Circadian rhythm and sudden death in heart failure : Results from prospective randomized amlodipine survival trial

OBJECTIVE The purpose of this study was to address the timing of sudden death in advanced heart failure patients. BACKGROUND Sudden death is a catastrophic event in cardiovascular disease. It has a circadian pattern prominent in the early , which has been thought to be due to a surge of sympathetic stimulation. We postulated that the distribution of events in advanced heart failure, with chronic sympathetic activation, would be more uniform implicating other potential mechanisms. METHODS We analyzed data from Prospective Randomized Amlodipine Survival Trial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and 1-h blocks for uniformity of distribution in the entire cohort, and in the prespecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receiving background therapy of aspirin and warfarin. RESULTS Sudden deaths in the overall cohort showed a nonuniform distribution with a peak but not an peak. The ischemic stratum also showed a peak, but sudden deaths within the nonischemic stratum were uniformly distributed. Neither amlodipine treatment nor aspirin or warfarin use altered the distribution. CONCLUSIONS Sudden death in advanced heart failure did not show an peak, suggesting that circadian sympathetic activation did not strongly influence these events. The peak noted is likely complex in origin and was not affected by antiischemic or antithrombotic medications.