What is the optimal management for a patient with dilated cardiomyopathy with preserved ejection fraction?

Optimal Management of Dilated Cardiomyopathy with Preserved Ejection Fraction

For a patient with dilated cardiomyopathy and preserved ejection fraction (≥50%), initiate SGLT2 inhibitors as first-line disease-modifying therapy, combined with diuretics for symptom management, while carefully monitoring for the development of systolic dysfunction that would necessitate transition to heart failure with reduced ejection fraction (HFrEF) guideline-directed medical therapy. 1, 2

Disease-Modifying Pharmacotherapy

SGLT2 Inhibitors (First-Line)

• Dapagliflozin or empagliflozin should be initiated as the cornerstone of therapy, with Class 2a evidence demonstrating significant reductions in heart failure hospitalizations and cardiovascular death 1, 2
• The DELIVER trial showed dapagliflozin reduced the composite endpoint of worsening heart failure and cardiovascular death by 18% (HR: 0.82; 95% CI: 0.73-0.92) 1, 2
• The EMPEROR-PRESERVED trial demonstrated empagliflozin reduced hospitalization for heart failure and cardiovascular death by 21% (HR: 0.79; 95% CI: 0.69-0.90) 1, 2
• Ensure eGFR >30 mL/min/1.73m² for dapagliflozin and >60 mL/min/1.73m² for empagliflozin before initiation 2

Mineralocorticoid Receptor Antagonists

• Spironolactone should be considered (Class 2b recommendation) particularly when ejection fraction is in the lower preserved range (40-50%) 1, 2
• The TOPCAT trial showed spironolactone reduced heart failure hospitalizations (HR: 0.83; 95% CI: 0.69-0.99) despite not meeting the primary composite endpoint 1, 2
• Monitor potassium and renal function closely to minimize hyperkalemia risk 2

Angiotensin Receptor-Neprilysin Inhibitors

• Sacubitril/valsartan may be considered (Class 2b recommendation) for selected patients, particularly women and those with LVEF 45-57% 1, 2
• The PARAGON-HF trial showed potential benefit in prespecified subgroups despite not achieving statistical significance in the overall population (rate ratio 0.87; 95% CI 0.75-1.01) 1, 2

Symptom Management

Diuretic Therapy

• Loop diuretics should be used at the lowest effective dose to manage fluid retention and relieve congestion 1, 2
• For acute symptoms like orthopnea or paroxysmal nocturnal dyspnea, initiate 20-40 mg IV furosemide (or equivalent) for new-onset symptoms 2
• If inadequate response despite dose increases, consider sequential nephron blockade by adding a thiazide diuretic 2
• Avoid excessive diuresis which may lead to hypotension and worsening renal function 2

Rate Control Agents

• Beta-blockers, verapamil, or diltiazem should be considered (Class IIa recommendation) in NYHA Class II-IV patients with EF ≥50% and no left ventricular outflow tract obstruction to improve heart failure symptoms 1
• Critical caveat: Beta-blockers should be used cautiously as they may cause chronotropic incompetence and worsen exercise tolerance in HFpEF 1, 2
• Beta-blockers are specifically indicated only for prior myocardial infarction (up to 3 years), angina, or atrial fibrillation rate control 1

Critical Monitoring for Transition to Systolic Dysfunction

This is the most important aspect of managing dilated cardiomyopathy with preserved EF, as these patients can deteriorate:

• Perform serial echocardiography at 6,12,24, and 36 months to detect declining ejection fraction 3
• If LVEF falls below 50%, immediately transition to HFrEF guideline-directed medical therapy 1
• Monitor brain natriuretic peptide (BNP) levels; persistently elevated BNP despite initial improvement predicts re-worsening of LVEF 3
• Older age and higher BNP levels after initial improvement are significantly associated with re-worsening LVEF 3

Management Algorithm When LVEF Declines Below 50%

When systolic dysfunction develops (LVEF <50%), the treatment paradigm changes completely:

1. Discontinue negative inotropic agents (verapamil, diltiazem, disopyramide) if causing worsening heart failure symptoms 1
2. Initiate standard HFrEF guideline-directed medical therapy including ACE inhibitors/ARBs, beta-blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors 1
3. Evaluate for cardiac resynchronization therapy if QRS duration is prolonged and LVEF remains <35% 1
4. Consider heart transplant evaluation for advanced symptoms refractory to medical therapy 1

Comorbidity Management

Hypertension

• Target blood pressure <130/80 mmHg using appropriate antihypertensive medications 1, 2

Diabetes Mellitus

• Prioritize SGLT2 inhibitors for glycemic control given their additional heart failure benefits 1, 2

Atrial Fibrillation

• Anticoagulation is mandatory with direct-acting oral anticoagulants as first-line option, independent of CHA₂DS₂-VASc score 1
• Rate control with beta-blockers, verapamil, or diltiazem according to patient preferences and comorbid conditions 1

Non-Pharmacological Interventions

• Supervised exercise training programs (Class 1 recommendation) improve functional capacity and quality of life 1, 2
• Multidisciplinary heart failure programs should be offered to all patients 2
• Weight loss should be encouraged in obese patients 1

Common Pitfalls to Avoid

Do not treat dilated cardiomyopathy with preserved EF the same as typical HFpEF from other etiologies - these patients have fundamentally different pathophysiology with chamber dilation and are at high risk for progression to systolic dysfunction 1, 3

Do not assume preserved ejection fraction means the patient is stable - dilated cardiomyopathy with preserved EF represents a precarious state that can deteriorate rapidly, requiring vigilant monitoring 3

Do not use ivabradine in patients with preserved ejection fraction - pharmacological heart rate lowering is not beneficial and may be harmful in patients with normal or preserved ejection fraction, as it increases central blood pressures and left ventricular wall stress 4

Do not discontinue GDMT if ejection fraction normalizes - if a patient with dilated cardiomyopathy achieves normalization of LVEF with medical therapy, continue all guideline-directed medications indefinitely, as withdrawal results in 40% relapse rate within 6 months 5

Do not overlook the importance of serial imaging - re-worsening LVEF is associated with poor cardiac outcomes and occurs in approximately 7% of patients despite initial improvement 3