Evaluation and Management of Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction

Evaluation and Management of Patients with Heart Failure and Preserved Left Ventricular Ejection Fraction

Overview

A substantial number of patients with heart failure (HF) have preserved left ventricular ejection fraction (LVEF), variably defined as an LVEF >40%, >45%, or >50%.1,2 When these patients have invasive or non-invasive evidence of abnormal diastolic function (either abnormal relaxation, filling or stiffness) they are said to have "diastolic HF".3 Although the term "HF with normal LVEF" is often used to denote this group, because "normal" is variously defined, "HF with preserved LVEF" will be the active definition in this document. Few randomized clinical trials have been performed in this patient group, but appropriate treatment strategies have been proposed by the American College of Cardiology, American Heart Association, Canadian Society of Cardiology, and the European Society of Cardiology, and are proposed in this document by the Heart Failure Society of America.4-10 Patients with a previously reduced LVEF whose LVEF has returned to normal with medical and/or device therapy should not be included in the classification of HF with preserved LVEF, but they should be treated as outlined in Section 7.

Pathophysiology. The left ventricle in HF with preserved LVEF may be characterized by LV hypertrophy,11 concentric remodeling, increased extracellular matrix,12 abnormal calcium handling, abnormal relaxation and filling and decreased diastolic distensibility.6,13 Activation of the neurohormonal milieu, including the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, is common in HF with and without preserved LVEF.6

Prevalence. In prospective studies, approximately 50% of the population of patients with HF has normal or near normal resting LVEF. 2,5,14-16 HF with preserved LVEF is particularly prevalent among the elderly, females, and patients with hypertension.2,15,17,18 Among 4 prospective studies of HF with preserved LVEF, the average age range of patients was 73 to 79 years, and the percentage of females ranged from 61% to 76%.2,14,19 However, neither age <70 years nor male gender excludes the diagnosis of HF with preserved LVEF.

Mortality and Morbidity. The mortality of patients with HF with preserved LVEF is considerable, and in the general population of unselected patients it may be comparable to mortality in patients with HF and reduced LVEF.2,14,16 An analysis from the Framingham Heart Study showed that HF patients with preserved LVEF had lower 5 year mortality compared with those with reduced LVEF.16 This difference was even more pronounced in the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) study. However, in a study from Olmsted County, survival was similar for patients with HF and either reduced or preserved LVEF.15

This variability in relative clinical outcomes may reflect differences in criteria for the diagnosis of HF, the number of co-morbidities present, and the demographic and clinical composition of the populations studied. In the Olmstead County report, the mean age of the patients with HF with preserved LVEF was 77 +/- 12 years.15 In a recent review by the same investigators, mortality in HF with preserved LVEF was similar to that in patients with HF and reduced LVEF when patients were older than 65; among patients younger than 65, mortality was lower in those with preserved LVEF.18

HF with preserved LVEF is also associated with considerable morbidity. There is a 50% chance of re-hospitalization for HF in 6 months in patients with HF with preserved LVEF. A recent study comparing patients with preserved or reduced LVEF found similar rates of hospital readmissions, HF readmissions, and functional decline.2

Women make up a majority of patients with HF with preserved LVEF.14,16,20 Most studies have shown no difference in survival by gender, but in the Digitalis Investigation Group (DIG) study 21 and one other study,16 female gender was associated with improved survival.

An analysis of the Coronary Artery Surgery Study registry showed that the presence of coronary artery disease (CAD) was an adverse factor for survival in patients with HF and LVEF >45%.22 A review of the available literature in 2002 showed that the prevalence of CAD in patients with HF and preserved LVEF ranged widely from 0% to 67%, but is clearly less than the prevalence in HF and a reduced LVEF.6