Heart failure with preserved ejection fraction diagnosis and treatment: An updated review of the evidence

Abstract

Over the last several decades, clinicians and clinical scientists have had growing interest in heart failure (HF) diagnosis and treatment. While HF with reduced ejection fraction (EF) is a well-known clinical entity with several therapeutic strategies proven to be successful, HF with preserved ejection fraction is a more heterogenous syndrome with a prevalence that has increased in the last two decades, without effective therapeutic strategies. Great strides have been made in the detection of predisposing risk factors and pathological mechanisms; however, pharmacological therapies have shown to be ineffective in reducing cardiovascular mortality in the HF with preserved EF (HFpEF) population, opening the way to the necessity of developing new precision medicine based approaches. On the other hand, novel therapies and device interventions still require refinements with the ultimate goal of offering new clinically treatments for the HFpEF population. The aim of the present review is to provide insights into the HFpEF pathophysiology, diagnostic pathways and the latest updates on treatment strategies and their potential future application in routine clinical practice.

Introduction

Heart failure (HF) with preserved ejection fraction (EF; HFpEF) is a clinical entity characterized by symptoms of HF despite a “preserved” (i.e. 50%) left ventricular (LV) ejection fraction (LVEF) with evidence of cardiac dysfunction as a primary cause of symptoms (eg, abnormal LV filling and elevated filling pressures). Currently, HFpEF affects approximately 4.9% of the general population aged ≥60 years and accounts for approximately half of total HF hospitalizations.¹ Initial retrospective and observational studies including mostly hospitalized patients classified on LVEF alone, the rates of hospitalization and death in patients with HFpEF were similar to those of patients diagnosed with HF with reduced EF (HFrEF).² In prospective and randomized studies in which the diagnosis of HFpEF was made using stricter criteria and other causes of HF (eg, valvular heart diseases, restrictive/infiltrative cardiomyopathies, pericardial diseases) were excluded, however, the cardiovascular (CV) mortality observed was lower in HFpEF compared to those with HFrEF.^3,4

To date, several randomized controlled trials have failed to identify effective pharmacological therapies on clinical outcomes in HFpEF, perhaps due to the unfavorable one-size-fits-all approach for its management⁵. The scientific community of clinicians and clinical scientists has a growing interest in understanding the underlying pathophysiological mechanisms and phenotypic heterogeneity of HFpEF, with hopes to develop new therapeutic strategies.⁶ The aim of the present review is to provide an overview on HFpEF pathophysiology and diagnostic pathways, with a focus on the latest developments of treatment strategies and their potential future applications in routine clinical practice.