Heart failure with a normal ejection fraction: treatments for a complex syndrome?

opinion statementHeart failure with a normal ejection fraction (HFNEF) now comprises more than 50 % of all patients with heart failure. As the population ages, HFNEF will continue to be a growing public health problem. Recent studies highlight the heterogeneity of this syndrome with regards to underlying pathophysiologic mechanisms. It has been recognized that multiple physiologic domains of cardiovascular function are abnormal in afflicted patients resulting in a reduced reserve capacity, which contributes in an integrated fashion to produce the observed phenotype. Additionally, the realization that differing aspects of this syndrome (eg, exercise limitations, pulmonary edema, and labile blood pressure) likely each have distinct physiologic causes further adds to the complexity. As a result of the heterogeneous nature of the pathophysiologic processes and comorbid illnesses in this population, there is a wide range of clinical outcomes. Accordingly, appreciation of the global nature of HFNEF ideally will better inform optimal design for future diagnostic and therapeutic strategies. Completed clinical trials have not resulted in any evidence-based treatments available for improving survival. Given the disappointing results of these investigations, there has been renewed interest in developing interventions that target underlying comorbidities and peripheral mechanisms. Additionally, nonpharmacologic interventions such as diet and exercise have shown promise in early, small clinical investigations. Finally, methods to more rationally subgroup patients to identify cohorts that could respond to targeted intervention are essential. Recognizing the success achieved in the treatment of systolic heart failure, or heart failure with a reduced ejection fraction (HFREF) by addressing neurohormonal and renal mechanisms, new therapies for HFNEF may be achieved by a similar shift in attention away from the heart.