Coronary endothelial dysfunction appears to be common in patients with INOCA
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In a cohort of patients with ischemia and nonobstructive coronary arteries, nearly four of five had coronary endothelial dysfunction, researchers reported in Circulation: Cardiovascular Interventions.
In addition, nearly two-thirds had coronary artery spasm and nearly one-third had impaired adenosine-mediated vasodilation.
“These results indicate the relevance to perform endothelial function testing in patients with ischemia and nonobstructive coronary arteries in view of its therapeutic implication,” Rutger G.T. Feenstra, MSc, from the department of cardiology at Amsterdam University Medical Center, and colleagues wrote.
In patients with ischemia and nonobstructive coronary arteries (INOCA), it is common to perform coronary function testing using adenosine-mediated vasodilation and acetylcholine spasm provocation, according to the study background. “The purpose of this study was to evaluate the diagnostic value of additional endothelial function testing for the diagnosis of vasomotor dysfunction in patients with INOCA,” Feenstra and colleagues wrote.
The researchers retrospectively analyzed 110 patients with INOCA who had coronary function testing.
The outcomes of interest were coronary endothelial dysfunction, defined as a less than 50% increase in coronary blood flow as determined by Doppler flow, and/or epicardial constriction compared with baseline after response to low-dose acetylcholine; coronary artery spasm, defined as vasospastic angina or microvascular angina after response to high-dose acetylcholine; and impaired adenosine-mediated vasodilation, defined as coronary flow reserve less than 2.5 and/or hyperemic microvascular resistance of 2.5 or greater.
In the overall cohort, 79% of patients had coronary endothelial dysfunction, 62% had coronary artery spasm and 29% had impaired adenosine-mediated vasodilation, Feenstra and colleagues found.
In patients with coronary artery spasm and/or impaired adenosine-mediated vasodilation, 80% had coronary endothelial dysfunction, according to the researchers.
When endothelial function testing was added to adenosine testing and spasm provocation, diagnostic yield increased by 17% to 92%, the researchers wrote.
In patients with normal adenosine-mediated vasodilation and no inducible coronary artery spasm, 68% had coronary endothelial dysfunction, they wrote.
“These data illustrate the diagnostic impact of routine endothelial function testing in coronary function testing protocols with implications for medical treatment in this complex patient cohort,” Feenstra and colleagues wrote. “Further studies are required to identify the clinical and prognostic characteristics of both lone and concomitant endothelial dysfunction in INOCA patients undergoing coronary function testing.”
Perspective
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This study demonstrates the high prevalence of underlying endothelial dysfunction as a mechanistic contributor to microvascular angina and vasospastic angina in patients with INOCA. The findings are consistent with prior publications showing a high prevalence of coronary vasomotor dysfunction in patients who undergo comprehensive invasive coronary function testing. Importantly, endothelial function testing increased the diagnostic yield of testing beyond adenosine and vasospasm provocation from 75% to 92%.
Endothelial function testing can be considered in patients with INOCA without existing traditional endothelial risk factors or coronary atherosclerosis, in which identification of endothelial dysfunction would prompt initiation of medical therapy aimed at improving endothelial function, such as statins and ACE inhibitors/angiotensin receptor blockers. Given the high prevalence of endothelial dysfunction in patients with INOCA, the European Society of Cardiology recommends to consider statin and ACE inhibitors/angiotensin receptor blockers in all patients with INOCA (Kunadian V, et al. Eur Heart J. 2020;doi:10.1093/eurheartj/ehaa503), but we do not have evidence that this is the optimal strategy for all INOCA patients. The WARRIOR clinical trial (ClinicalTrials.gov ID: NCT03417388) aims to determine whether intensive medication treatment with statin plus ACE inhibitors/angiotensin receptor blockers in women with suspected INOCA will reduce major adverse CV events.
As INOCA is a heterogenous condition with various endotypes associated with differing therapeutic targets and varying levels of long-term CV risk, more precise coronary function testing may lead to targeted therapy to improve CV outcomes. The CorMICA trial (Ford TJ, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.09.006) demonstrated that stratified medical therapy based on diagnosis of microvascular angina vs. vasospastic angina improved 6-month and 1-year angina and quality of life measures.
The 2021 American College of Cardiology/American Heart Association chest pain guideline does not mention endothelial function testing in its proposed INOCA algorithm. I would like to thank the authors for sharing their finding that of patients with normal adenosine-mediated vasodilation (CFR) and no inducible coronary artery spasm, 68% had endothelial dysfunction. These results indicate that endothelial function testing provides more comprehensive assessment of vasomotor dysfunction in patients with INOCA.
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