This is a revised application for a K23 Career Development award for Dr. Amit Shah, Assistant Professor of Epidemiology and Medicine at Emory University, and preventive cardiologist at the Atlanta VA Medical Center. Dr. Shah is establishing himself as a young investigator in patient-oriented clinical research. This K23 will provide Dr. Shah with support necessary to accomplish the following goals: (1) to become an expert in signal processing of electrocardiogram (ECG) data, including the use of custom and commercial software to derive heart rate variability (HRV), T-wave alternans (TWA), and spatial QRS-T angle (SA); (2) learn, through formal didactics and hands on experience, the necessary skills to evaluate genetic and ischemic determinants of arrhythmia risk due to acute emotional stress; and (3) learn core clinical research skills to plan and execute patient-oriented studies, including hands-on training with patients in the clinical research lab. Dr. Shah has assembled a mentoring team comprised of a primary mentor, Dr. Viola Vaccarino, Chair of Epidemiology, and renown expert on psychological risk factors of heart disease, and 2 co-mentors who are long-standing collaborators with Dr. Vaccarino, including Dr. Rachel Lampert, a Yale electrophysiologist who is an expert in emotional determinants of arrhythmia, and Dr. J Douglas Bremner (co-mentor), an Emory psychiatrist and radiologist with expertise in nuclear imaging and traumatic stress. The epidemiology, mechanisms, and therapies for emotionally-triggered arrhythmia are difficult to study because many ventricular arrhythmias are fatal. As a solution to this conundrum, Dr. Shah proposes to study surrogate ECG markers of arrhythmia during laboratory-induced acute mental stress in a large study of nearly 1,000 CHD patients led by his mentor, Dr. Vaccarino (R01 HL109413), and advisor, Dr. Quyyumi (P01 HL101398). In this well-characterized, genotyped and phenotyped cohort, he will study the relationships of autonomic modulation during stress and mental stress ischemia with arrhythmia risk during stress (T-wave alternans and spatial QRS-T angle) in Aim 1. Specifically, he will evaluate to what extent electrical instability may develop due to parasympathetic withdrawal (reduced HRV), and sympathetic activation (increased norepinephrine and vasoconstriction). To assess potential molecular targets and better risk stratify high-risk subjects, he will study select adrenergic/cholinergic genetic receptor polymorphisms that may influence electrical instability during mental stress (Aim 2). Finally, in aim 3, he will evaluate the prognostic value of stress reactivity based on autonomic and electrophysiologic measures under study towards major adverse cardiac events and death. Overall, this research will form the basis for larger studies that systematically evaluate risk prediction strategies and possible treatments such as cognitive therapy and biofeedback in CHD patients.

Public Health Relevance

Psychological stress is common amongst patients with coronary heart disease (CHD), and may be a major risk factor for ventricular arrhythmias and death. Psychological stress may have significant autonomic effects (sympathetic arousal, vagal withdrawal) and lead to ischemia, electrophysiologic instability, and ultimately increased risk of arrhythmia and death. Some patients may also have a genetic predisposition for arrhythmia, and based on this, qualify for certain therapies. Elucidation of the mechanisms by which psychological stress may lead to arrhythmia is an important step towards risk stratifying CHD patients and finding effective treatments.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL127251-03
Application #
9406050
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Stoney, Catherine
Project Start
2016-01-15
Project End
2019-12-31
Budget Start
2018-01-01
Budget End
2018-12-31
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Emory University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Sullivan, Samaah; Kelli, Heval M; Hammadah, Muhammad et al. (2018) Neighborhood poverty and hemodynamic, neuroendocrine, and immune response to acute stress among patients with coronary artery disease. Psychoneuroendocrinology 100:145-155
Mehta, Puja K; Hermel, Melody; Nelson, Michael D et al. (2018) Mental stress peripheral vascular reactivity is elevated in women with coronary vascular dysfunction: Results from the NHLBI-sponsored Cardiac Autonomic Nervous System (CANS) study. Int J Cardiol 251:8-13
Harzand, Arash; Witbrodt, Bradley; Davis-Watts, Michelle L et al. (2018) Feasibility of a Smartphone-enabled Cardiac Rehabilitation Program in Male Veterans With Previous Clinical Evidence of Coronary Heart Disease. Am J Cardiol 122:1471-1476
Reinertsen, Erik; Shashikumar, Supreeth P; Shah, Amit J et al. (2018) Multiscale network dynamics between heart rate and locomotor activity are altered in schizophrenia. Physiol Meas 39:115001
Shah, Amit; Chen, Chuqing; Campanella, Carolina et al. (2018) Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease. Psychophysiology :e13291
Vaccarino, Viola; Sullivan, Samaah; Hammadah, Muhammad et al. (2018) Mental Stress-Induced-Myocardial Ischemia in Young Patients With Recent Myocardial Infarction: Sex Differences and Mechanisms. Circulation 137:794-805
Sullivan, Samaah; Hammadah, Muhammad; Al Mheid, Ibhar et al. (2018) Sex Differences in Hemodynamic and Microvascular Mechanisms of Myocardial Ischemia Induced by Mental Stress. Arterioscler Thromb Vasc Biol 38:473-480
Huang, Minxuan; Shah, Amit; Su, Shaoyong et al. (2018) Association of Depressive Symptoms and Heart Rate Variability in Vietnam War-Era Twins: A Longitudinal Twin Difference Study. JAMA Psychiatry 75:705-712
Isakadze, Nino; Soliman, Elsayed Z; Vaccarino, Viola et al. (2018) Association of positive well-being with reduced cardiac repolarization abnormalities in the First National Health and Nutrition Examination Survey. Int J Cardiol 265:246-250
Hayek, Salim S; Ko, Yi-An; Awad, Mosaab et al. (2017) Depression and chest pain in patients with coronary artery disease. Int J Cardiol 230:420-426

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