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 Mortality (millions) World Health Organization. The World Health Report 2003: Shaping the Future. 2003. Cardiovascular disease Malignant neoplasms Injuries Respiratory infections COPD and asthma HIV/AIDS Perinatal conditions Digestive diseases Diarrhoeal diseases Tuberculosis Childhood diseases Malaria Diabetes
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 factors Probability of CAD occurring within next 10 years 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 Endothelial Dysfunction Dyslipidaemia Hypertension Liao. Clin Chem . 1998:44:1799-1808; adapted from Mason. Cerebrovasc Dis. 2003;16(suppl 3):11-17. Diabetes Smoking NO Synthesis Vasoconstriction Thrombosis Superoxide COX Activity Thromboxane A 2 Prostaglandin H 2 Prostacyclin Inflammation Leukocyte adhesion Endothelial permeability Angiotensin II T-cell activation Endothelin Vasoconstriction Calcium mobilization
Coronary Artery Disease Angiogram of the left coronary artery and its branches
Manifestations of CAD
Chronic stable angina
Vasospastic angina (Variant Angina)
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 is common
- affects over 10% of men and women > 60
Angina is disabling
- quality of life can be poor
Angina affects outcome variably
- 3% to 20% annual rate of cardiac events
The Holy Trinity of treatment
Statins and Anti platelets
New mechanistic approaches to stable angina Sinus node inhibition (ivabradine) Late I Na inhibition (ranolazine) Rho kinase inhibition (fasudil) Metabolic modulation (trimetazidine) Preconditioning (nicorandil) O H 3 C O H 3 C O N CH 3 O CH 3 O CH 3 O O NO 2 H N N N N O N CH 3 H CH 3 CH 3 O O H N SO 2 NH N O OH CH 3 CH 3 OCH 3 H N N N O
Acute Coronary Syndrome
Pathophysiology of ACS: Disrupted Plaque Unstable angina or NSTEMI Temporary resolution of instability Future high-risk lesion Acute STEMI Adapted from Yeghiazarians et al. N Engl J Med . 2000;342:101-114. Plaque rupture Thin cap High macrophage content Large lipid core Incomplete coronary occlusion Complete coronary occlusion Spontaneous lysis, repair, and wall remodeling
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 Deaths / 100 pts / month Acute MI Unstable angina Stable angina Duke Cardiovascular Database N = 21,761; 1985-1992 Diagnosis 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 Symptoms Clinical Examination ECG 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.
ST-segment deviation > 0.05 mV
New or presumed new LBBB
T wave inversion or presence of Q waves
No ECG changes during CP
Accelerating Tempo of CP in preceding 48 hrs or prolonged CP for >20 min
Recent prolonged angina at rest for >20 min now resolved; Rest angina of <20 min.
New onset Angina with no other High/Intermediate risk features on symptoms or ECG.
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
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)
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 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. 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 Goal Publication
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.