Abstract Body (Do not enter title and authors here): Background: Tobacco cigarette (TCIG) smoking is the most prevalent modifiable risk factor for cardiovascular (CV) disease, including sudden arrhythmic death. Although TCIG smoking among current young adults has never been lower, cannabis smoking and co-use of cannabis and electronic cigarettes (ECIG) now approaches 50%. The arrhythmia risk associated with cannabis smoking and potential amplification of risk through co-use with ECIGs remain largely unknown.

Purpose: To test the hypothesis that arrhythmia risk as estimated by abnormal ventricular repolarization is increased in people who smoke cannabis and amplified by ECIG co-use.

Methods: Three groups were assessed in a parallel group comparison study: 1) chronic (≥ 1 year) ECIG and inhaled cannabis co-users, 2) chronic exclusive cannabis smokers, and 3) control non-users. Participants were healthy adults aged 21-30 who do not smoke TCIGs. Participants fasted and abstained from ECIGs, cannabis, caffeine, and exercise for 8 hours before the study. Blood pressure (BP) and heart rate (HR) were recorded, followed by 12-lead ECG recordings for 5 minutes in supine position. ECG recordings were then analyzed for T(peak-end) (Tp-e) interval as well as Tp-e/QT and Tp-e/QTc ratios as a measure of ventricular repolarization and predictors of arrhythmia risk.

Results: A total of 134 participants were enrolled (49 Controls, 59 Exclusive Cannabis, 26 ECIG/Cannabis Co-users). Subgroups did not differ by sex (54% F), age (24.1±2.9 y), BP, or HR. The Tp-e interval was significantly shorter in the cannabis/ECIG co-users compared to both exclusive cannabis smokers and control non-users (Figure panel A). Overall, ventricular repolarization tended to be shorter in co-users compared to both other groups (Figure panels B & C).

Conclusion: In otherwise healthy young people, chronic cannabis/ECIG co-use impacts ventricular repolarization in the direction not typically associated with increased arrhythmia risk. The clinical implications of Tp-e shortening in co-users require further investigation. Additionally, these outcomes only provide a glimpse of the implications of cannabis and ECIG co-use, and other outcomes of CV risk warrant investigation.