HF symptoms with LVEF ≥50% from diastolic dysfunction — now has class I medical therapy.
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?
ASGLT2 inhibitors
BAldosterone antagonists
CAngiotensin-converting enzyme inhibitors
DBeta-adrenergic blockers
Reveal answer & full explanation
Correct answer: A — SGLT2 inhibitors
ASGLT2 inhibitors✓
BAldosterone antagonists
CAngiotensin-converting enzyme inhibitors
DBeta-adrenergic blockers
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 — Spironolactone produced only a modest, borderline hospitalization signal in HFpEF (TOPCAT), weaker than SGLT2 inhibitors; choosing it is premature closure on a familiar HF drug
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
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?
ASpironolactone
BACE inhibitor plus beta-blocker
CDigoxin
DSGLT2 inhibitor
Reveal answer & full explanation
Correct answer: D — SGLT2 inhibitor
ASpironolactone
BACE inhibitor plus beta-blocker
CDigoxin
DSGLT2 inhibitor✓
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 showed significant reduction in heart failure (HF) hospitalizations and cardiovascular (CV) death in HFpEF regardless of ejection fraction (EF).
SGLT2 inhibitors now carry a class IIa recommendation for HFpEF.
Why the others are wrong
A) Spironolactone — TOPCAT trial showed borderline benefit in HFpEF with EF below 57%; not a proven first-line agent.
B) ACE inhibitor plus beta-blocker — angiotensin-converting enzyme inhibitor (ACEi) and beta-blockers have no proven mortality benefit in HFpEF.
C) Digoxin — no established 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; manage with full 4-pillar GDMT
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
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
GDMT (mortality benefit)
ARNI + BB + MRA + SGLT2i
SGLT2i (class I)
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; only SGLT2i carries class I in HFpEF.
Treatment
First-line
SGLT2 inhibitor — dapagliflozin or empagliflozin; class I recommendation across full EF range (EMPEROR-Preserved, DELIVER); reduces HF hospitalization
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) — reasonable, especially in HFmrEF and lower end of HFpEF (PARAGON-HF subgroup)
MRA — spironolactone or eplerenone; reasonable per TOPCAT subgroup analysis, especially with elevated BNP
Second-line / adjunct
Address phenotype-specific drivers:
• Amyloid → tafamidis if transthyretin amyloid confirmed
• AFib → rate control and anticoagulation per CHA2DS2-VASc; consider rhythm strategy
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