Holt-Oram syndrome (HOS) is an autosomal dominant hearthand syndrome characterized by congenital heart disease (CHD) and upper limb deformity, and caused by mutations in the TBX5 gene. To date, the sensitivity of TBX5 genetic testing for HOS has been unclear. We now report mutational analyses of a nongenetically selected population of 54 unrelated individuals who were consecutively referred to our center with a clinical diagnosis of HOS. TBX5 mutational analyses were performed in all individuals, and clinical histories and findings were reviewed for each patient without reference to the genotypes. Twenty-six percent of the complete cohort was shown to have mutations of the TBX5 gene. However, among those subjects for whom clinical review demonstrated that their presentations met strict diagnostic criteria for HOS, TBX5 mutations were identified in 74%. No mutations were identified in those subjects who did not meet these criteria. Thus, these studies validate our clinical diagnostic criteria for HOS including an absolute requirement for preaxial radial ray upper limb malformation. Accordingly, TBX5 genotyping has high sensitivity and specificity for HOS if stringent diagnostic criteria are used in assigning the clinical diagnosis. HOS is the most common of the heart-hand syndromes. It segregates in an autosomal dominant fashion and is estimated to occur in at least 1/100,000 live births (1). HOS is characterized by upper limb anomalies involving the preaxial radial ray and CHD (2,3). Upper limb deformity may be bilateral but asymmetric or even unilateral. The most common forms of CHD associated with HOS are ASD, usually of the ostium secundum variety, and VSD, usually occurring in the muscular trabeculated septum. Cardiac conduction disease may also occur, regardless of the presence or absence of structural cardiac disease (3

Background Pre-transplant sensitization is a limiting factor in solid organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed the generation of Nabs following VAD implantation in pre-transplant sera and examined their contribution to the cardiac allograft outcome. Methods IgM and IgG Nabs were tested in pre-transplant serum samples collected from 206 orthotopic heart transplant (OHT) recipients, including 128 VAD and 78 no-VAD patients. Nabs were assessed by testing serum reactivity to apoptotic cells by flow cytometry and to the generic oxidized epitope, malondialdehyde, by ELISA. Results No difference was observed in serum levels of IgM Nabs between VAD and no-VAD patients. However, serum IgG Nabs levels were significantly increased in VAD compared to no-VAD patients. This increase was likely due to presence of VAD, as revealed by lower serum IgG Nabs levels before implantation. Lastly, elevated pre-transplant IgG Nabs level was associated with the development of primary graft dysfunction in this patient series. Conclusions Our study demonstrates that VAD support elicits IgG Nabs reactive to apoptotic cells and oxidized epitopes. These findings further support the idea of a broad and non-specific B-cell activation by VAD, resulting in IgG sensitization. Moreover, the association of serum IgG Nabs levels with the development of primary graft dysfunction suggests a possible role for these antibodies in the inflammatory reaction accompanying this complication.

Left ventricular assist device (LVAD) withdrawal with ventricular recovery represents the optimal outcome for patients previously implanted with an LVAD. The aim of this systematic review was to examine the patient outcomes of device withdrawal via minimally invasive pump decommissioning as compared with reoperation for pump explantation. An electronic search was performed to identify all studies in the English literature assessing LVAD withdrawal. All identified articles were systematically assessed for inclusion and exclusion criteria. Overall, 44 studies (85 patients) were included in the analysis, of whom 20% underwent decommissioning and 80% underwent explantation. The most commonly used LVAD types included the HeartMate II (decommissioning 23.5% vs. explantation 60.3%; p = 0.01) and HeartWare HVAD (decommissioning 76.5% vs. explantation 17.6%; p < 0.001). At median follow-up of 389 days, there were no significant differences in the incidence of cerebrovascular accidents (p = 0.88), infection (p = 0.75), and survival (p = 0.20). However, there was a trend toward a higher recurrence of heart failure in patients who underwent decommissioning as compared with explantation (decommissioning 15.4% vs. explantation 8.2%, cumulative hazard; p = 0.06). Decommissioning appears to be a feasible alternative to LVAD explantation in terms of overall patient outcomes.

Background: Heparin-induced thrombocytopenia (HIT) is a severe antibody-mediated reaction leading to transient prothrombosis. However, its incidence in patients on extracorporeal life support (ECLS) is not well described. The aim of this systematic review was to report the incidence of HIT in patients on ECLS, as well as compare the characteristics and outcomes of HIT in patients undergoing veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and veno-venous ECMO (VV-ECMO). Methods: An electronic search was performed to identify all studies in the English literature examining outcomes of patients with HIT on ECLS. All identified articles were systematically assessed using specific inclusion and exclusion criteria. Random effects meta-analysis as well as univariate analysis was performed. Results: Of 309 patients from six retrospective studies undergoing ECLS, 83% were suspected, and 17% were confirmed to have HIT. Due to the sparsity of relevant retrospective data regarding patients with confirmed HIT on ECLS, patient-based data was subsequently collected on 28 patients from case reports and case series. Out of these 28 patients, 53.6% and 46.4% of them underwent VA-ECMO and VV-ECMO, respectively. Patients on VA-ECMO had a lower median platelet count nadir (VA-ECMO: 26.0 vs. VV-ECMO: 45.0 per µL, P=0.012) and were more likely to experience arterial thromboembolism (VA-ECMO: 53.3% vs. VV-ECMO: 0.0%, P=0.007), though there was a trend towards decreased likelihood of experiencing ECLS circuit oxygenator thromboembolism (VA-ECMO: 0.0% vs. VV-ECMO: 30.8%, P=0.075) and thromboembolism necessitating ECLS device or circuit exchange (VA-ECMO: 13.3% vs. VV-ECMO 53.8%, P=0.060). Kaplan-Meier survival plots including time from ECLS initiation reveal no significant differences in survival in patients supported on VA-ECMO as compared to VV-ECMO (P=0.300). Conclusions: Patients who develop HIT on VA-ECMO are more likely to experience more severe thrombocytopenia and arterial thromboembolism than those on VV-ECMO. Further research in this area and development of standardized protocols for the monitoring, diagnosis and management of HIT in patients on ECLS support are warranted.

Background: Saphenous vein grafts (SVG) are a commonly used conduit for coronary artery bypass graft (CABG) surgery and can be harvested by either an open or endoscopic technique. Our goal was to evaluate long-term angiographic and clinical outcomes of open compared to endoscopic SVG harvest for CABG. Methods: Electronic search was performed to identify all studies in the English literature that compared open and endoscopic SVG harvesting for CABG with at least one year of follow-up. The primary outcome was graft patency. Secondary outcomes included perioperative morbidity and mortality. Results: Of 3,255 articles identified, a total of 11 studies were included for analysis. Of 18,131 patients, 10,873 (60%) patients underwent open SVG harvest and 7,258 (40%) patients underwent endoscopic SVG harvest. The mean age of patients was 65 years and 87% were male. The overall mean follow-up period was 2.6 years. During follow-up, patients who underwent open SVG harvest had superior graft patency per graft [open 82.3% vs. endoscopic 75.1%; OR: 0.61 (95% CI, 0.43-0.87); P=0.01], but higher rates of overall wound complications in the immediate post-operative period [open 3.3% vs. endoscopic 1.1%; OR: 0.02 (95% CI, 0.01-0.06); P<0.001]. Patients who underwent open SVG harvest had higher postoperative 30day mortality [open 3.4% vs. endoscopic 2.1%; OR: 0.59 (95% CI, 0.37-0.94); P=0.03], but no significant difference in overall mortality [open 4.9% vs. endoscopic 4.9%; OR: 0.34 (95% CI, 0.50-1.27); P=0.34]. Conclusions: Patients who underwent an open SVG harvest technique had improved graft patency and comparable overall mortality to endoscopic SVG harvest at average follow-up time of 2.6 years. Patients with open SVG harvest had higher rates of early wound complications and postoperative 30-day mortality, however, there was no difference in overall mortality.