Ischemic Heart Disease

1. Ischemic Heart Disease Amish C. Sura, M.D. F.A.C.C. Clinical Cardiologist Mercy Medical Center September 2008

2. Disclosures • I have no relevant financial relationships with any commercial interest with the manufacturer of any commercial product and/or provider of commercial services discussed in this presentation.

3. What is Ischemic Heart Disease? Cardiac dysfunction due to a decrease in the blood supply caused by constriction or obstruction of the blood vessels. Manifestations: • “Silent” Myocardial Ischemia. • Acute Coronary Syndromes (STEMI, NSTEMI, USA). • Cardiomyopathies and Congestive Heart Failure. • Sudden Cardiac Death (SCD) and other arrhythmias.

4. Diagnostic Tests for IHD • Symptoms • EKG • Stress Testing • Bio-markers • Imaging (CT, MRI, PET) • Coronary Angiography

5. Indications for Stress Testing • Evaluation of patients with known or suspected coronary heart disease (CHD). (etiology of chest pain, planned revascularization, myocardial viability etc.) • Assessment of the therapeutic effects of cardiac drugs. • Assessment of functional capacity. • Try to predict risk of future coronary events among patients with documented CHD, a prior myocardial infarction, or a history of unstable angina.

6. Types of Stress Tests Stress: • Physical vs. pharmacologic • Treadmill, bicycle, isometric hand grip. • Adenosine, Dipyridamole, Dobutamine. Imaging Modalities: • EKG. • Echocardiogaphy. • Perfusion imaging (SPECT MPI). • CT. • PET. • MRI.

7. Who should get perfusion imaging? • Patients with un-interpretable baseline EKGs. (significant baseline ST or T wave abnormalities, LBBB, paced rhythm, pre-excitation (WPW), Digoxin). • Women-lower accuracy and greater incidence of false-positive EKG changes with standard tests; perfusion imaging increases diagnostic accuracy. • Patients who receive pharmacologic stress with adenosine/dipyridamole.

8. Estimated positive predictive value of Exercise EKG Stress test • Depends on the pretest probability of coronary heart disease (CHD), ie, the prevalence of CHD in the population studied.

9. How Good are the Tests? Depends on the Question

10. Functional Capacity during stress testing is related to Mortality Poor N=3400 N=3400 Good Snader CE, Marwick TH et al. JACC 1997;30:641-8

11. Duke treadmill score predicts survival • n=2,578 (70% men). • Duke prognostic treadmill score = Exercise time (minutes based on the Bruce protocol) - (5  x  max ST segment deviation in mm) - (4  x  exercise angina [0=none, 1=non-limiting, and 2=exercise limiting]) • Effective for risk-stratifying men but not women. >97% 90% 65% • Low-risk — score ≥+5 • Moderate-risk — score from -10 to +4 • High-risk — score ≤-11 Data from Shaw, LJ, Peterson, ED, Shaw, LK, et al. Circulation 1998; 98:1622.

12. Cardiac markers classified according to the different pathologic processes they indicate Maisel AS et al.(2006) Cardiac biomarkers: a contemporary status report Nat Clin Pract Cardiovasc Med3:24–34 doi:10.1038/ncpcardio0405

13. What makes a biomarker clinically useful? Morrow, DA, de Lemos, JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circ.2007;115:949-52.

14. Widely used biomarkers • All meet criteria of Morrow & de Lemos. • Brain Natriuretic peptide (BNP). • C-reactive protein (CRP). • Cardiac specific Troponins (TN-I, TN-T).

15. BNP Protein secreted by the heart in response to excessive stretching of heart muscle cells. Causes excretion of sodium (water) and increases cardiac output. • Has been studied in many manifestations of ischemic heart disease. • Adds prognostic significance beyond other measures. • Trends in individual levels maybe more important than discrete measurements.

16. BNP levels correlate with NYHA Class NYHA Classes: I: No symptoms and no limitation in ordinary physical activity. II. Mild symptoms and slight limitation during ordinary activity. III.Marked limitation in activity due to symptoms, even during less-than-ordinary activity. Comfortable only at rest. IV.Severe limitations. Experiences symptoms even while at rest, mostly bed-bound patients Tokunaga, A.Onda, M et al. Biochemical Assessment of Cardiac Function in patients undergoing surgery for gastric cancer. J Nippon Med Sch. 2001.

17. BNP and mortality in CHF From VAL-HeFT: n=4300 NYHA Class II-III patients. Followed for 35 months. Mortality rates at two years after randomization were significantly higher in higher quartiles of plasma BNP . Anand IS et al. Changes in Brain Natriuretic Peptide and norepinephrine over time and mortality and morbidity in the Valsartan Heart Failure Trial (VAL-HeFT).Circ. 2003; 107:1278-83.

18. BNP predicts mortality in Acute Coronary Syndromes 5-43.6 pg/ml 43.7-81.2 pg/ml 81.3-137.8 pg/ml 137.9-1456.6 pg/ml de Lemos JA; Morrow DA; Bentley JH et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001 Oct 4;345(14):1014-21.

19. C-reactive Protein (CRP) • Non-specific acute phase marker of inflammation that is produced predominantly by hepatocytes under the influence of cytokines such as IL-6 and TNF-α. • Confers prognostic information in asymptomatic patients and patients with known ischemic heart disease. Rader, DJ. Inflammatory Markers of Coronary Risk.N Engl J Med 343:1179

20. Actual 8-Year Cardiovascular Events Compared with Framingham Estimate & hs-CRP in the WHS hs-CRP Cardiovascular Events Framingham Estimate of 10-Year Risk Ridker PM et al, N Engl J Med 2002;347:1557

21. CRP Predicts outcome in ACS Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease . N Engl J Med 343:1139

22. CRP is an independent predictor in CHF Ishikawa C, Tsutamoto T et al. Prediction of mortality by high-sensitivity C-reactive protein and brain natriuretic peptide in patients with dilated cardiomyopathy. Circ J. 2006 Jul;70(7):857-63.

23. CRP is prognostic, but clinically useful? From CDC and AHA: • hs-CRP may be useful as an independent marker of prognosis in patients with stable CHD or an ACS. • At present there is insufficient evidence to recommend that CRP determine the application of specific therapies for acute management of ACS or for secondary prevention. • Though CRP may be an independent risk factor for IHD, there is no direct evidence that lowering CRP alone will result in a reduction in cardiovascular risk. Pearson, TA, Mensah, GA, Alexander, RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107:499.

24. Cardiac Troponin • Part of cardiac muscle. • Damage causes release of these proteins into the blood. • Confer independent prognostic information.

25. Troponin in ACS predicts mortality Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L. Markers of Myocardial Damage and Inflammation in Relation to Long-Term Mortality in Unstable Coronary Artery Disease . N Engl J Med 343:1139

26. Troponin I independently predicts mortality in CHF N=251 advanced heart failure patients referred for cardiac transplantation. Horwich TB; Patel J; MacLellan WR; Fonarow GC. Cardiac troponin I is associated with impaired hemodynamics, progressive left ventricular dysfunction, and increased mortality rates in advanced heart failure. Circulation 2003 Aug 19;108(7):833-8

27. Coronary Calcium Scoring • Based on relationship of vascular calcification and vascular disease. • Detected initially using electron beam CT (EBCT), now usually detected using Multi-detector (MDCT) or Multi-slice CT.(MSCT) • Studies are based on EBCT and applied to MDCT/MSCT. • Most utilized scoring system is Agatston score. (derived by multiplying the calcified plaque area by a coefficient based on plaque attenuation values)

28. CAC predicts coronary stenosis Women Men Dx Uncertain • N=1764 patients with chest pain. • Significant stenosis defined as >50%. • There are gender, age and ethnic differences affecting sensitivity and specificity • of calcium scoring. Haberl R, Becker A, et al. Correlation of coronary calcification and angiographically documented stenoses in patients with suspected coronary artery disease: results of 1,764 patients. J Am Coll Cardiol. 2001 Feb;37(2):451-7

29. CAC independently predicts outcome • N=1461 asymptomatic patients (90% men) with risk factors for CAD. • 7 year follow-up. • Demonstrates that CAC adds prognostic value to Framingham Model. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC. Coronary Artery Calcium Score Combined With Framingham Score for Risk Prediction in Asymptomatic Individuals. JAMA. 2004 Jan 14;291(2):210-5.

30. Significant Limitations preclude routine use of CAC • No clear evidence that preventive measures based upon the CAC score leads to an improvement in outcomes. • The potential harm associated with false-positive tests and radiation exposure (especially with repeated testing) is not known. • Though the presence of CAC is highly sensitive for the presence of ≥50% angiographic stenosis, it is only moderately specific, especially in older patients (unclear to what extent data can be extrapolated to patients other than Caucasian men). • Providing patients with the results of CAC testing has not been shown to motivate patients to make lifestyle changes for managing their cardiovascular risk factors.

31. ACC/AHA Recommendations 2007 • Coronary artery calcium scoring has been less well studied in women and ethnic minorities than in Caucasian, non-Hispanic men. As a result, the recommendations are less clearly applicable to these groups. • CAC NOT recommended for asymptomatic patients with low or high ten-year CHD risk as established by the Framingham and modified Framingham/ATP risk scores. • For asymptomatic patients with an intermediate CHD ten year risk (10-20%), CAC suggested when the result might lead to a change in management based upon reclassification to a lower or higher risk group. • In patients who have undergone screening coronary CT scanning, additional noninvasive or invasive testing is not recommended when the CAC score is high (eg, greater than 400). • In patients categorized as high risk by the Framingham risk score, there is no evidence that additional testing will lead to any change in management plan. • In patients assessed to be a low risk, a negative exercise test would confirm the low likelihood of disease. Greenland, P, Bonow, RO, Brundage, BH, et al.ACCF/AHA 2007 Clinical Expert Consensus Document on Coronary Artery Calcium Scoring By Computed Tomography in Global Cardiovascular Risk Assessment and in Evaluation of Patients With Chest Pain: A Report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) Developed in Collaboration With the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2007; 49:378.

32. Gender Differences • Under-estimation of coronary risk in women. • Delayed and underuse of testing in women. • Limited diagnostic accuracy of some tests in women. • Women may have more co-morbidities than men at time of presentation. • These probably contribute to the increased mortality in women after MI or CABG.