Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Abstract

OverviewLeft ventricular (LV) remodeling and reduced ejection fraction (EF) should be distinguished from the syndrome of clinical heart failure (HF). When LVEF is reduced (<40%), but there are no signs and symptoms of HF, the condition frequently is referred to as asymptomatic LV dysfunction (ALVD). It is important to distinguish between ALVD and patients categorized as New York Heart Association (NYHA) Class I HF. Although patients with NYHA Class I HF do not currently have HF symptoms, they may have ALVD currently, or they may have clinical systolic HF with symptoms in the past. In contrast, patients with ALVD have no past history of HF symptoms. It is now well recognized that there may be a latency period when the LVEF is reduced before the development of symptomatic HF. Although most attention in the HF literature has centered on patients with symptoms, evidence now indicates that ALVD is more common than previously assumed. The recent realization that therapies aimed at symptomatic HF may improve outcomes in patients with ALVD has increased the importance of recognizing and treating patients with this condition.Prevalence. The prevalence of systolic ALVD ranges from 6% to 16% in population-based studies.1Lee E.T. Cowan L.D. Welty T.K. Sievers M. Howard W.J. Oopik A. et al.All-cause mortality and cardiovascular disease mortality in three American Indian populations, aged 45–74 years, 1984–1988. The Strong Heart Study.Am J Epidemiol. 1998; 147: 995-1008Crossref PubMed Scopus (140) Google Scholar, 2McDonagh T.A. Morrison C.E. Lawrence A. Ford I. Tunstall-Pedoe H. McMurray J.J. et al.Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population.Lancet. 1997; 350: 829-833Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar, 3Mosterd A. Hoes A.W. de Bruyne M.C. Deckers J.W. Linker D.T. Hofman A. et al.Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.Eur Heart J. 1999; 20: 447-455Crossref PubMed Scopus (568) Google Scholar, 4Redfield M.M. Jacobsen S.J. Burnett Jr., J.C. Mahoney D.W. Bailey K.R. Rodeheffer R.J. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.JAMA. 2003; 289: 194-202Crossref PubMed Scopus (2456) Google Scholar The prevalence of ALVD was 16.7% among a cohort of 1046 asymptomatic diabetic patients without known coronary artery disease.5Chareonthaitawee P. Sorajja P. Rajagopalan N. Miller T.D. Hodge D.O. Frye R.L. et al.Prevalence and prognosis of left ventricular systolic dysfunction in asymptomatic diabetic patients without known coronary artery disease referred for stress single-photon emission computed tomography and assessment of left ventricular function.Am Heart J. 2007; 154: 567-574Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Some studies suggest that patients with ALVD equal or outnumber those with overt HF. The First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHANES I) reported only a 2% prevalence of overt HF in individuals ages 25 to 74 years, though this value likely is an underestimate.6He J. Ogden L.G. Bazzano L.A. Vupputuri S. Loria C. Whelton P.K. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.Arch Intern Med. 2001; 161: 996-1002Crossref PubMed Scopus (909) Google Scholar The prevalence of both ALVD and overt HF dramatically increase with age. The lifetime risk of developing HF is approximately 20% in octogenarians.7Ho K.K. Pinsky J.L. Kannel W.B. Levy D. The epidemiology of heart failure: the Framingham Study.J Am Coll Cardiol. 1993; 22: 6A-13AAbstract Full Text PDF PubMed Scopus (1854) Google Scholar, 8Lloyd-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 (1189) Google Scholar, 9Remes J. Reunanen A. Aromaa A. Pyorala K. Incidence of heart failure in eastern Finland: a population-based surveillance study.Eur Heart J. 1992; 13: 588-593PubMed Google Scholar In specific populations, such as those who have received cardiotoxic agents and those screened due to a family history of dilated cardiomyopathy, the incidence of ALVD is likely much higher.Prognosis. Patients with ALVD have approximately half the mortality rate (5% annualized) of those with overt symptoms of HF, but their risk of death is 5 to 8 times higher than a normal age-matched population. In the Study of Left Ventricular Dysfunction (SOLVD) prevention study, patients with untreated ALVD developed overt HF at a 10% annual rate, with a further 8% annual risk of death or hospitalization for HF.10Jong P. Yusuf S. Rousseau M.F. Ahn S.A. Bangdiwala S.I. Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study.Lancet. 2003; 361: 1843-1848Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar These data indicate patients with ALVD are at high risk for developing HF. The majority of data regarding outcomes in patients with ALVD come from the SOLVD-prevention study; it would be valuable to have more recent data to fully understand the mortality risk of ALVD in the current era.One trial that can be used to evaluate ALVD outcomes in the current era is the Occluded Artery Trial (OAT).11Hochman J.S. Lamas G.A. Buller C.E. Dzavik V. Reynolds H.R. Abramsky S.J. et al.Coronary intervention for persistent occlusion after myocardial infarction.N Engl J Med. 2006; 355: 2395-2407Crossref PubMed Scopus (580) Google Scholar The study enrolled 2216 subjects 3–28 days post-myocardial infarction (MI) with mean LVEF 48% (LVEF <40% in 21% of the study population). The large majority of subjects (83%) were asymptomatic. A high proportion of subjects received multiple drug therapies including >80% treated with beta blockers, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), statins, and aspirin. Subjects were randomly assigned to a percutaneous coronary intervention (PCI) strategy to open the infarct-related artery or medical management. During a mean follow-up period of 1059 days, adverse cardiac event rates (all-cause mortality, non-fatal MI, and HF hospitalization) were much lower than that reported in the SOLVD study population (301 events with calculated crude event rate 4.8 per 100 patient-years). There were no significant differences in rates of adverse outcome events in the two treatment groups. Lower cardiac event rates in the OAT study population may be attributable to less severe systolic dysfunction and more widespread use of post-MI medical therapies.Managing Patients With ALVD. The management of patients with ALVD focuses on cardiovascular risk factors and on preventing, controlling, or reducing progressive ventricular remodeling.A number of risk factors have the potential to promote progression of ventricular remodeling and adverse outcomes in patients with ALVD. These include systemic hypertension, coronary artery disease, diabetes, obesity, and metabolic syndrome.6He J. Ogden L.G. Bazzano L.A. Vupputuri S. Loria C. Whelton P.K. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.Arch Intern Med. 2001; 161: 996-1002Crossref PubMed Scopus (909) Google Scholar, 12Kenchaiah S. Evans J.C. Levy D. Wilson P.W. Benjamin E.J. Larson M.G. et al.Obesity and the risk of heart failure.N Engl J Med. 2002; 347: 305-313Crossref PubMed Scopus (2125) Google Scholar, 13Levy D. Larson M.G. Vasan R.S. Kannel W.B. Ho K.K. The progression from hypertension to congestive heart failure.JAMA. 1996; 275: 1557-1562Crossref PubMed Google Scholar, 14UK Prospective Diabetes Study GroupTight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.BMJ. 1998; 317: 703-713Crossref PubMed Scopus (0) Google Scholar, 15Wilhelmsen L. Rosengren A. Eriksson H. Lappas G. Heart failure in the general population of men–morbidity, risk factors and prognosis.J Intern Med. 2001; 249: 253-261Crossref PubMed Scopus (229) Google Scholar Population-attributable risk for hypertension and MI may be as high as 60% to 70%, underscoring the importance of preventing and managing these two conditions.12Kenchaiah S. Evans J.C. Levy D. Wilson P.W. Benjamin E.J. Larson M.G. et al.Obesity and the risk of heart failure.N Engl J Med. 2002; 347: 305-313Crossref PubMed Scopus (2125) Google Scholar, 13Levy D. Larson M.G. Vasan R.S. Kannel W.B. Ho K.K. The progression from hypertension to congestive heart failure.JAMA. 1996; 275: 1557-1562Crossref PubMed Google Scholar, 16Haider A.W. Larson M.G. Franklin S.S. Levy D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study.Ann Intern Med. 2003; 138: 10-16Crossref PubMed Scopus (401) Google Scholar, 17Kannel W.B. Castelli W.P. McNamara P.M. McKee P.A. Feinleib M. Role of blood pressure in the development of congestive heart failure. The Framingham study.N Engl J Med. 1972; 287: 781-787Crossref PubMed Scopus (489) Google Scholar, 18Kannel W.B. Hjortland M. Castelli W.P. Role of diabetes in congestive heart failure: the Framingham study.Am J Cardiol. 1974; 34: 29-34Abstract Full Text PDF PubMed Scopus (1584) Google Scholar The 30% or more of patients with ALVD who do not have ischemic heart disease may suffer from hypertension, diabetes mellitus, alcohol overuse, or familial or idiopathic dilated cardiomyopathy. Surveillance studies suggest that relatives of those with idiopathic dilated cardiomyopathy often have asymptomatic LV dilatation and may be at increased risk for developing HF.19Mahon N.G. Murphy R.T. MacRae C.A. Caforio A.L. Elliott P.M. McKenna W.J. Echocardiographic evaluation in asymptomatic relatives of patients with dilated cardiomyopathy reveals preclinical disease.Ann Intern Med. 2005; 143: 108-115Crossref PubMed Scopus (120) Google Scholar, 20Michels V.V. Moll P.P. Miller F.A. Tajik A.J. Chu J.S. Driscoll D.J. et al.The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy.N Engl J Med. 1992; 326: 77-82Crossref PubMed Scopus (560) Google Scholar In addition, those exposed to toxins through alcohol overuse, ionizing radiation, or chemotherapy with anthracyclines may develop ALVD, which may progress to HF in the absence of intervention.21Seymour L. Bramwell V. Moran L.A. Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group.Cancer Prev Control. 1999; 3: 145-159PubMed Google ScholarRecommendations5.1It is recommended that all patients with ALVD exercise regularly according to a physician-directed prescription to avoid general deconditioning; to optimize weight, blood pressure, and diabetes control; and to reduce cardiovascular risk. (Strength of Evidence = C)5.2Smoking cessation is recommended in all patients including those with ALVD. (Strength of Evidence = B)5.3Alcohol abstinence is recommended if there is current or previous history of excessive alcohol intake. (Strength of Evidence = C)5.4It is recommended that all patients with ALVD with hypertension achieve optimal blood pressure control. (Strength of Evidence = B)BackgroundTherapeutic Approaches. Cardiovascular risk factor reduction is advocated in patients with ALVD to decrease the risk of developing overt HF. Control of blood pressure and treatments that slow the progression of ischemic heart disease may have substantial benefit. (See Section 3 for more on the control of cardiovascular risk factors.)Recommendation5.5ACE inhibitor therapy is recommended for asymptomatic patients with reduced LVEF (<40%). (Strength of Evidence = A)BackgroundA twelve-year follow up in SOLVD demonstrated that the initial benefit of enalapril was maintained.10Jong P. Yusuf S. Rousseau M.F. Ahn S.A. Bangdiwala S.I. Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study.Lancet. 2003; 361: 1843-1848Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar Survival curve analysis has confirmed an absolute 9.2-month benefit in life expectancy conferred by 40 months of treatment with an ACE inhibitor, a benefit conferred despite the fact that nearly all patients enrolled in SOLVD went on to receive ACE inhibitors after termination of the randomized portion of the trial. The likelihood of death after 12 years in the treatment group remained fairly constant at approximately 5% annually.A substudy of the SOLVD trial found that administration of enalapril reduced the tendency to progressive LV enlargement in patients with ALVD.22Konstam M.A. Kronenberg M.W. Rousseau M.F. Udelson J.E. Melin J. Stewart D. et al.Effects of the angiotensin converting enzyme inhibitor enalapril on the long-term progression of left ventricular dilatation in patients with asymptomatic systolic dysfunction. SOLVD (Studies of Left Ventricular Dysfunction) Investigators.Circulation. 1993; 88: 2277-2283Crossref PubMed Scopus (284) Google Scholar This beneficial effect on LV remodeling, in combination with prevention of MI, most likely explains the mechanism of reduction of both cardiovascular mortality and progression to HF observed in the SOLVD Prevention trial.23Pouleur H. Rousseau M.F. van E.C. Melin J. Youngblood M. Yusuf S. Cardiac mechanics during development of heart failure. SOLVD Investigators.Circulation. 1993; 87: IV14-IV20PubMed Google Scholar, 24Pouleur H.G. Konstam M.A. Udelson J.E. Rousseau M.F. Changes in ventricular volume, wall thickness and wall stress during progression of left ventricular dysfunction. The SOLVD Investigators.J Am Coll Cardiol. 1993; 22: 43A-48AAbstract Full Text PDF PubMed Scopus (48) Google Scholar, 25Quinones M.A. Greenberg B.H. Kopelen H.A. Koilpillai C. Limacher M.C. Shindler D.M. et al.Echocardiographic predictors of clinical outcome in patients with left ventricular dysfunction enrolled in the SOLVD registry and trials: significance of left ventricular hypertrophy. Studies of Left Ventricular Dysfunction.J Am Coll Cardiol. 2000; 35: 1237-1244Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar Thus ACE inhibitors are indicated in patients with reduced LVEF, regardless of symptoms.Recommendation5.6ARBs are recommended for asymptomatic patients with reduced LVEF who are intolerant of ACE inhibitors from cough or angioedema. (Strength of Evidence = C)Routine use of the combination of ACE inhibitors and ARBs for prevention of HF is not recommended in this population. (Strength of Evidence = C)BackgroundRandomized clinical trials of ARBs in asymptomatic patients with LV systolic dysfunction who are intolerant of ACE inhibitors have not been conducted. Despite the absence of definitive data, based on the results of the Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM)-Alternative and the Valsartan Heart Failure Trial (Val-HeFT) and a variety of pathophysiologic and clinical considerations, it is reasonable to use an ARB in a patient with ALVD if the patient is intolerant to an ACE inhibitor.26Granger C.B. McMurray J.J. Yusuf S. Held P. Michelson E.L. Olofsson B. et al.Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: the CHARM-Alternative trial.Lancet. 2003; 362: 772-776Abstract Full Text Full Text PDF PubMed Scopus (1501) Google Scholar, 27Maggioni A.P. Anand I. Gottlieb S.O. Latini R. Tognoni G. Cohn J.N. Effects of valsartan on morbidity and mortality in patients with heart failure not receiving angiotensin-converting enzyme inhibitors.J Am Coll Cardiol. 2002; 40: 1414-1421Abstract Full Text Full Text PDF PubMed Scopus (293) Google Scholar The addition of an ARB to an ACE inhibitor in asymptomatic patients with reduced LVEF has not been investigated.Recommendation5.7Beta blocker therapy should be considered in asymptomatic patients with reduced LVEF. (post-MI, Strength of Evidence = B; non post-MI, Strength of Evidence = C)BackgroundIschemic Heart Disease With ALVD. A strong rationale exists for the use of beta blocker therapy in the management of patients with ALVD from ischemic heart disease, based on the benefits seen in patients with cardiac dysfunction and no overt HF after acute MI. The Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction (CAPRICORN) study examined the effects of carvedilol in asymptomatic patients with reduced LVEF after MI, with concomitant use of ACE inhibitors, aspirin, and statins in the majority of patients. Although there was no difference between the carvedilol and placebo groups in the number of patients meeting the primary endpoint of all-cause mortality or hospital admission, carvedilol use was associated with fewer deaths, as well as a reduction in the combined endpoint of death or recurrent MI, classical end points in previous studies of beta blockade after MI.28Dargie 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 (1446) Google ScholarBeta blockade has been shown to attenuate LV remodeling in patients with ALVD. The Reversal of Ventricular Remodeling with Toprol-XL (REVERT) Trial randomized 149 patients to metoprolol succinate 50 mg, 200 mg, or placebo for 12 months. LV end-systolic volume, end-diastolic volume, and LVEF were measured at baseline and 6 and 12 months. Patients randomized to metoprolol succinate 200 mg had a significant decrease in LV end-systolic volume index and a significant increase in LVEF as compared to baseline and placebo at 12 months.29Colucci W.S. Kolias T.J. Adams K.F. Armstrong W.F. Ghali J.K. Gottlieb S.S. et al.Metoprolol reverses left ventricular remodeling in patients with asymptomatic systolic dysfunction: the REversal of VEntricular Remodeling with Toprol-XL (REVERT) trial.Circulation. 2007; 116: 49-56Crossref PubMed Scopus (116) Google Scholar Approximately half of the patients in REVERT had a non-ischemic HF etiology.Nonischemic Heart Disease With ALVD. No trial has specifically examined the effect of beta blockers on mortality in asymptomatic patients with reduced LVEF but no recent MI. Given the consistency of benefit observed with beta blockers across symptomatic populations, with and without ischemic heart disease, and in patients with prior MI, regardless of HF symptoms, it is reasonable to recommend use of these agents in asymptomatic patients with reduced LVEF in the absence of identifiable ischemic heart disease. See more about beta blockers in Section 7.Aldosterone Antagonists in Patients With ALVD. Although aldosterone antagonists have been demonstrated to decrease morbidity and mortality in patients with moderate to severe symptoms of HF and reduced LVEF, there are currently no substantial data to suggest that these agents should be recommended as treatment for patients with ALVD. Studies are ongoing to determine the potential of aldosterone antagonists to impact the process of remodeling.Device Therapies in Patients With ALVDCardiac resynchronization therapy (CRT) in patients with ALVD has not been investigated in a large clinical trial. Two trials, the Resynchronization Reverses Remodeling in systolic Left Ventricular Dysfunction (REVERSE)30Daubert C. Gold M.R. Abraham W.T. Ghio S. Hassager C. Goode G. et al.Prevention of disease progression by cardiac resynchronization therapy in patients with asymptomatic or mildly symptomatic left ventricular dysfunction: insights from the European cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.J Am Coll Cardiol. 2009; 54: 1837-1846Abstract Full Text Full Text PDF PubMed Scopus (304) Google Scholar and the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT)31Moss A.J. Hall W.J. Cannom D.S. Klein H. Brown M.W. Daubert J.P. et al.Cardiac-resynchronization therapy for the prevention of heart-failure events.N Engl J Med. 2009; 361: 1329-1338Crossref PubMed Scopus (2292) Google Scholar have studied CRT in patients with NYHA class I and II HF. Further research in a true ALVD population is needed to evaluate the efficacy of CRT in this setting. OverviewLeft ventricular (LV) remodeling and reduced ejection fraction (EF) should be distinguished from the syndrome of clinical heart failure (HF). When LVEF is reduced (<40%), but there are no signs and symptoms of HF, the condition frequently is referred to as asymptomatic LV dysfunction (ALVD). It is important to distinguish between ALVD and patients categorized as New York Heart Association (NYHA) Class I HF. Although patients with NYHA Class I HF do not currently have HF symptoms, they may have ALVD currently, or they may have clinical systolic HF with symptoms in the past. In contrast, patients with ALVD have no past history of HF symptoms. It is now well recognized that there may be a latency period when the LVEF is reduced before the development of symptomatic HF. Although most attention in the HF literature has centered on patients with symptoms, evidence now indicates that ALVD is more common than previously assumed. The recent realization that therapies aimed at symptomatic HF may improve outcomes in patients with ALVD has increased the importance of recognizing and treating patients with this condition.Prevalence. The prevalence of systolic ALVD ranges from 6% to 16% in population-based studies.1Lee E.T. Cowan L.D. Welty T.K. Sievers M. Howard W.J. Oopik A. et al.All-cause mortality and cardiovascular disease mortality in three American Indian populations, aged 45–74 years, 1984–1988. The Strong Heart Study.Am J Epidemiol. 1998; 147: 995-1008Crossref PubMed Scopus (140) Google Scholar, 2McDonagh T.A. Morrison C.E. Lawrence A. Ford I. Tunstall-Pedoe H. McMurray J.J. et al.Symptomatic and asymptomatic left-ventricular systolic dysfunction in an urban population.Lancet. 1997; 350: 829-833Abstract Full Text Full Text PDF PubMed Scopus (551) Google Scholar, 3Mosterd A. Hoes A.W. de Bruyne M.C. Deckers J.W. Linker D.T. Hofman A. et al.Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.Eur Heart J. 1999; 20: 447-455Crossref PubMed Scopus (568) Google Scholar, 4Redfield M.M. Jacobsen S.J. Burnett Jr., J.C. Mahoney D.W. Bailey K.R. Rodeheffer R.J. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic.JAMA. 2003; 289: 194-202Crossref PubMed Scopus (2456) Google Scholar The prevalence of ALVD was 16.7% among a cohort of 1046 asymptomatic diabetic patients without known coronary artery disease.5Chareonthaitawee P. Sorajja P. Rajagopalan N. Miller T.D. Hodge D.O. Frye R.L. et al.Prevalence and prognosis of left ventricular systolic dysfunction in asymptomatic diabetic patients without known coronary artery disease referred for stress single-photon emission computed tomography and assessment of left ventricular function.Am Heart J. 2007; 154: 567-574Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Some studies suggest that patients with ALVD equal or outnumber those with overt HF. The First National Health and Nutrition Examination Survey Epidemiologic Follow-up Study (NHANES I) reported only a 2% prevalence of overt HF in individuals ages 25 to 74 years, though this value likely is an underestimate.6He J. Ogden L.G. Bazzano L.A. Vupputuri S. Loria C. Whelton P.K. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.Arch Intern Med. 2001; 161: 996-1002Crossref PubMed Scopus (909) Google Scholar The prevalence of both ALVD and overt HF dramatically increase with age. The lifetime risk of developing HF is approximately 20% in octogenarians.7Ho K.K. Pinsky J.L. Kannel W.B. Levy D. The epidemiology of heart failure: the Framingham Study.J Am Coll Cardiol. 1993; 22: 6A-13AAbstract Full Text PDF PubMed Scopus (1854) Google Scholar, 8Lloyd-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 (1189) Google Scholar, 9Remes J. Reunanen A. Aromaa A. Pyorala K. Incidence of heart failure in eastern Finland: a population-based surveillance study.Eur Heart J. 1992; 13: 588-593PubMed Google Scholar In specific populations, such as those who have received cardiotoxic agents and those screened due to a family history of dilated cardiomyopathy, the incidence of ALVD is likely much higher.Prognosis. Patients with ALVD have approximately half the mortality rate (5% annualized) of those with overt symptoms of HF, but their risk of death is 5 to 8 times higher than a normal age-matched population. In the Study of Left Ventricular Dysfunction (SOLVD) prevention study, patients with untreated ALVD developed overt HF at a 10% annual rate, with a further 8% annual risk of death or hospitalization for HF.10Jong P. Yusuf S. Rousseau M.F. Ahn S.A. Bangdiwala S.I. Effect of enalapril on 12-year survival and life expectancy in patients with left ventricular systolic dysfunction: a follow-up study.Lancet. 2003; 361: 1843-1848Abstract Full Text Full Text PDF PubMed Scopus (296) Google Scholar These data indicate patients with ALVD are at high risk for developing HF. The majority of data regarding outcomes in patients with ALVD come from the SOLVD-prevention study; it would be valuable to have more recent data to fully understand the mortality risk of ALVD in the current era.One trial that can be used to evaluate ALVD outcomes in the current era is the Occluded Artery Trial (OAT).11Hochman J.S. Lamas G.A. Buller C.E. Dzavik V. Reynolds H.R. Abramsky S.J. et al.Coronary intervention for persistent occlusion after myocardial infarction.N Engl J Med. 2006; 355: 2395-2407Crossref PubMed Scopus (580) Google Scholar The study enrolled 2216 subjects 3–28 days post-myocardial infarction (MI) with mean LVEF 48% (LVEF <40% in 21% of the study population). The large majority of subjects (83%) were asymptomatic. A high proportion of subjects received multiple drug therapies including >80% treated with beta blockers, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB), statins, and aspirin. Subjects were randomly assigned to a percutaneous coronary intervention (PCI) strategy to open the infarct-related artery or medical management. During a mean follow-up period of 1059 days, adverse cardiac event rates (all-cause mortality, non-fatal MI, and HF hospitalization) were much lower than that reported in the SOLVD study population (301 events with calculated crude event rate 4.8 per 100 patient-years). There were no significant differences in rates of adverse outcome events in the two treatment groups. Lower cardiac event rates in the OAT study population may be attributable to less severe systolic dysfunction and more widespread use of post-MI medical therapies.Managing Patients With ALVD. The management of patients with ALVD focuses on cardiovascular risk factors and on preventing, controlling, or reducing progressive ventricular remodeling.A number of risk factors have the potential to promote progression of ventricular remodeling and adverse outcomes in patients with ALVD. These include systemic hypertension, coronary artery disease, diabetes, obesity, and metabolic syndrome.6He J. Ogden L.G. Bazzano L.A. Vupputuri S. Loria C. Whelton P.K. Risk factors for congestive heart failure in US men and women: NHANES I epidemiologic follow-up study.Arch Intern Med. 2001; 161: 996-1002Crossref PubMed Scopus (909) Google Scholar, 12Kenchaiah S. Evans J.C. Levy D. Wilson P.W. Benjamin E.J. Larson M.G. et al.Obesity and the risk of heart failure.N Engl J Med. 2002; 347: 305-313Crossref PubMed Scopus (2125) Google Scholar, 13Levy D. Larson M.G. Vasan R.S. Kannel W.B. Ho K.K. The progression from hypertension to congestive heart failure.JAMA. 1996; 275: 1557-1562Crossref PubMed Google Scholar, 14UK Prospective Diabetes Study GroupTight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38.BMJ. 1998; 317: 703-713Crossref PubMed Scopus (0) Google Scholar, 15Wilhelmsen L. Rosengren A. Eriksson H. Lappas G. Heart failure in the general population of men–morbidity, risk factors and prognosis.J Intern Med. 2001; 249: 253-261Crossref PubMed Scopus (229) Google Scholar Population-attributable risk for hypertension and MI may be as high as 60% to 70%, underscoring the importance of preventing and managing these two conditions.12Kenchaiah S. Evans J.C. Levy D. Wilson P.W. Benjamin E.J. Larson M.G. et al.Obesity and the risk of heart failure.N Engl J Med. 2002; 347: 305-313Crossref PubMed Scopus (2125) Google Scholar, 13Levy D. Larson M.G. Vasan R.S. Kannel W.B. Ho K.K. The progression from hypertension to congestive heart failure.JAMA. 1996; 275: 1557-1562Crossref PubMed Google Scholar, 16Haider A.W. Larson M.G. Franklin S.S. Levy D. Systolic blood pressure, diastolic blood pressure, and pulse pressure as predictors of risk for congestive heart failure in the Framingham Heart Study.Ann Intern Med. 2003; 138: 10-16Crossref PubMed Scopus (401) Google Scholar, 17Kannel W.B. Castelli W.P. McNamara P.M. McKee P.A. Feinleib M. Role of blood pressure in th