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 dea th in advanced heart failure patients. BACKGROUND Sudden death is a catastrophic event in cardiovascular disease. ft has a circadian pattern prominent in the early AM, which has been though t to be due to a surge of sympathetic stimulation. We postulated that the d istribution of events in advanced heart failure, with chronic sympathetic a ctivation, mould be more uniform implicating other potential mechanisms. METHODS We analyzed data from Prospective Randomized Amlodipine Survival Tr ial (PRAISE). Sudden deaths were analyzed by time of death in 4-h and l-h b locks for uniformity of distribution in the entire cohort, and in the presp ecified ischemic and nonischemic stratum. Further analyses were undertaken in the treatment groups of amlodipine and placebo, and among those receivin g background therapy of aspirin and warfarin. RESULTS Sudden deaths in the overall cohort showed a nonuniform distributio n with a PM peak but not an AM peak. The ischemic stratum also showed a PM peak, but sudden deaths within the nonischemic stratum were uniformly distr ibuted. Neither amlodipine treatment nor aspirin or warfarin use altered th e distribution. CONCLUSIONS Sudden death in advanced heart failure did not show an AM peak, suggesting that circadian sympathetic activation did not strongly influenc e these events. The PM peak noted is likely complex in origin and was not a ffected by antiischemic or antithrombotic medications. (C) 2000 by the Amer ican College of Cardiology.