It appears that nonatherosclerotic processes, including left ventricular hypertrophy and fibrosis, account for most of the excess cardiovascular risk in uremic patients . Equally, the increased pressure and volume overload usually result in compensatory myocardial hypertrophy and fibrosis, and the varying degrees of anemia, hypertension, hypocalcemia, and hyperphosphatemia aggravate their progress . Therefore, as a result of the changes in intracellular Ca2+ handling, myocardial hypertrophy, fiber disarray, and fibrosis, diastolic dysfunction seems to be more common and occurs earlier than systolic dysfunction in young uremic patients [15-17]. At the early stage, it usually seems difficult to find obvious changes in parameters reflecting diastolic dysfunction by conventional echocardiography, while LV hypertrophy and myocardial fibrosis are already present.
According to guidelines , among the following four variables: e¢, E/e’, LAVI and TR, <50% abnormal indicates normal LV diastolic function. In our study, although e¢ was decreased, there was no significant difference between E/e¢, TR and LAVI compared with controls. Considering the accuracy of e’ may be limited for several reasons: It depends greatly on the angle and easily influenced by LV relaxation and LA pressure. Mitral valve disease and annular calcification can affect its accuracy. And e’ cannot exactly reflect the global LV relaxation in patients with LV hypertrophy or heart failure with preserved LVEF, or in which regional systolic dysfunction is present [6, 18]. And previous researches have confirmed the incidence of cardiac valve calcification in PD patients is high , and some of them already exhibited regional myocardial systolic dysfunction . Therefore, using e’ to reflect the global LV diastolic dysfunction is unsuitable. Moreover, the wall thickness of the LV ventricular such as IVST, LVPWT and LVMI were significantly increased compared to controls, showing that the patients we studied already exhibited myocardial hypertrophy, which is a strong and independent factor for cardiovascular risk [13, 21]. Above all, we concluded that although our patients were diagnosed with normal diastolic function by conventional echocardiography, this diagnosis was inappropriate, more sensitive indicators are needed to determine whether abnormal diastolic function exists.
LV end-diastolic pressure (LVEDP) measured by cardiac catheterization and the cardiac catheterization-derived time constant of LV relaxation, (Ʈ), are important factors for evaluating the severity of diastolic dysfunction . And the late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) imaging is the gold standard to assess myocardial fibrosis and function. However, cardiac catheterization is invasive, and the contrast agents in LGE CMR are contraindicated for patients with end-stage renal disease, making them of great limitation in clinical application. 2D-STI is confirmed to have a reasonable correlation with myocardial fibrosis as defined by LGE CMR, and global DSrE and DSrIVR derived by 2D-STI have a strong correlation with haemodynamic indices (Ʈ and LVEDP) both in patients and in animal models. Moreover, DSr is less angle and load dependent and not influenced by valvular pathology . So global DSrE and DSrIVR reveal higher accuracy in diagnosing diastolic dysfunction and the degree of myocardial fibrosis in PD patients [5, 24-27].
In our study, we found that both DSrE and DSrIVR in young PD patients were significantly different as compared to the age- and sex-matched controls, and the severity of diastolic dysfunction was associated both with low DSrE and DSrIVR, as other studies previously reported [6, 28]. Combined them with E, E/DSrE still had a significant difference, while E/DSrIVR had none. That may because SRIVR was superior to E/SRIVR for the prediction of filling pressures in some cases  or the insufficient number of samples in this current study made the results of E/DSrIVR insignificant.
We also found that there was a significant difference in E/A, DSrA, and E/DSrA between the two groups, which is in accordance with the known idea that LA function is closely coupled to LV diastolic function, and the increase in LA function is thought to be a mechanism counterbalancing the progression of LV diastolic dysfunction [7, 29]. In the presence of normal LA pressure, this shifts a greater proportion of LV filling to late diastole after atrial contraction in order to maintain the early filling pressures, leading to decreased E and increased A. From another point of view, the decrease in the ratio of E/A and E/DSrA may suggest that potential diastolic dysfunction may exist in young PD patients at the early stage .
By using stepwise multivariate linear regression and multilayer perceptron neural networks, we estimated the association between DSr and conventional echocardiography parameters. We found that only DSrE has a strong relationship with LVPWT and E/A, indicating that the increase in the LV wall thickness and LA function indirectly reflects the impairment of LV diastolic function, as we mentioned above. Our study suggests that for clinical purposes, when patients are not yet diagnosed with LV diastolic dysfunction by conventional echocardiography, the increase in LV wall thickness and LA function should be considered as risk factors and the combined assessment of the DSrE , LVPWT and E/A should be taken into account to evaluate abnormal LV diastolic function .
At the end of our study, we still would like to add one more point, the LV systolic function is not preserved accompanying with diastolic abnormalities. Our study found that the GLS avg was lower than we would expect in our patients with preserved LVEF, indicating that these young PD patients may have subclinical LV systolic dysfunction. It also suggested that GLS deterioration proceeds and/or coexists with LV diastolic dysfunction, just as diabetic cardiomyopathy . GLS may reflect predominantly longitudinal motion which is affected more frequently and earlier in the evolution of diastolic dysfunction.
Our study had its strengths. First, this was an original study performed by a group of researchers who were one of the first to focus on LV diastolic function in young PD patients. Second, we used novel and noninvasive measurements to evaluate LV diastolic dysfunction that may be detected in a preclinical phase. Third, we elucidated the possible relationship between the strain rate and conventional echocardiography parameters, making it possible and more reliable to predict the LV diastolic dysfunction by observing conventional echocardiography parameters. One limitation of our study was the small sample size, and that it was only a single-center observational and cross-sectional study. Our study subsequently did not have the hemodynamic parameters obtained by cardiac catheterization as standards to compare data. And how much of diastolic abnormalities were due to reduced GLS avg versus intrinsic diastolic dysfunction was difficult to ascertain.