Cold pressor testing and sympathetic nervous system contribution to ischemia with no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction Project

• Published in: American heart journal plus Vol. 13; p. 100080
• Main Authors: Wei, J., Barsky, L.L., Jalnapurkar, S., Zarrini, P., Cook-Wiens, G., AlBadri, A., Nelson, M.D., Shufelt, C., Sharif, B., Berman, D.S., Thomson, L.E.J., Handberg, E.M., Petersen, J.W., Anderson, R.D., Pepine, C.J., Bairey Merz, C.N., Mehta, P.K.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2022; Elsevier
• Subjects: Cardiovascular; Magnetic resonance imaging; Microcirculation; Perfusion; Sympathetic nervous system; NTG; EF; INOCA; ACH; CBF; CPT; CAD; CMR; LV; WISE; Sympathetic nervous system; CFR; CVD; Microcirculation; RPP; NHLBI; Magnetic resonance imaging; Perfusion; SNS; MPRI; coronary artery disease; ejection fraction; cardiac magnetic resonance imaging; left ventricle; National Heart, Lung, and Blood Institute; myocardial perfusion reserve index; nitroglycerin; cold pressor testing; rate pressure product; sympathetic nervous system; coronary flow reserve; acetylcholine; coronary blood flow; coronary vascular dysfunction; Women's Ischemia Syndrome Evaluation; ischemia and no obstructive coronary arteries
• ISSN: 2666-6022; 2666-6022
• DOI: 10.1016/j.ahjo.2021.100080

Cold pressor testing (CPT) is a known stimulus of the sympathetic nervous system (SNS). To better understand sympathetic contribution to coronary blood flow regulation in women with suspected ischemia and no obstructive coronary arteries (INOCA), we compared myocardial perfusion reserve during CPT stress cardiac magnetic resonance (CMR) imaging between women with suspected INOCA and reference subjects. Prospective cohort. Academic hospital. 107 women with suspected INOCA and 21-age-matched reference women. CPT stress CMR was performed with measurement of myocardial perfusion reserve index (MPRI), adjusted for rate pressure product (MPRIRPP). Invasive coronary function testing in a subset of INOCA women (n = 42) evaluated for endothelial dysfunction in response to acetylcholine, including impaired coronary diameter response ≤0% and coronary blood flow response (ΔCBF) <50%. MPRIRPP. Compared to reference women, the INOCA group demonstrated higher resting RPP (p = 0.005) and CPT MPRIRPP (1.09 ± 0.36 vs 0.83 ± 0.18, p = 0.002). Furthermore, INOCA women with impaired ΔCBF (n = 23) had higher CPT MPRIRPP (p = 0.044) compared to reference women despite lower left ventricular ejection fraction (64 ± 7% vs 69 ± 2%, p = 0.005) and higher mass-to-volume ratio (0.79 ± 0.15 vs 0.62 ± 0.09, p < 0.0001). These differences in CPT MPRIRPP did not persist after adjusting for age, body mass index, and history of hypertension. CPT MPRIRPP among INOCA women did not differ based on defined acetylcholine responses. Myocardial perfusion reserve to CPT stress is greater among women with INOCA compared to reference subjects. This CPT response was also noted in women with coronary endothelial dysfunction, suggesting a greater contribution of the SNS to coronary flow than endothelial dysfunction. Therapies to modulate sympathetic activity should be studied in this population. •Ischemia with no obstructive coronary arteries (INOCA) is increasingly recognized.•Women with INOCA often have dysregulation of myocardial blood flow.•Myocardial blood flow is influenced by sympathetic activity and the endothelium.•Sympathetic activity may predominate over endothelial dysfunction in INOCA women.