Reduced Microvascular Blood Volume as a Driver of Coronary Microvascular Disease in Patients With Non-obstructive Coronary Artery Disease: Rationale and Design of the MICORDIS Study

Background: Ischemia with non-obstructive coronary arteries (INOCA) is part of the ischemic heart disease spectrum, and is particularly observed in women. INOCA has various mechanisms, such as coronary vasospasm and coronary microvascular dysfunction (CMD). A decreased coronary flow reserve (CFR) and-or increased myocardial resistance (MR) are commonly used to diagnose CMD. However, CFR and MR do not describe all pathophysiological mechanisms underlying CMD. Increased myocardial oxygen consumption (MVO2) normally increases myocardial blood volume (MBV), independently from myocardial blood flow (MBF). In addition insulin enhances MBV in healthy skeletal muscle, and this effect is impaired in INOCA-related conditions such as diabetes and obesity. Therefore, we propose that MBV is reduced in INOCA patients.Aim: To assess whether myocardial blood volume (MBV) is decreased in INOCA patients, at baseline, during hyperinsulinemia and during stress.Design: The MICORDIS-study is a single-center observational cross-sectional cohort study (identifier NTR7515). The primary outcome is MBV, compared between INOCA patients and matched healthy controls. The patient group will undergo coronary function testing using a Doppler guidewire, intracoronary adenosine and acetylcholine to measure CFR and coronary vasospasm. Both the patient- and the control group will undergo myocardial contrast echocardiography (MCE) to determine MBV at baseline, during hyperinsulinemia and during stress. Subsequently, cardiac magnetic resonance (CMR) will be evaluated as a new and noninvasive diagnostic tool for CMD in INOCA patients. Microvascular endothelial function is a determinant of MBV and will be evaluated by non-invasive microvascular function testing using EndoPAT and by measuring NO production in circulating endothelial cells (ECFCs).

Influence of cardiac phase on myocardial native T1 values by a segmental approach

Funding Acknowledgements Type of funding sources: None. Background. Native T1 values are usually assessed in the end-diastole to minimize motion artifacts while the systolic data acquisition offers the advantage of a thicker myocardium, with reduced partial-volume effects. Higher myocardial T1 values have been detected in diastole at both 1.5T and 3T but the dependence of this difference on myocardial segments or gender has not been fully explored. Aim. We provided a systematic comparison of myocardial native T1 values in diastole and systole, by considering separately myocardial segments and dividing males and females. Methods. Sixty-one healthy subjects (46.0 ± 14.1 years, 32 males) underwent CMR at 1.5T (Signa Artist; GE Healthcare). Three short-axis slices of the left ventricle acquired in diastole and systole using a Modified Look–Locker Inversion Recovery sequence. Image analysis was performed with a commercially available software package. T1 value was assessed in all 16 myocardial segments and global value was the mean. Results. Table 1 shows the comparison between T1 values calculated from maps obtained in diastole and systole. Systolic T1 values were significantly lower in the basal anterolateral segment, in all medium segments except for the medium inferior segment, and in all apical segments. The percentage difference between diastolic and systolic T1 values was considered to compensate for the higher T1 values in females, and a significantly higher value was detected in females for the majority of medium segments, for all apical segments, and for the global value. Conclusion. The diastolic-systolic discrepancy was more pronounced for the females and at the apical level, supporting the hypothesis that, besides the physiologic variations in myocardial blood volume during the cardiac cycle, the partial volume-effect may be a strong additional contributing factor. Native T1 values should be obtained always in the same cardiac phase to avoid a potential bias in the discrimination between healthy and pathologically affected myocardium.

Myocardial blood volume and coronary resistance during and after coronary angioplasty

Animal experiments have shown that the coronary circulation is pressure distensible, i.e., myocardial blood volume (MBV) increases with perfusion pressure. In humans, however, corresponding measurements are lacking so far. We sought to quantify parameters reflecting coronary distensibility such as MBV and coronary resistance (CR) during and after coronary angioplasty. Thirty patients with stable coronary artery disease underwent simultaneous coronary perfusion pressure assessment and myocardial contrast echocardiography (MCE) of 37 coronary arteries and their territories during and after angioplasty. MCE yielded MBV and myocardial blood flow (MBF; in ml·min−1·g−1). Complete data sets were obtained in 32 coronary arteries and their territories from 26 patients. During angioplasty, perfusion pressure, i.e., coronary occlusive pressure, and MBV varied between 9 and 57 mmHg (26.9 ± 11.9 mmHg) and between 1.2 and 14.5 ml/100 g (6.7 ± 3.7 ml/100 g), respectively. After successful angioplasty, perfusion pressure and MBV increased significantly ( P < 0.001 for both) and varied between 64 and 118 mmHg (93.5 ± 12.8 mmHg) and between 3.7 and 17.3 ml/100 g (9.8 ± 3.4 ml/100 g), respectively. Mean MBF increased from 31 ± 20 ml·min−1·g−1 during coronary occlusion, reflecting collateral flow, to 121 ± 33 ml·min−1·g−1 ( P < 0.01), whereas mean CR, i.e., the ratio of perfusion pressure and MBF, decreased by 20% ( P < 0.001). In conclusion, the human coronary circulation is pressure distensible. MCE allows for the quantification of CR and MBV in humans.