Treatment of Heart Failure With Preserved Ejection Fraction (HFpEF): the Phenotype-Guided Approach

The syndrome of heart failure with preserved ejection (HFpEF) continues to rise in prevalence without persuasive evidence of current pharmacologic interventions that can reduce mortality. Clinical trials thus far have generally enrolled “all-comers” with the clinical syndrome of heart failure and objective evidence of a preserved ejection fraction. However, HFpEF is increasingly understood to be a heterogeneous syndrome likely borne from the interplay of genetic predisposition, lifestyle factors, and high burden of associated comorbidities with each contributing to a variety of incompletely understood pathophysiologic abnormalities. Complicating management further, such abnormalities appear to be present to varying degrees among individual patients. Ongoing studies, along with the use of computational statistics/machine learning, offer the hope of clarifying the pathophysiological substrates giving rise to the syndrome of HFpEF in different patient subsets. With better understanding of the syndrome’s underpinnings, there will be the potential for development of truly targeted therapies. However, for now, there is substantial evidence for the use of currently available pharmacologic device and lifestyle therapy for the optimized management of patients. Such therapy can be tailored to presently identifiable patient clusters—called “phenotypes”—distinguished by both the presence of predominant presenting symptoms and/or predominant comorbidity profiles. Examples of clinical presentation phenotypes include lung congestion, chronotropic incompetence, pulmonary hypertension, or skeletal muscle weakness as predominant features. Additionally, such patients may have underlying metabolic syndrome, systemic (arterial) hypertension, renal dysfunction, atrial fibrillation, and/or coronary artery disease as principal underlying comorbidities. Here, we review a “phenotype-guided” approach to the management of patients with HFpEF, based on a stepwise method of making the HFpEF diagnosis, identifying the prominent sources of organ dysfunction, and treating accordingly.