Temporal Variability of Atrial Fibrillation in Pacemaker Recipients for Bradycardia: Implications for Crossover Designed Trials, Study Sample Size, and Identification of Responder Patients by Means of Arrhythmia Burden

• Published in: Journal of cardiovascular electrophysiology 2007-03, Vol.18 (3), p.250-257
• Main Authors: BOTTO, GIOVANNI LUCA, SANTINI, MASSIMO, PADELETTI, LUIGI, BORIANI, GIUSEPPE, LUZZI, GIANNI, ZOLEZZI, FRANCESCO, ORAZI, SERAFINO, PROCLEMER, ALESSANDRO, CHIARANDÀ, GIACOMO, FAVALE, STEFANO, SOLIMENE, FRANCESCO, LUZI, MARIO, VIMERCATI, MARCO, DeSANTO, TIZIANA, GRAMMATICO, ANDREA
• Format: Article
• Language: English
• Subjects: Aged; atrial fibrillation; Atrial Fibrillation - complications; Bradycardia - complications; Bradycardia - therapy; Cardiac Pacing, Artificial - statistics & numerical data; Clinical Trials as Topic - methods; Cost of Illness; Cross-Over Studies; Female; Humans; Male; Monte Carlo Method; pacing therapies; Prospective Studies; Research Design; Sample Size; tachyarrhythmia; Time Factors; trials
• ISSN: 1045-3873; 1540-8167
• DOI: 10.1111/j.1540-8167.2006.00731.x

Background: Most clinical trials that have tested pacing therapies to prevent and treat atrial tachyarrhythmias (AT) have chosen endpoints such as AT frequency or burden (defined as percentage of time a patient is in AT), but failed to show unequivocal evidence of a clinical impact. Aim: The aim of our multicenter prospective observational study was to measure the variability of AT burden and estimate its impact on study outcomes. Methods and Results: Two hundred and fifty patients indicated for permanent pacing and suffering from AT (age 71 ± 9 years; 47.2% male) received a dual‐chamber pacemaker. AT burden was measured in two consecutive, 2‐month observation periods; the Monte Carlo method was then applied to simulate findings of a crossover design study. We simulated several models of therapy impact, each model being characterized by the percentage of responder patients and the percentage reduction in AT burden. To show a significant impact of AT therapies in a sample of 250 patients in whom 100, 75, or 50% would be theoretical responders to therapies, AT burden reduction should be at least 27, 32, or 57%, respectively. Temporal fluctuations in AT burden were so high that about 60% of patients would falsely appear as responders or nonresponders in a crossover study, regardless of AT burden reduction. Conclusions: In patients paced for bradycardia and suffering from AT, high intrapatient variability in AT burden was measured. Various models of therapy impact showed that, in crossover trials of AT therapies, time‐related fluctuations in AT burden negatively impact on sample sizes and impair the ability to identify patients as responders or nonresponders.