2023 ACC Expert Consensus Decision Pathway on HFpEF

What's New in HFpEF Management (2023)

The 2023 ACC Consensus Pathway represents a major update to HFpEF diagnosis and treatment, emphasizing evidence-based pharmacologic and nonpharmacologic interventions:

• SGLT2 Inhibitors as cornerstone therapy — Now Class 1 recommendation for all HFpEF patients; proven to reduce hospitalization and improve symptoms (EMPEROR-Preserved, DELIVER trials)
• Refined diagnostic algorithms — H2FPEF score (simple, bedside) and HFA-PEFF algorithm (comprehensive); sex-specific diagnostic considerations for women
• GLP-1 RA for obesity-HFpEF — STEP-HFpEF trial demonstrates sustained weight loss and symptomatic improvement with semaglutide in obese HFpEF patients
• Phenotype-directed comorbidity management — Integrated approach to hypertension, diabetes, obesity, atrial fibrillation, CKD, sleep apnea, CAD, pulmonary hypertension
• Multidisciplinary care model — Team-based approach with structured referral pathways (CHECK-IN to cardiologist; INHALE to HF specialist)
• Early palliative care integration — Emphasis on symptom management, quality-of-life focus, and advance care planning

HFpEF Definition & Diagnostic Criteria

Universal Definition of Heart Failure

Heart failure is defined by symptoms and/or signs of HF caused by structural or functional cardiac abnormality, with at least one of:

1. Elevated natriuretic peptides: BNP ≥35 pg/mL, NT-proBNP ≥125 pg/mL (or ≥100 pg/mL in atrial fibrillation)
2. Objective evidence of cardiogenic congestion: Pulmonary or systemic (elevated JVP, rales, edema, elevated LVEDP)

HFpEF-Specific Criteria

LVEF ≥50% PLUS one of the following:

• Elevated filling pressures (natriuretic peptides): BNP ≥35 or NT-proBNP ≥125 pg/mL
• Elevated invasive LV end-diastolic pressure: LVEDP >16 mm Hg or PA wedge pressure >12 mm Hg
• Diastolic dysfunction on echo: E/e' >9, LA volume index >34 mL/m², or increased LV wall thickness

Diagnostic Approach to HFpEF

Four-Step Clinical Pathway

H2FPEF Diagnostic Score

Simple 6-component scoring system derived from invasive hemodynamic reference standard. Each component yields 1–3 points. Score ≥6 points = high probability HFpEF.

HFA-PEFF Diagnostic Algorithm

Comprehensive diagnostic framework from Heart Failure Association of the European Society of Cardiology. Four-step sequential assessment: Pretest probability → Echo/natriuretic peptides → Functional testing → Final etiology. More nuanced than H2FPEF; incorporates major/minor criteria with point-based scoring.

HFA-PEFF Four-Step Approach

HFA-PEFF Scoring

≥25 points: HFpEF diagnosis confirmed. Major criteria (2 pts each): abnormal E/e', LA enlargement, LV hypertrophy, elevated natriuretic peptides. Minor criteria (1 pt): abnormal diastolic dysfunction measures, reduced peak VO₂, elevated LV filling pressure on stress test.

HFpEF Phenotypes & Targeted Management

HFpEF is heterogeneous disease with distinct phenotypes driving different pathophysiology and therapy responses. Identify predominant phenotype for personalized management.

Obesity-HFpEF (Most Common, ~80%)

• Pathophysiology: Increased plasma volume, concentric LV remodeling, elevated epicardial fat, pericardial restraint, right ventricular dilatation
• Management: SGLT2i (dapagliflozin, empagliflozin), GLP-1 RA (semaglutide 2.4mg weekly), weight loss goal 5–10%, aerobic exercise ≥150 min/week, caloric restriction
• Evidence: STEP-HFpEF: Semaglutide achieved >10% weight loss, improved KCCQ scores

Hypertensive HFpEF

• Pathophysiology: LV hypertrophy, concentric remodeling, diastolic dysfunction substrate
• Management: Intensive BP control (target SBP <130 mm Hg); ACEi/ARB, beta-blockers, CCBs, thiazides, MRA
• Benefit: Every 5 mm Hg SBP reduction associated with fewer HF events

Atrial Fibrillation–HFpEF (50–80% prevalence)

• Bidirectional relationship: AF causes HFpEF; HFpEF predisposes to AF; shared substrates (fibrosis, inflammation)
• Rate control: Target HR <110 bpm; beta-blockers, diltiazem, verapamil
• Anticoagulation: CHADS2-VASc ≥1 → anticoagulation indicated (nearly all HFpEF with AF); DOAC preferred over warfarin
• GDMT: SGLT2i, MRA, diuretics for HFpEF control

Coronary Artery Disease–HFpEF (>50% incidence)

• Mechanism: Epicardial stenosis, microvascular dysfunction, subendocardial ischemia
• Evaluation: Stress imaging, angiography if symptomatic or high-risk features
• Management: Revascularization if significant stenosis; GDMT optimization (SGLT2i, ACEi/ARB, beta-blockers)

Pulmonary Hypertension–HFpEF

• Etiology: Group 2 (left heart disease–related PH, most common), Group 3 (respiratory), Group 4 (thromboembolic), Group 5 (miscellaneous)
• Management: Optimize HFpEF GDMT; PH-specific therapies (phosphodiesterase-5i, endothelin antagonists) limited evidence

Cardiac Amyloidosis-HFpEF

• Diagnosis: Monoclonal protein screen, technetium-99m pyrophosphate imaging, biopsy (endomyocardial or subcutaneous fat)
• ATTR cardiac amyloidosis: Transthyretin stabilizer tafamidis slows HF progression, improves outcomes (ATTR-ACT trial)
• Management: Diuretics carefully; avoid excessive volume depletion; monitor kidney function

Hypertrophic Cardiomyopathy (HCM)

• Features: LVEF preserved, LV hypertrophy, SAM, mitral regurgitation, LV outflow tract obstruction
• Management: Beta-blockers, non-dihydropyridine CCBs; avoid diuretics if possible; invasive septal reduction if LVOT obstruction and refractory symptoms
• Screening: Family screening essential given genetic inheritance

Constrictive Pericarditis & Restrictive Cardiomyopathy

• Diagnosis: Cardiac catheterization (dip-and-plateau pattern), echo (pericardial thickening, septal bounce), CMR
• Management: Pericardiectomy for constrictive; supportive care for restrictive

SGLT2 Inhibitors in HFpEF

Class 1 SGLT2 inhibitors recommended for ALL HFpEF patients to reduce hospitalization, improve symptoms, and enhance quality of life.

Clinical Evidence

• EMPEROR-Preserved (Empagliflozin, 10mg daily): LVEF ≥40%; 27% reduction in CV death or HF hospitalization; consistent benefit across EF spectrum
• DELIVER (Dapagliflozin, 10mg daily): EF 41–≤49%; reduced HF hospitalization in HFmrEF/HFpEF cohorts
• Meta-analysis: SGLT2i reduce HF hospitalization/CV death composite by ~20% in HFpEF; benefits independent of diabetes status or glucose control

Recommended Dosing

Safety & Special Considerations

• Acute kidney injury: Risk in dehydration, aggressive diuresis, or eGFR <20; dose carefully in CKD
• Genital infections: SGLT2 increase glucosuria; counsel on hygiene; incidence ~10%
• Diabetic ketoacidosis (DKA): Rare but serious; contraindicated in type 1 diabetes, active DKA history; educate on symptoms
• Volume depletion: May reduce diuretic requirement; monitor orthostasis and hypotension
• Amputation: Not increased in HF trials (unlike diabetes trials); benefit-risk favorable in HFpEF

Diuretic Management in HFpEF

Class 1 Loop diuretics essential for symptom relief and volume management. Titrate to euvolemia; use minimum effective dose to minimize adverse effects.

Loop Diuretics

• Agents: Furosemide (40–80 mg daily), bumetanide (0.5–1 mg daily), torsemide (10–20 mg daily; preferred for superior bioavailability)
• Titration: Increase dose if orthopnea, rales, JVD, edema persist; decrease if euvolemic and low fill pressures
• Monitoring: Daily weights (alert if gain >2–3 lbs/day); electrolytes (K+, Na+, Cl−, HCO3−); renal function; orthostatic BP

Dosing Strategy by Clinical Status

• Acute decompensation: IV loop diuretic; target negative 0.5–1.0 kg/day; transition to oral when euvolemic
• Chronic outpatient: Lowest dose maintaining euvolemia; many HFpEF respond to lower doses than HFrEF
• CKD Stage 4–5: Higher doses often required; coordinate with nephrology for kidney protection strategies

Mineralocorticoid Receptor Antagonists (MRAs)

Class 2a Consider spironolactone or eplerenone in HFpEF patients to improve diastolic function and reduce HF hospitalization risk.

Mechanism & Evidence

• TOPCAT Trial: Spironolactone 15–45 mg daily in LVEF ≥45%; modest 20% reduction in HF hospitalization; greater benefit in North America vs. Russia/Georgia cohorts
• Mechanism: Aldosterone antagonism reduces cardiac fibrosis, improves diastolic relaxation, decreases atrial fibrillation burden, reduces inflammation

Dosing & Monitoring

Safety & Contraindications

• Hyperkalemia: Risk if K+ >5.0 mEq/L, eGFR <30, or concomitant ACEi/ARB/ARNI without close K+ monitoring. Use careful drug combinations and regular labs
• Contraindications: K+ >5.0 mEq/L at baseline, eGFR <30, end-stage renal disease, acute kidney injury
• Gynecomastia: Spironolactone 10–20%; eplerenone preferred if problematic
• Drug interactions: NSAIDs, trimethoprim, ACEi/ARB increase hyperkalemia risk

GLP-1 Receptor Agonists for Obesity-HFpEF

Class 2b Consider GLP-1 RA (semaglutide) in obese HFpEF patients for weight loss and symptom improvement.

Evidence: STEP-HFpEF Trial

• Design: 529 obese HFpEF patients randomized to semaglutide 2.4 mg SC weekly vs. placebo
• Results: Semaglutide achieved sustained weight loss (>10% body weight reduction), improved KCCQ (symptom score) by ~5–8 points, improved 6-minute walk distance
• Safety: Gastrointestinal side effects (nausea, vomiting) common initially; adjustable with dose titration

Dosing & Administration

• Semaglutide: Start 0.25 mg SC weekly; increase by 0.25 mg every 4 weeks to target 2.4 mg weekly (maintenance: 2.4 mg weekly)
• Timing: Begin after stable GDMT; reassess diuretic requirement as weight decreases
• Monitoring: Weekly weights, volume status, kidney function; adjust diuretics downward if >5 lbs weight loss observed

Special Considerations

• Volume depletion: GLP-1 RA + diuretics carry risk of acute kidney injury, hypotension, syncope; educate on hydration
• Gastrointestinal symptoms: Nausea, vomiting, constipation, diarrhea; often improve with slower titration or dietary modification
• Pancreatitis: Rare but serious; counsel on symptoms (epigastric pain, elevated amylase)
• Contraindications: Personal history medullary thyroid cancer, MEN syndrome Type 2; relative: severe renal/hepatic disease

Comorbidity Management in HFpEF

Hypertension

Class 1 Blood pressure control foundational. Target <130/80 mm Hg (older adults may tolerate <140/90). Antihypertensive agents: ACEi/ARB, beta-blockers, CCBs (diltiazem, verapamil preferred), thiazides.

• Note: Many HFpEF require ≥2 agents for BP control; avoid sudden withdrawal (rebound HTN)
• Caution: Avoid hypotension precipitating acute HF decompensation; titrate GDMT (ACEi/ARB/ARNi) slowly

Diabetes Mellitus

Class 1 SGLT2i first-line for all HFpEF with diabetes; benefits independent of glucose control. GLP-1 RA if obesity present. Target HbA1c 7–8% (individualize).

• Agents: Metformin (safe if eGFR >30); avoid if eGFR <30. DPP-4i neutral on HF. TZD caution (fluid retention).
• Dosing: SGLT2i 10mg daily, GLP-1 RA titrate to 2.4mg weekly

Chronic Kidney Disease (CKD)

Class 1 SGLT2i slow CKD progression, reduce ESRD risk. RAAS inhibitors (ACEi/ARB) protective; coordinate with nephrology for monitoring.

• eGFR ≥30: SGLT2i, ACEi/ARB, ARNI, MRA with close K+ monitoring
• eGFR 15–29: SGLT2i (if tolerated), RAAS inhibitors with caution, diuretics adjusted
• eGFR <15 (Stage 5): SGLT2i contraindicated; focus diuretics, fluid restriction, nephrology co-management

Obstructive Sleep Apnea (OSA)

Class 2b Screen with STOP-BANG; treat OSA with CPAP to improve symptoms, reduce AF burden, enhance quality of life. Prevalence 55–80% in HFpEF.

Atrial Fibrillation

See dedicated section below.

Coronary Artery Disease

• Prevalence: >50% of HFpEF; evaluate with stress imaging or angiography if anginal symptoms
• Management: Revascularization if significant stenosis; GDMT optimization (SGLT2i, ACEi/ARB, beta-blockers)

Anemia & Iron Deficiency

• Assessment: CBC, ferritin, TSAT; distinguish iron deficiency from anemia of chronic disease
• Iron replacement: IV iron if TSAT <20% or ferritin <100; may improve exercise capacity and symptoms

Pulmonary Hypertension

• Identify etiology: Group 2 (left heart–related, most common); optimize HFpEF GDMT first
• PH-specific agents: Limited evidence; phosphodiesterase-5i or endothelin antagonist may be considered in select cases

Atrial Fibrillation in HFpEF

Atrial fibrillation present in 50–80% HFpEF; bidirectional relationship with shared pathophysiologic substrates. Management focuses on rate control, anticoagulation, and GDMT optimization.

Rate Control Strategy

• Target: Ventricular rate <110 bpm at rest (lenient strategy per 2019 ACC/AHA AF guidelines acceptable)
• First-line: Beta-blockers (metoprolol, carvedilol, bisoprolol) or non-dihydropyridine CCBs (diltiazem, verapamil)
• Dosing: Titrate to symptom control and HR target; avoid excessive beta-blockade if low BP

Anticoagulation

Class 1 Anticoagulation if CHA2DS2-VASc score ≥1 (nearly all HFpEF with AF meet threshold).

• DOAC preferred: Apixaban 5mg BID, edoxaban 60mg daily, dabigatran 110–150mg BID, rivaroxaban 20mg daily (more convenient, better adherence than warfarin)
• Monitoring: Renal function at baseline, 1 year, then as clinically indicated; HAS-BLED score assesses bleeding risk

Rhythm Control

• Rhythm vs. Rate Control: Similar long-term outcomes in recent trials; choose based on symptom burden and HF stability
• Antiarrhythmic agents: Flecainide, sotalol, amiodarone; amiodarone most efficacious but toxicity concern (thyroid, lung, liver, neuropathy)

Device Therapy

• CRT: Not beneficial in AF-only HFpEF (LVEF ≥40%); no mortality reduction
• ICD: Primary prevention only if EF drops <35% (rare in HFpEF)

Exercise Training & Lifestyle Modifications

Structured Exercise Training

Class 2a Aerobic and resistance exercise improves peak VO₂, quality of life, exercise tolerance, and functional capacity in HFpEF.

• Aerobic: Brisk walking, cycling, swimming ≥150 min/week moderate intensity or 75 min/week vigorous
• Resistance: 2–3 sessions/week strengthens muscle, improves quality of life; safe and effective in HFpEF
• Cardiac rehabilitation: Recommended post-hospitalization; improves adherence, exercise capacity, and outcomes

Weight Loss & Caloric Restriction

• Target: 5–10% weight loss in overweight/obese; greater reductions (15–20%) yield greater symptom improvement
• Mechanisms: Reduces LV filling pressures, improves diastolic function, lowers BP, decreases inflammatory markers
• Methods: Caloric restriction (500–1000 kcal/day deficit), structured diet program, GLP-1 RA adjunct

Dietary Modifications

• Sodium: Limit to <3 g/day; lower intake (<2.3 g/day) may improve symptoms in select patients (evidence mixed)
• Fluid: 1.5–2 L/day; individualize based on volume status, sodium intake, diuretic requirement
• Mediterranean diet: Plant-based, lean protein, olive oil; associated with improved HF outcomes

Substance Use Counseling

• Alcohol: Limit to moderate intake (≤1 drink/day women, ≤2 men); excessive use accelerates HF progression
• Smoking: Cessation crucial; reduces CV risk, improves exercise tolerance, improves symptoms
• NSAIDs: Avoid if possible; increase HF hospitalization risk, worsen renal function

Multidisciplinary Care & Referral Pathways

CHECK-IN: Primary Care → Cardiology

Acronym to identify HFpEF patients needing cardiology specialist referral:

• C: Collaboration needed to manage multiple comorbidities (HTN, DM, CAD, CKD)
• H: High-risk features (HF hospitalizations, pulmonary HTN, complex hemodynamics)
• E: Extensive diagnostic evaluation needed (stress testing, invasive hemodynamics, CMR)
• C: Cardiorenal syndrome or need for cardioprotective drug expertise
• K: Knowledge of HFpEF mimics (HCM, amyloidosis, pericardial disease) required
• I: Increased need for diuretic optimization or inotropic support
• N: NYHA Class III–IV symptoms or recent hospitalization

INHALE: Cardiologist → HF Specialist

Referral to advanced HF/heart transplant specialist when:

• I: In need of diagnosis (infiltrative cardiomyopathy, complex hemodynamics, diagnostic uncertainty)
• N: Nonresponsive to medical therapy or diuretics ineffective
• H: Hospitalized frequently for HF decompensation
• A: Acute or chronic end-organ dysfunction (cardiorenal, hepatorenal, cardiac cachexia)
• L: Low blood pressure limiting GDMT optimization
• E: Evidence of rare/unusual cardiomyopathy (amyloidosis, HCM, constrictive pericarditis, myocarditis)

Core Multidisciplinary Team

• Cardiologist: Diagnosis, GDMT optimization, risk stratification
• HF nurse coordinator: Symptom monitoring, patient/caregiver education, transitions of care
• Clinical pharmacist: Medication reconciliation, drug-drug interactions, adherence optimization, side effect management
• Registered dietitian: Sodium/fluid counseling, weight management, nutrition education
• Social worker: Psychosocial support, resource navigation, financial counseling, caregiver support
• Geriatrician: Frailty assessment, medication deprescribing, goals-of-care conversations (if age >75)
• Comorbidity specialists: Endocrinologist (diabetes), nephrologist (CKD), pulmonologist (PAH, OSA), sleep medicine (sleep apnea)
• Palliative care: Early integration for symptom management, quality-of-life focus, advance care planning

Clinical Decision Support Tools & Calculators

Interactive web-based calculators to support diagnosis, risk stratification, and treatment optimization in HFpEF management.

Clinical Pearl Summary: Do & Don't in HFpEF

Disclaimer: This quick reference is based on the 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction (Kittleson MM, et al. J Am Coll Cardiol. 2023;81:1835–1878). It is intended for medical professionals and should supplement, not replace, clinical judgment or the full guideline text. Always consult the complete publication and individualize management to each patient. For full citations and details, see the original guideline at https://doi.org/10.1016/j.jacc.2023.03.393.