HFnrEF management
LVEF >40% — encompasses what was previously called HFmrEF and HFpEF. Accounts for ~50% of all HF, particularly older patients, women, and those with HTN, DM, obesity, and OSA. No therapy has demonstrated mortality reduction. The goal is to reduce HF hospitalisations and improve symptoms. SGLT2i and MRA form the pharmacologic backbone.
key differences from HFrEF
| HFrEF (≤40%) | HFnrEF (>40%) |
|---|
| mortality benefit from GDMT | yes — quadruple therapy | no intervention reduces mortality |
| primary treatment goal | reduce death + HF hospitalisation | reduce HF hospitalisation + symptoms |
| quadruple therapy | standard of care | not applicable as a bundle |
| beta-blockers | mortality benefit | no HF-specific benefit (use for rate control / HTN only) |
| comorbidity burden | variable | typically high — HTN, DM, AF, obesity, CKD, OSA |
pharmacotherapy
recommended (strong evidence for reducing HF hospitalisation)
steroidal vs non-steroidal MRAs — not interchangeable
Same receptor target, different drugs, different patients. Steroidal MRAs (spironolactone, eplerenone) have proven mortality benefit in HFrEF but equivocal data in HFpEF (TOPCAT). Non-steroidal MRAs (finerenone) have more even heart/kidney tissue distribution, higher MR antagonism potency, and fewer off-target effects (less gynecomastia and hyperkalaemia). Finerenone is the preferred MRA for HFnrEF based on FINEARTS-HF (2024). Favour finerenone especially if concurrent diabetic kidney disease. — Harrington et al. JACC Heart Fail. 2025
suggested (moderate evidence or specific subgroups)
| Agent | Evidence | Notes |
|---|
| ARNI | PARAGON-HF (2019) | primary endpoint narrowly missed; benefit signal in LVEF <57% and in women; suggest if low risk of hypotension |
| GLP-1RA (semaglutide) | STEP-HFpEF (2024) | if LVEF ≥45% + BMI ≥30; improves symptoms, exercise capacity, weight; HF hospitalisation benefit emerging |
symptom management
- loop diuretics for euvolaemia — lowest effective dose; no mortality benefit
- treat comorbidities aggressively: HTN, AF (rate/rhythm), OSA (CPAP), obesity, diabetes
comorbidity-driven approach
HFnrEF is a comorbidity-driven syndrome
Unlike HFrEF where the myocardial disease is central, HFnrEF is often driven by systemic inflammation from metabolic comorbidities → endothelial dysfunction → myocardial fibrosis and stiffness. Treating comorbidities IS treating the HF.
| Comorbidity | Action |
|---|
| HTN | aggressive BP control — single most important modifiable factor |
| AF | rate or rhythm control; OAC per CHADS₂-VASc (or CHADS-65 in Canada) |
| obesity | GLP-1RA (semaglutide) if BMI ≥30; weight loss improves symptoms and exercise capacity |
| diabetes | SGLT2i first-line; GLP-1RA additive benefit |
| OSA | screen (high prevalence); CPAP improves symptoms |
| iron deficiency | IV iron if ferritin <100 or ferritin 100–299 + TSAT <20% (extrapolated from HFrEF data) |
| CKD | SGLT2i beneficial for both HF and renal outcomes; finerenone for DKD |
| coronary disease | standard secondary prevention; revascularisation if ischaemia-driven symptoms |
what NOT to do
- do not reflexively use beta-blockers for HFnrEF — no HF-specific benefit; may worsen exercise intolerance (chronotropic incompetence is common)
- do not assume “diastolic HF is benign” — 5-year mortality approaches HFrEF
- do not neglect volume assessment — these patients are highly preload-sensitive; over-diuresis causes low output symptoms