HF symptoms with LVEF ≥50% from diastolic dysfunction — SGLT2i and MRAs reduce HF hospitalization; no therapy has a proven mortality benefit.
Also known as: HFpEF, diastolic heart failure, diastolic dysfunction
Overview
Clinical syndrome of heart failure (signs/symptoms) with LVEF ≥50% on echo. Driven by impaired LV relaxation and filling rather than reduced contractility. Accounts for ~50% of all HF cases and is now the more common phenotype.
Epidemiology
Disproportionately affects older women, often with multiple comorbidities (HTN, obesity, diabetes, CKD, AFib). Mortality approaches HFrEF.
Try two board-style Heart Failure with Preserved Ejection Fraction questions
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Question 1CardiovascularMedium
A 72-year-old woman with longstanding hypertension presents with dyspnea on exertion and orthopnea. ECG shows left ventricular hypertrophy (LVH). Echocardiography reveals concentric LVH, an ejection fraction of 70%, impaired relaxation, and elevated left ventricular (LV) filling pressures. Which of the following drug classes has the strongest evidence for reducing heart failure with preserved ejection fraction (HFpEF) hospitalizations?
AAngiotensin-converting enzyme inhibitors
BBeta-adrenergic blockers
CCalcium channel blockers
DAldosterone antagonists
ESGLT2 inhibitors
Reveal answer & full explanation
Correct answer: E — SGLT2 inhibitors
AAngiotensin-converting enzyme inhibitors
BBeta-adrenergic blockers
CCalcium channel blockers
DAldosterone antagonists
ESGLT2 inhibitors✓
Why SGLT2 inhibitors are correct
The concentric LVH, preserved EF of 70%, impaired relaxation, and elevated LV filling pressures define hypertensive HFpEF; unlike HFrEF, few drug classes reduce events in this phenotype
SGLT2 inhibitors are the first drug class with consistent evidence for reducing heart failure (HF) hospitalizations in HFpEF across the EF spectrum, and carry a Class 2a recommendation in current AHA/ACC/HFSA HF guidance
The benefit is largely independent of glucose lowering, driven by reduced congestion (natriuresis/diuresis) that directly addresses this patient's elevated filling pressures
Empagliflozin (EMPEROR-Preserved) and dapagliflozin (DELIVER) each cut HF hospitalizations in dedicated HFpEF trials and are approved for this indication
Why the others are wrong
Aldosterone antagonists — Mineralocorticoid receptor antagonists do reduce HF events in HFpEF (finerenone in FINEARTS-HF; spironolactone only borderline in TOPCAT), but on a smaller, less consistent evidence base and with a lower guideline class than SGLT2 inhibitors, which cut HF hospitalizations in two dedicated trials; choosing it overweights a single positive trial
Angiotensin-converting enzyme inhibitors — ACE inhibitors treat this patient's hypertension but lack outcome evidence in HFpEF (PEP-CHF was neutral); picking it is buzzword-matching on 'hypertensive heart disease' rather than the HFpEF endpoint asked about
Beta-adrenergic blockers — Beta-blockers have no strong HFpEF hospitalization evidence (SENIORS subgroup) and may worsen exercise tolerance by blunting chronotropy in a stiff ventricle; this is an HFrEF therapy applied to the wrong phenotype
Calcium channel blockers — non-dihydropyridine calcium channel blockers such as verapamil were once used to slow the heart rate and improve relaxation in a stiff, hypertrophied ventricle, but no calcium channel blocker has outcome evidence for reducing HFpEF hospitalizations; they can treat hypertension or control rate, but choosing them targets the impaired relaxation on echo rather than the HF-event endpoint asked about
Question 2CardiovascularMedium
A 60-year-old male with heart failure with preserved ejection fraction (HFpEF) (EF 58%) has dyspnea on exertion and 2 hospitalizations for decompensated heart failure (HF) in the past year. BNP is 680. He has hypertension, diabetes mellitus (DM), and obesity. Which of the following medications reduces HF hospitalizations in HFpEF?
ASGLT2 inhibitor
BACE inhibitor plus beta-blocker
CIvabradine
DIsosorbide mononitrate
EDigoxin
Reveal answer & full explanation
Correct answer: A — SGLT2 inhibitor
ASGLT2 inhibitor✓
BACE inhibitor plus beta-blocker
CIvabradine
DIsosorbide mononitrate
EDigoxin
Why SGLT2 inhibitor is correct
Heart failure with preserved ejection fraction (HFpEF) has historically had few proven therapies.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors: EMPEROR-Preserved trial (empagliflozin) and DELIVER trial (dapagliflozin) both significantly reduced the composite of worsening heart failure (HF) events or cardiovascular (CV) death across the preserved ejection fraction (EF) range, driven by fewer HF hospitalizations.
SGLT2 inhibitors now carry a class IIa recommendation for HFpEF.
Why the others are wrong
Isosorbide mononitrate — in NEAT-HFpEF, isosorbide mononitrate did not improve symptoms or quality of life and reduced daily activity levels; nitrates have no role in reducing HF hospitalization in HFpEF.
ACE inhibitor plus beta-blocker — angiotensin-converting enzyme inhibitor (ACEi) and beta-blockers have no proven mortality benefit in HFpEF.
Digoxin — no established benefit in HFpEF.
Ivabradine — tempting because it reduced HF hospitalizations in the SHIFT trial, but that benefit was limited to heart failure with reduced ejection fraction (HFrEF) (EF 35% or less, sinus rhythm, resting heart rate 70 or more despite a maximally tolerated beta-blocker); it has not shown benefit in HFpEF.
Additional high-yield points
Aggressive risk factor management is also recommended: blood pressure below 130/80, diabetes mellitus (DM) control, and weight loss — 10% weight reduction improves symptoms significantly.
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Hypertension (most common driver — LVH from chronic pressure overload)
Obesity
Diabetes mellitus
Older age, female sex
Atrial fibrillation
Coronary artery disease, CKD, sleep apnea
Infiltrative: cardiac amyloidosis (consider in elderly with HFpEF + carpal tunnel, low-voltage ECG, or apical sparing on strain echo)
Pathophysiology
Impaired LV relaxation (active, ATP-dependent) and reduced compliance (passive stiffening from fibrosis, hypertrophy) elevate filling pressures at any given volume. The resulting pulmonary venous congestion produces classic HF symptoms despite normal contractility and stroke volume at rest.
Clinical presentation
Symptoms
Indistinguishable from HFrEF clinically: DOE, orthopnea, PND, fatigue, edema
Symptoms may be more exertion-dependent early on (preserved resting CO)
Atrial fibrillation often unmasks symptoms (loss of atrial kick)
Signs / physical exam
Similar to HFrEF: JVD, crackles, S4 gallop (vs S3 in HFrEF — stiff ventricle accentuates A wave)
Hypertension on exam common
Lower-extremity edema, weight gain
Differential diagnosis
HFrEF / HFmrEF — Reduced EF on echo distinguishes; HFrEF gets full 4-pillar GDMT, while in HFmrEF (LVEF 41-49%) SGLT2i is class 2a and the other pillars are class 2b (2022 AHA/ACC/HFSA)
Cardiac amyloidosis — Elderly with HFpEF + carpal tunnel syndrome (often bilateral), low-voltage ECG despite LVH on echo, apical sparing on strain imaging; technetium pyrophosphate or biopsy
Hypertrophic cardiomyopathy — Disproportionate LVH (often septal), LVOT obstruction with dynamic murmur, family history of sudden death; HCM management diverges from HFpEF
Constrictive pericarditis — Pericardial thickening on CT/MRI, respirophasic interventricular dependence on echo, Kussmaul sign; surgically curable
Restrictive cardiomyopathy (infiltrative) — Biventricular failure, low voltage, atrial enlargement out of proportion to ventricles; amyloid most common
Pulmonary hypertension (any cause) — Right HF dominates over left HF; PA pressure elevated on echo; consider chronic thromboembolic, idiopathic, secondary causes
Severe obesity / deconditioning — Exertional dyspnea without elevated BNP and with normal echo; address activity, weight
Chronic kidney disease with volume overload — Elevated BUN/Cr, oliguria; volume status responds to dialysis or aggressive diuresis
Diagnostic workup
Diagnostic criteria
H2FPEF score (heavy, hypertensive, AFib, pulmonary HTN, elder, filling pressure) — ≥6 makes HFpEF likely. EF cutoff ≥50% (41-49% = HFmrEF, heart failure with mildly reduced EF).
Labs
BNP / NT-proBNP — elevated, though may be lower than in HFrEF for same severity (especially in obesity)
TTE: LVEF ≥50% with diastolic dysfunction parameters (E/e' >14, LA dilation >34 mL/m², elevated PASP, abnormal mitral inflow patterns)
Stress echo can unmask exercise-induced diastolic dysfunction
Cardiac MRI if amyloid or HCM suspected
Diagnostic algorithm
Feature
HFrEF
HFpEF
LVEF
≤40%
≥50%
Primary defect
Reduced contractility
Impaired relaxation / stiffness
Gallop
S3
S4
Typical demographic
Older men, CAD
Older women, HTN, obesity, DM
Disease-modifying therapy
ARNI + BB + MRA + SGLT2i (each ↓ mortality)
SGLT2i + finerenone (↓ HF hospitalization; no proven mortality benefit)
Beta-blocker
Class I (carvedilol, metop succ, bisop)
Use for HTN/AFib indications, not HF per se
AFib prevalence
~30%
~50%+
Common phenotypes
Ischemic, dilated CM
HTN, obese, amyloid
HFrEF vs HFpEF — clinical and management differences. The 4-pillar GDMT framework applies fully to HFrEF; in HFpEF, SGLT2i (class 2a) and MRAs reduce HF hospitalization, but no drug has a proven mortality benefit.
Treatment
First-line
SGLT2 inhibitor — dapagliflozin or empagliflozin; class 2a in the 2022 AHA/ACC/HFSA guideline (class I in the 2023 ESC focused update) and foundational alongside finerenone in the 2026 ACC Expert Consensus Decision Pathway; reduces HF hospitalization without a proven mortality benefit (EMPEROR-Preserved, DELIVER)
Finerenone (nonsteroidal MRA) — foundational alongside the SGLT2 inhibitor in the 2026 ACC Expert Consensus Decision Pathway and preferred over spironolactone; reduced the composite of worsening HF events and CV death in HF with LVEF ≥40% (FINEARTS-HF) and is FDA-approved for this indication; no proven all-cause mortality benefit; monitor K+ and Cr
Loop diuretic for volume overload — furosemide, torsemide, or bumetanide; titrated to symptom relief; avoid overdiuresis (preload-dependent ventricles drop CO)
Aggressive treatment of comorbidities: HTN, AFib, CAD, sleep apnea, weight loss
ARNI (sacubitril-valsartan) — may be considered (class 2b) to reduce HF hospitalization, mainly in HFmrEF and at the lower end of the HFpEF EF range (PARAGON-HF)
Spironolactone — the alternative MRA when finerenone is not used; may be considered (class 2b, TOPCAT), mainly at the lower end of the EF range; monitor K+ and Cr
Second-line / adjunct
Address phenotype-specific drivers:
• Amyloid → tafamidis if transthyretin amyloid confirmed
• AFib → rate control and anticoagulation per CHA2DS2-VASc; consider rhythm strategy
• Obesity (BMI ≥30) → structured weight loss plus semaglutide or tirzepatide (recommended in the 2026 ACC Expert Consensus Decision Pathway); semaglutide showed symptom benefit in STEP-HFpEF
• Hypertension → strict BP control (<130/80)
Complications
Recurrent HF hospitalizations
Atrial fibrillation (50%+ lifetime incidence)
Pulmonary hypertension, right HF
Renal dysfunction
PANCE pearls
ACEi, ARB, and traditional beta-blockers do NOT have the same mortality benefit in HFpEF as in HFrEF. Don't extrapolate.
Always screen elderly HFpEF patients for cardiac amyloid — occult wild-type ATTR amyloid is found in ~13% of older HFpEF patients with LV hypertrophy.
Diuretics provide symptomatic relief only — don't overdiurese (pre-load dependent ventricles drop CO with volume depletion).
AFib is common and poorly tolerated in HFpEF (the stiff ventricle depends on atrial kick and adequate diastolic filling time); control rate or rhythm, anticoagulate per CHA2DS2-VASc, and consider rhythm control, including catheter ablation, in selected symptomatic patients.
Acute decompensated HFpEF: IV loop diuretic (oral absorption is unreliable with gut edema) plus IV nitroglycerin when hypertensive with pulmonary congestion; avoid inotropes unless there is shock (tachycardia shortens diastolic filling of the stiff ventricle).
References
AHA/ACC/HFSA 2022 — 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure (Heidenreich et al., Circulation 2022)
EMPEROR-Preserved — Empagliflozin in Heart Failure with a Preserved Ejection Fraction (Anker et al., NEJM 2021)
DELIVER — Dapagliflozin in Heart Failure with Mildly Reduced or Preserved EF (Solomon et al., NEJM 2022)
PARAGON-HF — Angiotensin-Neprilysin Inhibition in HFpEF (Solomon et al., NEJM 2019)
STEP-HFpEF — Semaglutide in Patients with Obesity-Related HFpEF (Kosiborod et al., NEJM 2023)
FINEARTS-HF — Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (Solomon et al., NEJM 2024)
ESC 2023 Focused Update — 2023 Focused Update of the 2021 ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure (McDonagh et al., Eur Heart J 2023)
ACC 2026 ECDP — 2026 ACC Expert Consensus Decision Pathway on the Management of HFpEF (J Am Coll Cardiol 2026; doi:10.1016/j.jacc.2026.06.018)
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