Patients with atrial fibrillation whose cardiac function recovered following catheter ablation may be able to discontinue guideline-directed medical therapy in some cases, although heart failure deterioration occurred in a subset of patients who underwent treatment withdrawal.
In the DEFINITION-AF trial, researchers randomly assigned 50 patients with suspected atrial fibrillation-mediated cardiomyopathy to phased withdrawal of guideline-directed medical therapy (GDMT) or continued treatment. Eligible patients had maintained sinus rhythm for 3 months following ablation, achieved recovery of left ventricular ejection fraction to at least 55%, normalized left ventricular size, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels below 250 ng/L, and had no signs or symptoms of heart failure. The primary endpoint was heart failure deterioration, defined by worsening ventricular function, ventricular enlargement, elevated NT-proBNP levels, or recurrent heart failure symptoms. Forty-seven patients completed the 6 months of follow-up.
Heart failure deterioration occurred in 3 of 23 patients (13%) assigned to GDMT withdrawal and in none of the 24 patients assigned to continued therapy. Two patients met deterioration criteria because of increases in NT-proBNP levels, and one met criteria because the left ventricular ejection fraction declined below 55%. Researchers reported that cardiac function or biomarker levels improved in all three patients after heart failure medications were restarted.
No cardiovascular deaths, heart failure hospitalizations, nonfatal strokes, or nonfatal myocardial infarctions occurred in either treatment group during follow-up.
Researchers found no meaningful differences between groups in changes in echocardiographic measures, cardiac magnetic resonance imaging parameters, or Kansas City Cardiomyopathy Questionnaire scores over 6 months. Changes in left ventricular ejection fraction, left ventricular dimensions, and cardiac magnetic resonance imaging measures of ventricular structure and function were similar between the groups.
NT-proBNP levels declined more among patients who continued GDMT than among those assigned to withdrawal. Blood pressure also increased more among patients who discontinued therapy.
Atrial tachyarrhythmia recurrence occurred in three patients in each group, corresponding to recurrence rates of 13% in the withdrawal group and 13% in the continuation group. One patient assigned to continued therapy underwent repeat ablation.
Medication-related adverse events occurred only among patients who remained on GDMT. Five of 24 patients (21%) in the continuation group experienced adverse drug events, compared with none in the withdrawal group. Reported events included symptomatic hypotension requiring dose reduction, bradycardia leading to beta-blocker discontinuation, and urogenital infection associated with sodium-glucose cotransporter-2 inhibitor therapy.
The researchers noted that the findings were derived from a highly selected population with suspected atrial fibrillation-mediated cardiomyopathy who had achieved normalization of cardiac structure and function following ablation. They also acknowledged several limitations, including the pilot design, small sample size, the 6-month follow-up period, and the possibility that some patients assigned to withdrawal remained on components of GDMT during follow-up. The study was not powered to detect differences in clinical outcomes.
"Further larger studies with longer follow-up are needed to determine whether GDMT can be safely discontinued in this population," wrote lead study author Sitong Li, MD, of Beijing Anzhen Hospital, Capital Medical University, Beijing, China, and colleagues.
Disclosures: The researchers reported no conflicts of interest. The study was funded by the National Key Research and Development Program of China and the Science and Technology Plan Project of Tongzhou District.
Source: JAMA Network Open
