122 Chapter 6 Myocardial blood volume in ANOCA entities As described above, 16 out of 28 ANOCA patients were diagnosed with coronary vasomotor dysfunction according to the COVADIS criteria, 9 patients had equivocal results, and 3 had completely normal CFT results. No difference in MBV or MVR during baseline, hyperinsulinemia and dobutamine-induced stress was found between the different coronary vasomotor disorders (Figure 2B). Although abnormal HMR and reduced MBV are both associated with structural microvascular disease, no correlation was observed between them (Supplemental Figure 4). Myocardial blood flow Supplemental Figure 5 and Supplemental Table 3 show MBF, and the change in MBF in response to hyperinsulinemia and dobutamine-induced stress. ANOCA patients had a lower maximal MBF during dobutamine-induced stress (29.93 ± 16.46 mL/min/g vs 43.32 ± 18.46 mL/min/g, respectively p = 0.008) and a significantly lower increase in MBF from baseline to dobutamine-induced stress (dobutamine-induced stress 0.87 [0.52–1.12 vs 1.08 [0.86–1.52], respectively p = 0.030) compared to controls. There was no difference in the MBF response to hyperinsulinemia (Supplemental Table 3). Myocardial response to hyperinsulinemia and dobutamine-induced stress The M-value was significantly lower in ANOCA-patients compared to healthy controls (36.8 mol/kg/min [32.2–44.3] vs 69.1 mol/kg/min [40.4–83.7], respectively p < 0.001). No differences were found between the ANOCA entities (p = 0.790) (Supplement Figure 6). We did not find a correlation between the M-value and MVR in response to hyperinsulinemia (Supplemental Figure 7A), or between the M-value and MBF in response to hyperinsulinemia (Supplemental Figure 7B). Heart rate reserve was significantly lower in ANOCA patients compared to healthy controls (54.8 BPM ± 21.6 vs. 67.1 BPM ± 11.9, respectively p = 0.018) (Figure 3C). After adjustment for age, a trend towards a lower heart rate reserve was observed in ANOCA patients compared to healthy controls (100.0 [69.4–118.9] vs. 107.2 [103.8–120.7], respectively p = 0.070). No correlation was identified between the HRR and MVR in response to dobutamine-induced stress (Supplemental Figure 8A), or MBF in response to dobutamine-induced stress (Supplemental Figure 8B). DISCUSSION In the present study, we evaluated the role of myocardial blood volume and microvascular recruitment in the pathophysiology of ANOCA, using myocardial contrast echocardiography. We report that relative myocardial blood volume is significantly lower in ANOCA patients compared with healthy controls both in resting conditions as well as during hyperinsulinemia and dobutamine-induced stress. Moreover, insulin-sensitivity and heart rate reserve are reduced in ANOCA patients compared to healthy controls.
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