acute coronary syndromes dr. jacoba

Acute Acute Coronary Coronary

SyndromesSyndromesKurt Glenn C. Jacoba*, MD, MHSAFPCP, FPCC, FPSCCII, FACC, FAHA

*CHAIRMAN – QMMC INTERNAL MEDICINE CHAIRMAN – CLINICAL CARDIOLOGY DIVIISION, PHILIPPINE HEART CENTER

Acute Coronary Acute Coronary SyndromesSyndromes

Coronary arterial

thrombosis

Unstable angina (UA)

Non-ST-elevation myocardial

infarction (MI)

ST-elevation MI

Chase SL, et.al.: Pharmacological Considerations In Acute Coronary Syndrome (ACS): An Expert Debate. Pharmacy and Therapeutics Vol 32(3):Suppl 1; March 2007

15-20%

Endothelium Platelet Fn

Inflammatory State

Atherosclerotic Plaque

Gene

Profile

Adipocyte Products

Circulating Endothelial

Cells

vWF

EPCs CD40/CD40L P-Selectin

CRP/CD40MPOIL-18

MMPs/?PAPP-AFLAP/LTA4

AdinopectinTNF-αVEGFPAI-1IL-6

Endothelial Dysfunction

+ InflammationPlaque

Morphology/ Stability

Endothelial Dysfunction

+ + + +Endothelial Dysfunction

Proinflammatory/ Prothrombotic

State

=

ACS

Anwaruddin, S et al, Redefining Risk in Acute Coronary Syndromes Using Molecular Medicine. J Am Coll Cardiol 2007; 49:279-89

A Model of Risk Stratification Based on a A Model of Risk Stratification Based on a Representative Panel of Molecular and Representative Panel of Molecular and

Genetic FactorsGenetic Factors

vWF = Von Wille-brand factorEPC = endothelial progenitor cell

fn = platelet functionCRP = C-reactive protein

FLAP = 5-lipoxygenase activating protein pathwayLTA4 = leukotriene A4 pathway

MPO = myeloperoxidaseIL = interleukinMMP = matrix metalloproteinasesPAPP-A = pregnancy-associated plasma protein A

TNF-α = tumor necrosis factor alphaVEGF = vascular endothelial growth factorPAI-1 = plasminogen activator inhibitor

Acute Coronary Acute Coronary SyndromesSyndromes

Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.

75%25%

WBC Blood clotFoam cell

NATURAL HISTORY OF ACUTE CORONARY SYNDROME

PREPATHOGENESIS PERIOD PERIOD OF PATHOGENESIS

Factors that lead to ACS

ENVIRONMENTAL FACTORSOccupation, income, lifestyleMedical care availability

HOST FACTORSAge men: >45y

women: >55 yFamilial dispositionHistory of Coronary Artery DiseaseGenetic predispositionConcomittant medical illness

Above mentioned factors occurring singly or in combination can cause ACS

ASYMPTOMATIC PHASE

50 years

Early Pathogenesis Progression of the disease Convalescence or death

Natural Course of ACS

Death

STEMI Non-STEMI Unstable angina

Elevated/ Not elevated markers of myocardial necrosis

Acute cardiac ischaemia with or w/o ST segment elevation

Thrombus formation with or w/o embolisation

Plaque disruption

PREPATHOGENESIS PERIOD PERIOD OF PATHOGENESIS

Health Promotion

•Awareness

•Right nutrition

•Lifestyle modification

SPECIFIC PROTECTION

•Genetic counseling

•Drug use prevention

•Health care promotion

EARLY DIAGNOSIS & TREATMENT

•Medical Therapy

•Mechanopharmacolgical approaches

•Thrombolytics

•Percutaneous Coronary Intervention

•Coronary Artery Bypass Graft

DISABILITY LIMITATION

•Continuous medical therapy

•Lifestyle modification

REHABILITATION

•Cardiac rehabilitation

•Manageable exercise regimen

Primary Prevention Secondary Prevention Tertiary

Typical Chest PainTypical Chest Pain

UAUA NSTEMINSTEMI STEMISTEMI

ThrombusThrombus Non-occlusive Non-occlusive Partial occlusion, Partial occlusion, sufficient to cause sufficient to cause tissue damage & tissue damage & mild myocardial mild myocardial necrosisnecrosis

Complete occlusionComplete occlusion

ECGECG Non-specificNon-specific ST depression ST depression

+/- T wave inversion +/- T wave inversion

No Q waveNo Q wave

ST-elevationST-elevation

New LBBBNew LBBB

Q waveQ wave

Cardiac markersCardiac markers NormalNormal ElevatedElevated ElevatedElevated

UNSTABLE UNSTABLE ANGINA ANGINA

and and NSTEMINSTEMI

Timing of Release of Various Biomarkers After Acute Myocardial Infarction

Anderson JL, et al.. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non–ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, American College of Physicians, Society for Academic Emergency Medicine, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2007;50:e1–157.


Troponin I Levels to Predict the Risk of Mortality in Acute Coronary Syndromes

Selection of Initial Treatment Strategy: Selection of Initial Treatment Strategy: Invasive Versus Conservative StrategyInvasive Versus Conservative Strategy

Preferred strategyPreferred strategy Patient CharacteristicsPatient Characteristics

InvasiveInvasive Recurrent angina or ischemia at rest or with low-level activities despite Recurrent angina or ischemia at rest or with low-level activities despite intensive medical therapyintensive medical therapy

Elevated cardiac biomarkers (TnT or TnI)Elevated cardiac biomarkers (TnT or TnI)

New or presumably new ST-segment depressionNew or presumably new ST-segment depression

Signs and symptoms of HF or new or worsening mitral regurgitationSigns and symptoms of HF or new or worsening mitral regurgitation

High-risk findings from noninvasive testingHigh-risk findings from noninvasive testing

Hemodynamic instabilityHemodynamic instability

Sustained ventricular tachycardiaSustained ventricular tachycardia

PCI within 6 monthsPCI within 6 months

Prior CABGPrior CABG

High risk score (e.g., TIMI, GRACE)High risk score (e.g., TIMI, GRACE)

Reduced left ventricular function (LVEF less than 40 %)Reduced left ventricular function (LVEF less than 40 %)

ConservativeConservative Low risk score (e.g., TIMI, GRACE)Low risk score (e.g., TIMI, GRACE)

Patient or physician preference in the absence of high-risk featuresPatient or physician preference in the absence of high-risk features

CABG = coronary artery bypass graft surgery; GRACE = Global Registry of Acute Coronary Events; HF = heart failure; LVEF = CABG = coronary artery bypass graft surgery; GRACE = Global Registry of Acute Coronary Events; HF = heart failure; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis In Myocardial Infarction; TnI = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis In Myocardial Infarction; TnI = troponin I; TnT = troponin Ttroponin I; TnT = troponin T


UA/NSTEMI

ASA, enoxaparin or heparin,

Β-block., nitrates, clopidogrel

Risk stratify

High or intermediate risk Low risk

Algorithm for the management of patients Algorithm for the management of patients with unstable angina or non-ST elevation with unstable angina or non-ST elevation

myocardial infarction.myocardial infarction.

Older Trials of Antiplatelet and Anticoagulant Therapy in UA/NSTEMI

ATACS = Antithrombotic Therapy in Acute Coronary SyndromesCAPTURE = c73e Fab AntiPlatelet Therapy in Unstable REfractory anginaFRISC = FRagmin and fast Revascularization during InStability in Coronary artery diseasePARAGON = Platelet IIb-IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization NetworkPRISM = Platelet Receptor inhibition in Ischemic Syndrome ManagementPRISM-PLUS = Platelet Receptor inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and symptomsPURSUIT = Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin TherapyRISC = Research on InStability in Coronary artery disease

0.012

0.005

0.0005

0.018

0.001 0.0005

0.003

0.034

0.042

0.0022

SYNERGY Primary Outcomes at 30 d

Superior Yield of the New strategy of Enoxaparin, Revasculariation and Glycoprotein IIb/IIIa inhibitors

ACUITY Clinical Outcomes at 30 d

Acute Catheterization and Urgent Intervention Triage strategy

OASIS 5 Cumulative Risks of Death, MI, or Refractory Ischemia

Fifth Organization to Assess Strategies for Ischemic Syndromes

Kaplan-Meier Curves Showing Cumulative Incidence of Death or MI

Cumulative Risk of Death or Myocardial Infarction (top) orDeath (bottom) in RITA-3

Relative Risk of Outcomes With Early Invasive Versus Conservative Therapy in UA/NSTEMI

FRISC-II = FRagmin and fast Revascularization during InStability in Coronary artery diseaseICTUS = Invasive versus Conservative Treatment in Unstable coronary SyndromesISAR-COOL = Intracoronary Stenting with Antithrombotic Regimen COOLing-off studyRITA-3 = Third Randomized Intervention Treatment of Angina trialTIMI-18 = Thrombolysis In Myocardial Infarction-18TRUCS = Treatment of Refractory Unstable angina in geographically isolated areas without Cardiac SurgeryVINO = Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction

Relative Risk of All-Cause Mortality for Early Invasive Therapy Compared With Conservative Therapy at a mean

follow-up of 2 years

Relative Risk of Recurrent Nonfatal Myocardial Infarction for Early Invasive Therapy Compared With Conservative Therapy at a mean follow-up of 2 years

Relative Risk of Recurrent Unstable Angina Resulting in Hospitalization for Early Invasive Therapy Compared With Conservative Therapy at a mean follow-up of 13

months

Weaver WD and Block P: Is There a Conservative Strategy for NSTEMI? American College of Cardiology. February 2006.

TIMI III B1 year

(p = 0.42)

VANQWISH1 year

(p = 0.025)

MATE2 years (p = 0.6)

FRISC II1 year

(p = 0.005)

TACTICS-TIMI 18

6 months (p = 0.0498)

VINO6 months (p < 0.001)

RITA-31 year

(p < 0.007)

ICTUS1 year

nonfatal MI (p = 0.005)

death (p = 0.97)

STEMISTEMI

Cardiac biomarkers in ST-elevation myocardial infarction (STEMI)

Major components of time delay between onset of symptoms from ST-elevation MI and restoration of flow in the infarct artery.


Onset of symptoms of STEMI

911EMS

Dispatch

EMS on-scene•Encourage12-lead ECGs•Consider prehospital fibrinolytic if capableand EMS-to-needle within 30 min

Call 9-1-1

Call fast

EMSTriage Plan

Not PCI capable

Hospital fibrinolysis: Door-to-Needle within 30 min

PCI capable

Inte

r-hosp

ital

Tra

nsfe

r

Goals


Patient

5 min after symptom onset

Dispatch

1 min Within 8 min

EMS on scene

Prehospital fibrinolysis: EMS-to-Neddle within 30 min

EMS transport

Patient self-transport: Hospital Door-to-Balloon within 30 min

EMS transport: EMS-to-Balloon within 90 min

Total ischemic time: Within120 min*

*Golden hour = First 60 minutes

Options for transportation of patients with STEMI and initial reperfusion treatment


Options for transportation of patients with STEMI and initial reperfusion treatment

Fibrinolysis

Primary PCI

Noninv Risk Stratification

PCI or CABG

Late Hosp Care & Secondary PrevNot PCI

capable

PCI capable

Receiving Hospital

Isch

em

ia d

riven

Rescu

e

Noninvasive Risk Noninvasive Risk StratificationStratification

High risk (>3% annual mortality rate)High risk (>3% annual mortality rate)

1.1. Severe Severe resting LV dysfunctionresting LV dysfunction (LVEF <0.35) (LVEF <0.35)2.2. High-risk High-risk treadmill scoretreadmill score (score ≤ -11) (score ≤ -11)3.3. Severe Severe LV dysfunctionLV dysfunction (exercise LVEF <0.35) (exercise LVEF <0.35)4.4. Stress-induced Stress-induced large perfusion defectlarge perfusion defect (particularly if (particularly if

anterioranterior))5.5. Stress-induced Stress-induced multiple perfusion defects of moderate sizemultiple perfusion defects of moderate size6.6. Large, fixed perfusion defect with LV dilation or increased Large, fixed perfusion defect with LV dilation or increased

lung uptake (thallium-201)lung uptake (thallium-201)7.7. Stress-induced moderate perfusion defect with LV dilation Stress-induced moderate perfusion defect with LV dilation

or increased lung uptake (thallium-201)or increased lung uptake (thallium-201)8.8. Echocardiographic wall motion abnormality (involving > 2 Echocardiographic wall motion abnormality (involving > 2

segements) developing at a low dose of dobutamine (≤ 10 segements) developing at a low dose of dobutamine (≤ 10 mg·kgmg·kg-1-1·min·min-1-1) or at a low heart rate (<120 bpm)) or at a low heart rate (<120 bpm)

9.9. Stress echocardiographic evidence of extensive ischemiaStress echocardiographic evidence of extensive ischemia

Braunwald E, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non–ST-segment elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). 2002.


Intermediate risk (1-3% annual mortality Intermediate risk (1-3% annual mortality rate)rate)

1.1. Mild/moderate Mild/moderate resting LV dysfunctionresting LV dysfunction (LVEF 0.35- (LVEF 0.35-0.49)0.49)

2.2. Intermediate-risk Intermediate-risk treadmill scoretreadmill score (-11 < score <5) (-11 < score <5)

3.3. Stress-induced Stress-induced moderate perfusion defect without moderate perfusion defect without LV dilation or increased lung intakeLV dilation or increased lung intake (thallium- (thallium-201)201)

4.4. Limited stress echocardiographic ischemia with a Limited stress echocardiographic ischemia with a wall motion abnomality only at higher doses of wall motion abnomality only at higher doses of dobutamine involving ≤2 segmentsdobutamine involving ≤2 segments



Low risk (<1% annual mortality Low risk (<1% annual mortality rate)rate)

1.1. Low-risk Low-risk treadmill scoretreadmill score (score ≥5) (score ≥5)

2.2. Normal or small myocardial Normal or small myocardial perfusion perfusion defect at rest or with stressdefect at rest or with stress

3.3. Normal stress echocardiographic wall Normal stress echocardiographic wall motionmotion or no change of limited resting or no change of limited resting wall motion abnormalities during wall motion abnormalities during stressstress


Assessment of Reperfusion Assessment of Reperfusion Options for STEMI PatientsOptions for STEMI Patients

STEP 1: Assess time and riskSTEP 1: Assess time and risk

STEP 2: Determine if fibrinolysis or STEP 2: Determine if fibrinolysis or invasive strategy is preferred invasive strategy is preferred

Fibrinolysis generally Fibrinolysis generally preferred if:preferred if:

Early Presentation Early Presentation Invasive Strategy is not an optionInvasive Strategy is not an option Delay to Invasive StrategyDelay to Invasive Strategy

Prolonged transportProlonged transport (Door-to-Balloon)-(Door-to-Needle) >1hr(Door-to-Balloon)-(Door-to-Needle) >1hr Medical contact-to-balloon or door-to-Medical contact-to-balloon or door-to-

balloon >90minballoon >90min

Contraindications and Contraindications and Cautions for Fibrinolytic Cautions for Fibrinolytic

Use in STEMIUse in STEMIAbsolute contraindicationsAbsolute contraindications Prior intracranial hemorrhagePrior intracranial hemorrhage Structural cerebral vascular lesionStructural cerebral vascular lesion Malignant intracranial neoplasmMalignant intracranial neoplasm Ischemic stroke w/in 3 mo. EXCEPT acute Ischemic stroke w/in 3 mo. EXCEPT acute

ischemic stroke w/in 3 hischemic stroke w/in 3 h Suspected aortic dissectionSuspected aortic dissection Active bleeding or bleeding diathesisActive bleeding or bleeding diathesis Significant closed head or facial trauma w/in Significant closed head or facial trauma w/in

3 mo.3 mo.

49

37

8

-14-20

-10

0

10

20

30

40

50

60Liv

es S

aved p

er

Thousand

BBB ANT STElevation

INF STElevation

ST DEP

Effect of fibrinolytic therapy on mortality according to admission electrocardiogram

BBB=bundle-branch block; ANT ST Elevation=anterior ST-segment elevation; INF ST Elevation=Inferior ST-segment elevation; ST DEP= ST-segment depression


Invasive Strategy Invasive Strategy preferred if:preferred if:

Skilled PCI lab availableSkilled PCI lab available Medical contact-to-balloon or door-to-Medical contact-to-balloon or door-to-

balloon <90 minballoon <90 min (Door-to-Balloon)-(Door-to-Needle) <1 hr(Door-to-Balloon)-(Door-to-Needle) <1 hr

High risk from STEMIHigh risk from STEMI Contraindications to fibrinolysis Contraindications to fibrinolysis

including risk of bleeding and ICHincluding risk of bleeding and ICH Late presentationLate presentation Diagnosis of STEMI is in doubt Diagnosis of STEMI is in doubt

Primary Angioplasty Primary Angioplasty StrategyStrategy

Provides a greater chance for restoring Provides a greater chance for restoring blood flow and stabilization of the infarct blood flow and stabilization of the infarct artery compared to thrombolysisartery compared to thrombolysis

The expanded latitude of temporal benefit The expanded latitude of temporal benefit may mitigate the logical constraints may mitigate the logical constraints

Stents enhance the durability of the Stents enhance the durability of the procedureprocedure

The promise for evolution of the science The promise for evolution of the science of microcirculatory and myocardial of microcirculatory and myocardial protection during infarctionprotection during infarction

Comparison of Revascularization Comparison of Revascularization Strategies in Multivessel DiseaseStrategies in Multivessel Disease

AdvantagesAdvantages DisadvantagesDisadvantages

Percutaneous Coronary InterventionPercutaneous Coronary Intervention

Less invasiveLess invasive

Shorter hospital stayShorter hospital stay

Lower initial costLower initial cost

Easily repeatedEasily repeated

Effective in relieving symptomsEffective in relieving symptoms

RestenosisRestenosis

High incidence of incomplete High incidence of incomplete revascularizationrevascularization

Relative inefficacy in patients with Relative inefficacy in patients with severe left severe left

ventricular dysfunctionventricular dysfunction

Less favorable outcome in diabeticsLess favorable outcome in diabetics

Limited to specific anatomical Limited to specific anatomical subsetssubsets

Coronary Artery Bypass Graft Coronary Artery Bypass Graft SurgerySurgery

Effective in relieving symptomsEffective in relieving symptoms

Improved survival in certain Improved survival in certain subsetssubsets

Ability to achieve complete Ability to achieve complete revascularizationrevascularization

Wider applicability (anatomical Wider applicability (anatomical subsets)subsets)

CostCost

MorbidityMorbidity

TRIAL TRIAL NN EndpointsEndpoints PCIPCI(%)(%)

CABGCABG(%)(%)

pp

AArterial rterial RRevascularization evascularization TTherapy herapy SStudytudy

12051205 At 1 yearAt 1 yearRate of event-free survivalRate of event-free survivalRate of freedom from anginaRate of freedom from angina Use of antianginal Use of antianginal medicationsmedicationsAt 3 yearsAt 3 yearsRepeat revascularizationRepeat revascularization

73.873.890904242

26.726.7

87.887.879792121

6.66.6

<0.001 <0.001 <0.001<0.001<0.001<0.001

0.00010.0001

OCTOSTENTOCTOSTENT 280280 At 1 yearAt 1 yearEvent-free survivalEvent-free survivalTotal mortalityTotal mortalityCardiac deathCardiac death

85.585.50000

91.591.51.41.42.82.8

NSNSNSNS

SStent tent oor r SSurgeryurgery 988988 At median follow-up of 2 yearsAt median follow-up of 2 yearsRequired additional Required additional revascularizationrevascularizationDeath or QWMIDeath or QWMIDeathDeath

2121

9955

66

101022

<0.0001<0.0001

0.800.800.010.01

ERACI IIERACI II 450450 First 30 daysFirst 30 daysMajor adverse cardiac events: Major adverse cardiac events: Death, Q-wave MI, repeat Death, Q-wave MI, repeat revascularization or strokerevascularization or strokeMean follow-up 18.5 monthsMean follow-up 18.5 monthsSurvival rateSurvival rateFree from MIFree from MIRepeat revascularizationRepeat revascularization

3.63.6

96.996.997.797.716.816.8

12.312.3

92.592.593.493.44.84.8

0.002 0.002

<0.017<0.017<0.017<0.017<0.002<0.002

PCI VS CABG

Percutaneous coronary Percutaneous coronary intervention (PCI) versus intervention (PCI) versus

fibrinolysisfibrinolysis

Short-term clinical outcomes of patients in Short-term clinical outcomes of patients in 23 randomized trials of primary angioplasty 23 randomized trials of primary angioplasty

versus thrombolysisversus thrombolysis

0

5

10

15

20

Perc

enta

ge

Death Death (excludeSHOCK trial)

Reinfarction Stroke Hemorrhagic stroke Death, reinfarction,strokeAngioplasty Thrombolysis

P = 0.0003

P = 0.0003 P < 0.0001

P = 0.0004

P < 0.0001

P < 0.0001

For every 1,000 patients treated, PTCA compared with lytic therapy: 20 lives saved 43 re-MI prevented 13 ICH prevented

acute coronary syndromes dr. jacoba

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