Epidemiologic studies indicate that up to 50% of patients with heart failure have a preserved ejection fraction, and this proportion has increased over time. In observational studies, rates of hospitalization and death among patients who have heart failure with a preserved ejection fraction approach those among patients who have heart failure with a reduced ejection fraction, but in clinical-trial populations, outcomes are better in patients who have heart failure with a preserved ejection fraction. Management of heart failure with preserved ejection fraction includes diuretics, treatment of coexisting conditions, aerobic exercise, self-care, and disease management programs, but medications that are effective for reduced ejection fraction have not been beneficial. A new Clinical Practice article explains further.
• How is heart failure with a preserved ejection fraction defined?
In observational studies and clinical trials, the value used to define a “preserved” ejection fraction has ranged from 40 to 55%, but current guidelines recommend a partition value of 50%. An ejection fraction of 40 to 49% is a gray area.
• Is the pathophysiology of heart failure with a preserved ejection fraction well understood?
The fundamental pathophysiology perturbation leading to heart failure with a preserved ejection fraction remains incompletely defined, but traditionally it has been attributed to hypertensive left ventricular remodeling. Systemic microvascular endothelial inflammation related to coexisting conditions has been proposed as an additional mechanism leading to myocardial inflammation and fibrosis, increases in oxidative stress, and alterations in cardiomyocyte signaling pathways. These alterations promote cardiomyocyte remodeling and dysfunction as well as microvascular dysfunction and rarefaction in cardiac and skeletal muscle.
Morning Report Questions
Q: Are circulating levels of natriuretic peptides elevated in patients with heart failure and preserved ejection fraction?
A: Ventricular wall stress and thus circulating levels of natriuretic peptides are lower in patients who have heart failure with a preserved ejection fraction than in patients who have heart failure with a reduced ejection fraction. Levels of natriuretic peptides may be normal in up to 30% of patients who have heart failure with a preserved ejection fraction, particularly in those who are obese or have purely exertional symptoms. The higher the natriuretic peptide level, the more likely it is that the patient has heart failure. However, some elderly patients or patients who have atrial fibrillation without heart failure may have natriuretic peptide levels that are similar to those of patients with heart failure.
Q: What is the role of angiotensin antagonists, spironolactone, and beta-blockers in the management of heart failure with a preserved ejection fraction?
A: Since no therapy has been shown to improve outcomes in patients who have heart failure with a preserved ejection fraction, current therapy includes the relief of volume overload (when present), treatment of coexisting conditions, additional strategies that may increase exercise tolerance or reduce symptoms, and strategies to manage chronic disease and prevent hospitalizations. Individually or in a meta-analysis, three randomized trials of angiotensin antagonists (angiotensin-converting–enzyme [ACE] inhibitors or angiotensin-receptor antagonists) involving patients who had heart failure with a preserved ejection fraction did not show significant effects of these agents on composite end points of all-cause or cardiovascular mortality and hospitalizations for heart failure. The mineralocorticoid-receptor antagonist spironolactone did not reduce rates of the primary composite outcome of death from cardiovascular causes, aborted cardiac arrest, or hospitalization for heart failure in these patients. Spironolactone reduced the rate of hospitalization for heart failure but not the rate of death from any cause or hospitalization for any cause, and it increased the rate of renal dysfunction and hyperkalemia. Analyses that were limited to patients who were enrolled in centers in the Americas (which had higher event rates) showed beneficial effects of spironolactone on the composite primary end point, but these post hoc analyses must be interpreted with caution. The effect of beta-blockers in patients with heart failure and a preserved ejection fraction has not been evaluated in an adequately powered study, and the limited available data are conflicting. Thus, the use of angiotensin antagonists and beta-blockers in the treatment of patients who have heart failure with a preserved ejection fraction should be limited to patients who have alternative indications for their use.