Evaluation of computed tomography myocardial perfusion in women with angina and no obstructive coronary artery disease.

Women with angina and no obstructive coronary artery disease (CAD) have worse cardiovascular prognosis than asymptomatic women. Limitation in myocardial perfusion caused by coronary microvascular dysfunction (CMD) is one of the proposed mechanisms contributing to the adverse prognosis. The aim of this study was to assess myocardial perfusion in symptomatic women with no obstructive CAD suspected for CMD compared with asymptomatic sex-matched controls using static CT perfusion (CTP). We performed a semi-quantitative assessment of the left ventricular myocardial perfusion and myocardial perfusion reserve (MPR), using static CTP with adenosine provocation, in 105 female patients with angina and no obstructive CAD (< 50% stenosis) and 33 sex-matched controls without a history of angina or ischemic heart disease.  Patients were on average 4 years older (p = 0.04) and had a higher burden of cardiovascular risk factors. While global perfusion during rest was comparable between the groups (age-adjusted p = 0.12), global perfusion during hyperemia was significantly reduced in patients compared with controls (163 ± 23 HU vs. 171 ± 25 HU; age-adjusted p = 0.023). The ability to increase myocardial perfusion during adenosine-induced vasodilation was significantly diminished in patients (MPR 148% vs. 158%; age-adjusted p < 0.001). This remained unchanged after adjustment for cardiovascular risk factors (p = 0.008). Women with angina and no obstructive CAD have reduced hyperemic myocardial perfusion and MPR compared with sex-matched controls. Impaired myocardial perfusion may be related to the presence of CMD in some of these women.

Effect of liraglutide on body weight and microvascular function in non-diabetic overweight women with coronary microvascular dysfunction.

BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with adverse cardiovascular outcomes and CMD is a hallmark of type 2 diabetes. Liraglutide improves cardiovascular prognosis through partly unknown mechanisms. We hypothesized that treatment with liraglutide improves CMD and symptoms through weight loss, in non-diabetic overweight patients with angina and no obstructive coronary artery disease (CAD). METHODS: We included 33 non-diabetic overweight women (BMI > 25) with CMD (Coronary flow velocity reserve (CFVR) ≤2.5), angina symptoms and no obstructive CAD, in an open-label proof-of-concept study. The protocol included a control period of 5 weeks followed by an intervention period with liraglutide aiming at 3 mg daily for 12 weeks. Participants were investigated before and after the control period and again 1-2 weeks after last liraglutide dose. Primary outcomes were change in CFVR and change in angina symptoms measured by the Seattle Angina Questionnaire (SAQ) in the intervention period compared with the control period. (clinicaltrials.gov, NCT02602600, and ethically approved). RESULTS: Twenty-nine participants completed the study. Liraglutide treatment led to a significant weight loss (mean 6.03 kg (95%CI: 5.22;6.84)) and decrease in systolic blood pressure (mean 10.95 mm Hg (95%CI: 4.60;17.30)). Baseline median CFVR was 2.30 (IQR 1.91;2.51) and remained unchanged after liraglutide treatment (mean change 0.07 (95%CI: -0.07;0.21)). There were no effects on symptoms measured by SAQ or parameters of left ventricular systolic as well as diastolic function. CONCLUSIONS: Treatment with liraglutide led to significant weight loss and lowering of blood pressure with no concomitant symptoms alleviation during treatment and no improvement in coronary microvascular function.

Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial.

OBJECTIVE: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD). METHODS: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081). RESULTS: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported. CONCLUSIONS: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction.