ABSTRACT Psychological stress is a potentially major risk factor for sudden cardiac death (SCD), but unfortunately not studied very well. This may in part be is due to the fact that many SCDs are unwitnessed, which makes the study of SCD triggers difficult. As a possible solution to this problem, we propose to study electrocardiographic (ECG) markers of cardiac electrical instability in a cohort of 1,000 Veteran male twins who are recruited from the Vietnam Era Twin Registry. Dr. Shah is an Early Stage Investigator who is poised to lead this effort that follows from his previous work on arrhythmia risk due to acute mental stress (K23 HL127251). His team includes several established investigators in the field of PTSD and heart disease (Viola Vaccarino, Douglas Bremner), stress and arrhythmia (Rachel Lampert), and signal processing/mobile health technologies (Gari Clifford, Larry Jamner). Dr. Shah, over the past several years, has worked closely with the Vietnam veteran twins and is an experienced investigator with this cohort. They have generated important preliminary data that demonstrates a potential relationship between PTSD and TWA; in addition, they have demonstrated feasibility of studying Veterans continuously for one week in their currently funded study which measures PTSD, autonomic function, and sleep. Dr. Shah is also leading telehealth efforts at the Atlanta Veterans Affairs Medical Center, which has provided important methodologies for the current study to recruit and enroll participants from around the United States remotely. The first aim seeks to evaluate the relationship of PTSD symptoms and cardiac electrical instability using two ECG-based markers for arrhythmia: microvolt T-wave alternans (TWA) and morphological beat variability (MVB). Both are expected to be associated with higher PTSD symptoms, suggesting an acutely increased risk of sudden cardiac death. The relationship is also hypothesized to be moderated by genetic factors: when adjusting for genetic factors by evaluating monozygotic twin pairs discordant for PTSD, the relationship is attenuated. Aim 2 examines the relationship between everyday PTSD symptoms with an ecological momentary assessment and MVB/TWA. We hypothesize that acute increases in PTSD symptoms and stress also increase cardiac electrical instability, measured by higher TWA and MVB. Finally, aim 3 explores fragmented sleep and other behavioral correlates of PTSD as possible mechanisms through which PTSD may indirectly impact SCD risk through modifiable behaviors. Our hypothesis is that sleep fragmentation and other maladaptive behaviors such as low physical activity will result higher TWA/MVB on a daily basis. Overall, Dr. Shah is a poised and well-equipped to carry out this large project with novel methods and unprecedented reach in terms of impact and