Endotypes of angina with non-obstructive coronary arteries

Abstract Background Angina with non-obstructive coronary arteries (ANOCA) is a prevalent myocardial ischemic syndrome. Mechanisms of ischemia are challenging to assess and medical therapy is empirical. Methods Patients with suspected ANOCA were prospectively enrolled in nine centers in Europe and North America. Hemodynamic endotypes were assessed measuring coronary flow reserve and resistance using an intracoronary pressure- and temperature-sensitive sensor and bolus thermodilution. Measurements were obtained during resting conditions and following intracoronary infusion of adenosine and acetylcholine. Chest pain and electrocardiographic ischemic changes were also recorded. The participant characteristics associated with each hemodynamic endotype were investigated using regression analysis. A three-step Delphi consensus method to identify endotype-specific therapies was completed by thirteen invasive cardiologists. Results 1001 participants (mean age 62±11years, 56% female) were enrolled and eight distinct endotypes were defined by adenosine testing (n=3) and acetylcholine testing (n=5), respectively: elevated resting coronary blood flow, n=195 (19%); impaired endothelium-independent vasodilation, n=125 (13%); compensated endothelium-independent dysfunction, n=112 (11%); epicardial coronary spasm, n=162(17%); microvascular spasm, n=75 (8%); endothelial dysfunction, n=96 (10%); ischemia w/o hemodynamic changes (microvascular steal), n=68 (7%); and enhanced cardiac nociception, n=79 (8%). More than one endotype occurred in 186(19%) individuals and normal responses occurred in 234 (23%) individuals. Each endotype was associated with distinct clinical correlates. The Delphi clinician consensus (100% "agree" or "strongly agree") identified endotype-specific medical therapy with a Likert scale score ≥6 for all endotypes. Conclusion In patients with suspected ANOCA a systematic assessment of the symptomatic, electrocardiographic and hemodynamic responses to adenosine and acetylcholine identifies distinct endotypes and enables mechanism-guided stratified angina therapy.Summary of Endotypes Heat Map of Endotypes and risk factors