What is the primary management strategy for a patient with heart failure with preserved ejection fraction (HFpEF), including optimal medication and lifestyle modifications?

Management of Heart Failure with Preserved Ejection Fraction (HFpEF)

Initiate an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) as first-line disease-modifying therapy for all patients with HFpEF, regardless of diabetes status, combined with loop diuretics for symptom management. 1

First-Line Pharmacological Management

Disease-Modifying Therapy (Start Immediately)

• SGLT2 inhibitors are the cornerstone of HFpEF treatment with Class 2a recommendation from the American College of Cardiology, showing significant reductions in heart failure hospitalizations and cardiovascular death 1
• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) in the DELIVER trial 1
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED 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 are essential for relieving congestion in patients presenting with orthopnea, paroxysmal nocturnal dyspnea, or peripheral edema 1, 2
• Start with furosemide 20-40 mg IV for new-onset symptoms; for patients already on chronic diuretics, use at least the equivalent of their oral dose 1
• Titrate to the lowest effective dose to avoid excessive diuresis, which can cause hypotension and worsening renal function 1, 2
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade 1, 2

Additional Pharmacological Options for Selected Patients

Mineralocorticoid Receptor Antagonists

• Consider adding spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%) 1
• Spironolactone reduced heart failure hospitalizations by 17% (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial 1
• Monitor potassium and renal function closely to minimize hyperkalemia risk 1

Angiotensin Receptor-Neprilysin Inhibitors

• Sacubitril/valsartan may be considered (Class 2b recommendation) specifically for women and patients with LVEF 45-57%, as these subgroups showed benefit in PARAGON-HF post-hoc analyses 1
• The overall PARAGON-HF trial did not achieve statistical significance (rate ratio 0.87,95% CI 0.75-1.01, p=0.06) 1
• Prespecified subgroup analyses showed potential benefit in patients with LVEF 45-57% (rate ratio 0.78,95% CI 0.64-0.95) and women (rate ratio 0.73,95% CI 0.59-0.90) 1

Blood Pressure Management

• Target blood pressure <130/80 mmHg using medications already prescribed for heart failure 1, 2
• Six guidelines strongly recommended tight control of hypertension as a primary prevention strategy 3
• Use ACE inhibitors or ARBs as first-line agents for additional blood pressure control if needed, though they have not shown mortality benefit in HFpEF 1

Management of Key Comorbidities

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefit for both diabetes and heart failure 1, 2
• Five guidelines recommended initiation of SGLT2 inhibitors in patients with type 2 diabetes and high cardiovascular risk 3
• The European Society of Cardiology also recommended finerenone (a non-steroidal mineralocorticoid receptor antagonist) in type 2 diabetes with concomitant chronic kidney disease 3

Atrial Fibrillation Management

• Prescribe anticoagulation based on CHA₂DS₂-VASc score to prevent thromboembolic events 4
• Control ventricular rate using beta-blockers (preferred if cardioselective, especially with COPD) or digoxin 2
• Use beta-blockers cautiously in patients with COPD, with preference for cardioselective agents 4

Obesity Management

• Weight loss through dietary modification and increased physical activity improves symptoms and functional capacity in obese HFpEF patients 5

Non-Pharmacological Interventions

Exercise Training (Class 1 Recommendation)

• Prescribe supervised exercise training programs (Class 1 recommendation from the American College of Cardiology) to improve functional capacity and quality of life 3, 1, 2
• Exercise training improves aerobic exercise capacity by 12-14% with clinically meaningful benefits 1
• Programs typically involve 3 sessions per week for 1-8 months at 40-90% of exercise capacity, using walking, stationary cycling, or high-intensity interval training 1
• Exercise-based trials have consistently demonstrated large, significant, clinically meaningful improvements in symptoms and objectively determined exercise capacity 3

Dietary Modifications

• Restrict sodium intake to <2-3 g/day to reduce congestive symptoms 2
• Consider fluid restriction when appropriate, particularly in patients with severe congestion 2

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with mineralocorticoid receptor antagonist therapy 1, 4, 2
• Monitor symptoms, vital signs, weight, and functional capacity to guide treatment adjustments 1, 2
• Adjust diuretic doses based on congestion status to avoid overdiuresis 2
• Consider wireless implantable pulmonary artery monitors in selected patients with recurrent hospitalizations for optimizing volume status 1, 2

Critical Medications to AVOID

• Do not prescribe nondihydropyridine calcium channel blockers (diltiazem or verapamil) as they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization 1
• Avoid nitrates as they are associated with a signal of harm in HFpEF 1
• Do not delay initiation of SGLT2 inhibitors, which have proven mortality and morbidity benefits 2

Common Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with reduced ejection fraction, as response to therapies differs significantly between these populations 1
• Avoid excessive diuresis, which may lead to hypotension, worsening renal function, and impaired tolerance of other medications 1, 2
• Do not overlook the importance of managing comorbidities (hypertension, diabetes, obesity, atrial fibrillation), which significantly impact outcomes in HFpEF 1
• Do not assume all traditional heart failure medications work in HFpEF, as most have not shown efficacy in this population 2

Advanced Treatment Considerations

• Consider referral to an advanced heart failure specialist team for patients with advanced HFpEF refractory to standard therapies 1
• Cardiac transplantation can be considered in eligible patients with advanced HFpEF 1
• Four guidelines recommended consideration of right heart catheterization to aid with diagnosis or monitor pulmonary artery pressure in select patients 3

Diagnostic Confirmation Before Treatment

• Confirm HFpEF diagnosis using LVEF ≥50%, elevated natriuretic peptides (NT-proBNP ≥125 ng/L in sinus rhythm or >365 ng/L in atrial fibrillation), and evidence of structural heart disease or elevated filling pressures 3, 2
• Rule out HFpEF mimics such as cardiac amyloidosis, hypertrophic cardiomyopathy, or pericardial disease, which may require specific treatments 2
• Transthoracic echocardiography with left ventricular diastolic function assessment is the key diagnostic test 3
• Consider cardiopulmonary exercise testing to help identify the cause of dyspnea when uncertain and/or quantify functional capacity 3

Evidence on Mortality Reduction

• No single agent has definitively proven mortality reduction in HFpEF as a standalone endpoint 1
• SGLT2 inhibitors reduce composite cardiovascular outcomes (cardiovascular death plus heart failure hospitalizations), with the benefit driven primarily by reductions in heart failure hospitalizations rather than mortality alone 1
• Multiple other agents including perindopril, irbesartan, beta-blockers, nitrates, digoxin, ivabradine, sildenafil, and serelaxin have failed to show any mortality benefit in HFpEF 1
• The goal of therapy in HFpEF is to alleviate symptoms, improve quality of life, and reduce hospitalizations 1