What is the recommended treatment for an older adult with heart failure with preserved ejection fraction and comorbid hypertension, diabetes mellitus, obesity, and chronic kidney disease?

Treatment for Heart Failure with Preserved Ejection Fraction

Start dapagliflozin 10 mg daily or empagliflozin 10 mg daily immediately as first-line disease-modifying therapy for this patient, regardless of diabetes status, and titrate diuretics to relieve congestion while targeting blood pressure <130/80 mmHg with ACE inhibitors or ARBs. 1

First-Line Disease-Modifying Therapy: SGLT2 Inhibitors

Initiate an SGLT2 inhibitor as the cornerstone of HFpEF treatment because this is the only drug class with robust evidence for reducing heart failure hospitalizations and composite cardiovascular outcomes. 1

• Dapagliflozin 10 mg daily if eGFR >30 mL/min/1.73 m² (given this patient's chronic kidney disease, verify eGFR meets this threshold) 1, 2
• Empagliflozin 10 mg daily if eGFR >60 mL/min/1.73 m² 1
• The DELIVER trial demonstrated dapagliflozin reduced worsening heart failure and cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92) 1
• The EMPEROR-PRESERVED trial showed empagliflozin reduced heart failure hospitalization and cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) 1
• No dose titration is required, and benefits occur within weeks independent of diabetes status, background therapy, or age 1

Acute Symptom Management: Diuretics

Use loop diuretics at the lowest effective dose to control volume overload in this patient presenting with orthopnea and paroxysmal nocturnal dyspnea. 3

• Diuretics are the only antihypertensive agents that adequately control fluid retention in heart failure 3
• Start with furosemide 20-40 mg daily (or equivalent) and titrate based on symptoms, daily weights, and volume status 1
• If inadequate response despite dose escalation, add hydrochlorothiazide 12.5-25 mg daily for sequential nephron blockade 1
• Monitor serum creatinine, BUN, and electrolytes closely during diuretic titration to avoid excessive diuresis leading to hypotension and worsening renal function 1, 4
• Once euvolemia is achieved, reduce to the lowest maintenance dose that prevents recurrent congestion 1

Blood Pressure Control

Target systolic blood pressure <130/80 mmHg using medications that also address heart failure. 3, 4

• ACE inhibitors (e.g., lisinopril 10-40 mg daily) or ARBs (e.g., losartan 50-100 mg daily) are first-line antihypertensive agents for persistent hypertension after volume management 3, 4
• These agents effectively lower blood pressure and modestly reduce heart failure hospitalizations, though they lack the mortality benefit seen in HFrEF 3
• Beta-blockers should be titrated to target blood pressure if hypertension persists; the current metoprolol ER 100 mg may be insufficient and can be increased to 200 mg daily 4
• Nebivolol showed a 19% reduction in mortality or cardiovascular hospitalization in HFpEF patients 3

Additional Pharmacotherapy: Mineralocorticoid Receptor Antagonists

Consider adding spironolactone 12.5-25 mg daily if this patient's LVEF is in the lower preserved range (40-50%) and potassium <5.0 mmol/L with eGFR >30 mL/min/1.73 m². 1, 4

• The TOPCAT trial demonstrated spironolactone reduced heart failure hospitalizations by 17% (HR 0.83,95% CI 0.69-0.99) 1
• Monitor potassium and renal function closely when combining spironolactone with ACE inhibitors or ARBs due to hyperkalemia risk 1, 4
• This is a Class 2b recommendation with lower strength of evidence compared to SGLT2 inhibitors 1

Management of Comorbidities

Diabetes Mellitus

• SGLT2 inhibitors serve dual purposes for both glycemic control and heart failure management, making them the optimal first-line diabetes medication 1

Hypertension

• Achieve blood pressure <130/80 mmHg using the medications already prescribed for heart failure (SGLT2 inhibitors, ACE inhibitors/ARBs, beta-blockers) 1, 4
• Hypertension is present in 60-89% of HFpEF patients and is the most important modifiable cause 3

Obesity

• Implement supervised weight-loss programs as obesity worsens diastolic dysfunction and HFpEF outcomes 1
• Dietary sodium restriction to <2-3 g/day supports diuretic effectiveness 1

Chronic Kidney Disease

• Monitor eGFR and electrolytes regularly, especially when initiating or adjusting RAAS inhibitors and MRAs 1, 4
• Dapagliflozin was specifically studied in 4,304 patients with CKD (eGFR 25-75 mL/min/1.73 m²) in the DAPA-CKD trial with consistent safety 2

Non-Pharmacological Interventions

Prescribe supervised exercise training programs consisting of 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 training improves aerobic capacity by 12-14% and quality of life with clinically meaningful benefits 1
• This is a Class 1 recommendation with strong evidence 1

Critical Medications to Avoid

Do not use nondihydropyridine calcium channel blockers (verapamil, diltiazem) as they have myocardial depressant activity and worsen outcomes in heart failure patients. 3, 1

Avoid nitrates as they are associated with a signal of harm in HFpEF. 3, 1

Common Pitfalls

• Do not treat HFpEF the same as HFrEF—response to therapies differs significantly between these populations 1
• Avoid excessive diuresis which precipitates hypotension and worsening renal function, limiting tolerance of other guideline-directed therapies 1, 4
• Do not overlook comorbidity management—hypertension, diabetes, obesity, and atrial fibrillation significantly impact HFpEF outcomes 1
• Recognize that no single agent has demonstrated definitive mortality reduction in HFpEF; the primary benefit of SGLT2 inhibitors is reduction in heart failure hospitalizations driving composite cardiovascular outcomes 1

Monitoring and Follow-Up

• Assess volume status, renal function (creatinine, BUN, eGFR), and electrolytes (especially potassium) at baseline and 1-2 weeks after initiating or adjusting RAAS inhibitors, MRAs, or diuretics 1, 4
• Monitor symptoms and functional capacity to guide treatment adjustments 1
• Track daily weights to detect early fluid retention and guide diuretic dosing 1