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Thrombotic events in patients with continuous flow left ventricular assist devices (CF-LVADs) are associated with significant morbidity and mortality. The objective of this study was to delineate the frequency, clinical characteristics, and outcomes of patients with hypercoagulable states who undergo CF-LVAD implantation.We performed a retrospective review of 168 consecutive patients who underwent CF-LVAD implantation between 2010 and 2013. Chart and laboratory data were reviewed for the presence of a hereditary and/or acquired hypercoagulable state. Adverse outcomes were defined as death, confirmed pump thrombosis, aortic root clot, stroke, deep vein thrombosis, and pulmonary embolism. Fisher's exact test and Kaplan-Meier estimate were used to analyze frequency of adverse outcomes and event free survival, respectively.A hypercoagulable state was identified in 20 patients (11.9%). There were 18 patients with acquired, 1 with a congenital, and 1 with both congenital and acquired hypercoagulable states. The median follow-up was 429 days and 475 days in patients with and without hypercoagulable states, respectively. During the study period, 15% (3/20) of the patients with a hypercoagulable state had a diagnosis of deep vein thrombosis vs 3% (4/148) of the patients without a hypercoagulable state (P = .030). Only patients with a hypercoagulable state had a subarachnoid hemorrhage (3/20 vs 0/148; P .01). The event-free survival was lower in the patients with hypercoagulable states (P = .005).Hypercoagulable states are not uncommon in patients with CF-LVADs and may be associated with increased morbidity. Prospective studies are needed to more accurately identify the incidence, prevalence, and significance of hypercoagulable states in patients being considered for CF-LVAD.

Background Cardiac Allograft Hypertrophy (CAH) assessed by left ventricular mass (LVM) on imaging at 1 year has been validated as an early predictor of mortality and vasculopathy. The biology of such changes could be starting much earlier in the life of the graft and reflect the beginning of a continuum of remodeling of the transplanted heart that finally leads to chronic rejection and graft failure. However, definitive mechanisms and predictors have not been established. Therefore, we aimed to study the molecular mechanisms of CAH characterized by abnormal echo mass in heart transplant patients. We hypothesized there is a specific genetic signature in the myocardium that can predict the morphological mechanisms of CAH. Methods We used data from our heart transplant biopsy repository where consented patients agree for an extra biopsy and blood to be stored for research during their protocol visits. Biopsies are stored at -80C in RNA later. We used samples from 6 month time-point in a small cohort of randomly selected patients and performed full gene expression profiling using Ilumina Beadarray Microarray Technology. Additionally, clinical and echocardiogram parameters were collected at the same time-point. LVM index and relative wall thickness at 6m from transplant were used to define CAH according to ASE Guidelines. Results A total of 16 patients were included in the analysis. 5 patients had normal LV geometry, 8 had concentric remodeling and 3 concentric hypertrophy (CH). Patients in the abnormal group were significantly older than the patients in the normal group (53.4 vs 60.7 years, respectively, p=0.0478) while there were no other statistically significant differences in the rest of the baseline and clinical parameters. Gene expression data showed a distinct signature on the heatmap for CH (Figure 1). There were 40 genes that were differentially expressed in CH group compared to the rest. Conclusion Only 31% of the patients have a normal echo LVM by 6 months and there is a distinct genetic signature for CH suggesting that there is a specific biological change occurring in the heart as early as 6 months that contribute to hypertrophy. We hope to elicit the biological basis of these changes so as to create therapeutic interventions to temper these changes and promote longevity of grafts.

Background: Endothelial to Mesenchymal Transition (EndMT) and the reverse phenomenon of mesenchymal to endothelial transitioning (MET) has been shown to contribute to fibrosis in rodent models of heart failure. There are no studies documenting the same in human cardiac tissue. Methods: We performed immunofluorescence dual staining on end stage heart failure myocardial samples obtained from our bio repository. Staining for endothelial and mesenchymal markers were performed with Anti-VE-Cadherin (Santa Cruz Biotechnologies) and anti-Fibroblast specific protein 1 (Dako Antibodies) respectively using standard immunofluoresence techniques. Presence of dual staining on fluorescence microscopy was considered as positive for the presence of EndMT. Vascular density was assessed using a DAB (3-3’ Diaminobenzidine) technique with Anti-CD31 (PECAM, Abcam). Results: Of the end stage heart failure samples, 18 were from left ventricular core during LVAD implant and 5 during a direct transplant as status 1A (axillary intraaortic balloon pump). 10 hearts of patients bridged to transplant with a continuous flow LVAD (Days under support 3436228) were also studied. Mean age was 55y with 82% males and 74% white. 70% of all samples had evidence of EndMT. The number of cells ranged from 1 to 5 per high power field. There was no significant difference between patient characteristics between those with evidence of EndMT versus not, except a higher prevalence of diabetes in the latter group. (Fig 1B) 74% of the end-stage heart failure samples and 60% of the post-VAD samples showed the presence of EndMT cells. Vascular Density was higher in the samples exhibiting EndMT phenomenon. (Figure 1A). Conclusion: We have documented for the first time, the existence of endothelial-mesenchymal transition in human end stage myocardial samples corroborating earlier pioneering studies in rodents. Interestingly the existence of such dual staining cells in end stage hearts (which is highly fibrotic) suggests a possible role of ongoing fibrosis with endothelial to mesenchymal transitioning or potential antifibrotic mechanism though mesenchymal to endothelial transitioning. Further studies of the later process will be warranted to explore potential anti-fibrotic therapeutic implications.

Cardiac Arrhythmias in Patients with a HeartWare Ventricular Assist Device Salpy V. Pamboukian, Mark S. Slaughter, Howard K. Song, Charles T. Klodell, David R. Hathaway, Keith D. Aaronson; University of Alabama at Birmingham, Birmingham, AL; University of Louisville, Louisville, KY; Oregon Health and Science University, Portland, OR; University of Florida Health, Gainesville, FL; Heartware Inc, Framingham, MA; University of Michigan Medical Center, Ann Arbor, MI