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

Giovanni Luca Botto, Massimo Santini, Luigi Padeletti, Giuseppe Boriani, Gianni Luzzi, Francesco Zolezzi, Serafino Orazi, Alessandro Proclemer, Giacomo Chiarandà, Stefano Favale, Francesco Solimene, Mario Luzi, Marco Vimercati, Tiziana DeSanto, Andrea Grammatico

Research output: Contribution to journalArticlepeer-review

Abstract

Variability ofAT Burden. 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.

Original languageEnglish
Pages (from-to)250-257
Number of pages8
JournalJournal of Cardiovascular Electrophysiology
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • Atrial fibrillation
  • Pacing therapies
  • Tachyarrhythmia
  • Trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology

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