The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell–derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardiopulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell–specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell–specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.

BACKGROUND:Degenerative mitral valve (MV) disease is a common cause of severe mitral regurgitation (MR) and accounts for the majority of MV operations. Conventional MV surgery requires cardiopulmonary bypass, aortic cross-clamping, cardioplegia, and a thoracotomy or sternotomy and, therefore, is associated with significant disability, risks, and unpredictable rates of MV repair. Transesophageal echocardiography-guided beating-heart MV repair with expanded polytetrafluoroethylene cordal insertion has the potential to significantly reduce surgical morbidity. We report the first-in-human clinical experience with a novel preformed expanded polytetrafluoroethylene knot implantation device (Harpoon TSD-5) designed to treat degenerative MR. METHODS:Through a small left thoracotomy, the device was inserted into the heart and guided by transesophageal echocardiography to the ventricular surface of the prolapsed leaflet. Multiple expanded polytetrafluoroethylene cords were anchored in the leaflet and then adjusted to the correct length to restore MV leaflet coaptation and secured at the epicardium. RESULTS:Eleven patients with posterior leaflet prolapse and severe MR, with mean±SD age of 65±13 years and mean ejection fraction of 69±7%, were treated with 100% procedural success. Immediate postprocedural mean MR grade was trace. At 1 month, the mean MR grade was mild with significant decreases in end-diastolic volume (139 to 107 mL; P=0.03) and left atrial volume (118 to 85 mL; P=0.04). CONCLUSIONS:A novel device used for beating-heart image-guided MV repair demonstrates a significant reduction in MR with favorable left ventricular and left atrial reverse remodeling. This approach has the potential to decrease invasiveness and surgical morbidity. Further follow-up is necessary to assess long-term efficacy. CLINICAL TRIAL REGISTRATION: 190M itral valve disease is the most prevalent heart valve disorder and is 3 to 4 times more common than aortic valve disease. Significant mitral regurgitation (MR) affects ≈2% of the total population and 9% of the population >75 years of age.1 MR causes volume overload of the left ventricle (LV), which in turn can progress to ventricular dilation, decreased ejection performance, pulmonary hypertension, congestive heart failure, atrial fibrillation (AF), right ventricular dysfunction, and eventually death. Degenerative MR is the most common indication for mitral valve surgery in North America.2 Introduced clinically in 1986, mitral valve repair with expanded polytetrafluoroethylene (ePTFE) artificial cords has been shown to be equivalent to leaflet resection techniques 3 and is increasingly being used in conventional mitral valve repair operations. 4 Although effective, conventional mitral valve surgery requires cardiopulmonary bypass, aortic crossclamping, cardioplegia, and a thoracotomy or sternotomy. It is therefore associated with significant disability and risks, including stroke, renal failure, widely variable rates of mitral valve repair versus replacement, and death.5 As a result, the...

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In this single institution experience, surgical pulmonary embolectomy is a safe and effective therapy to treat patients with a submassive or massive pulmonary embolism. Although survival in this study is higher than previously reported for patients treated with medical therapy alone, a prospective trial comparing surgical therapy with medical therapy is necessary to further elucidate the role of surgical pulmonary embolectomy in the treatment of pulmonary embolism.

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Background Pediatric patients awaiting orthotopic heart transplantation frequently require bridge to transplantation (BTT) with mechanical circulatory support. Posttransplant survival outcomes and predictors of mortality have not been thoroughly described in the modern era using a large-scale analysis. Methods The United Network for Organ Sharing database was reviewed to identify pediatric heart transplant recipients from 2005 through 2012. Patients were stratified into three groups: extracorporeal membrane oxygenation (ECMO), ventricular assist device (VAD), and direct transplantation (DTXP). The primary outcome was posttransplant survival. Results Two thousand seven hundred seventy-seven pediatric patients underwent orthotopic heart transplantation. There were 617 patients who required BTT with mechanical circulatory support (22.2%), of whom there were 428 VAD BTT (69.4%) and 189 ECMO BTT (30.6%). An increase in VAD use was observed during the study period (p < 0.0001). Compared with DTXP, patients in the ECMO BTT group had a lower median age (<1 versus 5 years; p < 0.0001) and were significantly smaller (8 versus 14 kg; p < 0.001), whereas patients in the VAD BTT group were older (8 versus 5 years; p = 0.0002) and larger (24 versus 14 kg; p < 0.001). Actuarial survival was greater in the DTXP group compared with ECMO BTT, but similar to VAD BTT at 30 days and 1, 3, and 5 years. However, this survival difference was lost after censoring the first 4 months after transplant. In multivariable analysis, when restricted to the first 4 months of survival, independent predictors for mortality were ECMO BTT, age, diagnosis, and functional status, whereas VAD BTT was not. Conclusions Pediatric patients with DTXP or VAD BTT have equivalent posttransplant survival. However, those requiring ECMO BTT have inferior early post-transplant survival compared with those receiving DTXP.

ACS problems occur frequently in LVAD patients and are not associated with adverse outcomes in HMII patients. The acute care surgeon is an integral member of a comprehensive approach to effective LVAD management.