High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation

Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction 21 ng/L (p<0.001). Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes

Risk Assessment after ST-Segment Elevation Myocardial Infarction: Can Biomarkers Improve the Performance of Clinical Variables?

Introduction: Myocardial infarction with ST-segment elevation (STEMI) is the coronary artery disease associated with the highest risk of morbimortality; however, this risk is heterogeneous, usually being evaluated by clinical scores. Risk assessment is a key factor in personalized clinical management of patients with this disease. Aim: The aim of this study was to assess whether some new cardiac biomarkers considered alone, combined in a multibiomarker model or in association with clinical variables, improve the short- and long-term risk stratification of STEMI patients. Materials and Methods: This was a retrospective observational study of 253 patients with STEMI. Blood samples were obtained before or during the angiography. The assessed biomarkers were C-terminal fragment of insulin-like growth factor binding protein-4 (CT-IGFBP4), high sensitive cardiac troponin T (hs-cTnT), N-terminal fragment of probrain natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15); they reflect different cardiovascular (CV) physiopathological pathways and underlying pathologies. We registered in-hospital and follow-up mortalities and their causes (cardiovascular and all-cause) and major adverse cardiac events (MACE) during a two year follow-up. Discrimination, survival analysis, model calibration, and reclassification of the biomarkers were comprehensively evaluated. Results and Discussion: In total, 55 patients (21.7%) died, 33 in-hospital and 22 during the follow-up, most of them (69.1%) from CV causes; 37 MACE occurred during follow-up. Biomarkers showed good prognostic ability to predict mortality, alone and combined with the multibiomarker model. A predictive clinical model based on age, Killip–Kimball class, estimated glomerular filtration rate (eGFR), and heart rate was derived by multivariate analysis. GDF-15 and NT-proBNP significantly improved risk assessment of the clinical model, as shown by discrimination, calibration, and reclassification of all the end-points except for all-cause mortality. The combination of NT-proBNP and hs-cTnT improved CV mortality prediction. Conclusions: GDF-15 and NT-proBNP added value to the usual risk assessment of STEMI patients

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation

Antecedents. Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Aim. Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. Methods. 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction  21 ng/L (p<0.001). Conclusion. Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes

High-Sensitivity Troponin T and Soluble Form of AXL as Long-Term Prognostic Biomarkers after Heart Transplantation.

Antecedents. Cardiac allograft vasculopathy (CAV) is a frequent complication limiting the long-term (>1 year) survival after heart transplantation (HTx). CAV is initiated by endothelial dysfunction and can lead to severe cardiovascular (CV) complications. Since CAV is often clinically silent, biomarkers could help identifying HTx patients at risk of CAV and their severe complications. Aim. Evaluate the clinical yield of high-sensitivity cardiac troponin T (hs-cTnT), marker of cardiomyocyte damage, and the soluble form of AXL (sAXL), biomarker of endothelial dysfunction, to assess the prognosis of long-term cardiovascular (CV) events occurring after HTx. Methods. 96 patients were evaluated at least > 1 year after HTx. CAV was evaluated by coronary angiography or multisliced tomography, and hs-cTnT and sAXL measured 6 months before or after CAV evaluation. Patients were followed during 42 ± 15 months for a combined end point including cardiac death, angina or acute myocardial infarction, left ventricular ejection fraction  21 ng/L (). Conclusion. Hs-cTnT, but not sAXL, measured during the long-term follow-up of HTx patients appears as a helpful biomarker to identify patients at low risk of adverse CV outcomes.This study was supported in part by the Instituto de Salud Carlos III Spanish Network on Cardiovascular Research (RIC, n° RD12/0042/000), CIBERCV, and FEDER (Fondo Europeo de Desarrollo Regional).Peer reviewe

Estimulación multisensorial y realidad virtual para mejorar procesos educativos en la comunicación audiovisual

Depto. de Ciencias de la Comunicación AplicadaFac. de Ciencias de la InformaciónFALSEsubmitte

Safety of Everolimus With Reduced Calcineurin Inhibitor Exposure in De Novo Kidney Transplants: An Analysis From the Randomized TRANSFORM Study

BACKGROUND: The safety profiles of standard therapy versus everolimus with reduced-exposure calcineurin inhibitor (CNI) therapy using contemporary protocols in de novo kidney transplant recipients have not been compared in detail. METHODS: TRANSFORM was a randomized, international trial in which de novo kidney transplant patients were randomized to everolimus with reduced-exposure CNI (N = 1014) or mycophenolic acid (MPA) with standard-exposure CNI (N = 1012), both with induction and corticosteroids. RESULTS: Within the safety population (everolimus 1014, MPA 1012), adverse events with a suspected relation to study drug occurred in 62.9% versus 59.2% of patients given everolimus or MPA, respectively (P = 0.085). Hyperlipidemia, interstitial lung disease, peripheral edema, proteinuria, stomatitis/mouth ulceration, thrombocytopenia, and wound healing complications were more frequent with everolimus, whereas diarrhea, nausea, vomiting, leukopenia, tremor, and insomnia were more frequent in the MPA group. The incidence of viral infections (17.2% versus 29.2%; P < 0.001), cytomegalovirus (CMV) infections (8.1% versus 20.1%; P < 0.001), CMV syndrome (13.6% versus 23.0%, P = 0.044), and BK virus (BKV) infections (4.3% versus 8.0%, P < 0.001) were less frequent with everolimus. CMV infection was less common with everolimus versus MPA after adjusting for prophylaxis therapy in the D+/R- subgroup (P < 0.001). Study drug was discontinued more frequently due to rejection or impaired healing with everolimus, and more often due to BKV infection or BKV nephropathy with MPA. CONCLUSIONS: De novo everolimus with reduced-exposure CNI yielded a comparable incidence, though a distinctly different pattern, of adverse events versus current standard of care. Both regimens are safe and effective, yet their distinct profiles may enable tailoring for individual kidney transplant recipients.status: publishe

Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease

BACKGROUND: Although inhibitors of the renin-angiotensin-aldosterone system can slow the progression of diabetic kidney disease, the residual risk is high. Whether nuclear 1 factor (erythroid-derived 2)-related factor 2 activators further reduce this risk is unknown. METHODS: We randomly assigned 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease (estimated glomerular filtration rate [GFR], 15 to <30 ml per minute per 1.73 m2 of body-surface area) to bardoxolone methyl, at a daily dose of 20 mg, or placebo. The primary composite outcome was end-stage renal disease (ESRD) or death from cardiovascular causes. RESULTS: The sponsor and the steering committee terminated the trial on the recommendation of the independent data and safety monitoring committee; the median follow-up was 9 months. A total of 69 of 1088 patients (6%) randomly assigned to bardoxolone methyl and 69 of 1097 (6%) randomly assigned to placebo had a primary composite outcome (hazard ratio in the bardoxolone methyl group vs. the placebo group, 0.98; 95% confidence interval [CI], 0.70 to 1.37; P=0.92). In the bardoxolone methyl group, ESRD developed in 43 patients, and 27 patients died from cardiovascular causes; in the placebo group, ESRD developed in 51 patients, and 19 patients died from cardiovascular causes. A total of 96 patients in the bardoxolone methyl group were hospitalized for heart failure or died from heart failure, as compared with 55 in the placebo group (hazard ratio, 1.83; 95% CI, 1.32 to 2.55; P<0.001). Estimated GFR, blood pressure, and the urinary albumin-to-creatinine ratio increased significantly and body weight decreased significantly in the bardoxolone methyl group, as compared with the placebo group. CONCLUSIONS: Among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, bardoxolone methyl did not reduce the risk of ESRD or death from cardiovascular causes. A higher rate of cardiovascular events with bardoxolone methyl than with placebo prompted termination of the trial. Copyright © 2013 Massachusetts Medical Society