Heart Failure with Preserved Ejection Fraction (HFpEF)

Pathophysiology

• Left ventricular hypertrophy and cardiac stiffening.
• Impaired ventricular relaxation and filling.
• Elevated filling pressures at rest or with exertion.
• Frequent comorbidity with obesity, T2D, hypertension, atrial fibrillation, chronic kidney disease.
• Underlying substrates include microvascular dysfunction, myocardial fibrosis, and inflammation.

Presentation

Exertional dyspnoea, fatigue, oedema. Diagnosis requires demonstration of elevated filling pressures alongside preserved LVEF.

Management

• SGLT2 inhibitors (dapagliflozin, empagliflozin): first-line disease-modifying therapy.
• GLP-1 agonists (semaglutide, tirzepatide): reduce symptoms and events in obese HFpEF.
• Diuretics for volume management.
• Comorbidity treatment: BP control, AFib rhythm/rate management, T2D optimisation, weight loss.
• Exercise training improves functional capacity.

Longevity relevance

HFpEF is the archetypal age-related cardiovascular disease — a composite of every hallmark of aging expressed cardiovascularly. Modifying its trajectory is one of the most consequential wins of the GLP-1/SGLT2 era.

Related entries

Cardiovascular disease, Heart failure, SGLT2 inhibitors, GLP-1 agonists.