Long-term angina-related healthcare utilization in women with ANOCA and impaired coronary flow velocity reserve

Background Most women evaluated for angina have no obstructive coronary artery disease (ANOCA), yet many have persistent symptoms1, and the long-term burden of angina-related healthcare utilization remains poorly defined. Coronary microvascular dysfunction (CMD), reflected by impaired coronary flow velocity reserve (CFVR), is common in ANOCA2 and may contribute to ongoing angina. We aimed to quantify recurrent angina-related hospital contacts and diagnostic testing in women with ANOCA and to examine whether impaired CFVR is associated with increased long-term healthcare utilization. Methods We conducted a registry-based follow-up study of women with ANOCA from the iPower cohort (2012-2018), a prospective study of women with angina, left ventricular ejection fraction >45%, and no obstructive coronary artery disease on invasive coronary angiography3. CFVR was assessed at baseline using transthoracic Doppler echocardiography. Women were stratified according to baseline CFVR (<2.25 vs. ≥2.25). Using Danish National registries, we identified angina-related hospitalizations (>1 day), outpatient contacts and ischemia-related procedures (coronary angiography, coronary CT angiography, stress echocardiography, positron emission tomography and myocardial perfusion scintigraphy). The primary endpoint was a composite of recurrent angina-related hospitalizations, outpatient contacts, and ischemia-related procedures. Recurrent events were analyzed using the Andersen-Gill extension of the Cox proportional hazards model: Hazard ratios (HRs) therefore reflect the total burden of events, rather than time to first event. Analyses were performed unadjusted and with multivariable adjustment for cardiovascular risk factors (age, BMI, hypertension, diabetes, smoking, dyslipidemia, atherosclerosis and baseline angina severity using the Seattle Angina Questionnaire). Results Among 1,681 women (CFVR ≥2.25: n=958; CFVR <2.25: n=723), impaired CFVR was associated with higher angina-related event rates. The composite event rate was 11.48 vs. 7.31 per 100 person-years in women with impaired and preserved CFVR, respectively (p<0.001). In unadjusted analyses, impaired CFVR was associated with increased recurrent events (HR 1.46, 95% CI 1.14-1.86), remaining significant after multivariable adjustment (HR 1.47, 95% CI 1.10-1.97). Hospitalizations were nearly doubled in women with impaired CFVR (adjusted HR 1.80, 95% CI 1.00-3.24). Ischemia-related procedures were also significantly increased (HR 1.28, 95% CI 1.02-1.60). Conclusion Among women with ANOCA, impaired CFVR is associated with increased recurrent angina-related healthcare utilization, independent of cardiovascular risk factors and baseline symptom severity. This suggest that CMD identifies a phenotype characterized by a higher burden of hospital contact and diagnostic testing. Recognition of CMD may therefore improve risk stratification and inform more targeted management strategies in this population.