What is the recommended treatment plan for a patient with heart failure with preserved ejection fraction?

Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis in all HFpEF patients, regardless of diabetes status, as this is the only disease-modifying therapy with proven reduction in cardiovascular death and heart failure hospitalizations. 1, 2, 3

First-Line Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors – The Cornerstone of Treatment

• Dapagliflozin 10 mg daily (if eGFR >30 mL/min/1.73 m²) reduces 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). 1, 2, 4
• Empagliflozin 10 mg daily (if eGFR >60 mL/min/1.73 m²) reduces heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90). 1, 2, 4
• These benefits occur independent of glucose-lowering effects, require no dose titration, and begin within weeks of initiation. 1, 2
• This is a Class 2a recommendation from the 2022 ACC/AHA/HFSA guidelines. 1, 2

Acute Symptom Management with Diuretics

Loop Diuretics for Congestion

• Use loop diuretics at the lowest effective dose to relieve orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. 1, 2, 3
• For acute decompensation in diuretic-naïve patients, start with furosemide 20-40 mg IV; for patients already on oral diuretics, give an IV dose at least equivalent to their oral regimen. 1, 2
• If inadequate response despite dose escalation, add a thiazide diuretic (e.g., metolazone) for sequential nephron blockade or consider IV acetazolamide. 1
• Monitor serum electrolytes, BUN, and creatinine closely during diuretic titration. 1, 2
• Critical pitfall: Avoid excessive diuresis, which precipitates hypotension and worsening renal function, compromising tolerance of other therapies. 1, 2

Additional Pharmacological Options for Selected Patients

Mineralocorticoid Receptor Antagonists (MRAs)

• Consider adding spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly when LVEF is in the lower preserved range (40-50%). 1, 2
• Spironolactone reduces heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but does not reduce cardiovascular mortality. 1, 2
• Requires careful monitoring of potassium and renal function due to hyperkalemia risk. 1, 2

Angiotensin Receptor-Neprilysin Inhibitor (ARNI)

• Sacubitril/valsartan may be considered (Class 2b recommendation) specifically for women and patients with LVEF 45-57%, where subgroup analyses showed benefit (rate ratio 0.73-0.78). 1, 2
• The overall PARAGON-HF trial did not achieve a significant reduction in the primary endpoint (rate ratio 0.87,95% CI 0.75-1.01, p=0.06). 1

Blood Pressure and Comorbidity Management

Hypertension Control

• Target blood pressure <130/80 mmHg using medications that provide heart failure benefits. 1, 2, 3
• Use ACE inhibitors or ARBs as first-line antihypertensive therapy after volume status is optimized; they modestly reduce HF hospitalizations but do not confer mortality benefit. 1, 2
• Nebivolol reduces the combined endpoint of mortality or cardiovascular hospitalization by approximately 19% in HFpEF patients when additional blood pressure control is needed. 1

Diabetes Management

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefit on glucose and heart failure outcomes. 1, 2, 3

Atrial Fibrillation Management

• Use beta-blockers for rate control, with careful monitoring of exercise tolerance due to potential chronotropic incompetence. 2
• Anticoagulate according to CHA₂DS₂-VASc score. 2

Non-Pharmacological Interventions

Exercise Training – Class 1 Recommendation

• Prescribe supervised exercise training programs: 3 sessions per week for 1-8 months at 40-90% of maximal exercise capacity (walking, stationary cycling, or high-intensity interval training). 1, 2, 3
• This improves aerobic capacity by 12-14% and yields clinically meaningful quality-of-life gains. 1, 2

Lifestyle Modifications

• Advise dietary sodium restriction to <2-3 g per day to lessen congestive symptoms and support diuretic effectiveness. 1, 2
• Recommend weight reduction in obese patients. 2, 3

Medications to Avoid – Critical Safety Considerations

• Never use nondihydropyridine calcium channel blockers (diltiazem, verapamil) in HFpEF—they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization. 1, 2
• Avoid nitrates—they are associated with a signal of harm in HFpEF. 1, 2
• Do not routinely use beta-blockers as primary HFpEF therapy unless indicated for other conditions (e.g., atrial fibrillation rate control, post-MI). 2
• Avoid digoxin in patients with HFpEF in sinus rhythm—it provides no benefit. 2

Monitoring and Follow-Up

• Regularly assess volume status, renal function, and electrolytes, especially with MRA therapy. 1
• Monitor symptoms and functional capacity to guide treatment adjustments. 1, 3
• Consider wireless, implantable pulmonary artery monitors in selected patients with recurrent hospitalizations for optimizing volume status. 1

Advanced Heart Failure Management

• Refer patients with refractory symptoms despite optimal medical therapy to an advanced heart failure specialist team. 1, 2
• Cardiac transplantation can be considered in eligible patients with end-stage HFpEF. 1, 2
• Ultrafiltration may be employed as a last-resort strategy for persistent congestion despite maximal diuretic therapy. 1, 2

Critical Evidence Gaps and Realistic Expectations

• No single pharmacologic agent has definitively reduced mortality as a standalone endpoint in HFpEF. 1, 2
• The principal benefit of SGLT2 inhibitors is a reduction in heart failure hospitalizations, which drives improvement in composite cardiovascular outcomes rather than mortality alone. 1, 2
• Multiple agents—including perindopril, irbesartan, routine beta-blockers, digoxin, ivabradine, sildenafil, and serelaxin—have failed to demonstrate mortality benefit in HFpEF. 1, 2
• Current therapeutic goals focus on symptom relief, quality-of-life improvement, and hospitalization reduction. 1, 2

Common Pitfalls to Avoid

• Do not treat HFpEF patients the same as those with reduced ejection fraction—response to therapies differs significantly between these populations. 1
• Do not overlook comorbidity management—hypertension, diabetes, obesity, and atrial fibrillation significantly impact outcomes in HFpEF. 1, 2
• Avoid delaying SGLT2 inhibitor initiation—early treatment maximizes morbidity benefits. 1, 2