## 4 Discussion
demonstrated the transverse/longitudinal ratio of RMS as a potential biomarker for identifying patients with HF [22]. Another recent study by [PERSON]. [PERSON] et al. showed an association between the degree of dysysynchrony and the HDF ratio measured using 4D-flow MRI in patients with HF [40]. Our study also found a significant divergence in the transverse/longitudinal ratio of RMS between controls and MR patients with preserved EF and MR severities. Our findings indicate that HDF can effectively differentiate between healthy individuals and those with MR.  
A clinical study by [PERSON] et al. identified the correlation between severe congestive HF and MR. The congestive heart failure was defined as EF less than or equal to 35%. MR was severe in 4.3%, moderate-severe in 12.5%, moderate in 21.9%, mild-moderate in 11.8%, mild in 39.1%, and absent or present in 10.4% of the patients [41]. A comprehensive study by [PERSON] et al. described HDF for various cardiac conditions such as HF, idiopathic dilated cardiomyopathy, and CRT and for competitive athletes (healthy). They concluded that HDF analysis could offer invaluable insights into myocardial dysfunction [15]. Previous studies on HDF demonstrated functional correlation with various cardiac disease states but lacked data on MR severities. Our study filled this knowledge gap and focused on the impact of HDF on different MR severities. MR is associated with increased cardiovascular mortality among patients with prior myocardial infarction or systolic dysfunction [41]. We know that LV function plays a vital role in assessing LV remodeling and MR classification [42]. Therefore, our study focused on the association between HDF and LV function (specifically LVESV, LVEDV, LVM, and LVEF) among different MR severities. This study was designed separately for systolic and diastolic HDF and volume. However, the correlation analysis was performed for both systolic and diastolic phases between HDF and EF, LVM. MR leads to an LV volume overload due to increased SV, caused by increased blood volume within the LA and an increased preload delivered to the LV during diastole. Volume overload from MR causes the ventricle to expand, widens the mitral annulus, and reduces leaflet coaptation, leading to the progressive worsening of MR. Eventually, the volume overload becomes so severe that the membrane's excitation-contraction coupling becomes impaired, and the afterload on the LV due to wall stress leads to dilation with decreased contractility, resulting in a reduction in EF [2, 6, 43]. We hypothesized that LV volume in both the systolic and diastolic phases is related to HDF among MR patients with preserved EF. We found a positive correlation between LVESV and systolic HDF (AVG S-L and systolic ratio) among healthy controls. On the contrary, an altered correlation was observed among moderate-severe MR and trivial-mild MR, respectively. AVG S-L HDF was significantly reduced (54.5%), while the systolic ratio was significantly increased in patients (86.2%) compared to controls. This altered correlation revealed that AVG S-L decreases with increased systolic volume indicating systolic dysfunction. Increased LVESV is reportedly associated with severe MR and with the combination with reduced EF is suggested for surgical intervention. The systolic AVG B-A demonstrated a negative correlation with LVESV among controls; however, we did not find any significant association among patients. Therefore, further investigation is warranted. In the diastolic phase, we found a positive correlation between RMS HDF in the S-L and B-A direction and volume among patients with moderate-severe MR. This reveals that, as the HDF increases, the volume also increases potentially. It is important to note that we found an altered relation among controls with a weak-negative correlation for RMS B-A; however, this result was insignificant. EF is typically significantly reduced in patients with severe MR [44]. EF is sensitive to changes in LV hemodynamic loading conditions.