Endotype-guided medical therapy and symptom response in ANOCA

BACKGROUND: Invasive coronary functional testing enables the classification of angina with non-obstructive coronary arteries (ANOCA) into distinct endotypes. However, real-world data linking endotype identification to subsequent pharmacological management and patient-reported symptom outcomes remain limited. AIMS: We sought to evaluate the association between coronary endotypes, post-testing pharmacological treatment patterns, and changes in angina-related quality of life in patients with ANOCA in a multicentre real-world registry. METHODS: Consecutive ANOCA patients undergoing invasive coronary functional testing were included. Patients were classified into six endotypes using adenosine- and acetylcholine-based testing. Pharmacological therapy was adjusted at the discretion of the treating physician based on the functional test results. The primary endpoint was a clinically meaningful improvement in angina-related health status, defined as a ≥5-point increase in the 7-item Seattle Angina Questionnaire (SAQ-7) summary score, assessed within each endotype. RESULTS: Among 525 patients, endotype distribution was as follows: normal physiology 10.5%, elevated resting coronary blood flow 8.8%, high resistance 13.9%, compensated high resistance 14.9%, epicardial spasm 33.3%, and microvascular spasm 18.7%. After testing, prescription patterns differed across the endotypes, with increased use of beta blockers, ranolazine, and renin-angiotensin-aldosterone system blockers in coronary microvascular dysfunction endotypes and greater use of non-dihydropyridine calcium channel blockers in vasospastic endotypes. At follow-up, a ΔSAQ-7 summary score ≥5 points was observed in elevated resting flow, high-resistance, compensated high-resistance, and epicardial spasm endotypes (all p<0.001) but not in microvascular spasm or normal physiology. CONCLUSIONS: In this multicentre real-world registry, invasive coronary endotyping was associated with distinct pharmacological management patterns and differential changes in angina-related quality of life across ANOCA endotypes.