What are the treatment guidelines for Heart Failure with preserved Ejection Fraction (HFpEF)?

HFpEF Treatment Guidelines

First-Line Disease-Modifying Therapy

SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) should be initiated immediately upon diagnosis in all HFpEF patients, as they are the only medications proven to reduce cardiovascular death and heart failure hospitalizations. 1, 2

• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) and heart failure hospitalizations by 23% (HR 0.77,95% CI 0.67-0.89) in the DELIVER trial 1, 2
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 1, 2
• These agents carry a Class 2a recommendation from the American College of Cardiology and American Heart Association 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 1

Symptom Management with Diuretics

Loop diuretics at the lowest effective dose are essential for managing congestion, orthopnea, and paroxysmal nocturnal dyspnea. 3, 1, 2

• Start with furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, torasemide 5-10 mg) and titrate based on volume status 3
• For acute decompensation with orthopnea/PND, use 20-40 mg IV furosemide initially; if already on chronic diuretics, use at least the equivalent of the oral dose 1
• Train patients to self-adjust diuretic doses based on daily weight monitoring and symptoms 3
• Critical pitfall: Excessive diuresis causes hypotension, worsening renal function, and reduced cardiac output in HFpEF patients 3, 1
• If inadequate response despite dose escalation, consider switching to a different loop diuretic or adding a thiazide (hydrochlorothiazide 25-100 mg or metolazone 2.5-10 mg) for sequential nephron blockade 3, 1, 4
• Do not use thiazides if eGFR <30 mL/min except when combined synergistically with loop diuretics 3

Additional Pharmacological Options

Mineralocorticoid Receptor Antagonists (MRAs)

Consider spironolactone 12.5-50 mg daily, particularly in patients with LVEF in the lower preserved range (40-50%). 1, 2

• Spironolactone carries a Class 2b recommendation, indicating it "may be considered to decrease hospitalizations" 1
• The TOPCAT trial showed spironolactone reduced heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but did not reduce the primary composite outcome 1
• Most effective in patients with LVEF closer to 45-50% rather than higher preserved fractions 1
• Monitor potassium and renal function closely to prevent hyperkalemia and worsening renal dysfunction 1

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

Sacubitril/valsartan may be considered for selected patients, especially women and those with LVEF 45-57%. 1, 2

• Carries a Class 2b recommendation from the American College of Cardiology 1
• The PARAGON-HF trial did not achieve statistical significance for the primary endpoint (rate ratio 0.87,95% CI 0.75-1.01, p=0.06) 1
• Subgroup analyses showed benefit in patients with LVEF 45-57% (rate ratio 0.78,95% CI 0.64-0.95) and in women (rate ratio 0.73,95% CI 0.59-0.90) 1
• FDA approved for selected HFpEF patients in February 2021 1

Comorbidity Management

Hypertension Control

Target blood pressure <130/80 mmHg using appropriate antihypertensive medications. 3, 1, 2

• Tight blood pressure control is strongly recommended by all major guidelines 3
• The American Heart Association/American College of Cardiology recommends <130/80 mmHg if high cardiovascular disease risk (>10%) 3

Diabetes Management

Prioritize SGLT2 inhibitors for glycemic control given their dual benefits for diabetes and heart failure. 3, 1, 2

• Five major guidelines recommend SGLT2 inhibitors in patients with type 2 diabetes and high cardiovascular disease risk 3
• The European Society of Cardiology also recommends finerenone (a non-steroidal MRA) in patients with type 2 diabetes and chronic kidney disease 3

Atrial Fibrillation Management

Control ventricular rate using beta-blockers or non-dihydropyridine calcium channel blockers (verapamil or diltiazem). 3, 4

• Rate-limiting calcium channel blockers may improve exercise capacity and symptoms in small studies 3
• Beta-blockers are also effective for rate control in HFpEF patients with atrial fibrillation 3
• Important distinction: Unlike HFrEF, calcium channel blockers are NOT contraindicated in HFpEF and may be beneficial 3

Coronary Artery Disease

Revascularization is reasonable when angina or demonstrable myocardial ischemia adversely affects symptomatic HFpEF despite guideline-directed medical therapy. 3

Non-Pharmacological Interventions

Exercise Training

Prescribe supervised exercise training programs to all HFpEF patients to improve functional capacity and quality of life (Class 1 recommendation). 1, 4, 2

• Provides substantial improvements in aerobic exercise capacity and quality of life 4
• Regular physical activity is recommended by all major guidelines 3

Dietary Modifications

Implement sodium restriction to <2-3 g/day and fluid restriction when appropriate. 4, 2

• Weight reduction is recommended in obese patients 2
• Salt and fluid restriction help control congestion 5

Multidisciplinary Care

Refer all patients to multidisciplinary heart failure programs. 3

• Improves outcomes through coordinated care and patient education 3

Monitoring and Follow-Up

Regularly assess volume status, renal function, electrolytes, symptoms, and functional capacity. 1, 4, 2

• Adjust diuretic doses based on congestion status to avoid overdiuresis 4, 2
• Monitor potassium and renal function especially with MRA therapy 1
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 1, 4

Medications to AVOID in HFpEF

Do not use most antiarrhythmic drugs, NSAIDs, or thiazolidinediones, as they worsen clinical status. 3

• Long-term infused positive inotropic drugs are potentially harmful except for palliation in end-stage disease 3
• Critical distinction: Unlike HFrEF, calcium channel blockers (especially verapamil and diltiazem) are NOT contraindicated and may be beneficial in HFpEF 3
• Digoxin is not beneficial in HFpEF patients in sinus rhythm 6

Advanced Treatment Considerations

Refer to an advanced heart failure specialist for patients with refractory symptoms despite optimal medical therapy. 3, 1

• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 3
• Right heart catheterization should be considered to aid diagnosis, monitor pulmonary artery pressure, or as workup for advanced treatment 3

Treatment Algorithm Summary

1. Immediate initiation: SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg daily) 1, 2
2. Symptom control: Loop diuretic at lowest effective dose, titrated to euvolemia 3, 1, 2
3. Consider adding: Spironolactone if LVEF 40-50% 1, 2
4. Selected patients: Sacubitril/valsartan for women or LVEF 45-57% 1, 2
5. Optimize comorbidities: BP <130/80 mmHg, diabetes control with SGLT2i, rate control for AF 3, 1, 4, 2
6. Non-pharmacological: Supervised exercise, sodium restriction <2-3 g/day 4, 2
7. Monitor closely: Volume status, renal function, electrolytes, symptoms 1, 4, 2

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation – these have proven mortality benefits and should be started immediately 4
• Do not treat HFpEF the same as HFrEF – response to therapies differs significantly between these populations 1, 4
• Do not over-diurese – excessive diuresis leads to hypotension, renal dysfunction, and impaired tolerance of other medications 3, 1, 4
• Do not overlook comorbidity management – hypertension, diabetes, obesity, and atrial fibrillation significantly impact outcomes 1, 4
• Do not assume all heart failure medications work in HFpEF – most traditional HFrEF therapies have not shown efficacy in HFpEF 4