Ultimate Longevity Bible

Disease of aging

Heart Failure (HFpEF / HFrEF)

Last updated Sat May 30 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

RCT evidenceRecently transformed by SGLT2 inhibitor trials

What it is

Heart failure is the clinical syndrome of impaired cardiac filling or ejection causing symptoms (dyspnoea, oedema, fatigue) and elevated filling pressures. The two main phenotypes differ markedly in biology and treatment.

HFrEF — reduced ejection fraction

Four pillars of guideline-directed medical therapy (GDMT) for HFrEF all have mortality-benefit RCT evidence:

  1. ACE inhibitor / ARB / sacubitril-valsartan (ARNi).
  2. Beta-blocker (carvedilol, bisoprolol, metoprolol succinate).
  3. Mineralocorticoid receptor antagonist (spironolactone, eplerenone).
  4. SGLT2 inhibitor (dapagliflozin, empagliflozin) — the newest pillar.

Plus diuretics for symptom control and device therapy (ICD, CRT) in selected patients.

HFpEF — preserved ejection fraction

Historically treatment-resistant. Recent advances:

  • SGLT2 inhibitors: EMPEROR-Preserved and DELIVER both reduced composite cardiovascular endpoints. First class with clear HFpEF evidence.
  • Finerenone: selective non-steroidal MRA, benefit in HFpEF.
  • Tirzepatide (SUMMIT trial): reduced HFpEF composite endpoint in obese patients.

Common contributors to address

  • Hypertension control.
  • Sleep apnea screening + treatment.
  • Iron deficiency repletion (improves symptoms).
  • Cardiac amyloidosis screening (especially in older men with HFpEF + LVH).
  • Atrial fibrillation rate/rhythm management.

Related entries

NT-proBNP, SGLT2 inhibitors, Sleep apnea, Atrial fibrillation.

References

  • McDonagh, T. A. et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 42, 3599–3726 (2021).

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