• Author
    Dyuthi Mathews Tharakan
  • Discovery PI

    Noel Bairey Merz, MD

  • Project Co-Author

    Peng-Sheng Chen, MD

  • Abstract Title

    Beyond the Arteries: Ambulatory Sympathetic Nerve Activity and Coronary Microvascular Dysfunction in Women

  • Discovery AOC Petal or Dual Degree Program

    Basic, Clinical, & Translational Research

  • Abstract

    Background: Coronary microvascular dysfunction (CMD) is a major cause of ischemia with no obstructive coronary arteries and is associated with adverse outcomes including myocardial infarction, heart failure, and sudden cardiac death. The mechanisms linking CMD to ischemic symptoms is not well understood but the autonomic nervous system (ANS) is implicated in the pathophysiology. Coronary arteries contain multiple autonomic receptors and prior studies have demonstrated greater stress-induced vagal withdrawal in women with CMD compared to reference controls. Skin sympathetic nerve activity (SKNA) measured using an ambulatory ECG monitor provides a novel noninvasive method to understanding sympathetic nervous system tone and its influence of ischemia. The relationship between sympathetic nervous system activity and measures of coronary microvascular function, myocardial perfusion, and angina-related quality of life has not been characterized in women with CMD.

     

    Methods: This is a prospective, observational pilot study enrolling 10 women with CMD and 10 age-matched reference controls. All participants wear a Bittium Faros 180 single lead skin ECG monitor on their chest for 7 days and complete a daily symptom diary, SKNA metrics such as baseline sympathetic nerve activity, sympathetic nerve burst, heart rate variability and symptom-related SKNA events are extracted from recordings. Correlative analyses will be performed with existing clinical data including invasive coronary function testing variables (coronary flow reserve, CFR and coronary blood flow, CBF), cardiac MRI myocardial perfusion reserve index (MPRI) and angina quality of life assessed by the Seattle Angina Questionnaire (SAQ).

     

    Results: Enrollment is currently ongoing with 2 remaining controls scheduled to be enrolled. Based on the study hypotheses and prior study data, we anticipate that women with CMD will demonstrate higher ambulatory SKNA – including greater burst frequency and amplitude, compared to reference controls. We further anticipate that elevated SKNA will correlate inversely with CFR and CBF on invasive CFT and MPRI on cardiac MRI consistent with sympathetically mediated microvascular vasoconstriction. Finally, we anticipate higher SKNA will be associated with worse anginal quality of life and SKNA bursts will temporally co-occur with patient-reported ischemic symptoms in the symptom diary.

     

    Conclusions: This ambulatory SKNA study represents the first prospective investigation of ambulatory sympathetic nerve activity in women with CMD and compared to invasive imaging and quality of life outcomes. If hypotheses are confirmed, these findings would support sympathetic nervous system hyperactivity as a mechanistic contributor to CMD severity and symptom burden in women with INOCA, providing rationale for autonomic modulation strategies in this population.

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