What is the optimal treatment approach for an older adult patient with Heart Failure with preserved Ejection Fraction (HFpEF), hypertension, and diabetes?

Treatment for Heart Failure with Preserved Ejection Fraction (HFpEF)

Start an SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg daily) immediately as first-line disease-modifying therapy, combined with loop diuretics titrated to relieve congestion. 1, 2, 3

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors: The Cornerstone of Treatment

• Initiate dapagliflozin 10 mg once daily OR empagliflozin 10 mg once daily in all patients with HFpEF, regardless of diabetes status (Class 2a recommendation). 1, 2, 3

• Dapagliflozin reduced 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) in the DELIVER trial. 2, 3

• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79,95% CI 0.69-0.90) in EMPEROR-PRESERVED. 1, 2, 3

• These benefits occur independent of glucose-lowering effects and represent a class effect for cardiovascular protection. 2

• Verify eGFR >30 mL/min/1.73m² before starting dapagliflozin; empagliflozin requires eGFR >60 mL/min/1.73m². 4

Mineralocorticoid Receptor Antagonists (MRAs)

• Add spironolactone 12.5-25 mg daily (titrating to 50 mg) if LVEF is in the lower preserved range (40-50%) (Class 2b recommendation). 1, 2, 3

• Spironolactone reduced heart failure hospitalizations (HR 0.83,95% CI 0.69-0.99) but showed no mortality benefit in the TOPCAT trial. 2, 3

• Check potassium and creatinine within 1 week of initiation and after each dose change—hyperkalemia is a significant risk, especially with concurrent ACE inhibitor or ARB use. 2

Angiotensin Receptor-Neprilysin Inhibitors (ARNIs)

• Consider sacubitril/valsartan only in selected patients: women and those with LVEF 45-57% (Class 2b recommendation). 1, 3

• The PARAGON-HF trial did not achieve a significant reduction in the primary composite endpoint overall (rate ratio 0.87; 95% CI 0.75-1.01; p=0.06), but subgroup analyses showed potential benefit in women (rate ratio 0.73; 95% CI 0.59-0.90) and patients with LVEF 45-57% (rate ratio 0.78; 95% CI 0.64-0.95). 3

Symptom Management with Diuretics

• Start loop diuretics immediately to relieve congestion: furosemide 20-40 mg daily (or bumetanide 0.5-1.0 mg, or torsemide 5-10 mg). 1, 2, 4

• For acute decompensation with orthopnea/paroxysmal nocturnal dyspnea, use 20-40 mg IV furosemide initially; if already on chronic diuretics, the initial IV dose should equal or exceed the oral dose. 4

• Titrate diuretics to the lowest effective dose to maintain euvolemia ("dry weight") based on daily weight monitoring, symptoms, and physical exam findings. 2, 4

• Train patients to self-adjust diuretic doses based on daily weights and congestion symptoms—this is critical for preventing hospitalizations. 2

• Avoid excessive diuresis—this leads to hypotension, renal dysfunction, and reduced cardiac output, which is particularly problematic in HFpEF where cardiac output is already compromised. 2, 4

• If inadequate response despite dose increases, consider switching to a different loop diuretic or adding a thiazide diuretic for sequential nephron blockade. 4

Blood Pressure Management

• Target blood pressure <130/80 mmHg using the medications already prescribed for heart failure. 1, 2, 3

• The SGLT2 inhibitor, loop diuretic, and potentially MRA will contribute to blood pressure control. 2

• Use ACE inhibitors or ARBs as first-line agents for additional blood pressure control if needed, given their experience in HFpEF trials, though they have not shown mortality benefit in HFpEF specifically. 1

• Beta-blockers are reasonable for blood pressure control, particularly if atrial fibrillation is present for rate control or if there is a history of myocardial infarction. 1, 2

• Balance beta-blocker use against the potential contribution of chronotropic incompetence to exercise intolerance in some patients. 1

Diabetes Management Beyond SGLT2 Inhibitors

• If additional glucose lowering is needed after starting an SGLT2 inhibitor, add a GLP-1 receptor agonist (such as semaglutide, dulaglutide, or liraglutide) for additional cardiovascular protection. 2

• Metformin can be continued or added for glycemic control but does not provide specific heart failure benefits. 2

• Avoid thiazolidinediones (pioglitazone, rosiglitazone) entirely—they cause fluid retention and worsen heart failure. 2, 4

Non-Pharmacological Interventions

• Prescribe supervised exercise training programs (Class 1 recommendation)—this improves aerobic exercise capacity and quality of life with clinically meaningful benefits comparable to or greater than those seen in other cardiovascular conditions. 1, 2, 3

• Multiple randomized controlled trials demonstrate that supervised exercise training in chronic, stable HFpEF is safe and provides substantial improvements in exercise capacity and quality of life. 1

• Recommend dietary sodium restriction to <2-3 g/day to help control volume status and reduce congestion. 2, 4

Monitoring and Follow-Up

• At each visit, assess: volume status (weight, edema, jugular venous pressure), renal function (creatinine, eGFR), electrolytes (especially potassium if on MRA), and symptoms (dyspnea, orthopnea, exercise tolerance). 2, 4

• Adjust diuretic doses based on congestion status—avoid overdiuresis leading to hypotension and renal dysfunction. 2, 4

• Monitor for signs of volume overload: weight gain >2-3 lbs in 1 day or >5 lbs in 1 week, worsening dyspnea, orthopnea, peripheral edema, and elevated jugular venous pressure. 4

Critical Medications to Avoid

• Never use nondihydropyridine calcium channel blockers (diltiazem, verapamil)—they have negative inotropic effects and increase the risk of heart failure worsening and hospitalization. 1, 3, 4

• Amlodipine appeared safe in severe HFrEF in the PRAISE trial and may be used if needed for blood pressure control. 1

• Avoid nitrates—they are associated with a signal of harm in HFpEF. 4

• Use alpha-blockers (doxazosin) with caution or avoid—the ALLHAT trial showed a 2-fold increase in risk of developing heart failure compared with chlorthalidone. 1

• Avoid centrally acting agents like moxonidine, which was associated with increased mortality in heart failure. 1

• Use NSAIDs with extreme caution due to effects on blood pressure, volume status, and renal function. 1

Common Pitfalls and How to Avoid Them

• Do not treat HFpEF patients the same as those with HFrEF—response to therapies differs significantly between these populations. 3

• Do not overlook comorbidity management—hypertension, diabetes, obesity, atrial fibrillation, and coronary artery disease significantly impact outcomes and must be aggressively treated. 1, 3, 4

• Do not delay SGLT2 inhibitor initiation—start immediately at diagnosis, as these are the only agents with robust evidence for reducing heart failure hospitalizations. 1, 2, 3

• Do not use medications proven effective in HFrEF and assume they work in HFpEF—multiple drug classes (ACE inhibitors, ARBs, beta-blockers) that reduce mortality in HFrEF have failed to show mortality benefit in HFpEF. 3, 5

Treatment Algorithm Summary

1. Immediate initiation: SGLT2 inhibitor (dapagliflozin 10 mg or empagliflozin 10 mg daily) + loop diuretic (furosemide 20-40 mg daily, titrated to symptoms). 1, 2, 3, 4

2. Blood pressure control: Target <130/80 mmHg using ACE inhibitor/ARB and/or beta-blocker if needed beyond SGLT2i and diuretic. 1, 2, 3

3. Consider adding: Spironolactone 12.5-25 mg daily if LVEF 40-50%, monitoring potassium closely. 1, 2, 3

4. Selected patients only: Sacubitril/valsartan if female or LVEF 45-57%. 1, 3

5. Diabetes management: If additional glucose lowering needed, add GLP-1 receptor agonist. 2

6. Non-pharmacological: Supervised exercise training program + sodium restriction <2-3 g/day. 1, 2, 3, 4

7. Avoid entirely: Nondihydropyridine calcium channel blockers, thiazolidinediones, nitrates. 1, 2, 3, 4