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 Total Patients Sensitivity[†] Specificity[†] Exercise ECG 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 0.79 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 Reduction in myocardial oxygen demand 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 Non-HDL 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 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 In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events. Methods We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). Results There were 211 primary events in the PCI group and 202 events in the medicaltherapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P = 0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P = 0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P = 0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P = 0.33). Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657.) Boden. NEJM, 2007.