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Navigating the Crossroads of Coronary Artery Disease and Heart Failure

2006; Lippincott Williams & Wilkins; Volume: 114; Issue: 11 Linguagem: Inglês

10.1161/circulationaha.106.623199

1524-4539

Mihai Gheorghiade, George Sopko, Leonardo De Luca, Eric J. Velazquez, John D. Parker, Philip F. Binkley, Zygmunt Sadowski, Krzysztof S. Gołba, David L. Prior, Jean L. Rouleau, Robert O. Bonow,

Cardiac Imaging and Diagnostics

HomeCirculationVol. 114, No. 11Navigating the Crossroads of Coronary Artery Disease and Heart Failure Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBNavigating the Crossroads of Coronary Artery Disease and Heart Failure Mihai Gheorghiade, MD, George Sopko, MD, Leonardo De Luca, MD, Eric J. Velazquez, MD, John D. Parker, MD, Philip F. Binkley, MD, Zygmunt Sadowski, MD, Krzysztof S. Golba, MD, David L. Prior, MBBS, Jean L. Rouleau, MD and Robert O. Bonow, MD Mihai GheorghiadeMihai Gheorghiade From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , George SopkoGeorge Sopko From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Leonardo De LucaLeonardo De Luca From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Eric J. VelazquezEric J. Velazquez From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , John D. ParkerJohn D. Parker From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Philip F. BinkleyPhilip F. Binkley From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Zygmunt SadowskiZygmunt Sadowski From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Krzysztof S. GolbaKrzysztof S. Golba From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , David L. PriorDavid L. Prior From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). , Jean L. RouleauJean L. Rouleau From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). and Robert O. BonowRobert O. Bonow From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., R.O.B.); National Heart, Lung, and Blood Institute, Bethesda, Md (G.S.); European Hospital, Rome, Italy (L.D.L.); Duke University Medical Center, Durham, NC (E.J.V.); Mount Sinai Hospital, Toronto, Ontario, Canada (J.D.P.); Ohio State University, Columbus (P.F.B.); National Institute of Cardiology, Warsaw, Poland (Z.S.); Medical University of Silesia, Katowice, Poland (K.S.G.); St Vincent's Hospital, Melbourne, Victoria, Australia (D.L.P.); and Montreal Heart Institute, Montreal, Quebec, Canada (J.L.R.). Originally published12 Sep 2006https://doi.org/10.1161/CIRCULATIONAHA.106.623199Circulation. 2006;114:1202–1213Chronic heart failure (HF) affects 5 million patients in the United States and is responsible for &1 million hospitalizations and 300 000 deaths annually.1 The total annual costs associated with this disorder have been estimated to exceed $40 billion.1,2 Chronic HF is the only category of cardiovascular diseases for which the prevalence, incidence, hospitalization rate, total burden of mortality, and costs have increased in the past 25 years.1,2 Fueling this epidemic is the increasing number of elderly patients developing impaired left ventricular (LV) function as a manifestation of chronic coronary artery disease (CAD).1,2 With the aging of the population and decline in mortality of other forms of cardiovascular diseases, it is likely that the incidence of HF and its impact on public health will continue to increase.1–3CAD and HF: Epidemiology and PrognosisIn the past 3 decades, considerable attention has focused on LV dysfunction, loading conditions, neuroendocrine activation, and ventricular remodeling as the principal pathophysiological mechanisms underlying HF progression.4 There has been a fundamental shift, however, in the origin of HF that often is underemphasized.3–5 The Framingham Heart Study suggests that the most common cause of HF is no longer hypertension or valvular heart disease, as it was in previous decades, but rather CAD.4This shift may be related to improved survival of patients after acute myocardial infarction (MI). Over the past 40 years in the United States, the odds of previous MI as a cause for HF increased by 26% per decade in men and 48% per decade in women. In contrast, there has been a 13% decrease per decade for hypertension as a cause of HF in men and a 25% decrease in women, as well as a decrease in valvular disease by 24% per decade in men and 17% in women.In the 24 multicenter HF treatment trials reported in the New England Journal of Medicine over the past 20 years involving >43 000 patients, CAD was the underlying cause of HF in nearly 65% of patients (Table).6–30 This percentage is probably an underestimate of the true prevalence of CAD among unselected HF patients, when one considers that origin was not explored in a systemic manner in many trials. Another reason for probable underestimation is that most of these trials excluded patients with a recent MI, angina, or objective evidence of active ischemia. However, as recently suggested in a population-based incidence cohort study from Olmsted County, although HF remains frequent after MI, its incidence is declining over time.31Prevalence of CAD in Multicenter HF Trials Published in the New England Journal of Medicine From 1986 to 2005TrialYearAll PatientsCAD PatientsV-HeFT indicates Vasodilator–Heart Failure Trial; Consensus, Cooperative North Scandinavian Enalapril Survival Study; Milrinone, Milrinone Trial; PROMISE, Prospective Randomized Milrinone Survival Evaluation; RADIANCE, Randomized Assessment of the effect of Digoxin on Inhibitors of the Angiotensin-Converting Enzyme; Vesnarinone, Vesnarinone Trial; CHF-STAT, Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy; Carvedilol, Carvedilol Trial; DIG, Digitalis Investigation Group trial; VEST, Vesnarinone Trial; RALES, Randomized Aldactone (spironolactone) Evaluation Study for Congestive Heart Failure; DIAMOND, Distensibility Improvement With ALT-711 Remodeling in Diastolic Heart Failure; COPERNICUS, Carvedilol (Coreg) Prospective Randomized Cumulative Survival; BEST, Beta-Blocker Evaluation of Survival Trial; Val-HeFT, Valsartan Heart Failure Trial; MIRACLE, Multicenter InSync Randomized Clinical Evaluation (North America); COMPANION, Comparison of Medical Therapy, Pacing and Defibrillation in Chronic Heart Failure; A-HeFT, African-American Heart Failure Trial; and CARE-HF, Cardiac Resynchronization–Heart Failure study.V-HeFT I1986642282CONSENSUS1987253146Milrinone1989230115PROMISE19911088590SOLVD-T199125691828V-HeFT II1991804427SOLVD-P199242283518RADIANCE1993178107Vesnarinone1993477249CHF-STAT1995674481Carvedilol19961094521PRAISE19961153732DIG199768004793VEST199838332230RALES19991663907DIAMOND199915181017COPERNICUS200122891534BEST200127081587Val-HeFT200150102866MIRACLE2002453244COMPANION20041520842A-HeFT20041050242SCD-HeFT200525211310CARE-HF2005813309Total19 y43 56826 877 (62%)In HF patients, the presence of CAD has been shown to be independently associated with a worsened long-term outcome in numerous studies.32 In the Studies of Left Ventricular Dysfunction Treatment (SOLVD-T) trial, patients who developed MI had an &2-fold-higher rate of hospitalization for chronic HF and a 4-fold-higher mortality rate compared with patients who did not develop MI.9 Similarly, in the Survival and Ventricular Enlargement (SAVE) trial, evidence of a previous MI before the enrollment identified patients with a significantly greater risk of cardiovascular death and/or LV enlargement.33 Recent data from the Global Registry of Acute Coronary Events (GRACE) study demonstrated that patients with CAD who present with HF on admission are at increased risk of both in-hospital and long-term mortality.34 The Duke database35 showed that CAD significantly and independently increases mortality rates in HF patients. During a mean follow-up period of 4.4 years, patients with CAD had a much worse prognosis than patients with idiopathic cardiomyopathy after adjustment for baseline variables.36 In a more recent study, Felker et al37 assessed angiographic data in 1921 patients with HF and demonstrated that the extent of CAD provides additional important prognostic information in patients with HF caused by LV systolic dysfunction. Retrospective analyses of the SOLVD Prevention (SOLVD-P) and SOLVD-T trials indicated that the adverse prognosis of ischemic cardiomyopathy could be limited to HF patients with diabetes mellitus.38,39 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.40 Among patients with HF or evidence of LV dysfunction after acute MI enrolled in the Optimal Trial in Myocardial Infarction With the Angiotensin II Antagonist Losartan (OPTIMAAL), recurrent MI found at autopsy was common and often had not been clinically detected.41 These findings emphasize the importance of accurate differentiation between ischemic and nonischemic causes of HF and the potential role of revascularization in patients with ischemic cardiomyopathy.Impact of CAD on the Pathophysiology of HFReduced Systolic FunctionTraditionally, the progression of HF has been attributed to LV remodeling and thought to be unrelated to the causes of LV dysfunction (eg, hypertension, diabetes, CAD) (Figure 1A).39,41,42 Accordingly, therapies have been directed at neurohormonal modulation and the prevention of LV remodeling. However, the available data suggest that the factors (eg, hypertension, diabetes, CAD) that initiate LV dysfunction also contribute to its progression (Figure 1B). Download figureDownload PowerPointFigure 1. The progression of HF has been attributed mostly to LV remodeling and thought to be unrelated to the causes of LV dysfunction (A). Currently available data suggest that the factors that initiate LV dysfunction also contribute to its progression (B).In particular, the presence and extent of CAD may accelerate the progression of HF, explaining the higher mortality among ischemic compared with nonischemic HF patients.36,37 After acute MI, loss of functioning myocytes occurs, with ensuing myocardial fibrosis and LV dilatation. The resulting neurohormonal activation and LV remodeling lead to progressive deterioration of the remaining viable myocardium.43 This well-recognized but incompletely understood process can be ameliorated by the use of angiotensin-converting enzyme (ACE) inhibitors,44 β-blockers,45 and aldosterone antagonists46 in the post-MI period. Although revascularization with thrombolytic agents or percutaneous coronary intervention has been shown to significantly decrease mortality in post-MI patients, it is important to note that LV remodeling may occur despite sustained patency of the infarct-related artery.47Ischemia can produce a rapid and massive increase in the concentration of endogenous catecholamines such as norepinephrine, epinephrine, endothelin, and dopamine in the myocardial interstitial fluid with a deleterious effect on cardiac myocytes,48 culminating in myocardial apoptosis, fibrosis, and susceptibility to ventricular arrhythmias. Thus, ischemia may contribute to the progression of LV systolic dysfunction without an obvious clinical ischemic event.49Chronic ischemia may result in hibernation/stunning with further decline in LV function.50 In a meta-analysis of 24 studies, patients with evidence of viability who underwent revascularization had an 80% reduction in mortality compared with those who were treated medically.51 In contrast, patients without viability had a similar mortality with the 2 therapeutic strategies.51 Unfortunately, most studies examining treatment of hibernating myocardium have been biased by variability in the methods used to identify and define hibernation and by the influence that the results of these investigations have had on patient treatment strategies. So far, no prospective trials have evaluated the role of noninvasive testing in determining the most suitable candidates for revascularization in patients with severe LV systolic dysfunction.52Another complication of CAD is ischemic mitral regurgitation (MR) caused by changes in ventricular structure and function.53 Higher incidence and greater severity of ischemic MR are associated with the chronic phase of inferior rather than anterior MI because of more severe geometric changes in the mitral valve apparatus.54 Notably, even mild MR is an independent predictor of long-term mortality after MI53,55 (Figure 2). All these processes can be "punctuated" at any time by a sudden coronary occlusion leading to sudden death. Download figureDownload PowerPointFigure 2. Role of CAD in the pathophysiology of HF with reduced systolic function.HF With Preserved Systolic FunctionDuring the past 20 years, the percentage of patients with HF and preserved systolic function has been increasing and may account for 30% to 40% of patients admitted with a diagnosis of HF.56 This is an intriguing, challenging group of patients in whom, until now, diagnostic and therapeutic measures have been disappointing. When systolic function is preserved, it is assumed that most of these patients have HF signs and symptoms on the basis of abnormal LV diastolic function.57A variety of factors contribute to abnormalities in LV diastolic function and lead to elevated filling pressures, impaired forward output, or both, despite normal systolic function.58 Myocardial ischemia, together with gender, age, and hypertension, is one of the leading factors. Pulmonary congestion can be caused by transient "reversible" episodes of ischemia, which impair LV relaxation and elevate LV filling pressures.59 Vasan et al56 showed that CAD accounts for one half to two thirds of patients with HF and normal systolic function; the prevalence of CAD in patients with HF and preserved systolic function varies from 14% to 100%.There has been much controversy about the prognosis of HF patients with preserved systolic function. The prognosis for such patients has been reported to be better than for patients with chronic systolic dysfunction in some series,60 whereas others reported a similar overall mortality rate for hospitalized patients with depressed systolic function compared with those with normal systolic function.56 Tsutsui et al61 showed that the prognosis of CAD patients with HF and preserved systolic function was similar to that of patients with systolic dysfunction. The disparity in prognosis among clinical studies of HF and normal systolic function may correlate to the differences in prevalence and severity of CAD.62Ischemic Events in Patients With HFReinfarctionMost patients surviving an acute MI also have CAD present in other than the infarct-related artery63 and are therefore at high risk of reinfarction. In clinical trials, the rate of infarction or reinfarction is relatively low using clinical criteria, with a fatal MI rate of 3%.64 However, 56% of patients with HF and CAD who die suddenly have autopsy evidence of an acute ischemic event (eg, coronary clot, recent infarct); this percentage does not take into account the number of patients with plaque rupture.65 It is possible that even a small MI in patients with severe LV dysfunction may present as sudden death rather than a nonfatal MI. Death may therefore be attributed to a lethal arrhythmia rather than MI, and this may account for the apparently low observed rate of MI in patients with HF and CAD.Sudden DeathLV dysfunction is a major independent predictor of total cardiovascular mortality and sudden cardiac death in patients with both CAD and primary cardiomyopathy origins. In several clinical HF trials, sudden death ranged between 20% and 60%, depending on the severity of HF.66 In the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF), 64% of patients with New York Heart Association class II HF had sudden and unexpected death compared with 59% of patients with class III and 33% of patients with class IV HF.67 Several factors have been implicated in the high rate of sudden death in patients with HF with or without CAD. These include subendocardial ischemia, ventricular hypertrophy, stretching of myocytes, high sympathetic tone, abnormal baroreceptor responsiveness that lowers the threshold for a malignant arrhythmia, potassium and magnesium depletion, and coronary artery emboli from atrial or LV thrombi.66 It is likely, however, that CAD contributes directly to sudden death.66 Some patients with CAD and HF have dilated hearts, with large regions of myocardial scarring.68 In addition, CAD, with its major consequences (ie, plaque rupture, thrombosis, and infarct), constitutes the most common structural basis of sudden cardiac death.69Holmes et al70 compared the impact of medical therapy alone with that of coronary artery bypass grafting (CABG) on the incidence of sudden cardiac death among 13 476 patients enrolled in the Coronary Artery Surgery Study (CASS) registry who had significant CAD, operable vessels, and no significant valvular disease. Notably, in a high-risk patient subset with 3-vessel disease and history of HF, 91% of surgically revascularized patients had not suffered sudden death compared with 69% of medically treated patients.70 Uretsky et al65 reported the relative importance of an acute coronary event as a trigger for sudden death in patients with HF in the Assessment of Treatment With Lisinopril and Survival (ATLAS) trial, including 3164 patients with moderate to severe HF caused by systolic dysfunction. There were 1383 deaths (43.7%) during the follow-up period of 3 to 5 years. An autopsy was performed in only 188 patients, and the postmortem data were available in only 171 patients (12.4% of the total). Patients who died were older and had both more symptoms and a higher prevalence of CAD than the surviving patients. Acute coronary findings were observed in 54% of the patients with significant CAD who died suddenly.65 The ATLAS study was the first to demonstrate that recent coronary events are frequently unrecognized in patients with moderate to advanced symptoms of HF who die suddenly, especially in patients with CAD. Other studies have documented a high percent of plaque rupture or coronary thrombosis in CAD patients without HF who died suddenly.69A recent analysis of the Valsartan in Acute Myocardial Infarction Trial (VALIANT) assessed the incidence and timing of sudden death in post-MI patients with LV systolic dysfunction. Of 14 609 patients, 1067 (7%) had an event a median of 180 days after MI: 903 died suddenly and 164 were resuscitated after cardiac arrest.40 The event risk was highest (1.4%) in the first 30 days after MI and decreased to 0.14% per month after 2 years. The rate of sudden death according to LV ejection fraction (LVEF) showed that the increased early incidence was most apparent among patients with low LVEF.40CAD and HF: ManagementThe most important evaluation for risk of adverse events, in addition to extent and severity of CAD and LV function, is the assessment of the presence and severity of MR, loading conditions, and myocardial ischemia, stunning, or hibernation. All of these parameters can be evaluated with a combination of invasive and noninvasive testing such as dobutamine echocardiography, nuclear myocardial perfusion imaging, positron-emission tomography, cardiac magnetic resonance, and cardiac catheterization.Patients with LV dysfunction and CAD may be classified into 2 distinct groups for whom the workup and management may be very different: (1) patients presenting with chronic HF who have CAD and/or a remote history of MI and (2) patients presenting with an acute MI that results in LV dysfunction with or without signs of HF.The management of these patients should be aimed at preventing progression of CAD, LV remodeling, sudden death, and reinfarction and should be tailored for the individual patient. There are 3 important management considerations in patients with CAD and HF: pharmacological treatment, electrophysiological devices, and revascularization strategies. Although there are a multitude of options for the management of these patients, a comprehensive strategy that includes surgery often is not used. Better care of the post-MI CAD patient with LV dysfunction and HF requires a management strategy that draws on all evidence-based therapies.Pharmacological TreatmentIn recent years, large-scale clinical trials have documented the benefits of pharmacological therapies in the post-MI period aimed at limiting LV remodeling, recurrent ischemia, and progressive CAD.ACE InhibitorsTreatment with ACE inhibitors is beneficial for all patients with moderate to severe HF and impaired LV systolic function but may have additional benefits on ischemic events in those patients with underlying CAD.71,72Several studies have shown that ACE inhibition reduces the incidence of HF and mortality after an acute MI, possibly by preventing LV remodeling, reinfarction, and sudden death.73 In the SAVE trial, which enrolled patients with LVEF 60% of HF patients had CAD. Similar beneficial effects of β-blockers were noted in patients with ischemic or nonischemic origin.81,82 In patients with stable CAD, treatment with β-blockers reduces the number and duration of ischemic episodes, mortality, or hospitalization.83 In a meta-analysis of multiple trials of β-blockers and HF, the impact on total mortality was as much on sudden death as on MI.84The Beta-Blocker Heart Attack Trial (BHAT) excluded patients with HF at randomization.85 However, a subset analysis revealed that propranolol reduced total mortality to a simila