Lahore: Jan 2011

Principles of Coronary Disease Evaluation & Management

Dr Syed Imran Ahmad MB, MRCP, FRCP (London)

Consultant Cardiologist (Clinical & Invasive) Head, Cardiology Section, Clifton Campus,

Faculty Member Ziauddin University, Karachi:&

Medilink Clinic, Clifton Karachi

Global Disease Mortality

0 5 10 15 20

Mortality (millions)Mortality (millions)

World Health Organization. World Health Organization. The World Health Report 2003: Shaping the Future.The World Health Report 2003: Shaping the Future. 2003. 2003.

Cardiovascular diseaseCardiovascular disease

Malignant neoplasmsMalignant neoplasms

InjuriesInjuries

Respiratory infectionsRespiratory infectionsCOPD and asthmaCOPD and asthma

HIV/AIDSHIV/AIDSPerinatal conditionsPerinatal conditionsDigestive diseasesDigestive diseases

Diarrhoeal diseasesDiarrhoeal diseasesTuberculosisTuberculosis

Childhood diseasesChildhood diseasesMalariaMalaria

DiabetesDiabetes

Atherosclerosis Is a Chronic Inflammatory Disease With LDL-C at the Core

•

Libby P. J Intern Med. 2000;247:349-358.

PHASE I: Initiation PHASE II: Progression PHASE III: Complication

CAD in relation to risk factorsProbability of CAD occurring within next 10 years

36

8

13

23

42

69

13

19

25

44

0 %

10 %

20 %

30 %

40 %

50 %

Women

Men

HBP (150-160) + + + + + +HDL (33-35) - + + + + +Chol (240-262) - - + + + +Cigarettes - - - + + +Diabetes - - - - + +LVH - - - - - +

Kannel WB, Europ.Heart J. 1992; 13:34-42

Integrated Cellular Mechanisms of Cardiovascular Disease

NO SynthesisNO Synthesis

VasoconstrictionVasoconstriction

ThrombosisThrombosis

SuperoxideSuperoxide

COX ActivityCOX Activity

Thromboxane AThromboxane A22

Prostaglandin HProstaglandin H22

ProstacyclinProstacyclin

InflammationInflammation

Leukocyte Leukocyte adhesionadhesion

EndothelialEndothelialpermeabilitypermeability

Angiotensin IIAngiotensin II

T-cell activationT-cell activation

EndothelinEndothelin

VasoconstrictionVasoconstriction

CalciumCalciummobilizationmobilization

Endothelial Dysfunction

DyslipidaemiaDyslipidaemiaHypertensionHypertension

Liao. Liao. Clin ChemClin Chem. 1998:44:1799-1808; adapted from Mason. . 1998:44:1799-1808; adapted from Mason. Cerebrovasc Dis.Cerebrovasc Dis. 2003;16(suppl 3):11-17. 2003;16(suppl 3):11-17.

DiabetesDiabetes SmokingSmoking

Coronary Arteries

Coronary Artery Disease

Angiogram of the left coronary artery and its branches

Initial Presentation of CAD May Be MI orInitial Presentation of CAD May Be MI orSudden Death: Sudden Death: Framingham Heart StudyFramingham Heart Study

MenMen

WomenWomen

0 20 40 60 80

MI or SuddenMI or SuddenDeath as InitialDeath as InitialPresentationPresentation46%

62%

% Patients% PatientsMurabitoMurabito et al. et al. Circulation.Circulation. 1993;88:2548-2555. 1993;88:2548-2555.

Patients Who Developed CAD (N=5144)Patients Who Developed CAD (N=5144)

Manifestations of CAD

• Chronic stable angina

• Unstable angina

• Vasospastic angina (Variant Angina)

• Silent ischaemia

• Myocardial infarction

• Congestive heart failure

• Sudden death (SCD)

Classification of stable angina

Severity I Conduct of daily work and activities without complaints (angina occurs only when load is extreme or over a

very extended period of time)

Severity II Slight restriction of daily work and activities (angina occurs when individual walks fast, climbs stairs or feels stressed)

Severity III Marked restriction of daily work and activities(angina occurs after walking a short distance, or climbing a flight of stairs)

Severity IV Daily work and activities not possible (angina constantly present)

Angina PectorisAngina Pectoris

– Angina is commonAngina is common

- - affects over 10% of men and women > 60affects over 10% of men and women > 60

– Angina is disablingAngina is disabling

- - quality of life can be poorquality of life can be poor

– Angina affects outcome variablyAngina affects outcome variably

- - 3% to 20% annual rate of cardiac events3% to 20% annual rate of cardiac events

Angina PectorisAngina Pectoris

– The The Holy TrinityHoly Trinity of treatment of treatment• Oral NitratesOral Nitrates• Beta BlockersBeta Blockers• Calcium AntagonistsCalcium Antagonists

• Statins and Anti plateletsStatins and Anti platelets

New mechanistic approaches to stable angina

Sinus node inhibition (ivabradine)

Late INa inhibition (ranolazine)

Rho kinase inhibition (fasudil) Metabolic modulation (trimetazidine)

Preconditioning (nicorandil)

OH3C O

H3C O

N

CH3

O CH3

O CH3

NO

N

CH3

H

CH3

CH3 O

O H

N

SO2 NHN

O

O NO2H

N

O

OHCH3

CH3

OCH3HN N N O

N

N

Acute Coronary Syndrome

Unstable anginaor NSTEMI

Temporary resolution of instability

Future high-risk lesion

AcuteSTEMI

Pathophysiology of ACS: Disrupted Plaque

Adapted from Yeghiazarians et al. Adapted from Yeghiazarians et al. N Engl J MedN Engl J Med. 2000;342:101-114.. 2000;342:101-114.

PlaquePlaquerupturerupture

Thin capThin cap

High High macrophagemacrophage

contentcontent

Large lipid coreLarge lipid core

Incomplete Incomplete coronarycoronaryocclusionocclusion

CompleteCompletecoronarycoronaryocclusionocclusion

Spontaneous lysis,Spontaneous lysis,repair, and wall repair, and wall

remodelingremodeling

Pathogenesis of ACS

White HD. Am J Cardiol. 1997; 80(4A):2B-10B.

Cumulative 6-month mortality from CAD

0 1 2 3 4 5 6

5

10

0

15

20

25

Months after hospital admission

Dea

ths

/ 100

pts

/ m

onth

Acute MIUnstable anginaStable angina

Duke Cardiovascular Database

N = 21,761; 1985-1992Diagnosis on adm to hosp

EARLY RISK STRATIFICATION

• In all patients with CP the likelihood of Acute coronary Ischaemia should be determined (High, Intermediate and Low)

• The process of early RS focuses on:Anginal SymptomsClinical ExaminationECG findings Biomarkers of

Cardiac Injury

Why Early Risk Stratification?• Assessment of prognosis, based upon the likelihood of

death/MI should set the pace of Initial Evaluation & Management of ACS.

• The process of RS is needed for

– Selection of the site of care (CCU, Monitored unit, OPD)

– Selection of Therapy specially newer agents like GP

IIb/IIIa inhibitors

– Determination for the need of an early invasive course.

Tools for Risk Assessment(12-lead ECG)

• It remains the sheet-anchor of the decision making for evaluation and management in CP

• A tracing during CP is of particular importance.• High Risk: • ST-segment deviation > 0.05 mV• New or presumed new LBBB

• Sustained VT• Intermediate Risk:• T wave inversion or presence of Q waves• Low Risk:• No ECG changes during CP

Anginal Symptoms

• High Risk:• Accelerating Tempo of CP in preceding 48 hrs or

prolonged CP for >20 min• Intermediate Risk:• Recent prolonged angina at rest for >20 min now

resolved; Rest angina of <20 min.• Low Risk:• New onset Angina with no other High/Intermediate

risk features on symptoms or ECG.

BIOMARKERS• Biomarkers of Cardiac Injury should be

measured in all patients with suspected ACS

• Cardiac Specific Troponin (cTnT or cTnI) is the preferred marker, if available.

• CK-MB is also acceptable

• Total CK (without MB), AST, LDH are considered useless now in this setting.

Principles of Hospital Care in ACS

• Bed Rest

• Continuous ECG monitoring in a CCU for Ischaemia/Arrhythmia

• Nitrates S/L followed by an IV infusion

• Pulse Oximetry with Oxygen if needed

• Morphine Sulphate IV if pain persists and specially with LVF

• Beta Blockade with first dose IV, if CP persists

Principles of Hospital Care in ACS

• ACE-I, early on ( a lot of evidence with drugs like Ramipril: also evidence with ARB e.g. Valsartan)

• Antiplatelets (Aspirin and Clopidogrel)

• Anticoagulants (UFH/LMWH or Fondaparinux)

• Statins

• Early Invasive vs. planned ischaemia driven

Lipid Management in Clinical Practice

• For patients with CHD or diabetes, a new, lower optimal goal for LDL-C is <70 mg/dl —NCEP Coordinating Committee Circulation 2004;110:227–239

What is an appropriate therapeutic target for LDL-C?

Changes to NCEP ATP III LDL-C Goals

Modification

Modification

2+ risk factors (10-year risk 20%)

CHD or CHD risk equivalents(10-year risk >20%)

Risk Category

Optional goal of <100 mg/dl (2.5 mmol/L)

for 10%–20% risk group

Optional goal of <70 mg/dl (1.8 mmol/L)

<130 mg/dl (3.4 mmol/L)ATP III

<100 mg/dl (2.5 mmol/L)ATP III

LDL-C GoalPublication

NCEP=National Cholesterol Education Program; ATP III=Adult Treatment Panel III

Adapted from Grundy SM et al Circulation 2004;110:227–239; Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults JAMA 2001;285:2486–2497.

Rationale for Lower LDL-C Goals

• Both HPS and PROVE IT suggest that additional benefit may be obtained by reducing LDL-C levels to substantially less than 100 mg/dl (2.5 mmol/L)

• Recent trials indicate that there is no threshold below which lower LDL-C concentrations provide no further benefit

Adapted from Grundy SM et al Circulation 2004;110:227–239; HPS Study Group Lancet 2002;360:7–22; Cannon CP et al N Engl J Med 2004;350:1494–1502; O’Keefe JH et al J Am Coll Cardiol 2004;43:2142–2146; Stamler J et al JAMA 2000;284:311–318; Chen Z et al BMJ 1991;303:276–282.

Investigations in CAD

• Non-invasive Testing:

– Echocardiography (Resting and Stress)– ETT– Myocardial Perfusion Studies (Thallium)– CT Angiogram– Cardiac MRI– PET

Investigations in CAD

• Invasive Testing:

– Selective Coronary Angiography & Ventriculography

– Invasive Electrophysiological (EP) Studies

Further Management

• Medical Treatment

• Interventional Treatment– Percutaneous Coronary Intervention (PCI)

– Surgical Intervention (CABG)

Prognosis in CAD

• More closely related to – Left Ventricular Function; &

– Extent of Coronary Disease

than

– The severity of Symptoms

Thank You

Dr Syed Imran Ahmad MB,FRCP(London)