Off-pump coronary artery bypass grafting for patients with severely reduced ventricular function-A justified strategy?

BACKGROUND AND AIM: Low ejection fraction (EF) has been identified as a main risk factor for perioperative complications and mortality after coronary artery bypass grafting (CABG). The purpose of this study was to compare the efficacy and early as well as midterm outcomes of off-pump CABG (OPCAB) and conventional CABG (ONCAB) surgery in patients with reduced EF. METHODS: We performed a retrospective review of patient demographics, preoperative risk factors, operative and postoperative outcomes of patients with left ventricular EF (LV-EF) ≤35%, who underwent CABG at our institution between January 2015 and December 2017. Propensity score and multivariate logistic regression analysis were used to compare risk adjusted outcomes between groups. RESULTS: Overall, 111 consecutive CABG-patients with LV-EF ≤ 35% underwent either ONCAB (46 patients, 41.4%) or OPCAB surgery (65 patients, 58.6%). There was no difference in early mortality (5% vs. 7.5%, p = .64) between groups. After propensity score matching, OPCAB-patients required significantly less re-sternotomies for bleeding (20% vs. 2.5%, p = .03) and consequently received significantly less blood transfusions (57.5% vs. 32.5%, p = .03). Fewer OPCAB-patients experienced low cardiac output syndrome (22.5% vs. 42.5%, p = .06) and suffered from postoperative delirium (22.5% vs. 42.5%, p = .06). There were no differences in completeness of revascularization between groups (median 1 (1.0-1.33; 1.0-1.33) OPCAB versus median 1 (1-1.33; 0.67-2) ONCAB, p = .95). Survival after 6 months, one year and three years was similar for ONCAB- and OPCAB-patients (ONCAB 92.3%, 89.4%, and 89.4% vs. OPCAB 89.8%, 85.7%, and 82.1%; p = .403). More ONCAB-patients needed a coronary re-intervention during follow-up (8.6% vs. 2.3%, p = .402). CONCLUSION: OPCAB-surgery is a safe and effective option for patients with reduced EF. Furthermore, it does not come at the expense of less complete revascularization or increased coronary re-intervention during early follow-up.

Off-Pump Coronary Artery Bypass Grafting in Acute Coronary Syndrome: Focus on Safety and Completeness of Revascularization.

BACKGROUND: Emergency coronary artery bypass grafting (CABG) in the setting of acute coronary syndrome (ACS) has been associated with increased morbidity and mortality. Avoiding cardiopulmonary bypass might be advantageous, but the role of off-pump CABG (OPCAB) remains controversial, as it has been associated with incomplete revascularization in several studies. The objective of this study was to evaluate the feasibility, efficacy, and outcome of OPCAB surgery in ACS patients. METHODS: We performed a retrospective review of ACS patients who underwent on-pump CABG (ONCAB) or OPCAB, either emergently or delayed, at our institution. RESULTS: Between January 2015 and December 2016, a total of 205 consecutive ACS patients underwent either ONCAB (109 patients, 53.2%) or OPCAB surgery (96 patients, 46.8%). EuroSCORE II levels (5.6 ± 7.2 vs 4.9 ± 6.5, p = 0.226) and demography were comparable between groups.A trend towards lower postoperative mortality was observed in OPCAB patients (2.1 vs 5.5%). The incidence of postoperative stroke and low cardiac output syndrome, as well as the duration of inotropic support and the need for re-sternotomy, was significantly lower in the OPCAB group (p < 0.05).CABG performed instantly in an emergency situation was not associated with increased mortality or morbidity when compared with delayed procedures, and OPCAB surgery in emergency patients was associated with lower postoperative morbidity and shorter stays in the intensive care unit (p < 0.05).There were no differences in completeness of revascularization between groups (median 1 [1-1.33;0.33-1.67] OPCAB versus median 1 (1-1.33;0.67-2) ONCAB, p = 0.617), even in the emergency setting. CONCLUSION: OPCAB surgery is safe and effective in ACS and may be considered in hemodynamically stable patients in the emergency setting.

Novel Cytokine Score and Cardiac Allograft Vasculopathy.

To date, there are no established noninvasive biomarkers available for prediction of cardiac allograft vasculopathy (CAV) after orthotopic heart transplantation (OHT). Inflammatory processes are supposed to play a central role in the pathogenesis of CAV. Recent studies have suggested that immune mediators could serve as biomarkers for cardiovascular diseases. We hypothesized particular cytokines or a combination thereof may serve as noninvasive biomarkers for CAV. Plasma cytokines were screened from 27 patients with CAV and 27 patients without CAV after OHT. The concentrations of interleukins-4, -6, -10, -21, -23, -31, -33, interferon gamma, tumor necrosis factor alpha, and the soluble activation marker CD40 ligand were determined using Luminex-based multiplex analyses. Although concentrations of all cytokines except interferon gamma were on average higher in the CAV group, there were no significant differences between the groups for any 1 cytokine. Using a binary logistic regression model, we were able to develop a probability score for detecting patients at elevated risk for advanced CAV with a sensitivity of 92.31% and a specificity of 60.71% (receiver-operating characteristic area under the curve 0.799 ± 0.06; p<0.0001). In conclusion, analyzing the concentration of specific inflammatory cytokines could be meaningfully included in evaluation of CAV after OHT.

MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains the leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Because of its clinically silent progression and lack of symptoms, detection is often difficult and invasive coronary angiography is performed routinely. To date, there are no established noninvasive biomarkers available for prediction of CAV in transplanted patients.MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that negatively regulate gene expression. As they are detectable in peripheral blood, recent studies have suggested miRNAs as biomarkers for various cardiovascular diseases. Thus, we hypothesized that circulating miRNAs may serve as noninvasive biomarkers for CAV. METHODS: To determine the regulation of circulating miRNAs, we performed miRNA profiling studies in plasma samples of OHT patients with confirmed high-degree CAV and a matched control group consisting of patients without any signs of CAV at least 5 years after OHT. Candidate miRNAs were verified by quantitative reverse transcriptase polymerase chain reaction. RESULTS: Microarray analysis revealed 5 candidate miRNAs (miR-34a, miR-98, miR-155, miR-204, miR-628-5p) that were differentially regulated in plasma samples of patients with CAV and therefore were selected for verification by quantitative reverse transcriptase polymerase chain reaction. In CAV patients, plasma levels of miR-628-5p and miR-155 were significantly increased (P = 0.001 and P = 0.028, respectively). A miR628-5p value above 1.336 was able to predict CAV with a sensitivity of 72% and a specificity of 83%. CONCLUSIONS: For the first time, the present study identifies the circulating miRNA miR-628-5p as a novel potential biomarker of CAV in patients after OHT.

Complex aortic arch repair in a patient with Takayasu's disease presenting with acute aortic dissection type Stanford A and complete collateral perfusion of the brain.

We describe a rare case of a 46-year old woman suffering from Takayasu's disease. She had undergone aorto-biaxillary bypass and aorto-cerebral bypass surgery in 1985 for occlusive arterial disease and developed a large ascending pseudoaneurysm of the aorto-biaxillary bypass. The aorto-cerebral bypass and right axillary bypass were occluded. Native supra-aortic arteries were found to be proximally occluded and arterial blood supply to the brain was maintained by a dense arterial collateral network. The patient did not show neurological deficits and was able to work using both arms without restrictions. She refused early surgery but suffered from acute aortic dissection type Stanford A shortly after. Supracommissural ascending aortic and aortic arch repair under deep hypothermic circulatory arrest with no additional bypass to the head vessels was performed. This case demonstrates the significance of aortic complications in Takayasu's disease and the effectiveness of collateral brain perfusion in selected patients.

Surgical repair of aortoventricular tunnel connected to the apex of the right ventricle in a neonate.

We describe a neonate in whom early symptoms of heart failure developed because of a rare aorta-right ventricular tunnel connected to the apex of the right ventricle. Successful immediate surgical repair was carried out with closure of both ends of the tunnel.

Early systemic cellular immune response in children and young adults receiving decellularized fresh allografts for pulmonary valve replacement.

OBJECTIVES: The longevity of homografts is determined by the activation of the recipients' immune system resulting from allogenic antigen exposition. Fresh decellularized pulmonary homografts (DPH) have shown promising early results in pulmonary valve replacement in children and young adults and could potentially avoid significant activation of the immune system, as more than 99% of the donor DNA is removed during the decellularization process. While the humoral immune response to decellularized allografts has been studied, detailed information on the more significant cellular immune response is currently lacking. METHODS AND RESULTS: Peripheral blood samples were obtained from patients undergoing pulmonary valve replacement with DPH before, after, and for approximately 3 years after implantation. Absolute counts and percentages of mature T- (CD3(+)), B- (CD19(+)), and natural killer- (CD16(+)/CD56(+)) cells, as well as T helper- (CD4(+)) and cytotoxic T-cell- (CD8(+)) subsets, were determined by fluorescence-activated cell sorting (FACS). Between May 2009 and September 2013, 199 blood samples taken from 47 patients with a mean age at DPH implantation of 16.6±10.8 years were analyzed. The hemodynamic performance of DPH was excellent in all but one patient, and no valve-related deaths or conduit explantations were observed. The short-term follow up revealed a significant postoperative decrease in cell counts of most subtypes with reconstitution after 3 months. Continued assessment did not show any significant deviations in cell counts from their baseline values. CONCLUSION: The absence of cellular immune response in patients receiving DPH supports the concept that decellularization can provide a basis for autologous regeneration.

Identification of HLA ligands and T-cell epitopes for immunotherapy of lung cancer.

INTRODUCTION: Lung cancer is the most common cancer worldwide. Every year, as many people die of lung cancer as of breast, colon and rectum cancers combined. Because most patients are being diagnosed in advanced, not resectable stages and therefore have a poor prognosis, there is an urgent need for alternative therapies. Since it has been demonstrated that a high number of tumor- and stromal-infiltrating cytotoxic T cells (CTLs) is associated with an increased disease-specific survival in lung cancer patients, it can be assumed that immunotherapy, e.g. peptide vaccines that are able to induce a CTL response against the tumor, might be a promising approach. METHODS: We analyzed surgically resected lung cancer tissues with respect to HLA class I- and II-presented peptides and gene expression profiles, aiming at the identification of (novel) tumor antigens. In addition, we tested the ability of HLA ligands derived from such antigens to generate a CTL response in healthy donors. RESULTS: Among 170 HLA ligands characterized, we were able to identify several potential targets for specific CTL recognition and to generate CD8+ T cells which were specific for peptides derived from cyclin D1 or protein-kinase, DNA-activated, catalytic polypeptide and lysed tumor cells loaded with peptide. CONCLUSIONS: This is the first molecular analysis of HLA class I and II ligands ex vivo from human lung cancer tissues which reveals known and novel tumor antigens able to elicit a CTL response.

Heart valve engineering: decellularized allograft matrices in clinical practice.

The purpose of this review is to update the current clinical experience with tissue-engineered, nonseeded, allogenic matrices for pulmonary and aortic valve replacement. Allogenic heart valve replacement using an aortic root homograft was first performed 50 years ago on July 24, 1962, by Donald Ross at Guy's Hospital, London. Cryopreserved homografts have been the gold standard for many years in selected indications such as for pulmonary valve replacement in congenital heart disease, severe bacterial endocarditis, or for right ventricular outflow tract reconstruction during the Ross pulmonary autograft operation. However, there is evolving evidence that tissue-engineered decellularized homografts may be superior to conventional cryopreserved homografts.