SCA - Síndromes

Coronarios Agudos

de la Fisiopatología
Héctor Luciardi - 2019
al manejo de los SCA
Arritmia Sinusal Respiratoria - Hallazgo fisiológico fcte en mujeres
Casterella P. 2006 - University of Utah
 “Man lives w/
arteriosclerosis
& dies of the
complicating
thrombosis”
Dedichen J
Brit Med J 1956;11:1038-9
Vasa Vasorum
Thrombus Injury
Formation Stimuli Erosion
Rupture

Impaired endothelial Abnormal

function threshold

Exogenous
Pro-thrombotic state
therapy

Endogenous inhibitors
Normal
Normal Endothelial threshold
Function

Thrombosis
ACS Physiology

Atherosclerosis

Rupture

Local Effects Distal Effects

Thrombosis
Embolism Thrombosis Vasospasm

Obstruction

Large vessel Injury Microvascular Injury

ACS: Tip of the Atherothrombotic “Iceberg”
Acute Plaque Rupture ACS (UA-NSTEMI-STEMI)

Clinical

Subclinical

Persistent Hyperreactive
Platelets
Presence of Multiple Vascular
Coronary Plaques Inflammation

Adapted from Goldstein JA. J Am Coll Cardiol. 2002;39:1464-1467.

Multiple Complex Coronary Plaques in ACS

Multiple plaques
detected

Multiple plaques
detected
Culprit lesion

Goldstein JA, et al. N Eng J Med. 2000; 343: 915-922.

 Time is Muscle - TIMI 3
16% rise in risk of a closed muscle for every hour of delay in STEMI (p=0.0005)
Gibson, JACC 2004

Time Dependent Swollen / Closed Anterior

Wavefront of Necrosis Myocardium
Hamm Lancet 358:1533,2001

Presentation Ischemic Discomfort

Working Dx Acute Coronary Syndrome

Davies MJ
Heart 83:361, 2000

ECG No ST Elevation ST Elevation

NSTEMI

Biochem.
Marker
Myocardial Infarction
Final Dx Unstable Angina NQMI Qw MI
Acute MI
Impact of Modern Critical Care on Mortality

Short-Term Mortality (%)

40
Defibrillation
30 Hemodynamic
30 Monitoring
20 -Blockers Aspirin
Thrombolysis
PTCA
10 15
6.5
0
Pre-CCU CCU Reperfusion
Era Era Era

Adapted from Antman, Braunwald In:Braunwald ed. Heart Disease p 1184.

Acute Management of UA / NSTEMI
Anti-Ischemic Therapy
• Oxygen, bed rest,
ECG monitoring
• Nitroglycerin
• -Blockers
• ACE inhibitors
• Statins
Antithrombotic Therapy
• Antiplatelet therapy
• Anticoagulant therapy
Braunwald E, et al. J Am Coll Cardiol. 2000; 36:970-1062
 Acute Coronary Syndrome

No ST Elevation ST Elevation
NSTEMI

Myocardial Infarction
Uns Angina NQMI Qw MI
- PCI Fibrinolytics - PCI

Antiplatelet Rx

Antithrombin Rx
Hamm Lancet 358: 1533; 2001
Prothrombotic effects of fibrinolytic therapy
Aspirin in Acute MI
ISIS-2
35 Day Mortality (%)
20

15
13.2
10 10.7 10.4
8
5
4300 4295 4300 4292
0
Placebo ASA SK SK + ASA

ISIS-2 Collaborative Group, Lancet 1988;2:349.

 EMERAS

ACS - Topol E 3ed. 2005

DES
t-PA r-PA alteplase TNK-tPA n-PA
“Techo de benefico clínico”
“ Golden
hour ”

23
 TIMI FLOW

“Time is
muscle”
24
DES
 Primary PCI vs Thrombolysis
in STEMI: Meta-analysis
25 Short-term P<.0001
Outcomes PCI
20 Thrombolytic therapy
P<.0001
Frequency (%)

15
P=.0002 P=.0003 P<.0001
P=.032
10

5 P=.0004
P<.0001

0
Death Death, Nonfatal Recurrent Total Hemor- Minor Death,
Excluding MI Ischemia Stroke rhagic Bleed Nonfatal
SHOCK Stroke Reinfarction,
or Stroke

Adapted w/ permission from Keeley EC, et al. Lancet. 2003;361:13-20.

- DES
 Times to Treatment in Patients Transferred

Total Door-to-Balloon Time

35
• NRMI Registry 3-4
Pt (%)
• 1999-2002 30

• 4,608 pt transf for 25

PPCI 20
15.4%
Median times 15

Door-to-balloon – 10
184 min
5
Door-to-door – 3.9%
0
122 min <1 1 to 2 to 3 to 4 to 5 to 6 to 7
Hours <2 <3 <4 <5 <6 <7
Nallamothu & Krumholz
 TIMI Myocardial Perfusion (TMP) Grades

8 TMP Grade 3 TMP Grade 2 TMP Grade 1 TMP Grade 0

7 No or minimal blush
Stain present
Blush persists
6 Dye strongly persistent on next injection 6.2%
5
p = 0.05 at end of washout
Gone by next injection
5.1%
4 Normal ground glass
appearance of blush 4.4%
3 Dye mildly persistent
at end of washout
2

1
2.0%
n = 203 n = 46 n = 79 n = 434
0
Gibson et al, Circulation 2000
Treatment Delayed is Treatment Denied

Symptom Call to Pre-Hospital ED Cath Lab

Recognition Medical
System

Increasing Loss of Myocytes

Delay in Initiation of Reperfusion Therapy

Antman E, Van de Werf
Circulation 2004
Time is
Muscle

We must
translate
that into
practice

JACC 2008; 52:1216–21

 Randomized Trials of Lytic
vs. Transfer for PCI
Study n Results with Transfer for PCI

Air PAMI 138 ↓ MACE at 1 mo. (8.4 vs 13.6%)

LIMI 224 ↓ MACE (8%) compared to on-site tPA
(16%) or tPA with transfer (14%)

PRAGUE – I 300 ↓ MACE (8%) compared to on-site SK

(23%) or SK with transfer (15%)

↓ Death / MI *8.4% vs 15.2% with SK)

850
PRAGUE – II ↓ Death if presentation >3 hrs
(6% vs 15.3%, p 0.02)

↓ Death / MI / CVA (8.5% vs 14.2% with

DANAMI – II 1129
on-site tPA)
 Morrow D, Antman E, Sayah A.
Evaluation of the time saved by
prehospital initiation of reteplase
for ST-elevation MI:
Results of the ER-TIMI-19 trial
Early Retavase Thromb in MI
JACC 2002; 40: 71-77

Nallamothu BK, Bates ER.

PCI vs fibrinolytic therapy in AMI:
Is timing (almost) everything ?
Am J Cardiol 2003; 92: 824-826
45
Fondaparinux
Idraparinux

Prasugrel
Ticagrelor

Ximelagatrán
 Aspirin
Ticlopidine Platelet
Clopidogrel
Injury
Prasugrel
Activation
Ticagrelor

IIb/IIIa Platelet
blockers Aggregation

Heparin
LMW heparins Thrombin
FXa inhibitors Generation

Heparin Thrombus
Antihrombins Thrombin
DTI – DFXI Activity
+ Ticagrelor
Schömig A. NEJM 2009; 361: 1108-11



 ...Trials
Test specific
hypotheses
in defined, relatively
homogeneous
populations
... Registries
If appropriately
designed ... provide
the reference standard
for management and
outcome & raise
hypotheses for
further testing
 Hasta lo más difícil
se puede decir de manera simple.
... pero es difícil.

Hasta lo más simple

se puede decir de forma difícil.
... y es fácil.

Soya