Adenosine vs Regadenoson Pharmacologic Stress Differs in Women with Suspected Coronary Microvascular Dysfunction: A Report from the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) Study.

Background: Stress cardiac magnetic resonance (CMR) imaging with myocardial perfusion reserve index (MPRI) measurement has emerged as a noninvasive method for assessing coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD). Pharmacologic stress with adenosine or regadenoson is typically used with comparable coronary vasodilation, but higher unadjusted MPRI has been reported with regadenoson in healthy men. This difference has not been assessed in symptomatic or healthy women. Methods: In a prospective cohort study, 139 symptomatic women with suspected CMD and no obstructive CAD underwent stress CMR and invasive coronary flow reserve (CFR) testing. Adenosine was the default vasodilator (n=99), while regadenoson was used if history of asthma or prior adenosine intolerance (n=40). Stress CMR was also performed in 40 age-matched healthy controls using adenosine (n=20) and regadenoson (n=20). Unpaired t-tests and analysis of covariance were performed to compare MPRI with adenosine and regadenoson in the symptomatic women and healthy controls. Results: Compared to regadenoson cases, adenosine cases had lower invasive CFR (2.64±0.62 vs 2.94±0.68, p=0.01) and pharmacologic heart rate change (28±16 vs 38±15 bpm, p=0.0008). Unadjusted MPRI was lower in the adenosine compared to regadenoson cases (1.73±0.38 vs 2.27±0.59, p<0.0001). When adjusted for heart rate, rate-pressure-product, and invasive CFR, MPRI remained lower in the adenosine cases (p<0.0001). Invasive CFR to adenosine correlated with adenosine MPRI (r 0.17, p=0.02) but not regadenoson MPRI (r -0.14, p=0.19). There was no significant difference in MPRI in the controls who received adenosine vs regadenoson (2.27±0.33 vs 2.38±0.44, p=0.36). Conclusion: In women undergoing stress CMR for suspected CMD, those who received adenosine had lower MPRI than those who received regadenoson. However, there were no differences in MPRI in the healthy controls. These findings suggest there may be physiologic differences in adenosine and regadenoson response in the coronary microcirculation of symptomatic women.

Coronary microvascular dysfunction: sex-specific risk, diagnosis, and therapy.

Cardiovascular disease is the leading cause of death worldwide. In the presence of signs and symptoms of myocardial ischaemia, women are more likely than men to have no obstructive coronary artery disease (CAD). Women have a greater burden of symptoms than men, and are often falsely reassured despite the presence of ischaemic heart disease because of a lack of obstructive CAD. Coronary microvascular dysfunction should be considered as an aetiology for ischaemic heart disease with signs and symptoms of myocardial ischaemia, but no obstructive CAD. Coronary microvascular dysfunction is defined as impaired coronary flow reserve owing to functional and/or structural abnormalities of the microcirculation, and is associated with an adverse cardiovascular prognosis. Therapeutic lifestyle changes as well as antiatherosclerotic and antianginal medications might be beneficial, but clinical outcome trials are needed to guide treatment. In this Review, we discuss the prevalence, presentation, diagnosis, and treatment of coronary microvascular dysfunction, with a particular emphasis on ischaemic heart disease in women.