Challenging aspects of treatment strategies in heart failure with preserved ejection fraction: "Why did recent clinical trials fail?"

Abstract

Heart failure (HF) is the leading cause of hospitalization among older adults and the prevalence is growing with the aging populations in the Western countries. Epidemiologic reports suggest that approximately 50% of patients who have signs or symptoms of HF have preserved left ventricular ejection fraction. This HF type predominantly affects women and the elderly with other co-morbidities, such as diabetes, hypertension, and overt volume status. Most of the current treatment strategies are based on morbidity benefits such as quality of life and reduction of clinical HF symptoms. Treatment of patients with HF with preserved ejection fraction displayed disappointing results from several large randomized controlled trials. The heterogeneity of HF with preserved ejection fraction, understood as complex syndrome, seems to be one of the primary reasons. Here, we present an overview of the current management strategies with available evidence and new therapeutic approach from drugs currently in clinical trials, which target diastolic dysfunction, chronotropic incompetence, and risk factor management. We provide an outline and interpretation of recent clinical trials that failed to improve outcome and survival in patients with HF with preserved ejection fraction.

Keywords: Clinical trials; Co-morbidities; Diastolic dysfunction; Preserved ejection fraction.

Figure 1

Overview of multiple effectors for the heterogeneity of the heart failure has preserved left ventricular ejection fraction syndrome. COPD: Chronic obstructive pulmonary disease; HFpEF: Heart failure has preserved left ventricular ejection fraction.

Figure 2

Diagnostic algorithm of diastolic heart failure. BNP: B-type natriuretic peptide; NT-proBNP: N-terminal of the B-type natriuretic peptide; E/É: Pulsed-wave Doppler E wave velocity divided by tissue Doppler E wave velocity; HFpEF: Heart failure has preserved left ventricular ejection fraction.

Figure 3

Scheme of co-morbidities causing or worsening heart failure has preserved left ventricular ejection fraction pathophysiology. LV: Left ventricular; HFpEF: Heart failure has preserved left ventricular ejection fraction.