Introduction: Pulmonary hypertension (PH) is highly prevalent in patients receiving dialysis. The precise mechanisms underlying PH in hemodialysis (HD) patients have not been adequately addressed. Emerging experimental evidence indicates that circulating fibrocytes may contribute significantly to this process. Methods: We measured the proportion of circulating fibrocytes using flow cytometry analysis and prospectively analyzed patients during HD from February 1, 2017, to February 1, 2022. Then we investigated correlations between circulating fibrocytes, inflammation cytokines, PH, and their affective factors that predict the prognosis of HD patients. Results: The cohort included 192 patients. During a follow‐up of 5 years, we registered 66 all‐cause deaths, and 11 patients received kidney transplantation. The incidence of PH among HD patients was 30.9%. We found that the circulating fibrocyte level significantly correlated with pulmonary arterial systolic pressure (r = 0.412, p < 0.05). In the multiple logistic regression analysis, the percentage of circulating fibrocytes was an independent predictor of PH (odds ratio [OR]: 2.080, 95% confidence interval [CI]: 1.539–2.812, p < 0.001). Controlling for confounding covariates in the multivariate Cox regression models, the presence of PH conferred an increased risk of all‐cause mortality in HD patients [hazard ratio (HR): 2.183, 95% CI:1.257–3.788, p = 0.006]. Conclusion: The prevalence of PH was high in HD patients and was associated with higher all‐cause mortality. Higher circulating fibrocyte level was an independent predictor of the presence of PH; these fibrocytes may serve as early detection markers and novel therapeutic targets.

Background: Lung cancer is one of the major cause of death globally. Crizotinib is a first-line drug used in treating non-small-cell lung cancer (NSCLC). However, the pathophysiological mechanisms underlying its cardiotoxicity are unknown. This study investigated the mechanisms of crizotinib-induced cardiotoxicity and explored whether this toxicity can be prevented by the angiotensin receptor/neprilysin inhibitor sacubitril/valsartan. Methods: Male C57BL/6 mice were randomly divided into three groups: control, crizotinib (40 mg for four weeks), and crizotinib + sacubitril/valsartan (40 mg /60 mg for four weeks). Expression of genes in myocardial tissue were detected by transcriptomic sequencing, with verification of the differentially expressed genes (DEGs) using Real time-polymerase chain reaction (RT-PCR). Blood pressure (BP) and cardiac function of animals were measured using non-invasive monitoring and echocardiography approaches. Ventricular refractory period (RP), as well as the induction rate and score of ventricular arrhythmias (VAs) were detected by in vivo electrophysiology. Epicardial conductance was measured by mapping. Expression of Myh7 in myocardium was detected by western blot and RT-PCR. Results: DEGs detected using transcriptomic sequencing included 10 up-regulated and 20 down-regulated genes. The first 5 DEGs identified were Myh7 , Ngp , Lcn2 , Ciart and Ptgds . Kyoto Encyclopedia of Genes and Genomes (KEGG) result indicated that Myh7 is involved in myocarditis, cardiomyopathy, and cardiac muscle contraction. Crizotinib treatment increased blood pressure, prolonged QTc interval, shortened ventricular RP, increased the incidence and score of right VAs, and increased Myh7 expression. Most of these responses were limited by sacubitril/valsartan. Conclusions: Crizotinib induced a range of cardiotoxic side effects in a mouse model and increased Myh7 expression represents a biomarker for this response. These cardiovascular toxic responses can be largely prevented by sacubitril/valsartan.

Background Cardiovascular disease (CVD) is the most common cause of mortality in end‐stage renal disease (ESRD) patients. Fragmented QRS complex (fQRS) has been reported as a helpful marker in evaluating various cardiovascular pathologies. We aimed to investigate the value of the fQRS complex clinical decision of ESRD patients receiving dialysis. Methods This prospective observational study included 411 patients receiving hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) between 2016‐01‐01 and 2020‐12‐31. The primary outcomes were all‐cause and cardiovascular (CV) mortality. Results HD patients have elevated values of fQRS complex compared to CAPD patients (39.1% vs. 28.2%, P = 0.027). Significantly, fQRS complex in the anterior/lateral leads is associated with all‐cause and CV mortality stronger than fQRS in the inferior leads (P = 0.008). In a multivariate Cox regression analysis, HD patients with fQRS complex had a higher incidence of all‐cause mortality (hazard ratio [HR] = 1.860; 95% confidence interval [CI]: [1.032, 3.349]; p = 0.041) and CV mortality (HR = 2.989; 95% CI [1.357, 6.584]; p = 0.007). For CAPD patients, fQRS complex was also associated with increased risk of all‐cause mortality (HR = 1.593; 95% CI [1.023, 2.580]; p = 0.049) and increased risk of CV mortality (HR = 2.392; 95% CI [1.348, 4.173]; p = 0.013). Conclusions The presence of the fQRS complex was an independent predictor of all‐cause and CV mortality in HD and CAPD patients. We suggested a potential role of the fQRS complex in CV risk strata for dialysis patients and the choice of dialysis modality.