Search

Given the central role of sarcomeric dysfunction in cardiomyocyte biology and sarcomere alterations described in endomyocardial biopsies of transplant patients with rejection, we hypothesized that the serum expression levels of genes encoding sarcomeric proteins were altered in acute cellular rejection (ACR). The aim of this study is to identify altered sarcomere-related molecules in serum and to evaluate their diagnostic accuracy for detecting rejection episodes.Serum samples from transplant recipients undergoing routine endomyocardial biopsies were included in an RNA sequencing analysis (n = 40). Protein concentrations of alpha-cardiac actin were determined using a specific enzyme-linked immunoassay (n = 80).We identified 17 sarcomeric genes differentially expressed in patients with clinically relevant rejection (grade ≥2R ACR). A receiver operating characteristic curve was done to assess their accuracy for ACR detection and found that 6 relevant actins, myosins, and other sarcomere-related genes showed great diagnostic capacity with an area under the curve (AUC)0.800. Specifically, the gene encoding alpha-cardiac actin (ACTC1) showed the best results (AUC = 1.000, P0.0001). We determine ACTC1 protein levels in a larger patient cohort, corroborating its overexpression and obtaining a significant diagnostic capacity for clinically relevant rejection (AUC = 0.702, P0.05).Sarcomeric alterations are reflected in peripheral blood of patients with allograft rejection. Because of their precision to detect ACR, we propose sarcomere ACTC1 serum expression levels as potential candidate for to be included in the development of molecular panel testing for noninvasive ACR detection.

Background Noninvasive detection of primary graft dysfunction (PGD) remains a major challenge. SERCA2a plays an important role in cardiac homeostasis and its dysregulation has been associated with ventricular dysfunction and rejection. This study aimed to determine the potential utility of plasma levels of SERCA2a as a biomarker of PGD. Methods 135 plasma samples were collected from adult recipients 2-6 hours prior to heart transplantation (HT). Plasma concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. Variables related to the recipient, the donor, and the periprocedural were collected in order to determine a multivariate predictive model of PGD. Results Levels of SERCA2a were decreased in patients who developed PGD (median 0.430 ng/mL [IQR 0.260 - 0.945] versus 0.830 ng/mL [IQR 0.582 - 1.052]; p = 0.001). Receiver operating characteristic (ROC) curve analysis revealed that SERCA2a discriminated between patients with and without PGD (AUC = 0.682, p = 0.001), and a cutoff point ≥ 0.60 ng/ml was a protective independent predictor of PGD (odds ratio 0.215 [p = 0.004]). Three independent predictors of PGD in this study were reduced levels of pre-HT SERCA2a, increased bilirubin levels, and short-term mechanical circulatory support bridge to transplantation. The analysis of the ROC curve of the model obtained a significant AUC 0.788, p = 0.0001. Conclusions Our findings suggest that assessment of SERCA2a plasma levels may improve risk prediction for the occurrence of PGD, and could be considered as a novel noninvasive biomarker in patients undergoing HT.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main cause of graft failure and death 1 year after heart transplantation (HTx). Metabolic syndrome (MS) increases the risk of cardiovascular events by endothelial dysfunction. The purpose of this study was to determine if patients with MS developed a higher risk of CAV 1 year after HTx. METHODS: Since January 2004 until April 2009, 155 HTx patients were recruited. Cardiopulmonary transplants were excluded (12 patients), as well as retransplants (5 patients), pediatric transplants (11 patients), patients who refused to participate (3 patients), and those who died during the first year (35 patients). The final analysis included 89 patients. MS was diagnosed when Adult Treatment Panel III modified and revised criteria were met, before HTx or after the first 3 months. CAV was diagnosed through intravascular ultrasound performed 1 month and 1 year after HTx. CAV was defined as an intimal thickening ≥ 0.5 mm in the follow-up with regard to the one of the basal study. RESULTS: Development of CAV was significantly higher in patients with MS (59% vs. 19%, P

Background. Renal dysfunction (RD) is one of the most significant long-term complications of heart transplantation (HT). Although RD is generally attributed to a direct effect of calcineurin inhibitors, it is more probable that multiple factors contribute to its development. The aim of this study was to search for predictor variables of RD at 1 year after HT. Methods. Three hundred sixteen consecutive HT patients were evaluated. The relationship between RD at 1 year (glomerular filtration rate

The aim of this study was to analyze, in heart transplant patients, if renal function improvement after cyclosporine replacement by everolimus persists at the middle term and its predictors. We studied prospectively 56 patients in whom conversion was consecutively made. Forty-five patients completed the follow-up period. Significant improvement was observed at 6 and 12 months in plasma creatinine levels (1.92+/-0.7 vs. 1.67+/-0.6 and 1.69+/-0.6 mg/dL; P=0.047) and glomerular filtration rate (43.9+/-17 vs. 52.5+/-23 and 51.3+/-22.3 mL/min; P=0.004). Glomerular filtration rate increased in 32 patients (71%). Baseline characteristics comparison showed a lower percentage of patients with smoking history and new onset diabetes in responders group, but only previous smoking was shown as independent factor (Exp B: 0.083; 95% confidence interval: 0.010-0.793; P=0.024). No differences regarding age, gender, body mass index, disease leading to transplantation, time between transplantation and replacement, cardiovascular risk factors, lipid levels, and hematologic parameters were found.