Ann C. Gaffey

Tissue Engineered, Hydrogel-Based Endothelial Progenitor Cell Therapy Robustly Revascularizes Ischemic Myocardium and Preserves Ventricular Function

OBJECTIVES Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage. METHODS Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents. RESULTS Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control. CONCLUSIONS We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.

Minimally invasive mitral valve surgery is associated with equivalent cost and shorter hospital stay when compared with traditional sternotomy

OBJECTIVE Mitral valve surgery is increasingly performed through minimally invasive approaches. There are limited data regarding the cost of minimally invasive mitral valve surgery. Moreover, there are no data on the specific costs associated with mitral valve surgery. We undertook this study to compare the costs (total and subcomponent) of minimally invasive mitral valve surgery relative to traditional sternotomy. METHODS All isolated mitral valve repairs performed in our health system from March 2012 through September 2013 were analyzed. To ensure like sets of patients, only those patients who underwent isolated mitral valve repairs with preoperative Society of Thoracic Surgeons scores of less than 4 were included in this study. A total of 159 patients were identified (sternotomy, 68; mini, 91). Total incurred direct cost was obtained from hospital financial records. RESULTS Analysis demonstrated no difference in total cost (operative and postoperative) of mitral valve repair between mini and sternotomy (

Combined Heart and Liver Transplantation Can Be Safely Performed With Excellent Short- and Long-Term Results

25,515 ±

In Vivo Anastomosis and Perfusion of a Three-Dimensionally-Printed Construct Containing Microchannel Networks.

7598 vs

Injectable, Guest–Host Assembled Polyethylenimine Hydrogel for siRNA Delivery

26,049 ±

Low ejection fraction in donor hearts is not directly associated with increased recipient mortality

11,737; P = .74). Operative costs were higher for the mini cohort, whereas postoperative costs were significantly lower. Postoperative intensive care unit and total hospital stays were both significantly shorter for the mini cohort. There were no differences in postoperative complications or survival between groups. CONCLUSIONS Minimally invasive mitral valve surgery can be performed with overall equivalent cost and shorter hospital stay relative to traditional sternotomy. There is greater operative cost associated with minimally invasive mitral valve surgery that is offset by shorter intensive care unit and hospital stays.

HeartMate II left ventricular assist device geometry on chest radiograph does not correlate with risk of pump thrombosis

BACKGROUND Heart transplant has become the gold standard therapy for end-stage heart failure. Short- and long-term outcomes after orthotopic heart transplant have been excellent. Many patients with heart failure manifest hepatic failure as a result of a chronically elevated central venous pressure. Concomitant hepatic failure has been a contraindication to heart transplant in most centers. A few select institutions are currently performing combined heart-liver transplantation to treat dual organ failure. The outcomes after dual organ transplant are largely unknown, with limited data from a few select centers. We undertook this study to analyze our large experience with combined heart-liver transplant and determine the short-term and long-term outcomes associated with this procedure. METHODS We have performed 1,050 heart transplants at our center to date. Of these patients, 26 underwent combined heart and liver transplant (largest single-center experience). We reviewed demographic, perioperative, and short- and long-term outcomes after this combined procedure. RESULTS All 26 patients underwent successful dual organ transplant, without any episodes of primary graft dysfunction. Average length of intensive care unit stay was 10 ± 5 days, and average hospital stay was 25 ± 11 days. Kaplan-Meier analysis demonstrated excellent short-term survival (1 year, 87% ± 7%) and long-term survival (5 years, 83% ± 8%). Interestingly, only 3 patients (11%) demonstrated any evidence of rejection long-term by myocardial biopsy, suggesting that concomitant hepatic transplantation may provide immunologic protection for the cardiac allograft. CONCLUSIONS We present the largest single-center series of combined heart and liver transplant. This dual organ strategy is highly feasible, with excellent long-term survival. Concomitant liver transplant may confer immunologic protection for the cardiac allograft.

Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction

The field of tissue engineering has advanced the development of increasingly biocompatible materials to mimic the extracellular matrix of vascularized tissue. However, a majority of studies instead rely on a multiday inosculation between engineered vessels and host vasculature rather than the direct connection of engineered microvascular networks with host vasculature. We have previously demonstrated that the rapid casting of three-dimensionally-printed (3D) sacrificial carbohydrate glass is an expeditious and a reliable method of creating scaffolds with 3D microvessel networks. Here, we describe a new surgical technique to directly connect host femoral arteries to patterned microvessel networks. Vessel networks were connected in vivo in a rat femoral artery graft model. We utilized laser Doppler imaging to monitor hind limb ischemia for several hours after implantation and thus measured the vascular patency of implants that were anastomosed to the femoral artery. This study may provide a method to overcome the challenge of rapid oxygen and nutrient delivery to engineered vascularized tissues implanted in vivo.

Higher Body Mass Index Increases Risk of HeartMate II Pump Thrombosis But Does Not Adversely Affect Long-Term Survival

While siRNA has tremendous potential for therapeutic applications, advancement is limited by poor delivery systems. Systemically, siRNAs are rapidly degraded, may have off-target silencing, and necessitate high working concentrations. To overcome this, we developed an injectable, guest-host assembled hydrogel between polyethylenimine (PEI) and polyethylene glycol (PEG) for local siRNA delivery. Guest-host modified polymers assembled with siRNAs to form polyplexes that had improved transfection and viability compared to PEI. At higher concentrations, these polymers assembled into shear-thinning hydrogels that rapidly self-healed. With siRNA encapsulation, the assemblies eroded as polyplexes which were active and transfected cells, observed by Cy3-siRNA uptake or GFP silencing in vitro. When injected into rat myocardium, the hydrogels localized polyplex release, observed by uptake of Cy5.5-siRNA and silencing of GFP for 1 week in a GFP-expressing rat. These results illustrate the potential for this system to be applied for therapeutic siRNA delivery, such as in cardiac pathologies.

Preoperative renal dysfunction does not affect outcomes of left ventricular assist device implantation

BACKGROUND Reduced left ventricular ejection fraction (EF) in the donor heart is often a contraindication for transplant. However, small studies have validated the use of hearts with evidence of myocardial dysfunction to boost the number of organs available for transplant. We hypothesize that donor hearts with reduced EF undergo myocardial recovery after transplant and result in equivalent recipient survival compared with grafts with normal function. METHODS We examined post-operative outcomes of heart recipients in the database of the United Network for Organ Sharing. Patients were grouped by donor EF as follows: <40% (reduced EF); between 40% and 50% (borderline EF); and ≥50% (normal EF). Propensity score matching was performed to compare separately reduced and borderline EF patients with normal EF patients. RESULTS Of 30,993 donors from 1996 to 2015, 127 (0.4%) had reduced EF, 613 (2.0%) had borderline EF and 30,253 (97.6%) had normal EF. In each of the 2 propensity score comparisons, the odds of post-operative stroke (p = 0.139, p = 0.551), pacemaker requirement (p = 0.238, p = 0.739), primary graft failure (p = 0.569, p = 0.817), rejection (p = 0.376, p = 0.533) and death at 1 year (p = 0.124, p = 0.247) were equivalent. At roughly 1-year follow-up after transplant, the mean EF of the reduced EF group was 58.0 ± 10.3% compared with 59.5 ± 7.5% in the matched normal EF group (p = 0.289). The mean follow-up EF of the borderline EF group was 58.3 ± 9.1% compared with 59.3 ± 7.7% in the matched normal EF group (p = 0.106). CONCLUSIONS Recipients of hearts with reduced EF have equivalent 1-year survival compared with recipients of hearts with normal EF. Donor hearts with reduced EF show significant functional recovery after transplant.