What is the difference in management between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF)?

Management Differences Between HFpEF and HFrEF

The fundamental difference is that HFrEF has robust evidence-based guideline-directed medical therapy (GDMT) proven to reduce mortality, while HFpEF management centers on SGLT2 inhibitors for prognostic benefit, diuretics for symptom relief, and aggressive comorbidity control—with most traditional HFrEF therapies lacking proven benefit in HFpEF. 1, 2

HFrEF Management: Comprehensive Mortality-Reducing GDMT

Core Pharmacotherapy (All Class I Recommendations)

• Initiate all four pillars of GDMT to achieve substantial mortality and hospitalization reduction 1:
  • ACE inhibitors/ARBs or preferably ARNIs (sacubitril/valsartan): ARNIs reduce cardiovascular death or HF hospitalization by 20% compared to ACE inhibitors in HFrEF 3
  • Beta-blockers (carvedilol, metoprolol succinate, bisoprolol): Reduce mortality by approximately 35% 1
  • Mineralocorticoid receptor antagonists (spironolactone, eplerenone): Reduce mortality by 30% 1
  • SGLT2 inhibitors (dapagliflozin, empagliflozin): Reduce cardiovascular death and HF hospitalization by 25% 4

Additional HFrEF-Specific Therapies

• Ivabradine for patients in sinus rhythm with heart rate ≥70 bpm despite beta-blocker optimization 4
• Vericiguat for patients with recent decompensation to further reduce cardiovascular death and HF hospitalization 4
• Digitoxin in advanced HFrEF reduces mortality and hospitalizations based on DIGIT-HF 4
• Intravenous iron supplementation for iron deficiency improves exercise capacity and reduces hospitalization risk, especially post-decompensation 4
• Device therapy (ICD, CRT) based on QRS duration and LVEF thresholds 1

Rapid Implementation Strategy

• Implement all four GDMT pillars rapidly and comprehensively—this substantially improves prognosis in HFrEF 4
• Titrate medications to target or maximally tolerated doses 1

HFpEF Management: Limited Disease-Modifying Options

Disease-Modifying Pharmacotherapy (The Only Proven Therapies)

• SGLT2 inhibitors are the cornerstone: Initiate dapagliflozin 10 mg daily or empagliflozin 10 mg daily immediately upon diagnosis 1, 2

  • Dapagliflozin reduced composite endpoint of worsening HF and cardiovascular death by 18% (HR 0.82) and HF hospitalizations by 23% (HR 0.77) in DELIVER 2
  • Empagliflozin reduced HF hospitalization or cardiovascular death by 21% (HR 0.79) in EMPEROR-PRESERVED 2
  • These are the only medications proven to reduce cardiovascular death and HF hospitalizations in HFpEF 2

• Mineralocorticoid receptor antagonists have limited evidence: Consider spironolactone 12.5-25 mg daily particularly in patients with LVEF 40-50% or persistent symptoms despite SGLT2 inhibitors 2

  • Evidence is substantially weaker than in HFrEF 1

• Finerenone (non-steroidal MRA) recently showed promise in FINEARTS-HF, reducing cardiovascular death/hospitalizations in HFpEF 4

Critical Distinction: What NOT to Use in HFpEF

• ARNIs show marginal benefit: Sacubitril/valsartan demonstrated only numerical reduction in HFpEF (RR 0.87; 95% CI [0.75,1.01], p=0.06) in PARAGON-HF, driven primarily by HF hospitalizations, not mortality 3

  • Treatment effect was greater in patients with LVEF below normal, suggesting benefit diminishes as EF increases 3

• Traditional HFrEF therapies lack proven efficacy: ACE inhibitors, ARBs (without neprilysin inhibition), and beta-blockers have not demonstrated mortality benefit in HFpEF 1, 5

  • Use these agents only when indicated for comorbidities (hypertension, atrial fibrillation, coronary disease), not for HFpEF itself 2, 5

Symptom Management

• Loop diuretics for congestion: Furosemide 20-40 mg daily, bumetanide 0.5-1.0 mg daily, or torasemide 5-10 mg daily 1, 2
  • Titrate to lowest effective dose maintaining euvolemia—excessive diuresis causes hypotension, renal dysfunction, and impaired tolerance of other medications 2
  • No prognostic benefit, only symptomatic relief 1, 5
  • Add thiazide (metolazone 2.5 mg) only in refractory cases with eGFR >30 mL/min 2

Comorbidity Management: More Critical in HFpEF

Hypertension Control

• HFpEF: Achieve BP <130/80 mmHg as hypertension is a primary driver of HFpEF pathophysiology 2

  • Prioritize ACE inhibitors, ARBs, or ARNIs combined with diuretics 2
  • Hypertension treatment reduces incident HF risk by approximately 50% 1

• HFrEF: Use GDMT agents that simultaneously treat hypertension and reduce mortality 1

Atrial Fibrillation Management

• HFpEF: Control ventricular rate to 60-100 bpm using beta-blockers or non-dihydropyridine calcium channel blockers (diltiazem, verapamil) 2

  • Anticoagulate based on CHA₂DS₂-VASc score 2
  • AF is present in 52-83% of HFpEF patients and contributes to RV dysfunction 6

• HFrEF: Use beta-blockers for rate control (dual benefit for HF and AF) 1

  • Avoid non-dihydropyridine calcium channel blockers due to negative inotropic effects 1

Obesity and Metabolic Management

• HFpEF: Weight reduction in patients with BMI >30 kg/m² is critical as obesity is a major contributor to HFpEF pathophysiology 2

  • GLP-1 receptor agonists are gaining importance in obese HFpEF patients, improving quality of life and reducing HF-related events 4

• HFrEF: Weight management important but less central to pathophysiology 7

Non-Pharmacological Interventions

Exercise Training

• Both HFpEF and HFrEF: Supervised exercise training programs are Class I recommendation 1, 2
  • Consistently demonstrate large, clinically meaningful improvements in exercise capacity and quality of life 1, 2
  • HFpEF patients present with similar or greater functional impairments (lower 6MWT distance: 299.6m vs 350.6m, lower BERG balance scores) but achieve similar or greater improvements following cardiac rehabilitation compared to HFrEF 8

Dietary Modifications

• Both subtypes: Restrict sodium intake to <2-3 g/day to reduce fluid retention and congestion 2, 5

Diagnostic Considerations

Ejection Fraction Thresholds

• HFrEF: LVEF ≤40% 1
• HFmrEF: LVEF 41-49% (intermediate group with characteristics similar to HFpEF) 1
• HFpEF: LVEF ≥50% 1

Additional Diagnostic Requirements for HFpEF

• Must have: Elevated natriuretic peptides AND evidence of structural heart disease or diastolic dysfunction on echocardiography 1, 2
• Rule out mimics: Cardiac amyloidosis, hypertrophic cardiomyopathy, constrictive pericarditis—these require entirely different treatment strategies 2
• Use diagnostic scores (H2FPEF or HFA-PEFF) when initial investigations are equivocal despite high clinical suspicion 1
• Proceed to stress testing if diagnosis remains uncertain 2

Monitoring and Follow-Up

HFrEF-Specific Monitoring

• Monitor for GDMT titration and optimization 1
• Device interrogation if ICD/CRT present 1

HFpEF-Specific Monitoring

• Check renal function and electrolytes regularly, especially with MRAs (within 1 week of initiation, then monthly for 3 months, then quarterly) 2
• Monitor symptoms, vital signs, and daily weights at every visit 2
• Schedule follow-up at minimum 6-monthly intervals for stable patients 2

Multidisciplinary Care

Both Subtypes Require

• Cardiac rehabilitation programs providing medical assessment, patient education, psychosocial support, and structured exercise training 2
• Heart failure nurses for medication adherence education, symptom monitoring, and guidance on when to seek medical attention 2
• Early palliative care discussions with referral to specialist palliative care if needs are unmet 2

Key Clinical Pitfalls

Common Errors in HFpEF Management

• Treating HFpEF like HFrEF: Do not reflexively prescribe ACE inhibitors, ARBs, or beta-blockers expecting mortality benefit—use them only for specific comorbidity indications 5, 7
• Over-diuresis: Excessive diuretic use in HFpEF causes hypotension and renal dysfunction without prognostic benefit 2
• Missing the diagnosis: HFpEF is often under-recognized despite accounting for >50% of HF cases with outcomes comparable to HFrEF 1
• Ignoring comorbidities: HFpEF pathophysiology is driven by comorbidities (hypertension, obesity, diabetes, AF)—aggressive comorbidity management is essential 1, 2, 7

Common Errors in HFrEF Management

• Slow GDMT implementation: Delayed or incomplete implementation of all four GDMT pillars substantially worsens prognosis 4
• Inadequate dose titration: Failure to reach target or maximally tolerated doses reduces therapeutic benefit 1