Treatment of Heart Failure with Preserved Ejection Fraction (HFpEF)
None of the options listed (HCTZ, ACEI, or alpha blocker) represent the mainstay of treatment for HFpEF—the correct answer is SGLT2 inhibitors (dapagliflozin or empagliflozin) combined with loop diuretics for symptom management. 1, 2
Current Evidence-Based Mainstay Therapy
SGLT2 inhibitors are now the first-line disease-modifying therapy for HFpEF, with the strongest evidence for reducing heart failure hospitalizations and cardiovascular mortality. 1, 2 The DELIVER trial demonstrated that dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82; 95% CI 0.73-0.92), and the EMPEROR-PRESERVED trial showed empagliflozin reduced hospitalization for heart failure and cardiovascular death by 21% (HR 0.79; 95% CI 0.69-0.90). 1
Loop diuretics (not thiazides like HCTZ) are essential for symptom management, used at the lowest effective dose to relieve congestion and manage volume overload. 3, 1, 2 The 2013 ACC/AHA guidelines give diuretics a Class I recommendation for relief of symptoms due to volume overload in HFpEF. 3
Why the Listed Options Are Not Mainstays
HCTZ (Hydrochlorothiazide)
Thiazide diuretics like HCTZ are not recommended as first-line therapy in HFpEF. 1, 2 Loop diuretics (furosemide, bumetanide, torsemide) are preferred for managing congestion. 2 Thiazides are only considered as add-on therapy for sequential nephron blockade when loop diuretics alone are inadequate. 1
ACE Inhibitors
ACE inhibitors have only a Class IIa recommendation for hypertension management in HFpEF, not as disease-modifying therapy. 3 The 2013 ACC/AHA guidelines state that "use of beta-blocking agents, ACE inhibitors, and ARBs for hypertension in HFpEF" receives a Class IIa, Level of Evidence C recommendation—meaning they may be reasonable but are not the mainstay. 3 Large trials (PEP-CHF, CHARM-PRESERVED) failed to demonstrate mortality benefit with ACE inhibitors or ARBs in HFpEF. 4, 5 These agents have only modest benefit (5-16% risk reduction) and do not reduce sudden death. 3
Alpha Blockers
Alpha blockers have no role in HFpEF treatment and are not mentioned in any guideline recommendations for this condition. 3, 1, 2 They are not part of guideline-directed medical therapy for heart failure.
Complete Treatment Algorithm for HFpEF
Step 1: Initiate SGLT2 Inhibitor
- Start dapagliflozin 10 mg daily (if eGFR >30 mL/min/1.73m²) or empagliflozin 10 mg daily (if eGFR >60 mL/min/1.73m²) in all patients regardless of diabetes status. 1, 2
Step 2: Manage Congestion with Loop Diuretics
- Use furosemide 20-40 mg, bumetanide 0.5-1.0 mg, or torsemide 5-10 mg at the lowest effective dose, titrated based on symptoms and volume status. 1, 2
Step 3: Optimize Blood Pressure
- Target <130/80 mmHg using appropriate antihypertensives (which may include ACE inhibitors or ARBs for this indication, not as HF therapy). 1, 2
Step 4: Consider Additional Disease-Modifying Therapy
- Mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily) have a Class IIb recommendation, particularly for patients with LVEF in the lower preserved range (40-50%). 3, 1, 2
- Sacubitril/valsartan has a Class IIb recommendation and may be considered for selected patients, especially women and those with LVEF 45-57%. 1, 2
Critical Pitfalls to Avoid
Do not treat HFpEF patients the same as those with reduced ejection fraction (HFrEF), as response to therapies differs significantly between these populations. 1
Avoid excessive diuresis, which reduces cardiac output in HFpEF and causes hypotension and renal dysfunction. 2
Do not use calcium channel blockers (diltiazem or verapamil) in HFpEF patients, as they increase the risk of heart failure worsening and hospitalization. 1
Monitor potassium and renal function closely when using mineralocorticoid receptor antagonists to prevent life-threatening hyperkalemia. 2