This study found that (1) the left ventricular global MW indices of NHCM patients, GLS, PSD, GCW, GWW, GWE, and GWI, were all impaired compared with those of healthy individuals; (2) there were differences in the global MW of the different types of NHCM patients, and a significant difference in GCW was observed; and (3) the MW indices derived from LV-PSLs can be used to assess myocardial function in NHCM patients.
HCM is an inherited cardiomyopathy characterized by increased myocardial mass. Most NHCM patients do not have obvious symptoms or signs at the early stage. As the disease progresses, abnormal myocardial hypertrophy and disordered myocardial fibers are observed in HCM patients, which can cause cardiomyocyte contractile dysfunction and impaired overall myocardial deformation capacity[15–17], ultimately leading to left ventricular diastolic and systolic dysfunction[18, 15–17]. LVEF reflects changes in left ventricular volume. When cardiac hypertrophy is not sufficient to cause a significant left ventricular volume change, LVEF loses its significance in the evaluation of the changes in left ventricular volume. Moreover, LVEF only significantly falls when there is severe hypertrophy or complications in the myocardium. Even though the body can maintain a positive level of LVEF through a compensatory mechanism, some patients may have cardiovascular events such as sudden cardiac death, malignant arrhythmias, and heart failure[19]. Among young people with sudden cardiac death, more than half suffer from pumping dysfunction due to HCM[20]. Accurate assessment of myocardial function in NHCM patients can provide valuable clinical information that will help us determine the prognosis of patients and take precautionary treatment measures as soon as possible.
In recent years, ECG has continuously advanced in the evaluation of cardiac function. Conventional M-mode ultrasound is affected by the sampling line, so the error is very large[21]. Many studies have used speckle-tracking imaging (STI) to evaluate LV myocardial function. STI is not affected by the sampling line and is noninvasive and convenient. However, due to the impact of afterload, it cannot reflect true myocardial contractile function, and its specificity is low[18]. Suga et al.[22, 23] studied invasive left ventricular pressure–volume loops and showed that regardless of the contractile state of the left ventricle, the pressure–volume area was linearly correlated with myocardial oxygen consumption. Recently, Russell et al.[10] replaced invasive measurement of left ventricular pressure by blood pressure measurement combined with left ventricular deformation parameters to construct the noninvasive LV-PSLs, used the LV-PSLs area to represent MW, and verified the feasibility of applying noninvasive LV-PSLs to evaluate MW. MW is a new parameter that takes into account cardiac afterload, largely eliminates the impact of afterload on myocardial strain, and can more realistically reflect left ventricular myocardial function. The effectiveness of noninvasive LV-PSLs in assessing left ventricular myocardial function has been confirmed in dog models and in screens of patients with acute coronary syndrome and cardiac resynchronization therapy response[24, 13, 8, 25].
Conventional echocardiography and two-dimensional STI of NHCM patients
LVEDd, LVEDs, and LVEF are commonly used to measure left ventricular global systolic function. GLS reflects myocardial contractile function by quantifying the degree of myocardial deformation. In this study, there was no significant difference in LVEF between the NHCM group and the control group, but the left ventricular GLS in the NHCM group was significantly lower than that in the control group, indicating that myocardial compliance had been reduced in the presence of no change in the LVEF of NHCM patients. On the one hand, during normal left ventricular wall contraction, the degree of myocardial thickening gradually decreased from the endocardium to the epicardium, 58% of which was endocardial fibrous thickening[26]. Subendocardial myocardium is composed of longitudinal myocardial fibers. On the other hand, the coronary flow reserve of HCM patients is insufficient, and the endo-myocardium is more sensitive to hypoxia. Therefore, when there is no change in LVEF, GLS shows a significant decrease[27–29]. The PSD represents synchronous myocardial contraction, and the PSD in the NHCM group was significantly prolonged. PSD can be prolonged because the cardiomyocyte hypertrophy in HCM patients and the extensive and uneven proliferation of myocardial interstitial cells lead to reduced elasticity during systole, which affects synchronous myocardial contraction, leading to prolonged peak contraction time. These results indicate that myocardial dysfunction is already present in NHCM patients before LVEF has changed.
Noninvasive MW of NHCM
The left ventricular wall gradually becomes thinner from the basal to the apical ventricular side in healthy people. Compensatory thickening occurs when the myocardium of NHCM patients cannot meet the needs of normal myocardial function. This thickening is not an increase in the number of cardiomyocytes but an increase in the volume of cardiomyocytes. Galli et al. [30]evaluated MW in HCM patients, and the results showed that the GCW of HCM patients was significantly lower than that of the control group (1599 ± 432 vs 2248 ± 249 mmHg%, P < 0.001), while the GWW of the two groups was not significantly different (141 ± 125 vs 101 ± 88 mmHg%, P = 0.18). In our study, GCW, GWI, and GWE were significantly lower in the NHCM group than in the control group, and the GWW level in NHCM group was higher than that of the control group, in line with the results of Hiemstra et al[31].These changes may be related to myocardial pathological changes in these patients. Irregular arrangement of myocardial fibers, interstitial proliferation, and an increase in stiffness resulted in weakened myocardial elasticity and deformability, leading to global MW failure. Changes in coronary artery structure in myocardial hypertrophy sites, insufficient microcirculation perfusion, and reduced capillary distribution density result in insufficient blood supply in the corresponding segments. In addition, myocardial hypertrophy causes reduced myocardial compliance, further affecting the synchronicity of myocardial contraction, thereby causing disorders of myocardial contraction, which may also GCW, GWE, and GWI to decrease and GWW to increase. The asynchronous contraction of the myocardium and reduced myocardial deformation capacity affect the global MW, increase myocardial oxygen consumption, and even aggravate myocardial remodeling, eventually leading to impaired myocardial work.
Differences in the MW of patients with different types of NHCMs
In this study, NHCMs were divided into three types, apical HCM, ventricular septal HCM, and concentric HCM, and the MW in patients with the different types of NHCM was analyzed. The global MW of patients with either of the three types of NHCM was not as good as that of the control group, especially the patients with concentric HCM. A significant difference in GCW was observed between all three types of NHCMs. The GCW of apical HCM was significantly higher than that of ventricular septal HCM and concentric HCM. However, GWW was not significantly different between three types of NHCMs, which may be related to the fact that GWW is mainly affected by bundle branch block and is consistent with the study of Galli et al[30]. Patients with apical HCM have more limited hypertrophy, which less affects the left ventricular systolic and diastolic function. Therefore, apical HCM has a weaker effect on global MW than the other two types. Ventricular septal HCM involves more segments, and the arrangement of cardiomyocytes in the hypertrophic site is disordered. The shortening rate of sarcomeres during contraction is significantly reduced compared to that of normal myocardium, and the regional myocardial strain rate is decreased. These greatly impact left ventricular contraction synchronization and fibrosis. In contrast, the overall left ventricular wall was thickened in patients with concentric HCM, and their cardiomyocytes were more hypertrophic and irregularly arranged than those of normal people, resulting in narrowing of the microvascular lumen within the ventricular wall under pressure, impaired microvascular perfusion, more severe cardiomyocyte ischemia, and more obvious myocardial fibrosis. These changes may have caused the lower GCW and GWW and the more obvious increase in GWW in patients with concentric HCM.
Hiemstra et al[31]. studied myocardial function in each segment of HCM patients, and the results showed that constructive work (CW) of the apical segments of patients with apical HCM was significantly reduced, septal CW was reduced in patients with ventricular septal HCM, and segmental CW (except for the apical segments) was reduced in patients with concentric HCM. The fibrosis and disordered arrangement of myocardium in hypertrophic segments of HCM is more obvious than those of non-hypertrophic segments[32], and the hypertrophic segment has weakened myocardial contractility due to severe lesions, while the myocardial contractile function in non-hypertrophic segments may be enhanced due to compensatory mechanisms to maintain the overall contraction strength. Therefore, studying the changes in MW in different types of HCM may provide a reference for the treatment options for different types of NHCM patients.