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Endotypes of angina with non-obstructive coronary arteries: a prospective multicentre study
Steve Miner1, Hernan Mejia-Renteria2, Antonio Maria Leone3
1Southlake Regional Health Centre Toronto, Canada.
Insights
Angina with non-obstructive coronary arteries (ANOCA) is common, especially in women. This study identified eight distinct endotypes of ANOCA using coronary functional testing, enabling tailored, mechanism-guided therapies.
Area of Science:
- Cardiology
- Vascular Biology
- Clinical Medicine
Background:
- Angina with non-obstructive coronary arteries (ANOCA) is a frequent cause of chest pain, disproportionately affecting women.
- The underlying mechanisms of ischaemia in ANOCA are often difficult to diagnose, leading to empirical treatment strategies.
Purpose of the Study:
- To investigate the haemodynamic endotypes of angina with non-obstructive coronary arteries (ANOCA).
- To identify endotype-specific therapies for ANOCA through a Delphi consensus method.
Main Methods:
- Prospective enrollment of 1001 patients with angina and no obstructive coronary artery disease across nine European and North American centers.
- Assessment of coronary flow reserve and resistance using intracoronary sensors and bolus thermodilution during resting conditions and pharmacologic stress (adenosine, acetylcholine).
- Defined eight distinct haemodynamic endotypes and investigated their clinical correlates using regression analysis; Delphi consensus identified endotype-specific therapies.
Main Results:
- Eight distinct endotypes were identified, including epicardial coronary spasm, microvascular spasm, endothelial dysfunction, and enhanced cardiac nociception, with some patients exhibiting multiple endotypes.
- Each endotype was associated with specific clinical characteristics.
- A consensus was reached on endotype-specific medical therapies for all identified ANOCA endotypes.
Conclusions:
- Pharmacologic stress testing with adenosine and acetylcholine effectively identifies distinct haemodynamic endotypes in patients with suspected ANOCA.
- This mechanism-guided approach enables stratified medicine for ANOCA, moving beyond empirical treatment.
Background And Aims:
Angina with non-obstructive coronary arteries (ANOCA) is a prevalent myocardial ischaemic syndrome, and women are disproportionately affected. Mechanisms of ischaemia are challenging to diagnose and treatment is empirical.
Methods:
Consecutive patients with angina (or equivalent symptoms), no angiographically severe stenosis and fractional flow reserve > 0.80 undergoing coronary functional testing were prospectively enrolled in nine centres in Europe and North America. Haemodynamic 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 adenosine and acetylcholine. Chest pain and electrocardiographic ischaemic changes were recorded. The participant characteristics of each haemodynamic endotype were investigated using regression analysis. A three-step Delphi consensus method was applied to identify endotype-specific therapies.
Results:
Overall, 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: high resting coronary blood flow (n = 195, 19%); high resistance (n = 125, 13%); compensated high resistance (n = 112, 11%); epicardial coronary spasm (n = 162, 17%); microvascular spasm (n = 75, 8%); endothelial dysfunction (n = 96, 10%); ischaemia w/o haemodynamic changes (n = 68, 7%); and enhanced cardiac nociception (n = 79, 8%). More than one endotype occurred in 119 (12%) individuals and normal responses occurred in 234 (23%) individuals. Each endotype was associated with distinct clinical correlates. The Delphi consensus (100% 'agree' or 'strongly agree') identified endotype-specific medical therapy with a Likert scale score ≥ 6 for all endotypes.
Conclusions:
In patients with suspected ANOCA, assessment of the symptomatic, electrocardiographic, and haemodynamic responses to adenosine and acetylcholine identifies distinct endotypes and enables mechanism-guided stratified medicine.
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