Cardiovascular · Topic 8 of 48

Heart Failure with Preserved EF (HFpEF)

Cardiovascular · heart failure

Heart Failure with Preserved EF (HFpEF)

HF with LVEF 50% or more. Give an SGLT2 inhibitor, diurese congestion, and control blood pressure and atrial fibrillation.

Key numbers

HF symptoms with LVEF ≥ 50%LVEF ≥ 50%

H2FPEF score: 6 or more makes HFpEF likelyH2FPEF ≥ 6

01 · Defined byHF symptoms with LVEF ≥ 50%

HFpEF is the clinical HF syndrome with LVEF ≥ 50% plus evidence of raised filling pressure — elevated natriuretic peptides, echo diastolic dysfunction or invasive hemodynamics. HFrEF is LVEF ≤ 40%; 41–49% is mildly reduced.

02 · GiveGive an SGLT2 inhibitor

An SGLT2 inhibitor (empagliflozin or dapagliflozin 10 mg daily) is the core HFpEF drug for every patient who can take it: it lowers the composite of HF hospitalization or cardiovascular death, mainly by preventing hospitalizations.

03 · DoTreat hypertension to guideline targets

Titrate antihypertensives to guideline blood-pressure targets (Class 1) and manage atrial fibrillation (Class 2a) — uncontrolled hypertension and AF drive HFpEF symptoms and hospitalizations.

Causes & risk factors

Why it happens

Comorbidities drive HFpEFHFpEF is about half of all HF and rises with age; obesity, hypertension, diabetes and CKD cause systemic inflammation and myocardial stiffening — unlike HFrEF, which usually follows primary myocardial injury (MI, myocarditis, dilated cardiomyopathy).

Presentation

What you'll see

BNP can be normal in HFpEFNatriuretic peptides run about half the HFrEF level in HFpEF and are lowered by obesity; up to 30% of acute HFpEF patients have BNP below 100 pg/mL, so a normal BNP does not exclude it.

Diagnosis & monitoring

Work-up

H2FPEF score: 6 or more makes HFpEF likelyH2FPEF (0–9): AF 3 points, BMI > 30 2 points, and 1 each for ≥ 2 antihypertensives, age > 60, E/e′ > 9 and PA systolic > 35 mmHg. Under 2 unlikely; 2–5 needs testing.

Management

Orders

Loop diuretics for congestion must knowUse loop diuretics to relieve congestion and symptoms, titrated to the lowest dose that keeps the patient euvolemic; diuretics are a primary therapy in symptomatic HFpEF.

Consider an MRA in selected patientsSpironolactone may be considered (Class 2b) to reduce HF hospitalization, especially at lower LVEF, if eGFR > 30, creatinine < 2.5 mg/dL and K⁺ < 5.0 mEq/L; monitor potassium closely.

Finerenone approved for LVEF 40% or moreFinerenone, a nonsteroidal MRA, cut total worsening-HF events plus cardiovascular death by 16% in HF with LVEF ≥ 40% (FINEARTS-HF) and was FDA-approved for this group in July 2025; hyperkalemia is the main risk.

ARNI or ARB may be consideredSacubitril/valsartan or an ARB may be considered (Class 2b) to reduce hospitalization, particularly at the lower end of the LVEF range; the ARNI signal was strongest in women and with LVEF below 57%.

GLP-1 therapy for HFpEF with obesityIn HFpEF with BMI ≥ 30, semaglutide 2.4 mg weekly improved symptoms, exercise capacity and weight, and tirzepatide lowered cardiovascular death or worsening HF (HR 0.62).

Red flags & don'ts

Avoid harm

Beta-blockers only for another indication avoidBeta-blockers are not an HFpEF therapy — use them for AF rate control, angina or prior MI; in severe restrictive physiology cardiac output is rate-dependent, so slowing the heart can drop output.

No routine nitrates or PDE-5 inhibitors avoidRoutine nitrates or phosphodiesterase-5 inhibitors do not improve activity or quality of life in HFpEF (Class 3: No Benefit).

HFrEF or HFpEF?

Commonly confused

LVEF	40% or less
Usual driver	Primary myocardial injury (MI, myocarditis, dilated cardiomyopathy)
Natriuretic peptides	Higher
Beta-blocker	Mortality benefit — a pillar
Proven drug therapy	Four pillars: ARNI, beta-blocker, MRA, SGLT2i

More detail

Reference

Show 5 reference facts

HFA-PEFF support for raised filling pressure: E/e′ ≥ 15, TR velocity > 2.8 m/s, LV wall ≥ 12 mm; in sinus rhythm, NT-proBNP > 125 or BNP > 35 pg/mL is the lowest supportive level.

HF with mildly reduced EF (41–49%): an SGLT2 inhibitor can be beneficial (Class 2a); HFrEF beta-blockers, ARNI/ACEi/ARB and MRA may be considered (2b), especially at the lower end of the range.

Look for causes with specific treatments: cardiac MRI detects amyloidosis, sarcoidosis and hemochromatosis, and invasive hemodynamics separate restrictive cardiomyopathy and constrictive pericarditis when HFpEF is uncertain.

In HFpEF, impaired relaxation and a stiff ventricle raise LV end-diastolic pressure with a normal end-diastolic volume; high left atrial pressure causes pulmonary congestion and pulmonary hypertension.

Exercise training through cardiac rehabilitation is likely helpful in chronic HFpEF; weight loss and sodium restriction support symptom control.

Pearl

In HFpEF the drug list is short — SGLT2 inhibitor plus a diuretic — so the comorbidities (blood pressure, weight, AF) are the treatment.

Sources · Heidenreich PA et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. J Am Coll Cardiol 2022;79:e263–e421 · Merck Manual Professional — Chronic Heart Failure · Merck Manual Professional — Overview of Heart Failure · Merck Manual Professional — Medications for Heart Failure · Merck Manual Professional — Acute Heart Failure · ACC — 2022 AHA/ACC/HFSA Heart Failure Guideline: Key Perspectives · Reddy YNV et al. A simple, evidence-based approach to help guide diagnosis of HFpEF (H2FPEF score). Circulation 2018;138:861–870 · Solomon SD et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (FINEARTS-HF). N Engl J Med 2024 · TCTMD — FDA Approves Finerenone for HF Patients With Mildly Reduced or Preserved EF (July 2025) · Kosiborod MN et al. Semaglutide in Patients with HFpEF and Obesity (STEP-HFpEF). N Engl J Med 2023 · Packer M et al. Tirzepatide for HFpEF and Obesity (SUMMIT). N Engl J Med 2025 · Pieske B et al. How to diagnose HFpEF: the HFA-PEFF diagnostic algorithm (Heart Failure Association of the ESC). Eur Heart J 2019;40:3297–3317 · Practical Implementation of Steroidal and Nonsteroidal MRAs in the Management of Heart Failure. JACC: Advances 2026 (finerenone FDA approval July 2025) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).