What are the clinical presentation, diagnosis, and management of Heart Failure with preserved Ejection Fraction (HFpEF)?

Clinical Presentation, Diagnosis, and Management of HFpEF

Clinical Presentation

HFpEF patients typically present with dyspnea on exertion, exercise intolerance, and peripheral edema, often accompanied by a high burden of cardiovascular and metabolic comorbidities including hypertension, obesity, diabetes, atrial fibrillation, and chronic kidney disease. 1

Key presenting features include:

• Dyspnea and exercise intolerance as the predominant symptoms, often with marked limitation of physical activity (NYHA Class II-III most common) 1
• Signs of congestion including peripheral edema, elevated jugular venous pressure, and pulmonary rales 1, 2
• Comorbidity clusters that drive the pathophysiology: metabolic syndrome, arterial hypertension, atrial fibrillation, coronary artery disease, and renal dysfunction 3
• Chronotropic incompetence and pulmonary hypertension may be prominent features in certain phenotypes 3

Diagnostic Approach

Confirm HFpEF using a two-step approach: first establish heart failure symptoms with LVEF ≥50%, elevated natriuretic peptides, and evidence of structural heart disease or diastolic dysfunction on echocardiography; if uncertain, proceed to stress testing. 2, 4

Step 1: Initial Diagnostic Criteria

• LVEF ≥50% on transthoracic echocardiography 1
• Elevated natriuretic peptides (BNP or NT-proBNP) 1, 2
• Objective evidence of structural heart disease (left atrial enlargement, left ventricular hypertrophy) or elevated filling pressures 2, 4
• Symptoms and signs of heart failure including dyspnea, fatigue, and congestion 1

Step 2: Rule Out HFpEF Mimics

Exclude alternative diagnoses that require entirely different treatment strategies before confirming HFpEF. 2, 4, 5

Critical mimics to exclude:

• Cardiac amyloidosis (requires specific amyloid-directed therapy) 2, 4
• Hypertrophic cardiomyopathy 1, 4
• Constrictive pericardial disease 4
• Significant valvular disease 1
• High-output heart failure 1

Step 3: Advanced Testing if Diagnosis Uncertain

• Exercise echocardiography or invasive hemodynamic testing to demonstrate elevated filling pressures with exertion 2, 4
• Additional workup including ECG, thyroid function, renal and hepatic function tests 5

Pharmacological Management

Disease-Modifying Therapy (First-Line)

Initiate SGLT2 inhibitors (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) immediately upon diagnosis—these are the only medications proven to reduce cardiovascular death and heart failure hospitalizations in HFpEF. 2, 4, 6

• 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 4
• Empagliflozin reduced heart failure hospitalization or cardiovascular death by 21% (HR 0.79) in EMPEROR-PRESERVED 4
• Do not delay initiation of SGLT2 inhibitors—this is a common and harmful pitfall 2, 5
• Particularly beneficial in patients with concurrent COPD as they do not affect respiratory function 5

Symptom Management with Diuretics

Use loop diuretics as the cornerstone for congestion relief, titrating to the lowest effective dose that maintains euvolemia. 2, 4

• Starting doses: furosemide 20-40 mg daily, bumetanide 0.5-1.0 mg daily, or torsemide 5-10 mg daily 4
• Titrate carefully to avoid excessive diuresis leading to hypotension, renal dysfunction, and impaired tolerance of other medications 2, 4
• Increase diuretic dose before adding combination therapy if initial response is inadequate 2
• Consider thiazide combination (metolazone 2.5 mg) only in refractory cases with eGFR >30 mL/min 4

Additional Disease-Modifying Agents

Consider mineralocorticoid receptor antagonists (spironolactone 12.5-25 mg daily) particularly in patients with LVEF in the lower range of preservation (40-50%) or persistent symptoms despite SGLT2 inhibitors. 2, 4

• Monitor potassium and creatinine within 1 week of initiation, then monthly for 3 months, then quarterly 4
• Dose adjustments required with impaired renal function 5

ARNIs (sacubitril/valsartan) may be beneficial in selected patients, especially women and those with LVEF below the upper range. 2

Aggressive Comorbidity Management

Hypertension Control

Achieve blood pressure target <130/80 mmHg using appropriate antihypertensive medications—hypertension is a primary driver of HFpEF pathophysiology. 2, 4, 5

• Prioritize agents with proven benefit: ACE inhibitors, ARBs, or ARNIs combined with diuretics 4

Atrial Fibrillation Management

Control ventricular rate to 60-100 bpm using beta-blockers (metoprolol, carvedilol) or non-dihydropyridine calcium channel blockers (diltiazem, verapamil). 4, 5

• Use cardioselective beta-blockers cautiously in patients with concurrent COPD 5
• Anticoagulate based on CHA₂DS₂-VASc score to prevent thromboembolic events 4, 5

Diabetes Management

Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits. 2, 5

Other Comorbidities

• Evaluate underlying causes of anemia (nutritional, chronic disease, blood loss) 5
• For gout: consider xanthine oxidase inhibitors (allopurinol) for prophylaxis and avoid NSAIDs 5

Non-Pharmacological Interventions

Prescribe supervised exercise training programs—these consistently demonstrate large, clinically meaningful improvements in exercise capacity and quality of life. 1, 4

• Cardiac rehabilitation is a Class 1 recommendation with proven efficacy 1, 4
• Restrict sodium intake to <2-3 g/day to reduce fluid retention and congestion 2, 4
• Recommend weight reduction in obese patients (BMI >30 kg/m²) as obesity is a major contributor to HFpEF pathophysiology 4

Monitoring and Follow-Up

Monitor symptoms, vital signs, daily weights, renal function, and electrolytes regularly to detect early decompensation. 2, 4, 5

• Schedule follow-up visits at minimum 6-monthly intervals for stable patients, increasing frequency with worsening clinical stability 4
• Check renal function and electrolytes especially when using MRAs 4, 5
• Consider wireless pulmonary artery pressure monitoring in selected patients with recurrent hospitalizations 2

Multidisciplinary Team Approach

Engage the wider multidisciplinary team early to provide holistic, personalized care. 1

• Refer to cardiac rehabilitation programs for medical assessment, patient education, psychosocial support, and structured exercise training 4
• Engage heart failure nurses for education on medication adherence, symptom monitoring, and when to seek medical attention 4
• Initiate palliative care discussions early in the disease trajectory, with referral to specialist palliative care if patient needs are unmet by the primary team 1, 4
• Seek input from relevant specialists (pharmacists, cardiologists, HF specialists, endocrinologists, nephrologists) as needed 1

Common Pitfalls to Avoid

• Delaying SGLT2 inhibitor initiation which have proven mortality and morbidity benefits 1, 2, 5
• Excessive diuresis leading to hypotension and impaired tolerance of other medications 2, 4
• Failure to recognize HFpEF mimics that require different treatment approaches 2, 4, 5
• Polypharmacy without regular medication review increases risk of adverse drug interactions in elderly patients 5