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.
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.
Authors: Shivshankar Thanigaimani; Anthony G Brooks; Pawel Kuklik; Darragh J Twomey; Samantha Franklin; Erik Noschka; Darius Chapman; Rajeev K Pathak; Rajiv Mahajan; Prashanthan Sanders; Dennis H Lau Journal: J Arrhythm Date: 2016-07-27
Authors: Giuseppe Boriani; Raymond Tukkie; Antonis S Manolis; Lluis Mont; Helmut Pürerfellner; Massimo Santini; Giuseppe Inama; Paolo Serra; João de Sousa; Giovanni Luca Botto; Lorenza Mangoni; Andrea Grammatico; Luigi Padeletti Journal: Eur Heart J Date: 2014-04-25 Impact factor: 29.983