Is bilateral internal thoracic artery grafting a safe option for chronic dialysis patients?

BACKGROUND: The use of bilateral internal thoracic artery (BITA) grafting has been proposed for dialysis patients with multivessel coronary artery disease, primarily because of hypothetical long-term survival benefits. AIMS: To investigate the outcome of BITA grafting in dialysis patients. METHODS: This was a retrospective analysis of the use of BITA grafting in 105 consecutive patients with end-stage renal failure on chronic dialysis in three European centres with extensive experience in BITA. Baseline patient characteristics, operative data, early postoperative complications and late survival were reviewed. Outcomes of patients from one of the three centres who underwent either BITA (n=40) or single internal thoracic artery (SITA) grafting (n=19) were also analysed; a one-to-one propensity score (PS)-matched analysis was performed. RESULTS: There were 19 (18.1%) hospital deaths. Despite differences in preoperative patient characteristics and surgical features, in each centre, hospital mortality was greater than the 75th percentile of expected operative risk (EuroSCORE II). Diseased ascending aorta and extracardiac arteriopathy were found to be predictors of hospital death (odds ratio 9.7; P=0.006) and complicated hospital course (odds ratio 2.54; P=0.035), respectively. The 7-year non-parametric estimates of freedom from all-cause death and cardiac or cerebrovascular death were 59% (95% confidence interval: 52.3-65.7%) and 75.6% (95% confidence interval: 71.2-80%), respectively. There were no significant differences in early and late outcomes between BITA and SITA PS-matched groups. CONCLUSIONS: BITA grafting remains a risky operation for chronic dialysis patients, even when performed routinely. No long-term survival benefits for the use of BITA versus SITA were proven

Endothelium-Derived Relaxing Factors and Endothelial Function: A Systematic Review

Background: The endothelium plays a pivotal role in homeostatic mechanisms. It specifically modulates vascular tone by releasing vasodilatory mediators, which act on the vascular smooth muscle. Large amounts of work have been dedicated towards identifying mediators of vasodilation and vasoconstriction alongside the deleterious effects of reactive oxygen species on the endothelium. We conducted a systematic review to study the role of the factors released by the endothelium and the effects on the vessels alongside its role in atherosclerosis. Methods: A search was conducted with appropriate search terms. Specific attention was offered to the effects of emerging modulators of endothelial functions focusing the analysis on studies that investigated the role of reactive oxygen species (ROS), perivascular adipose tissue, shear stress, AMP-activated protein kinase, potassium channels, bone morphogenic protein 4, and P2Y2 receptor. Results: 530 citations were reviewed, with 35 studies included in the final systematic review. The endpoints were evaluated in these studies which offered an extensive discussion on emerging modulators of endothelial functions. Specific factors such as reactive oxygen species had deleterious effects, especially in the obese and elderly. Another important finding included the shear stress-induced endothelial nitric oxide (NO), which may delay development of atherosclerosis. Perivascular Adipose Tissue (PVAT) also contributes to reparative measures against atherosclerosis, although this may turn pathological in obese subjects. Some of these factors may be targets for pharmaceutical agents in the near future. Conclusion: The complex role and function of the endothelium is vital for regular homeostasis. Dysregulation may drive atherogenesis; thus, efforts should be placed at considering therapeutic options by targeting some of the factors noted

Myocardial Gene Expression Profiling to Predict and Identify Cardiac Allograft Acute Cellular Rejection: The GET-Study

International audienceAims: Serial invasive endomyocardial biopsies (EMB) remain the gold standard for acute cellular rejection (ACR) diagnosis. However histological grading has several limitations. We aimed to explore the value of myocardial Gene Expression Profiling (GEP) for diagnosing and identifying predictive biomarkers of ACR.Methods: A case-control study nested within a retrospective heart transplant patients cohort included 126 patients with median (IQR) age 50 (41-57) years and 111 (88%) males. Among 1157 EMB performed, 467 were eligible (i.e, corresponding to either ISHLT grade 0 or ≥3A), among which 36 were selected for GEP according to the grading: 0 (CISHLT, n = 13); rejection ≥3A (RISHLT, n = 13); 0 one month before ACR (BRISHLT, n = 10).Results: We found 294 genes differentially expressed between CISHLT and RISHLT, mainly involved in immune activation, and inflammation. Hierarchical clustering showed a clear segregation of CISHLT and RISHLT groups and heterogeneity of GEP within RISHLT. All EMB presented immune activation, but some RISHLT EMB were strongly subject to inflammation, whereas others, closer to CISHLT, were characterized by structural modifications with lower inflammation level. We identified 15 probes significantly different between BRISHLT and CISHLT, including the gene of the muscular protein TTN. This result suggests that structural alterations precede inflammation in ACR. Linear Discriminant Analysis based on these 15 probes was able to identify the histological status of every 36 samples.Conclusion: Myocardial GEP is a helpful method to accurately diagnose ACR, and predicts rejection one month before its histological occurrence. These results should be considered in cardiac allograft recipients' care