Early Life Trauma Is Associated With Increased Microvolt T-Wave Alternans During Mental Stress Challenge: A Substudy of Mental Stress Ischemia: Prognosis and Genetic Influences

Amit J Shah, Virginia Weeks, Rachel Lampert, J Douglas Bremner, Michael Kutner, Paolo Raggi, Yan V Sun, Tené T Lewis, Oleksiy Levantsevych, Ye Ji Kim, Muhammad Hammadah, Ayman Alkhoder, Matthew Wittbrodt, Brad D Pearce, Laura Ward, David Sheps, Arshed A Quyyumi, Viola Vaccarino, Amit J Shah, Virginia Weeks, Rachel Lampert, J Douglas Bremner, Michael Kutner, Paolo Raggi, Yan V Sun, Tené T Lewis, Oleksiy Levantsevych, Ye Ji Kim, Muhammad Hammadah, Ayman Alkhoder, Matthew Wittbrodt, Brad D Pearce, Laura Ward, David Sheps, Arshed A Quyyumi, Viola Vaccarino

Abstract

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T-wave alternans (TWA), a measure of repolarization heterogeneity and sudden cardiac death risk. Methods and Results In a cohort with stable coronary artery disease (NCT04123197), we examined early life trauma with the Early Trauma Inventory Self Report-Short Form. Participants underwent a laboratory-based mental stress speech task with Holter monitoring, as well as a structured psychiatric interview. We measured TWA during rest, mental stress, and recovery with ambulatory electrocardiographic monitoring. We adjusted for sociodemographic factors, cardiac history, psychiatric comorbidity, and hemodynamic stress reactivity with multivariable linear regression models. We examined 320 participants with noise- and arrhythmia-free ECGs. The mean (SD) age was 63.8 (8.7) years, 27% were women, and 27% reported significant childhood trauma (Early Trauma Inventory Self Report-Short Form ≥10). High childhood trauma was associated with a multivariable-adjusted 17% increase in TWA (P=0.04) during stress, and each unit increase in the Early Trauma Inventory Self Report-Short Form total score was associated with a 1.7% higher stress TWA (P=0.02). The largest effect sizes were found with the emotional trauma subtype. Conclusions In a cohort with stable coronary artery disease, early life trauma, and in particular emotional trauma, is associated with increased TWA, a marker of increased arrhythmic risk, during mental stress. This association suggests that early trauma exposures may affect long-term sudden cardiac death risk during emotional triggers, although more studies are warranted.

Keywords: psychological stress; repolarization heterogeneity; sudden cardiac death risk.

Figures

Figure 1. Histogram of ETISR‐SF scores in…
Figure 1. Histogram of ETISR‐SF scores in a sample of patients with coronary artery disease.
ETISR‐SF indicates Early Trauma Inventory Self‐Report‐Short Form.
Figure 2. T‐wave alternans with rest, stress,…
Figure 2. T‐wave alternans with rest, stress, and recovery in patients with coronary artery disease with high and low early trauma exposure.
*P<0.05 for the difference between high trauma (solid line) and low trauma (dashed line) groups.

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