Journal of the American College of Cardiology (JACC)CATHEDRAL-HF: Is Carvedilol Effective as Monotherapy in HFimpEF?

The CATHEDRAL-HF trial represents a groundbreaking pilot study examining carvedilol monotherapy in heart failure with improved ejection fraction (HFimpEF), challenging conventional multi-drug approaches. This single-center Brazilian randomized controlled trial provides preliminary evidence for de-escalation strategies in stable HFimpEF patients with optimized cardiac function.

⚕️ Key Clinical Considerations ⚕️

• Study Design Limitations: Single-center, open-label pilot with only 60 patients limits generalizability, requiring larger multicenter validation before widespread clinical adoption.
• Patient Selection Criteria: Strict inclusion parameters (NT-proBNP <250 pg/mL, asymptomatic, LVEF ≥50%) may not represent broader HFimpEF populations seen in routine practice.
• Primary Endpoint Achievement: Non-inferiority demonstrated at 52 weeks (14.8% vs 15.4% ventricular dysfunction recurrence) suggests safety of selective de-escalation approach.
• Biomarker Stability: Maintained NT-proBNP, LVEF, and LV end-diastolic volume indices support hemodynamic stability with carvedilol monotherapy in selected patients.
• Medication Withdrawal Protocol: Systematic stepwise reduction (diuretics/spironolactone first, then RAAS inhibitors) provides structured approach for clinical implementation consideration.

🎯 Clinical Practice Impact 🎯

• Patient Communication: Clinicians should emphasize this represents preliminary evidence requiring individual risk-benefit assessment, particularly for patients expressing medication burden concerns or experiencing polypharmacy-related adverse effects.
• Practice Integration: Implementation requires robust monitoring protocols including serial echocardiography, NT-proBNP surveillance, and symptom assessment at predetermined intervals during any de-escalation attempt.
• Risk Management: Consider this approach only in highly selected, asymptomatic patients with normal biomarkers, excellent medication adherence, and reliable follow-up capabilities.
• Action Items: Establish institutional protocols for HFimpEF medication withdrawal if considering this strategy, including clear criteria for intervention reversal and emergency management pathways.

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