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The Evaluation Of Ischemia Case • A 58 year old woman with diabetes and hypertension presents with symptoms of chronic chest pain. She reports that she can walk about 4 blocks at a moderate pace before developing squeezing chest pain, shortness of breath and diaphoresis that resolves with rest. An EKG in the office is normal. Case • What is the best next step? – Give her nitroglycerin sublingual and order a treadmill stress test – Refer for emergent angiography – Order nuclear perfusion imaging – Start ASA, BB, nitrates and monitor symptoms Case • During a treadmill stress test she exercises for 6 minutes and stops for chest discomfort. There are infer-lateral ST depressions and nuclear imaging shows a moderate sized reversible inferior defect and no fixed defects. Which of the following is true? – An angiogram followed by a stent will improve her symptoms – An angiogram follow by a stent with improve her symptoms and prolong her life – The patient should be sent for a CABG – The patients medical therapy is not optimized CAD And Angina: Significant Morbidity and Mortality • • • • • • • • Incidence 213/100,000 over 30 Lifetime risk: nearly 50% men, 32% women 13,200,000 with CAD, 6,500,000 with angina 7,200,000 post MI 53% of cardiovascular deaths About 1 in 5 deaths in Americans 142.5 billion in 2006 11.1 million deaths worldwide by 2020 Libby. Braunwald’s Heart Disease. 8th Ed. Cumulative Risk Of CAD Remains High In Advanced Age Lloyd-Jones. Lancet, 1999. Angina • • • • Chest or surrounding area caused by ischemia Brought on by exertion No associated with myocardial necrosis Variety of discomfort – Heavy, squeezing, pressure numb burning • Location – Substernal, arms, epigastric • Anginal equivalents – Dyspnea, faintness, fatigue • Duration – Better with rest or nitroglycerin Not Angina • • • • • • Pleuritic pain Highly localized pain Reproduced by movement Duration very long or very short Pain radiating to the lower extremities Resolution more than 5-10 minutes after nitrates or rest Features That Decrease The Liklihood Of Chest Pain Being Angina Panju. JAMA, 1998. Grading Angina • • • • Class I: angina with strenuous activity Class II: Slight limitation of ordinary activity Class III: Marked limitation of ordinary activity Class IV: Inability to do any physical activity or angina at rest Goldman. Circulation, 1981. If It Is Not From The Heart…. Panju. JAMA, 1998. Pathophysiology • Regional myocardial ischemia – Inadequate coronary blood flow – Increased myocardial oxygen demand Pathology of Atherosclerosis Abrams. NEJM, 2005. Factors Influencing Myocardial Oxygen Supply and Demand Libby. Braunwalds Heart Diseasea. 8th Ed. Cardiovascular Risk Assessment • Very high risk: no further estimation – Established vascular disease • Prior MI = 5-7x risk of recurrent MI • Prior stroke= 2-3x risk of MI • PVD = 4x risk of MI – Diabetes – Chronic kidney disease – Hereditary dislipidemia Canto. JAMA, 2003. Risk of MI In Diabetics With No History of CAD Haffner. NEJM, 1998. Why Assess Risk? • Required for determination of medical management • More than 90% of CHD events in patients with at least one risk factor Risk Factors Associated With CAD Yusuf. Lancet, 2004. Framingham Risk Calculator • Predicts risk of MI, CAD death and angina – Low risk <10% risk in 10 years – Intermediate 10-20% risk in 10 years – High risk >20% in 10 years Risk Assessment Tools: Framingham Risk Calculator Other Risk Calculators • SCORE • QRISK/QRISK 2 • Reynolds Limitations Of Risk Calculation • Falsely reassure patients with borderline risk factors • Does not consider lifetime risk • Inability to account for effects of current therapy • Variation in severity of first event • Variation by type of vascular disease High Sensitivity CRP: Additive Value? • Most patients with CAD have traditional risk factors • Unclear that CRP adds value in clinical practice to traditional risk factors Evaluation of Anginal Chest Pain • Risk factor assessment • Physical Examination • Resting electrocardiogram Asymptomatic Patients • No need for stress testing Non Invasive Stress Testing In Symptomatic Patients • Not useful for diagnosis of CAD in low risk or high risk patients • Useful if it will alter the planned management strategy Treadmill Stress Testing • Useful in patients who can: – Exercise on the treadmill adequately – Have a interpretable EKG Echo Stress Testing • Can be performed with exercise or with dobutamine • Requires adequate echo visualization of the heart Nuclear Stress Testing • Can be performed with exercise vasodilator drugs – Adenosine – Dipyridamole • Nuclear tracer is distributed in areas with normal blood flow • Requires contrast between areas of the heart – False negatives with global ischemia Sensitivity And Specificity Of Stress Testing Modality Exercise ECG Total Sensitivity Specificity [†] [†] Patients 24,047 0.68 0.77 Exercise SPECT 5,272 0.88 0.72 Adenosine SPECT 2,137 0.90 0.82 Exercise echocardiography 2,788 0.85 0.81 Dobutamine echocardiography 2,582 0.81 0.79 Gibbons. JACC, 2002. High Risk Stress Test Features: Proceed to Angiography Gibbons. JACC, 2002. Moderate And Low Risk Exercise Testing Gibbons. JACC, 2002. CT Coronary Angiography • Sensitity 90% • Specificity 50% • Not recommended for clinical use Coronary Angiography • • • • Gold standard for identification of significant CAD Potential for revascularization Cannot predict future site of plaque rupture and MI Indications – – – – Concern for left main or triple vessel disease Poorly controlled symptoms Ischemia at a low workload (5-6 mets) Large or multiple defects or WMA Assessment of Left Ventricular Function • Echocardiography or nuclear study • Necessary for strategizing the approach to management Treat Medical Conditions That Can Worsen Ischemia • • • • • • • Anemia Weight gain Thyroid disease Fever Infections Tachycardia Cocaine Necessary Lifestyle Modification • • • • Diet Exercise Work activities Leisure activities – Avoidance of sudden exertion or isometric exercise • Sexual activity – If equivalent level of activity is well tolerated – Sildenafil cannot be taken with nitrates Hypertension Management • For adults, the risk of CAD double for every increase of 20 mmHg over SBP 115 • Predisposes to vascular injury, accelerates CAD, increases myocardial O2 demand and worsens ischemia • Goals of treatment – Less than 140/90 or – Less than 130/80 in DM or CKD Smoking Cessation Decreases MI Risk • Meta analysis of 20 studies • 30% reduction in risk of recurrent event in patients who quit smoking • The most effective and least expensive approach Critchley. JAMA, 2003. Goals Of Medical Management In Stable CAD • Improve mortality and morbidity • Manage symptoms – Improve treadmill performance and time to ST changes • Prevent progression of atherosclerotic disease • Requires adequate dosing and combination approach Aspirin • Myocardial infarction reduction of 34-87% • No difference in 81 vs 325 mg dose • Clopidogrel may substitute for aspirin in intolerant patients Nitrates • Nitrates – Systemic vasodilator -> reduced LV wall stress – Reduced myocardial oxygen demand – Acute or chronic treatment – Tolerance can develop – Improved ex tolerance, time to angina, and ST changes Chen. Proc Natl Acad Sci, 2002. Beta Blockers • Beta receptors – B1: increase HR, contractility, AV conduction • cardioselective – B2: vasodilation and bronchodilation – B3: catecholamine induced thermogenesis • Reduction in myocardial oxygen demand – Heart rate, contractility and wall stress • Improved mortality – Prior MI or heart failure ACE Inhibitors • No benefit in the reduction of ischemia • Benefits shown in patients with CAD and normal LV function • Improve endothelial functioning • HOPE Trial and EUROPA – 20-22% RR ischemic event HOPE Investigators. NEJM, 2000. Cholesterol Lowering Improves Mortality NCEP. NHLBI, 2003. Number Needed To Treat Is Low NCEP. NHLBI, 2003. LDL Target Based On Presence of Risk Factors After Reaching LDL Goals, Target NonHDL Cholesterol, Then HDL • Total cholesterol – HDL= LDL + VLDL • 30 mg/dl higher than LDL goal • Treatment – Statin followed by niacin or fibrates • Low HDL: <40 • Treatment – Lifestyle modification – Niacin or fibrates Ranolazine: Novel Antianginal • No significant changes in heart rate or blood pressure • Reduction in calcium overload via inhibition of the late Na current • Improved exercise performance and time to ischemia • Slight prolongation of the the QT interval, but no association with TDP • Contraindicated in pre-existing QT prolongation Revascularization • CABG or PCI • No evidence for mortality reduction in patients with stable angina and normal LV function Courage Trial: Initial Medical Management vs PCI • Unclear benefit of PCI in stable CAD • Inclusion criteria – At least one70% proximal stenosis, and objective ischemia – At least one 80% stenosis and classic angina • Exclusion criteria – – – – – – Persistent CCS class IV angina Markedly positive stress test Refractory heart failure or cardiogenic shock EF < 30% Revascularization within 6 months Anatomy unfavorable to PCI • Randomized 1149-> PCI, 1138-> medical management • Endpoints – Death and nonfatal MI – Death, MI, stroke or unstable angina Courage Trial: No Difference Between Initial PCI And Medical Management Boden. NEJM, 2007.