Heart Failure with Preserved Ejection Fraction: A Complex Syndrome

Heart failure with preserved ejection fraction (HFpEF; left ventricular ejection fraction ≥50%) confounds many clinicians who view it as a minor variant of reduced ejection fraction — distinct from heart failure with mid‐range ejection fraction (HFmrEF; EF 41–49%) — yet it is characterized by a constellation of diastolic dysfunction, myocardial fibrosis, inflammation and comorbidities such as hypertension and obesity, creating a complex syndrome that demands a nuanced approach to diagnosis and management, as outlined in the 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure.

Recent hemodynamic insights from a European Heart Journal study demonstrate that diastolic dysfunction drives increased myocardial stiffness and impaired ventricular relaxation, which underlie hallmark symptoms such as exercise intolerance and pulmonary congestion. This process is often amplified in patients with obesity, diabetes or hypertension, where interstitial fibrosis and low-grade inflammation further compromise ventricular compliance.

Accurate identification of HFpEF relies on the 2021 ESC HFA-PEFF diagnostic algorithm, which integrates a pretest probability score with functional (echocardiographic measures of diastolic function), morphological (left atrial size and left ventricular mass) and biomarker (natriuretic peptide levels) domains to confirm the diagnosis.

Therapeutic strategies have traditionally focused on symptom relief, rigorous blood pressure control and management of comorbidities. However, recent evidence for SGLT2 inhibitors demonstrates significant reductions in heart failure hospitalizations and cardiovascular deaths in HFpEF populations regardless of diabetic status, making them an essential consideration for all eligible patients.

Loop diuretics remain the mainstay for volume management, while individualized blood pressure targets and weight optimization address underlying contributors to ventricular stiffness.

The therapeutic horizon for HFpEF is expanding, with ongoing clinical trials for HFpEF exploring novel pharmacological agents aimed at modulating myocardial fibrosis, inflammation and ventricular-arterial coupling (the interaction between ventricular performance and arterial load), as well as device-based interventions designed to improve diastolic filling.

Key Takeaways:

• HFpEF involves diastolic dysfunction, myocardial fibrosis and systemic comorbidities, necessitating a tailored diagnostic and therapeutic approach.
• Structured criteria incorporating echocardiographic parameters and natriuretic peptides are essential to distinguish HFpEF from other causes of dyspnea.
• SGLT2 inhibitors significantly reduce the composite endpoint of heart failure hospitalization and cardiovascular death in HFpEF populations.
• Ongoing trials targeting myocardial fibrosis, inflammation and ventricular-arterial coupling may soon expand treatment options.