Acute coronary syndrome

Acute Coronary Syndromes

ACS: Definition

• A spectrum of clinical diagnoses comprising unstable angina, Non-STEMI, and STEMI that share similar pathological features involving intracoronary thrombosis

ACS: Definition

From: Braunwald’s Heart Disease

Pathophysiology• atherosclerosis with superimposed coronary thrombosis

• Slowly growing high-grade stenoses can progress to complete occlusion but do not usually precipitate acute STEMI d/t collateral circulation

• During development of plaques, abrupt transition can occur, resulting in

• Platelet activation

• Thrombin generation

• Thrombus formation

• Blood flow occlusion leads to imbalance between supply and demand and could lead to myocardial necrosis

• Pts with non-transmural infarction more likely to have more significan stenosis in IRA

• Less severe stenosis with lipid-laden plaques and fragile caps more likely to rupture and causing thrombsis and STEMI

PathophysiologyStable Angina•Progressive narrowing of coronary lumen•Stable fibrous cap

Unstable Angina•Progressive narrowing•Acute worsening of coronary lumen due to thrombus formation

NSTEMI•Acute worsening of coronary lumen due to thrombus formation•Sub-occlusive/transient coronary thrombus with myocardial necrosis

STEMI•Minimal prior narrowing of coronary lumen•Acute rupture of thin fibrous cap•Occlusive thrombus formation•Acute injury pattern•Myocardial necrosis

ACS Evaluation

Angina• Definition: Discomfort in the chest/ “choking,” that

characteristically comes on with exertion, relieved by rest and/or NTG

Favors Ischemic Origin

Against Ischemic Origin

Character Constricting

Squeezing

Burning

Heaviness

Dull ache

Knife-like, sharp

Jabs

Pleuritic

Location Substernal

Anterior thorax

Arms, shoulders

Neck, teeth,

Interscapular

Left submammary area

Left hemithorax

Provoking Factors

Exertion

Excitement

Cold, meals, stress

Pain after completion of exercise

Pain with movement

NormalNormalElevated cardiac TnI, TnT or CK-MB

Cardiac Marker

T wave flattening or inversion in leads with dominant R wave

Normal EKG

Fixed Q waves

Abnormal ST segments or T waves not documented to be new

New or presumably new, transient ST segment deviation (≥0.05mV) or T wave inversion (≥0.2mV) with symptoms

EKG

Chest discomfort reproduced by palpation or respiration

Extracardiac vascular disease

Transient MR, hypotension, diaphoresis, pulmonary edema or rales

Exam

Probable ischemic symptoms in absence of the intermediate likelihood characteristics

Recent cocaine use

Chest or left arm pain or discomfort as chief symptom

Age > 70

Male gender

Diabetes mellitus

Chest or left arm pain or discomfort as chief symptom reproducing prior documented angina

Known history of CAD, including MI

History

LowIntermediateHighFeature

Likelihood that signs & symptoms represent an ACS secondary to CAD

Braundwald 1994 AHCPR Publication No. 94-0602

Chest Pain Classification

• Substernal• Exertional• Relieved with rest

• Interpretation – Typical Angina: 3 criteria from above – Atypical Angina: 2 criteria from above – Non-Anginal Chest Pain: 1 or less criteria from

above

Classification of Angina

• STABLE vs UNSTABLE

• CCS Classification for STABLE Angina

– I: No symptoms, or angina with strenuous exertion

– II: Slight limitation of ordinary physical activity

• Walking more than two blocks, climbing more than one flight of stairs brings on angina

– III: Marked limitation of ordinary physical activity

• Walking less than two blocks, climbing less than one flight of stairs

– IV: Any physical activity brings on angina; angina at rest

UA/NSTEMI 9/00

UA/NSTEMITHREE PRINCIPAL PRESENTATIONS

Rest Angina* Angina occurring at rest and prolonged, usually > 20 minutes

New-onset Angina New-onset angina of at least CCS Class III severity

Increasing Angina Previously diagnosed angina that hasbecome distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by > 1 CCS)class to at least CCS Class III severity.




BraunwaldCirculation 80:410; 1989BraunwaldCirculation 80:410; 1989

* Pts with NSTEMI usually present with angina at rest.* Pts with NSTEMI usually present with angina at rest.

UA/NSTEMI 9/00

UA/NSTEMITHREE PRINCIPAL PRESENTATIONS







BraunwaldCirculation 80:410; 1989BraunwaldCirculation 80:410; 1989

* Pts with NSTEMI usually present with angina at rest.* Pts with NSTEMI usually present with angina at rest.

Pre-Test Likelihood of CAD

Nonanginal pain Atypical angina Typical angina Age (y.)

Men Women Men Women Men Women

30-39

4 2 34 12 76 26

40-49

13 3 51 22 87 55

50-59

20 7 65 31 93 73

60-69 27 14 72 51 94 86

Diamond and Forrester, NEJM, 1979

Relationship of Rise in Biochemical Markers to Onset of AMI

Troponin

• cTnT (33 kDa) binds to tropomyosin to complex molecule to thin filament

• cTnI (24kDa) inhibits actin-myosin interactions

• cTnC binds Ca2+

• Generally not detectable in plasma of normal persons

Troponin• TnT and TnI have different amino acid sequence in cardiac

vs. skeletal muscle– Permits development of cardiac specific antibodies

• More sensitive and specific than CKMB– Detects minimal amounts of cardiac necrosis (neg. CKMB)

• “minor myocardial damage/microinfarction”– Elevated in MI (pos. CKMB)– New guidelines suggest troponin is sufficient to dx MI

• Other situations assoc. with increased troponin:• CHF• ICU• Renal failure• CVA• Myocarditis/other myocardial injury

Changes in Focus on Heart FailureTROPONIN I LEVELS PREDICT THE RISK OF MORTALITY IN UA/NSTEMITROPONIN I LEVELS PREDICT THE RISK OF MORTALITY IN UA/NSTEMI

1.01.0

1.71.7

3.43.4

3.73.7

6.06.0

7.57.5

00

22

44

66

88

0 to <0.40 to <0.4 0.4 to <1.00.4 to <1.0 1.0 to <2.01.0 to <2.0 2.0 to <5.02.0 to <5.0 5.0 to <9.05.0 to <9.0 >9.0>9.0

831 174 148 134 6750

Cardiac Troponin I (ng/ml)Risk Ratio 1. 1. 3.5 3.9 6.2 7.8

Antman N Engl J Med. 335:1342, 1996

Cardiac Troponin I (ng/ml)Risk Ratio 1. 1. 3.5 3.9 6.2 7.8

Antman N Engl J Med. 335:1342, 1996

Mo

rtal

ity

at

42 D

ays

(%

of

pat

ien

ts)

Mo

rtal

ity

at

42 D

ays

(%

of

pat

ien

ts)

2.02.0

6.46.4

3.33.3

1.71.7

6.96.9

5.05.0

00

11

22

33

44

55

66

77

19931993 10571057 RRRR 16411641 792792 RRRR

Total MortalityTotal Mortality Cardiac MortalityCardiac Mortality

66

PTSPTS

77No. TrialsNo. TrialsTrop.Trop. Neg PosNeg Pos Neg PosNeg Pos

TROPONINS T AND IAS PREDICTORS OF MORTALITY

TROPONINS T AND IAS PREDICTORS OF MORTALITY

N Engl J Med 1997;337:1648-53

Prognostic Significance of Cardiac Troponin

Risk Stratification of Patients with ACS in ER

US/NSTEMI Rx

Management of UA/NSTEMI• 8 medication • Oxygen• ASA , clopidogrel • Anticoagulant: UFH, LMWH• Nitrates for pain

– Nitropatch 0.4 mg/hr x 12 hours daily– IV NTG

• Beta-blocker– Metoprolol 25-50 mg PO BID

• + Calcium channel blocker• ACEI for secondary prevention• Statin

• Investigations:– Serial cardiac enzymes– Definitive in-hospital risk stratification.

Platelet Inhibitors in the ACS

• “A platelet GpIIb/IIIa receptor antagonist should be administered, in addition to ASA and UFH, to patients with continuing ischemia or with other high risk features—”

• “Level of the evidence: A”

ACC/AHA Guideline Circulation 2000;102:1193-1209

DEATH OR MI AT 30 DAYSP

erce

nt

of

Pat

ien

ts 10.9

1.8

9

4.8

10.1

3.6

14.1

3.9

10.2

5.9

16.7

11.6

0

2

6

10

14

18

EPIC CAPTURE EPILOG EPISTENT PRISM-PLUS PURSUIT

Placebo GP IIb-IIIa Inhibitor

ACC SlideACC Slide

ANTIPLATELET Rx

Class I

Definite ACS with continuingPossible ACS Likely/Definite ACS Ischemia or Other High-Risk

Features or planned PCI

Aspirin Aspirin Aspirin++ ++

Subcutaneous LMWH IV heparinor

IV heparin IV platelet GP IIb/IIIa antagonist++

ACC Slide

Primary efficacy endpoints in the CURE trial

18.8%

11.4%

Placebo

<0.0010.8616.4% CV death/MI/stroke/refractory ischemia

<0.0010.809.3%CV death/MI/stroke

p valueRelative risk

ClopidogrelEndpoint

The CURE Investigators. N Engl J Med 2001;345: 494 -502.

Other Antiplatelet Agents: Clopidogrel

Role at this point in combination with 2b3a inhibitorunclear: a useful option in ASA allergic pt’

.

Bleeding results

1.8%

2.7%

Placebo

0.132.1%Life-threatening bleeding

0.0013.7%Major bleeding

p valueClopidogrelEndpoint

The CURE Investigators. N Engl J Med 2001;345: 494-502.

Effect of Clopidogrel in ACS: the CURE trial

In Hospital Risk Stratification with ACS: Principles

• Spectrum of risk

• Features associated with poor prognosis (high probability of short term MI, etc.)– EKG features: dynamic ST depression– Cardiac markers: increased troponin

• Risk stratification refers to identifying patients at risk

Strategies for Risk Stratification

• Non-invasive– EST

• Sensitivity 70%• Specificity 70%

– MIBI scan• Sensitivity 86-90%• Specificity 90%

• Invasive– Diagnostic coronary angiography

Exercise Stress Testing– Positive response: horizontal 1mm ST depression and

symptoms– High risk response:

• Deep ST depression• Poor exercise tolerance: unable to exercise past stage 2 (<6

mins)• Exercise induced hypotension and dysrhythmias

– Uninterpretable:• LBBB• Digoxin• LVH

– Contra-indications:• Severe Aortic stenosis• Aortic dissection• MI/ACS within 24 h• PE

Angiography• Gold standard

– Defines anatomy: 1VD, 2VD, 3VD, LM– Assesses LV function– Guides treatment: PCI, CABG or medical therapy

• Indications– UA/post MI with ongoing pain, ST depresssion– Hemodynamic instability– CHF, ventricular arrhythmias– Previous PCI, CABG– High risk non-invasive test– Emerging as the strategy of choice for initial evaluation of most

ACS with elevated troponins or EKG changes• Based on FRISC II, TACTICS trials

• Strategy needs to be individualized.

Angiography

Indications for Invasive Risk Stratification Strategy in UA/NSTEMI

• Class I– Recurrent ischemia at rest despite medical Rx– Elevated troponin I or T– New ST depression– High risk findings on non-invasive testing– Depressed LV function– Hemodynamic instability– Sustained VT– PCI within 6 months– Prior CABG

• In the absence of the above, either non-invasive or invasive strategy can be followed.

ACC/AHA Guidelines for Management of UA/NSTEMI 2002

SUMMARY: ER Evaluation of Patient with Chest Pain

Symptoms Suggestive of

Cardiac Origin?

Consider Alternative Diagnosis

Stable Unstable

NO YES

Early Risk Stratification in ER

SUMMARY: Management of UA/NSTEMIHIGH RISK (12-30%)*

•Prolonged CP (>20 minutes or ongoing), plus:•EKG:

•Transient ST changes•Sustained ST depr.•Deep T wave inv. (>5 leads)

•Biochemical markers:•Troponin/CKMB abnormal

•Recurrent ischemia•AMI in last 4 weeks•Hemodynamic compromise

INTERM. RISK(4-8%)

•No high risk features but >=1 of:

•Ongoing chest pain•Crescendo angina•Borderline positive troponin I (0.4-2.0)•Previous intervention: PCI or CABG•Increased baseline risk (DM, elderly)

LOW RISK(<2%)

•No high or intermediated features•Chest pain, single episode, exertional•EKG: normal or nonspecific or unchanged

•May include previous hx of CAD or risk factors

•ASA + heparin/LMWH•GP IIb/IIIa•Early cardiac cath

•ASA + clopidogrel•UFH or LMWH•Cardiac cath lab

•ASA•No heparin•Observe/outpt tests

*30

day

rate

of d

eath

or

MI

STEMI

• WHO defn: 2 of – characteristic chest pain– ECG changes – ST elevation– Biochemical changes

• ACC + ESC– Rise and fall of biochemical marker (Tn, CK-MB) +

one of • ischemic symptoms• development of pathological Q waves• ECG changes suggestive of ischemia• Coronary angiography

STEMI

• More than 1 million MI’s per year in US

• Fatal in 1/3 of pts, ½ of death occurs within 1 hr of symptoms (arrhythmias)

Symptoms• prolonged pain > 30 min usually• constricting, crushing, or compressing; heaviness or

squeezing• can be choking, burning, knife-like• retrosternal, radiating to L>R side of chest, ulnar sides of

arms L>R, shoulder, upper extremity, jaw, neck, interscapular region sometimes epigastric

• pain usually implies ischemia• other sx

– nausea/vomiting more common in inferior MI – weakness– dizziness– palpitation– cold perspiration– sense of impending doom

STEMI

• Pre-hospital care– EMS

• Dispatch, first response, EMS ambulance

• AED to first responders

• Relief of pain to reduce sympathetic tone

• Rapid transfer to hospital

– Prehosp fibrinolysis• Some evidence suggesting improved mortality

STEMI

• ER Management– Early recognition

• Ischemic type chest pain• ECG signs

– ECG monitor rhythm– IV access– O2– Reperfusion strategy will depend on

• Time since symptoms• Risk assoc with STEMI• Risk of lytics• Time required for PCI

Time to Rx

STEMI - Acute Rx• ASA

– Block formation of thromboxane A2 in platelets by blocking cox– Chew 160-325 mg to allow for buccal absorption

• Pain control– Try to decrease sympathetic activity– Analgesics– Nitrates

• Coronary vasodilation, decrease preload by increasing venous capacitance

• Avoid if suspect RV infarct– Beta blockers

• Reduce HR, decrease myocardial oxygen demand• Reduce pain• Reduce the need for analgesics• Reduce infarct size

– Oxygen

STEMI - Reperfusion

• “Time is muscle”• Increased mortality with delay in reperfusion

regardless of strategy• Less time:

– Recovery of LV systolic fxn– Improved diastolic dysfxn– Reduced mortality– Post ischemic contractile dysfxn can occur after

reperfusion– Myocardial stunning

STEMI - Lytics

• Benefits– Recanalize thrombotic occlusion– Restores coronary flow– Reduce infarct size– Improves myocardial function– Improves survival– May result in microvascualr damage and

reperfusion injury– STR strong predictor of reperfusion

STEMI - lytics

• GISSI first trial to demonstrate benefit of streptokinase

• Other fibrinolytics– Alteplase (t-PA)

• GUSTO I

– Reteplace (rtPA)• GUSTO III (equivalence)

– Tenecteplase (TNK)• ASSENT II (equiv with t-PA)

Evidence for Fibrinolysis: GISSI

n >11,000

ARR: 2%

RRR: 18%

Circ. 1998

Comparison of Thrombolytics: GUSTO

n=>41,000

ARR 0.9%RRR 12.5%

NEJM, 1993

ASSENT 2

• N= 16949

• Design: non-inferiority

• Trend toward decrease in bleeding

• Improve ease of use with Bolus infusion

• Combination with heparin IV

Lancet 1999; 354: 716-22

Time to Rx

Efficacy of Thrombolysis: Subgroups

FibrinolyticTherapy Trialists’ Group.Lancet, 1988

n=56,800

Choosing a Fibrinolytic

• Patients in whom t-PA is proven superior to SK:– Age < 75– Anterior MI, presenting within 4 hours– High risk/extensive MI at other site within 4 hours– Cardiogenic shock– Previous SK exposure

• TNK = rtPA > tPA

– Easy administration

– Lower chance of med error

– Less non-cerebral bleeds• Patients in whom SK appears to be equivalent to t-PA:

– Inferior, posterior or lateral MI– MI at any site after 6 hours– Age > 75 years

Bleeding complications with Lytics

• Major bleeding 0.5-2%

• Minor bleeding: 10-20 %

• Intracranial hemorrhage: 0.5-2%

• Management:– D/C thrombolytic– Cryoprecipitate (fibrinogen enriched)– If heparin, give protamine sulfate

Indications for Primary PCI

• Class I– Alternative to thrombolytic if performed in a timely fashion by skilled

individuals– Patients within 36 hours of AMI, with cardiogenic shock, <75 years

• Class IIa– Contraindication to thrombolysis

• Class IIb– NSTEMI within 12 hours, with less than TIMI II flow in infarct

related artery• Class III

– Elective PCI of non-IRA at time of AMI– Beyond 12 hours of symptoms, no evidence of ischemia– Successful thrombolysis

From ACC/AHA Guidelines, 2000

STEMI -PCI

• Meta analyis shows improved clinical endpoints favoring PCI– Factors to consider

• Time to treatment

• Risk of STEMI

• Cardiogenic shock

• Kilip class >= II

• Risk of bleeding

• Time to transport to skilled PCI center

STEMI – Other Rx• ASA

– ISIS-2• Thienpyridines

– Clopidogrel• CLARITY

– Ticlopidine• Inhibit binding to adenosine diphosphate receptor

• GPIIb/IIIa inhibitors– Abciximab– Tirofiban– Eptifibatide

• GUSTO V– rtPA vs 1/2rtPA and abciximab– similar efficace endpoints but increased bleeds with IIb/IIIa

ASA: ISIS 2

Lancet, 1988

n > 17, 000

STEMI – Other Rx

• Heparin – reduces reinfarction, stroke, PE– reduces mortality in pts receiving lytic

• LMWH– ASSENT III showed benefit over UFH in pts

receiving TNK

• Others– Bivalirudin (HITT)

Post- STEMI Rx• BB • ACEi

– Prevents ventricular remodeling– Improved hemodynamics– Reduces CHF– Selected population: (long-term, started day 3-16)

• SAVE• AIRE• TRACE

– Unselected pop (short term, started early)• GISSI 3• SMILE• ISIS-4• CCS-1

Post- STEMI Rx

• ARB – OPTIMAAL (losartan)– VALIANT (valsartan)

• Aldasterone antagonists– EPHESUS (acute MI, LV dysfxn, HF)– Reduction in mortality

• Statins– PROVE-IT

Variable VSD Free Wall Rupture

Papillary Muscle Rupture

Age 63 69 65

Days, post MI 3-5 3-6 3-5

Anterior MI 66% 50% 25%

New Murmur 90% 25% 50%

Thrill Yes No Rare

Previous MI 25% 25% 30%

Echo: VSD Pericardial Effusion

Flail leaflet

MR

PA catheter: O2 step-up RA-RV

Equalization of diastolic press.

Prominent V-wave

Mortality:

Medical

Surgical

90%

50%

90%

?

90%

40-90%

Mechanical Complications of MI

Other Complications

• Arrhythmias– Electrical instability

• VPB• VT• VF• AIVR

– Pump failure/inc symp drive• Sinus tachy• AFib/Flutter• SVT

– Brady/conduction• Sinus brady• Junctional escape• AVB

Other Complications

• Recurrent chest pain– Distinguish reinfarction from recurrent

ischemia from non-ischemic chest pain

• Pericarditis

• LV aneurysm

Risk Stratification

• survival after STEMI depends on– LV fxn

• Stress/pharma Echo, PET

– Residual potentially ischemic myocardium• Submaximal ETT

– Susceptibility to vent arrhythmias

Risk Stratification

Discharge Planning

• usually 5 days post STEMI

• counseling– ambulation but avoid heavy lifting– graded activity (symptom limited)– Rehabilitation

Questions

Documents

Acute coronary syndrome