What are the differences in management approaches for patients with heart failure with preserved ejection fraction (HFPEF) versus heart failure with reduced ejection fraction (HFrEF)?

Management Differences Between HFpEF and HFrEF

Core Pharmacological Differences

HFrEF has four foundational medication classes with proven mortality benefit (ACE inhibitors/ARBs/ARNi, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors), while HFpEF management centers primarily on SGLT2 inhibitors for reducing hospitalizations without clear mortality benefit, plus aggressive comorbidity treatment. 1

HFrEF Guideline-Directed Medical Therapy (GDMT)

The following medications reduce mortality and must be initiated in all eligible HFrEF patients (LVEF ≤40%):

• ARNi (sacubitril/valsartan) is preferred over ACE inhibitors or ARBs as first-line therapy, providing superior mortality reduction 1
• Beta-blockers (carvedilol, metoprolol succinate, or bisoprolol) reduce mortality and are Class I recommendations 1
• Mineralocorticoid receptor antagonists (spironolactone or eplerenone) for NYHA class II-IV symptoms reduce mortality 1
• SGLT2 inhibitors (dapagliflozin or empagliflozin) reduce cardiovascular death and HF hospitalizations 1
• Hydralazine plus isosorbide dinitrate specifically for self-identified African American patients with NYHA class III-IV on optimal therapy 1

HFpEF Medical Therapy

The therapeutic landscape differs dramatically for HFpEF (LVEF ≥50%):

• SGLT2 inhibitors (dapagliflozin 10 mg or empagliflozin 10 mg daily) are the only medications with proven benefit, reducing the composite endpoint of cardiovascular death and HF hospitalizations by 18-21% 2, 1
• Diuretics for congestion management are essential for symptom relief but do not modify disease progression 1, 2
• ARNi may reduce hospitalizations, particularly in patients with LVEF closer to 50% (lower end of preserved range) 1
• Mineralocorticoid receptor antagonists may provide benefit in patients with LVEF 40-50% but evidence is weaker than in HFrEF 1, 2
• ARBs may decrease hospitalizations in select patients with lower-end preserved LVEF 1

Device Therapy Differences

HFrEF Device Indications

• Implantable cardioverter-defibrillators (ICDs) for primary prevention in patients with LVEF ≤35% and NYHA class II-III symptoms reduce sudden cardiac death 1
• Cardiac resynchronization therapy (CRT) for patients with LVEF ≤35%, sinus rhythm, left bundle branch block with QRS ≥150 ms, and NYHA class II-IV improves mortality and symptoms 1

HFpEF Device Considerations

• No device therapies have proven mortality or morbidity benefit in HFpEF 3
• Device consideration is limited to standard indications (e.g., bradycardia requiring pacing) unrelated to HF management

Diagnostic Approach Differences

HFrEF Diagnosis

• Echocardiography demonstrating LVEF ≤40% with HF symptoms establishes the diagnosis 3
• Ischemic vs. non-ischemic etiology determination via coronary CTA, stress testing, or cardiac MRI guides revascularization decisions 1
• Natriuretic peptides support diagnosis but are not required when LVEF is clearly reduced

HFpEF Diagnosis

HFpEF diagnosis requires a two-step approach beyond just demonstrating preserved LVEF 2:

• Confirm HF symptoms with LVEF ≥50% on echocardiography 3
• Elevated natriuretic peptides (BNP >35 pg/mL or NT-proBNP >125 pg/mL ambulatory) 1
• Evidence of increased LV filling pressures: E/e' ≥15 or invasive hemodynamics 1
• Structural heart disease: increased left atrial volume index or increased LV mass index 1
• Exercise stress echocardiography with diastolic parameters if diagnosis remains uncertain after initial evaluation 1, 2
• Rule out HFpEF mimics including cardiac amyloidosis, hypertrophic cardiomyopathy, and constrictive pericarditis, as these require entirely different treatment strategies 2

Comorbidity Management Emphasis

HFrEF Comorbidity Approach

• Comorbidities are important but primary focus remains on GDMT optimization for mortality reduction 3
• Atrial fibrillation management with rate control and anticoagulation 1
• Blood pressure control as tolerated while maximizing GDMT doses

HFpEF Comorbidity Approach

Aggressive comorbidity management is central to HFpEF treatment strategy because non-cardiac comorbidities drive substantial morbidity and mortality 4, 5:

• Achieve blood pressure target <130/80 mmHg as hypertension is a primary driver of HFpEF pathophysiology 2
• Control ventricular rate to 60-100 bpm in atrial fibrillation using beta-blockers or non-dihydropyridine calcium channel blockers 2
• Weight reduction in obese patients (BMI >30 kg/m²) as obesity is a major contributor to HFpEF pathophysiology 2, 6
• Diabetes management is particularly important as diabetes predisposes more strongly to HFpEF than HFrEF 6, 5
• Pulmonary disease treatment given higher prevalence in HFpEF 5

Non-Pharmacological Interventions

HFrEF Non-Pharmacological Management

• Sodium restriction <2-3 g/day 2
• Fluid restriction in advanced HF
• Cardiac rehabilitation when appropriate

HFpEF Non-Pharmacological Management

Exercise training is a Class I recommendation with large, clinically meaningful improvements in exercise capacity and quality of life 2:

• Supervised exercise training programs consistently demonstrate benefit in HFpEF 2
• Sodium restriction to <2-3 g/day to reduce fluid retention 2
• Weight reduction programs for obese patients 2

Intermediate Category: HFmrEF (LVEF 41-49%)

HFmrEF represents a dynamic trajectory between HFrEF and HFpEF 3, 1:

• Patients may be improving from HFrEF or deteriorating from HFpEF 3
• One EF measurement is inadequate; trajectory over time is critical 3
• Treatment approach resembles HFrEF GDMT, particularly for those with improving EF from lower baseline 1
• MRAs and ARNi may have greater benefit in HFmrEF compared to HFpEF with LVEF ≥50% 1

Critical Pitfall: HF with Improved EF (HFimpEF)

Patients with HFrEF who improve LVEF to >40% must continue HFrEF GDMT to prevent relapse, even if asymptomatic 1:

• This is a Class I recommendation from the American College of Cardiology 1
• Improvement in LVEF does not mean full myocardial recovery 3
• Cardiac structural abnormalities persist in most patients 3
• Discontinuing GDMT leads to EF deterioration and clinical decompensation

Prognosis and Outcomes Differences

• Cardiac causes account for a smaller proportion of hospitalizations and deaths as LVEF increases 4
• Non-cardiac comorbidities drive outcomes more in HFpEF than HFrEF 4, 5
• Both conditions carry similar symptom burden and quality of life impairment despite different therapeutic options 7

Sex-Specific Considerations

Women have higher prevalence of HFpEF 3:

• Women have higher EFs and more preserved LV global longitudinal strain compared to men 3
• History of pre-eclampsia increases risk for subsequent HFpEF hospitalization 3
• Female sex independently predicts HFpEF over HFrEF 8

Clinical Features Distinguishing HFpEF from HFrEF

At presentation, specific clinical features discriminate between subtypes 8:

• HFrEF predictors: male sex, coronary heart disease, higher heart rate, higher potassium, left bundle branch block, ischemic ECG changes 8
• HFpEF predictors: female sex, atrial fibrillation, older age, higher body mass index, smoking 6, 8
• These features predict HF subtype with good discrimination (c-statistic 0.75-0.78) 8