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Determining the Cause of Coronary Vasomotor Disorders in Patients With...

Samit M. Shah, MD, PhD, Jennifer A. Tremmel, MD, MS, Timothy D. Henry, MD, Nathaniel R. Smilowitz, MD, MS, Megha Prasad, MD, Yuhei Kobayashi, MD, Glen A. Henry, MD, Habib Samady, MD, Bruce A. Samuels, MD, Amir Lerman, MD, Jeffrey W. Moses, MD, Cody Pietras, BA, Zhiyuan Zhang, MD, MPH, Daniela Tirziu, PhD, Helen Parise, ScD, Ecaterina Cristea, MD, Daniel Chamié, MD, PhD, Daniel Grubman, BS, Kyna Henrici, RN, Elzar Matmusaeva, MD, Nida Latif, MBBS, Natasha Cigarroa, MD, Alexandra J. Lansky, MD https://doi.org/10.1016/j.jscai.2024.102046

Abstract

Background

Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown.

Methods

The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled.

Conclusions

DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.

Introduction

Among patients referred for invasive coronary angiography (ICA) with or without ischemia on noninvasive stress testing, nearly 50% are found to have no obstructive coronary artery disease (CAD). Myocardial ischemia and nonobstructive coronary arteries (INOCA) is an umbrella term encompassing specific syndromes including coronary microvascular dysfunction (CMD) due to structural abnormalities or abnormally elevated resting flow, vasospastic angina (VSA), diffuse physiologically significant epicardial CAD, endothelial dysfunction, and symptomatic myocardial bridging. Previous studies suggest that there are 3 to 4 million people in the United States who suffer from INOCA. Compared with patients with obstructive CAD, these patients are more likely to suffer from anxiety, depression, and recurrent symptoms. Furthermore, compared with healthy controls, these patients are at increased risk for major adverse cardiovascular events (MACE) and cardiovascular mortality.

Invasive anatomic and physiologic assessment of patients with INOCA has revealed epicardial endothelial dysfunction, CMD, myocardial bridging, or diffuse epicardial atherosclerosis in >75% of patients. Recent studies have shown that angina and quality of life can be improved when coronary physiology assessment is incorporated into clinical care. However, comprehensive assessments of coronary physiology (including the epicardial vessels and microvascular bed) with coronary function testing (CFT) are currently not performed routinely in most medical centers despite being recommended by professional society guidelines. The rationale for performing intravascular imaging and comprehensive coronary physiology assessment in patients with INOCA is that ICA alone cannot diagnose or exclude CMD, diffuse atherosclerosis, physiologically significant myocardial bridging, endothelial dysfunction, or dynamic processes such as coronary vasospasm. Additionally, determining the specific INOCA physiologic phenotype can help guide medical therapy and long-term prognosis.

This prospective, multicenter registry will enroll up to 500 patients presenting with symptomatic ischemic heart disease and referred for ICA based on clinical indications. The overall objective of the Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries (DISCOVER INOCA) Registry is to characterize phenotypes of INOCA and long-term outcomes based on both an anatomic evaluation (ICA and intravascular imaging) and physiologic assessment with the CoroFlow Cardiovascular System (Abbott Vascular) (Central Illustration). In this study, we aim to: (1) describe the prevalence of the INOCA phenotypes: CMD, VSA, mixed CMD/VSA, myocardial bridging, and other disorders of coronary physiology; (2) characterize the burden of epicardial coronary artery atherosclerosis and myocardial bridging; and (3) characterize the natural history and outcomes of patients with INOCA and determine variables associated with MACE.

Central Illustration The DISCOVER INOCA multicenter registry aims to identify specific phenotypes of ischemia and nonobstructive coronary arteries through combined anatomic and physiological assessments (CoroFlow Cardiovascular System) and determine long-term outcomes. MACE, major adverse cardiovascular events (composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization).

Keywords

coronary, intravascular imaging, physiology, stable ischemic heart disease

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https://doi.org/10.1016/j.jscai.2024.102046

Samit M. Shah, MD, PhD, Jennifer A. Tremmel, MD, MS, Timothy D. Henry, MD, Nathaniel R. Smilowitz, MD, MS, Megha Prasad, MD, Yuhei Kobayashi, MD, Glen A. Henry, MD, Habib Samady, MD, Bruce A. Samuels, MD, Amir Lerman, MD, Jeffrey W. Moses, MD, Cody Pietras, BA, Zhiyuan Zhang, MD, MPH, Daniela Tirziu, PhD, Helen Parise, ScD, Ecaterina Cristea, MD, Daniel Chamié, MD, PhD, Daniel Grubman, BS, Kyna Henrici, RN, Elzar Matmusaeva, MD, Nida Latif, MBBS, Natasha Cigarroa, MD, Alexandra J. Lansky, MD