With an incidence of 34.88% (30/86) and a predominant location in the segments proximal to MB of the LAD, our results are in line with previous reports based on CTA[1-4]. Studies have shown that the milking effect of MB triggers abnormal hemodynamics in MB-located arteries, which was manifested as low and oscillating blood flow in the proximal segment[22]. The abovementioned alterations not only decrease wall shear stress (WSS) but also damage endothelial cells, which increases the residence time of some atherosclerotic blood particles and subendothelial accumulation, ultimately promoting the atherosclerotic stenosis process[5, 8, 23]. In addition, with increasing age and risk factors for atherosclerosis such as hyperlipidemia and diabetes[12, 19], patients with MBs are often accompanied by non-MBRS. Therefore, it is worth studying the roles of the two types of stenoses (MBRS and non-MBRS) in the hemodynamics of MB patients.
1. The imaging characteristics analysis of MBRS and non-MBRS in MB patients.
According to the findings of our study, on the one hand, no significant differences in MBRS incidence and location were identified between MB patients with and without concomitant non-MBRS, which revealed that the risk factors for non-MBRS, such as hyperlipidemia, obesity and diabetes, do not alter the occurrence and location of MBRS. On the other hand, the prevalence and distribution of non-MBRS in the LCX and/or RCA had no significant difference in the MB population regardless of the presence of MBRS, which meant that MBRS had no impact on the occurrence and location of atherosclerotic stenoses in coronary arteries other than MB.
However, we found that in the concomitant non-MBRS group, the severity of MRBS tended to be greater than 50%. This implies that non-MBRS risk factors may worsen the severity of MBRS.
2. The hemodynamic alterations induced by MBRS
2.1 The impact of MBRS on the hemodynamic alterations in MB-located arteries
Generally, atherosclerotic stenosis may result in hemodynamic changes[24]. Before the onset of stenosis, the hemodynamics of the MB-located artery are determined by the milking effect; however, once MBRS occurs, the hemodynamic alterations will be the result of a combination of the “milking effect” and stenosis.
Our study found that the rCBF redistribution of the MB-located artery was altered before the occurrence of MBRS, which manifested as a decrease in rCBF in segments proximal to the MB and bridge segments, as well as an increase in rCBF in distal segments, compared with the non-MB control group. The abovementioned findings indicate that the milking effect of MB contributes to the redistribution of blood flow in the MB-located artery, which is the hemodynamic reason why the proximal segment is prone to stenosis while the distal segment is far from stenosis.
Nonetheless, with the presence of MBRS, the rCBF distribution of the MB-located artery further changed. There was an elevation in rCBF in the proximal and bridge segments, and a decrease in rCBF in the distal segments, particularly at adenosine stress, which suggested that MBRS was a possible protective factor for CBF in the MB-located artery and partially corrected the abnormal CBF redistribution due to the “milking effect” of MB because rCBF in the proximal and distal segments was not significantly different from that in the control group, except for the still reduced rCBF in the middle segment. We speculate that the possible reason may be that MBRS is somewhat similar to a heart valve, reducing the bidirectional disturbed blood flow from bridge artery compression and improving the rCBF distribution.
2.2 Effect of MBRS on the hemodynamics of coronary arteries other than MB located
The results of our study exhibited a prominent reduction in CFR in the LCX after the occurrence of MBRS in the LAD. We further found that the elevated rCBF at rest rather than the reduced rCBF at stress was considered to contribute to this CFR reduction in LCX. The elevated rCBF at rest implied that the LCX, another branch of the LM, benefited in terms of rCBF redistribution after the occurrence of MBRS in the LAD.
3. Effect of non-MBRS on the hemodynamics of the MB-located artery
Some factors (e.g., hyperlipidemia, obesity and diabetes) increase the risk of non-MBRS[12, 19], and concomitant non-MBRS is frequently observed in patients with MB. Then, what about the effect of non-MBRS on the hemodynamics in MB-located artery? After administration of adenosine to dilate vessels, MB patients with concomitant non-MBRS had significantly lower absolute CBF in the MB-located artery compared to the without non-MBRS group. Based on the fact that the causative agent of non-MBRS is usually nonspecific and does not target a specific vessel, all three coronary arteries are usually affected simultaneously. However, unlike the other two coronary arteries, the MB-located artery shows specific hemodynamic changes due to the milking effect, which could explain the unchanged location and incidence of MBRS. The above suggests that the milking effect dominates the hemodynamic alterations in the MB-located artery.
In addition, in MB patients with non-MBRS, the absolute CBF of the MB-located artery is still inevitably lower than that in the group without non-MBRS. Therefore, MB patients also need to reduce the risk factors for non-MBRS.
Therefore, we propose a hypothesis that MB itself determines the incidence and location of MBRS, mediated through redistribution of rCBF in the MB-located artery due to the "milking effect". However, the risk factors for non-MBRS worsen the severity of MBRS rather than the incidence and location by altering the absolute CBF rather than the relative CBF (rCBF redistribution).
4. Limitations:
The CBF data of the RCA in this study are incomplete, providing only a portion of the segments corresponding to the left ventricular myocardium due to the limitations of the analysis software. Another limitation is the inadequate number of MB cases. Enrolled cases in this study not only completed all CCTA, D-SPECT and CA but also D-SPECT and CA within a 4-week interval. In addition, MB cases for which milking effects were not observed were excluded. Therefore, further studies with a large sample size are needed.