Abstract 11767: Mechanisms of Nighttime Sudden Death: Arrhythmogenic Potential of Central Nervous System-Affecting Medications

Abstract

Introduction: We have previously reported an independent association between central nervous system-affecting medications (CNS-Meds) and nighttime sudden cardiac death (N-SCD). Hypoxia remains a possible trigger due to somnolence and respiratory depression but direct myocardial effects resulting in lethal arrhythmia have not been explored. Hypothesis: Heart rate is significantly lower during sleep, and this increases vulnerability to lethal arrhythmias mediated by prolongation of the QTc interval. Methods: From the population-based Oregon Sudden Unexpected Death Study, we evaluated SCD cases that occurred in the community (2002-2016) between 10 pm and 6 am (nighttime) and compared them with daytime cases. Analysis was restricted to subjects with available pre-arrest information regarding prescribed medications. We identified QT prolonging drugs from the comprehensive list at crediblemeds.com. Time of SCA was determined by the 911 call and review of circumstances provided by the emergency medical services. Univariate comparisons were evaluated using Pearson’s chi-square tests and independent samples t-tests. Results: A total of 3328 SCD cases (65% male, mean age 67y) met criteria for analysis, and 22% (n=739) were N-SCD. Women were more likely to suffer N-SCD compared to men (25% vs 21%, p=0.002). Anti-depressants (36%) were the most frequently used CNS-Meds among N-SCD cases, followed by pain medications (34%) and anti-epilepsy drugs (26%). Specifically, opioids and serotonin modulators were more likely to be used during N-SCD vs. daytime SCD (34% vs 27%, p<0.01, and 11% vs 8%, p<0.01). Importantly, CNS-Meds that prolong QTc interval were more likely to be used during N-SCD than daytime SCD (48% vs 42%, p<0.01). Conclusion: Nighttime SCD was associated with high usage of CNS-Meds especially anti-depressants, pain medications and anti-epileptic drugs. These findings suggest that CNS-Meds may be contributing to nighttime SCD via occurrence of bradycardia-dependent prolonged QTc-associated ventricular arrhythmias. Further investigation is needed to optimize use of CNS-Meds in order to minimize risk of nighttime SCD.