## 4 Discussion
A decrease in the myocardial contractile state or an increase in LV afterload may cause a reduction in the EF. Regardless of the mechanism, a depressed EF can be an indication of surgical correction of MR [45]. [PERSON] et al. showed no correlation between EF and HDF in patients with HFpEF [19]. On the other hand, [PERSON] et al. showed that HDF is directly proportional to EF in patients with HF [15]. We shed light on the contradicting prior research. Our study demonstrated a positive correlation between EF and HDF (systolic average HDF, systolic RMS HDF, and average HDF in the S-L direction) among MR patients with trivial-mild severity grading. This result indicates the impairment of LV systolic ejection force in MR. Our study suggests a significant reduction in systolic average HDF in the S-L direction as the severity increases, and it is associated with systolic impairment. Studies have shown that elevated LVM and lower LV systolic function are associated with various cardiovascular diseases, including HF, VHD, and stroke [46; 47; 48; 49]. It is established that LVM is a key marker of severe MR. [PERSON] et al. concluded a positive linear correlation between LVM and MRV. Therefore, as the severity of MR increases, the LVM also increases linearly [29]. Another study by \(p\). [PERSON] et al. demonstrated that LVM significantly increases with MR severity [48]. A study by [PERSON] et al. demonstrated that elevated LVM and LV volume are associated with severe MR and eccentric LV hypertrophy (LVH) [3]. This gives strong evidence to conclude that LVM is a vital biomarker for evaluating MR severity and LVH. Our study revealed a significant positive association between LVM and systolic RMS HDF in all three directions. AVG HDF in the I-A direction demonstrated a linear increment of both parameters among MR patients with a severity of trivial-mild and moderate-severe. This contributes to existing knowledge, and we propose that systolic RMS HDF in all directions and AVG HDF in the I-A direction are linked to severe MR and LV remodeling. The HDF significantly increases with LVM and increased severity. After conducting the differential and correlation analysis, we extended our study to test the predictive ability of HDF. Since HDF demonstrated significant association with LV function, it revealed the platform for us to hypothesize HDF as a novel biomarker to detect MR. Finally, the multilinear regression model showed that systolic RMS B-A and diastolic RMS S-L were independently predictive parameters for detecting MR with preserved EF. Considerations and challenges in integrating 4D-flow derived HDF into clinical practice. Several challenges remain to achieve the widespread adoption and application of 4D-flow MRI. This includes limited velocity dynamic range, long and unpredictable scan times, data storage of large datasets, and time-consuming data processing. It is important to note that 4D-flow MRI is an established research technique typically conducted following clinical diagnostic sequences. But things are progressing rapidly, and some centers are now adding 4D-flow MRI to the routine clinical cardiac MRI protocols with clinically validated applications and postprocessing software [50]. Accuracy in 4D-flow MRI can be influenced by the choice of vendor sequences [51], acquisition parameters [52], and postprocessing software [53]. Therefore, local validation and quality assurance are essential. Currently, the workflow for 4D-flow derived-HDF assessment is non-standardized and time-consuming, which limits reproducibility and clinical translation. Addressing these limitations will require the development of efficient image analysis strategies with minimal user interaction. Furthermore, creating user-friendly software tools that simplify the visualization and interpretation of these metrics could facilitate their integration into clinical practice.