Refractory angina in women with ischemia and no obstructive coronary artery disease — A report from the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study

Women with suspected ischemia and no obstructive coronary artery disease (INOCA) are often challenging to manage. We aimed to understand mechanisms and treatable pathways of refractory angina. The Women's Ischemia Syndrome Evaluation – Coronary Vascular Dysfunction ( NCT00832702 ) recruited women between 2008 and 2015. In a pre-defined subgroup ( n = 198) with repeat cardiac magnetic resonance imaging (CMRI) at 1-year, we investigated severity of angina (Seattle Angina Questionnaire-7) in relation to risk factors, baseline invasive coronary function testing, and CMRI parameters. Refractory angina was defined as SAQ-7 score < 75 at baseline and < 10-point improvement at 1-year. Women with refractory angina ( n = 60, 30 %), compared to those without, had lower incomes, and higher proportion of hypertension and nitrate use at 1-year ( p < 0.05). They also had significantly lower baseline coronary blood flow (CBF) response to acetylcholine ( p < 0.01). Myocardial perfusion reserve index was not different at baseline or follow-up. At 1-year, changes in SAQ domain scores significantly differed between groups, with persistent lack of improvement in physical limitation, disease perception, angina stability, and angina frequency ( p < 0.05) in the refractory group. In an age-adjusted regression model, hypertension (OR 4.48; 95 % CI 1.23–16.25; p = 0.02) and abnormal CBF (OR 3.34; 95 % CI 1.04–10.72; p = 0.04) were associated with refractory angina. Refractory angina is common in women with INOCA. Hypertension and endothelial-dependent microvascular dysfunction are independently associated with a 4- and 3-fold increase in refractory angina at 1-year, respectively. These findings may identify potential treatment targets to reduce angina burden in INOCA.