Therapeutic Efficacy of Cryopreserved, Allogeneic Extracellular Vesicles for Treatment of Acute Myocardial Infarction.

Extracellular vesicles (EV) that are derived from endothelial progenitor cells (EPC) have been determined to be a novel therapy for acute myocardial infarction, with a promise for immediate "off-the-shelf" delivery. Early experience suggests delivery of EVs from allogeneic sources is safe. Yet, clinical translation of this therapy requires assurances of both EV stability following cryopreservation and absence of an adverse immunologic response to EVs from allogeneic donors. Thus, more bioactivity studies on allogeneic EVs after cold storage are necessary to establish quality standards for its widespread clinical use. Thus, in this study, we aimed to demonstrate the safety and efficacy in delivering cryopreserved EVs in allogeneic recipients as a therapy for acute myocardial infarction.In this present study, we have analyzed the cardioprotective effects of allogeneic EPC-derived EVs after storage at -80°C for 2 months, using a shear-thinning gel (STG) as an in vivo delivery vehicle. EV size, proteome, and nucleic acid cargo were observed to remain steady through extended cryopreservation via nanoparticle tracking analysis, mass spectrometry, and nanodrop analysis, respectively. Fresh and previously frozen EVs in STG were delivered intramyocardially in a rat model of myocardial infarction (MI), with both showing improvements in contractility, angiogenesis, and scar thickness in comparison to phosphate-buffered saline (PBS) and STG controls at 4 weeks post-MI. Pathologic analyses and flow cytometry revealed minimal inflammatory and immune upregulation upon exposure of tissue to EVs pooled from allogeneic donor cells.Allogeneic EPC-EVs have been known to elicit minimal immune activity and retain therapeutic efficacy after at least 2 months of cryopreservation in a post-MI model.

Transplant Volume Is Associated With Graft Acceptance Threshold and Center Resource Availability.

BACKGROUND: Heart transplant volume varies significantly among centers. We hypothesized that centers where the transplant team routinely accepts organs previously declined by other centers and where operating room availability is unrestricted have higher transplant volumes. METHODS AND RESULTS: We used the potential transplant recipient sequence number in the United Network for Organ Sharing database as a surrogate for graft acceptance threshold and the number of transplantations occurring on weekends and 8 major holidays as a marker of center resource availability. Centers were classified as low-, medium-, or high-volume if the average annual number of transplants were, respectively, <10, 10-30, or >30 over a 10-year period. From July 12, 2006, to December 31, 2015, 19,054 transplants were performed by 142 centers. There were 59 low-volume centers, 69 medium-volume centers, and 14 high-volume centers with median potential transplant recipient sequence numbers for transplanted candidates of 7 (interquartile range 3-11), 7 (5-10), and 15 (7-40), respectively (P = .002). The median proportion of off-hours transplantations performed by medium-volume centers was 28% (25%-31%) compared with 32% (29%-33%) by high-volume centers (P = .009). Five-year survival was equivalent among all centers (P = .053). CONCLUSIONS: Transplants for candidates with high sequence numbers and unrestricted operating room availability are associated with increased center volume without sacrificing post-transplantation survival.

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

BACKGROUND: Obesity has been correlated with various adverse events in patients who receive left ventricular assist devices (LVAD). In this study, we sought to further characterize the role of obesity in this patient population.Methods and Results:We performed a retrospective analysis of 164 patients implanted with a HeartMate II from August 2008 to December 2014. Patients were categorized into 2 BMI groups based on WHO guidelines: BMI 18.5-30 kg/m2(n=99) and BMI >30 kg/m2(n=65). Patient demographics, adverse outcome and long-term survival were compared between the 2 groups. For any outcome associated with BMI groups, we performed a Cox regression to identify confounding comorbidities. Preoperative demographics and comorbidities were similar. Patients with BMI >30 were younger (P=0.01) and had a higher incidence of type 2 diabetes (P=0.01). While rate of pump thrombosis was higher among patients with BMI >30 (P=0.02), overall survival at 2 years did not differ. The most common cause of death was hemorrhagic stroke in the obese group. On multivariable cox regression analysis, BMI was an independent risk factor of pump thrombosis. CONCLUSIONS: Higher BMI does not reduce survival after VAD implantation but it does appear to increase the risk of pump thrombosis. Further studies to characterize the role of BMI in survival and thrombosis rates are warranted.

Bridge with a left ventricular assist device to a simultaneous heart and kidney transplant: Review of the United Network for Organ Sharing database.

BACKGROUND: Left ventricular assist device (LVAD) implantation as a bridge to cardiac transplantation (BTT) is an effective treatment for end-stage heart failure patients. Currently, there is an increasing number of patients with a LVAD who need a heart and kidney transplant (HKT). Little is known of the prognostic outcomes in these patients. This study was undertaken to determine whether an equivalent outcome would be present in HKTs as compared to a non-LVAD primary HKT cohort. METHODS: We reviewed the United Network for Organ Sharing database from 2004 to 2013. Orthotropic heart transplant recipients (n = 49 799) were subcategorized as dual organ HKT (n = 1 921) and then divided into cohorts of HKT following continuous flow left ventricular assist device placement (CF-VAD-HKT, n = 113) or no LVAD placement (HKT, n = 1 808). Survival after transplantation was analyzed. RESULTS: For CF-LVAD-HKT and HKT cohorts, preoperative characteristics were similar regarding age (50.8 ± 13.7, 50.1 ± 13.7, p = 0.75) and panel reactive antibody (12.3 ± 18.4 vs 7.1 ± 18.4, p = 0.06). Donors were similar in age, gender, creatinine, and ejection fraction. Post-transplant, there was no difference in complications. Survival for CF-LVAD-HKT and HKT were similar at 1 year (77% vs 82%) and 3 years (75% vs 77%, log rank p = 0.2814). CONCLUSIONS: For patients with advanced heart failure and persistent renal dysfunction, simultaneous HKT is a safe option. Survival after CF-LVAD-HKT is equivalent to conventional HKT.

Better With Time: An Economic Assessment of Long-Term Mechanical Circulatory Support in a Population Surviving at Least 1 Year with a Left Ventricular Assist Device.

This study aims to identify the major components of left ventricular assist device (LVAD)-related costs in a population on long-term mechanical circulatory support to gain insight into opportunities for improvements in quality, safety, and efficiency of care for end-stage heart failure patients. This was a single institution, retrospective cost analysis of patients who received a Heartmate II or HeartWare LVAD between November 2005 and October 2015. Payments for hospitalization for device implantation and subsequent readmissions were represented as the institution's 2015 Medicare reimbursement rate. The incidence, average Medicare reimbursement, and length of stay of readmissions were analyzed for the first year postimplant. A full year of LVAD-related hospitalizations in patients surviving ≥12 months, has a median Medicare reimbursement of $247,208. The most common complications related to ventricular assist devices were gastrointestinal bleeding, driveline infection, stroke, and pump thrombosis. Over 90% of total costs were incurred during the initial hospitalization. Seventy-five percent of first-time readmissions occurred within the first 4 months post discharge. Intensive care unit costs accounted for the single largest cost category during readmissions for all of the 4 most common complications. The trends demonstrated suggest that longer lengths of LVAD support in appropriately selected patients results in progressively decreasing cost-per-month up to 12 months, given the large upfront cost of device implantation and relatively modest additional costs of readmissions. This analysis emphasizes the importance of devices with improved complication profiles and clinical protocols to reduce unnecessary intensive care unit stays to increase the cost effectiveness of long-term ventricular assist device therapy.

Delayed delivery of endothelial progenitor cell-derived extracellular vesicles via shear thinning gel improves postinfarct hemodynamics.

BACKGROUND: Extracellular vesicles (EVs) are promising therapeutics for cardiovascular disease, but poorly-timed delivery might hinder efficacy. We characterized the time-dependent response to endothelial progenitor cell (EPC)-EVs within an injectable shear-thinning hydrogel (STG+EV) post-myocardial infarction (MI) to identify when an optimal response is achieved. METHODS: The angiogenic effects of prolonged hypoxia on cell response to EPC-EV therapy and EV uptake affinity were tested in vitro. A rat model of acute MI via left anterior descending artery ligation was created and STG+EV was delivered via intramyocardial injections into the infarct border zone at time points corresponding to phases of post-MI inflammation: 0 hours (immediate), 3 hours (acute inflammation), 4 days (proliferative), and 2 weeks (fibrosis). Hemodynamics 4 weeks post-treatment were compared across treatment and control groups (phosphate buffered saline [PBS], shear-thinning gel). Scar thickness and ventricular diameter were assessed histologically. The primary hemodynamic end point was end systolic elastance. The secondary end point was scar thickness. RESULTS: EPC-EVs incubated with chronically versus acutely hypoxic human umbilical vein endothelial cells resulted in a 2.56 ± 0.53 versus 1.65 ± 0.15-fold increase (P = .05) in a number of vascular meshes and higher uptake of EVs over 14 hours. End systolic elastance improved with STG+EV therapy at 4 days (0.54 ± 0.08) versus PBS or shear-thinning gel (0.26 ± 0.03 [P = .02]; 0.23 ± 0.02 [P = .01]). Preservation of ventricular diameter (6.20 ± 0.73 mm vs 8.58 ± 0.38 mm [P = .04]; 9.13 ± 0.25 mm [P = .01]) and scar thickness (0.89 ± 0.05 mm vs 0.62 ± 0.03 mm [P < .0001] and 0.58 ± 0.05 mm [P < .0001]) was significantly greater at 4 days, compared wit PBS and shear-thinning gel controls. CONCLUSIONS: Delivery of STG+EV 4 days post-MI improved left ventricular contractility and preserved global ventricular geometry, compared with controls and immediate therapy post-MI. These findings suggest other cell-derived therapies can be optimized by strategic timing of therapeutic intervention.

Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia.

OBJECTIVES: The ventricle undergoes adverse remodeling after myocardial infarction, resulting in abnormal biomechanics and decreased function. We hypothesize that tissue-engineered therapy could minimize postischemic remodeling through mechanical stress reduction and retention of tensile myocardial properties due to improved endothelial progenitor cell retention and intrinsic biomechanical properties of the hyaluronic acid shear-thinning gel. METHODS: Endothelial progenitor cells were harvested from adult Wistar rats and resuspended in shear-thinning gel. The constructs were injected at the border zone of ischemic rat myocardium in an acute model of myocardial infarction. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed: control (phosphate-buffered saline), endothelial progenitor cells, shear-thinning gel, and shear-thinning gel + endothelial progenitor cells. Novel high-resolution, high-sensitivity ultrasound with speckle tracking allowed for global strain analysis. Uniaxial testing assessed tensile biomechanical properties. RESULTS: Shear-thinning gel + endothelial progenitor cell injection significantly increased engraftment and retention of the endothelial progenitor cells within the myocardium compared with endothelial progenitor cells alone. With the use of strain echocardiography, a significant improvement in left ventricular ejection fraction was noted in the shear-thinning gel + endothelial progenitor cell cohort compared with control (69.5% ± 10.8% vs 40.1% ± 4.6%, P = .04). A significant normalization of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with shear-thinning gel + endothelial progenitor cell therapy compared with control was also evident (0.84 + 0.3 cm/s vs 0.11 ± 0.01 cm/s, P = .03). A significantly positive and higher myocardial strain was observed in shear-thinning gel + endothelial progenitor cell (4.5% ± 0.45%) compared with shear-thinning gel (3.7% ± 0.24%), endothelial progenitor cell (3.5% ± 0.97%), and control (8.6% ± 0.3%, P = .05). A resultant reduction in dynamic stiffness was noted in the shear-thinning gel + endothelial progenitor cell cohort. CONCLUSIONS: This novel injectable shear-thinning hyaluronic acid hydrogel demonstrates stabilization of border zone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. The cellular construct provides a normalization of strain measurements and reduces left ventricular dilatation, thus resulting in improvement of left ventricular function.

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

OBJECTIVE: Selection criteria for durable left ventricular assist device (LVAD) implantation remain unclear. One such criterion is renal function. In this study we evaluated outcomes of LVAD implantation in patients with preoperative renal dysfunction. METHODS: Patients with implanted LVADs as destination therapy (DT) or bridge to transplantation (BTT) at a single institution between 2006 and 2015 were included. Primary stratification was according to pre-implantation glomerular filtration rate (GFR): >60 mL/min versus <60 mL/min or dialysis dependence. The primary outcome was post-LVAD implantation overall survival. RESULTS: Two hundred thirty-eight patients underwent LVAD implantation during the study period as DT (60%; n = 142) or BTT (40%; n = 96). Reduced GFR was present in 56% (n = 132), with 8% (n = 18) being dialysis-dependent. Normal versus reduced GFR cohorts were well matched except for a higher incidence of coronary artery disease in the patients with reduced GFR (61% vs 48%; P = .04). Mean follow-up was 13.5 ± 17.0 months. Unadjusted and risk-adjusted survival at 1, 3, 6, and 12 months after LVAD implantation were similar between the cohorts for DT and BTT. Rates of transplantation were comparable in BTT patients (61% normal vs 53% reduced GFR; P = .43). Recovery of renal function to a GFR >60 mL/min occurred in 43% (n = 17) and 57% (n = 42) of patients with reduced GFR in the BTT and DT cohorts, respectively, by 1 year post implantation. CONCLUSIONS: Well selected patients with preexisting renal dysfunction can undergo LVAD implantation with acceptable outcomes. Approximately half of LVAD recipients with preimplantation renal dysfunction will recover normal renal function within the first postoperative year. Renal dysfunction alone should not serve as an absolute contraindication to LVAD therapy.

Is there a difference in bleeding after left ventricular assist device implant: centrifugal versus axial?

BACKGROUND: Continuous-flow left ventricular assist devices (CF-LVAD) have become the standard of care for patients with end stage heart failure. Device reliability has increased, bringing the potential for VAD, compared to transplant, into debate. However, complications continue to limit VADs as first line therapy. Bleeding is a major morbidity. A debate exists as to the difference in bleeding profile between the major centrifugal and axial flow devices. We hypothesized that there would be similar adverse bleeding event profiles between the 2 major CF-LVADs. METHODS: We retrospectively investigated isolated CF LVADs performed at our institution between July 2010 and July 2015: HeartMateII (HMII, n = 105) and HeartWare (HVAD, n = 34). We reviewed demographic, perioperative and short- and long-term outcomes. RESULTS: There was no significant difference in demographics or comorbidities. There was a low incidence of gastrointestinal (GI) bleed 3.9% in HMII and 2.9% in HVAD (p = 0.78). Preoperatively, the cohorts did not differ in coagulation measures (p = 0.95). Within the post-operative period, there was no difference in product transfusion: red blood cells (p = 0.10), fresh frozen plasma (p = 0.19), and platelets (p = 0.89). Post-operatively, a higher but not significantly different number of HMII patients returned to the operating room for bleeding (n = 27) compared to HVAD (n = 6, p = 0.35). There was no difference in rates of stroke (p = 0.65), re-intubation (p = 0.60), driveline infection (p = 0.05), and GI bleeding (p = 0.31). The patients had equivalent ICU LOS (p = 0.86) and index hospitalization LOS (p = 0.59). CONCLUSION: We found no difference in the rate of bleeding complications between the current commercially available axial and centrifugal flow devices.

Different Clinical Course and Complications in Interagency Registry for Mechanically Assisted Circulatory Support 1 (INTERMACS) Patients Managed With or Without Extracorporeal Membrane Oxygenation.

Extracorporeal membrane oxygenation (ECMO) as a bridge to left ventricular assist device (LVAD) implantation has shown promise in improving end-organ function and optimizing outcomes in some critically ill patients, but the practice remains controversial. Retrospective review of patients who received LVADs from May 2008 to September 2016 at a high-volume, tertiary care cardiovascular center was performed. Subjects were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) class 1 patients divided into ECMO bridge and non-ECMO bridge cohorts. Patient demographics, adverse events, and survival at immediate and 1 year postoperative time points were compared between groups. In total, 235 patients received a HeartMate II or HVAD during the study period. Among INTERMACS 1 patients, 18 were ECMO bridge and 17 were non-ECMO bridge. Age, gender and bridge-to-transplant proportions (50% vs. 53%) were similar between groups. The ECMO bridge group had lower hemoglobin (7.9 ± 1.1 vs. 10.2 ± 2.2; p < 0.01), platelet (101 [70] vs. 176 [115]; p < 0.05), and prealbumin levels (10.6 ± 4.3 vs. 17.3 ± 7.7; p < 0.01). Nearly half (n = 8; 44%) of the ECMO bridge patients required packed red blood cell transfusions before VAD and were more likely to be on an epinephrine drip (78% vs. 12%; p < 0.01). However, along with these adjunctive measures, the ECMO bridge did effectively improve hemodynamic profiles by the time of VAD implant resulting in lower central venous pressure (7.7 ± 2.5 vs. 10.4 ± 4.8; p < 0.01) and mean pulmonary arterial pressure (18 ± 9 vs. 32 ± 8; p < 0.01). It also allowed for restoration of end-organ function as noted by comparable creatinine (1.0 [1.2] vs. 1.4 [0.6]) and total bilirubin levels (1.6 ± 1 vs.1.5 ± 1.7) between the two groups. There was no difference in rates of adverse events. Survival at 30 days postoperative and at 1 year (77% vs. 88%; p = 0.6) was similar. This study demonstrates that ECMO bridge is a central component of a multifaceted strategy for stabilization of select patients with severe hemodynamic instability before LVAD implantation. Further studies to optimize patient selection should be further explored.

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

Aims: Previous studies have demonstrated improved cardiac function following myocardial infarction (MI) after administration of endothelial progenitor cells (EPCs) into ischaemic myocardium. A growing body of literature supports paracrine effectors, including extracellular vesicles (EVs), as the main mediators of the therapeutic benefits of EPCs. The direct use of paracrine factors is an attractive strategy that harnesses the effects of cell therapy without concerns of cell engraftment or viability. We aim to reproduce the beneficial effects of EPC treatment through delivery of EPC-derived EVs within a shear-thinning gel (STG) for precise localization and sustained delivery. Methods and results: EVs were harvested from EPCs isolated from adult male Rattus norvegicus (Wistar) rats and characterized by electron microscopy, nanoparticle tracking analysis (NTA), and mass spectrometry. EVs were incorporated into the STG and injected at the border zone in rat models of MI. Haemodynamic function, angiogenesis, and myocardial remodelling were analyzed in five groups: phosphate buffered saline (PBS) control, STG control, EVs in PBS, EVs in STG, and EPCs in STG. Electron microscopy and NTA of EVs showed uniform particles of 50-200 nm. EV content analysis revealed several key angiogenic mediators. EV uptake by endothelial cells was confirmed and followed by robust therapeutic angiogenesis. In vivo animal experiments demonstrated that delivery of EVs within the STG resulted in increased peri-infarct vascular proliferation, preservation of ventricular geometry, and improved haemodynamic function post-MI. Conclusions: EPC-derived EVs delivered into ischaemic myocardium via an injectable hydrogel enhanced peri-infarct angiogenesis and myocardial haemodynamics in a rat model of MI. The STG greatly increased therapeutic efficiency and efficacy of EV-mediated myocardial preservation.

Extended distance cardiac allograft can successfully be utilized without impacting long-term survival.

BACKGROUND: Despite the severe shortage of donor cardiac allografts, the general belief in worse outcomes with donors from prolonged distances has resulted in many centers greatly limiting the acceptable geographic distance of acceptable donors. However, with improvements in allograft preservation, it is likely that distance may be extended without compromising graft integrity. We hypothesized that recipients of appropriately selected allografts from greater distances would have equivalent long-term survival compared with recipients from closer geographic regions. METHODS: We retrospectively analyzed the United Network for Organ Sharing (UNOS) adult heart transplant data from January 2000 to December 2013. Recipients were stratified by donor distance. Demographic and outcomes data were analyzed, with a primary end-point of survival. RESULTS: During the study period, 25,996 isolated orthotopic heart transplantations (OHTs) were performed. Patients were stratified by distance: 0 to 500 miles (n = 24,645); 501 to 1,000 miles (n = 1,201); 1,001 to 1,500 miles (n = 134); and 1,501+ miles (n = 16). Increased donor allograft distance correlated with significantly longer ischemic times (3.1 miles for 0 to 500 miles vs 7.5 hours for 1,501+ miles, p = 0.0001). One- and 5-year survival was similar in all cohorts, using Kaplan-Meier survival analysis (log rank, p = 0.8025). There was no difference in rate of stroke (p = 0.82), dialysis (p = 0.60) or reoperation (p = 0.28). Length of stay was equivalent across cohorts (p = 0.11). CONCLUSIONS: Appropriately selected allografts from donors at a greater distance should be considered to increase organ availability. Donor heart procurement from increased distance may not directly increase morbidity and mortality post-heart transplant.

Non-cardiac surgery in patients with continuous-flow left ventricular assist devices: a single institutional experience.

With improvements in life expectancy for patients with continuous-flow left ventricular assist devices (LVADs), non-cardiac surgeons will increasingly encounter surgical problems in this population. 209 patients underwent LVAD placement between 10/1/2007 and 6/1/2015 at a single institution. Survival was compared between patients who had non-cardiac surgery (NCS) during the initial LVAD implantation hospitalization (n=36) and those who had NCS only in subsequent hospitalizations (n=33). Postoperative complication rates were examined. Index admission NCS was associated with lower 5-year survival compared with subsequent admission NCS (27.1% vs 39.4%, p=0.017). In subsequent admissions, the risks of bleeding and infectious complications were the same for elective or urgent NCS, but the risk of death was higher in the urgent surgery group. We conclude that elective NCS can be performed with low risk of death or LVAD dysfunction after sufficient recovery of patients from LVAD implantation.

Improved Approach With Subcostal Exchange of the HeartMate II Left Ventricular Assist Device: Difference in On and Off Pump?

BACKGROUND: The HeartMate II (St. Jude Medical, Inc, St. Paul, MN [previously Thoratec]) left ventricular assist device (LVAD) exchange has traditionally involved a redo sternotomy. Alternate minimally invasive subcostal approaches have the advantage of avoiding sternal reentry, excessive bleeding, and prolonged recovery. METHODS: This retrospective review included patients who underwent an exchange from May 2009 to March 2016. The patients were divided into three cohorts: (1) redo sternotomy, (2) subcostal approach involving cardiopulmonary bypass (CPB) (ON-CPB SC), and (3) subcostal approach off the CPB pump (OFF-CPB SC). Data pertaining to patients' baseline characteristics and outcomes were collected and analyzed. RESULTS: From May 1, 2009 to July 31, 2016, 33 HeartMate II LVAD exchanges were performed. There were 11 redo sternotomies and 22 subcostal exchanges, 12 of which were in the OFF-CPB SC group. There was no significant difference among the groups in terms of age (p = 0.75), sex (p = 0.95), and indication for exchange (p = 0.94). There was a higher red blood cell transfusion requirement within the sternotomy cohort (p < 0.001). The median time to extubation and the intensive care unit length of stay were significantly shorter in the OFF-CPB SC group (1 and 2.5 days, respectively) than in the sternotomy (2.5 and 21 day, respectively) and ON-CPB SC groups (1.5 and 5 days, respectively). The 30-day and 90-day survival rates were equivalent among the cohorts. CONCLUSIONS: Exchange of the HeartMate II LVAD can be accomplished with significantly improved recovery time and transfusion requirement through a less invasive subcostal approach when compared with sternotomy. The subcostal approach can be performed safely both on and off cardiopulmonary bypass.

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

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.

Transplantation of "high-risk" donor hearts: Implications for infection.

BACKGROUND: Heart transplantation is the gold-standard treatment for end-stage heart failure. Short- and long-term outcomes have been excellent, but the shortage of organs persists. The number of potential recipients who die while awaiting orthotopic heart transplantation increases yearly. In 2004, the label "high-risk donor" (HRD) was applied, by the United Network for Organ Sharing (UNOS), to any organ donor who met the Centers for Disease Control (CDC) criteria for behavior that put them at high risk of infection. Despite organ shortages, grafts from HRD CDCs are often declined, because of concerns regarding infection. We undertook this study to analyze our extensive experience with orthotopic heart transplantation of grafts from HRD CDCs, and to determine the short- and long-term outcomes associated with recipients of hearts from HRD CDCs, particularly transmission of infection. METHODS: We performed 367 heart transplantations at our center from September 2008 to September 2014, a timeframe during which the HRD CDC labeling had been implemented. Of the total number of orthotopic heart transplantations performed, 55 patients (15%) received organs from HRD CDCs that had known negative serology for human immunodeficiency virus (HIV), hepatitis B, and hepatitis C. We reviewed demographic, perioperative, and short- and long-term outcomes. The recipients of grafts from HRD CDCs were followed closely, with 3- and 12-month surveillance laboratory testing of viral load for HIV, for hepatitis B, and for hepatitis C core- and surface-antigen serology. RESULTS: All 55 patients (72.7% were men) underwent a successful transplantation procedure. One patient was excluded from follow-up analysis because he was re-transplanted within 4 days owing to the posttransplant finding of metastatic lung adenocarcinoma within the donor. Primary etiology of heart failure was ischemic in 18 of the patients. The most common blood type was O positive, in 20 patients (37.1%), followed by A positive, in 19 patients (35.2%). A total of 19 (35.2%) patients were supported with a mechanical assist device before the transplantation. The average allograft ischemic time was 173 ± 96 minutes. The median length of hospital stay was 19.5 days. A low incidence was observed of the postoperative complications of stroke (1.9%), dialysis (3.9%), and complete heart block (3.9%). Kaplan-Meier analysis demonstrated excellent survival, both short-term (1 year; 94%) and long-term (3 years; 80%). Allograft function was excellent at time of discharge with a left ejection fraction of 67.8% ± 7.3%. Only one patient (1.9%) was noted to have hepatitis C seroconversion at 105 days after receiving the transplant. After antiviral treatment, the patient has had undetectable viral loads to date. All other patients had undetectable plasma viral loads of HIV, hepatitis C, and hepatitis B, determined using rigorous testing. CONCLUSIONS: We present the only single-center series on recipients of heart transplants from HRD CDCs. This potential source of suitable donor organs is shown to lead to excellent survival, without an increased incidence of perioperative or postoperative complications. Furthermore, the risk of transmission of infection from donors in this subgroup seems to be minimal.