Carol W. Chen

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.

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.

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.

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.

Better With Time: An Economic Assessment of Long Term Mechanical Circulatory Support in a Population Surviving at Least One 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 institutions 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

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

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.

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

BackgroundContinuous-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.MethodsWe 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.ResultsThere 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).ConclusionWe found no difference in the rate of bleeding complications between the current commercially available axial and centrifugal flow devices.

Expanded donor selection criteria can increase organ utilization

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.

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

We appreciate the opportunity to respond to the letter by Chinnadurai et al, and we are encouraged that, after a similar propensity-score matching analysis utilizing the same database, they are in agreement that low left ventricular ejection fraction (LVEF) organs from young brain-dead donors should be aggressively evaluated for transplant. As we have discussed previously, we recognize there are several important limitations in our retrospective study using a large national database. Most notably, the timing of the last recorded LVEF in relation to the time of allograft explant may vary slightly among procurement centers. Unfortunately, as with all studies using this valuable database, we must accept the trade-offs in detail to appreciate the exceptional advantage of having a large sample size collected from all corners of the nation, allowing the results to be widely generalizable.

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

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.