Reynolds HR, Picard MH, Spertus JA, et al. - In this study, the natural history of symptoms and ischemia in INOCA (ischemia with no obstructive coronary artery disease) was analyzed. An international cohort study CIAO-ISCHEMIA (Changes in Ischemia and Angina over One year in ISCHEMIA trial screen failures with INOCA) was undertaken from 2014-2019 including angina evaluations (Seattle Angina Questionnaire [SAQ]) and stress echocardiograms 1-year apart. In this ancillary study, patients with history of angina who were not randomized in the ISCHEMIA trial were incorporated. Correlation between alterations in SAQ Angina Frequency score and change in echocardiographic ischemia was the primary outcome. Findings revealed that in INOCA, patients commonly exhibited improvement in ischemia and improvement in angina but both did not correlate. The degree of inducible wall motion abnormalities in the INOCA cohort was similar to that noted in concurrently enrolled ISCHEMIA participants with obstructive coronary artery disease. The complicated nature of INOCA pathophysiology as well as the multifactorial nature of angina was emphasized by the findings.