What is the recommended management of heart failure with preserved ejection fraction in an older female patient with hypertension, obesity, diabetes mellitus, atrial fibrillation, and chronic kidney disease?

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 as first-line disease-modifying therapy, regardless of diabetes status, and use loop diuretics as needed to relieve congestion. 1, 2, 3, 4

Immediate Pharmacological Management

SGLT2 Inhibitors: The Cornerstone of Therapy

• Initiate dapagliflozin 10 mg daily (if eGFR >30 mL/min/1.73m²) or empagliflozin 10 mg daily (if eGFR >60 mL/min/1.73m²) as the first medication prescribed for all HFpEF patients. 2, 4

• Dapagliflozin reduced 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. 3, 4

• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED. 1, 3, 4

• These agents require no dose titration, have minimal impact on blood pressure and heart rate, and provide benefit within weeks of initiation. 2

• The benefit occurs independent of diabetes status, background heart failure therapy, and age. 2

Diuretic Therapy for Congestion

• Use loop diuretics at the lowest effective dose to relieve orthopnea, paroxysmal nocturnal dyspnea, and peripheral edema. 1, 2, 3, 4

• For acute presentations with congestion, initiate intravenous loop diuretics at a dose equal to or greater than the chronic oral dose, or 40-80 mg furosemide-equivalent IV if diuretic-naïve. 2

• If inadequate response to initial loop diuretic therapy, escalate by: (1) increasing the IV loop diuretic dose, (2) adding a thiazide diuretic (e.g., hydrochlorothiazide) for sequential nephron blockade, or (3) adding IV acetazolamide. 2

• Once euvolemia is achieved, taper diuretics to the lowest dose that maintains volume balance to avoid excessive diuresis leading to hypotension and worsening renal function. 2, 3

Additional Pharmacological Options for Selected Patients

Mineralocorticoid Receptor Antagonists (MRAs)

• Consider adding spironolactone 12.5-25 mg daily (Class 2b recommendation) particularly in patients with LVEF in the lower preserved range (40-50%). 1, 2, 4

• Spironolactone reduced heart failure hospitalizations by 17% (HR 0.83,95% CI 0.69-0.99) in the TOPCAT trial, though it did not reduce the primary composite outcome of cardiovascular death and heart failure hospitalization. 2, 4

• Monitor potassium levels and renal function closely when prescribing spironolactone to minimize the risk of hyperkalemia. 2

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• 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. 2, 4

• The overall PARAGON-HF trial did not achieve a significant reduction in the primary composite endpoint (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06). 2

• Prespecified subgroup analyses showed potential benefit in patients with LVEF below the median (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). 2

Management of Key Comorbidities

This patient's comorbidity profile (hypertension, obesity, diabetes, atrial fibrillation, chronic kidney disease) is typical for HFpEF and requires systematic management. 1, 5, 6

Hypertension

• Target blood pressure <130/80 mmHg using medications already prescribed for heart failure. 2, 3, 4

• If additional blood pressure control is needed beyond SGLT2 inhibitors and diuretics, use ACE inhibitors or ARBs as first-line agents, though they have not shown mortality benefit in HFpEF. 2

• Avoid nondihydropyridine calcium channel blockers (diltiazem or verapamil) as they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization. 2, 4

Diabetes Mellitus

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefit for both diabetes and heart failure. 3, 4

• This approach addresses both conditions simultaneously and is supported by multiple guidelines. 1, 4

Atrial Fibrillation

• Rate control is essential; beta-blockers may be used for rate control in atrial fibrillation, though exercise tolerance should be monitored due to potential chronotropic incompetence. 1

• Anticoagulation should follow standard atrial fibrillation guidelines based on CHA₂DS₂-VASc score. 1

Chronic Kidney Disease

• Monitor renal function and electrolytes regularly, especially when using MRAs and diuretics. 2, 3, 4

• Ensure eGFR thresholds are met before initiating SGLT2 inhibitors (>30 mL/min/1.73m² for dapagliflozin, >60 mL/min/1.73m² for empagliflozin). 2, 4

Obesity

• Recommend weight reduction through dietary sodium restriction to <2-3 g/day and supervised exercise training programs. 2, 3

Non-Pharmacological Interventions

Exercise Training

• Prescribe supervised exercise training programs (Class 1 recommendation) to improve functional capacity and quality of life. 1, 2, 3, 4

• Exercise training improves aerobic exercise capacity by 12-14% with clinically meaningful benefits. 2, 4

• 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. 2

Dietary and Lifestyle Modifications

• Advise dietary sodium restriction of <2-3 g per day to lessen congestive symptoms and support diuretic effectiveness. 2, 3

• Weight reduction is recommended in obese patients to improve symptoms and functional capacity. 3

Monitoring and Follow-Up

• Regularly assess volume status, renal function (BUN, creatinine), and electrolytes (especially potassium), particularly when using MRAs. 2, 3, 4

• Monitor symptoms, vital signs, weight, and functional capacity to guide treatment adjustments. 3, 4

• Serial monitoring during diuretic titration is essential to detect electrolyte disturbances and renal function changes. 2

• Adjust diuretic doses based on congestion status to avoid overdiuresis leading to hypotension. 3

Critical Medications to AVOID

• Do not prescribe nitrates as they are associated with a signal of harm in HFpEF. 2, 4

• Avoid nondihydropyridine calcium channel blockers (diltiazem or verapamil) as they increase heart failure worsening and hospitalization risk. 2, 4

• Multiple other agents have failed to show benefit in HFpEF, including perindopril, beta-blockers (unless indicated for other reasons), digoxin (in sinus rhythm), ivabradine, sildenafil, and serelaxin. 1, 2

Advanced Treatment Options

• In patients with recurrent hospitalizations and persistent congestion despite maximal diuretic therapy, ultrafiltration may be employed as a last-resort strategy. 1, 2

• Consider wireless, implantable pulmonary artery monitors in selected patients with history of hospital admission for decompensated heart failure to optimize volume status. 1, 7

• Referral to an advanced heart failure specialist team should be considered for patients with advanced HFpEF refractory to standard therapies. 1

Important Evidence Gaps and Realistic Expectations

• No single agent has definitively proven mortality reduction in HFpEF as a standalone endpoint. 2, 4

• 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. 2, 4

• The goal of therapy in HFpEF is to alleviate symptoms, improve quality of life, and reduce hospitalizations. 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. 2

• Do not overlook the importance of managing comorbidities, which significantly impact outcomes in HFpEF. 1, 2, 5, 6

• Avoid excessive diuresis which may lead to hypotension and worsening renal function, thereby compromising tolerance of other guideline-directed therapies. 2, 3