Pharmacologic Approaches and Evidence in Diagnosing and Treating Heart Failure with Preserved Ejection Fraction: An Updated Review for Pharmacists

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome characterized by heart failure symptoms despite a normal left ventricular ejection fraction (≥50%). HFpEF accounts for nearly half of all heart failure hospitalizations and is associated with significant morbidity and mortality. The pathophysiology of HFpEF is multifactorial, involving impairments in cardiac, pulmonary, vascular, and peripheral function, often driven by comorbidities such as aging, obesity, hypertension, and metabolic disorders. Diagnosis of HFpEF requires the presence of compatible symptoms and signs, elevated natriuretic peptide levels, and objective evidence of cardiac structural and functional alterations. The H2FPEF score and the HFA-PEFF diagnostic algorithm have been proposed to aid in the diagnosis of HFpEF. Despite numerous clinical trials, no pharmacological therapies have consistently demonstrated a reduction in mortality or hospitalizations in HFpEF patients. Current management focuses on symptom relief with diuretics and treatment of comorbidities. Promising therapies under investigation include SGLT2 inhibitors, anti-inflammatory agents, anti-fibrotic drugs, and novel devices targeting interatrial shunting and left atrial pacing. Non-pharmacological interventions, such as exercise training and dietary modifications, have shown improvements in exercise capacity and quality of life in HFpEF patients. Further research is needed to elucidate the complex pathophysiology of HFpEF and develop targeted therapies that improve clinical outcomes in this challenging patient population.