Source: Harrison’s Internal Medicine 20th edition

Chapter 267: Ischemic heart disease

Chapter 268: NSTEMI

Chapter 269: STEMI

Ischemic heart disease

- a condition in which there is an inadequate supply of blood and oxygen to a portion of the
myocardium

- occurs when there is an imbalance between myocardial oxygen supply and demand

- The common cause of myocardial ischemia is atherosclerotic disease of an epicardial coronary artery
(or arteries)

Pathophysiology

- concept of myocardial supply and demand

- major determinants of myocardial oxygen demand are heart rate, myocardial contractility, and
myocardial wall tension

- 75% of the total coronary resistance to ow occurs across three sets of arteries: (1) large
epicardial arteries (Resistance 1 = R1), (2) prearteriolar vessels (R2), and (3) arteriolar and
intramyocardial capillary vessels (R3)

Coronary atherosclerosis

- epicardial coronary arteries are the major site of atherosclerotic disease.

- the major risk factors for atherosclerosis are (high levels of plasma low-density lipoprotein [LDL], low
plasma high-density lipoprotein [HDL], cigarette smoking, hypertension, and diabetes mellitus

- functional changes in the vascular milieu ultimately result in the subintimal collections of fat, smooth
muscle cells, broblasts, and intercellular matrix that de ne the atherosclerotic plaque

- atherosclerosis develops at irregular rates in di erent segments of the epicardial coronary tree and
leads eventually to segmental reductions in cross-sectional area, i.e., plaque formation

- there is also a predilection for atherosclerotic plaques to develop at sites of increased turbulence in
coronary ow, such as at branch points in the epicardial arteries

- segmental atherosclerotic narrowing of epicardial coronary arteries is caused most commonly by the
formation of a plaque, which is subject to rupture or erosion of the cap separating the plaque from the
bloodstream

Upon exposure of the plaque contents to blood, two important and interrelated processes are set in
motion:

(1) platelets are activated and aggregate

(2) the coagulation cascade is activated, leading to deposition of brin strands.

A pressure gradient develops across the proximal stenosis, and poststenotic pressure falls.

When the resistance vessels are maximally dilated, myocardial blood ow becomes dependent on the
pressure in the coronary artery distal to the obstruction.

In these circumstances, ischemia, manifest clinically by angina or electrocardiographically by ST-

segment deviation, can be precipitated by increases in myocardial oxygen demand caused by physical
activity, emotional stress, and/or tachycardia.

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 E ects of ischemia

Regional disturbances of ventricular contractility cause:

- segmental hypokinesia

- akinesia,

- or, in severe cases, bulging (dyskinesia), which can reduce myocardial pump function.

* Mitral regurgitation can occur if the papillary muscle apparatus is involved in transient left ventricular
failure

When ischemia is transient, it may be associated with angina pectoris;

when it is prolonged, it can lead to myocardial necrosis and scarring with or without the clinical picture
of acute myocardial infarction.

The normal myocardium metabolizes fatty acids and glucose to carbon dioxide and water.

severe oxygen deprivation:

- fatty acids cannot be oxidized

- glucose is converted to lactate

- intracellular pH is reduced

Impaired cell membrane function leads to the leakage of potassium and the uptake of sodium by
myocytes as well as an increase in cytosolic calcium.

- severity and duration of the imbalance between myocardial oxygen supply and demand determine
whether the damage is reversible (≤20 min for total occlusion in the absence of collaterals) or permanent,
with subsequent myocardial necrosis (>20 min)

ECG changes:

- Intramyocardial ischemia: Transient T wave inversion

- Subendocardial ischemia: Transient ST segment depression

- Transmural ischemia: ST segment elevation

- Isolated ventricular premature beats or even ventricular tachycardia or ventricular brillation due to
electrical instability

* Most patients who die suddenly from IHD do so as a result of ischemia- induced ventricular
tachyarrhythmias

Stable Angina Pectoris

- Due to transient myocardial ischemia

- Males constitute ~70% of all patients with angina pectoris and an even greater proportion of those
aged <50 years.

- It is, however, important to note that angina pectoris in women is often atypical in presentation.

History

The typical patient with angina

- man >50 years or a woman >60 years of age

- complains of episodes of chest discomfort

- described as heaviness, pressure, squeezing, smothering, or choking and only rarely as frank pain

- Levine’s sign

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 Anginal pain:

- crescendo-decrescendo in nature

- typically lasts 2–5 min

- can radiate to either shoulder and to both arms (especially the ulnar surfaces of the forearm and hand)

- can arise in or radiate to the back, inter scapular region, root of the neck, jaw, teeth, and epigastrium

* Angina is rarely localized below the umbilicus or above the mandible and myocardial ischemic
discomfort does not radiate to the trapezius muscles.

- typically caused by exertion or emotion

- relieved by rest

- Angina decubitus: angina at rest and while the patient is recumbent

However, especially in women and diabetic patients, angina pectoris may be atypical in location and not
strictly related to provoking factors.

Anginal equivalents: symptoms of myocardial ischemia other than angina

- They include dyspnea, nausea, fatigue, and faintness and are more common in the elderly and in
diabetic patients.

* The history of typical angina pectoris establishes the diagnosis of IHD until proven otherwise. The
coexistence of advanced age, male sex, the postmenopausal state, and risk factors for atherosclerosis
increase the likelihood of hemodynamically signi cant coronary disease.

Laboratory evaluation:

- urinalysis: evidence of diabetes mellitus (glucosuria), renal disease

- lipid panel: cholesterol, LDL, HDL, Triglycerides

- glucose (hemoglobin A1C)

- creatinine

- hematocrit

- if indicated based on the physical examination, thyroid function

- chest xray: may show the consequences of IHD, i.e., cardiac enlargement, ventricular aneurysm, or
signs of heart failure

- electrocardiogram

- stress test

- cardiac imaging

- echocardiography

Coronary Arteriography:

- outlines the lumina of the coronary arteries and can be used to detect or exclude serious coronary
obstruction

Indications:

(1) patients with chronic stable angina pectoris who are severely symptomatic despite medical therapy
and are being considered for revasculariza-tion, i.e., a percutaneous coronary intervention (PCI) or
coronary artery bypass grafting (CABG)

(2) patients with troublesome symptoms that present diagnostic di culties in whom there is a need to
con rm or rule out the diagnosis of IHD

(3) patients with known or possible angina pectoris who have survived cardiac arrest

(4) patients with angina or evidence of ischemia on noninvasive testing with clinical or laboratory
evidence of ventricular dysfunction

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 (5) patients judged to be at high risk of sustaining coronary events based on signs of severe ischemia
on noninvasive testing, regardless of the presence or severity of symptoms

Other indications:

1. Patients with chest discomfort suggestive of angina pectoris but a negative or nondiagnostic stress
test who require a de nitive diag-nosis for guiding medical management, alleviating psychological
stress, career or family planning, or insurance purposes

2. Patients who have been admitted repeatedly to the hospital for a suspected acute coronary
syndrome but in whom this diagnosis has not been established and in whom the presence or
absence of CAD should be determined

3. Patients with careers that involve the safety of others (e.g., pilots, re ghters, police) who have
questionable symptoms or suspicious or positive noninvasive tests and in whom there are
reasonable doubts about the state of the coronary arteries

4. Patients with aortic stenosis or hypertrophic cardiomyopathy and angina in whom the chest pain
could be due to IHD

5. Male patients >45 years and females >55 years who are to undergo a cardiac operation such as
valve replacement or repair and who may or may not have clinical evidence of myocardial ischemia

6. Patients after myocardial infarction, especially those who are at high risk after myocardial infarction
because of the recurrence of angina or the presence of heart failure, frequent ventricular premature
contractions, or signs of ischemia on the stress test

7. Patients with angina pectoris, regardless of severity, in whom noninvasive testing indicates a high
risk of coronary events (poor exercise performance or severe ischemia)

8. Patients in whom coronary spasm or another nonatherosclerotic cause of myocardial ischemia (e.g.,
coronary artery anomaly, Kawasaki disease) is suspected.

CT angiography and CMR angiography: Noninvasive alternatives to diagnostic coronary arteriography

Treatment:

Management plan should include the following components

1. explanation of the problem and reassurance about the ability to formulate a treatment plan

2. identi cation and treatment of aggravating conditions

3. recommendations for adaptation of activity as needed

4. treatment of risk factors that will decrease the occurrence of adverse coronary outcomes

5. drug therapy for angina

6. consideration of revascularization

Drug therapy:

1. Nitrates

Action: systemic venodilation and concomitant reducation in LV diastolic volume and pressure

2. Beta adrenergic blockers

Action: reduce myocardial oxygen demand by inhibiting the increases in heart rate, arterial pressure, and
myocardial contractility caused by adrenergic activation

Relative contraindications include asthma and reversible airway obstruction in patients with chronic lung
disease, atrioventricular conduction disturbances, severe bradycardia, Raynaud’s phenomenon, and a
history of mental depression.

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 3. Calcium channel blockers

Action: coronary vasodilators that produce variable and dose- dependent reductions in myocardial
oxygen demand, contractility, and arterial pressure.

- indicated when beta blockers are contraindicated, poorly tolerated, or ine ective

4. Aspirin

Action: irreversible inhibitor of platelet cyclooxygenase and thereby interferes with platelet activation

- should be considered in all patients with IHD in the absence of gastrointestinal bleeding, allergy,
or dyspepsia

5. Clopidogrel

Action: an oral agent that blocks P2Y12 ADP receptor–mediated platelet aggregation

Dosage: 300–600 mg loading and 75 mg/d

- may be substituted for aspirin if aspirin causes side e ects

Alternative antiplatelet agents that block the P2Y12 platelet receptor such as prasugrel and ticagrelor
have been shown to be more e ective than clopidogrel for prevention of ischemic events after
placement of a stent for an acute coronary syndrome, but are associated with an increased risk of
bleeding

6. ACE inhibitors

- when despite treatment with nitrates, beta blockers, or calcium channel blockers, some patients with
IHD continue to experience angina

- Ranolazine

- a piperazine derivative, may be useful for patients with chronic angina despite standard medical
therapy

- Its antianginal action is believed to occur via inhibition of the late inward sodium current (INa)

- The bene ts of INa inhibition include limitation of the Na overload of ischemic myocytes and
prevention of Ca2+ overload via the Na+–Ca2+ exchange

- A dose of 500–1000 mg orally twice daily is usually well tolerated

- contraindicated in patients with hepatic impairment or with conditions or drugs associated with
QTc prolongation and when drugs that inhibit the CYP3A metabolic system

7. Ivabradine

Action: speci c sinus node inhibiting agent that may be helpful for preventing cardio-vascular events in
patients with IHD who have a resting heart rate ≥70 beats/min (alone or in combination with a beta
blocker) and LV systolic dysfunction in patients who have clinical heart failure

Coronary revascularization

- considered in the presence of unstable phases of the disease, intractable symptoms, severe ischemia
or high-risk coronary anatomy, diabetes, and impaired LV function

Percutaneous coronary intervention

- involving balloon dilatation usually accompanied by coronary stenting is widely used to achieve
revascularization of the myocardium in patients with symptomatic IHD and suitable stenoses of
epicardial coronary arteries

- indication for PCI is symptom-limiting angina pectoris, despite medical therapy, accompanied by
evidence of ischemia during a stress test

Coronary Artery Bypass Graft

Indications:

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 - three-vessel disease (or two-vessel disease that includes the proximal left descending coronary
artery)

- impaired global LV function (LV ejection fraction <50%) or diabetes mellitus

- left main CAD

- other lesions unsuitable for catheter-based procedure

Acute Coronary Syndrome

Acute coronary syndrome ST elevation myocardial infarction

-myocardial injury caused by the abrupt decrease in coronary blood ow after a coronary artery
thrombotic occlusion caused by atherosclerosis

-Causative mechanism: PLAQUE RUPTURE

-UNLIKELY from slow-developing high grade coronary artery stenosis eluding development of a rich
collateral circulation

-precipitated by rapid vascular occlusion at the site of injury

• atherosclerotic plaque disruption (usually having rich lipid core & thin brous cap)

• factors favoring thrombogenesis (local or systemic)

PATHOPHYSIOLOGY
1. initial platelet monolayer forms at the site of the disrupted plaque, then various agonists (collagen,
ADP, epinephrine, serotonin) promote platelet activation

2. thromboxane A2 (a potent local vasoconstrictor) is released and further platelet activation occurs,
and potential resistance to brinolysis develops

3. conformational change in the glycoprotein IIb/IIIa receptor -high a nity for soluble adhesive
proteins (i.e., integrins) such as brinogen

4. brinogen -platelet cross-linking and aggregation

5. exposure of tissue factor in damaged endothelial cells activates coagulation cascade

6. Factors VII and X are activated - leading to conversion of prothrombin to thrombin, which then
converts brinogen to brin

7. uid-phase and clot-bound thrombin participate in an autoampli cation reaction leading to further
activation of the coagulation cascade then ultimately leading to further stenosis and occlusion of
culprit artery

Extent of myocardial damage caused by coronary occlusion depends on the :

1. territory supplied by the a ected vessel

2. whether or not the vessel becomes totally occluded

3. duration of occlusion

4. quantity of collateral circulation to the a ected tissue

5. demand for oxygen of the myocardium whose blood supply has been suddenly limited

6. endogenous factors that can produce early spontaneous lysis of the occlusive thrombus

7. adequacy of myocardial perfusion in the infarct zone when ow is restored in the occluded epicardial
coronary artery

CLINICAL PRESENTATION

-precipitating factors present before STEMI, such as vigorous physical exercise, emotional stress, or a
medical or surgical illness in up to 50% of cases

-PAIN = most common presenting complaint (deep and visceral); described as heavy, squeezing, and
crushing; occasionally described as stabbing or burning

>30 minutes of substernal chest pain in combination with diaphoresis strongly suggests STEMI

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**similar in character of angina pectoris but commonly occurs at rest, and is usually more severe and
lasts longer

pain involves the central portion of the chest and/or the epigastrium, and, on occasion, it radiates to the
arms. Less common sites of radiation include the abdomen, back, lower jaw, and neck

-may radiate as high as the occipital area but not below the umbilicus

-often accompanied by weakness, sweating, nausea, vomiting, anxiety, and a sense of impending doom.

PHYSICAL FINDINGS

-anxious & restless

-“autonomic phenomena”: pallor with perspiration & coolness of extremities, diaphoresis

-most have normal heart rate and blood pressure within 1st hour of STEMI, ~25% of patients with
ANTERIOR infarction have sympathetic nervous system hyperactivity (tachycardia, hypertension), ~50%
of INFERIOR infarction have parasympathetic hyperactivity (bradycardia, hypotension)

-precordium is usually quiet and apical impulse may be di cult to palpate

• ANTERIOR wall infarction: abnormal systolic pulsation caused by dyskinetic bulging of infarcted
myocardium in the periapical area within rst days of illness and then resolves

-ventricular dysfunction: presence of 3rd & 4th heart sounds, decreased intensity if 1st heart sound,
paradoxical splitting of 2nd heart sound

-mitral valve dysfunction: transient midsystolic or late systolic apical systolic murmur

-transmural STEMI: pericardial friction rub

-reduced stroke volume: decreased carotid pulse volume

LABORATORY FINDINGS

Electrocardiogram

The ECG leads are usually more helpful in localizing regions of ST elevation than non-ST elevation
ischemia.

For example:

-acute transmural anterior (including apical and lateral) wall ischemia is re ected by ST elevations or
increased T-wave positivity in one or more of the precordial leads (V1–V6) and leads I and aVL.

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 -inferior wall ischemia produces changes in leads II, III, and aVF

-posterior wall ischemia (usually associated with lateral or inferior involvement) may be indirectly
recognized by reciprocal ST depressions in leads V1 to V3 (thus constituting an ST elevation
“equivalent” acute coronary syndrome).

-right ventricular ischemia usually produces ST elevations in rightsided chest leads

During the initial stage, total occlusion of an epicardial coronary artery produces ST-segment elevation.
Most patients initially presenting with ST-segment elevation ultimately evolve Q waves on the ECG

A small proportion of patients initially presenting with ST-segment elevation will not develop Q waves
when the obstructing thrombus is not totally occlusive, obstruction is transient, or if a rich collateral
network is present.

In patients presenting with ischemic discomfort and without ST-segment elevation, when serum cardiac
biomarker of necrosis is detected, the diagnosis of NSTEMI is ultimately made.

Di erential Diagnosis of ST-Segment Elevations

Ischemia/myocardial infarction

• Noninfarction, transmural ischemia (Prinzmetal’s angina, and probably Takotsubo syndrome,

which may also exactly simulate classical acute infarction)

• Acute myocardial infarction

• Postmyocardial infarction (ventricular aneurysm pattern)

Acute pericarditis

Normal variants (including benign “early repolarization” patterns)

Left ventricular hypertrophy/left bundle branch block**

Other (rarer)

• Acute pulmonary embolism**

• Brugada patterns (right bundle branch block–like pattern with ST elevations in right precordial
leads)**

• Class 1C antiarrhythmic drugs**

• DC cardioversion

• Hypercalcemia**

• Hyperkalemia**

• Hypothermia (J [Osborn] waves)

• Nonischemic myocardial injury

- Myocarditis Tumor invading left ventricle

- Trauma to ventricles

**usually localized to V1-V2 or V3

anterior wall infarction (early phase)

anterior infarction with Q-waves (evolving phase)

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 Serum Cardiac Biomarkers

-the criteria for AMI requires a rise and/or fall in cardiac biomarker values with at least one value above
the 99th percentile of the upper reference limit for normal individuals.

Cardiac-speci c troponin T (cTnT) and Cardiac-speci c troponin I (cTnI) have amino acid
sequences di erent from skeletal muscle forms of these proteins

-cTnI & cTnT levels may remain elevated for 7-10 days after STEMI

-CK rises within 4-8hrs and generally returns to normal by 48-72 hrs

-drawback of total CK is lack of speci city for STEMI as it may be elevated with skeletal muscle disease
or trauma, including intramuscular injection

-CK-MB advantage over total CK is that it is not present in signi cant concentrations in extracardiac
tissue and, therefore is more speci c - **clinically useful in assessing for reinfarction due to short half life
as compared to cardiac troponins

-the nonspeci c reaction to myocardial injury is associated with polymorphonuclear leukocytosis, which
appears within a few hours after the onset of pain and persists for 3-7 days

-WBC often reaches levels of 12,000-15,000 uL

-ESR rises more slowly than WBC, peaking during the 1st week and sometimes remaining elevated for 1
or 2 weeks

Cardiac Imaging

Echocardiography

-early detection of the presence or absence wall motion abnormalities

-cannot distinguish old myocardial scar from acute severe ischemia

-prognostic estimation of LV function

-identify presence of RV infarction, ventricular aneurysm, pericardial e usion, LV thrombus

-doppler echocardiography - useful in detecting and quantifying VSD and MR (serious complications of
STEMI)

Radionuclide imaging
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 -used less often; cumbersome, lack sensitivity and speci city in many clinical circumstances

• Myocardial perfusion imaging

-with [201Tl] or [99mTc]- sestamibi - distributed in myocardial blood ow and concentrated by

viable myocardium

-defects or “cold spots” in rst few hours in patients with transmural infarcts

-extremely sensitive but cannot distinguish acute infarcts from chronic scars

• Radionuclide ventriculography

-carried out with [99mTc]-labeled RBCs

-wall motion disorders and reduction in the ventricular ejection fraction in patients with STEMI

Cardiac MRI
-late enhancement technique

-gadolinium agent - little enters normal myocardium - bright signals in infarcted areas in contrast to dark
cular (RV) infarction, ven- TABLE 269-1 Definition of Myocardial Infarction areas of normal myocardium

LV thrombus. In addition,
etection and quantitation
egurgitation, two serious
hap. 236) are available for
However, these imaging
Criteria for Acute Myocardial Infarction
The term acute myocardial infarction (MI) should be used when there is INITIAL MANAGEMENT
evidence of myocardial necrosis in a clinical setting consistent with acute
myocardial ischemia. Under these conditions, any one of the following criteria
meets the diagnosis for MI:
Major elements of prehospital care include:

ography because they are cardiac troponin [cTn]) with at least one value above the 99th percentile 1. recognition of symptoms and prompt seeking medical
pecificity in many clinical upper reference limit (URL) and with at least one of the following:
ng with [201Tl] or [99mTc]- – Symptoms of ischemia attention

ion to myocardial blood
m (Chap. 267), reveals a
the first few hours after
ugh perfusion scanning is
– New or presumed new significant ST-segment T-wave (ST-T) changes or
new left bundle branch block (LBBB)
– Development of pathologic Q waves in the electrocardiogram (ECG)
– Imaging evidence of new loss of viable myocardium or new regional wall
2. rapid deployment of an emergency medical team
capable of performing resuscitative maneuvers,
including de brillation

ute infarcts from chronic motion abnormality

osis of acute MI. Radionu-
c]-labeled red blood cells,
ders and reduction in the
h STEMI. While of value
s of infarction and in aid-
– Identification of an intracoronary thrombus by angiography or autopsy
presumed new ischemic ECG changes of new LBBB, but death occurred
before cardiac biomarkers were obtained or before cardiac biomarker
values would be increased.
3. expeditious transportation of the patient to a hospital
facility that is continuously sta ed by physicians and
nurses skilled in managing arrhythmias and providing
advanced cardiac life support

he RV ejection fraction is
any cardiac abnormalities by elevation of cTn values (>5 × 99th percentile URL) in patients with 4. expeditious implementation of reperfusion therapy

normal baseline values (≤99th percentile URL) or a rise of cTn values

logram.
h-resolution cardiac MRI
as late enhancement. A
ministered and images are
adolinium enters normal
>20% if the baseline values are elevated and are stable or falling. In
addition, either (i) symptoms suggestive of myocardial ischemia, or (ii) ED MANAGEMENT
new ischemic ECG changes, or (iii) angiographic findings consistent with a
procedural complication, or (iv) imaging demonstration of new loss of viable
myocardium or new regional wall motion abnormality are required.
Aspirin

d myocytes, but does per-

of the infarct zone, there angiography or autopsy in the setting of myocardial ischemia and with a rise -antiplatelet

and/or fall of cardiac biomarker values with at least one value above the
ppears in stark contrast to 99th percentile URL. - rapid inhibition of cyclooxygenase-1, reduction of
iversal Definition of Myo- by elevation of cardiac biomarker values (>10 × 99th percentile URL)
thromboxane A2

sive set of criteria for the in patients with normal baseline cTn values (≤99th percentile URL). In -buccal absorption (chewed)

d laboratory findings dis-

cation of MI into five types
it may occur (Table 269-2).
addition, either (i) new pathologic Q waves or new LBBB, or (ii) angiographic
documented new graft or new native coronary artery occlusion, or (iii) -160 to 325 mg in the ER followed by daily oral
imaging evidence of new loss of viable myocardium or new regional wall
motion abnormality.
administration of 75-162 mg

Criteria for Prior Myocardial Infarction

Any one of the following criteria meets the diagnosis for prior MI:

e occurrence of two general nonischemic causes. Oxygen

cations (arrhythmias) and -if Sa02 <90%, supplemental oxygen at 2-4 L/min for the
e”). Most out-of-hospital and fails to contract, in the absence of a nonischemic cause.
evelopment of ventricular 1st 6-12 h after infarction

to ventricular fibrillation Source: Data from K Thygesen: Eur Heart J 33:2551, 2012.
ptoms, and of these, over
major elements of prehos-
of ECGs and management of STEMI, and online medical command and
include (1) recognition of Nitroglycerin

g of medical attention; (2) control that can authorize the initiation of treatment in the field.
team capable of perform- -for control of discomfort

brillation; (3) expeditious -upMANAGEMENT

to 3 doses ofIN 0.4 THE
mgEMERGENCY
tablets at 5 minute intervals (sublingual)

cility that is continuously DEPARTMENT

-diminishes chest pain/discomfort

anaging arrhythmias and In the Emergency Department, the goals for the management of
nd (4) expeditious imple- -decreases preload
patients with suspected STEMI thereby reducing
include control of cardiacmyocardial
discomfort, oxygen demand

t delay usually occurs not rapid identification of patients who are candidates for urgent reperfu-
-increases myocardial oxygen supply by
her, between the onset of sion therapy, triage of lower-risk patients to the appropriate location
dilating infarct-related coronary vessels

lp. This delay can best be in the hospital, and avoidance of inappropriate discharge of patients
ng the public concerning with STEMI. Many aspects of the treatment of STEMI are initiated in
mportance of seeking early the Emergency Department and then continued during the in-hospital
atients having a history of, phase of management (Fig. 269-4). The overarching goal is to minimize
are important “teachable the time from first medical contact to initiation of reperfusion therapy.
ptoms of STEMI and the This may involve transfer from a non-PCI hospital to one that is PCI
capable, with a goal of initiating PCI within 120 min of first medical
re carried out by trained contact (Fig. 269-4).
ing the time between the Aspirin is essential in the management of patients with suspected
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 --AVOID in low systolic pressures (<90 mmHg) or in clinically suspected RV infarction (inferior wall on
ECG, elevated JVP, clear lungs and hypotension)

-DO NOT administer in patients who’ve taken phosphodiesterase-5 inhibitors within the last 24 hrs
(synergistic hypotensive e ect)

Morphine

-e ective analgesic

-reduce arteriolar and venous constriction causing venous pooling that may reduce cardiac output and
arterial pressure

-vagotonic e ect and may cause bradycardia or advanced degrees of heart block in patients with inferior
infarction; usually responds to atropine (0.5 mg IV)

-2-4 mg IV injection every 5min

Beta blockers

-intravenous BBs can control pain in STEMI

-diminishes myocardial oxygen demand

-risk reduction for reinfarction and ventricular brillation

-IV metoprolol: 5 mg every 2-5 min for 3 doses (provided with HR of>60/min, systolic pressure >100
mmHg, PR interval <0.24s, and rales no higher than 10 cm up from diaphragm

-oral metoprolol 15 mins after last IV dose 50 mg every 6 hrs for 48 hrs followed by 100 mg every 12 hrs

Management Strategies

Limitation of infarct size

-central zone: necrotic tissue - irretrievably lost

-surrounding ischemic myocardium (ischemic penumbra) - may be improved by timely restoration of

coronary perfusion, reduction of myocardial O2 demands, prevention of the accumulation of noxious
metabolites, and blunting of the impact of mediators of reperfusion injury (e.g., calcium overload and
oxygen-derived free radicals).

Reperfusion Strategies
• Primary Percutaneous Coronary Intervention

- more e ective than brinolysis, better short- and long-term clinical outcomes

- generally preferred when diagnosis is in doubt, cardiogenic shock is present, bleeding risk is
increased, or symptoms have been present at least 2-3 hrs when the clot is more mature

• Fibrinolysis

- ideally done within 30 minutes of presentation (door-to-needle time <30min)

- tissue plasminogen activator, streptokinase, tenecteplase, reteplase

Thrombolysis in Myocardial Infarction (TIMI) grading system:

grade 0 - complete occlusion of the infarct-related artery

grade 1 - some penetration of the contrast material beyond the point of obstruction, but without
perfusion of the distal coronary bed

grade 2 - perfusion of the entire infarct vessel into the distal bed, but with ow that is delayed compared
with that of a normal artery

grade 3 - full perfusion of the infarct vessel with normal ow.

The latter is the goal of reperfusion therapy

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 Hospital Phase Management

Coronary Care Units

- De brillators, respirators, noninvasive transthoracic pacemakers, and facilities for introducing pacing
catheters and ow-directed balloon-tipped catheters are usually available

- close monitoring by highly trained nurses who can recognize arrhythmias adjust antiarrhythmic,
vasoactive, and anticoagulants drugs, perform cardiac resuscitations when necessary

Activity

- bed rest for 6-12 hrs

- in absence of complications, may resume upright posture by dangling feet over the side of the bed
and sitting in the chair within 24 hrs

- ambulating in the room by the 2nd or 3rd day (in the absence of hypotension or other complications)

- Day 3 after infarction - increase ambulation progressively to a goal of 185 m (600ft) at 3x a day

Diet

- NPO or clear liquids by mouth for the rst 4-12 hrs due to risk of emesis and aspiration

- coronary care unit diet - <30% of total calories as fat with cholesterol content of <300 mg/d; 50-55%
complex carbohydrates

- portions rich in potassium, magnesium, ber but low in sodium

Bowel movement

-bedside commode rather than bedpan

-diet rich in bulk

-stool softener (i.e. dioctyl sodium sulfosuccinate 200 mg/d), laxative can be prescribed if still with
constipation

Sedation

-diazepam 5mg, oxazepam 15-30 mg, or lorazepam 0.5-2mg given 3-4x daily is e ective

-not routinely recommended

PHARMACOTHERAPY

Antithrombotic agents

Antiplatelets:

- clopidogrel, prasugrel, ticagrelor: P2Y ADP receptor inhibition

- aspirin: cyclooxygenase-1 inhibition

- abciximab, tiro ban, epti batide: glycoprotein IIb/IIIa receptor inhibitors appear useful for preventing
thrombotic complications in patients with STEMI undergoing PCI

Anticoagulants:

- Unfractionated heparin: bolus 60 U/kg (max 4000 U) then infusion of 12 U/kg per hr (1000 U/hr)

• mortality bene t (5 patients saved per 1000 treated when added to regimen of aspirin and a non-
brin-speci c thrombolytic agent, such as streptokinase)

• goal activated partial thromboplastin time: 1.5-2 times the control value

- Low molecular weight heparin (enoxaparin): high bioavailability thereby can be given SC, reliable
anticoagulation without monitoring, greater antiXa:IIa activity

- Fondaparinux: Factor Xa inhibitor; superior to placebo in STEMI patients not receiving reperfusion
therapy

- bivalirudin: direct antithrombin; lower rate of bleeding

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 Patients with anterior location of infarction, severe LV dysfunction, heart failure, a history of embolism,
two-dimensional echocardiographic evidence of mural thrombus, or atrial brillation receive full
therapeutic levels of anticoagulant therapy (LMWH or UFH) while hospitalized, followed by at least 3
months of warfarin therapy.

Inhibitors of Renin-Angiotensin-Aldosterone System

-ACE inhibitors

• reduce mortality rate after STEMI; additive to those achieved with aspirin and BBs

• should be continued inde nitely in patients who have clinically evident CHF, those with reduction
in global LV function or a large regional wall motion abnormality, or in those who are hypertensive

-Angiotensin receptor blockers (ARBs)

• administered to patients who are intolerant of ACE inhibitors and have either clinical or radiologic
signs of heart failure

• Long-term aldosterone blockade should be prescribed for STEMI patients without signi cant renal
dysfunction (creatinine ≥2.5 mg/dL in men and ≥2.0 mg/dL in women) or hyperkalemia (potassium
≥5.0 mEq/L) who are already receiving therapeutic doses of an ACE inhibitor, have an LV ejection
fraction ≤40%, and have either symptomatic heart failure or diabetes mellitus

COMPLICATIONS AND THEIR MANAGEMENT


• Ventricular Dysfunction

- ventricular remodeling - precedes the development of clinically evident CHF in the months to years
after infarction

- LV dilatation after STEMI resulting from expansion of infarct, slippage of muscle bundles, disrupted
myocardial cells, and tissue loss within the necrotic zone

- patients with an ejection fraction <40%, regardless of whether or not heart failure is present, ACE
inhibitors or ARBs should be prescribed to ameliorate progressive dilatation and clinical
consequences

• Hemodynamic Assessment

- Pump failure: primary cause of in-hospital death from STEMI

- characterized by elevated LV lling pressure and elevated pulmonary artery pressure but hese
ndings may result from a reduction of ventricular compliance (diastolic failure) and/or a reduction
of stroke volume with secondary cardiac dilation (systolic failure)

- Killip clasi cation (congestive heart failure in STEMI)

• class I - no signs of pulmonary or venous congestion

• class II - moderate heart failure as evidenced by rales at the lung bases, S3 gallop, tachypnea, or
signs of failure of the right side of the heart, including venous and hepatic congestion

• class III - severe heart failure

• class IV - shock with systolic pressure <90 mmHg and evidence of peripheral vasoconstriction,
peripheral cyanosis, mental confusion, and oliguria

• **the expected hospital mortality rate of patients in these classes was as follows: class I, 0-5%;
class II, 10–20%; class III, 35–45%; and class IV, 85–95%. With advances in management, the
mortality rate in each class has fallen, perhaps by as much as one-third to one-half.

Cardiogenic Shock

- Prompt reperfusion, e orts to reduce infarct size and treatment of ongoing ischemia and other
complications of MI reduce the incidence of cardiogenic shock from 20 to about 7%.

- Typically, patients who develop cardiogenic shock have severe multi-vessel coronary artery disease
with evidence of “piecemeal” necrosis extending outward from the original infarct zone

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 Right Ventricular Infarction

- Approximately one-third of patients with inferior infarction demonstrate at least a minor degree of RV
necrosis.

- Clinically signi cant RV infarction causes signs of severe RV failure (jugular venous distention,
Kussmaul’s sign, hepatomegaly) with or without hypotension

- Two-dimensional echocardiography is helpful in determining the degree of RV dysfunction.

- Catheterization of the right side of the heart often reveals a distinctive hemodynamic pattern
resembling constrictive pericarditis (steep right atrial “y” descent and an early diastolic dip and
plateau in RV waveforms)

- treated with volume expansion to maintain adequate RV preload and e orts to improve LV
performance with attendant reduction in pulmonary capillary wedge and pulmonary arterial pressures.

ARRHYTHMIAS

Ventricular premature beats

- infrequent, sporadic ventricular premature depolarizations occur in almost all patients with STEMI and
do not require therapy

**prophylactic antiarrhythmic therapy (either intravenous lidocaine early or oral agents later) is
contraindicated for ventricular premature beats in the absence of clinically important ventricular
tachyarrhythmias, because such therapy may actually increase the mortality rate

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 - Beta-adrenoceptor blocking agents are e ec- tive in abolishing ventricular ectopic activity in patients
with STEMI and in the prevention of ventricular brillation

- hypokalemia and hypomagnesemia are risk factors for ventricular brillation in patients with STEMI; to
reduce the risk, the serum potassium concentration should be adjusted to ~4.5 mmol/L and
magnesium to about 2.0 mmol/L

Ventricular tachycardia and brillation

- Within the rst 24 h of STEMI, ventricular tachycardia and brillation can occur without prior warning
arrhythmias

- The occurrence of ventricular brillation can be reduced by prophylactic administration of intravenous

lidocaine. However, prophylactic use of lidocaine has not been shown to reduce overall mortality from
STEMI

Supraventricular arrhythmias
- Sinus tachycardia is the most common supraventricular arrhythmia. If it occurs secondary to another
cause (such as anemia, fever, heart failure, or a metabolic derangement), the primary problem should
be treated rst.

- If due to sympathetic overstimulation (e.g., as part of a hyperdynamic state), then treatment with a
beta blocker is indicated.

- If the abnormal rhythm persists for >2 h with a ventricular rate >120 beats/min, or if tachycardia
induces heart failure, shock, or ischemia (as manifested by recurrent pain or ECG changes), a
synchronized electroshock (100–200 J mono- phasic waveform) should be used.

Sinus bradycardia
- Atropine: most useful drug for increasing heart rate; given intravenously in doses of 0.5 mg initially.

- If the rate remains <50–60 beats/min, additional doses of 0.2 mg, up to a total of 2.0 mg, may be
given.

- Persistent bradycardia (<40 beats/min) despite atropine may be treated with electrical pacing.

- Isoproterenol should be avoided.

PERICARDITIS

- Pericardial friction rubs and/ or pericardial pain are frequently encountered in patients with STEMI
involving the epicardium.

- This complication can usually be managed with aspirin (650 mg four times daily).

- Anticoagulants potentially could cause tamponade in the presence of acute pericarditis (as
manifested by either pain or persistent rub) and therefore should not be used unless there is a
compelling indication.

THROMBOEMBOLSIM

- an important contributing cause of death in 25% of patients with STEMI who die after admission to
the hospital

- Arterial emboli originate from LV mural thrombi, while most pulmonary emboli arise in the leg veins.

- occurs in association with large infarcts (especially anterior), CHF, and an LV thrombus detected by
echocardiography

- arterial embolism often presents as a major complication, such as hemiparesis when the cerebral
circulation is involved or hypertension if the renal circulation is compromised.

- When a thrombus has been demonstrated by echocardiographic or other techniques or when a large
area of regional wall motion abnormality is seen even in the absence of a detectable mural thrombus,
systemic anticoagulation should be undertaken (in the absence of contraindications)

- 3–6 months duration

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 LEFT VENTRICULAR ANEURYSM

- Ventricular aneurysm is usually used to describe dyskinesis or local expansile paradoxical wall motion

- LV aneurysm complications do not usually occur for weeks to months after STEMI; they include CHF,
arterial embolism, and ventricular arrhythmias.

- Apical aneurysms - most common and the most easily detected by clinical examination

• The physical nding of greatest value is a double, di use, or displaced apical impulse.
Ventricular aneurysms are readily detected by two-dimensional echocardiography, which may
also reveal a mural thrombus in an aneurysm.

POST INFARCTION RISK STRATIFICATION AND MANAGEMENT

- Some of the most important factors include persistent ischemia (spontaneous or provoked),
depressed LV ejection fraction (<40%), rales above the lung bases on physical examination or
congestion on chest radiograph, and symptomatic ventricular arrhythmias.

- Other risk factors to consider include history of previous MI, age >75, diabetes mellitus, prolonged
sinus tachycardia, hypotension, ST-segment changes at rest without angina (“silent ischemia”), an
abnormal signal-averaged ECG, nonpatency of the infarct-related coronary artery (if angiography is
undertaken), and persistent advanced heart block or a new intraventricular conduction abnormality on
the ECG.

- The goal of preventing reinfarction and death after recovery from STEMI has led to strategies to
evaluate risk after infarction.

- The usual duration of hospitalization for an uncomplicated STEMI is about 3–5 days.

- During the rst 1–2 weeks, the patient should be encouraged to increase activity by walking about the
house and outdoors in good weather. Normal sexual activity may be resumed during this period.

- After 2 weeks, the physician must regulate the patient’s activity on the basis of exercise tolerance.

- Most patients will be able to return to work within 2–4 weeks.

SECONDARY PREVENTION

- Long-term antiplatelet therapy (usually aspirin) after STEMI is associated with a 25% reduction in the
risk of recurrent infarction, stroke, or cardiovascular mortality (36 fewer events for every 1000 patients
treated); alternatively - clopidogrel at 75 mg daily

- RAAS inhibitors (ACEi & ARBs and, in appropriate patients, aldosterone antagonists) should be used
inde nitely by patients with clinically evident heart failure, a moderate decrease in global ejection
fraction, or a large regional wall motion abnormality to prevent late ventricular remodeling and
recurrent ischemic events.

- Evidence suggests that warfarin lowers the risk of late mortality and the incidence of reinfarction after
STEMI. Several studies suggest that in patients <75 years old a low dose of aspirin (75–81 mg/d) in
combination with warfarin administered to achieve an international normalized ratio >2.0 is more
e ective than aspirin alone for preventing recurrent MI and embolic cerebrovascular accident.
However, there is an increased risk of bleeding and a high rate of discontinuation of warfarin that has
limited clinical acceptance of combination antithrombotic therapy.

Non ST- Segment elevation ACS

Pathophysiology

- imbalance between myocardial oxygen supply and demand resulting from one or more of the
following four processes that lead to thrombus formation :

(1) disruption of an unstable coronary plaque due to plaque rupture, erosion, or a calci ed protruding
nodule that leads to intracoronary thrombus formation and an in ammatory response;

(2) coronary arterial vasoconstriction;

(3) gradual intraluminal narrowing;

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 (4) increased myocardial oxygen demand produced by conditions such as fever, tachycardia, and
thyrotoxicosis in the presence of xed epicardial coronary obstruction.

* Most common etiology of coronary thrombosis:

- Plaque rupture

- Erosion of an intracoronary plaque

Vulnerable plaques: composed of lipid rich core with a thin brous cap

Most common lesions:

10%- stenosis of Left main coronary artery

30%- CAD

20%- 2- vessel disease

20%- single vessel disease

15%- no apparent critical epicardial coronary artery stenosis

Clinical presentation:

Severe chest discomfort and at least one of three features:

- occurrence at rest or with minimal exertion, lasting > 10 mins

- Relatively recent onset

- Crescendo pattern

- Location: substernal region, radiates to the left arm, left shoulder and/ or superiorly to the neck and
jaw

- Anginal equivalents: dyspnea, epigastric discomfort, nausea or weakness

- more common in women, elderly and patients with diabetes mellitus

Physical examination:

- resembles patients with stable angina

- may be unremarkable

Physical examination of patients with large area of myocardial ischemia:

- diaphoresis,

- pale, cool skin,

- sinus tachycardia,

- A third and fourth heart sound,

- basilar rales

- and sometimes hypotension

Diagnosis of NSTEMI:

Clinical features WITHOUT electrocardiographic ST segment elevations

Plus

evidence of myocardial necrosis as re ected in abnormally elevated levels of biomarkers

ECG nding:

- new ST segment depression —> may be transient but may persist for several days following NSTEMI

- T wave changes: more common but are less speci c signs of ischemia, unless they are new and deep
T- wave inversions (>0.3 mV)

Cardiac biomarkers:

- Cardiac troponin I or T

- speci c, sensitive and preferred markers of myocardial necrosis

- CK-MB

- less sensitive alternative

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Other clinical conditions that may cause elevated cardiac troponin levels:

- Heart failure

- Myocarditis

- Pulmonary embolism

Clinical monitoring, continuous monitoring of ECGs and cardiac markers, typically obtained at baseline
and at 4–6 h and 12 h after presentation.Risk strati cation:

Assessment of Risk:

- 30 day risk of death ranging from 1- 10% and a recurrent ACS rate of 5-15% during the rst year

- Thrombolysis in Myocardial Infarction (TIMI)

Initial Treatment

Non pharmacologic:

- Bed rest

- Inhaled Oxygen in patients with arterial O2 saturation < 90% and/or in those with heart failure and
rales

- Continuous ECG monitoring

- Ambulation: permitted if the patient shows no recurrence of ischemia (symptoms or ECG changes)
and does not develop an elevation of a biomarker or necrosis for 12-24 h.

Medical therapy:

- acute phase: focused on the clinical symptoms and stabilization of the culprit lesions

- long term phase: involves therapies directed at the prevention of disease progression and future
plaque rupture/ erosion

Pharmacologic:

Anti ischemic treatment

- provide relief and prevention of recurrence of ischemic discomfort

- Nitrates

- Beta adrenergic blockers

Antithrombotic therapy

- Anti platelet drugs

- Anticoagulants

Invasive vs conservative strategy

Invasive strategy

- coronary arteriography is carried out within 48 hours of presentation

- followed by coronary revascularization

Conservative strategy

- anti- ischemic and antithrombotic therapy followed by a selective invasive approach

- patient is closely observed and coronary arteriography is carried out if rest pain or ST-segment
changes recur, a biomarker of necrosis becomes positive, or there is evidence of severe ischemia on a
stress test

Long term management:

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 Risk-factor modi cation

- importance of smoking cessation, achieving optimal weight, daily exercise, blood-pressure control,
following an appropriate diet, control of hyperglycemia (in diabetic patients), and lipid management as
recommended for patients with chronic stable angina

- There is evidence of bene t with long-term therapy with ve classes of drugs that are directed at
di erent components of the atherothrom-botic process

- Beta blockers

- lipid lowering therapy (statins at high dose, e.g., atorvastatin 80 mg/d, with ezetimibe if needed
to achieve an LDL-C below 70 mg/dL)

- ACE inhibitors or angiotensin receptor blockers

- Antiplatelet regimen consists of the combination of low-dose (75–100 mg/d) aspirin and a P2Y12
inhibitor (clopidogrel, prasugrel, or ticagrelor) for 1 year, with aspirin continued thereafter

Prinzmetal’s Variant Angina

- syndrome of severe ischemic pain that usually occurs at rest and is associated with transient ST-
segment elevation

- caused by focal spasm of an epicardial coronary artery with resultant transmural ischemia and
abnormalities in left ventricular function that may lead to acute MI, ventricular tachycardia or
brillation, and sudden cardiac death

- may be related to hyper contractility of vascular smooth muscle due to adrenergic vasoconstrictors,
leukotrienes, or serotonin

Clinical and angiographic manifestations:

- Patients with PVA are generally younger and, with the exception of cigarette smoking, have fewer
coronary risk factors than do patients with NSTE-ACS

- Cardiac examination is usually unremarkable in the absence of ischemia

- a minority of patients have a generalized vasospastic disorder associated with migraine and/or
Raynaud’s phenomenon.

Clinical diagnosis of PVA:

- detection of transient ST-segment elevation with rest pain

- Coronary angiography demonstrates transient coronary spasm as the diagnostic hallmark of PVA.

Diagnostic hallmark: transient coronary spasm in coronary angiography

Treatment:

- Nitrates

- Calcium channel blockers

Prognosis:

- Survival at 5 years is excellent (~90–95%), but as many as 20% of patients experience an MI

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