In the present study, we examined the feasibility of MW parameters for evaluating the LV function in MHD patients with or without LVH and found that GWI, GCW, GWW, and GWE had appreciable AUC, specificity, and sensitivity in the LVH group. Therefore, we believe that these MW parameters may be reliably used to accurately evaluate the LV function in MHD patients, thus providing a prediction for the development and progression of LVH in these patients.
In this study, we first analyzed the conventional echocardiographic parameters for participants in the three groups and found that although the LVEF of patients in the LVH group was significantly lower than that in the normal group, the NLVH and normal groups had comparable LVEF. Further, the NLVH and LVH groups had significantly higher LVIDD, LVIDS, LAD, LVEDV, and LVESV than the normal group, indicating that the MHD patients underwent LV remodeling, a structural basis for LV dysfunction [18, 19]. A previous study showed that there was no significant difference in LV diameter and wall thickness between non-hemodialysis and hemodialysis patients [20], indicating that hemodialysis does not significantly improve LV remodeling and cardiac contractile function in patients. On the contrary, with the prolongation of dialysis time and the aggravation of LV remodeling, the LV systolic function in MHD patients will be further impaired. The main feature of LV lesions in MHD patients is the progression of the compensatory phase of LVH to the decompensatory phase, because these patients have long-term pressure overload, including chronic hypertension, anemia, secondary hyperparathyroidism, and arteriovenous fistula[21, 22].
Our further analysis revealed that LVH and NLVH patients had significantly lower GLS than the normal subjects. Moreover, with the increase in the LV thickness and prolongation of the dialysis time, the GLS decreased significantly, which was accompanied by a decrease in the LV systolic function, as evidenced by the lower GLS in LVH patients than in NLVH patients. These findings were in line with our previous report [23]. GLS is usually obtained from 2D-STI technology, which quantitatively measures the mechanical parameters for LV function [24, 25]. GLS is considered to be a better indicator than EF and is widely used in clinics to assess LV function[26]. However, some scholars recently suggested that strain measurements are susceptible to load, which in turn affects the accurate assessment of myocardial function [27]. Therefore, it is important to use effective screening methods to verify the GLS.
Recently, the MW parameters derived from PSL have been used to determine LV function and shown to have a good agreement between the noninvasively measured PSL and the invasively directly measured PSL [28]. In this study, we examined the possibility of using MW parameters to assess LV function in MHD patients. We found that the LVH group had significantly lower GLS, GWI, GCW, and GWE but higher GWW than the normal and NLVH groups. LVH patients have pathological cardiac changes including disordered arrangement of myocardial fibers and increased myocardial interstitial fibrosis due to damage to myocardial cells [29]. In addition, LVH reduces the density of myocardial microcirculation and myocardial blood supply [30], resulting in decreased GWI and GCW. Early studies have shown that GWI has a strong correlation with myocardial glucose metabolism, basically reflecting the local myocardial oxygen consumption [31, 32]. Galli et al. found that patients with ischemic or dilated cardiomyopathy had increased GWI and GCW after cardiac resynchronization therapy [33, 34]. Thus, GWI and GCW can be used as indicators of myocardial survival. It is noteworthy that GCW is also the main predictor of LV fibrosis [35].
In LVH patients, the LV myocardium is significantly damaged by the accumulated metabolites and increased myocardial fibrosis, resulting in the impairment of LV systolic function. In the normal heart, all myocardial segments contract in a synchronized manner, but MHD patients with LVH and myocardial fibrosis have altered electrophysiological characteristics in the myocardium, which causes myocardial excitation-contraction uncoupling [36]. Thus, the LV contraction is not synchronized in MHD patients with LVH, as reflected by the increased PSD. Hence, some LV segments elongate during contraction, significantly wasting MW, which is reflected by increased GWW. The decrease in GWE probably derived from increased GWW and decreased GCW in LVH patients, indicating that LVH in MHD patients can cause a significant reduction in LV systolic function.
The NLVH group had comparable GWI and GCW as the normal group, but higher GWI and GCW than the LVH group. Since the degree of LV myocardial impairment in the NLVH patients was smaller than that in the LVH patients, LV remodeling and fibrosis were not as severe as those in the LVH patients. Thus, it is understandable that NLVH patients had higher GWI and GCW than the LVH patients. MHD patients usually have poorly controlled hypertension [37]. In order to counteract the increased afterload during contraction [14], the heart pump function is compensated by shifting to a higher energy level [38], which is evidenced by higher GWI and GCW. This also suggests that the LV myocardium was not significantly impaired in NLVH patients and that LVEF was maintained at a normal level by enhanced myocardial contractility. However, if the high GWI persists and exceeds the compensatory capacity of the myocardium, LV remodeling and dysfunction will occur [39]. In addition, the NLVH group had higher GWW but lower GWE than the normal group, with no significant difference in the LV PSD between the groups. This suggests that the GWW of the LV begins to increase while the LV thickness and synchronicity are still within the normal range in MHD patients. However, due to a slight increase in GCW, GWE decreased slightly. In other words, MW increased in the NLVH patients to maintain the contractile function at a normal level, but myocardial ineffective work also increased, which can potentially lead to impaired myocardial systolic function.
LVEF is the most commonly used evaluator for LV systolic function in the clinic [40]. In the present study, we found that LVEF was positively correlated with GWI, GCW, and GWE, and negatively correlated with GWW. LV segments of the normal heart contract synchronously, and the MW generated by the myocardium to overcome the afterload can be quantified using GWI and GCW, both of which have a positive effect on LV ejection [34]. However, when GWW is at a low level, GWE should be close to 100% [41]. As the degree of myocardial injury increases in MHD patients, the decrease in LV systolic function is accompanied by an increase in GWW and a decrease in GWI, GCW, and GWE. MW can thus be used to quantitatively analyze the degree of LV injury in MHD patients, thus serving as a new sensitive indicator.
Our further analysis of the GLS and MW parameters for LVH patients revealed that the AUCs of GWE, GWW, and GLS were significantly higher than that of GWI and GCW. This observation was different from that in a previous study [42], in which the AUCs of GWI and GCW in CHD patients were higher than those of GLS, GWE, and GWW. This discrepancy may be explained by the different mechanisms underlying CHD and LVH in MHD patients. CHD is caused by the reduction or interruption of blood supply in the coronary arteries, leading to ischemia and necrosis of myocardial cells and early development of myocardial dysfunction [43]. This directly leads to a reduction in GWI and GCW. On the contrary, the damage from hemodialysis to the heart muscles is independent of the existence of coronary atherosclerosis [44]. Instead, the cardiac muscle damage in MHD patients is caused by the rapid changes in load [45], and the LV systolic function will only be significantly weakened during the decompensation period. Therefore, the test efficacy of GWI and GCW in MHD patients is relatively low. On the other hand, we found that the AUCs of GWE and GWW were higher than that of GLS. In addition, one of the main limitations of GLS is its load-dependence, and the increase in afterload can reduce the wall tension, leading to a misinterpretation of the true contractile function of the myocardium [42, 46]. However, for MW measurement, the non-invasive PSL integrates the afterload into the LV strain parameters, and thus MW is an optimization of the strain values [47]. Hence, the conclusions obtained from using non-invasive PSL are more comprehensive and objective.