Unexpected deviation in circadian variation of ventricular arrhythmias: the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)

Abstract

Objectives: This study sought to determine whether circadian patterns in ventricular arrhythmias (VAs) occur in a current primary prevention defibrillator (implantable cardioverter-defibrillator [ICD]) population.

Background: Cardiovascular events, including VAs, demonstrate biorhythmic periodicity.

Methods: We tested for deviation from the previously described occurrences of a morning peak, early morning nadir, and peak on Mondays in ICD therapies using generalized estimating equations and Student t tests. All hypothesis tests were performed in the entire cohort of patients with VAs as well as pre-specified subgroups.

Results: Of 811 patients with an ICD, 186 subjects experienced 714 ICD therapy episodes for life-threatening VA. There was no morning (6 am to 12 pm) peak in therapies for the entire cohort or any subgroups. The overall cohort and several subgroups had a typical early morning (12 am to 6 am) nadir in therapies, with significantly less than 25% of therapies occurring during this 6-h block (all p < 0.05). A significant peak in therapies on Mondays occurred only in patients not on beta-blocker therapy (22% of events for the week, p = 0.029).

Conclusions: In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) population, the distribution of life-threatening VA failed to show a typical early morning peak or increased VA events on Mondays. A typical early morning nadir was seen in the entire cohort. An increased rate of events on Mondays was found in the subgroup of subjects not on beta-blocker therapy. These findings may indicate suppression of the neurohormonal triggers for VA by current heart failure therapy, particularly the use of beta-blockers in heart failure.

Keywords: circadian; implantable cardioverter-defibrillator; septadian; ventricular arrhythmia.

Figure 1. ICD therapies for ventricular arrhythmias during the 24-hour period

Blue bars show the proportion of all episodes that occurred during each 3-hour period. Green bars show the proportion of episodes, calculated for each patient and then averaged across patients, that occurred during each 3-hour period.

Figure 2. Mean weighted frequency of ICD therapies during the 12 midnight to 6 a.m. interval, overall and by subgroup

Bars show the average proportion of each patient’s episodes that occurred between midnight and 6 a.m. Asterisks denote subgroups in which this average proportion is less than 0.25, the proportion under the null hypothesis.

Figure 3. ICD therapies for ventricular arrhythmias during the 7-day week

Blue bars show the proportion of all episodes that occurred during each day. Green bars show the proportion of episodes, calculated for each patient and then averaged across patients, that occurred during each day.