Section 13: Evaluation and Therapy for Heart Failure in the Setting of Ischemic Heart Disease

Abstract

Overview In the US it is estimated that 12,900,000 people have a history of myocardial infarction (MI), angina pectoris, or both.1American Heart Association. Heart disease and stroke statistics—2003 update. Available from http://www.americanheart.org. Accessed September 15, 2003.Google Scholar The most common cause of chronic heart failure (HF) is no longer hypertension or valvular heart disease; it is coronary artery disease (CAD).2Gheorghiade M. Bonow R.O. Chronic heart failure in the United States: a manifestation of coronary artery disease.Circulation. 1998; 97: 282-289Crossref PubMed Google Scholar The changing pattern in the risk factors for HF is evidenced in the Framingham Heart Study, which documents a decrease in valvular disease and LV hypertrophy and an increase in MI from 1950 to 1998.3Lloyd-Jones D.M. Larson M.G. Leip E.P. Beiser A. D'Agostino R.B. Kannel W.B. et al.Lifetime risk for developing congestive heart failure: the Framingham Heart Study.Circulation. 2002; 106: 3068-3072Crossref PubMed Scopus (626) Google Scholar In 21 multicenter HF treatment trials reported in the New England Journal of Medicine over the past 15 years, involving more than 35,000 patients, CAD was present in nearly 65%.4Cohn J.N. Archibald D.G. Ziesche S. Franciosa J.A. Harston W.E. Tristani F.E. et al.Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.N Engl J Med. 1986; 314: 1547-1552Crossref PubMed Google Scholar, 5Effects of enalapril on mortality in severe congestive heart failure Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group.N Engl J Med. 1987; 316: 1429-1435Crossref PubMed Google Scholar, 6DiBianco R. Shabetai R. Kostuk W. Moran J. Schlant R.C. Wright R. A comparison of oral milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure.N Engl J Med. 1989; 320: 677-683Crossref PubMed Google Scholar, 7Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors.N Engl J Med. 1992; 327: 685-691Crossref PubMed Google Scholar, 8Cohn J.N. Johnson G. Ziesche S. Cobb F. Francis G. Tristani F. et al.A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.N Engl J Med. 1991; 325: 303-310Crossref PubMed Google Scholar, 9Packer M. Carver J.R. Rodeheffer R.J. Ivanhoe R.J. DiBianco R. Zeldis S.M. et al.Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group.N Engl J Med. 1991; 325: 1468-1475Crossref PubMed Google Scholar, 10Packer M. Gheorghiade M. Young J.B. Costantini P.J. Adams K.F. Cody R.J. et al.Withdrawal of digoxin from patients with chronic heart failure treated with angiotensin-converting-enzyme inhibitors. RADIANCE Study.N Engl J Med. 1993; 329: 1-7Crossref PubMed Google Scholar, 11Feldman A.M. Bristow M.R. Parmley W.W. Carson P.E. Pepine C.J. Gilbert E.M. et al.Effects of vesnarinone on morbidity and mortality in patients with heart failure. Vesnarinone Study Group.N Engl J Med. 1993; 329: 149-155Crossref PubMed Scopus (314) Google Scholar, 12Singh S.N. Fletcher R.D. Fisher S.G. Singh B.N. Lewis H.D. Deedwania P.C. et al.Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.N Engl J Med. 1995; 333: 77-82Crossref PubMed Scopus (825) Google Scholar, 13Packer M. Bristow M.R. Cohn J.N. Colucci W.S. Fowler M.B. Gilbert E.M. et al.The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (3225) Google Scholar, 14Packer M. O'Connor C.M. Ghali J.K. Pressler M.L. Carson P.E. Belkin R.N. et al.Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.N Engl J Med. 1996; 335: 1107-1114Crossref PubMed Scopus (853) Google Scholar, 15The effect of digoxin on mortality and morbidity in patients with heart failure The Digitalis Investigation Group.N Engl J Med. 1997; 336: 525-533Crossref PubMed Scopus (1786) Google Scholar, 16Cohn J.N. Goldstein S.O. Greenberg B.H. Lorell B.H. Bourge R.C. Jaski B.E. et al.A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators.N Engl J Med. 1998; 339: 1810-1816Crossref PubMed Scopus (427) Google Scholar, 17Pitt B. Zannad F. Remme W.J. Cody R. Castaigne A. Perez A. et al.The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.N Engl J Med. 1999; 341: 709-717Crossref PubMed Scopus (4822) Google Scholar, 18Torp-Pedersen C. Moller M. Bloch-Thomsen P.E. Kober L. Sandoe E. Egstrup K. et al.Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group.N Engl J Med. 1999; 341: 857-865Crossref PubMed Scopus (629) Google Scholar, 19Colucci W.S. Elkayam U. Horton D.P. Abraham W.T. Bourge R.C. Johnson A.D. et al.Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group.N Engl J Med. 2000; 343: 246-253Crossref PubMed Scopus (646) Google Scholar, 20Packer M. Coats A.J. Fowler M.B. Katus H.A. Krum H. Mohacsi P. et al.Effect of carvedilol on survival in severe chronic heart failure.N Engl J Med. 2001; 344: 1651-1658Crossref PubMed Scopus (1908) Google Scholar, 21A trial of the beta-blocker bucindolol in patients with advanced chronic heart failure.N Engl J Med. 2001; 344: 1659-1667Crossref PubMed Scopus (716) Google Scholar, 22Cohn J.N. Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure.N Engl J Med. 2001; 345: 1667-1675Crossref PubMed Scopus (1927) Google Scholar, 23Abraham W.T. Fisher W.G. Smith A.L. Delurgio D.B. Leon A.R. Loh E. et al.Cardiac resynchronization in chronic heart failure.N Engl J Med. 2002; 346: 1845-1853Crossref PubMed Scopus (2896) Google Scholar This figure probably underestimates the true prevalence of CAD among unselected HF patients, because the presence of CAD was not explored systematically in many trials. Prognostic Significance of Underlying CAD Etiology in Patients With HF Several studies have shown that CAD independently increases mortality rates in patients with HF.24Follath F. Cleland J.G. Klein W. Murphy R. Etiology and response to drug treatment in heart failure.J Am Coll Cardiol. 1998; 32: 1167-1172Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar, 25Bart B.A. Shaw L.K. McCants Jr., C.B. Fortin D.F. Lee K.L. Califf R.M. et al.Clinical determinants of mortality in patients with angiographically diagnosed ischemic or nonischemic cardiomyopathy.J Am Coll Cardiol. 1997; 30: 1002-1008Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar, 26Felker G.M. Thompson R.E. Hare J.M. Hruban R.H. Clemetson D.E. Howard D.L. et al.Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy.N Engl J Med. 2000; 342: 1077-1084Crossref PubMed Scopus (517) Google Scholar One assessing angiographic data in patients with HF demonstrated that the extent of CAD in patients with HF from left ventricular (LV) systolic dysfunction provides important prognostic information about their HF.27Felker G.M. Shaw L.K. O'Connor C.M. A standardized definition of ischemic cardiomyopathy for use in clinical research.J Am Coll Cardiol. 2002; 39: 210-218Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar Recent data also suggest that the mechanism of sudden death may differ between ischemic and nonischemic HF patients, with acute coronary events representing the major cause of sudden death in patients with CAD.28Uretsky B.F. Thygesen K. Armstrong P.W. Cleland J.G. Horowitz J.D. Massie B.M. et al.Acute coronary findings at autopsy in heart failure patients with sudden death: results from the assessment of treatment with lisinopril and survival (ATLAS) trial.Circulation. 2000; 102: 611-616Crossref PubMed Google Scholar These findings further emphasize the importance of accurate differentiation between ischemic and nonischemic causes of HF. Managing HF in patients with CAD or a history of CAD is significantly different than managing HF from primary cardiomyopathy. Antiplatelet agents, smoking cessation, and lipid-lowering therapy are particularly important interventions in patients with HF due to CAD.29Smith Jr., S.C. Blair S.N. Bonow R.O. Brass L.M. Cerqueira M.D. Dracup K. et al.AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology.Circulation. 2001; 104: 1577-1579Crossref PubMed Google Scholar Trials of milrinone,30Felker G.M. Benza R.L. Chandler A.B. Leimberger J.D. Cuffe M.S. Califf R.M. et al.Heart failure etiology and response to milrinone in decompensated heart failure: results from the OPTIME-CHF study.J Am Coll Cardiol. 2003; 41: 997-1003Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar amiodarone,12Singh S.N. Fletcher R.D. Fisher S.G. Singh B.N. Lewis H.D. Deedwania P.C. et al.Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure.N Engl J Med. 1995; 333: 77-82Crossref PubMed Scopus (825) Google Scholar amlodipine,14Packer M. O'Connor C.M. Ghali J.K. Pressler M.L. Carson P.E. Belkin R.N. et al.Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group.N Engl J Med. 1996; 335: 1107-1114Crossref PubMed Scopus (853) Google Scholar and digoxin31Gheorghiade M. Young J.B. Uretsky B.F. Packer M. The effects of digoxin withdrawal in patients with stable heart failure due to coronary artery disease compared to primary cardiomyopathy: Insights from the PROVED and RADIANCE studies.Circulation. 1995; 92: 1-142Crossref PubMed Google Scholar suggest that patients with HF in the setting of CAD may have a less favorable outcome than patients with HF from primary cardiomyopathy. Revascularization in highly selected patients with low LV ejection fraction (LVEF) and significant CAD, particularly angina, may be associated with improved survival and may be considered in addition to risk modification.32O'Connor C.M. Velazquez E.J. Gardner L.H. Smith P.K. Newman M.F. Landolfo K.P. et al.Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank).Am J Cardiol. 2002; 90: 101-107Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 33Alderman E.L. Fisher L.D. Litwin P. Kaiser G.C. Myers W.O. Maynard C. et al.Results of coronary artery surgery in patients with poor left ventricular function (CASS).Circulation. 1983; 68: 785-795Crossref PubMed Google Scholar, 34Baker D.W. Jones R. Hodges J. Massie B.M. Konstam M.A. Rose E.A. Management of heart failure. III. The role of revascularization in the treatment of patients with moderate or severe left ventricular systolic dysfunction.JAMA. 1994; 272: 1528-1534Crossref PubMed Google Scholar, 35Pigott J.D. Kouchoukos N.T. Oberman A. Cutter G.R. Late results of surgical and medical therapy for patients with coronary artery disease and depressed left ventricular function.J Am Coll Cardiol. 1985; 5: 1036-1045Abstract Full Text PDF PubMed Google Scholar, 36Bounous E.P. Mark D.B. Pollock B.G. Hlatky M.A. Harrell Jr., F.E. Lee K.L. et al.Surgical survival benefits for coronary disease patients with left ventricular dysfunction.Circulation. 1988; 78: I151-I157PubMed Google Scholar, 37Muhlbaier L.H. Pryor D.B. Rankin J.S. Smith L.R. Mark D.B. Jones R.H. et al.Observational comparison of event-free survival with medical and surgical therapy in patients with coronary artery disease. 20 years of follow-up.Circulation. 1992; 86: II198-II204PubMed Google Scholar, 38Elefteriades J.A. Tolis Jr., G. Levi E. Mills L.K. Zaret B.L. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state.J Am Coll Cardiol. 1993; 22: 1411-1417Abstract Full Text PDF PubMed Google Scholar However, no prospective randomized trials have been completed in patients with clinical HF. Pathophysiology of HF in the Setting of CAD. HF in the setting of CAD is a heterogeneous condition with several factors contributing to LV systolic dysfunction and HF symptoms. After an MI, there is loss of functioning myocytes, development of myocardial fibrosis, and subsequent LV remodeling, resulting in chamber dilatation and neurohormonal activation—all leading to progressive dysfunction of the remaining viable myocardium.39Sutton M.G. Sharpe N. Left ventricular remodeling after myocardial infarction: pathophysiology and therapy.Circulation. 2000; 101: 2981-2988Crossref PubMed Google Scholar This well-recognized process may be ameliorated after an acute MI by myocardial revascularization32O'Connor C.M. Velazquez E.J. Gardner L.H. Smith P.K. Newman M.F. Landolfo K.P. et al.Comparison of coronary artery bypass grafting versus medical therapy on long-term outcome in patients with ischemic cardiomyopathy (a 25-year experience from the Duke Cardiovascular Disease Databank).Am J Cardiol. 2002; 90: 101-107Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 40Challapalli S. Bonow R.O. Gheorghiade M. Medical management of heart failure secondary to coronary artery disease.Coron Artery Dis. 1998; 9: 659-674Crossref PubMed Google Scholar, 41Ragosta M. Beller G.A. The assessment of patients with congestive heart failure as a manifestation of coronary artery disease.Coron Artery Dis. 1998; 9: 645-651Crossref PubMed Google Scholar and by medical therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor antagonists (ARBs),42Adams Jr., K.F. Angiotensin-converting enzyme inhibition and vascular remodeling in coronary artery disease.Coron Artery Dis. 1998; 9: 675-684Crossref PubMed Google Scholar, 43Pfeffer M.A. McMurray J.J. Velazquez E.J. Rouleau J.L. Kober L. Maggioni A.P. et al.Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both.N Engl J Med. 2003; 349: 1893-1906Crossref PubMed Scopus (1478) Google Scholar β-blockers,44Dargie H.J. Effect of carvedilol on outcome after myocardial infarction in patients with left-ventricular dysfunction: the CAPRICORN randomised trial.Lancet. 2001; 357: 1385-1390Abstract Full Text Full Text PDF PubMed Scopus (933) Google Scholar and aldosterone antagonists.45Pitt B. Remme W. Zannad F. Neaton J. Martinez F. Roniker B. et al.Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.N Engl J Med. 2003; 348: 1309-1321Crossref PubMed Scopus (2517) Google Scholar The majority of patients surviving a MI have significant atherosclerotic disease in coronary arteries other than the infarct-related vessel.46Goldstein J.A. Demetriou D. Grines C.L. Pica M. Shoukfeh M. O'Neill W.W. Multiple complex coronary plaques in patients with acute myocardial infarction.N Engl J Med. 2000; 343: 915-922Crossref PubMed Scopus (556) Google Scholar Under basal conditions, episodes of reversible myocardial ischemia caused by a severe coronary artery stenosis superimposed on the left ventricle with depressed systolic function may produce transient worsening of LV function. In many patients, these HF symptoms, such as dyspnea or fatigue induced by exercise, may represent an anginal equivalent that may occur in the absence of chest pain. Episodes of transient myocardial ischemia may cause prolonged systolic dysfunction that persists after the ischemic insult itself has resolved. This process, called stunning, is similar to the more severe and protracted myocardial stunning that results from coronary occlusion and reperfusion.47Bolli R. Myocardial ‘stunning’ in man.Circulation. 1992; 86: 1671-1691Crossref PubMed Google Scholar Another important mechanism for systolic dysfunction with additive effects on LV performance is myocardial hibernation,48Wijns W. Vatner S.F. Camici P.G. Hibernating myocardium.N Engl J Med. 1998; 339: 173-181Crossref PubMed Scopus (328) Google Scholar a process in which myocardial contraction is downregulated in response to chronic reduction in myocardial blood supply.49Lim H. Fallavollita J.A. Hard R. Kerr C.W. Canty Jr., J.M. Profound apoptosis-mediated regional myocyte loss and compensatory hypertrophy in pigs with hibernating myocardium.Circulation. 1999; 100: 2380-2386Crossref PubMed Google Scholar, 50Shan K. Bick R.J. Poindexter B.J. Nagueh S.F. Shimoni S. Verani M.S. et al.Altered adrenergic receptor density in myocardial hibernation in humans: A possible mechanism of depressed myocardial function.Circulation. 2000; 102: 2599-2606Crossref PubMed Google Scholar More than 50% of patients with HF and CAD have evidence of viable but dysfunctional (hibernating) myocardium.51Auerbach M.A. Schoder H. Hoh C. Gambhir S.S. Yaghoubi S. Sayre J.W. et al.Prevalence of myocardial viability as detected by positron emission tomography in patients with ischemic cardiomyopathy.Circulation. 1999; 99: 2921-2926Crossref PubMed Google Scholar, 52Cleland J.G. Pennell D.J. Ray S.G. Coats A.J. Macfarlane P.W. Murray G.D. et al.Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial.Lancet. 2003; 362: 14-21Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar Hibernation may develop as an adaptive response to sustained reduction of myocardial blood flow. Thus the level of tissue perfusion is sufficient to maintain cellular viability but insufficient for normal contractile function.53Kloner R.A. Przyklenk K. Patel B. Altered myocardial states. The stunned and hibernating myocardium.Am J Med. 1989; 86: 14-22Abstract Full Text PDF PubMed Google Scholar Recent evidence supports the long-held concept that hibernation represents a precarious balance between perfusion and tissue viability that cannot be maintained indefinitely, and that myocardial necrosis will occur eventually if blood flow is not increased.48Wijns W. Vatner S.F. Camici P.G. Hibernating myocardium.N Engl J Med. 1998; 339: 173-181Crossref PubMed Scopus (328) Google Scholar In addition to ischemia, hibernating myocardium should be considered in all patients with CAD and chronic LV systolic dysfunction of any degree.54Challapalli S. Hendel R.C. Bonow R.O. Clinical profile of patients with congestive heart failure due to coronary artery disease: stunned/hibernating myocardium, ischemia, scar.Coron Artery Dis. 1998; 9: 629-644Crossref PubMed Google Scholar Hibernating myocardium can be identified using low-dose dobutamine stress echocardiography to assess contractile reserve, single photon emission tomography with thallium-201 or technetium-99m perfusion tracers to assess membrane integrity, and positron emission tomography to assess residual metabolic activity.55Allman K.C. Shaw L.J. Hachamovitch R. Udelson J.E. Myocardial viability testing and impact of revascularization on prognosis in patients with coronary artery disease and left ventricular dysfunction: a meta-analysis.J Am Coll Cardiol. 2002; 39: 1151-1158Abstract Full Text Full Text PDF PubMed Scopus (673) Google Scholar, 56Bonow R.O. Myocardial viability and prognosis in patients with ischemic left ventricular dysfunction.J Am Coll Cardiol. 2002; 39: 1159-1162Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar More recently, magnetic resonance imaging (MRI) has been used to identify potentially viable but dysfunctional myocardium.57Kim R.J. Wu E. Rafael A. Chen E.L. Parker M.A. Simonetti O. et al.The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction.N Engl J Med. 2000; 343: 1445-1453Crossref PubMed Scopus (1645) Google Scholar Identification of hibernating myocardium is important, as the restoration of blood flow by revascularization or with agents that improve endothelial function and blood flow (eg, statins) may improve contractility in hibernating areas.58McFarlane S.I. Muniyappa R. Francisco R. Sowers J.R. Clinical review 145: Pleiotropic effects of statins: lipid reduction and beyond.J Clin Endocrinol Metab. 2002; 87: 1451-1458Crossref PubMed Scopus (205) Google Scholar, 59Gould K.L. New concepts and paradigms in cardiovascular medicine: the noninvasive management of coronary artery disease.Am J Med. 1998; 104: 2S-17SAbstract Full Text Full Text PDF PubMed Google Scholar, 60Schulz R. Rose J. Martin C. Brodde O.E. Heusch G. Development of short-term myocardial hibernation. Its limitation by the severity of ischemia and inotropic stimulation.Circulation. 1993; 88: 684-695Crossref PubMed Google Scholar, 61Chen C. Li L. Chen L.L. Prada J.V. Chen M.H. Fallon J.T. et al.Incremental doses of dobutamine induce a biphasic response in dysfunctional left ventricular regions subtending coronary stenoses.Circulation. 1995; : 92756-92766Google Scholar Evaluation for CAD Recommendations13.1Assessment for risk factors for CAD is recommended in all patients with chronic HF regardless of EF. (Strength of Evidence = A)The diagnostic approach for CAD should be individualized based on patient preference and comorbidities, eligibility, and willingness to perform revascularization. (Strength of Evidence = C)13.2It is recommended that patients with HF and angina undergo cardiac catheterization with coronary angiography to assess for potential revascularization. (Strength of Evidence = B)13.3It is recommended that patients with HF, no angina, and known CAD should undergo noninvasive stress imaging and/or coronary angiography to assess severity of coronary disease and the presence of ischemia. (Strength of Evidence = C)13.4It is recommended that patients with HF, no angina, and unknown CAD status who are at high risk for CAD should undergo noninvasive stress imaging and/or coronary angiography to assess severity of coronary disease and the presence of ischemia. (Strength of Evidence = C)13.5In patients with HF, no angina, and unknown CAD status who are at low risk for CAD noninvasive evaluation should be considered and coronary angiography may be considered. (Strength of Evidence = C)13.6Any of the following imaging tests may be used to identify inducible ischemia or viable but noncontractile myocardium:•Exercise or pharmacologic stress myocardial perfusion imaging•Exercise or pharmacologic stress echocardiography•Cardiac MRI•Positron emission tomography scanning(Strength of Evidence = B) Background Evaluation for CAD in Patents with HF. A thorough Medline search identified only 14 studies62Sciagra R. Pellegri M. Pupi A. Bolognese L. Bisi G. Carnovale V. et al.Prognostic implications of Tc-99m sestamibi viability imaging and subsequent therapeutic strategy in patients with chronic coronary artery disease and left ventricular dysfunction.J Am Coll Cardiol. 2000; 36: 739-745Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar, 63Petretta M. Cuocolo A. Nicolai E. Acampa W. Salvatore M. Bonaduce D. 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Salvatore M. et al.Successful coronary revascularization improves prognosis in patients with previous myocardial infarction and evidence of viable myocardium at thallium-201 imaging.Eur J Nucl Med. 1998; 25: 60-68Crossref PubMed Scopus (48) Google Scholar, 67Pagano D. Lewis M.E. Townend J.N. Davies P. Camici P.G. Bonser R.S. Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival.Heart. 1999; 82: 684-688PubMed Google Scholar, 68Pagley P.R. Beller G.A. Watson D.D. Gimple L.W. Ragosta M. Improved outcome after coronary bypass surgery in patients with ischemic cardiomyopathy and residual myocardial viability.Circulation. 1997; 96: 793-800Crossref PubMed Google Scholar, 69Chan R.K. Raman J. Lee K.J. Rosalion A. Hicks R.J. Pornvilawan S. et al.Prediction of outcome after revascularization in patients with poor left ventricular function.Ann Thorac Surg. 1996; 61: 1428-1434Abstract Full Text PDF PubMed Scopus (32) Google Scholar, 70Zhang X. 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Relative efficacy of medical therapy and revascularization.Circulation. 1994; 90: 2687-2694Crossref PubMed Google Scholar that evaluated the impact of nuclear viability imaging on intermediate to long-term survival in patients with CAD and LV systolic dysfunction. However, none of these studies met the criteria published by the Evidence-Based Medicine Group on therapeutic interventions and prognosis.76Guyatt G.H. Sackett D.L. Cook D.J. Users' guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group.JAMA. 1993; 270: 2598-2601Crossref PubMed Google Scholar, 77Laupacis A. Wells G. Richardson W.S. Tugwell P. Users' guides to the medical literature. V. How to use an article about prognosis. Evidence-Based Medicine Working Group.JAMA. 1994; 272: 234-237Crossref PubMed Google Scholar In these studies treatment allocation to revascularization or medical therapy was often made by physicians who requested and, in some cases, interpreted the viability tests. Viability was never blindly evaluated without impacting subsequent treatment allocation. A randomized clinical trial is necessary to properly evaluate the utility of viability imaging to determine treatment allocation between revascularization and medical therapy and subsequent prognosis. Recommendation13.7It is recommended that the following risk factors be managed according to the indicated guidelines:•Lipids (see National Cholesterol Education Program Adult Treatment Panel III) ∗http://www.nhlbi.nih.gov/guidelines/cholesterol/78Chobanian A.V. Bakris G.L. Black H.R. Cushman W.C. Green L.A. Izzo Jr., J.L. et al.Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003; 42: 1206-1252Crossref PubMed Scopus (5848) Google Scholar∗http://www.nhlbi.nih.gov/guidelines/cholesterol/78Chobanian A.V. Bakris G.L. Black H.R. Cushman W.C. Green L.A. Izzo Jr., J.L. et al.Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.Hypertension. 2003; 42: 1206-1252Crossref PubMed Scopus (5848) Google Scholar•Smoking (see Section 3)•Physical activity (see Section 6)•Weight (see Section 3)•Blood pressure (see Section 14 and JNC VII Guidelines) +http://www.nhlbi.nih.gov/guidelines/hypertension/79Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel o