What is the initial treatment approach for a patient with heart failure with preserved ejection fraction (HFpEF), including management of comorbid conditions such as hypertension, diabetes, and obesity?

Initial Treatment Approach for Heart Failure with Preserved Ejection Fraction (HFpEF)

Start SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis, as these are the only medications proven to reduce mortality and heart failure hospitalizations in HFpEF. 1, 2, 3

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors (First-Line)

• Initiate dapagliflozin 10 mg daily or empagliflozin 10 mg daily as the cornerstone of HFpEF treatment, regardless of diabetes status 1, 2, 3
• Dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR 0.82) and heart failure hospitalizations by 23% (HR 0.77) in the DELIVER trial 2, 3
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79) in EMPEROR-PRESERVED 2, 3
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 3
• Do not delay SGLT2 inhibitor initiation, as this is the most critical error in HFpEF management 1

Additional Pharmacotherapy Considerations

• Consider mineralocorticoid receptor antagonists (spironolactone) particularly in patients with LVEF in the lower range of preservation (40-50%) 1, 3
• ARNIs (sacubitril/valsartan) may be beneficial in selected patients, especially women and those with LVEF below the upper range 1, 3
• Monitor renal function and electrolytes regularly when using MRAs 3

Symptom Management with Diuretics

• Use loop diuretics (furosemide or torsemide) at the lowest effective dose to relieve congestion, orthopnea, and paroxysmal nocturnal dyspnea 1, 2, 3, 4
• Titrate diuretic dose based on symptoms and volume status to avoid overdiuresis, which can lead to hypotension and impaired tolerance of other medications 1, 2, 3
• Consider adding thiazide or thiazide-like diuretics for refractory edema or additional blood pressure control 5, 1
• Loop diuretics are preferred for congestion management, though they are less effective than thiazides for blood pressure lowering 5

Management of Comorbid Hypertension

• Target blood pressure <130/80 mmHg using appropriate antihypertensive medications 5, 1, 2, 3
• Use β-blockers, ACE inhibitors, or ARBs as reasonable options for blood pressure control in HFpEF 5
• ARBs may additionally decrease hospitalizations for HFpEF 5
• Hypertension control is particularly important as patients with HFpEF may respond well with regression of LV hypertrophy and improvement in filling pressures 5

Antihypertensive Medications to Avoid

• Avoid nondihydropyridine calcium channel blockers (verapamil and diltiazem) as they can worsen heart failure symptoms (Class III: Harm) 5
• Avoid α-adrenergic blockers (doxazosin) except as last resort when other agents fail at maximum tolerated doses (Class III: Harm) 5
• Avoid moxonidine (Class III: Harm) 5
• Avoid potent direct-acting vasodilators like minoxidil due to renin-related salt and fluid retention 5

Management of Comorbid Diabetes

• Prioritize SGLT2 inhibitors for glycemic control given their dual benefits for both diabetes and heart failure 1, 2, 3
• Consider finerenone (non-steroidal MRA) in patients with type 2 diabetes and concomitant chronic kidney disease 5
• Approximately 25-50% of HFpEF patients have diabetes, which carries adverse prognostic significance 5

Management of Comorbid Obesity

• Prescribe diet-induced weight loss programs for obese patients, as weight loss produces clinically meaningful increases in functional capacity and quality of life 4
• Excess adiposity is present in >80% of HFpEF patients and plays a pivotal role in disease development and severity 5
• Weight reduction is a Class I recommendation as part of behavioral modification 5

Non-Pharmacological Interventions

Exercise Training

• Prescribe supervised exercise training programs to improve functional capacity and quality of life (Class 1 recommendation) 1, 2, 3, 4
• Exercise training provides substantial improvements in aerobic exercise capacity and quality of life 1
• Reduced physical activity and low cardiorespiratory fitness are important contributors to HFpEF development 5

Dietary Modifications

• Recommend sodium restriction to <2-3 g/day to reduce congestive symptoms 1, 2, 3
• Advise a heart-healthy diet and moderation of alcohol intake 5
• Fluid restriction may be appropriate in select patients 1

Patient Education

• Provide education in heart failure self-care, including adherence to medications and dietary restrictions, monitoring of symptoms and vital signs 4
• This helps avoid heart failure decompensation 4

Monitoring and Follow-Up

• Monitor symptoms, vital signs, weight, renal function, and electrolytes regularly 1, 2, 3
• Adjust diuretic doses based on congestion status to avoid overdiuresis 1, 2
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 1

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation, as these have proven mortality and morbidity benefits 1
• Do not assume traditional heart failure medications work in HFpEF, as most have not shown efficacy in this population 1
• Avoid excessive diuresis leading to hypotension and impaired tolerance of other medications 1
• Use nonsteroidal anti-inflammatory agents with caution given their effects on blood pressure, volume status, and renal function 5

Special Considerations for Atrial Fibrillation

• Control heart rate using β-blockers or non-dihydropyridine calcium channel blockers in HFpEF patients with atrial fibrillation 5
• Note: This is one of the few scenarios where non-dihydropyridine calcium channel blockers may be used, specifically for rate control in atrial fibrillation 5