acute coronary syndromes in indian context

ACS – INITIAL DIAGNOSIS &

MANAGEMENT

Dr Uday Prashant M.D D.M

Very Alarming Scene

• India is the Diabetic capital of the world:- Highest no of diabetics in world at present

• Indians have one of highest rates of CAD

• Obesity in India is in rapid rise

Coronary Artery Disease in Indians = CADI

• How is it different from western world

• CADI strikes early !

• CADI strikes almost any one !!!

• CADI strikes unexpectedly !!!!

• Conventional RF can’t explain it away

• CADI is malignant in its onslaught.

The CADI Volcano• We are in the middle of the wave of CAD We are in the middle of the wave of CAD

epidemicepidemic

• This CADI epidemic will peak by 2015This CADI epidemic will peak by 2015

• 50% deaths in India are CVD deaths. 50% deaths in India are CVD deaths.

• CADI will overtake Infectious diseases in CADI will overtake Infectious diseases in morbidity toomorbidity too

• By 2015 CADI will be By 2015 CADI will be six timessix times more than the more than the WestWest

• CADI will be CADI will be 20 times20 times more than the Chinese, more than the Chinese,

ACS

• Spectrum of presentation– Myocardial infarction ( 25% – 30%)– Non Q wave MI ( 30% - 35% )– unstable angina (30% - 35%)– Sudden Cardiac Death (5% - 10%)

Non Q wave MI / USA compromises 2/3 rd of ACS cases

15% - 20% of USA are high risk cases.

Sudden Cardiac Death

Immediately next ECG

New Terminology in ACS

ACS, acute coronary syndrome; MI, myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention.Cannon CP. J Thromb Thrombolysis. 1995;2:205-218.

AntithromboticTherapy

Stable Angina

UnstableAngina

Non–Q-wave MI

ThrombolysisPrimary PCI

Q-wave MI

Minutes-hours

Days-weeks

STEMIUA/NSTEMIAtherothrombosisNew term

Old term

PlaqueRupture

Acute Coronary Syndrome

Ischemic DiscomfortUnstable Symptoms

No ST-segmentelevation

ST-segmentelevation

Unstable Non-Q Q-Waveangina AMI AMI

ECG

AcuteReperfusion

HistoryPhysical Exam

Pathogenesis of ACS

Non-Vulnerable Atherosclerotic

Plaque

Non-Vulnerable Atherosclerotic

Plaque

Vulnerable Atherosclerotic

Plaque

Vulnerable Atherosclerotic

Plaque

Davies MJ. Circulation. 1996;94:2013-2020.

Fissures inthe fibrous cap

The Matrix Skeleton of UnstableCoronary Artery Plaque

Vulnerable plaques

• Vulnerable plaques cause ACS• Depends upon inner free lipid content, thin

fibrous cap, active inflammation, hemodynamic stresses.

• More than one vulnerable plaques can be present which are not Rx by PCI.

• Vulnerable plaques cannot be detected by routine CAG.

• Can be inferred indirectly by hsCRP – Rx high dose statins

Chest pain with ACS

• 15 -25 % of chest pain cases in ED have ACS

• 2 % of ACS are missed• These are current US data• In India the percentages are far

higher• For Pt mortality / for us medicolegal

implications

Clinical Classification of Chest Pain

Diamond . J Am Coll Cardiol 1983

Typical Angna

• Cardiac symptoms: Presence of acute chest, epigastric, neck, jaw, or arm pain or discomfort or pressure without apparent noncardiac source.

• Levine`s sign may be +ve.• More general, atypical symptoms, such as

fatigue, nausea, vomiting, diaphoresis, faintness, and back pain, should not be used as a diagnosis of Angina

1. Diabetes Mellitus2. Peripheral Vascular Disease (PVD)3. Framingham risk score of > 20%

4. Carotid artery disease – • Stroke, TIA• > 50% Narrowing, Carotid Bruit

5. Abdominal Aortic Aneurysm (AAA)

CHD Risk Equivalents

Adult Treatment Panel III. NIH publication 01-3095.

Epidemiological definition of MI

• Typical chest pain lasting for > 30 min not relieved by nitrates

• ECG showing characteristic changes of MI

• Positive cardiac biomarkers of injury

WHO states any of two from above three should be present.

Definition of Acute/Evolving/Recent MI

1) Typical rise and fall of biochemical markers of MI with atleast 1 of them

• Ischaemic symptoms• ECG changes indicative of ischaemia (ST

elevation or depression or LBBB)• Development of pathological Q waves in

ECG

• New RWMA or imaging e/o loss of viable myocardium

ACC/AHA/EU/WHO Task force for redefinition of MI 2007 guidelines

ST elevation

R

P

Q

ST

• Occurs in the early stages

• Occurs in the leads facing the infarction

• Slight ST elevation may be normal in V1 or V2

Deep Q wave

R

P

Q

T

ST

• Only diagnostic change of myocardial infarction

• At least 0.04 seconds in duration

• Depth of more than 25% of ensuing R wave

T wave changes

R

P

Q

T

ST

• Late change

• Occurs as ST elevation is returning to normal

• Apparent in many leads

Bundle branch block

I II IIIaVR aVL aVF

V1 V2 V3 V4 V5 V6 I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

Anterior wall MI Left bundle branch block

Sequence of changes in evolving AMI

1 minute after onset 1 hour or so after onset A few hours after onset

A day or so after onset Later changes A few months after AMI

Q

R

P

QT

STR

P

Q

ST

P

Q

T

ST

R

P

S

T

P

QT

ST

R

P

Q

T

Anterior infarctionAnterior infarction

I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

Left coronary artery

Inferior infarctionInferior infarction

I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

Right coronary artery

Lateral infarctionLateral infarction

I II III aVR aVL aVF V1 V2 V3 V4 V5 V6

Left circumflexcoronary artery

Location of infarct combinations

aVR V1 V4I

II

III

LATERAL

INFERIOR

ANTPOST ANT

SEPTAL

ANT

LAT

aVL

aVF

V2

V3

V5

V6

Right Ventricular InfarctionRight Ventricular Infarction

Clinical findings:Shock with clear lungs, elevated JVPKussmaul sign

Hemodynamics: Increased RA pressure (y descent)Square root sign in RV tracing

ECG:ST elevation in R sided leads

Echo:Depressed RV function

Rx:Maintain RV preloadLower RV afterload (PA---PCW)Inotropic supportReperfusion

V4R

Modified from Wellens. N Engl J Med 1999;340:381.

Diagnostic criteria for AMI

• Q wave duration of more than 0.04 seconds

• Q wave depth of more than 25% of ensuing r wave

• ST elevation in leads facing infarct (or depression in opposite leads)

• Deep T wave inversion overlying and adjacent to infarct

• Cardiac arrhythmias

Cor pulmonale

MI presenting as Syncope

• 60 yrs sudden onset chest pain f/b syncope

• H/o associated sweating +

• Afterwards no chest pain

• No risk factors other than age

• Dilemma whether it is arrythmogenic syncope.

Trop T -Ve

Non ischaemic causes of ST elevation

• Early repolarization changes.

• Prinzmetal angina

• Ventricular aneurysm

• Pericarditis myocarditis

• Hyperkalemia, Hypercalcemia

• LVH, LBBB

• IC bleed mistaken as MI

Mistaken MI

• Lingam diagnosed as AWMI

• CAG revealed critical lesion LAD

• Underwent successful stenting to LAD

• But patient still symptomatic

• Presented with Grade IV dyspneoa

• ECHO showed COR PULMONALE

Non MI causes of pathalogical Q waves

• Norma septal Q waves V1-V2, III & AVF (narrow)

• Cardiomyopathies.

• Severe LVH, LBBB

• Dextrocardia/version.

• COPD

Young MI

• Devender 27 yrs male

• Non smoker

• Non diabetic

• H/O travel to dubai, elctrician

• Middle class family

• Chest pain 3 hrs duration

Homocysti(e)ne• Normal value is up to 10 μ mols/L

• Excess of homocystine generates oxidative stress on the cell membranes.

• Folic acid 5 mg/ day + Vit. B6 and B12 are to be given on regular basis

Hyper-homocyst(e)inemia

Blood Homocyst(e)ine Levels

Classification Values mmol/L

Normal

Moderate

Intermediate

Severe

05 – 10

11 – 30

31 – 100

> 100

Lipid Profile in Young Indian Patients with Angiographically Proven CHD

Parameter % Patients

Total cholesterol >200 mg/dl 54.3

Triglyceride >200 mg/dl 56.1

HDL <35 mg/dl 59.6

Lp(a) >30 mg/dl 61.4

n=57; age <40 yrsMishra et al (Cuttack)

Indian Heart J 2001; 53: Abst 60

CHD Risk Factors - Makers

• Modifiable – The New Six– hs-CRP

– Lp(a)

– sLDL

– Endothelial Dysfunction

– Apo B / Apo A1 ratio

– Homocysteine

Risk Factors for Future Cardiovascular Events: WHS

Relative Risk of Future Cardiovascular Events0

Ridker PM et al. N Engl J Med 2000;342:836-843.

Lipoprotein(a)

Homocysteine

IL-6

TC

LDL-C

sICAM-1

SAA

Apo B

TC:HDL-C

hs-CRP

hs-CRP + TC:HDL-C1.0 2.0 4.0 6.0

Post stent MI

• Mr Rathod 60 yrs male.

• 1999 had ACS, uderwent stenting and not on reqular follow up

• Asymptomatic since then

• Presented with typical h/o of MI

Clinical indicators of successful reperfusion

• Resolution of chest pain by > 50%

• Resolution of ST elevations by > 50%

• AIVR

• Rapid rise and fall of cardiac enzymes

• Clinically stable course

For Managment

• ST elevation MI :- Rapid thrombolysis vs immediate revascularization

(Complete occlusion of lumen by red thrombus)

• Non ST elevation MI:- Antithrombotics and plaque stabilization or cooling off. Early invasive strategy is controversial

(Partial occlusion of lumen by white thrombus)

Management of MI

• All management strategies focus on faster reperfusion of culprit artery.

• Spontaneous recanalization rates after MI is

40 %• But it is after 12 – 24 hrs• Permanent damage has already set

in

Management of MI

• Within 30 minutes if reperfused no damage to myocardium.

• Within 2- 4 hrs of reperfusion the damages are minimal.

• After 6 hrs what we save is much less than what myocardium we loose

Management of MI

• After 12 hrs no use of repurfusion • permanent damage sets in though

surrounding hibernating myocardium can be saved.

• To assess for hibernating myocardium we have

Presence of chest pain TMT Nuclear Scans Dobutamine Stress Echo MRI etc

• ITS NOT GIVING RIGHT TREATMENT THAT IS IMPORTANT IN MI MANAGEMENT BUT HOW FAST WE ADMINISTER THAT IS IMPORTANT

• For every 30 min delay in reperfusion the one year risk of relative mortality increases by 8%

y

? MI

• Laksmi presented with 2 hrs duration of severe chest pain

• She 35 years female• ECG not fulfilling criteria of MI• Enzymes useless• Later ECHO except mild apical

hypokinesia normal• CAG Prox LAD 90% stenosis.

Fibrinolysis generally preferred Early presentation ( ≤ 3 hours from symptom onset and delay to invasive strategy)

Invasive strategy not an option Cath lab occupied or not available Vascular access difficulties

No access to skilled PCI lab

Delay to invasive strategy Prolonged transport

Door-to-balloon more than 90 minutes > 1 hour vs fibrinolysis (fibrin-specific agent) now

Reperfusion Options for STEMI PatientsReperfusion Options for STEMI Patients Step 2:Step 2: Select Reperfusion Treatment. Select Reperfusion Treatment.

If presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy.

Invasive strategy generally preferred Skilled PCI lab available with surgical backup

Door-to-balloon < 90 minutes

• High Risk from STEMI Cardiogenic shock, Killip class ≥ 3

Contraindications to fibrinolysis, including increased risk of bleeding and ICH

Late presentation > 3 hours from symptom onset

Diagnosis of STEMI is in doubt

Reperfusion Options for STEMI PatientsReperfusion Options for STEMI Patients Step 2:Step 2: Select Reperfusion Treatment. Select Reperfusion Treatment.

If presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy.

FibrinolysisFibrinolysis

Fibrinolytic therapy should not be administered to

asymptomatic patients whose initial symptoms of

STEMI began more than 24 hours earlier.

Fibrinolytic therapy should not be administered to

patients whose 12-lead ECG shows only ST-

segment depression, except if a true posterior MI

is suspected.

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII

Contraindications and CautionsContraindications and Cautionsfor Fibrinolysis in STEMIfor Fibrinolysis in STEMI

Absolute Contraindications

• Any prior intracranial hemorrhage

• Known structural cerebral vascular lesion (e.g., arteriovenous malformation)

• Known malignant intracranial neoplasm (primary or metastatic)

• Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours

NOTE: Age restriction for fibrinolysis has been removed compared with prior guidelines.

Contraindications and CautionsContraindications and Cautionsfor Fibrinolysis in STEMIfor Fibrinolysis in STEMI

Absolute Contraindications

• Suspected aortic dissection

• Active bleeding or bleeding diathesis (excluding menses)

• Significant closed-head or facial trauma within 3 months

Contraindications and CautionsContraindications and Cautionsfor Fibrinolysis in STEMIfor Fibrinolysis in STEMI

• History of chronic, severe, poorly controlled hypertension

• Severe uncontrolled hypertension on presentation (SBP > 180 mm Hg or DBP > 110 mm Hg)

• History of prior ischemic stroke greater than 3 months, dementia, or known intracranial pathology not covered in contraindications

• Traumatic or prolonged (> 10 minutes) CPR or major surgery (< 3 weeks)

RelativeContraindications

Contraindications and CautionsContraindications and Cautionsfor Fibrinolysis in STEMIfor Fibrinolysis in STEMI

RelativeContraindications

• Recent (< 2 to 4 weeks) internal bleeding • Noncompressible vascular punctures • For streptokinase/anistreplase: prior

exposure (> 5 days ago) or prior allergic reaction to these agents

• Pregnancy• Active peptic ulcer • Current use of anticoagulants: the higher the

INR, the higher the risk of bleeding

Choice of Thrombolytic

• Underuse:- 50 – 70% of cases only given thrombolytics.

• tPA:• • Less allergic reactions• • Less fibrinogen depletion (“clot selective”)• • Faster thrombolysis• • Slightly lower overall mortality

• 2) Streptokinase (SK):• • Less expensive ($300 vs $2500)• • Lower stroke rate (0.3% vs 0.8%)• • Can’t use again secondary to antibody formation

Thrombolysis

• 90 minute patency better with rt-PA than SK (70% vs 55% in Euro CoopStudy and 70% vs 43% in TIMI-1)

• Patency at 24 hours roughly equal between tPA and SK• ISIS-3 – mortality identical in head to head comparison of tPA and SK• Many studies favor tPA over SK

Primary PTCA

• Gangasagar 52 yrs male

• H/O Diabetes

• Chest pain for 4 hrs

Adapted from Braunwald E. Circulation 1989;80:410-4

Classification of USA

Class I:- New onset angina or 7.1% accelerated angina.Class II:- Angina at rest but not within 48 hrs. 10.3%Class III:- Angina at rest within 48 hrs. 10.9%

A:- Secondary angina(14%), B:- Primary angina ( 8.5%), C:- Post infarct angina (18.5%)

Medical Management of Unstable Angina

• Nitrates:- ISIS 4• Beta Blockers:- HINT• Aspirin:- Cohen, RISC, Theroux et al• Clopidogrel:- CURE, CREDO, CAPRIE• Heparin • Or LMWH:- ESSENCE, TIMI 11B, FRIC,• GP2b3a inhibitors:- PRISM, EPIC PURSUIT,

CAPTURE, PARAGON• Statin:- LIPID, PROVE IT TIMI 18, TNT, A to Z• ACE:- SAVE, SOLVD

Authors/Task Force Members, et al. Eur Heart J 2007 28:1598-1660; doi:10.1093/eurheartj/ehm161

Death, myocardial infarction, and major bleeds at 30 days in randomized trials of glycoprotein IIb/IIIa inhibitors (filled bars) vs. control (open bars) in a conservative strategy

SHOCK Trial

• Early invasive strategy was first proved beneficial in high risk MI patients by SHOCK trail than

No role for Wait & Watch & Intervene

Primary PCI is better than thrombolysisPAMI, DINAMI, etc – 24 RCT`s

Does same apply for USA management?

Answer is:- NO

1) Plaque volume (constant) & vulnerability.

2) Type of Thrombus differs (white vs red)

3) Patent lumen

New Terminology in ACS

ACS, acute coronary syndrome; MI, myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention.Cannon CP. J Thromb Thrombolysis. 1995;2:205-218.

AntithromboticTherapy

Stable Angina

UnstableAngina

Non–Q-wave MI

ThrombolysisPrimary PCI

Q-wave MI

Minutes-hours

Days-weeks

STEMIUA/NSTEMIAtherothrombosisNew term

Old term

PlaqueRupture

Risk Stratification Tools• Clinical Assessment• Standard ECG and Non-standard ECG

leads• Markers

– Other: IMA, BNP, CRP

• Non-Invasive Studies– Echocardiogram– Exercise testing– Technetium-99m-sestamibi– MR angio, CT angio

Ischaemia

Inflammation

Myocyte Necrosis

Accelerated Atherosclerosis

Hemodynamic Stress

HbA1cBlood

glucose

IMA

Troponin

BNP, NT-proBNPhs-CRP, CD40L

Morrow DA, et al. Circulation. 2003;108:250-252.

Multimarker Strategy in ACS

Short-Term Risk of Death or Nonfatal Myocardial Infarction in Patients With Unstable Angina

Braunwald E et al.: Unstable angina: diagnosis and management. AHCPR Publication No 94-0602

Risk of Death or Myocardial Infarction According to Treatment Strategy and cTnI: TACTICS TIMI 18

Morrow DA et al. JAMA 2001;286:2405-12

TIMI, thrombosis in myocardial infarction; UA, unstable angina; NSTEMI, non–ST-segment elevation myocardial infarction; CAD, coronary artery disease.Antman EM, et al. JAMA. 2000;284:835-842.

TIMI Risk Score for UA/NSTEMI: 7 Independent Predictors

– ≥3 CAD risk factors

– Aged ≥65 years

– Prior CAD (stenosis >50%)

– Aspirin in last 7 days

– >2 anginal events in ≤24 hours

– ST deviation

– Elevated cardiac markers (CK-MB or troponin)

Global Registry of Acute Coronary Events (GRACE) risk score

• The GRACE risk score (on a scale of 1 to 372, with higher scores indicating greater risk) is derived from readily available hospital admission variables,

- including age, - heart rate, - systolic blood pressure, - creatinine level, - Killip class, - cardiac arrest at admission, - presence of ST-segment deviation, and - elevated cardiac biomarkers.

Values for these variables can be entered into the GRACE risk calculator

Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

GRACE Prediction Score Card and Nomogram for All-Cause Mortality From Discharge to 6 Months

Indications for early invasive strategy

• Recurrent rest angina

• Elevated troponin• New ST changes• LVF• Positive stress test

• EF<40%• Haemodynamic

instability• Malignant

arrhythmias• PCI<6 months• CABG

Timing of Invasive strategy in Non ST Elevation MI

What is early and late

• Early intervention is < 24 - 48 hours of presentation.

• Late intervention is >36 - 48 hours of presentation

ISAR COOL

• Early treatment reduces long term MI, mortality.

• However procedure complications increase.

• To offset it “cool off” or plaque pacifying strategy using prolonged antithrombotic & GP2b3a inhibitors.

ISAR COOL

SYNERGY Trial

(Circulation. 2007;116:2669-2677.)

Conclusions SYNERGY Trial

• High-risk patients with NSTE ACS who received earlier coronary angiography had a decreased risk of death/MI through 30 days.

Authors/Task Force Members, et al. Eur Heart J 2007 28:1598-1660; doi:10.1093/eurheartj/ehm161

Decision-making algorithm for the management of patients with non-ST-elevation acute coronary syndrome

Case of USA

• Mr Sheik Ahhmed 45 yrs male• Chronic smoker• Labourer• For past 2 months not able to work due to

chest pain• Somebody has to hit him in back for relief

of pain• Increasing frequency & duration of pain

y

Wallen`s Warning

Care of IHD patients

• Primary prevention

• Secondary prevention

The Progressive Development of Cardiovascular Disease

End stage Heart DiseaseEnd stage Heart Disease

Congestive Heart FailureCongestive Heart Failure

Ventricular DilationVentricular Dilation

RemodelingRemodeling

Arrhythmia & Muscle LossArrhythmia & Muscle Loss

Myocardial InfarctionMyocardial Infarction

Myocardial IschemiaMyocardial Ischemia

CADCAD

AtherosclerosisAtherosclerosis

Endothelial DysfunctionEndothelial Dysfunction

Risk FactorsRisk Factors

Coronary ThrombosisCoronary Thrombosis

Intervene here}

Public Awareness

A survey of people with Diabetes• Findings

– 68% do not consider cardiovascular disease to be complication of diabetes

– 50%+ don’t feel risk for heart condition or stroke

– 60% don’t feel at risk for high blood pressure or cholesterol

– Awareness lowest among elderly, minorities

2

Why is CAD becoming so rampant

• Is it people are living longer?

• Is it increasing habits like smoking cocaine?

• Is it raise in Diabetes?

• Is it food we eat?

• Or is it all in the genes?

With in no time !!

Where are we heading ? ?

Journal of internal medicine 2003:254(2):114-25

20000 B.C. 2004

Hunting-gatheringsubsistence

High level ofphysical activity

Processedfoods

Animal fatsand glucidesDietary fibre¯

Sedentary life

Paleolithic sup. age Neolithic age 19th century 21st century

Thrifty genotype Susceptibility genotype

This is how we take our dog to walk!

Secondary Prevention of CAD

Secondary prevention

• The above drugs are minimum for post MI/USA patients

• If diabetic then OHA`S 1 + 2 drugs• If severe LV dysfunction diuretics, digoxin• If PVD or BPH or OA or ED – extra drugs• Post stent tripple antiplatelets common• Antacids, vitamins, calcium etc

Hippocrates said ….

Let your FOOD be your Medicine – Lest,

Your Medicines will replace your Food !!

MedSlides.comMedSlides.com 1461465/985/98

THANK THANK YOUYOU