What is the primary goal and components of Guideline-Directed Medical Therapy (GDMT) for Heart Failure with preserved Ejection Fraction (HFpEF)?

GDMT for HFpEF

For HFpEF, SGLT2 inhibitors (dapagliflozin or empagliflozin) are the first-line disease-modifying therapy, combined with loop diuretics for symptom relief from congestion. 1

Primary Goal

The primary goal of GDMT in HFpEF is to reduce heart failure hospitalizations and cardiovascular mortality while improving quality of life through symptom management. 1 Unlike HFrEF where mortality reduction is dramatic, HFpEF therapy focuses predominantly on reducing morbidity and hospitalizations. 1

Core Pharmacological Components

SGLT2 Inhibitors (Class 2a Recommendation)

SGLT2 inhibitors should be initiated early as first-line therapy in all eligible HFpEF patients. 1

• Dapagliflozin reduces 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). 1
• Empagliflozin reduces hospitalization for heart failure and cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90). 1
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation. 1

Diuretics for Symptom Management (Class I Recommendation)

Loop diuretics should be used at the lowest effective dose to relieve congestion and manage volume overload. 2, 1

• Titrate diuretic dose based on symptoms and volume status before considering combination strategies. 1
• For acute symptoms (orthopnea/PND), start with 20-40 mg IV furosemide for new-onset HFpEF, or at least equivalent to oral dose for chronic users. 1
• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide for sequential nephron blockade. 1

Mineralocorticoid Receptor Antagonists (Class 2b Recommendation)

Spironolactone may be considered particularly in patients with LVEF in the lower preserved range (40-50%). 2, 1

• The TOPCAT trial showed spironolactone reduced heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but did not significantly reduce the primary composite outcome. 1
• More effective in patients with LVEF closer to 45-50%. 1
• Requires careful monitoring of potassium, renal function, and diuretic dosing to minimize hyperkalemia risk. 1

Angiotensin Receptor-Neprilysin Inhibitors (Class 2b Recommendation)

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

• The PARAGON-HF trial did not achieve significant reduction in the primary endpoint overall (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

Blood Pressure and Comorbidity Management (Class I and IIa Recommendations)

Control systolic and diastolic blood pressure according to published guidelines, targeting <130/80 mmHg. 2, 1

• Beta-blockers, ACE inhibitors, and ARBs are reasonable for hypertension management in HFpEF. 2
• Manage diabetes with preference for SGLT2 inhibitors given their additional heart failure benefits. 1
• Manage atrial fibrillation according to published guidelines to improve symptomatic heart failure. 2

Treatment Algorithm

1. Initiate SGLT2 inhibitor (dapagliflozin or empagliflozin) as first-line disease-modifying therapy. 1
2. Add loop diuretic at lowest effective dose for congestion/volume overload. 2, 1
3. Optimize blood pressure to <130/80 mmHg using ACE inhibitors, ARBs, or beta-blockers. 2, 1
4. Consider adding spironolactone if LVEF is 40-50% and patient tolerates monitoring. 1
5. Consider sacubitril/valsartan for women or those with LVEF 45-57% if additional therapy needed. 1

Non-Pharmacological Management

Prescribe supervised exercise training programs to improve functional capacity and quality of life. 2, 1

• Offer multidisciplinary heart failure programs to all patients. 2, 1
• Cardiac rehabilitation should be recommended despite less robust evidence than in HFrEF. 2

Monitoring Requirements

Regularly assess volume status, renal function, and electrolytes, especially with MRA therapy. 1

• Monitor symptoms and functional capacity to guide treatment adjustments. 1
• Consider wireless implantable pulmonary artery monitors in selected patients for optimizing volume status. 1
• Minimum follow-up every 6 months for stable patients, with increased frequency for clinical instability. 2

Critical Pitfalls to Avoid

Do not treat HFpEF patients identically to HFrEF patients—response to therapies differs significantly between these populations. 1

• Avoid excessive diuresis leading to hypotension and worsening renal function. 1
• Do not overlook comorbidity management (hypertension, diabetes, obesity, atrial fibrillation), which significantly impacts outcomes. 1
• Nutritional supplementation is not recommended in HFpEF. 2

Special Populations

For HFpEF patients with atrial fibrillation and COPD: 3

• Prescribe anticoagulation based on CHA₂DS₂-VASc score. 3
• Use beta-blockers cautiously for rate control, preferring cardioselective agents. 3
• Optimize COPD management while monitoring for drug interactions. 3