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, volume overload, anemia, hypocalcemia, and hyperphosphatemia usually result in compensatory myocardial hypertrophy and fibrosis, making diastolic dysfunction seem to be more common and occur earlier than systolic dysfunction in young uremic patients [14-16]. Furthermore, in our previous study, we found that patients with the normal LVEF, although under long-term regular peritoneal dialysis, maintaining well-controlled blood pressure and stable ultrafiltration and adequate total fluid removal, their LV diastolic function deteriorated as the CKD progressed, in contrast to the stable LV systolic function . Therefore, it seems important to detect diastolic dysfunction at the early stage of peritoneal dialysis.
According to guideline , our PD patients do not meet the diagnostic criteria for LV diastolic dysfunction. And considering the accuracy of e’ may be limited for several reasons such as angle, LA pressure, mitral valve disease and annular calcification, e’ cannot exactly reflect the global LV relaxation in patients with LV hypertrophy or heart failure with preserved LVEF, or in which the incidence of cardiac valve calcification is high and regional systolic dysfunction is present [6, 18-20]. 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 in PD patients 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]. Additionally, GLS is usually decreased in patients with heart failure with preserved ejection fraction, and is significantly correlated with LV end-diastolic pressure (LVEDP), showing that the decrease of GLS usually foreshadows LV diastolic dysfunction at the early stage. In our study, GLS in young PD patients was in the normal range, but lower than that in the control group, indicating that LV diastolic dysfunction probably exists at the early stage of peritoneal dialysis. So we urgently needed some sensitive indicators to quantitatively assess early LV diastolic dysfunction.
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. Global diastolic strain rate index derived by 2D-STI is confirmed to have a strong correlation with myocardial fibrosis defined by LGE CMR and haemodynamic indices (Ʈ and LVEDP) both in patients and in animal models, it is less angle and load dependent and not influenced by valvular pathology . And the guideline also indicated this novel parameter has been used in conjunction with mitral E velocity to estimate LV filling pressures and to predict outcomes in several disease states . So global diastolic strain rate index reveals higher accuracy in diagnosing diastolic dysfunction and the degree of myocardial fibrosis in PD patients [5, 24-27].
In our study, we found that diastolic strain rate index in young PD patients is significantly different as compared to the age- and sex-matched controls, and the severity of diastolic dysfunction was associated both with low diastolic strain rate index, as other studies previously reported [6, 28]. Combined with E, E/DSrE still had a significant difference, confirming that LV diastolic dysfunction does exist at the early stage of peritoneal dialysis in young uremic patients.
We also found that there was a significant difference in 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. From another point of view, the decrease in the ratio of E/DSrA may suggest that potential diastolic dysfunction may exist in young PD patients at the early stage .
By using stepwise multivariate linear regression, we estimated the association between diastolic strain rate index and conventional echocardiography parameters. We found that DSrE has a strong relationship with LVPWT and E/A. Considering the limitations of E/A, such as E/A ratio is age dependent, and the U-shaped relation between E/A and LV diastolic function may make it difficult to differentiate normal pseudonormal filling, particularly with normal LVEF , leading to E/A unsuitable for our case. Our study suggested that for clinical purposes, when patients are not yet diagnosed with LV diastolic dysfunction by conventional echocardiography suggested by guideline, the increase in LV wall thickness should be considered as risk factors. Previous studies have confirmed the important clinical significance of LVPWT, it is an independent risk factor for paroxysmal atrial fibrillation , and is significantly higher than those with dipper hypertension , and also highly reproducible measurements used as part of a multimodality approach when assessing morphologic LV preparedness in patients with CCTGA undergoing anatomic repair . AS we know, LV hypertrophy can occur at the early stage of end-stage renal disease, so we highly recommended that the combined assessment of the DSrE and LVPWT should be taken into account to evaluate abnormal LV diastolic function at the early stage .
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. Moreover, our study just simply provided a sensitive tool to early diagnosis of diastolic dysfunction.