What is the next best step in treatment for a 49-year-old patient with dilated cardiomyopathy, decreased ejection fraction (EF) of 45% in the left ventricle and 27% in the right ventricle, and mid-myocardial late gadolinium enhancement on cardiac MRI?

Treatment for Dilated Cardiomyopathy with Reduced Ejection Fraction

The next best step in treatment for this 49-year-old patient with dilated cardiomyopathy and reduced ejection fraction is to initiate comprehensive guideline-directed medical therapy (GDMT) with all four cornerstone medication classes: an SGLT2 inhibitor, a renin-angiotensin system inhibitor (preferably ARNI), an evidence-based beta-blocker, and a mineralocorticoid receptor antagonist. 1, 2

Initial Medication Regimen

First-Line Medications (Start Simultaneously or in Rapid Sequence)

1. SGLT2 Inhibitor (Class 2a recommendation for HFmrEF)

   • Empagliflozin 10mg daily or Dapagliflozin 10mg daily
   • Shown to reduce HF hospitalizations and cardiovascular mortality in patients with LVEF >40% 1

2. Renin-Angiotensin System Inhibitor (Class 2b recommendation for HFmrEF)

   • Preferably Sacubitril/valsartan (ARNI) starting at 24/26mg BID, titrating to 97/103mg BID
   • Alternative: ACE inhibitor such as Lisinopril starting at 2.5-5mg daily, titrating to 20-40mg daily 1, 3

3. Evidence-based Beta-blocker (Class 2b recommendation for HFmrEF)

   • Carvedilol starting at 3.125mg BID, titrating to 25mg BID (<85kg) or 50mg BID (≥85kg)
   • Alternative: Metoprolol succinate starting at 12.5-25mg daily, titrating to 200mg daily 1, 2, 4

4. Mineralocorticoid Receptor Antagonist (Class 2b recommendation for HFmrEF)

   • Spironolactone starting at 12.5-25mg daily, titrating to 25-50mg daily 1, 2

Medication Titration Strategy

• Initiate medications at low doses and titrate upward at 2-4 week intervals if tolerated 2
• Monitor blood pressure, heart rate, electrolytes, and renal function during titration 2
• Target achieving maximum tolerated doses of all four medication classes 5

Additional Diagnostic Workup

Given the cardiac MRI findings suggesting possible infiltrative cardiomyopathy:

1. Evaluate for specific etiologies of dilated cardiomyopathy:

   • Consider cardiac sarcoidosis given the patchy late gadolinium enhancement in the left lateral free wall 1
   • Less likely but consider testing for Anderson-Fabry disease and Chagas disease 1

2. Assess for arrhythmias given the biventricular dysfunction:

   • 24-hour Holter monitoring to detect ventricular arrhythmias or atrial fibrillation

Device Therapy Consideration

• Evaluate for ICD therapy given the severely reduced right ventricular EF (27%) and moderately reduced left ventricular EF (45%) 2, 6
• Consider cardiac resynchronization therapy (CRT) if ECG shows QRS duration ≥130 msec, particularly with left bundle branch block 2

Follow-up Plan

1. Early follow-up within 7-14 days to assess:

   • Medication tolerance
   • Volume status
   • Blood pressure
   • Renal function and electrolytes 2

2. Referral to heart failure specialist to optimize GDMT and evaluate for advanced therapies if needed 7

   • Heart failure clinic referral is associated with higher rates of GDMT initiation across all medication classes (HR 1.54-2.49) 7

Important Considerations

• Biventricular involvement with RV EF of 27% indicates more severe disease and potentially worse prognosis 1
• Late gadolinium enhancement on MRI is associated with adverse outcomes and should prompt aggressive medical therapy 1
• Continuation of GDMT is critical - discontinuation is associated with significantly higher 30-day mortality (8.8% vs 3.5%) and one-year mortality (41.6% vs 28.2%) 8

Common Pitfalls to Avoid

1. Delaying GDMT initiation while pursuing specific etiology - start GDMT promptly while diagnostic workup continues
2. Sequential rather than simultaneous initiation of the four cornerstone medication classes
3. Inadequate dose titration - less than 1% of patients receive all medications at target doses 2
4. Focusing only on left ventricular dysfunction without addressing right ventricular dysfunction
5. Failure to refer to heart failure specialist when biventricular dysfunction is present

This comprehensive approach to GDMT has been shown to significantly reduce mortality and hospitalization in patients with reduced ejection fraction and represents the cornerstone of treatment for dilated cardiomyopathy 5, 6.