Levosimendan versus Milrinone for Inotropic Support in Pediatric Cardiac Surgery: Results from a Randomized Trial

Objective : We aimed to determine the differential effects of intra-operative administration of milrinone versus levosimendan on myocardial function after pediatric cardiac surgery. Transthoracic echocardiography was employed for myocardial function evaluation, utilizing biventricular longitudinal strain with two-dimensional speckle tracking echocardiography in addition to conventional echocardiographic variables. Design : A secondary analysis of a randomized, prospective, double-blinded clinical drug trial Setting : Two pediatric tertiary university hospitals Participants : Infants between 1-12 months of age diagnosed with ventricular septal defect, complete atrioventricular septal defect, or tetralogy of Fallot who were scheduled for corrective surgery with cardiopulmonary bypass. Interventions : The patients were randomized to receive an infusion of milrinone or levosimendan at the start of cardiopulmonary bypass and for 26 consecutive hours. Measurements and main results : Biventricular longitudinal strain and conventional echocardiographic variables were measured preoperatively, on the first postoperative morning and prior to hospital discharge. The association between perioperative parameters and postoperative myocardial function was also investigated. Images were analyzed for left ventricular (n=67) and right ventricular (n=44) function. The day after surgery, left ventricular longitudinal strain was deteriorated in both the milrinone and levosimendan groups; 33% and 39%, respectively. The difference was not significant. The corresponding deterioration in right ventricular longitudinal strain was 42% and 50% (non-significant difference). For both groups, biventricular longitudinal strain approached their preoperative values at hospital discharge. Preoperative N-terminal pro-brain natriuretic peptide could predict the left ventricular strain on postoperative day one (p=0.014). Conclusions : Levosimendan was comparable to milrinone for left and right ventricular inotropic support in pediatric cardiac surgery.Peer reviewe

Incomplete revascularization reduces survival benefit of coronary artery bypass grafting: role of off-pump surgery.

OBJECTIVE: We sought to analyze the influence, if any, of incomplete revascularization and on/off-pump techniques on long-term mortality after coronary artery bypass grafting. METHODS: A total of 9408 patients undergoing coronary artery bypass grafting, 8461 on pump and 947 off pump, operated on between 1995 and 2004 were included in the study. Adjusted hazard function for long-term mortality was estimated with Poisson regression analysis in a model that included variables reflecting completeness of revascularization, operative method (on/off pump), and background risk factors for death. RESULTS: Mean follow-up after surgical intervention for survivors was 5.0 +/- 2.8 years (range, 0.5-10.5 years), with a total follow-up of 45,076 patient years. Leaving 1 diseased vascular segment without a bypass graft in 2- or 3-vessel disease did not increase the hazard ratio for death in comparison with complete revascularization (hazard ratio, 1.05; 95% confidence interval, 0.87-1.27; P = .60). In contrast, leaving 2 vascular segments without a bypass graft in 3-vessel disease was associated with an increased hazard ratio for death (hazard ratio, 1.82; 95% confidence interval, 1.15-2.85; P = .01). Incomplete revascularization was more common in the off-pump group (

Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome : 20 Years of National Data From Sweden

BACKGROUND: Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation. METHODS AND RESULTS: This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob-LV: HR, 2.1; P=0.03). CONCLUSIONS: Glob-LV and AA-MS are independent morphological risk factors for adverse short-and long-term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome

Clinical Outcome 3 Years After Autologous Chondrocyte Implantation Does Not Correlate With the Expression of a Predefined Gene Marker Set in Chondrocytes Prior to Implantation but Is Associated With Critical Signaling Pathways

BACKGROUND: There is a need for tools to predict the chondrogenic potency of autologous cells for cartilage repair. PURPOSE: To evaluate previously proposed chondrogenic biomarkers and to identify new biomarkers in the chondrocyte transcriptome capable of predicting clinical success or failure after autologous chondrocyte implantation. STUDY DESIGN: Controlled laboratory study and case-control study; Level of evidence, 3. METHODS: Five patients with clinical improvement after autologous chondrocyte implantation and 5 patients with graft failures 3 years after implantation were included. Surplus chondrocytes from the transplantation were frozen for each patient. Each chondrocyte sample was subsequently thawed at the same time point and cultured for 1 cell doubling, prior to RNA purification and global microarray analysis. The expression profiles of a set of predefined marker genes (ie, collagen type II α1 [COL2A1], bone morphogenic protein 2 [BMP2], fibroblast growth factor receptor 3 [FGFR3], aggrecan [ACAN], CD44, and activin receptor-like kinase receptor 1 [ACVRL1]) were also evaluated. RESULTS: No significant difference in expression of the predefined marker set was observed between the success and failure groups. Thirty-nine genes were found to be induced, and 38 genes were found to be repressed between the 2 groups prior to autologous chondrocyte implantation, which have implications for cell-regulating pathways (eg, apoptosis, interleukin signaling, and β-catenin regulation). CONCLUSION: No expressional differences that predict clinical outcome could be found in the present study, which may have implications for quality control assessments of autologous chondrocyte implantation. The subtle difference in gene expression regulation found between the 2 groups may strengthen the basis for further research, aiming at reliable biomarkers and quality control for tissue engineering in cartilage repair. CLINICAL RELEVANCE: The present study shows the possible limitations of using gene expression before transplantation to predict the chondrogenic and thus clinical potency of the cells. This result is especially important as the chondrogenic potential of the chondrocytes is currently part of quality control measures according to European and American legislations regarding advanced therapies.CC BY-NC-ND 3.0</p

Early and late outcomes after surgical repair of congenital supravalvular aortic stenosis: A European Congenital Heart Surgeons Association multicentric study

Thoracic Surger