Overview

Left 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.1-4 The prevalence of ALVD was 16.7% among a cohort of 1046 asymptomatic diabetic patients without known coronary artery disease.5 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.6 The prevalence of both ALVD and overt HF dramatically increase with age. The lifetime risk of developing HF is approximately 20% in octogenarians.7-9 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.10 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).11 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.6,12-15 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.12,13,16-18 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.19,20 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.21