Objective:

To evaluate the safety of discontinuing guideline-directed medical therapy (GDMT) in patients with atrial fibrillation after catheter ablation and recovery of cardiac function.

Approach:

• Study Design: The DEFINITION-AF trial randomly assigned 50 patients with suspected atrial fibrillation-mediated cardiomyopathy to phased withdrawal of GDMT or continued treatment.
• Eligibility Criteria: Patients had to maintain sinus rhythm for 3 months post-ablation, achieve left ventricular ejection fraction of at least 55%, normalize left ventricular size, and have NT-proBNP levels below 250 ng/L.
• Primary Endpoint: Heart failure deterioration was defined by worsening ventricular function, ventricular enlargement, elevated NT-proBNP levels, or recurrent heart failure symptoms.

Key Findings:

• Heart failure deterioration occurred in 3 of 23 patients (13%) assigned to GDMT withdrawal, while none occurred in the continued therapy group.
• Cardiac function or biomarker levels improved in all three patients after restarting heart failure medications.
• No cardiovascular deaths, heart failure hospitalizations, nonfatal strokes, or nonfatal myocardial infarctions occurred in either group during follow-up.
• NT-proBNP levels declined more among patients who continued GDMT than those who withdrew.
• Medication-related adverse events were reported only in the GDMT continuation group (21%).

Interpretation:

The findings suggest that while some patients may safely discontinue GDMT after AF ablation, there is a risk of heart failure deterioration in a subset of patients.

Limitations:

• Pilot design and small sample size.
• Short follow-up period of 6 months.
• Possibility that some patients in the withdrawal group remained on components of GDMT.
• Study not powered to detect differences in clinical outcomes.

Conclusion:

Further larger studies with longer follow-up are needed to determine whether GDMT can be safely discontinued in this population.

Sources:

• JAMA Network Open