
T IHD ; Timolol None No 10 mg twice daily
a
, , Esmolol is an ultra-short-acting beta blocker that is administered as a continuous
( . ., LDL, HDL) intravenous in usion. Its rapid o set o action makes esmolol an attractive agent
to use in patients with relative contraindications to beta blockade. bLabetolol is a
.W combined alpha and beta blocker.
. D Note: This list o beta blockers that may be used to treat patients with angina
, , pectoris is arranged alphabetically. The agents or which there is the greatest
IHD clinical experience include atenolol, metoprolol, and propranolol. It is pre erable to
use a sustained-release ormulation that may be taken once daily to improve the
, , . C - patient’s compliance with the regimen.
Source: Data rom RJ Gibbons et al: J Am Coll Cardiol 41:159, 2003.
.W ,
NITRATES
, CABG ,
. T
(T 267-4). T
DRUG THERAPY LV
T
Tables 267-4 through 267-6. P
IHD , TABLE 267-6 Calcium Channel Blockers in Clinical Use for Ischemic
Heart Disease
, . T
- DURATION
DRUGS USUAL DOSE OF ACTION SIDE EFFECTS
.T
IHD, - Dihydropyridines
Amlodipine 5–10 mg qd Long Headache, edema
, , Felodipine 5–10 mg qd Long Headache, edema
, . Isradipine 2.5–10 mg bid Medium Headache, atigue
Nicardipine 20–40 mg tid Short Headache, dizziness,
lushing, edema
TABLE 267-4 Nitrate Therapy in Patients with Ischemic Heart
Disease Ni edipine Immediate release:a Short Hypotension, dizziness,
30–90 mg daily orally lushing, nausea,
PREPARATION OF constipation, edema
AGENT DOSE SCHEDULE Slow release: 30–180
mg orally
Nitroglycerina
Nisoldipine 20–40 mg qd Short Similar to ni edipine
Ointment 0.5–2 in. Two or three times daily
Nondihydropyridines
Transdermal patch 0.2–0.8 mg/h Every 24 h; remove at
bedtime or 12–14 h Diltiazem Immediate release: Short Hypotension, dizziness,
30–80 mg 4 times lushing, bradycardia,
Sublingual tablet 0.3–0.6 mg As needed, up to three
daily edema
doses 5 min apart
Slow release: Long
Spray One or two sprays As needed, up to three
120–320 mg qd
doses 5 min apart
Verapamil Immediate release: Short Hypotension,
Isosorbide dinitratea
80–160 mg tid myocardial depression,
Oral 10–40 mg Two or three times daily heart ailure, edema,
Slow release: Long
Oral sustained release 80–120 mg Once or twice daily 120–480 mg qd bradycardia
(eccentric schedules)
a
May be associated with increased risk o mortality i administered during acute
Isosorbide 5-mononitrate myocardial in arction.
Oral 20 mg Twice daily (given Note: This list o calcium channel blockers that may be used to treat patients
7–8 h apart) with angina pectoris is divided into two broad classes, dihydropyridines and
Oral sustained release 30–240 mg Once daily nondihydropyridines, and arranged alphabetically within each class. Among
the dihydropyridines, the greatest clinical experience has been obtained with
a
A 10- to 12-h nitrate- ree interval is recommended. amlodipine and ni edipine. A ter the initial period o dose titration with a short-
Source: Modi ied rom DA Morrow, WE Boden: Stable ischemic heart disease. In acting ormulation, it is pre erable to switch to a sustained-release ormulation
RO Bonow et al (eds): Braunwald’s Heart Disease: A Textbook o Cardiovascular that may be taken once daily to improve patient compliance with the regimen.
Medicine, 9th ed. Philadelphia, Saunders, 2012, p. 1224. Source: Data rom RJ Gibbons et al: J Am Coll Cardiol 41:159, 2003.
- , B - 1861
; - -
; .W ,
, (NO)

, .T
, - LV ,
.N LV ,
NO- , .A
, .
T ,
. F , - . V (P ’)
0.4 0.6 .P (
),
~5 (Chap. 268).
.T V
. -
N . D
.
P ’ (Chap. 268). A A -
.W
, , - ,
/ .A
. -
Long-Acting Nitrates N - - ( , , - , )
.T
, , - .S -
(T 267-4). ,
T 24 , - .
.D / Choice Between Beta Blockers and Calcium Channel Blockers for
Initial Therapy S
- (Chaps. 268 and
.I . 269) ,
T , .
8 H ,
( ). : (1)
a-Adrenergic Blockers T - ;
(T 267-5).
T ; (2) ,
, , , ; (3)
.B ; (4) -
. ; (5) P ’
L - - - ; (6) .
- (T 267-5). T - A , ,
.T
Table 267-7.
. Antiplatelet Drugs A
R .
, C 75–325
, ,R ’ -
, .S , 50, ,
, , , , . T
, ( ), -
, LV , , - .I -
, 81–162 / .A
.R IHD
, , .C (300–600
. S , 75 / ) P2Y12 ADP –
2 .B .I
β1- IHD
- .C
.
Calcium Channel Blockers C (T 267-6) (Chap. 268)
-
, , (Chap. 270). A
. T P2Y12
-
.T
, , . ,
1862 TABLE 267-7 Antianginal Agents
AGENT COMMON SIDE EFFECTS CONTRAINDICATIONS POTENTIAL DRUG INTERACTIONS
Agents That Have a Physiological E ect
Short-acting and long-acting nitrates Headache, lushing, hypotension, Hypertrophic obstructive Phosphodiesterase type 5 inhibitors
PART 6
syncope and postural hypotension, cardiomyopathy (sildena il and similar agents), beta-
re lex tachycardia, methemoglobinemia adrenergic blockers, calcium-channel
blockers
Beta blockers Fatigue, depression, bradycardia, Low heart rate or heart conduction Heart-rate-lowering calcium-channel
heart block, bronchospasm, peripheral disorder, cardiogenic shock, asthma, blockers, sinus-node or AV conduction
vasoconstriction, postural hypotension, severe peripheral vascular disease, depressors

impotence, masked signs o decompensated heart ailure,
hypoglycemia vasospastic angina; use with caution
in patients with COPD (cardio-selective
beta blockers may be used i patient
receives adequate treatment with long-
acting beta agonists)
Calcium-channel blockers
Heart-rate-lowering agents Bradycardia, heart conduction de ect, Cardiogenic shock, severe aortic CYP3A4 substrates (digoxin,
low ejection raction, constipation, stenosis, obstructive cardiomyopathy simvastatin, cyclosporine)
gingival hyperplasia
Dihydropyridine Headache, ankle swelling atigue, Low heart rate or heart rhythm Agents with cardiodepressant e ects
lushing, re lex tachycardia disorder, sick sinus syndrome, (beta-blockers, lecainide), CYP3A4
congestive heart ailure, low blood substrates
pressure
Agents That A ect Myocardial Metabolism
Ranolazine Dizziness, constipation, nausea, Liver cirrhosis CYP3A4 substrates (digoxin,
QT-interval prolongation simvastatin, cyclosporine), drugs that
prolong the corrected QT interval
Abbreviations: COPD, chronic obstructive pulmonary disease; CYP3A4, cytochrome P-450 3A4.
Source: Data rom SE Husted: Lancet 386:691, 2015 and EM Ohman: N Engl J Med 374:1167, 2016.
. A NSAID ,
, .
- A ATP-
, , .
IHD. T , -
20 .
OTHER THERAPIES (N U S
T ACE .)
, IHD I (2.5–7.5 )
, -
.T ACE IHD
IHD , ≥70 / ( ) and
, LV .I
LDL IHD not .
.H , ACE
Angina and Heart Failure T LV
IHD LV
LDL .F
- . , LV -
.T
D , ,
, IHD , ACE , , (Chap. 252)
, , ,
.I
.R , ,
,
(
T 267-7). I
(IN ). T IN .A -
N -
C 2+
N +–C 2+
.A .N
500–1000 .R .
T
QT IHD -
CYP3A ( . ., ,
, , , HIV , .
) .
N - (NSAID) CORONARY REVASCULARIZATION
IHD C
.F , IHD,
IHD .I . R
, , ,
- , , LV . PCI . PCI 1863
Revascularization should be employed in conjunction with but not replace the
continuing need to modify risk factors and assess medical therapy. A - -
.H , ,

IHD Fig. 267-4. PCI
. PCI
■ PERCUTANEOUS CORONARY INTERVENTION
(See also Chap. 270) PCI - CABG.
IHD Risks W ,
.W - .H ,
- IHD , -
( / LV ) ,
CABG, PCI , (Chap. 270). O , P2Y12
,
- .L
( , , ) CABG. I
. , PCI -
,
Indications and Patient Selection T ; ,
PCI - , - .
, .
Efficacy P , . ., (
>20% <50%)
, >95% .R
MANAGEMENT OF THE PATIENT WITH IHD ~20% 6 PCI
, 6 10%
Initiate medical therapy:
1. Decrease demand ischemia .R ,
2. Minimize IHD risk factors , ,
3. ASA (clopidogrel if ASA intolerant) , , ,
, .
I ,
Any high-risk features? , ,
Low exercise capacity or ischemia at low workload, large .
area of ischemic myocardium, EF <40%, ACS presentation I
P2Y12 1–3
.A
No Yes
PCI -
,
.
Are exertional Refer for coronary T -
symptoms controlled? arteriography 10%. A PCI,
- ,
Anatomy suitable IHD. O ,
Yes No for revascularization? , -
. A
Yes No
P2Y12 ( [DAPT])
1 - .E
DAPT 30 ,
.W
Single vessel LM +/or multi Consider , -
disease vessel disease unconventional PCI
treatments
;
Assess:
PCI .T
PCI vs CABG
,
, , , .H , DAPT
Continue medical therapy periodic stress assessment
(see Fig. 267-3) .
S PCI >95% .
FIGURE 267-4 Algorithm or management o a patient with ischemic heart T IHD -
disease. All patients should receive the core elements o medical therapy as PCI. S PCI
shown at the top o the algorithm. I high-risk eatures are present, as established CABG initial
by the clinical history, exercise test data, and imaging studies, the patient should .S PCI CABG
be re erred or coronary arteriography. Based on the number and location o the , ,
diseased vessels and their suitability or revascularization, the patient is treated
with a percutaneous coronary intervention (PCI) or coronary artery bypass gra t .H , -
(CABG) surgery or should be considered or unconventional treatments. See text PCI -
or urther discussion. ACS, acute coronary syndrome; ASA, aspirin; EF, ejection .W
raction; IHD, ischemic heart disease; LM, le t main. - CAD, CABG
1864 PCI
12- - .
.C / LV ,
■ CORONARY ARTERY BYPASS GRAFTING (>80 ), , ,
A -
PART 6
.
. F LV
, ( ) ( -
- ). A
. , .T
A CABG ,
: , PET, MRI, -201
1. T , <1%
- . I ,
LV
, , .
.
2. I The Choice Between PCI and CABG A -
, , >80 ,
.T CABG ( . ., LV , , ). A
- PCI CABG
. CAD
3. O venous 10–20% . T
~2% 5- 7- PCI. T
- 4% . L - (
- )
.I .I
, PCI ,
.G (Fig. 267-5).
, . B , PCI.
4. A ~90% B ,
.A -
, .P
- - LV
.W 3 , - PCI (Chap. 270).
. P - ( -
5. S ) LV
- (LV <50%)
- CAD -
.T CABG
LV ( <50%). .I - ,
S may :( ) ,
CAD ’
;( ) , ’ -
CABG , .
; () PCI - ■ UNCONVENTIONAL TREATMENTS FOR IHD

. O
6. M CABG / -
( . .,
. ). I ,
7. A 2 .
, CABG Enhanced external counterpulsation
,
.T CABG .C
- , ,
- . .E ,
- RNA
CABG PCI (
( RNA), .
- ) , ,
IHD.
ASYMPTOMATIC (SILENT) ISCHEMIA
O CAD, , -
I CABG - . D
, , .T ECG ,
, <80 , ,
(ST- )
.G - .I -
,
PCI 1865

Stent Lesion
Coronary CABG
artery
Future
A culprit
lesion
Lesion
Bypass
graft
Future
culprit
lesion
B
FIGURE 267-5 Di erence in the approach to the lesion with percutaneous coronary intervention (PCI) and coronary artery bypass gra ting (CABG). PCI is targeted at
the “culprit” lesion or lesions, whereas CABG is directed at the epicardial vessel, including the culprit lesion or lesions and uture culprits, proximal to the insertion o
the vein gra t, a di erence that may account or the superiority o CABG, at least in the intermediate term, in patients with multivessel disease. (Reproduced rom BJ
Gersh, RL Frye: N Engl J Med 352:2235, 2005.)
.F (
) . A
( , - CAD, LV
). I , CABG.
. T ,
T ECG , ,
,
CAD. L -
CAD. A -
.
, , - ,
TREATMENT .
Asymptomatic Ischemia
■ FURTHER READING
T De Bruyne B :M ( )
. W , .JA C C 67:1170, 2016.
Fihn SD : 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS
.I ,
: (1) :A A C C -
, ECG F /A H A
; , A C P ,A A -
; LV T S ,P C N A -
,S C A I ,
/ ; (2) ECG S T S .C 126: 354, 2012.
, - Levine GN : 2016 ACC/AHA -
;
(3) ’ , , . :AR A C C /A
M 45- - H A T F C P G : A
(0.4- V) ST- U 2011 ACCF/AHA/SCAI G P
V1 V4 - C I , 2011 ACCF/AHA G C
, , 85- - A B G S , 2012 ACC/AHA/ACP/AATS/PCNA/
0.1- V ST- II III SCAI/STS G D M P
.H , S I H D , 2013 ACCF/AHA G
1866 M ST-E M I , 2014 (NSTEMI), , , ,
AHA/ACC G M P N -ST- (UA), (Fig. 268-1).
E A C S , 2014 ACC/AHA G - T NSTEMI
P C E M ,
P U N S .C 134: 123, 2016. STEMI , ,
PART 6
Mody P :A .A NSTE-ACS,
:A .C R 24:177, 2016. NSTEMI UA
Mozaffarian D : H —2016 ,
:A A H A .C UA NSTEMI.
2016;133: 38, 2016.
Omland T, White HD: S :B - ■ PATHOPHYSIOLOGY

.C C NSTE-ACS
63:165, 2017.
Singh M, Arora R: N : (1)
.A JT , ,
23: 1842, 2016.
(Fig. 268-2) ; (2) -
; (3) ; (4)
,
,
.W
Non-ST-Segment Elevation ,
268 Acute Coronary Syndrome ,
ACS.
(Non-ST-Segment Elevation A NSTE-ACS , ~10%
, 35% -
Myocardial Infarction and CAD, 20% - , 20% - ,
Unstable Angina) 15% ;
-
Robert P. Giugliano, Christopher P. Cannon, / .T - “
Eugene Braunwald ”
-
.V -
. P NSTE-ACS
P (ACS)
.
,
ST- (STEMI)
■ CLINICAL PRESENTATION
(ECG) (Chap. 269) -
ST- (NSTE-ACS). T Diagnosis T NSTE-ACS -
-ST- (Fig. 268-3).
Low likelihood High likelihood
1. Presentation
2. ECG
3. Troponin
4. Diagnosis Non-cardiac UA Other NSTEMI STEMI

cardiac
FIGURE 268-1 Assessment o patients with suspected acute coronary syndromes. The initial assessment is based on the integration o low-likelihood and/or high-
likelihood eatures derived rom clinical presentation (i.e., symptoms, vital signs), 12-lead electrocardiogram and cardiac troponin. The proportion o the nal diagnoses
derived rom the integration o these parameters is visualized by the size o the respective boxes. (From Ro f M et al: 2015 European Society o Cardiology Guidelines
or the management o acute coronary syndromes. Eur Heart J 37:267, 2016.)
1867
Thrombus Plaque rupture
CHAPTER 268 Non-ST-Segment Elevation AcuteCoronary Syndrome (Non-ST-Segment Elevation Myocardial Infarctionand Unstable Angina)
*
*
A B
Plaque erosion Calcified nodule
*
*
C D
FIGURE 268-2 Intracoronary thrombosis and the three most common plaque morphologies resulting in acute coronary syndrome as visualized by optical coherence
tomography. A. Thrombus (arrow) is identi ed as a protruding mass attached to the arterial wall. B. Plaque rupture is identi ed as lipid plaque with brous cap
discontinuity (arrow) and cavity ormation inside the plaque. C. Plaque erosion is con rmed by the presence o attached thrombus (arrows) overlying an intact and
visualized plaque. D. Calci ed nodule appears on optical coherence tomography as a site with brous cap disruption (dotted arrow) and underlying plaque characterized
by protruding calci cation, super cial calcium, and signi cant calcium adjacent to the lesion (arrows). The asterisks denote guidewire shadow arti act. (Modifed rom H
Jia et al: J Am Coll Cardiol 62:1748, 2013 and I Jang, D Ong: Optical coherence tomography and other emerging diagnostic procedures or vulnerable plaque, in D Morrow
(ed): Myocardial In arction: A Companion to Braunwald’s Heart Disease. Philadelphia, Elsevier Health Sciences, 2017.)
Symptoms suggestive of ACS
Noncardiac diagnosis Chronic stable angina Possible ACS Definite ACS
Treatment as indicated See Chap. 267 No ST-segment ST-segment

by alternative diagnosis elevation elevation
Observe 12 h or more Nondiagnostic ECG ST- and/or T-

from symptom onset Normal initial cTn wave changes
Ongoing pain
or elevated cTn
No recurrent pain; Recurrent ischemic pain or Hemodynamic
negative positive follow-up studies abnormalities
follow-up studies Diagnosis of ACS confirmed
Stress study to provoke ischemia See Chap. 269

Consider evaluation of LV function
if ischemia is present
Negative Positive Admit to hospital

Potential diagnoses: nonischemic Diagnosis of ACS confirmed or Manage via acute
discomfort; low-risk ACS highly likely ischemia pathway
Outpatient follow-up
FIGURE 268-3 Algorithm or evaluation and management o patients with suspected acute coronary syndrome (ACS). Follow-up studies re er to ST deviation and
elevation o troponin levels. cTn, cardiac troponin; ECG, electrocardiogram; LV, le t ventricular. (Modifed rom J Anderson et al: J Am Coll Cardiol 61:e179, 2013.)
1868 History and Physical Examination T , - ■ DIAGNOSTIC EVALUATION
: (1) I ,
( ), >10 ; (2) NSTEMI-ACS: ECG, -
( . ., 2 ); / (3) , .I , -
, . ., , , - (CCTA)
PART 6
.T NSTEMI .T : (1)
( ST (MI) , -
) , T ; (2) ( ECG );
( ). T (3) CCTA /
(Chap. 236).
, , / . P
A , , , “ ” -
.T .E
, , -
. T ECG ,
(Chap. 267) .H , 4–6 12 .I
NSTEMI, ST-T- ECG ,
; , ; .P -
; / ; ; ,
, . CCTA
(F . 268-3).
Electrocardiogram N ST- T T (3- 1- ) -
- NSTE-ACS. I MI 2015 E G -
NSTEMI. T- NSTE-ACS.
,
T- (≥0.3 V). ■ RISK STRATIFICATION
P NSTE-ACS
Cardiac Biomarkers P NSTEMI
(30 ) , 1 10%, ACS
, ( T )I T,
5–15% .A
, , .
T -
T MB (CK-MB) -
M I (TIMI) T ,
. E
( ≥ 65 ,3
NSTEMI UA. T
,
12–24
50%,
, 24 ,
.H , without
ST 0.5 , -
, T
). A
, ,
, , -
, - ( T )
, B- .M
.T , unclear ,
, -
T , ,
’
ACS. I , -
’ .P ACS
T (Table 268-1).
T (
) UA
TABLE 268-1 Causes of Elevated Cardiac Troponin Reflecting Direct T (NSTEMI).
Myocardial Damage Other Than Spontaneous Myocardial Infarction E
(Type 1) ( ).
CARDIAC NON-CARDIAC OR SYSTEMIC F , TACTICS-TIMI 18 T ,
Tachyarrhythmias Pulmonary embolism/pulmonary
40%
hypertension T , -
Congestive heart ailure Trauma (e.g., electrical shock, burns, .
blunt chest wall)
Hypertensive emergencies Hypo or hyperthyroidism
TREATMENT
In ection/in lammation (e.g., Toxicity (e.g., anthracyclines, snake
myocarditis, pericarditis) venom) Non-ST-Segment Elevation Acute Coronary
Stress cardiomyopathy (Tako-Tsubo Renal ailure Syndrome (Non-ST-Segment Elevation Myocardial
cardiomyopathy)
Structural heart disease (e.g., aortic Sepsis, shock Infarction and Unstable Angina)
stenosis)
Aortic dissection Stroke or other acute neurologic MEDICAL TREATMENT
event P ECG -
Coronary spasm Extreme endurance e orts (e.g., ST- ,
ultra-marathon) .A
Cardiac procedures (endomyocardial Rhabdomyolysis ( ECG )
biopsy, ablation, CABG, PCI) 12–24 .
In iltrative diseases (e.g., amyloidosis, M
hemochromatosis, malignancy) () -
Source: Data rom LK Newby et al: J Am Coll Cardiol 60:2427, 2012 and M Ro i:
Eur Heart J 37:267, 2016. / .
ANTI-ISCHEMIC TREATMENT (TABLE 268-2) HMG-C A ( ), - 1869
T - 80 / ,
, , , (PCI), , -
, O2 MI ACS. I
(<90%) / . ( . ., <50%
LDL-C LDL-C
Nitrates T >70 / L), 10
(0.3–0.6 ) . LDL-C .
I 5 , -
(5–10 μ / ) - ANTITHROMBOTIC THERAPY (FIG. 268-4 AND TABLE 268-3)
.T 10 μ / A
3–5 , .
<90 H , 200 μ / .T Antiplatelet Drugs (See Chap. 114) I
(Chap. 267) ,
162 ( -
- 12–24 . T ). L (75–100 / )
- , .
5 (PDE-5) , ( C .
24 ), ( 48 ). I , NSTE-
Beta-Adrenergic Blockers and Other Agents B ACS,
- .T ( ) , P2Y12
, .T
, - P2Y12 (
, , - - , , );
( . ., - , ). .
O , 50–60 / T
.H – -
, . ., , P2Y12 .T 600
ECG 300 75 .W -
- , - (DAPT),
.A 20%
- (ACE) , MI, , ,
. E ( 1%) .
TABLE 268-2 Drugs Commonly Used in Intensive Medical Management of Patients with Unstable Angina and Non-ST-Segment Elevation
Myocardial Infarction
DRUG CATEGORY CLINICAL CONDITION WHEN TO AVOIDa DOSAGE
Nitrates Patients with ACS who have chest Hypotension Initially administer via sublingual or buccal route, and,
discom ort or an anginal equivalent i symptoms persist, intravenously.
Right ventricular in arction Topical or oral nitrates are acceptable alternatives or
Severe aortic stenosis patients without ongoing or re ractory symptoms
Patient receiving a PDE-5 inhibitor 5–10 μg/min by continuous in usion titrated up to
75–100 μg/min until relie o symptoms or limiting
side e ects (headache or hypotension with a
systolic blood pressure <90 mmHg or >30% below
starting mean arterial pressure levels i signi icant
hypertension is present)
Beta blockersb All patients with ACS PR interval (ECG) >0.24 s Metoprolol 25–50 mg by mouth every 6 h
2° or 3° atrioventricular block I needed, and no heart ailure, 5-mg increments by
Heart rate <50 beats/min slow (over 1–2 min) IV administration
Systolic pressure <90 mmHg
Shock
Le t ventricular ailure
Severe reactive airway disease
Calcium channel Patients whose symptoms are not Pulmonary edema Dependent on speci ic agent
blockers relieved by adequate doses o nitrates Evidence o le t ventricular dys unction
and beta blockers, or in patients ( or diltiazem or verapamil)
unable to tolerate adequate doses
o one or both o these agents, or in
patients with variant angina
Morphine sul ate Patients whose symptoms are not Hypotension 2–5 mg IV dose
relieved a ter three serial sublingual Respiratory depression May be repeated every 5–30 min as needed to relieve
nitroglycerin tablets or whose symptoms and maintain patient com ort
Con usion
symptoms recur with adequate anti-
ischemic therapy Obtundation
a
Allergy or prior intolerance is a contraindication or all categories o drugs listed in this chart. bChoice o the speci ic agent is not as important as ensuring that
appropriate candidates receive this therapy.
Source: Modi ied rom J Anderson et al: J Am Coll Cardiol 61:e179, 2013.
1870 Initial Treatment DAPT and Anticoagulant therapy:
1. Aspirin (COR I, LOE A).
2. P2Y 12 inhibitor: clopidogrel or ticagrelor (COR I, LOE B).
3. Anticoagulant:
Enoxaparin (COR I, LOE A) or UFH (COR l, LOE B) or fondaparinux (COR I, LOE B)
PART 6
or bivalirudin (for early invasive strategy, COR I, LOE B).

4. Can consider GP Ilb/llla receptor inhibitors in high-risk patients stratified to early invasive
strategy (eptifibatide or tirofiban; COR IIb, LOE B).
During Medically treated patients: PCI treated patients:

Hospitalization 1. Aspirin (COR I, LOE A). 1. Aspirin (COR I. LOE A).
2. P2Y 12 inhibitor: either ticagrelor or 2. P2Y 12: inhibitor: clopidogrel or ticagrelor or prasugrel
clopidogrel (COR I, LOE B). (COR I, LOE B).
3. Anticoagulant: 3. Anticoagulant:
Enoxaparin (COR I, LOE A) or UFH Enoxaparin (COR I, LOE A) or UFH (COR l, LOE B)
(COR l, LOE B) or fondaparinux (COR I, or fondaparinux* (COR I, LOE B) or bivalirudin (COR I,
LOE B). LOE B).
4. Can consider GP Ilb/llla receptor inhibitors in high-
risk patients not adequately per-treated with
clopidogrel (COR I, LOE A) or in high-risk patients
adequately pre-treated with clopidogrel
(COR IIa, LOE B).
Long-term Medically treated patients: PCI treated patients:

1. Aspirin indefinitely (COR I, LOE A). 1. Aspirin indefinitely (COR I, LOE A).
2. P2Y 12 inhibitor: clopidogrel or ticagrelor 2. P2Y 12 inhibitor: clopidogrel or ticagrelor or prasugrel
for up to 12 months (COR I, LOE B) for at least 12 months (COR I, LOE B).
(*Supplemental UFH or bivalirudin is required during PCI to prevent procedure-related thrombosis in patients treated with fondaparinux.)
FIGURE 268-4 Antiplatelet and anticoagulation treatment summary or NSTE-ACS according to the 2014 American Heart Association/American College o
Cardiology Practice Guideline. COR, classes o recommendation; DAPT, dual antiplatelet therapy; GP IIb/IIIa, glycoprotein IIb/IIIa; LOE, levels o evidence; NSTE-ACS,
non-ST-segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; UFH, un ractionated heparin. (From A Eisen, RP Giugliano: Cardiol Rev
24;170, 2016.)
T P2Y12 ( , )
TABLE 268-3 Clinical Use of Antithrombotic Therapy
Oral Antiplatelet Therapy -
Aspirin Initial dose o 325 mg nonenteric ormulation ollowed by . P , ,
75–100 mg/d o an enteric or a nonenteric ormulation .I
Clopidogrel Loading dose o 300–600 mg ollowed by 75 mg/d ACS PCI
Prasugrel Pre-PCI: Loading dose 60 mg ollowed by 10 mg/d .I 60
Ticagrelor Loading dose o 180 mg ollowed by 90 mg twice daily 10 / . C ,
Intravenous Antiplatelet Therapy 19% -
, MI, , 50%.
Abciximab 0.25 mg/kg bolus ollowed by in usion o 0.125 μg/kg per
min (maximum 10 μg/min) or 12–24 h P
.I
Epti ibatide 180 μg/kg bolus ollowed 10 min later by second bolus
o 180 μg with in usion o 2.0 μg/kg per min or 72–96 h
ollowing irst bolus ( ).
Tiro iban 25 μg/kg per min ollowed by in usion o 0.15 μg/kg per T , , reversible P2Y12
min or 48–96 h ,
Cangrelor 30 μg/kg bolus ollowed immediately by a 4 μg/kg per min MI
in usion ACS. A 180 , 90 -
Anticoagulantsa . U ,
b
-
Un ractionated Bolus 70–100 U/kg (maximum 5000 U) IV ollowed by
heparin (UFH) in usion o 12–15 U/kg per h (initial maximum 1000 U/h)
.S
titrated to ACT 250–300 s ,
Enoxaparin 1 mg/kg SC every 12 h; the irst dose may be preceded by ,
a 30-mg IV bolus; renal adjustment to 1 mg/kg once daily .
i creatine clearance <30 mL/min DAPT 1 NSTE-
Fondaparinux 2.5 mg SC qd ACS, - ,
Bivalirudin Initial IV bolus o 0.75 mg/kg and an in usion o .U -
1.75 mg/kg per h ,
a
P450 2C19
Other low-molecular-weight heparins have been studied other than enoxaparin;
however there are less data to support their use. bI no glycoprotein IIb/IIIa
inhibitor planned. .T , P2Y12
Abbreviations: ACT, activated clotting time or HemoTec; IV, intravenous; SC, NSTE-ACS -
subcutaneous. , ,
Source: Modi ied rom J Anderson et al: J Am Coll Cardiol 61:e179, 2013. .C
TABLE 268-4 Factors Associated with Appropriate Selection of Early 1871
Invasive Strategy or Ischemia-Guided Strategy in Patients with
. NSTE-ACS
M , , , P2Y12 Immediate invasive Re ractory angina
, , (within 2 h) Signs or symptoms o heart ailure or new or worsening
>25,000 PCI - mitral regurgitation
( , UA, NSTEMI, STEMI). A Hemodynamic instability
14,282 PCI NSTE-ACS, Recurrent angina or ischemia at rest or with low-level
, MI, activities despite intensive medical therapy
- , 48 18% Sustained ventricular tachycardia or ventricular ibrillation
.T 3 1000 Early invasive None o the above, but GRACEa risk score >140
.T PCI (within 24 h) Temporal change in troponin
MI, -
New or presumably new ST segment depression
,
P2Y12 GP II /III . Delayed invasive None o the above but diabetes mellitus
I 1990 2000
(within 25–72 h) Renal insu iciency (eGFR <60 mL/min per 1.73 m 2)
II /III NSTE- Reduced le t ventricular systolic unction (ejection
ACS, raction <0.40)
P2Y12 .T , , ( . ., ~1% Early postin arction angina
MI 30 ) Percutaneous coronary intervention within 6 months prior
1% .T Prior coronary artery bypass gra t surgery
GRACEa risk score 109–140 or TIMIb risk score ≥2
Ischemia-guided Low-risk score (e.g., TIMIb [0 or 1], GRACE a [<109])
PCI. T P2Y12 strategy Low-risk, troponin-negative emale patients
( . ., )
Patient or clinician pre erence in the absence o high-
PCI. T risk eatures
, T , ECG ,
a
. See CB Granger (Arch Intern Med 163:2345, 2003). bSee EM Antman (JAMA
284:835, 2000).
Anticoagulants (See Chap. 114) F Abbreviations: eGFR, estimated glomerular iltration rate; GRACE, Global Registry
: (1) - o Acute Coronary Events; TIMI, Thrombolysis in Myocardial In arction.
(UFH), ; (2) Source: Modi ied rom EA Amsterdam et al: J Am Coll Cardiol 64:e139, 2014.
- - (LMWH), ,
UFH ■ LONG-TERM MANAGEMENT
, . T “ ”
H , - NSTE-ACS,
UFH; (3) , . R - ,
UFH LMWH ,
/ PCI; (4) , , - ,
X , , , (
.W UFH ),
(Chap. 267).
, T -
, -
UFH . B , (
PCI - . , . ., 80 / ,
E LDL-C 70 / L), ACE
, - . T
.T , - - (75–100 / )
, , , P2Y12 ( , , ) 1 ,
, .I
.P
( . ., MI, , ,
) ,
.
DAPT 3 .T ,
INVASIVE VERSUS CONSERVATIVE STRATEGY , ACS.
I , - R ,
, NSTE-ACS ,
~48 , (PCI ,
), -
.M . S
- ( . ., .
, ST- , / )
■ PRINZMETAL’S VARIANT ANGINA
(Table 268-4). I ,
I 1959, P .
.
ST- -
T -
.P ’ (PVA)
“ ,”
-
MI,
ST- ,
, .T
, .
,
1872 , , , ACS
.F , PVA .T
, A ,I , P ,
J N A W E . -S A .
Clinical and Angiographic Manifestations P H , ,
PART 6
PVA , - IHD
, NSTE-ACS. - ,
C - .W ,
.H , ACS
.I
/ R ’ .
T PVA IHD ACS
ST- elevation , -
. .T
C -
PVA. A .T -
.H - .A
,
, , .T
ST- .
- - .O
TREATMENT ,
, , ,
Prinzmetal’s Variant Angina , .
N ■ FURTHER READING
.A - Amsterdam EA : 2014 AHA/ACC G M
, - P N -ST-E A C S :A
.S A C C /A H A
, - T F P G .JA C C 64: 139, 2014.
.T Bohula EA :A
.C .JA C C 69:911, 2017.
, - , . Cannon CP :E -
P - .NE J M 372:2387, 2015.
de Luna AB :P : ECG -
- . :A .A N E 19:442, 2014.
Eisen A :U :A . JAMA
Prognosis M PVA , C 1:718, 2016.
, Fuster V, Kovacic JC ( ): A C S C .
6 .S 5 C R 114:1847, 2014.
(~90–95%), 20% MI. P Kolte D : T C A ,R ,
- O C S C N -ST-E
MI - M I .A JC 117:1, 2016.
, Lloyd-Jones DM : 2016 ACC E C D P
CAD .P PVA R N -S T LDL-C L
M A C D R .
.I JA C C 68:92, 2016.
3- 6- , Roffi M : 2015 ESC G -
. ST-
:T F M A C S -
■ GLOBAL CONSIDERATIONS P P P ST-S E -
I (IHD), - E S C .E H J 37:267, 2016.
, ACS, Steg PG :E -
.I - - :A -
.T .L 382:1981, 2013.
IHD
ACS -
,
.A N
A ,W E , J , -
,
.I E ,
R B
- 269 ST-Segment Elevation
Myocardial Infarction
, F ,I , S .
S Elliott M. Antman, Joseph Loscalzo
, -
.T , , ,
, - A (AMI)
, , - .I U S ,
, , ~660,000 AMI, 305,000
— , , , , AMI .A AMI-
.T , . O , -
(Chap. 291e 1873
Presentation Ischemic Discomfort
19 Harrison’s). A
, ( , ADP,
Working Dx Acute coronary syndrome , ) .A -
CHAPTER 269 ST-Segment Elevation Myocardial Infarction

, A2 ( )
, ,
.
I A2, -
II /III (Chap. 111). O ,

ECG No ST elevation ST elevation ( . .,
NSTEMI ) .S -
, ,
- .
Biochem.
marker
T
.F VII
Myocardial infarction
Final Dx Unstable angina NQMI Qw MI
X ,
, (Chap. 112).
FIGURE 269-1 Acute coronary syndromes. Following disruption o a vulnerable F - - -
plaque, patients experience ischemic discom ort resulting rom a reduction o .
fow through the a ected epicardial coronary artery. The fow reduction may T -
be caused by a completely occlusive thrombus (right) or subtotally occlusive (Fig. 269-2).
thrombus (le t). Patients with ischemic discom ort may present with or without
ST-segment elevation. O patients with ST-segment elevation, the majority (wide I , STEMI
red arrow) ultimately develop a Q wave on the ECG (Qw MI), while a minority , , ,
(thin red arrow) do not develop Q wave and, in older literature, were said to have
sustained a non-Q-wave MI (NQMI). Patients who present without ST-segment
elevation are su ering rom either unstable angina or a non-ST-segment elevation Vulnerable plaque Thro m b o gen ic b lo o d
MI (NSTEMI) (wide green arrows), a distinction that is ultimately made based • in flam m atio n • in flam m atio n
on the presence or absence o a serum cardiac biomarker such as CK-MB or a • extension • com or bidities
cardiac troponin detected in the blood. The majority o patients presenting with • severity • environmental factors
NSTEMI do not develop a Q wave on the ECG; a minority develop a Qw MI (thin • location • genetic background
green arrow). Dx, diagnosis; ECG, electrocardiogram; MI, myocardial in arction.
(Adapted rom CW Hamm et al: Lancet 358:1533, 2001, and MJ Davies: Heart
83:361, 2000; with permission rom the BMJ Publishing Group.)
AMI 10
5% .T 1- AMI
15%. M
( >75) .
W
,
(Fig. 269-1). T 12-
(ECG)
; Vulnerable myo car dium
• in flam m atio n
ST-
• ischem ia dur ation/extent
ST- .S • individualsusceptibility
(UA) -ST-
(NSTEMI)
ST- (STEMI). E Cardiomyocyte
AMI swelling
15 NSTEMI STEMI. T
STEMI, Interstitial
edema
Chap. 268 UA/NSTEMI.
Thrombus
PATHOPHYSIOLOGY: ROLE OF ACUTE debris
PLAQUE RUPTURE
STEMI Endothelial Leukocyte and platelet
dysfunction activation/interaction
.S , - -
FIGURE 269-2 Critical determinants o myocardial in arction injury. The
STEMI overlapping o vulnerable plaque and thrombogenic blood are critical determinants
.I , STEMI or myocardial in arction occurrence and extension. In addition, myocardial
. vulnerability, which is largely due to coronary microvascular dys unction,
T - contributes to extension and severity o ischemic injury. In the most severe
, , .I , STEMI orm (known as no-refow), structural and unctional impairment sustain vascular
obstruction. Endothelial dys unction triggers leukocyte and platelet activation/
interaction, whereas thrombotic debris may worsen the obstruction. Furthermore,
( ) ( ) cardiomyocyte swelling, interstitial edema, and tissue infammation promote
.A extravascular compression. (Reproduced rom F Montecucco et al: Eur Heart J
, .H - 37:1268, 2016. Published on behal o the European Society o Cardiology. All
rights reserved. © The Author 2015.)
1874 — — . T STEMI, -
(1) , (2) ( / ), -
, (3) -
, (4) ( / ).
PART 6
, (5) T ,
, (6) . I ,
, (7)
. .O
P STEMI ,
UA (Chap. 268). L ,
(Chap. 234). A -
STEMI , ,
, .A
. STEMI ,
T STEMI .T ,
“ ” .T 38°C
STEMI. T -
- ; ,
. ~10–15 H .
CLINICAL PRESENTATION LABORATORY FINDINGS

I - , STEMI : (1)
STEMI, , , ( –7 ), (2) (7–28 ), (3)
.A STEMI (≥29 ). W STEMI,
, .T -
.
Pain : (1) ECG, (2) , (3) ,
STEMI. T ; (4) .
heavy, squeezing, crushing; , ,
(Chap. 11). I ■ ELECTROCARDIOGRAM
(Chap. 267) T STEMI
, , .T , Chap. 235. D ,
/ , , ST- .M
, .L ST- Q
, , , .T ECG. H ,Q
’ ,
.T STEMI .A -
. ST- Q
I , , , , - ,
, .T , .A
, , without ST- -
, , ( ) ,
. NSTEMI (F . 269-1). A
T STEMI ST-
(Chap. 265), (Chap. 273), Q- MI. P ,
(Chap. 274), , . T (MI) ECG Q
. R , MI ECG
R ST- T- . H ,
STEMI - -
.H , pain is not uniformly present Q-wave MI, non-Q-wave MI, transmural MI,
in patients with STEMI. T STEMI nontransmural MI STEMI NSTEMI
, .I , (F . 269-1). C
STEMI - , - (MRI) Q ECG
.O , -
, , , .
, ,
, ■ SERUM CARDIAC BIOMARKERS
. C , ,
STEMI. T -
■ PHYSICAL FINDINGS ,
M , , . C
, , -
. P
. T .T -
>30 STEMI. .T
A AMI /
99 1875
.
Cardiac-specific troponin T ( T T) cardiac-specific troponin I ( T I)
-

.T
T T T I -
. T T T I STEMI
(
99% MI), - Zone of necrosing
T T T I , myocardium
MI (Fig. 269-3).
W - ,
<1 /L
Troponin free Cardiomyocyte
- .T
in cytoplasm
MI
(CK) MB (CK-MB) ,
, , UA
NSTEMI. I , -
STEMI. C
(
ECG )
.L T I T T
7–10 STEMI. Myosin Actin Troponin complex
CK 4–8 48–72 bound to actin filament
(F . 269-3). A CK
STEMI, CK Lymphatic system
, .T MB
CK CK Venous system
, ,
.H , , ,
MB
.A ( ) CK-MB CK ≥2.5 Myoglobin and
CK isoforms
Multiples of the AMI cutoff limit
CK-MB . 50
M T T T I CK-MB
STEMI, 20 Troponin
. I not - (large MI)
- CK-MB 10
.
W 5
, - CKMB
.R 2
( Troponin
) STEMI 1 (small MI)
(F . 269-3) 10% CV/99th percentile
0
, -
0 1 2 3 4 5 6 7 8 9
.
T nonspecific reaction - Days after onset of AMI
, FIGURE 269-3 The zone o necrosing myocardium is shown at the top o the
3–7 ; fgure, ollowed in the middle portion o the gure by a diagram o a cardiomyocyte
12,000–15,000/μL. T - that is in the process o releasing biomarkers. The biomarkers that are released
, - into the interstitium are rst cleared by lymphatics ollowed subsequently by
1 2 . spillover into the venous system. A ter disruption o the sarcolemmal membrane o
the cardiomyocyte, the cytoplasmic pool o biomarkers is released rst (le t-most
■ CARDIAC IMAGING arrow in bottom portion o fgure). Markers such as myoglobin and CK iso orms
are rapidly released, and blood levels rise quickly above the cuto limit; this is
A two-dimensional echocardiography then ollowed by a more protracted release o biomarkers rom the disintegrating
(Chap. 236) . A STEMI myo laments that may continue or several days. Cardiac troponin levels rise
to about 20–50 times the upper re erence limit (the 99th percentile o values
, - in a re erence control group) in patients who have a “classic” acute myocardial
E in arction (MI) and sustain su cient myocardial necrosis to result in abnormally
D .W ECG STEMI, elevated levels o the MB raction o creatine kinase (CK-MB). Clinicians can
now diagnose episodes o microin arction by sensitive assays that detect cardiac
troponin elevations above the upper re erence limit, even though CK-MB levels
, may still be in the normal re erence range (not shown). CV, coe cient o variation.
( . ., (Modifed rom EM Antman: Decision making with cardiac troponin tests. N Engl
[PCI]). E - J Med 346:2079, 2002 and AS Ja e, L Babiun, FS Apple: Biomarkers in acute
(LV) ; cardiac disease: The present and the uture. J Am Coll Cardiol 48:1, 2006.)
-
- - . E
1876 (RV) , - TABLE 269-1 Definition of Myocardial Infarction
, , LV .I ,
Criteria or Acute Myocardial In arction
D
The term acute myocardial in arction (MI) should be used when there is
,
evidence o myocardial necrosis in a clinical setting consistent with acute
STEMI. myocardial ischemia. Under these conditions, any one o the ollowing criteria
PART 6
S radionuclide imaging techniques (Chap. 236) meets the diagnosis or MI:

STEMI. H , • D etection of a rise and/or fall of cardiac biom arker valu es (preferably
cardiac troponin [cTn]) with at least one value above the 99th percentile
upper re erence limit (URL) and with at least one o the ollowing:
. M [201T ] [99 T ]- – Symptoms o ischemia
, – New or presumed new signi icant ST-segment T-wave (ST-T) changes or

(Chap. 267), new le t bundle branch block (LBBB)
(“ ”) – Development o pathologic Q waves in the electrocardiogram (ECG)
.A – Imaging evidence o new loss o viable myocardium or new regional wall
, motion abnormality
, , acute MI. R - – Identi ication o an intracoronary thrombus by angiography or autopsy
, [99 T ]- , • Cardiac death w ith sym ptom s su ggestive of m yocardial ischem ia and
presumed new ischemic ECG changes o new LBBB, but death occurred
STEMI. W be ore cardiac biomarkers were obtained or be ore cardiac biomarker
- values would be increased.
RV RV • P ercu taneou s coronary intervention (P CI)– related M I is arbitrarily defined
, , by elevation o cTn values (>5 × 99th percentile URL) in patients with
normal baseline values (≤99th percentile URL) or a rise o cTn values
MI . >20% i the baseline values are elevated and are stable or alling. In
MI - MRI addition, either (i) symptoms suggestive o myocardial ischemia, or (ii)
(Chap. 236) . A new ischemic ECG changes, or (iii) angiographic indings consistent with a
( ) procedural complication, or (iv) imaging demonstration o new loss o viable
10- . S myocardium or new regional wall motion abnormality are required.
, , - • Stent throm bosis associated w ith M I w hen detected by coronary
, angiography or autopsy in the setting o myocardial ischemia and with a rise
and/or all o cardiac biomarker values with at least one value above the
99th percentile URL.
.
• Coronary artery bypass grafting (CA BG )– related M I is arbitrarily defined
A E C T F U D M - by elevation o cardiac biomarker values (>10 × 99th percentile URL)
I in patients with normal baseline cTn values (≤99th percentile URL). In
MI - addition, either (i) new pathologic Q waves or new LBBB, or (ii) angiographic
(Table 269-1) MI documented new gra t or new native coronary artery occlusion, or (iii)
(Table 269-2). imaging evidence o new loss o viable myocardium or new regional wall
motion abnormality.
INITIAL MANAGEMENT Criteria or Prior Myocardial In arction
Any one o the ollowing criteria meets the diagnosis or prior MI:
■ PREHOSPITAL CARE • P athologic Q w aves w ith or w ithou t sym ptom s in the absence of
T STEMI nonischemic causes.
: (1) ( ) • Im aging evidence of a region of loss of viable m yocardiu m that is thinned
(2) (“ ”). M - - and ails to contract, in the absence o a nonischemic cause.
STEMI • P athologic findings of a prior M I.
.T Source: Data rom K Thygesen: Eur Heart J 33:2551, 2012.
24 , ,
.T , -
STEMI (1) ECG STEMI,
; (2) .
-
, ; (3) MANAGEMENT IN THE EMERGENCY
DEPARTMENT
I E D ,
; (4) - STEMI ,
.T -
, , , -
’ .T ,
STEMI. M STEMI
E D -
.R , (Fig. 269-4). T
“ .
” STEMI T -PCI PCI
. , PCI 120
I , (F . 269-4).
, Aspirin
.G STEMI
(F . 269-1). R -1
12- ECG , - A2
, 160–325- E D .
TABLE 269-2 Classification of Myocardial Infarction , , ). N 1877
-5
Type I: Spontaneous Myocardial In arction
24 ,
Spontaneous myocardial in arction related to atherosclerotic plaque rupture, .A -

ulceration, issuring, erosion, or dissection with resulting intraluminal
thrombus in one or more o the coronary arteries leading to decreased , ,
myocardial blood low or distal platelet emboli with ensuing myocyte necrosis. -
The patient may have underlying severe coronary artery disease (CAD) but on .
occasion nonobstructive or no CAD. Morphine
Type 2: Myocardial In arction Secondary to an Ischemic Imbalance STEMI. H ,
In instances o myocardial injury with necrosis where a condition other than ,
CAD contributes to an imbalance between myocardial oxygen supply and/ .T
or demand, e.g., coronary endothelial dys unction, coronary artery spasm, , ,
coronary embolism, tachy-brady-arrhythmias, anemia, respiratory ailure, .T
hypotension, and hypertension with or without le t ventricular hypertrophy. ,
Type 3: Myocardial In arction Resulting in Death When Biomarker - .
Values Are Unavailable M
Cardiac death with symptoms suggestive o myocardial ischemia and ,
presumed new ischemic electrocardiogram (ECG) changes or new le t bundle .T (0.5 -
branch block (LBBB), but death occurring be ore blood samples could be ). M (
obtained or be ore cardiac biomarker could rise, or in rare cases, cardiac
5 ) (2–4 ),
biomarkers were not collected.
,
Type 4a: Myocardial In arction Related to Percutaneous Coronary .
Intervention (PCI)
I beta blockers
Myocardial in arction associated with PCI is arbitrarily de ined by elevation o STEMI. T , -
cardiac troponin (cTn) values >5 × 99th percentile upper re erence limit (URL)
O2 .M
in patients with normal baseline values (≤99th percentile URL) or a rise o
cTn values >20% i the baseline values are elevated and are stable or alling. ,
In addition, either (i) symptoms suggestive o myocardial ischemia, or (ii) ( “B -A
new ischemic ECG changes or new LBBB, or (iii) angiographic loss o patency B ” ). A ,5
o a major coronary artery or a side branch or persistent slow or no low or 2–5 ,
embolization, or (iv) imaging demonstration o new loss o viable myocardium >60 / , >100 H , PR <0.24 ,
or new regional wall motion abnormality is required.
10 .F
Type 4b: Myocardial In arction Related to Stent Thrombosis ,
Myocardial in arction associated with stent thrombosis is detected by coronary 50 6 48 , 100 12 .
angiography or autopsy in the setting o myocardial ischemia and with a rise P
and/or all o cardiac biomarker values with at least one value above the STEMI. O 24
99th percentile URL.
: (1)
Type 5: Myocardial In arction Related to Coronary Artery Bypass , (2) - , (3) -
Gra ting (CABG) , (4) (PR
Myocardial in arction associated with CABG is arbitrarily de ined by elevation >0.24 , - - , ,
o cardiac biomarker values >10 × 99th percentile URL in patients with ).
normal baseline cTn values (≤99th percentile URL). In addition, either (i) new
U ,
pathologic Q waves or new LBBB, or (ii) angiographic documented new gra t or
new native coronary artery occlusion, or (iii) imaging evidence o new loss o , -
viable myocardium or new regional wall motion abnormality. .
Source: K Thygesen: Eur Heart J 33:2551, 2012.
MANAGEMENT STRATEGIES
T
T - 12- ECG. W ST- 2
75–162 . 1
I O2 , O2 , reperfusion
- . therapy (F . 269-1 269-4). T
H , , O2 PCI ( ; Chap. 270)
(2–4 L/ ) 6–12 - .I ST- ,
; , .
.
LIMITATION OF INFARCT SIZE
CONTROL OF DISCOMFORT T
S nitroglycerin STEMI.
U 0.4 5- .W
. I , ,
( ) -
( ) - , O2 ,
( - ). I ,
( . .,
, - - ). U -
ST- STEMI spontaneous - -
T- , - 24
.T . R , ( )
(<90 H ) PCI, -
RV ( ECG,
1878
STEMI patient who is a
candidate for reperfusion
Initially seen at a
non-PCI-capable
PART 6
Initially seen at a hospital*

PCI-capable DIDO time ≤30 min
hospital
Send to cath lab

for primary PCI
Transfer for Administer fibrinolytic
FMC-device time primary PCI agent within 30 min of
≤90 min FMC-device arrival when
(Class I, LOE: A) time as soon as anticipated FMC-
possible and device >120 min
≤120 min (Class I, LOE: B)
(Class I, LOE: B)
Diagnostic angiogram
Urgent transfer for Transfer for
PCI for patients angiography and
with evidence of revascularization
failed reperfusion within 3–24 h for
or reocclusion other patients as
Medical PCI CABG
(Class IIa, LOE: B) part of an
therapy only
invasive strategy†
(Class IIa, LOE: B)
*Patients with cardiogenic shock or severe heart failure initially seen at a non–PCI-capable hospital should be transferred for cardiac
catheterization and revascularization as soon as possible, irrespective of time delay from myocardial infarction (MI) onset (Class I, LOE: B).
†Angiography and revascularization should not be performed within the first 2–3 h after administration of fibrinolytic therapy.
FIGURE 269-4 Reper usion therapy or patients with ST-segment elevation myocardial in arction (STEMI). The bold arrows and boxes are the pre erred strategies.
Per ormance o percutaneous coronary intervention (PCI) is dictated by an anatomically appropriate culprit stenosis. CABG, coronary artery bypass gra t; DIDO,
door-in–door-out; FMC, rst medical contact; LOE, level o evidence; STEMI, ST-elevation myocardial in arction. (Adapted with permission rom P O’Gara et al: Circulation
127:e362, 2013.)
2–3
- .T .H , PCI ,
– , ,
(F . 269-4).
.P
O2 ■ FIBRINOLYSIS
, - I ( ),
(CHF), 30 ( . ., - -
“ ” ≤30 ). T -
. .T
G - , ( PA), , (TNK),
, STEMI. ( PA) U.S. F D A -
T STEMI. T
, .I , ,
, . A
. - ,
PA, - - , ,
■ PRIMARY PERCUTANEOUS CORONARY ,
INTERVENTION . TNK PA
(See also Chap. 270) PCI, / bolus fibrinolytics
, primary PCI, - .
STEMI W ,
MI. I Thrombolysis in
( ) Myocardial Infarction (TIMI) grading system: 0
. - ; 1 -
I ,
, when performed by experienced operators in dedicated ; 2 -
medical centers, - - - ,
.C , PCI ; 3
, , .T
, , -
, C - 1879
LV , - - (1)
.A ( ST-
>90 ), rescue PCI ; (2) -

- ( - ST /
(TIMI frame count) ) (
(TIMI myocardial per- ), urgent PCI .

fusion grade). T - R elective PCI
STEMI TIMI . -
PA - , ,
PA TNK,
— . ., TIMI 3 — .C
.T PA PCI
15- 50 -
30 , 35 60 .S - .
1.5 (MU) 1 . PA -
- 10-MU HOSPITAL PHASE MANAGEMENT
2–3 , 10-MU 30 . TNK
- 0.53 / 10 . I
■ CORONARY CARE UNITS
T -
,
-
-
. D , ,
, .
,
C
- -
, -
.E
,
;
(
, , ;
>180 H / >110 H )
, , .
, ,
P
( ). W
, -
.T -
-
- ( . .,
. )
Relative contraindications , - “ .”
- - , - T
( ≥2), (<2 ) .I
(>10 ) - , .A ,
, , , STEMI
( . ., ), ( , CHF,
, - , )
.B , 24 .
5 2 . Activity F -
Allergic reactions ~2% .T ,
.W 4–10% STEMI 6–12 .
, , , H , , -
. , ,
Hemorrhage
.B 24 . T
, .I
, ,
. H - -
~0.5–0.9% , .
.T , >70 B 3 , -
185 (600 ) .
<65 .L - Diet B STEMI,
PA PA .
■ INTEGRATED REPERFUSION STRATEGY 4–12 . T -

≤30%
E PCI -
≤300 / .C 50–55%
STEMI. P -
.P ,
-
, ,
, .D
STEMI PCI (F . 269-4). T
.
STEMI,
STEMI Bowel Management B
.A
- . , ,
1880 (200 / ) - .A LMWH
.I , , -
.C , , X :II .E -
STEMI.
/ / /
PART 6
Sedation M UFH STEMI

.D
.T
(5 ), (15–30 ), (0.5–2 ),
, —
, .A — UFH.
.
I
A
STEMI
, 24- -
(OASIS-6). F STEMI
’ .H , ,
, .M
UFH .O -
, , H2 , ,
,
, .T
PCI
,
UFH .
’
C -
.
UFH II /III
.B ,
PHARMACOTHERAPY ≥5
■ ANTITHROMBOTIC AGENTS .
T P , LV -
STEMI , , , - -
,
.T - .S -
- ,
.A (LMWH UFH) , 3
’ , , .
- ,
. T ■ BETA-ADRENOCEPTOR BLOCKERS
T STEMI
STEMI.
A ( “M E -
D ” ), .A
STEMI. T O2 - , ,
( )
STEMI , -
A T ’C . .I
D 20,000 MI 15 , -
27% - , .
, 14.2% 10.4% T , - STEMI
. ( -
I P2Y12 ADP - [ACE] )
.T P2Y12 ( LV ,
STEMI , , )
( , , ) , - (
, <1% , <55 , MI,
.N P2Y12 ADP , ,
, , ) .
STEMI
PCI, . ■ INHIBITION OF THE RENIN-ANGIOTENSIN-
G II /III ALDOSTERONE SYSTEM
STEMI PCI. ACE STEMI,
T - .
(UFH). T UFH T - (
- - , , /
, ( LV ), -
5 1000 ). I ACE
UFH, STEMI ( . .,
- ( PA, PA, TNK), >100 H ). T
- .T ( “V D ”
.T - ) CHF. T -
UFH 60 U/ ( 4000 U)
12 U/ ( 1000 U/ ). ACE .
T B , LV
1.5–2 . . ACE
A UFH STEMI CHF, -
- - (LMWH) , LV
( ), , .
A (ARB ) ; IV, <90 H 1881
STEMI ACE , , -
. L - , .W
STEMI - 1967,

( ≥2.5 / L : I, 0–5%; II, 10–20%; III, 35–45%;
≥2.0 / L ) ( ≥5.0 E /L) IV, 85–95%. W ,
ACE , , - - .
LV ≤40%, H LV
.A - 20–25% .
- I ≥40%
– – - (Chap. 298). P (S -G ) -
STEMI, ACE LV ;
STEMI . /
CHF. C
■ OTHER AGENTS .W
F ,
( ) intravenous .S
nitroglycerin (5–10 μ / 200 μ / STEMI LV (>22 H )
) 24–48 (2.6–3.6 L/[ / 2]),
.H , LV (<15 H )
- .T ,
ACE .
STEMI.
R ■ HYPOVOLEMIA
T
STEMI. T , STEMI
.S .I ,
STEMI .S , / -
, - .C ,
. STEMI
.C -
COMPLICATIONS AND THEIR MANAGEMENT RV LV
, LV
■ VENTRICULAR DYSFUNCTION RV
A STEMI, , STEMI. T LV -
, . .E ’
T ventricular remodeling - ( ~20 H ) -
CHF .E ,
.S STEMI, .
, LV
A , , . .,
, ,
.
,
.L ,
.T TREATMENT
, Congestive Heart Failure
, T CHF STEMI
, .P -
ACE ( , , ,
( . ., ). I - ) (Chap. 252), -
<40%, , ACE STEMI . B ,
ARB ( “I R - ,
A -A S ” ). / .
LV
■ HEMODYNAMIC ASSESSMENT -
P - .T , ,
STEMI. T
, ( 10 ) , , , , , -
.T S3 .N
S4 .P .O ,
.E LV - ,
,
.I ,
( ) / , -
( ) (Chap. 252). LV .V
A K .A ,
: I, ; ACE -
II, , STEMI, . (S
S3 , , , “I R -A -A S ” .)
; III, ,
1882 ■ CARDIOGENIC SHOCK ,
P , .F ,
MI , -
20 7%. O ,
10% , , is no
PART 6
90% .T , longer recommended.

S -
” “ (
. The evaluation and management of cardiogenic 150 10 , 1.0 / 6
shock and severe power failure after STEMI are discussed in detail 0.5 / ). A -
in Chap. 298. ( 15 / 20–30 ; 1–4 / ). I

,
■ RIGHT VENTRICULAR INFARCTION (Chap. 241). A 200–300 J ( -
A - - ; ~50% )
RV .A
LV RV , . V -
RV. C
RV RV ( (1
,K ’ , [Chap. 234]) 10 L 1:10,000 )
. ST- - ( 75–150- ).
ECG , V4R, 24 V ,
RV .T - (Chaps. 247 and 249),
RV .C STEMI
- ( , , -
( “ ” )
RV ) (Chap. 265). ( ). A
T RV - .
LV A - , -
.
primary ; . ., -
■ ARRHYTHMIAS 48
(See also Chaps. 239 and 241) T CHF, ,
STEMI . , .T
T -
, , - secondary .F
, .A ( . .,
48 ), -
. S - - .S
-
, (ICD) (Chap. 247). A -
. T
STEMI
STEMI. .A
Ventricular Premature Beats I , ICD
STEMI Fig. 269-5.
.W , , , Accelerated Idioventricular Rhythm A -
( - ) (AIVR, “ ”),
60–100 / ,
, .F
, AIVR,
. P ( ,
) .M AIVR
,
, .
.B - -
STEMI Supraventricular Arrhythmias S
.A .I
( “B -A B ”), ( , , , -
.I , - ), . H ,
( . .,
STEMI; , ), .
~4.5 /L 2.0 /L. O
, LV .D -
Ventricular Tachycardia and Fibrillation W
24 STEMI, - .I , , ,
. T - ,
.I -
.H , >2 >120 / ,
STEMI. I , , , (
1883
Sudden cardiac death
Learn more at
primary prevention protocols www. HRSonline.org

35% for Nonischemic cardiomyopathy
Ejection fraction ≤
40% for Ischemic cardiomyopathy
Any Post-MI or Ischemic Any

cardiomyopathy Post-MI
cardiomyopathy With revascularization Without revascularization cardiomyopathy
Not on optimal ICD waiting period >40 days Beyond ICD waiting period
(PCI or CAB)
medical therapy on Optimal Medical Therapy
ICD waiting period >3 months
Initiate or titrate medical therapy

Beta blocker — ACE/ARB — Aldosterone antagonist
Discharge home; Continue optimization of medical therapy

Consider consultation with heart rhythm specialist/consider wearable cardioverter defibrillator
Reassess EF @ 3 months Reassess EF @ 40 days
Nonischemic Consider further risk stratification/

Ischemic EF = 36–40% Consultation with heart rhythm
cardiomyopathy cardio- specialist*
EF ≤35% myopathy EF ≤35%
Refer for consultation with Heart Rhythm specialist
* Buxton AE, Lee KL, Fisher JD, Josephson ME, Prystowsky EN, Hafley G.A randomized study of the prevention of sudden death in patients with coronary artery disease.
Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med. December 16, 1999;341(25):1882–1890.
Recommended by SCA Prevention Protocols Working Group (Version 2; Revised; 9/10/2012; Review date: 9/10/2013) All rights reserved. Copyright ©2012 Heart Rhythm Society
FIGURE 269-5 Algorithm or assessment o need or implantation o a cardioverter-defbrillator. The appropriate management is selected based on measurement
o le t ventricular ejection raction, the timing ollowing in arction, and whether revascularization has been per ormed. (Reproduced rom data at www.hrsonline.org.)
ECG ), (100–200 J - P
) . ,
A , ,
. D .A , RV ,
.I LV ,
- .I , - AV
.R .
. E
“ ” (
Sinus Bradycardia T
<50 / ) ,M II -
.A -
AV , - ,
( . .,
0.5 . I
). R
<50–60 / , 0.2 , 2.0 ,
-
.P (<40 / )
.I .
- MI.
Atrioventricular and Intraventricular Conduction Distur-
bances (See also Chap. 239) B - ■ OTHER COMPLICATIONS
Recurrent Chest Discomfort B
(AV)
AV -
.T STEMI,
/ .
.I A -
, , - .
,
. Pericarditis (See also Chap. 265) P /
T - STEMI
AV .H - .T
, (650 ). I
,
- /
.I . , ,
1884 , , .W , - ,
,
.A - .A , , ( -
( ) 4–6 .
PART 6
) E LV .R
. LV
Thromboembolism C -
- - .P
STEMI ~10% , 20%
,
,
-
.T -
, ,
25% STEMI
.A LV
MI (F . 269-5).
, .
C /
T
.
( ), CHF, LV
E -
. T
,
.T -
. I
LV -
, -
-
, ’
.A
.
,
I , -
.W
.
I ,
-
.
,
T STEMI
(
3–5 .T
),
.D 1–2 ,
.T
-
, 3–6 .
.N
Left Ventricular Aneurysm T ventricular aneurysm .A 2 , ’
dyskinesis .M
. N 2–4 .
; , SECONDARY PREVENTION
.T V
. -
T LV STEMI. L - (
STEMI; CHF, , ) STEMI 25%
.A , , (36
.T 1000 ). A
, , .
V - - (75 ). ACE ARB
, . , ,
R , , -
, . O ,
, pseudoaneurysm ,
LV .B .
, . T -
2 STEMI - , -
POSTINFARCTION RISK STRATIFICATION .
AND MANAGEMENT E
M - STEMI. M -
STEMI. S (
( ), LV (<40%), “T ” ). S
<75 (75–81 / )
, . O
>2.0 MI
MI, >75, , , - .H ,
, ST- (“ ”),
- ECG, - - .
( ), T
(see Chap. 267). H ,
ECG. T
() . .S
T
STEMI .I
(PCI) 1885
. U S
F , atherosclerosis (Chap. 232) - : 900,000 .
, , . I
CHAPTER 270 Percutaneous Coronary Interventions and Other Interventional Procedures

1-
■ FURTHER READING 3-
Al-Khatib SM :D :S . T
.C 134:1390, 2016.
Claeys MJ: I ;
? JAMA I M 175:216, 2015. , -
Hollander JE :S - - - - , , ,
. .
C 134:547, 2016.
Kidambi A, Plein S: R TECHNIQUE
:G T
.E H J 37:1060, 2016. (Chap. 237). A
Levine GN : 2015 ACC/AHA/SCAI .T
ST- ,
: A 2011 ACCF/AHA/SCAI (325 ) P2Y12
2013 ( 600 ), (
ACCF/AHA ST- - 60 ), ( 180 ) .
:A A C C / C , IV P2Y12 ,
A H A T F C P G - . D
S C A I - , -
.C 133:1135, 2016. , ( - - ),
Mannsverk J :T ( ). I ST-
- , - ,
.C 133:7, 2016. , II /III
Montecucco F :P ST- - ( , , ) ,
: N .E H J .
37:1268, 2016. F , -
Mozaffarian D :H —2016 :
A A H A .C 133: 3, . T , ,
2016.
Sugiyama T :D ;
ST .T “ ”
U S , 2001–2011. JAMA 4: 001445, , ,
2015. .T
.T
.O
.B PCI
, (1- )
Percutaneous Coronary .
270 Interventions and Other A
, (Figs. 270-1
Interventional Procedures and 270-2). T -
.O ,
David P. Faxon, Deepak L. Bhatt
-
.I ,
P (PTCA) ( ). S
A G 1977
. T C (F . 270-1).
D 1964 .T - S >90% -
G .S (
.I - , )
- - .W ,
.A “ ” .T
, -
.O ,
.T , -
1994 .T .S
( ). .
F D - PCI. A -
- 2003. T - -
.P .T 1-
1886
PART 6
A B C D
FIGURE 270-1 Schematic diagram o the primary mechanisms o balloon angioplasty and stenting. A. A balloon angioplasty catheter is positioned into the stenosis
over a guidewire under fuoroscopic guidance. B. The balloon is infated, temporarily occluding the vessel. C. The lumen is enlarged primarily by stretching the vessel,
o ten resulting in small dissections in the neointima. D. A stent mounted on a defated balloon is placed into the lesion and pressed against the vessel wall with balloon
infation (not shown). The balloon is defated and removed, leaving the stent permanently against the wall acting as a sca old to hold the dissections against the wall
and prevent vessel recoil. (Adapted rom EJ Topol: Textbook o Cardiovascular Medicine, 2nd ed. Philadelphia, Lippincott Williams & Wilkins, 2002.)
3- .D -
50%, - .I ,
5–10% .N - (BVS)
, ; -
80–90% - . T - .A -
.S - .D -
- , , ,
.T - - - .
, O
, - , , .T -
- .B
. R
’ ,
1.25–2.5 .
T
.B
≤25 μ ,
.T
. G
, .O
.D
. I ST-
,
A
.
C
,
, PCI.
PCI
, PCI .A -
.M
PCI. I , -
, PCI,
.
B
FIGURE 270-2 Pathology o acute e ects o balloon angioplasty with intimal
SUCCESS AND COMPLICATIONS
dissection and vessel stretching (A) and an example o neointimal hyperplasia
A ( ),
and restenosis showing renarrowing o the vessel (B). (Panel A rom M Ueda et al: 20% , 95–99%
Eur Heart J 12:937, 1991; with permission. Panel B rom CE Essed et al: Br Heart . L ,
J 49:393, 1983; with permission.) , . C
- (TLR TVR) 1887
( 3 ) .T
.I PCI
- .O -

70–80%. , .T
S , , ,
0.1–0.3% , <3%, - , PCI .
<0.1%. P (>65 ),
, , INDICATIONS
ST- (STEMI), T A C C (ACC)/A H A -
.S (AHA) PCI
.M PCI , , NSTEMI, STEMI
, .
, B ,
, chronic stable angina (Chap. 267) (1)
.M -
(CPK) (2)
.O - .I
( ) , C O -
- .C U R A D E
. (COURAGE) B A R I
A (1–3%), 2D (BARI 2D)
(<24 ) (1–30 ), ( MI)
- -
(DAPT) ( , P2Y12 .W ,
[ , , ]). L (30 –1 ) PCI CABG .
(>1 ) T S P C I T
- - , C S (SYNTAX) PCI
DAPT 1 .U - - CABG 1800 -
.T
, DAPT (6 ) - 1 , -
.P DAPT, - (13.5 5.9%),
, (2.2 0.6%). T -
( - ). S , , , -
10–20% 30–70% CABG,
.E - .
- T 5- .T F R
3 6 , . E P W D M :O M
R , , M D (FREEDOM) 1900
20–50%
, 10–30% , , CABG
, 5–15% - PCI. R PCI CABG
. T -
.
D - -
-
.I
, -
(Fig. 270-3). C
12 -
.L , -
-ST-
(NSTEMI)
(10%) STEMI (2%) . V
1
-
.C
PCI. Target lesion revascu-

larization (TLR) target vessel revascular-
ization (TVR)
PCI
(CABG). B - FIGURE 270-3 Long-term results rom one o the frst patients to receive a sirolimus-eluting stent rom early
, Sao Paulo experience. (From GW Stone, in D Baim [ed]: Cardiac Catheterization, Angiography and Intervention,
7th ed. Philadelphia, Lippincott Williams & Wilkins, 2006; with permission.)
1888 , ,
.T - PCI, .
CABG -
.L OTHER INTERVENTIONAL TECHNIQUES
PCI,
PART 6
. ■ STRUCTURAL HEART DISEASE

T PCI CABG I (
PCI CABG. )
F PCI, .
.T ( ), T -
, .I (Chap. 264). T
, , -
, , , , .W
.T PCI ,
() ’ ,
.T .A
(>3 ) .A
.T A S O
PCI ACC/AHA. L (AGA M ,M ,M )
A ( - - U S .T 85–95%,
), ,
C ( ). I , .C (PFO)
B1 B2 . PFO
.A 25–30% (TIA)
PCI , 5%
CABG .T CLOSURE I 909 -
. T TIA PFO. C
CABG , 30
, (COPD), 2 - /TIA 2 .O
, .H , 10-
. R E R S C PFO
A C E C S C T (RESPECT)
.I ,
>2 - .T -
, PCI .
.A S
(FFR) .O
(Chap. 237) - ,
.T F F R A M - , , -
E (FAME) 30% .
PCI T
(FFR ≤0.80) .U , -
.T , , ,
(Chap. 256). M
.G
.T
, .T
, , .T
( - H T )
. .A
P -
- .R
PCI
, .A ,
. H - -
: , , .T
- , ST- , I .T
, , PCI CABG. PCI
- . T
95% (1–2%). T
. I STEMI, PCI ( PCI)

- .
12 .B PCI S
, M C (A , A P , I ) . T
90 . PCI -
- .A
. .T - 1889
T ,
A .I
E V E - -E R S (EVEREST II) , (Fig. 270-5). T -

-
.S .P
, ,
. -
S .T
.I , (Chap. 275).
■ CIRCULATORY SUPPORT TECHNIQUES
.T ,
2 T -
50% >1
-
25–50% 6–12 .T
PCI
-
.I
(TAVR). I ,
.T
- (10%).
1960 . A
R 7- 10-F , 25- 50- L
.
P TAVR .I
, - , .
C , , E SAPIEN (E - .A ,
L , I , C ) C V R V , ,
(M , M , M ) . I
50,000 2002, - ( ). T
, .I
- 5–10 .T C V , , .T
- , E .T .I
(14–22 F ), .
, .I A I (A ,D ,
, , , M ). T I
. F - .T
, 2.5–5 L/
- .T
.T >90%, 30- .O T -
2–15% .T P A T - H (C A ,P ,P ),
V (PARTNER) E 21-F
55% 1-
- TAVR - .A
.I , - - 5L .I
1 .A STEMI - - PCI. P
, - , - , (ECMO)
- . .T
A
, - , - - - .
.I
.
P
-
M
(M ). T
.
■ PERIPHERAL ARTERY
INTERVENTIONS
T
, , , -
-
.R
(Fig. 270-4). R -
- A B
, FIGURE 270-4 A. An example o a high-risk patient who requires carotid revascularization, but who is not a
’ - candidate or carotid endarterectomy. B. Carotid artery stenting resulted in an excellent angiographic result.
, (From M Belkin, DL Bhatt: Circulation 119:2302, 2009; with permission.)
1890
PART 6
A B C
D E
FIGURE 270-5 Peripheral interventional procedures have become highly e ective at treating anatomic lesions previously amenable only to bypass surgery. A.
Complete occlusion o the le t super cial emoral artery. B. Wire and catheter advanced into subintimal space. C. Intravascular ultrasound positioned in the subintimal
space to guide retrograde wire placement through the occluded vessel. D. Balloon dilation o the occlusion. E. Stent placement with excellent angiographic result. (From
A Al Mahameed, DL Bhatt: Cleve Clin J Med 73:S45, 2006; with permission. Copyright © 2006 Cleveland Clinic Foundation. All rights reserved.)
■ INTERVENTIONS FOR PULMONARY EMBOLISM —PCI CABG—

T , .T
.S
(PE) . P ,
.P - .
,
. ■ FURTHER READING
PE Faxon DP, Williams DO: I : C
.S .
PE C 133:2697, 2016.
Levine GN : 2011 ACCF/AHA/SCAI G P
.C - PE C I :E S :AR A
, . T C C F /A H A T
F P G S C A -
(10 F ), I .C 124:2574, 2011.
, - - , Moscucci M ( ): Grossman & Baim’s Cardiac Catheterization, Angiog-
.S raphy, and Intervention 8 .P ,L W &
80–90%, 2–4% W , 2014.
. Vahl TP :T 2016: A -
“T - ” . J A C C
■ INTERVENTIONS FOR REFRACTORY HYPERTENSION 67:1472, 2016.
T
-
.T -
.I
S HTN-2 ,
.T S -
(M ,M
U.S. S
)
HTN-3
E ,
.
271 Hypertensive
Disease
Vascular
F
U S . Theodore A. Kotchen
CONCLUSION
I .T H
, , - .E -
.T - , 9.4 .H
,
PCI. PCI (CHD), (CHF), -
.F , PCI , , (PAD). I
.U H T ,
. C , , 1891
.A - -
,
. - ,
CHAPTER 271 HypertensiveVascular Disease

, . .,
EPIDEMIOLOGY - - , ,
B , - - -2 , (
, ). O ,
.H ~1% ,
,
.I , 30–40%. O “
.I , ” DNA
. B .E
“ ” DNA .I
. I U S , DNA ,
, . E
- , .
. C , ≥60 , S
.A , .H ,
- DNA
~55 , .T - .
( P -
) 60.
I U S , ~78 .H - . F
33.5% -H , 28.9% - ,
H , 20.7% M A . T .F
,
≥60 , 65.4%. R . S
U S , CHD .I ,
. T DNA
U S .I A A , - .
, ,
, - MECHANISMS OF HYPERTENSION
, CHF, - (ESRD) A . T
A NHANES (N H N E ,
S ) , 2007–2010, 81.5%
, 74.9% , 52.5% .C -
. (Fig. 271-1). C
B ;
.S .P
“ ”
- ( 100–400 μ ) .
.O , -
■ INTRAVASCULAR VOLUME
.I 60%
S -
>20% . A , -
.W N C
N C , -
,
N C .
.H , -
L
,
.T - - (
,
)
,
.A
, , pressure across the vascular bed
. Blood Flow =
vascular resistance
■ GENETIC CONSIDERATIONS
T
A
;
M (T 271–5),
(>98%) -
.F , Stroke volume
Cardiac output
Heart rate
.F ,
, . ., , , Arterial pressure
. Vascular structure
A , , -
Peripheral resistance
.A
( ) Vascular function
FIGURE 271-1 Determinants o arterial pressure.
1892 , , ,
.W -
.W .C , -
, / , , -
, - , .
PART 6
.T C
; - , -
.A .
N C , F ,
α2 .R -
.T “ - ” - ,
α1 .
, , S - -
.I .O -
, .T
. ,
N C- ,
, .T
- ( -
) , ,
.R .H ,
.I , -
. .P -
C , -
. ESRD - - -
. I ~80% , - .
; 20%, I - ,
.B
- - (
- . ),
.S -
■ AUTONOMIC NERVOUS SYSTEM -
A , . B
, -
, - . “ ” .D
N , ,
. , -
T , ,
- (G ) - .
.I P
, - ,
- .B
“ ” .T α1
, - -
.B .
,
:α β. T ■ RENIN-ANGIOTENSIN-ALDOSTERONE
α1, α2, β1, β2 .R T - -
.αR -
, II - .R
β . α1 R
. α2 R , .M
.P
. W ,
α2 , .A
.I , α1- - ,
.D .T
α1 α2 : (1) N C
.A - H -
β1 ( ), (2)
. β1 R ( ), (3)
.A - - β1
β1 .A β2 .C ,
. N C H ,
C , β1
.D .I , II
- II 1 ,
, ,
.F , - (ACE) II .
A II 1893
Angiotensinogen
.A ,
Renin - -

. A
(ACTH) , ACTH
Angiotensin I .
Bradykinin
A
- (EN C)
ACE-kininase II -
(Chap. 303). E
. C ,
Inactive .B
Angiotensin II peptides
,
, , ,
, ,
.
C
11 β-
AT1 receptor AT2 receptor
2. C -
. P
- . I ,
- ,
.
Aldosterone
M
,
FIGURE 271-2 Renin-angiotensin-aldosterone axis. ACE, angiotensin-converting
enzyme. , ,
, , , -
O , , , -
, , I .T .I
(Fig. 271-2). A , - ,
, I , (
, II, C- - ) - .P -
.T -
, .
A II 1 (AT1) .I CHF, -
, II ,
- 30%. D ,
.I , II ,
- .
.T II 2 (AT2) I - -
AT1 . T AT2 .I -N C
, , , -
. E AT2 - -
.S ( . .,
- ), ,
. AT1 AT2 . CHF .
R - -
.I , - ■ VASCULAR MECHANISMS
, , V
, W ’ . R - .R
, , , , . , ,
R - - .I ,
.O - , ,
, .O , .R -
, .
- . H ( , -
A , , II )
, , , , , , , . A ,
, , , , , , , - ,
, , .A II .L .
, . ., , - V
, .I , , -
II ,
. E II .
, , , - A
.A -
. .A
1894 ,
.N - .M
T .
.D I .I ,
, ( , ) - , II,
PART 6
.E - (ROS), T
.T . ROS
- . ROS
.A -
, .I T
.I .R -
.
D , .C ,
, - .
. ., . T ,
, PATHOLOGIC CONSEQUENCES OF
- - .H , HYPERTENSION
. C
■ HEART
H
.C .H -
, - , CHF, -
. C ,
- . , .I -
I CHD, , CHF,
- - .A
, H ( H ). .
T H: CHF , ,
(1) N +-H+ , (2) N +- HCO3–-C – , .A
(3) - HCO3–-C – .B
. A -
( . ., , , , ), CHF .
N +-H+ , D -
.F ,
.C -
N +-C 2+
.S - .A , -
, H ,
, - .
.A , N +-H+
■ BRAIN
. S ;
V .T - 5 , 15
, .E -
, .E - - .A 85%
.T , -
- .T
5 . ,
A , - >65 .T
- - .
, . ., .E H
, ,
. - . H
C , - - ,
.I ,
.L - - -
- .
, , H -
. I “ ”
–
- .S
. -
, .
■ IMMUNE MECHANISMS, INFLAMMATION, AND C
OXIDATIVE STRESS ( 50–150 H )
I autoregulation .I
, -
. P ,
.B .S
, .T M 1895
( ), , R F I T (MRFIT), >350,000
.U , ,
, , , .I CHD ,

120 H .S ,
, . ., - 1
, , , , ,
, , , ,
, , , 115/75 H , .
. C 20- H
10- H .A
■ KIDNEY ,
T .P
.M - .
- C , -
, - –
, .C , - . C
ESRD. T
, , .O
.
R , , ( I II),
, ,
ESRD . (Table 271-1). I ,
A , - /
, >95 , , .B
.G 90 95
.
. S - H 24-
, , .B
-
,
, ,
.W .I ,
, - 24- ,
.B
.T , ,
.M
, , . .N 10–20%
G , ,
. “ ”
T .R ,
, 24- ,
, . ≥135/85 H ≥120/75 H .T
C , ( / 140/90 H .
>300 / ) ( / A 15–20% 1
30–300 / ) .T
<135/85 H , “ .” L - -
.
-
■ PERIPHERAL ARTERIES ( - - ).
I , T ,
-
.I , , -
, , - - -
.F , .I , “
. ”( - -
A ) .
, PAD.
T - PAD
TABLE 271-1 Blood Pressure Classification
( )
.A - <0.90 BLOOD PRESSURE
CLASSIFICATION SYSTOLIC, mmHg DIASTOLIC, mmHg
PAD >50%
.A - <0.80 Normal <120 and <80
, . Prehypertension 120–139 or 80–89
Stage 1 hypertension 140–159 or 90–99
DEFINING HYPERTENSION Stage 2 hypertension ≥160 or ≥100
F , Isolated systolic ≥140 and <90
.I , , hypertension
, , Source: Adapted rom AV Chobanian et al: JAMA 289:2560, 2003.
1896 CLINICAL DISORDERS OF HYPERTENSION TABLE 271-3 Secondary Causes of Systolic and Diastolic
D , ~80–95% - Hypertension
, “ ,” - Renal Parenchymal diseases, renal cysts (including
.I 5–20% , polycystic kidney disease), renal tumors (including
renin-secreting tumors), obstructive uropathy
PART 6
(Tables 271-2 and 271-3). I “ ” Renovascular Arteriosclerotic, ibromuscular dysplasia

, Adrenal Primary aldosteronism, Cushing’s syndrome,
. 17α-hydroxylase de iciency, 11β-hydroxylase
de iciency, 11-hydroxysteroid dehydrogenase
de iciency (licorice), pheochromocytoma
■ PRIMARY HYPERTENSION
Aortic coarctation
P -
. Obstructive sleep apnea
T , Preeclampsia/eclampsia
Neurogenic Psychogenic, diencephalic syndrome, amilial
.I dysautonomia, polyneuritis (acute porphyria, lead
poisoning), acute increased intracranial pressure,
acute spinal cord section
.I
Miscellaneous endocrine Hypothyroidism, hyperthyroidism, hypercalcemia,
, acromegaly
; , Medications High-dose estrogens, adrenal steroids,
, decongestants, appetite suppressants,
. cyclosporine, tricyclic antidepressants, monoamine
W (PRA) 24- oxidase inhibitors, erythropoietin, nonsteroidal
, ~10–15% PRA 25% anti-in lammatory agents, cocaine
PRA. H - Mendelian orms o See Table 271-4
, - - hypertension
. I
D
.T , ~25–50% ,
A A , PRA .T
A A .T , , ,
metabolic syndrome. A , - -
- ,
.F , , , ( )
, “ - ” .A
. ,
, .
■ OBESITY AND THE METABOLIC SYNDROME I
(See also Chap. 401) T - .T
2
( >30 / ) . F ,
- .E -
( ) . C
.
.I , S ,
.S >20% .I .
60–70%
. ■ RENAL PARENCHYMAL DISEASES
H V
- .T (T 271-3),
, , .H >80%
, .I - . I ,
.
, , , C , ,
.W , CHD,
, , .P >1000 /
. .I
,
.
TABLE 271-2 Systolic Hypertension with Wide Pulse Pressure
1. Decreased vascular compliance (arteriosclerosis) ■ RENOVASCULAR HYPERTENSION
2. Increased cardiac output H , -
a. Aortic regurgitation , .T
b. Thyrotoxicosis :
c. Hyperkinetic heart syndrome ,
d. Fever , .A -
e. Arteriovenous istula
. Patent ductus arteriosus
. A
, .T
, I 1897
, ,
. .I ,
R .P

.S
, ,
, , , -
.
ACE -
.A 50% ■ PRIMARY ALDOSTERONISM
, E
. I
. ,
I - , ,
, , PRA. T
(PTRA), ( ), <2 ~15% .
, I ,
.A , .
[131I]- (OIH) , - H
[99 T ]- .T
(DTPA) .H
( ACE ). I , , ; -
, . H
; , . M
( ; , , , -
<20 L/ ) . A , ,
.D .A - -
, .R
.P
, -
, .G - .
I ( . ., -
.A - , , ),
. 40–50%. I ,
C “ ” <3.1 /L (<3.1 /L)
. ; ,
S . S ~25%
50% , -
,
.
.E - T PRA (PA/PRA) -
, - . T
.F .A >30:1
>70% >555 /L (>20 / L)
.O , 90% 91% -
.A - .I M C , -
( >1.5 / ) >90%
90% PA/PRA ≥20 -
; , - ≥415 /L (≥15 / L). T , ,
50–60%. M . T “ ” -
. - .S -
I , ( . ., , ,
.I ACE ;
). C -
, - 4–6
.S .B -
PTRA - ,
.W ,
.I ,5 7
. T ,
- . A
-
.P
- , , , A A
.T .I , -
ACE .I
II ; , - PA/PRA ,
.
1898 <277 /L (<10 / L) IV 2L -
4 ; - 138 .T
277 /L (5–10 / L) .A - (18-
( - 18- ) .T
) N C , , .
PART 6
S 20–30 .T , -
, ACTH - -
.T - , , .A
- .P II
.T , >90% III .
.T
, <3 . M ■ CUSHING’S SYNDROME
(See also Chap. 379) C ’
( ). R , ACTH (
, . ., ) ACTH- -
.M - , .H 75–80%
, C ’ .T
.F
- . I
.A ACTH , -
,
.C , 24- - -
, - .L
ACTH, .F
, C ’ .
- - A .
.H , -
.R ■ PHEOCHROMOCYTOMA
- - (See also Chap. 380) C -
II III. G ( ) - -
. ( ) ~0.05%
A (CT) . I ,
. H - CT .C , -
0.3 , ,
90% .I CT ,
6 β-[I131] -19- .I , -
(0.5 6 ,
7 ); , - .T
<1.5 . / -
W , (Table 271-4). A 20%
-
- .I
.T (MEN) 2A 2B, H -L
(95 100%, ) - , (T 271-4). E
CT; , - .A ,
90–96%, <2.5%. O -
,
ACTH . A / .L -
>4, ACTH- , , . ., 24-
. - . T
H - . G
.U -
, , . S
40–70% .T
3 , , ~90% .
- -
, .P ■ MISCELLANEOUS CAUSES OF HYPERTENSION
.T , I , >50%
, obstructive sleep apnea. T
, , - .A 70%
. .H
G - , -
.T
, .T .I ,
.H .C
.N , II (CPAP) (B PAP) -
, ACTH - .
.O W CPAP B PAP, - -
8, ACTH .
TABLE 271-4 Rare Mendelian Forms of Hypertension 1899
DISEASE PHENOTYPE GENETIC CAUSE

Glucocorticoid-remediable Autosomal dominant Chimeric 11β-hydroxylase/aldosterone gene on
hyperaldosteronism

Absent or mild hypokalemia chromosome 8
17α-hydroxylase de iciency Autosomal recessive Random mutations o the CYP17 gene on
Males: pseudohermaphroditism chromosome 10
Females: primary amenorrhea, absent secondary sexual characteristics
11β-hydroxylase de iciency Autosomal recessive Mutations o the CYP11B1 gene on chromosome
Masculinization 8q21-q22
11β-hydroxysteroid dehydrogenase Autosomal recessive Mutations in the 11β-hydroxysteroid
de iciency (apparent Hypokalemia, low renin, low aldosterone dehydrogenase gene
mineralocorticoid excess
syndrome)
Liddle’s syndrome Autosomal dominant Mutation subunits o the epithelial sodium
Hypokalemia, low renin, low aldosterone channel SCNN1B and SCNN1C genes
Pseudohypoaldosteronism type II Autosomal dominant Linkage to chromosomes 1q31-q42 and
(Gordon’s syndrome) Hyperkalemia, normal glomerular iltration rate 17p11-q21
Hypertension exacerbated in Autosomal dominant Missense mutation with substitution o leucine or
pregnancy Severe hypertension in early pregnancy serine at codon 810 (MRL810)
Polycystic kidney disease Autosomal dominant Mutations in the PKD1 gene on chromosome 16
Large cystic kidneys, renal ailure, liver cysts, cerebral aneurysms, and PKD2 gene on chromosome 4
valvular heart disease
Pheochromocytoma Autosomal dominant
(a) Multiple endocrine neoplasia, type 2A (a) Mutations in the RET protooncogene
Medullary thyroid carcinoma, hyperparathyroidism
(b) Multiple endocrine neoplasia, type 2B (b) Mutations in the RET protooncogene
Medullary thyroid carcinoma, mucosal neuromas, thickened corneal
nerves, alimentary ganglioneuromatoses, mar anoid habitus
(c) von Hippel-Lindau disease (c) Mutations in the VHL tumor-suppressor gene
Retinal angiomas, hemangioblastomas o the cerebellum and spinal
cord, renal cell carcinoma
(d) Neuro ibromatosis type 1 (d) Mutations in the NF1 tumor-suppressor gene
Multiple neuro ibromas, ca é-au-lait spots
Coarctation of the aorta . S

(Chap. 264). T 1–8 1000 -
.I 35% T ’ .I 17α-
.E ,
, 30% (Fig. 271-3). C , ;
-
.P .B
.P - ACTH
, ACTH-
, , .H
.A
.T , . I
- . T , , -
, - . A 11β- -
.S , 1 100,000 .
- T ,
, , , ( . ., ), -
. .I
S , thyroid diseases , ,
acromegaly, .M ,
, ,
. Hypercalcemia , .A , ,
, -
.H . H -
- - medications. .P 11β-
-
MONOGENIC HYPERTENSION , , -
I - , .T ,
- . T
(T 271–4). T .T
, L ’ (Chaps. 49 and 379)
1900
Cholesterol
(17α hydroxylase)
PART 6
Pregnenolone 17 OH Pregnenolone DHEA

Progesterone 17 OH Progesterone Androstenedione Testosterone
(21 hydroxylase)
Deoxycorticosterone Deoxycortisol
(11β hydroxylase)
Corticosterone Cortisol
(11β hydroxysteroid dehydrogenase)
Aldosterone Cortisone
Mineralocorticoid Glucocorticoid Androgen

FIGURE 271-3 Adrenal enzymatic de ects. DHEA, dehydroepiandrosterone.
- EN C , TREATMENT
;
.H (Chap. 466) Hypertension
.
LIFESTYLE INTERVENTIONS
I
APPROACH TO THE PATIENT -
Hypertension .H -
HISTORY AND PHYSICAL

T
TABLE 271-5 Relevant History and Physical
, , History
, Duration o hypertension
, Previous therapies: responses and side e ects
– , - Family history o hypertension and cardiovascular disease
.M Dietary and psychosocial history
. Table 271-5 Other risk actors: weight change, dyslipidemia, smoking, diabetes, physical
inactivity
. Evidence o secondary hypertension: history o renal disease; change in
R appearance; muscle weakness; spells o sweating, palpitations, tremor;
. erratic sleep, snoring, daytime somnolence; symptoms o hypo- or
P , , hyperthyroidism; use o agents that may increase blood pressure
.O Evidence o target organ damage: history o TIA, stroke, transient blindness;
, angina, myocardial in arction, congestive heart ailure; sexual unction
Other comorbidities
. T - Physical
, . Body habitus
LABORATORY TESTING Blood pressure in both arms
Table 271-6 - Supine and standing blood pressures
.R - Funduscopic examination o retina
, , , Quality o emoral and pedal pulses
Vascular and abdominal bruits
.M Cardiac rate and rhythm
- Signs o congestive heart ailure
Signs o secondary hypertension
.
Abbreviation: TIA, transient ischemic attack.
TABLE 271-6 Basic Laboratory Tests for Initial Evaluation .I , 1901
SYSTEM TEST
Renal Microscopic urinalysis, albumin excretion, serum
BUN and/or creatinine .

T DASH (D A S H ) -
Endocrine Serum sodium, potassium, calcium, TSH
8-
Metabolic Fasting blood glucose, total cholesterol, HDL and
LDL (o ten computed) cholesterol, triglycerides
, , -
- -
Other Hematocrit, electrocardiogram
.R N C <6 (100 )
Abbreviations: BUN, blood urea nitrogen; HDL, high-density lipoprotein; LDL, low- .F
density lipoprotein; TSH, thyroid-stimulating hormone.
, , ,
.
. T
PHARMACOLOGIC THERAPY
.A
L 10–12 H
, - , 5–6 H
N C 35–40% 12–16% CHD 5 -
.I , - .T >50%;
, ,
.D
, N C - .
, , - T -
, (Table 271-7). ,
P
.I - , - .M -
- 7–13 H
.A 4–8 H .M
6.3/3.1 H , ,
9.2 .R , -
, , . S
.B 30 , ,
, , 6–7 , ,
, , . , , ,
T (Table 271-8).
N C, .S Diuretics L -
N C .B .T
- , N C N +/C –
4.4–7.4 (75–125 ) .I ,
3.7–4.9/0.9–2.9 H .T , , ,
. R . T –
, -
; , (ACEI ), (ARB ).
, I ,
.A .U 6.25
- 50 / .O
, - ( , , ),
.C
CHF .P - , -
, - , -
, , , . H , - (40–60
. 9–15 ) ~1.5–2.0
C ( .P -
~14 ) - .T - , ,
, EN C .T
.T
TABLE 271-7 Lifestyle Modifications to Manage Hypertension N +-K+-2C –
Weight reduction Attain and maintain BMI <25 kg/m2 H .L
Dietary salt reduction <6 g NaCl/d -
Adapt DASH-type dietary Diet rich in ruits, vegetables, and low- at dairy ( >220 μ /L [>2.5 / L]),
plan products with reduced content o saturated and CHF, ,
total at , . ., .
Moderation o alcohol For those who drink alcohol, consume ≤2
consumption drinks/d in men and ≤1 drink/d in women Blockers of the Renin–Angiotensin System ACEI
Physical activity Regular aerobic activity, e.g., brisk walking or II, ,
30 min/d . ARB -
Abbreviations: BMI, body mass index; DASH, Dietary Approaches to Stop AT1 , II
Hypertension (trial). AT2 .B
1902 TABLE 271-8 Examples of Oral Drugs Used in Treatment of Hypertension
USUAL TOTAL DAILY
DOSEa (DOSING
DRUG CLASS EXAMPLES FREQUENCY/DAY) OTHER INDICATIONS CONTRAINDICATIONS/CAUTIONS
Diuretics
PART 6
Thiazides Hydrochlorothiazide 6.25–50 mg (1–2) Diabetes, dyslipidemia,

Chlorthalidone 25–50 mg (1) hyperuricemia, gout, hypokalemia
Loop diuretics Furosemide 40–80 mg (2–3) CHF due to systolic dys unction, renal Diabetes, dyslipidemia,
Ethacrynic acid 50–100 mg (2–3) ailure hyperuricemia, gout, hypokalemia
Aldosterone antagonists Spironolactone 25–100 mg (1–2) CHF due to systolic dys unction, primary Renal ailure, hyperkalemia
Eplerenone 50–100 mg (1–2) aldosteronism
K+ retaining Amiloride 5–10 mg (1–2) Renal ailure, hyperkalemia
Triamterene 50–100 mg (1–2)
Beta blockers Asthma, COPD, 2nd- or 3rd-degree
Cardioselective Atenolol 25–100 mg (1) Angina, CHF due to systolic dys unction, heart block, sick-sinus syndrome
post-MI, sinus tachycardia, ventricular
tachyarrhythmias
Metoprolol 25–100 mg (1–2)
Nonselective Propranolol 40–160 mg (2)
Propranolol LA 60–180 (1)
Combined alpha/beta Labetalol 200–800 mg (2)
Carvedilol 12.5–50 mg (2)
Alpha antagonists
Selective Prazosin 2–20 mg (2–3) Prostatism
Doxazosin 1–16 mg (1)
Terazosin 1–10 mg (1–2)
Nonselective Phenoxybenzamine 20–120 mg (2–3) Pheochromocytoma
Sympatholytics
Central Clonidine 0.1–0.6 mg (2)
Clonidine patch 0.1–0.3 mg (1/week)
Methyldopa 250–1000 mg (2)
Reserpine 0.05–0.25 mg (1)
Guan acine 0.5–2 mg (1)
ACE inhibitors Captopril 25–200 mg (2) Post-MI, coronary syndromes, CHF with Acute renal ailure, bilateral
Lisinopril 10–40 mg (1) low ejection raction, nephropathy renal artery stenosis, pregnancy,
hyperkalemia
Ramipril 2.5–20 mg (1–2)
Angiotensin II antagonists Losartan 25–100 mg (1–2) CHF with low ejection raction, Renal ailure, bilateral renal artery
Valsartan 80–320 mg (1) nephropathy, ACE inhibitor cough stenosis, pregnancy, hyperkalemia
Candesartan 2–32 mg (1–2)
Renin inhibitors Aliskiren 150–300 mg (1) Diabetic nephropathy Pregnancy
Calcium antagonists
Dihydropyridines Ni edipine (long-acting) 30–60 mg (1)
Nondihydropyridines Verapamil (long-acting) 120–360 mg (1–2) Post-MI, supraventricular tachycardias, 2nd- or 3rd-degree heart block
Diltiazem (long-acting) 180–420 mg (1) angina
Direct vasodilators Hydralazine 25–100 mg (2) Severe coronary artery disease
Minoxidil 2.5–80 mg (1–2)
a
At the initiation o therapy, lower doses may be pre erable or elderly patients and or select combinations o antihypertensive agents.
Abbreviations: ACE, angiotensin-converting enzyme; CHF, congestive heart ailure; COPD, chronic obstructive pulmonary disease; MI, myocardial in arction.
S ACEI ARB -
, -
, . ACEI ARB .A
,
.A - CHF, - .D
, ( ), ~15% , <1%
( ARB) ACEI . A
- . ACEI/ARB - A A A
.H
ACEI ARB .
.I A -
, ACEI/ARB
( . ., , : . B -
, , )
. ACEI ARB . A ,
1903
. M - .A -
ACEI ARB , -
, .F , , -

.R
.C , - .
- . Calcium Channel Blockers C
Aldosterone Antagonists S - L- , -
. T
. I :
- , - ( ), ( ),
, .I CHF, - 1,4- ( - ). U -
(ACEI , , α1 - -
ACEI , ), ; ,
, .B - -
, - .S , ,
, , .T
, , ;
. , .
Beta Blockers β-A - Direct Vasodilators D
.O - , , -
- , . U ,
.B -
, .
- .I H
, β1 – ,
β2
; , .H
- ,
.S .I
, -
.B - .
-
COMPARISONS OF ANTIHYPERTENSIVES
, , .
I CHF, B , -
. O , -
–
, -
.H - : , , ACEI , ARB ,
, , α1 .O ,
. 8–10/4–7 H ;
C β , .
α- .T β- Y
α- ACEI , >50
.N .T
.P
.W - ACEI
. ARB , -
`-Adrenergic Blockers P , α- .H A A
ACEI ARB
.T ,
. H , . B
, A
A -A A .E
CHF - , , - ,
.T , -
.N -
α- .H ,
,
. . C ,
Sympatholytic Agents C α2 ,
. .
T - A - >30 –
- -
.D , , ,
. P .I -
,
1904 .S
.F ; ,
, A L -L T P - .E
H A T (ALLHAT) S
CHD , - 3, , ,
PART 6
, 535
ACEI ( ), ( ), - .A
( ). H ,
, ’ .I
, , , - , .
. BLOOD PRESSURE GOALS OF ANTIHYPERTENSIVE THERAPY

H , , ACEI B ,
, ,
. ACEI ARB - <135–140 H <80–85 H
; ,
, - -
, . .A - , -
I 2 , ACEI, ARB,
- ,
.I ,
ACEI .
ARB . H , 2 , - T
ACEI - .G -
. A A A - .A
, ACEI
, .F , SPRINT
, .T - 9361 >50
- , . I (
, - <120 H )
.I 25% (
/ , , ACEI 135–139 H ). M
ARB , .I - ( . ., , -
, , ),
, ACEI -
, .N ,
CHF, - .I ,
. S , .
CHF I ,
ARB . ACEI
, - ( , ). V -
ACEI .
R , - , (A 2 (<140/90, <140/85, <130/80). O
C E C T P A C C R D
L S H [ACCOMPLISH T ]) - (ACCORD) -
ACEI ( ) (<120 H )
( ) (<140 H ) ’ (
ACEI ( ) , , -
- ) .H ,
.H , ACEI
.
. I , , -
A , ACEI , -
ARB, - .T
.S - , ,
/ . .B
T -
, - . A ,
: (1) - .
; (2) H ,
.B - -
. >80 , ,
W ,
, - ( . ., 130–150 H ).
T ,
. B -
. T
. F ,
- ~20% TABLE 271-10 Usual Intravenous Doses of Antihypertensive Agents 1905
.A Used in Hypertensive Emergenciesa
ANTIHYPERTENSIVE
. AGENT INTRAVENOUS DOSE

T resistant hypertension - Nitroprusside Initial 0.3 (μg/kg)/min; usual 2–4 (μg/kg)/min;
>140/90 H maximum 10 (μg/kg)/min or 10 min
, .R - - Nicardipine Initial 5 mg/h; titrate by 2.5 mg/h at 5–15 min
>60 intervals; max 15 mg/h
.R Labetalol 2 mg/min up to 300 mg or 20 mg over 2 min, then
“ ” ( 40–80 mg at 10-min intervals up to 300 mg total
), , Enalaprilat Usual 0.625–1.25 mg over 5 min every 6–8 h;
( ), maximum 5 mg/dose
Esmolol Initial 80–500 μg/kg over 1 min, then 50–
(T 271-3). R , , 300 (μg/kg)/min
Phentolamine 5–15 mg bolus
.T Nitroglycerin Initial 5 μg/min, then titrate by 5 μg/min at 3–5-min
intervals; i no response is seen at 20 μg/min,
(O ). T incremental increases o 10–20 μg/min may be used
- . E Hydralazine 10–50 mg at 30-min intervals
- a
Constant blood pressure monitoring is required. Start with the lowest dose.
Subsequent doses and intervals o administration should be adjusted according
.A to the blood pressure response and duration o action o the speci ic agent.
. , .H -
-
HYPERTENSIVE EMERGENCIES
( . ., , ).
P A
, U S - ,
“ ” . . I ,
M
, , - ,
-
.T
- . R
.T , .T
,
. Tables 271-9 and 271-10 25% 2
- 160/100–110 H .T IV -
. , -
Malignant hypertension - - .P
-
.
. T I -
.P , ,
, , .T
.F -
, , , . , , .
C , A ,
( , , , ), - .A -
, ,
.A
TABLE 271-9 Preferred Parenteral Drugs for Selected Hypertensive ,
Emergencies .W
Hypertensive encephalopathy Nitroprusside, nicardipine, labetalol
Malignant hypertension (when IV Labetalol, nicardipine, nitroprusside, ( CT ),
therapy is indicated) enalaprilat
Stroke Nicardipine, labetalol, nitroprusside .C ,
Myocardial in arction/unstable Nitroglycerin, nicardipine, labetalol, ,
angina esmolol ,
Acute le t ventricular ailure Nitroglycerin, enalaprilat, loop
diuretics >220 H -
Aortic dissection Nitroprusside, esmolol, labetalol >130 H .I
Adrenergic crisis Phentolamine, nitroprusside , <185 H
Postoperative hypertension Nitroglycerin, nitroprusside, labetalol, <110 H .I -
nicardipine , -
Preeclampsia/eclampsia o pregnancy Hydralazine, labetalol, nicardipine
Source: Adapted rom DG Vidt, in S Oparil, MA Weber (eds): Hypertension, 2nd ed. 140–179 H . T
Philadelphia, Elsevier Saunders, 2005. .
1906 C / -
>130 H . (Fig. 272-1).
I ,
MACROVASCULAR DISEASE
, , , L -
PART 6
- , ,
.T (FMD), , , .A
.
Treatment of hypertension in patients with acute aortic dissec-
tion is discussed in Chap. 274, and treatment of hypertension in .B
pregnancy is discussed in Chap. 466. , -

“ ” .
■ FURTHER READING R -
Ettehad D :B - . FMD 3–5%
:A - . .I -
L 387:957, 2016. ( 15
Feinberg AP, Fallin MD: E 50), . FMD ,
. JAMA 314:1129, 2015.
Go AS :A : A .A (ARAS)
A H A , A (6.8% -
C C , C D C P - 65). T
.H 63:878, 2014.
Guo F :T , , , (18–23%) / (>30%).
U S , 1999 2010. J A C I , ARAS 50% 5-
C 60:599, 2012. , . I
Harrison DG : I , .
H 57:132, 2011. .
Hughes TM, Sink TM: H : C
C .A JH - , ,
29:149, 2016. .T
Oh YS :N H ,L , B I W G
R S H H S : B , , -
.H 68:281, 2016. (BP) , ,
Raman G :C .R
:A .A I -
M 165:635, 2016. .I
Sprint Research Group: A
.NE J M 373:2103, 2015. . M
BP
.
ARAS -
,
(GFR) ARAS. W -
, .M -
Renovascular Disease
272 Stephen C. Textor
GFR
.H , -
, .W , -
.U
T FMD, ARAS -
, -
.A , , .
, N 85%
- 3–5 (CKD) GFR <60 L/
. T 1.73 2. T ARAS -
, - ,
.V .
- - D
, , . Microvascular .N
injury, including inflammatory and primary hematologic disorders, , -
is described in Chap. 311. Table 272-1. A -
T - ,
, , . L ,
.R (UAE) , ,
.I UAE .R D
. UAE >200 /
. (>60% ),
E >300 / .T
.
1907
Medulla
CHAPTER 272 Renovascular Disease

Cortex
Normal MV proliferation MV rarefaction

(early atherosclerosis) (chronic renal ischemia)
FIGURE 272-1 Examples o micro-CT images rom vessels defned by radiopaque casts injected into the renal vasculature. These illustrate the complex, dense
cortical capillary network supplying the kidney cortex that can either proli erate or succumb to rare action under the infuence o atherosclerosis and/or occlusive
disease. Changes in blood supply are ollowed by tubulointerstitial brosis and loss o kidney unction. MV, microvascular. (From LO Lerman, AR Chade: Curr Opin
Nephrol Hyper 18:160, 2009, with permission.)
I - - , .C - -
. M
.M (MRA)
, - - BP .S
. C - , ,
(CT) , - ,
, . .
M -
, BP , , ,
TREATMENT .F -
Renal Artery Stenosis / BP .
R
W .
- , - T .W -
.P FMD - , 5–9% ,
, , ,
.T .A , -
. I BP -
ARAS, ,
TABLE 272-1 Summary of Imaging Modalities for Evaluating the Kidney Vasculature
Per usion Studies to Assess Di erential Renal Blood Flow
Captopril renography with Captopril-mediated all in iltration Normal study excludes renovascular Multiple limitations in patients with
technetium 99mTc mertiatide pressure ampli ies di erences in hypertension advanced atherosclerosis or creatinine
(99mTc MAG3) renal per usion >2.0 mg/dL (177 μmol/L)
Vascular Studies to Evaluate the Renal Arteries
Duplex ultrasonography Shows the renal arteries and Inexpensive; widely available, Heavily dependent on operator’s experience;
measures low velocity as a suitable or ollow-up studies less use ul than invasive angiography or the
means o assessing the severity o diagnosis o ibromuscular dysplasia and
stenosis abnormalities in accessory renal arteries
Computed tomographic Shows the renal arteries and Provides excellent images; stents Expensive, moderate volume o contrast
angiography perirenal aorta do not cause arti acts required
Magnetic resonance Shows the renal arteries and Not nephrotoxic, but concerns or Expensive; gadolinium excluded in renal
angiography perirenal aorta gadolinium toxicity exclude use in ailure, unable to visualize stented vessels
GFR <30 mL/min/1.73 m2; provides
excellent images
Intraarterial angiography Shows location and severity o Considered “gold standard” or Expensive, associated hazard o
vascular lesion diagnosis o large-vessel disease, atheroemboli, contrast toxicity, procedure-
usually per ormed simultaneous related complications, e.g., dissection
with planned intervention
Abbreviation: GFR, glomerular iltration rate.
1908 TABLE 272-2 Clinical Factors That Determine the Role of , (15%). E
Revascularization in Addition to Medical Therapy for Renal Artery .D
Stenosis
Factors Favoring Medical Therapy and Revascularization or Renal “ ” .B
Artery Stenosis
PART 6
• P rogressive decline in GFR du ring treatm ent of system ic hypertension

• Failu re to achieve adeq u ate blood pressu re control w ith optim al m edical .
therapy (medical ailure) N
• R apid or recu rrent decline in the GFR in association w ith a redu ction in .W .L
systemic pressure
• Decline in the GFR du ring therapy w ith A CE inhibitors or A RBs , .T

• R ecu rrent congestive heart failu re in a patient in w hom the adeq u acy of left , -
ventricular unction does not explain a cause .T
Factors Favoring Medical Therapy and Surveillance o Renal Artery
Disease .
• Controlled blood pressu re w ith stable renal fu nction (e.g., stable renal
insu iciency) THROMBOEMBOLIC RENAL DISEASE
• Stable renal artery stenosis w ithou t progression on su rveillance stu dies
T
(e.g., serial duplex ultrasound) .I
• Very advanced age and/or lim ited life expectancy , . T
• Extensive com orbidity that m ake revascu larization too risky
,
, , .L
• High risk for or previou s experience w ith atheroem bolic disease
, “ -
• O ther concom itant renal parenchym al diseases that cau se progressive
.” A
renal dys unction (e.g., interstitial nephritis, diabetic nephropathy)
, .I
Abbreviations: ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor , . .,
blockers; GFR, glomerular iltration rate.
, .C
.A
.S
,
- -
25% , 50%
, . ., .
.P
C
, ,
.A ,
, , , .I ,
.
(LDH) .I
W , -
,
. Table 272-2
.I ,
.
.H
,
ATHEROEMBOLIC RENAL DISEASE “ - ” .I
E , BP .D
- MRI, CT
.M , (Fig. 272-2).
, .I
■ MANAGEMENT OF ARTERIAL THROMBOSIS OF THE
, KIDNEY
.T - O
, , ,
.A >3% - , , -
- (ESRD) . .A
I , , ’ , ( . .,
.A ), ,
. .F -
M , - , , ,
, , , .A , -
, .C , .D
1 14 - ,
.S - .
, , , ,
, -
MICROVASCULAR INJURY ASSOCIATED WITH
. HYPERTENSION
W - ■ ARTERIOLONEPHROSCLEROSIS
, .P
.T “Malignant” Hypertension A BP ,
.
M 1 38%, - BP ,
, . , .P
B ,
, (60–80%), 20% 5 .I ,
1909
CHAPTER 272 Renovascular Disease

A B
FIGURE 272-2 A. CT angiogram illustrating loss o circulation to the upper pole o the right kidney in a patient with bromuscular disease and a renal artery aneurysm.
Activation o the renin-angiotensin system produced rapidly developing hypertension. B. Angiogram illustrating high-grade renal artery stenosis a ecting the le t kidney.
This lesion is o ten part o widespread atherosclerosis and sometimes is an extension o aortic plaque. This lesion develops in older individuals with preexisting
atherosclerotic risk actors.
“Hypertensive Nephrosclerosis” B
50% 6–12 , BP
“ .” P - ,
, “ ,” , ,
, .A ,
, .A ESRD
“ -
, .” P
, ,
“ ” .F , ( )
.P .C -
, , ( ,
- .T ), , BP. T
- . P
,
- , , -
.O , . A BP
, .
A CKD,
.W BP ,
, , .
.W
1- 90%, ■ FURTHER READING
5 50%. de Mast Q, Beutler JJ: T
M W , : A . J H
27:1333, 2009.
.I Freedman BI, Cohen AH: H - :
W ’ ?N R N 12:27, 2016.
, .R Herrmann SM :M -
- C O R A L
. B (CORAL). N D T 30:366, 2015.
( , , ) Modi KS, Rao VK: A .JA S N
.A -A 12:1781 2001.
Parikh SA : SCAI
U S .G .C C I 84:1163, 2014.
APOL1 A -A Persu A :E
, .JH 32:1367, 2014.
Textor SC :P -
. :T , .K I 83:28, 2013.
1910 T
- .
273 Deep Venous Thrombosis
and Pulmonary
V
, .
,
PART 6
Thromboembolism Prothrombotic States T -

VL ,
Samuel Z. Goldhaber , C(
V VIII), ,
(Chaps. 61 and 113).
■ EPIDEMIOLOGY A , C, S -
V (VTE) - .D VTE
(DVT) (PE) .A
.I U S , S G .O -
100,000 180,000 PE , , , ,
PE , , -
.I C , PE 1 , - , , - -
, , , , , , ,
.S .I ,
.C VTE. S
, . P PE. A J 2
( chronic venous insufficiency) 40%
PE.
, . I
, Embolization W (Fig. 273-2)
(Fig. 273-1). , , ,
, ,
■ PATHOPHYSIOLOGY PE. P ,
Inflammation and Platelet Activation V ’
.M PE DVT
, ,
.
, .T
- Physiology T
, - O2 -
- . , O2 .
A
.P
.
O :
1. Increased pulmonary vascular resistance -
. R
- ,
PE
- O2 .
FIGURE 273-1 Skin ulceration in the lateral malleolus rom postthrombotic

syndrome o the leg. FIGURE 273-2 Deep venous thrombosis at autopsy.
2. Impaired gas exchange TABLE 273-1 Clinical Decision Rules 1911
, - Low Clinical Likelihood o Deep Venous Thrombosis (DVT) I Point
, - - , Score Is Zero or Less; Moderate Likelihood I Score Is 1 to 2; High
Likelihood I Score Is 3 or Greater
CHAPTER 273 DeepVenousThrombosis and PulmonaryThromboembolism

. CLINICAL VARIABLE DVT SCORE
3. Alveolar hyperventilation .
Active cancer 1
4. Increased airway resistance
Paralysis, paresis, or recent cast 1
.
5. Decreased pulmonary compliance , - Bedridden or >3 days; major surgery <12 weeks 1
, . Tenderness along distribution o deep veins 1
Entire leg swelling 1
Pulmonary Hypertension, Right Ventricular (RV) Unilateral cal swelling >3 cm 1
Dysfunction, and RV Microinfarction P Pitting edema 1
Collateral super icial nonvaricose veins 1
. W RV Alternative diagnosis at least as likely as DVT –2
, RV ,
High Clinical Likelihood o Pulmonary Embolism (PE) i Point Score
, , Exceeds 4
RV . T
(LV). D LV CLINICAL VARIABLE PE SCORE
LV LV . I RV Signs and symptoms o DVT 3.0
, Alternative diagnosis less likely than PE 3.0
, RV Heart rate >100/min 1.5
, . Immobilization >3 days; surgery within 4 weeks 1.5
U LV LV - Prior PE or DVT 1.5
, . Hemoptysis 1.0
Cancer 1.0
■ CLASSIFICATION OF PULMONARY EMBOLISM AND
DEEP VENOUS THROMBOSIS
Pulmonary Embolism Massive PE 5–10% , W P S DVT
PE (Table 273-1). P - -
. D , , , DVT PE d-
PE. P PE ( “B T ”)
- (Fig. 273-3). H , VTE
. Submassive PE 20–25% , - d-
RV .T .
. Low-risk PE Clinical Pearls N DVT,

65–75% .T . PE (Table 273-2). S ,
B ’ .F
Deep Venous Thrombosis Lower extremity DVT DVT. P , , -
, .H , DVT
, . L DVT 10 , , . R
upper extremity DVT,
, , M -T S ,
. T DVT
. Superficial
venous thrombosis , , ALGORITHM FOR DIAGNOSTIC IMAGING
“ .” P Suspect DVT or PE
- .
■ DIAGNOSIS Assess clinical likelihood
Clinical Evaluation PE “ G M .”
D .
DVT PE
T . W
PE
,
.T Low Not low Not high High
PE.
H 17% D-dimer D-dimer
PE I 560 .A
, 25%
PE. E ,
Normal High Normal High
13% PE. W W
S d- , 42% PE. PE
, 42% No DVT Imaging test needed No PE Imaging test needed
.
W DVT, “ FIGURE 273-3 How to decide whether diagnostic imaging is needed. For
” . assessment o clinical likelihood, see Table 273-1.
1912 TABLE 273-2 Differential Diagnosis .I
(Fig. 273-4). T
Deep Venous Thrombosis (DVT)
, .
Ruptured Baker’s cyst
V D .
Muscle strain/injury N , D
PART 6
Cellulitis . L
Acute postthrombotic syndrome/venous insu iciency DVT .F
Pulmonary Embolism (PE) ,
Pneumonia, asthma, chronic obstructive pulmonary disease DVT,
(CT) .
Congestive heart ailure

Pericarditis CHEST ROENTGENOGRAPHY A -
Pleurisy: “viral syndrome,” costochondritis, musculoskeletal discom ort PE. W -
Rib racture, pneumothorax (W ’ ), -
Acute coronary syndrome (H ’ ),
(P ’ ).
Anxiety
CHEST CT CT
PE (Fig. 273-5). “T - CT
” , ≤1
.H , - .S - -
, DVT . M
.U -
. T CT -
-
. RV CT
.
30 PE
Pulmonary infarction PE. T
RV .W
,
, DVT -
. Nonthrombotic PE CT .I PE,
, ,
-
, . C
, ,
.I , , , -
.S , -
, , , . Amniotic fluid embolism
.M -
.
CT. “T - CT”
Nonimaging Diagnostic Modalities • BLOOD TESTS T ECG- , ,
plasma d-dimer enzyme-linked immunosorbent assay (ELISA)
DVT PE : PE,
.E d- , .
. T d- LUNG SCANNING L -
>80% DVT ( DVT) >95% PE. T PE,
d- DVT PE DVT . S
.A d- “ ” .H , -
d- .L - . T
, , , , , PE. V -
.T , ,
d- , , .A -
. ,
ELEVATED CARDIAC BIOMARKERS S PE,
- –
RV .M
NT- - No Compression Compression
.
ELECTROCARDIOGRAM T -
, , S1Q3T3 :
S I, Q III,
CFA CFA
T III (Chap. 235). T
. RV
, T- V1
V 4.
Noninvasive Imaging Modalities • VENOUS CFV CFV
ULTRASONOGRAPHY U -
-
DVT. W
- ,
.T -
“ .” W DVT,
FIGURE 273-4 Venous ultrasound, with and without compression o the leg veins. CFA, common
.T DVT emoral artery; CFV, common emoral vein; GSV, great saphenous vein; LT, le t.
1913
ALGORITHM FOR DVT AND PE DIAGNOSIS
DVT imaging test

Venous ultrasound
Diagnostic Nondiagnostic
Stop MR CT Phlebography
PE Imaging Test
Chest CT
FIGURE 273-5 Large bilateral proximal PE on a coronal chest CT image in

a 54-year-old man with lung cancer and brain metastases. He had developed Diagnostic Nondiagnostic, unavailable, or unsafe
sudden onset o chest heaviness and shortness o breath while at home. There
are lling de ects in the main and segmental pulmonary arteries bilaterally (white
arrows). Only the le t upper lobe segmental artery is ree o thrombus. Stop Lung scan
.A -
PE Diagnostic Nondiagnostic
.
T PE
Stop Venous ultrasound
, , 90%
- .U , -
, - -
PE .A 40% Positive Negative
PE “ - ”
, , PE .
Treat for PE Transesophageal ECHO or MR or
MAGNETIC RESONANCE (MR) (CONTRAST-ENHANCED) IMAGING W invasive pulmonary angiography
, MR
DVT. MR - FIGURE 273-6 Imaging tests to diagnose DVT and PE. ECHO, echocardiography.
PE,
PE.
ECHOCARDIOGRAPHY E not Integrated Diagnostic Approach A
PE PE (F . 273-3) DVT
.H , PE (Fig. 273-6).
PE,
, , .T
. T - TREATMENT
PE MC ’ Deep Venous Thrombosis
: RV
RV .O PRIMARY THERAPY
CT Primary therapy
- - -
- .T .T ,
, , PE. , DVT. T -
Invasive Diagnostic Modalities • PULMONARY ANGIOGRAPHY
C CT ( ) - - ,
.I - - .AN H ,L , B
I – ATTRACT
CT (NCT00790335) -
- .A PE DVT
- ,
.S PE (“ - ”) 2
, , .
, , . SECONDARY PREVENTION
CONTRAST PHLEBOGRAPHY V A (IVC)
secondary prevention VTE. I 2016, FDA
DVT. IVC
1914 TABLE 273-3 Anticoagulation of Venous Thromboembolism (VTE)
®
(A F )
Non-War arin Anticoagulation
.
Un ractionated heparin, bolus and continuous in usion, to achieve activated
F DVT -
partial thromboplastin time (aPTT) 2–3 times the upper limit o the laboratory
, - - normal, or
PART 6
, 30–40 H , .T
Enoxaparin 1 mg/kg twice daily with normal renal unction, or
3 .
Dalteparin 200 U/kg once daily or 100 U/kg twice daily, with normal renal
H , - unction, or
DVT
Tinzaparin 175 U/kg once daily with normal renal unction, or
.
Fondaparinux weight-based once daily; adjust or impaired renal unction

Direct thrombin inhibitors: argatroban or bivalirudin (with suspected or proven
heparin-induced thrombocytopenia)
TREATMENT
Rivaroxaban 15 mg twice daily or 3 weeks, ollowed by 20 mg once daily with
Pulmonary Embolism the dinner meal therea ter
Apixaban 10 mg twice daily or 1 week, ollowed by 5 mg twice daily therea ter
RISK STRATIFICATION Dabigatran 5 days o un ractionated heparin, low-molecular-weight heparin
H , RV , RV (LMWH), or ondaparinux ollowed by dabigatran 150 mg twice daily
CT, Edoxaban 5 days o un ractionated heparin, LMWH, or ondaparinux ollowed
RV - by edoxaban 60 mg once daily with normal renal unction, weight >60 kg, in
.W RV the absence o potent P-glycoprotein inhibitors
, War arin Anticoagulation
(Fig. 273-7). Requires 5–10 days o administration to achieve e ectiveness as
monotherapy
ANTICOAGULATION
(Un ractionated heparin, LMWH, and ondaparinux are the usual immediately
E e ective “bridging agents” used when initiating war arin)
DVT PE. T : (1) - Usual start dose is 5 mg
Titrate to international normalized ratio (INR), target 2.0–3.0
(UFH), - - (LMWH),
Continue parenteral anticoagulation or a minimum o 5 days and until two
“ ” , (2) 5 sequential INR values, at least 1 day apart, achieve the target INR range
(
) ( -X ), (3)
( -X ) Low-Molecular-Weight Heparins T UFH
3- 1- , , -
. F ,
VTE - , - UFH. N
,
: (Table 273-3). .
Unfractionated Heparin UFH
, Fondaparinux F , -X ,
. UFH - - -
( PTT) 60–80 . T .N .
80 U/ , F , LMWH
18 U/ - UFH, .I
. T UFH - , - . T
- - .
.H
. Warfarin T K -
II, VII, IX, X. T
5 , ,
, .I
ALGORITHM FOR PE MANAGEMENT , -
Risk stratify
.O UFH, LMWH, , -
5
Normotension Normotension .
Hypotension
plus normal RV plus RV hypokinesis
War arin dosing I - ,
5 .T -
Secondary Individualize Primary (INR),
prevention therapy therapy (Chap. 61). T INR
2.5, 2.0–3.0.
T
Anticoagulation INR. P -
Anticoagulation Embolectomy:
IVC filter plus - .I
alone catheter/surgical
thrombolysis .P -
. CYP2C9
FIGURE 273-7 Acute management o pulmonary thromboembolism. RV, right S- , -
ventricular; IVC, in erior vena cava. .V K
1 (VKORC1) VTE. H , 1915
, , .H , - -
. , VTE
C .

.P - INR
- - INFERIOR VENA CAVA FILTERS
- . T IVC
W , (1) (2)
, INR - .P
.W “ ” PE
.S -
. “ ” .T -
- - .L
Novel Oral Anticoagulants N (NOAC ) .
, P , ,
, - DVT , PE. T -
, - - . , DVT
B , X , FDA .R
2017 VTE
5 6 . PE, -
R , X ,
DVT PE. T ,
PE, “ ” .D , .T
, , X , ,
VTE 5- - , .
.
Complications of Anticoagulants T MANAGEMENT OF MASSIVE PE
.F - - F PE ,
LMWH, 500 L .A
. T
X . H , RV , RV ,
, , - LV -
.A LV. D -
-X , , - PE- .M
, FDA. . O , “ - - ”
M ;
.W , - , , .
K .O K FIBRINOLYSIS
INR S -
. PE
Duration of Anticoagulation F DVT - (1) -
, , , , (2)
,3 -
.F , (3)
DVT PE, 3–6 , PE.
.H , EINSTEIN CHOICE T
VTE 100 ( PA) -
VTE 2 .
VTE. F VTE, T , .
LMWH - H , 14 PE
- . .A - 50 TPA
A , VTE, - 2 . T
. VTE .
- .U C ,
VTE - , .T
, 10%, 2–3% . C
.A C
C P (ACCP) - (Chap. 269) .
INR 2 T F D A –
3 VTE .A PE PE. F PE,
6
INR RV , .R
1.5 2. A 1006- E -
, PE,
- , - - , 7
. 56% .H -
C , , 2%
VL 0.2% .
1916 PHARMACOMECHANICAL CATHETER-DIRECTED THERAPY TABLE 273-4 Prevention of Venous Thromboembolism Among
M - - Hospitalized Patients
. P - CONDITION PROPHYLAXIS STRATEGY
High-risk Un ractionated heparin 5000 units SC bid or tid
- - . M - nonorthopedic Enoxaparin 40 mg daily
PART 6
surgery
Dalteparin 2500 or 5000 units daily
, , , Cancer surgery, Enoxaparin 40 mg daily, consider 1 month o
- - . T including gynecologic prophylaxis
, 20–25 , cancer surgery
100 .I Major orthopedic War arin (target INR 2.0–3.0)

2014, FDA - - surgery Enoxaparin 40 mg daily
PE. U Enoxaparin 30 mg bid
PA 24 , RV , Dalteparin 2500 or 5000 units daily
, , Fondaparinux 2.5 mg daily
.L Rivaroxaban 10 mg daily, beginning 6-10 hours
TPA . postoperatively
Aspirin 81–325 mg daily
PULMONARY EMBOLECTOMY
Dabigatran 110 mg irst day, then 220 mg daily
T
Apixaban 2.5 mg bid, beginning 12–24 h
- postoperatively
, .M - Intermittent pneumatic compression (with or without
pharmacologic prophylaxis)
. Medically ill Un ractionated heparin 5000 units bid or tid
PULMONARY THROMBOENDARTERECTOMY patients, during Enoxaparin 40 mg daily
hospitalization Dalteparin 2500 or 5000 units daily
C
2–4% PE .T , PE Fondaparinux 2.5 mg daily
( D - Medically ill patients, Betrixaban 80 mg daily or 35–42 days
) 6 during and a ter
hospitalization
. P Anticoagulation Intermittent pneumatic compression devices (but
contraindicated whether graduated compression stockings are e ective
in medical patients remains uncertain)
, , ,
, , -
(Chap. 277). T ,
■ FURTHER READING
, , -
Becattini C, Giancarlo A: T
.T
.JA C C 67:1941, 2016.
~5%. I
Braekkan SK :V -
.JT H 14:1977, 2016.
.
Cohen AT : E
EMOTIONAL SUPPORT .NE JM 375:534, 2016.
P VTE Gibson CM :E -
PE DVT. S - -
.T : A APEX (
- ).
.T C 135:648, 2017.
.T Kahn SR :F
:R ELOPE
VTE. A B W ’ H - .C 151:1058, 2017.
, - – PE Kearon C : A VTE : CHEST
>25 . . CHEST 149:315, 2016.
T , N A T F Konstantinides SV :M .JA
(www.NATFonline.org), C C 67:975, 2015.
. Piazza G : A , - ,
- , - , -
. T SEATTLE
■ PREVENTION OF VTE II .JA C C C I 8:1382, 2015.
P DVT PE (Table 273-4) Poterucha TJ :M :D
VTE - ?T H 117:437, 2017.
. L - UFH LMWH Prandoni P :P
- .C .NE JM 375:1524, 2016.
, B W ’ Raskob GE :T MARINER
H , VTE >40%. A VTE. T H
115:1240, 2016.
.D Shirakawa T : W
.E - J .C
-X , , 134:355, 2016.
, , Weitz JI :R
FDA . . NE JM 376:1211, 2017.
.T 1917
, -
274 Diseases of the Aorta Mark A. Creager, Joseph Loscalzo
,
,
, ,
,
(Table 274-1). I ,
CHAPTER 274 Diseases of the Aorta

.T B
T , , ,
T
.I , -
~3 , 2.5
. T
, 1.8–2 .T
, , -
, -
, .F -
, ;
, , -
;
, , .
T -
.I
atherosclerosis. M
,
,
.T
.
,
.O
, TABLE 274-1 Diseases of the Aorta: Etiology and Associated Factors
- Aortic aneurysm
.T Degenerative
, , Aging
, L ’ ( . ., Cigarette smoking
), .
Hypercholesterolemia
CONGENITAL ANOMALIES OF THE AORTA Hypertension
C Atherosclerosis
. S , , Genetic or developmental
Mar an’s syndrome
.A Loeys-Dietz syndrome
, Ehlers-Danlos syndrome type IV
, - Turner’s syndrome
.AK ’ Familial
.M Bicuspid aortic valve
- .
Chronic aortic dissection
T
Aortitis (see below)
(CT)
(MR) .S . In ective (see below)
C (Chap. 264) - Trauma
, Acute aortic syndromes (aortic dissection, acute intramural hematoma,
.I , penetrating atherosclerotic ulcer)
, , - Degenerative disorders (see above)
.A Genetic/developmental disorders (see above)
.I Hypertension
, , CT MR Aortitis (see below)
.I , Pregnancy
.T Trauma
Aortic occlusion
.
Atherosclerosis
AORTIC ANEURYSM Thromboembolism
A aneurysm Aortitis
. A true aneurysm Vasculitis
pseudoaneurysm, Takayasu’s arteritis
Giant cell arteritis
, , .A Rheumatic
. A fusiform aneurysm Rheumatoid aortitis
, HLA-B27–associated spondyloarthropathies
.I , saccular aneurysm Behçet’s syndrome
,
Cogan’s syndrome
.A ,
IgG4-related systemic disease
. ., .A
Idiopathic aortitis
thoracoabdominal aortic aneurysms. In ective
Syphilis
■ ETIOLOGY Tuberculosis
A Mycotic (Salmonella, staphylococcal, streptococcal, ungal)
:
1918 M , cystic medial necrosis,
,
.M
PART 6
, ,
V .T
M ’ , L -D ,
E -D IV (Chap. 406), ,
,T ’ ,
;
.
F 20% ,
.M
-1 M ’ .
F -1 ,
. D -1
β (TGF-β). L -
D TGF-β
1 (TGFBR1) 2 (TGFBR2). I TGF-β
TGFBR1, TGFBR2, TGFBR3, TGFB2
TGFB3, .M SMAD3,
TGF FIGURE 274-1 A chest x-ray o a patient with a thoracic aortic aneurysm.
,
; , , ;
.M –
- (ACTA2), – .T
11 (MHC11), (MYLK) 0.1–0.2 .T -
TGFBR2 SMAD3 M ’
.M .T
III E -D IV ,
. 2–3% <4.0 7%
T , - >6 .M
, . Syphilis (Chap. 177) - ; ,
.S ,
, - , , , .A
.A 90%
. Tuberculous aneurysms ,
(Chap. 173) , , .
A -
.L (Fig. 274-1). F
. A mycotic aneurysm
, - .E , -
, Salmonella, , ,
. T .C - CT,
.B (MRI),
.
V T ’ (Fig. 274-2). I
, - ,
.S - CT MRI
, , , 6–12 .
, ( R ’ -
) .A -
B ç ’ (Chap. 357), C ’ TREATMENT
, I G4- .A Thoracic Aortic Aneurysms
. Traumatic aneurysms
β-A
, M ’ -
.C ,
.A
. .A
■ THORACIC AORTIC ANEURYSMS M ’ TGF-β .C

T
.M M ’ .
, O
A 1919
; , 25%
- .A

.A -
.I
, 65–74
- 42%.
F ,
65–75 .I ,
, -
,
. CT
MRI -
(Fig. 274-3). C
, -
, ,
.S
,
.
FIGURE 274-2 A magnetic resonance angiogram demonstrating a usi orm
aneurysm o the ascending thoracic aorta. (Courtesy o Dr. Michael Steigner, TREATMENT
Brigham and Women’s Hospital, Boston, MA, with permission.)
Abdominal Aortic Aneurysms
S
, .M , β-
, - ,
≥5.5 , >0.5 . .O
R >4.5 -
(F . 274-3)
.I
M ’ , .F , -
4–5 .O - ≥5.5 .
I
>6 , <5.5 , - (5- 8- ) -
>5.5 .
R .T ,
>1 . - (<5.5 ) -
.T
■ ABDOMINAL AORTIC ANEURYSMS
.E -
A
- , -
, .C
. L -
.A ≥4.0
CT MR -
1–2% >50 .A 90% -
.
>4.0 ,
I ,
.P
( -
-
) .P ,
.T
, , ,
: 5-
.W
<5 1–2%, 20–40% >5 .
,
T
1–2%. A ,
.
45–50%. E
A .
I , ,
.
, ,
. A
, , ACUTE AORTIC SYNDROMES
.S ; T (
, , .A - ), , ,
.A
.M , - , , .I
, - .R ,
.A .A
, .T
.
1920
PART 6
FIGURE 274-3 A computed tomographic angiogram depicting a usi orm abdominal aortic aneurysm be ore (le t) and a ter (right) treatment with a bi urcated stent
gra t. (Courtesy o Drs. Elizabeth George and Frank Rybicki, Brigham and Women’s Hospital, Boston, MA, with permission.)
.T L -D ,
E -D .T
.T ( . ., T ’ , ),
, ( . ., ),
. D
.I , - Type A
,
.
T
:
.A
. M
.A
.P
, ,
.T -
.T
Type B
, ,
.
S
. D B
I,
; II,
; III,
(Fig. 274-4). A (S )
A, ( -
), B, /
( ). F ,
FIGURE 274-4 Classifcation o aortic dissections. Stan ord classi cation: Type A
A B , D B I II dissections (top) involve the ascending aorta independent o site o tear and distal
. extension; type B dissections (bottom) involve transverse and/or descending
aorta without involvement o the ascending aorta. DeBakey classi cation: Type I
T -
dissection involves ascending to descending aorta (top le t); type II dissection is
limited to ascending or transverse aorta, without descending aorta (top center +
(T 274-1). S top right); type III dissection involves descending aorta only (bottom le t). (From
70% .A - DC Miller, in RM Doroghazi, EE Slater [eds]: Aortic Dissection. New York, McGraw-Hill,
M ’ (Chap. 406) 1983, with permission.)
, .I , - 1921
TREATMENT
.A Aortic Dissection
, , .

M
■ CLINICAL MANIFESTATIONS . T
T .U ,
.M 2:1. T -
, .F ,
, , , , β- -
.A , , ,
(Chap. 11), - ~60 / .T
.T
, - ≤120 H .L (Chap. 271),
, . β- α- ,
O , , .P .
, , T
, , β-
( , ) .T -
( ). B , , - (ACE) β-
. T .I
.F , .
( . ., , E
, , )
, H ’ , ( A). S ,
, , , . , .A
H -
A .A .T - -
(>50%) .
I 15–25%. T
, , , -
() , .S , , .T
, , B
, , , -
.T , ,
. .O ,
I , -
.A ( , .S
- ) .T - B , -
. H
.I ,
- .I , -
.F
.A ( B), -
.T -
.R , , , B ~10%. L -
. (
T )
, CT, MRI. A β- -
- , ACE .
.T P B
60–85% . 6–12
F , - CT MRI .
80%; P M ’
.T .T -
, - ; 10-
~60%.
, 98% ~90% . E -
■ CHRONIC ATHEROSCLEROTIC OCCLUSIVE DISEASE
. CT MRI A .O -
; - .F
>90%. T (Chap. 275). C
.T - , ,
, CT, MRI (L ’ ). T -
.W
, CT MRI ,
. .T
1922 . O - ( . .,
( )
) .A ,
, .I .H -
, .I
PART 6
.
T .B
, , D .
, , -
.T MRI, CT, - ■ RHEUMATIC AORTITIS
, . R (Chap. 351), (Chap. 355),

C - (Chap. 355), (
- - R ’ ) (Chap. 355), , -
.
. T
■ ACUTE AORTIC OCCLUSION V ,
A , .T
; , ,
( ) .
. R ,
■ IDIOPATHIC AORTITIS
. I
T . .I -
S , ,
. .A
D MRI, CT, . , , . R
E . . G
.
AORTITIS
A , , ■ INFECTIVE AORTITIS
T ’ I
, HLA-B27– - Staphylococcus, Streptococcus, Salmonella
,B ç ’ , .T
(ANCA)– ,C ’ ,E -C .B -
, I G4- , , , -
, Salmonella, .M
.A - .T
, ,
. , , , . M -
■ TAKAYASU’S ARTERITIS .P , ,
(See also Chap. 356) T , , ;
, .B .
.T ’ pulseless disease B CT MRI .T
.I
.A - .
.T S (Chap. 177)
, ,
, , , , .S
, .T
A . T
.D , , ,
, , . ; .
E C- T ,
.T , .T
, , .D
, , .T - ,
, .G .D
, ,
.B . .T
S .
. T
15–30 .S
■ GIANT CELL ARTERITIS , -
(See also Chap. 356) T , ( . ., ), .
.P - D , . .,
. T (RPR) .T
; .
■ FURTHER READING symptom , 1923
Buck DB :E . , , , , ;
N R C 11:112, 2014. .T
Erbel R : 2014 ESC G .F , , ,
CHAPTER 275 Arterial Diseases of the Extremities

:D , ,
.T T F -
D T A D E .S
S C (ESC). E H J 35:2873, 2014.
Gornik HL, Creager MA: A .C 117:3039, 2008. .I
Guirguis-Blake JM :U
:A US P , .P
S T F .A I M 160:321, 2014. .F -
Hiratzka LF : 2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/ ,
SIR/STS/SVM .W
T A D : A A , .
C C F /A H A T I physical findings PAD
F P G ,A A T S - , -
,A C R ,A S A , , .W , ,
S C A ,S C - , , ,
A I ,S I R - .I
,S T S , S V M . , .E
C 121: 266, 2010.
Isselbacher EM :H , , ,
.C 133:2516, 2016. .T
Kent KC: C .A .NE JM ’
371:2101, 2014.
Nienaber CA, Clough RE: M . .P
L 385:800, 2015.
.I
.
Noninvasive Testing T
PAD. A -
.A
Arterial Diseases of the
275 Extremities D
.N ,
Mark A. Creager, Joseph Loscalzo .I ,
- .I -
, -
■ PERIPHERAL ARTERY DISEASE .T ,
P (PAD) ( ankle:brachial index, ABI) 1.00–1.40
. ABI 0.91–0.99 “ -
.A PAD >40 ,” <0.90 PAD. ABI >1.40
.O , , , - .
, , , . O ,
T PAD , (
.A - B- D
, ), , (
PAD , - ). P
.T
, , .
Pathology (See also Chap. 291e from HPIM 19e) S .I ,
-
- .T - PAD. D
, , .
, T -
, . .D ABI
T PAD
(30% ), .
(80–90% ), , M (MRA),
(40–50% ). A (CTA), -
, ,
, , .I - (Fig. 275-1). E
. .
Clinical Evaluation F 50% PAD Prognosis T PAD -
, .T
1924
PART 6
FIGURE 275-1 Magnetic resonance angiography o a patient with intermittent claudication, showing stenoses o the distal abdominal aorta and right common iliac
artery (A) and stenoses o the right and le t super cial emoral arteries (B). (Courtesy o Dr. Edwin Gravereaux, with permission.)
. A - - ADP , ,
PAD
(CAD) , PAD, -
- CAD .
P PAD 15–25% 5- - .O
.M .T
PAD. M
ABI PAD
. T PAD .W
PAD CAD. , , -1
A 75–80% - ,
.D ,
, ~1–2% PAD. I
.A 25–30% ; ,
1 . . T
T -
. ; ,
PAD. T
X , -
TREATMENT ,
Peripheral Artery Disease , PAD,
.
P PAD T -
, , , ,
, , , . S
, . R - ,
.
.T W - .
.T E ,
.C . I ,
, ,
. .
I . P
A - . S
30- 45- ,
PAD. β-A - 12 , .T
, -
CAD. T
, . S
, .T 2013 ACC/AHA G T - .
B C R A C R P PAD
A CAD (Chap. 267). I ,
, PAD. P , .D ,
.A . T - 1925
, , - D .I
.D 99%, 5- 10-
α- , , >90% 80%, .O

, ,
PAD. ,
C , . T
, 40–60% 1 3%, .
.T O -
.P , , -
, - (PTFE) ,
. A .T 1
- 3%. T - ,
, ,
.S .P -
, 90% 1 70–80%
. 5 .F -
T . 60–70%. I , 5- -
V - PTFE <30%.
.E - P
DNA , .P , -
, , - , , ,
1α .S
( ), , -
.M – ,
(Chap. 270). P -
, - - .
.T C -
.
, -
REVASCULARIZATION
R , - -
, , - CAD.
,
- ■ FIBROMUSCULAR DYSPLASIA
. T F
. MRA, CTA, - .I
- .T -
.E ( ),
(PTA) ( ), ( ), . M
( ), , - , -
(Chap. 270). W , .M
,
. .T .
PTA T
PTA .I “
.A 90–95% PTA , ” -
3- >75%. P , - ,
.T , ,
- PTA 90% 60% , .W
3- .O - ,
(>5–10 ) PTA. S - , . PTA
- -
PTA, .
.P
; ■ THROMBOANGIITIS OBLITERANS
. E T (B ’ )
, , , -
, .C , ,
. .T
S <40 .T
- .T A E E .A
,
() . .
O I , -
, , - , -
1926 . T , 1 .P .P
, .A , -
, , , , , , , -
.L , , / .I
, , . ,
PART 6
T ,
,R ’ - .I ,
, . C
.P ,
.I . T
, , , D .T
.T
. I , MRA, CTA, -
, , / . MRA, CTA, -
. S , .
,
.P
.T TREATMENT
. Acute Limb Ischemia
T .T
, O ,
.A
, .I , -
, . ,
A ; .C - /
.I , . , ,
■ VASCULITIS , .
O I -
. Takayasu’s arteritis and giant cell (temporal) arteri- , ,
tis are discussed in Chap. 356. (<2 ) -
, ,
■ ACUTE LIMB ISCHEMIA . T ’
A -
.T , .
M
- . A -
.P
, , , .
T , , .T -
.C
; ; ; .S
; ; - 24
; .E
>2 .A ,
.L , - , ,
D - .
L -
. A
.E -
; -
, ,
, ,
.
, , .
A -
■ ATHEROEMBOLISM
.T A .I ,
, ,
’ - .
.A L
; , .A -
.L .S
,
, - ,
.P .P
(Chaps. 99 and 112) .D
. “ ” ;
(Fig. 275-2). L , ,
■ CLINICAL FEATURES ( ) .S -
T , .
, .O , - I
, , .L
1927
.
N , -
,

,
.
M .T
.M
.S
■ POPLITEAL ARTERY ENTRAPMENT

P
. T -
, , . T
FIGURE 275-2 Atheroembolism causing cyanotic discoloration and impending
necrosis o the toes (“blue toe” syndrome). .T
, CTA, MRA, -
.A .U .T
.
, , ■ POPLITEAL ARTERY ANEURYSM
.T P
, .A 50% .P
- ,
.S , . T
.S .R .
O
. .P -
.R
■ THORACIC OUTLET COMPRESSION SYNDROME
2–3 ,
T -
, , .
( , , )
.C , ■ ARTERIOVENOUS FISTULA
, , A ,
, . C -
, ,
.D ;
, , , ,
, .P - . A
, ,
.P -
,R ’ , .
.V A
; .
Paget-Schroetter syndrome. T .
F , ,
APPROACH TO THE PATIENT .W -
, ,
Thoracic Outlet Compression Syndrome ; , ;
E .
- E .
. O , S .L -
. -
S - (Chap. 252).
- T .C -
, , .
T , (N -B ). D
90° ,
; ( . CTA
); -
( ); .
( 180°). A - - M , -
.D , MRA, , .C
,
1928 .M - TABLE 275-1 Classification of Raynaud’s Phenomenon
Primary or idiopathic Raynaud’s phenomenon
. O ,
Secondary Raynaud’s phenomenon
, , , -
Collagen vascular diseases: scleroderma, systemic lupus erythematosus,
, .A rheumatoid arthritis, dermatomyositis, polymyositis, mixed connective tissue
PART 6
disease, Sjögren’s syndrome

.O , Arterial occlusive diseases: atherosclerosis o the extremities, thromboangiitis
obliterans, acute arterial occlusion, thoracic outlet syndrome
. Pulmonary hypertension
Neurologic disorders: intervertebral disk disease, syringomyelia, spinal cord

■ RAYNAUD’S PHENOMENON tumors, stroke, poliomyelitis, carpal tunnel syndrome, complex regional pain
R ’ , syndrome
, Blood dyscrasias: cold agglutinins, cryoglobulinemia, cryo ibrinogenemia,
, - myeloproli erative disorders, lymphoplasmacytic lymphoma
.E R ’ Trauma: vibration injury, hammer hand syndrome, electric shock, cold injury,
.T typing, piano playing
.T , Drugs and toxins: ergot derivatives, methysergide, β-adrenergic receptor
blockers, bleomycin, vinblastine, cisplatin, gemcitabine, vinyl chloride
(Fig. 275-3A). T , , -
.D , , R ’ :
, R ’ ,
.A R ’ ,
. (Table 275-1).
W , ,
. Primary Raynaud’s Phenomenon T
T “ ” .I R ’
, , .O 50% R ’
.A .W
R ’ , , 20 40 .
; . T .I
A B C
D E F
FIGURE 275-3 Vascular diseases associated with temperature: A. Raynaud’s phenomenon; B. acrocyanosis; C. livedo reticularis; D. pernio; E. erythromelalgia; and
F. rostbite.
, , , 1929
.T , , .
40% .A
, . TREATMENT

R , , , , ,
.R ’ Raynaud’s Phenomenon
.T
M R ’
. T
.
R ; ,
.I , -
, .T
, , -
.N .T .
, D .D -
.T , ,
(sclerodactyly) 10% .A ,
. R ’ . D
I , R ’ .T α1-
.F 1% ;
.A , . P 5
~15% 30%. , ,
Secondary Causes of Raynaud’s Phenomenon R ’ R ’ ,
80–90% .T -
( ) 30% (Chap. 353). I .D
.A - .I
R ’ .I R ’ -
.A 20% , .
(SLE) R ’
(Chap. 349). O , ■ ACROCYANOSIS
.I , I , -
. R -
’ 30% - , , .C
(Chap. 358). I .A
- .I -
. , ,
A R ’ <30 .G ,
>50 .T .T -
R ’ , , , .E
, .T - , , (Fig. 275-3B).
- T not .T
.O ,R ’ R ’
- , ,
. E .I
.T .C -
R ’ - .
. I , P
R ’ .P .
, , S ,
.R ’ , , , -
(Chap. 277); - , ,
.
. T .
A R ’
.C - , - ■ LIVEDO RETICULARIS
, I ,
, , - ( ) (Fig. 275-3C).
. H - T .
(W ö ’ T .T -
) , ,
R ’ . .T
R ’ , .
, - P
.T R ’ .T
.E .N .
R ’ P atrophie blanche
. en plaque. T .S -
S R ’ - ( ), SLE
. T , , β- , , ,
1930 , S ’ ( Kullo IJ, Rooke TW: P .NE JM 374:861,
). R , . 2016.
Olin JW :F :S
■ PERNIO (CHILBLAINS) : A S S A
P ; H A .C 129:1048, 2014.
PART 6
.R Thukkani AK, Kinlay S: E

(Fig. 275-3D). T . C R 116:1599, 2015.
, Vartanian SM, Conte MS: S -
. P . C R 116:1614, 2015.
Wigley FM, Flavahan NA: R ’ P .NE JM
.G
375:556, 2016.
. P
,
.S
.
■ ERYTHROMELALGIA
T
(Fig. 275-3E). T
, .E -
.
276 Chronic Venous Disease
and Lymphedema
I ( ) .M
Mark A. Creager, Joseph Loscalzo
SCN9A , N 1.7 -
,
. T
■ CHRONIC VENOUS DISEASE
.L C
, , , , , ,
; ; SLE; , . T
.P
,
.T . T U
.E - S ~15% 30% .C
- ~7.5% 5% ,
.T 2% <50
; 10% 70 .A 20%
. T .
.
■ VENOUS ANATOMY
■ FROSTBITE V
I , .T
.T .I ,
.F - .T
.I
, , , , .S
.P , .T
, .A , ,
, - - , , ,
.D , , .T -
.I , .T ,
, , (Fig. 275-3F). , ,
I , .S
. R , -
.T .
40°–44°C (104°–111°F). M , T
, .T ,
, ,
.A .A .P
.T , -
.A , .I
. , , ,
■ FURTHER READING .T
Bonaca MP, Creager MA: P , ,
. C R 116:1579, 2015. .
Creager MA :A .NE J M 366:2198, 2012. T
Gerhard-Herman MD : 2016 AHA/ACC - , , , , .T -
: -
A A C C /A H ,
A T F C P G .C .B
135: 726, 2017. .
Pathophysiology of Chronic Venous Disease Varicose veins 1931
, , ,
3 .T
, - , 1–3
CHAPTER 276 ChronicVenous Disease andLymphedema

, .T ,
, , , <1 ,
, , , , ,
- .
V .P
,
, .
A -
.O
, , , ,
.S ,
- - ,
-
. A
.
Chronic venous insufficiency
.I
.
FIGURE 276-1 Venous insu fciency with active venous ulcer near the medial
I .P - malleolus. (Courtesy o Dr. Steven Dean, with permission.)
.S - .A -
/ - .S
(Chap. 273). D - - .A
, ,
, (Fig. 276-1).
.A B -
, -
.S . W (
.O ), , . T
- M -T B –T
, - .A
; - , .T ,
;
- ; .F 30
K -T P -W . -
Clinical Presentation P . P -
.S , .T P
, , .S - .A
, , , .
T 5 .A -
, , -
;
.D -
.A , -
.
, , , .
T . Differential Diagnosis T -
V - -
.T .L , ,
. E , , , .O
. F - .B -
, , ,
, .T , ,
, , ,
.O , G ’ , -
.D .U
, , , - ,
, atrophie blanche, .L - , .C -
, , .L
, ; -
.A , , ; ,
; , , .
1932 TABLE 276-1 CEAP (Clinical, Etiologic, Anatomic, Pathophysiologic) TREATMENT
Classification
Clinical Classifcation
Chronic Venous Disease
C0 No visible or palpable signs o venous disease SUPPORTIVE MEASURES
PART 6
C1 Telangiectasias, reticular veins

V .
C2 Varicose veins S ,
C3 Edema without skin changes , .
C4 Skin changes, including pigmentation, eczema, lipodermatosclerosis, and E
atrophie blanche .
C5 Healed venous ulcer A ,

C6 Active venous ulcer .G
Etiologic Classifcation 20–30 H
Ec Congenital , 30–40
Ep Primary
H
.
Es Secondary (postthrombotic)
P
En No venous etiology identi ied
;
Anatomic Classifcation .G -
As Super icial veins
Ap Per orator veins , ,
Ad Deep veins CEAP C3–C6. G
An No venous location identi ied 30–40 H
.T
Pathophysiologic Classifcation
.C -
Pr Re lux , ; -
Po Obstruction , -
Pr,o Re lux and obstruction .E ,
Pn No venous pathophysiology identi iable ,
Source: Data rom B Eklö et al: J Vasc Surg 40:1248, 2004. ,
.O
T .
. I ,
Classification of Chronic Venous Disease T CEAP ( - -
, , , ) - .O (
. I ), ( -
, , ; >80% ),
, , ; - ( -
, , , (Table 276-1). ), ( ,
Diagnostic Testing T ),
- - .T
.A ,
B- D , .U
. C - .A
D . .T
O , .
, MEDICAL THERAPIES
, T U.S. F D A -
.V .D
,
V , .T
, .S
. , ( );
S - , ,
; F ,
.V - .
A - ,
,
.
M , , ,
.
.T INTERVENTIONAL AND SURGICAL THERAPIES
A , , -
, , ,
- ; ; ,
; M -T . ,
, , .A - .W , 1933
. , ,
E , -
. .B
CHAPTER 276 ChronicVenous Disease andLymphedema

T , - ,
.
.T
.T
, Lymphedema L
.A 1- 5-
90% .F -
.D -
- ,
. S .D , ,
O ,
, , , . ,
S .P
.S -
U.S. F D A - , , ,
, , , .T .
CO2/O2
.I Lymphatic Anatomy L -
, .T , .T -
.F , .L
, 30–40 H ,
1–2 .A 1- 5- 81 74%, .T ,
, .C , , -
- , , , .T
, .A .A ,
. , -
S .P
.T ,
.I .L -
.T
, .
.T T .
, . ., , .
S Etiology L -
(Table 276-2). T ~1.15
.C - 100,000 <20 .F
.P , -
- , , , , . , , .T
R 50% 5 , : ,
, - , ; , ;
. , 35. F
S (M ’ )
.A , (M ’ )
.T ; -
.A 19 -
.S (SEPS) . M
3 (VEGFR3),
.I . , M ’ ;
E , , VEGF-C, VEGFR3, M ’
- .A LSC1
- .M FOXC2 ,
.C - ,
, ,
.T - - ,
85% , - .A
~75% .I , SOX18,
, , ,
; , ( , , -
- ). M CCBE1 ,
. L - VEGF-C, H -
60% - , KIF11
.S - .M GATA2
- , ,
.V .P
1934 TABLE 276-2 Causes of Lymphedema
Primary
.I , -
Sporadic (no identi ied cause)
,
Genetic disorders , , , , , -
PART 6
Milroy’s disease (VEGFR3, VEGF-C) .L 13% -

Meige’s disease (gene mutation not established) 22%
Lymphedema-distichiasis syndrome (FOXC2) .L ~15%
Cholestasis-lymphedema (LSC1) .T ,
,
Hennekam’s lymphangiectasia-lymphedema syndrome (LCCBE1)

Emberger’s syndrome-lymphedema and predisposition to AML (GATA2) .L ,
Microcephaly-lymphedema syndrome (KIF11) , , -
.
Hypotrichosis-lymphedema-telangiectasia (SOX18)
Chromosomal aneuploidies Clinical Presentation L -
Turner’s syndrome , ,
Kline elter’s syndrome ,
Trisomy 13, 18, or 21 .L
Other disorders associated with primary lymphedema -
Noonan’s syndrome (Fig. 276-2). I ,
Klippel-Trénaunay syndrome
.O , ,
,
Parkes-Weber syndrome
.T S ’ ,
Yellow nail syndrome
.P ’
Intestinal lymphangiectasia syndrome ,
Lymphangiomyomatosis , .I ,
Neuro ibromatosis type 1
Secondary .T I S L -
In ection (Table 276-3).
Bacterial lymphangitis (Streptococcus pyogenes, Staphylococcus aureus) Differential Diagnosis L
Lymphogranuloma venereum (Chlamydia trachomatis) ,
Filariasis (Wucheria bancro ti, Brugia malayi, B. timori) - .I
Tuberculosis , ,
Neoplastic in iltration o lymph nodes , , ,
Lymphoma . O
Prostate .L
Others
.
Surgery or irradiation o axillary or inguinal lymph nodes or treatment o
cancer
Iatrogenic
Lymphatic division (during peripheral bypass surgery, varicose vein surgery,
or harvesting o saphenous veins)
Miscellaneous
Contact dermatitis
Podoconiosis
Rheumatoid arthritis
Pregnancy
Factitious
, T ’ ,K -
’ , 18, 13, 21, .
S
K -T P -W .
O N ’ -
, , ,
, 1.
S
.
R ,
, . T
>120 A B
14 -
FIGURE 276-2 A. Lymphedema characterized by swelling o the leg, nonpitting
(Chap. 228). R Streptococcus edema, and squaring o the toes. (Courtesy o Dr. Marie Gerhard-Herman, with
.O permission.) B. Advanced chronic stage o lymphedema illustrating the woody
. A appearance o the leg with acanthosis and verrucous overgrowths. (Courtesy o
, Dr. Je rey Olin, with permission.)
TABLE 276-3 Stages of Lymphedema O , 1935
Stage 0 (or Ia) .D
A latent or subclinical condition where swelling is not evident despite impaired
lymph transport. It may exist or months or years be ore overt edema occurs. .
CHAPTER 277 Pulmonary Hypertension

L
Stage I
,
Early accumulation o luid relatively high in protein content that subsides with . O
limb elevation. Pitting may occur. An increase in proli erating cells may also be
. M
seen.
Stage II
Limb elevation alone rarely reduces tissue swelling, and pitting is mani est. .L
Late in stage II, the limb may or may not pit as excess at and ibrosis
supervene.
.
Stage III T -
Lymphostatic elephantiasis where pitting can be absent and trophic skin . O VEGF-C
changes such as acanthosis, urther deposition o at and ibrosis, and warty
overgrowths have developed. , VEGF-C
Source: Adapted rom The 2013 Consensus Document o the International VEGF-D
Society o Lymphology: Lymphology 46:1, 2013. . T
.C
Diagnostic Testing T
.A - .
(CT)
. M
(MRI) - ■ FURTHER READING
Aspelund A :L .C
. MRI R 118:515, 2016.
.L - Brouillard P : G . J C I
, 124:898, 2014.
. L - Eberhardt RT, Raffetto JD: C .C
- 130:333, 2014.
Garg N, Gloviczki P: C , Vascular
, Medicine, MA C , JA B , JL ( ). P ,
. F E , 2013, 652–666.
Gloviczki P :T -
.F : C
S V S A V F .JV
. I , S 53:2S, 2011.
Kahn SR :T :E - -
.I , , , , :A
, .I , A H A .C 130:1636, 2014.
.T Karaca-Mandic P : T ,
.A - . JAMA D 151:1187, 2015.

- Lee BB :D .C -
. I U P .I A
32:541, 2013.
Mortimer PS, Rockson SG: N
TREATMENT .JC I 124:915, 2014.
Lymphedema Tafur AJ, Rathbun S: V V , Vascular Medicine. MA C ,
JA B ,JL ( ). P ,E , 2013, 639–651.
P
.S , -
.P
, .
P ;
, - ,
.P -
,
277 Pulmonary Hypertension
Aaron B. Waxman, Joseph Loscalzo
.
P , -
, . T P (PH)
,
( [PAP] >22 H
. M , PAP >36 H ). P -
. (PAH) PH
A - , , .I ,
, . ,
1936 . T (CO) .W CO, PAP
- . A CO
, , PAH. D , . T
, 2 . , , , -
I , - .
PART 6
A -
.T
(Table 277-1). T
- - ,
.A -2, -
.C , , -
PH - - -1α,
.I , , , T .A ,
. -
■ PATHOBIOLOGY .I ,
V , , , -
PAH (Fig. 277-1). I
, , in situ .
.
V - ■ DIAGNOSIS AND CLASSIFICATION
.A , T PH -
. PH , , -
.T ,
, .M
(PVR), , , .I / , , , ,
, PVR , .I
PAP PAH, .A
FIGURE 277-1. Panels on the le t show examples o plexogenic pulmonary arteriopathy. These are obstructive and proli erative lesions o the small muscular
pulmonary arteries, composed primarily o endothelial cells with intermixed infammatory cells, myo broblasts, and connective tissue components. The lower le t panel
demonstrates proli erating cells (red PCNA stain—white arrows). Panels on the right demonstrate medial hypertrophy o muscular pulmonary arteries. (Photograph on
the lower le t is courtesy o Dr. Stephen Archer, Queen’s University School o Medicine, Kingston, Ontario, Canada.)
TABLE 277-1 Molecular Determinants of the Pathogenesis of 1937
Pulmonary Arterial Hypertension , ,
Alterations in regulators o proli eration .A ,
• Grow th factors P2 , - S3

S4, .I -
• P DG F
PH:
• FGF
,
• VEGF ,
• EG F -
• TGF-β .
• BM P O ,
• Transcription factors .A bubble study
• MMPs .E -
• Cytokines
.A PH
(Fig. 277-2)
• Chem okines
. I
• M itochondria PH,
Alterations in in lammatory mediators , , -
• A ltered T-cell su bsets , .
• M onocytes and m acrophages A D ,
• IL-1 β
• IL-6 PH. A
• M CP -1
,
.W -
• RA NTES
, PH;
• Fractalkine .I ,
Alterations in vascular tone (RHC)
• Endothelin .A , -
• Nitric oxide , -
• Serotonin
• P rostaglandin .I , RHC.
• K + channels
I (CPET)
PH , -
• Ca2+ channels
Hypoxia induced remodeling .A
• HIF-1 α .
• RO S C
• M itochondria PH. S PH
Alterations in TGF-β signaling pathways
• BM P R2 , “ ,” (Fig. 277-3). H -
• A LK1
(CT)
.C PH CT
• Endoglin
: (Fig. 277-4), -
• Sm ad9 , .H -
• TGF-β1 , - CT ,
Abbreviations: ALK, anaplastic lymphoma kinase; BMP, bone morphogenic protein;
EGF, epidermal-derived growth actor; FGF, etal-derived growth actor; HIF-1α, .I , -
hypoxia-inducible actor-1; IL, interleukin; MCP-1, monocyte chemoattractant
protein-1; MMP, mucous membrane pemphigoid; PDGF, platelet-derived growth
, PAH
actor; ROS, reactive oxygen specie; TGFβ, trans orming growth actor β; VEGF, . CT -
vascular endothelial-derived growth actor. .
FR 45 Hz FR 47 Hz
18 cm 17 cm
BP
124/76
77 bpm 61 bpm
A B
FIGURE 277-2 Panel (A) is a representative echocardiogram showing the apical 4-chamber view rom a patient with pulmonary hypertension demonstrating an enlarged
right atrium and ventricle with some compression o the le t side o the heart. Panel (B) is the same echocardiographic view showing a normal echocardiogram.
1938 ,
. I ,
- -
-
PART 6
-
(VE/VCO2 ).
S -
PH,
’ . N -
PH, - -
.T ,
,
-
.
L
FIGURE 277-3 Postero-anterior (left) and lateral (right) chest radiograph showing enlarged pulmonary arteries HIV -
(black arrows) and pruning o the distal pulmonary vasculature (white arrows) commonly seen with advanced . I ,
pulmonary arterial hypertension. , -
, - -70
CT - PH. L
. . - .F ,
. V - ( V/Q )
PH. B (BNP)
.T CT N- - (NT- BNP) -
( ) , , PAH.
(CTEPH) . . , CT. RHC -
A V/Q CTEPH, PH
CT . .T PH PAH
P - (1) PAP ( PAP >25 H ); (2) -
.W (PCWP), ,
(DLCO) PAH, - (LVEDP) ≤15 H ; (3) PVR >3
W .P PH PH
PH. T 6- PCWP ≥15 H ; ,
<12 H , ,
>12 H PVR. I
, CO .
V ,
(NO), -
.A PAP ≥10 H ≤40 H
CO
, -
(CCB). L 15%
, - -
CCB. A - PVR PAP
-
CCB. T PH ,
,
.F ,
-
.
■ PULMONARY HYPERTENSION AS A COMORBID

DISEASE
PAH
.A
,
.T W H
O (WHO)
PH, PAH , -
. PH
FIGURE 277-4 Representative computed tomographic scan o the chest PAP .T PH

demonstrating enlarged main pulmonary arteries. There is also a mosaic pattern -
evident in both lungs. .E
- - 1939
, , .T PH
. . I ,
T , 2013 ,

F W S P H , (>12 H ) PVR
PH, PAH, PH , PH (>3 W ). P ,
, PH ,
PH. PAH.
Pulmonary Arterial Hypertension WHO G I PH, PAH, Pulmonary Hypertension Associated with Lung Disease
PH. PAH I PH,
. PH
, , .I
, . PAH - / -
( PAP) : , ,
5
≥25 H , PVR > 240 -/ , PCWP LVEDP ≤15 H , -
RHC. W PCWP PAP, .A ,
( PAP– PH ; ,
PCWP) PVR. PH “ ”
I PAH (IPAH) ,
.T N I H , .T PH,
PAH, DLCO.
36 , 9% IPAH A PH ,
60. H , ;
.T P H C , .E -
IPAH 45 , PH
8.5% 70 .T ,
R E E A L - .T -
PAH D M (REVEAL) , PAH PH .
, IPAH A G III PH - .S
44.9+/-0.6 . PH. H , PH
O PAH - .
HIV, , -
.A HIV PAH, PAH - PH Associated with Chronic Thromboembolic Disease
IPAH T PH
HIV- .I , ,
HIV PAH. .T PH
A , PAH ,
, .T CTEPH .M
.A . T
30 50 , - CTEPH . O
PAH .
O PAH ; , .
, A 10–15%
. PAH
P 2–10% .
. I -
■ OTHER DISORDERS AFFECTING THE PULMONARY
- .A - VASCULATURE
, ; Sarcoidosis P PH
, , -
PAH - PH .W
. I PH PAH,
, PH
- .
. Sickle Cell Disease C

, PH.
Pulmonary Hypertension Associated with Left Heart T , , , -
Disease WHO G II PH , CO, .T
, , PH .
(HF EF). PH
.T G II PH Schistosomiasis G ,
.I , PH. T PH
PVR .A . S
-
- , HF EF .T
PH. , -
W ( . ., .T PH
), .
1940 ■ PHARMACOLOGIC TREATMENT OF PAH Endothelin Receptor Antagonists ERA ET-1,
W PAH .T
PAH, - PAH .E
, NO , - PVR PAP, CO 6MWD.
(ERA ) ERA ET-1 A
PART 6
.W PAH, (ET-A) / B (ET-B). ET-A

, , . (PASMC) .I
, ET-B
■ PROSTANOIDS ET-1 ,
I PAH, NO. T ERA U
S , - ;
A2 .P (PGI2) , ET-A .
( AMP)- - S
. PGI2 . T ,
.P , III, B R E -
A THE (BREATHE)-1
PAH. T , 6MWD, WHO -
PAH. .T E A T M S
E P A H P (EARLY)
PAH. E PVR 6MWD.
PAH. T S , III - A -
WHO FC 3 4 PAH P A H , (ARIES)-1 ,
, PAP, PVR, , WHO ,
6- (MWD) .T , PAH. T
- (~4 ~6 ), ET-A
.T - ET
, , .
, , PAH.
I - Nitric Oxide Pathway N (NO) -
( , , GMP
) .B . GMP -
WHO FC
3 4 PAH. T .P 5
.I GMP. T , GMP
PAH 5 (PDE5) NO,
.P -5 (PDE5) GMP
( . ., ) .T PDE5 -
( GMP) GMP- PAH, .B
.T - 6MWD.
-5 (PDE5) , , R -
PAH. NO,
O ( ) NO . R -
- ï , , WHO
- .O - , PAH
6MWD (+23 CTEPH.
, P=0.0125)
.B , Combination Therapy C -
PDE5
ETRA 6MWD. A .C -
, .A
, , PAH
, FDA- WHO , -
1 PAH. O , .T
( ) . HIV, , . U
S ,
I2 (IP) .T .
- D
. T .
3 A F PAH -
PAH N Y H A (NYHA)
FC II III -1 (ET-1) .T 19
, , .T PAH , ,
- PAH .O
, 1100 19 , 18
1.4 .S 4 . T
43% (P<0.0001) -
.T 2 .M , 1-, 2-, 3-
.T 100%. A ,
. - , .
TABLE 277-2 FDA-Approved Therapies for the Treatment of Pulmonary Arterial Hypertension (PAH) 1941
GENERIC NAME ROUTE OF ADMINISTRATION DRUG CLASS INDICATION

Epoprostenol IV Prostacyclin derivative Treatment o PAH to improve exercise capacity

Iloprost Inhaled Prostacyclin derivative Treatment o PAH to improve a composite endpoint consisting
o exercise tolerance, symptoms (NYHA Class), and lack o
deterioration
Treprostinil IV or SC Prostacyclin derivative Treatment o PAH to diminish symptoms associated with
exercise
Treprostinil Inhaled Prostacyclin derivative Treatment o PAH to improve exercise ability
Treprostinil Oral Prostacyclin derivative Treatment o PAH to improve exercise ability
Selexipeg Oral Selective IP receptor agonist Treatment o PAH to improve a composite endpoint lack o
clinical deterioration
Bosentan Oral Endothelin receptor antagonist Treatment o PAH to improve exercise capacity and to decrease
clinical worsening
Ambrisentan Oral Endothelin receptor antagonist Treatment o PAH to improve exercise capacity and delay
clinical worsening
Macitentan Oral Endothelin receptor antagonist Treatment o PAH to improve a composite endpoint o delay o
clinical worsening
Sildena il Oral PDE5 inhibitor Treatment o PAH to improve exercise capacity and delay
clinical worsening
Tadala il Oral PDE5 inhibitor Treatment o PAH to improve exercise ability
Riociguat Oral Soluble guanylyl cyclase stimulator Treatment o PAH to improve exercise ability
Abbreviations: IV, intravenous; NYHA, New York Heart Association; PAH, pulmonary arterial hypertension; PDE5, phosphodiesterase-5; SC, subcutaneous.
T AMBITION
.P PH.
, -
, .U ■ FURTHER READING
50% Bossone E :E :
( , , - F .JA S E 26:1, 2013.
PAH , PAH) Galie N :I
.T .NE JM 373:834, 2015.
.I , Ghofrani HA :R
. .NE JM 369:330, 2013.
Huetsch JC :U
Unmet and Future Research Needs in Pulmonary .A JP L C M
Hypertension P P 311:L811, 2016.
PAH , , Pietra GG :P -
PAH 5–6 (Table 277-2). W .JA C C 43(12 S S):25S, 2004.
PH, - Rich JD, Rich S: C .C -
.N 130:1820, 2014.
PAH, Simonneau G :U -
PH. L , , - .JA C C 62(25 S ):D34, 2013.
.I Sitbon O :S -
- .NE J M 373:2522, 2015.
. PH Soubrier F :G -
.P . JA C C 62(25 S ):D13, 2013.
Waxman AB, F HW: U
, - .C 132:2152,
- - .F , 2015.

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Disorders of the Cardiovascular System PART 6

Section 1 Introduction to Cardiovascular .U -

activity without discom ort

CHAPTER 232 Basic Biology of the Cardiovascular System

■ ORIGIN OF VASCULAR CELLS

CHAPTER 232 Basic Biology of the Cardiovascular System

Control of Vascular Smooth-Muscle Cell Tone T -

CHAPTER 232 Basic Biology of the Cardiovascular System

Mitochondrion Contract Relax

CHAPTER 232 Basic Biology of the Cardiovascular System

4. Dissociation of Actin Actin 2. Formation of

Rigor complex Active complex

Via protein kinase A +

CHAPTER 232 Basic Biology of the Cardiovascular System

1. Body position Contractility Stroke volume

CHAPTER 232 Basic Biology of the Cardiovascular System

Abnormal relaxation Pericardial restraint

Thomas A. Gaziano, J. Michael Gaziano I age of delayed degenerative diseases, CVD

TABLE 233-1 Five Stages of the Epidemiologic Transition

CHAPTER 233 Epidemiology of Cardiovascular Disease

Number of CVD deaths in millions

CHAPTER 233 Epidemiology of Cardiovascular Disease

Obesity A CHD, Lozano R :G 235

~508 (BMI ≥30 / 2). O

■ FURTHER READING ■ THE GENERAL PHYSICAL EXAMINATION

CHAPTER 234 Physical Examination of the Cardiovascular System

CHAPTER 234 Physical Examination of the Cardiovascular System

CHAPTER 234 Physical Examination of the Cardiovascular System

Dorsalis pedis artery pressure

A Major arteries of the lower limb B Measurement of ankle systolic pressure

CHAPTER 234 Physical Examination of the Cardiovascular System

CHAPTER 235 Electrocardiography

■ ELECTROPHYSIOLOGIC BACKGROUND QRS

R 300 (0.04 ) 1500. T

CHAPTER 235 Electrocardiography

■ T WAVE AND U WAVE

R .H , ■ BUNDLE BRANCH BLOCKS AND RELATED PATTERNS

Normal Right Left LVH

CHAPTER 235 Electrocardiography

(Fig. 235-12). (Chap. 11). F ,

A ECG sequence with anterior Q-wave infarction

B ECG sequence with inferior Q-wave infarction

CHAPTER 235 Electrocardiography

Tricyclic overdose Subarachnoid hemorrhage

Hypocalcemia Normal Hypercalcemia

QT 0.48 s QT 0.36 s QT 0.26 s

Phased array Processing and scan conversion

M-mode image 2-D image

Thalium-201 SPECT 72 h Myocardial per usion imaging

Short axis Total perfusion deficit

Stress time activity curves Mid-VLA

TOT 2.30 1.06 2.18 100

CT .W , FIGURE 236-7 Examples o non-contrast- and contrast-enhanced coronary imaging with

0.75< E/A<1.5 E/A≤0.75 0.75 <E/A<1.5 E/A≥1.5 E/A>1.5

∆E/A<0.5 ∆E/A<0.5 ∆E/A≥0.5 ∆E/A≥0.5 ∆E/A≥0.5

E/e’<10 E/e’<10 E/e’≥10 E/e’≥10 E/e’≥10

S≥D S>D S<D or S<D or S<D or

Left ventricular relaxation Normal Impaired Impaired Impaired Impaired

Stress Radionuclide Imaging SPECT .C , CAC -

Reversible perfusion defect Fixed perfusion defect

Rest SEP LAT

Calcium score: 1330

Event rate (%/year)

Duke treadmill score Duke treadmill score