BACKGROUND:Extended criteria donor (ECD) hearts available with donation after brain death (DBD) are underutilized for transplantation due to limitations of cold storage. OBJECTIVES:This study evaluated use of an extracorporeal perfusion system on donor heart utilization and post-transplant outcomes in ECD DBD hearts. METHODS:In this prospective, single-arm, multicenter study, adult heart transplant recipients received ECD hearts using an extracorporeal perfusion system if hearts met study criteria. The primary outcome was a composite of 30-day survival and absence of severe primary graft dysfunction (PGD). Secondary outcomes were donor heart utilization rate, 30-day survival, and incidence of severe PGD. The safety outcome was the mean number of heart graft-related serious adverse events within 30 days. Additional outcomes included survival through 2 years benchmarked to concurrent nonrandomized control subjects. RESULTS:A total of 173 ECD DBD hearts were perfused; 150 (87%) were successfully transplanted; 23 (13%) did not meet study transplantation criteria. At 30 days, 92% of patients had survived and had no severe PGD. The 30-day survival was 97%, and the incidence of severe PGD was 6.7%. The mean number of heart graft-related serious adverse events within 30 days was 0.17 (95% CI: 0.11-0.23). Patient survival was 93%, 89%, and 86% at 6, 12, and 24 months, respectively, and was comparable with concurrent nonrandomized control subjects. CONCLUSIONS:Use of an extracorporeal perfusion system resulted in successfully transplanting 87% of donor hearts with excellent patient survival to 2 years post-transplant and low rates of severe PGD. The ability to safely use ECD DBD hearts could substantially increase the number of heart transplants and expand access to patients in need. (International EXPAND Heart Pivotal Trial [EXPANDHeart]; NCT02323321; Heart EXPAND Continued Access Protocol; NCT03835754).

Background. The increasing prevalence of heart failure has led to the expanded use of left ventricle assist devices (VADs) for end-stage heart failure patients worldwide. Technological improvements witnessed the development of miniaturized VADs and their implantation through less traumatic non-full sternotomy approaches using a lateral thoracotomy (LT). Although adoption of the LT approach is steadily growing, a lack of consensus remains regarding patient selection, details of the surgical technique, and perioperative management. Furthermore, the current literature does not offer prospective randomized studies or evidence-based guidelines for LT-VAD implantation. Methods. A worldwide group of LT-VAD experts was convened to discuss these key topics openly. After a PubMed search and review with all authors, a consensus was reached and an expert consensus paper on LT-VAD implantation was developed. Results. This document aims to guide clinicians in the selection of patients suitable for LT approaches and preoperative optimization. Details of operative techniques are described, with an overview of hemisternotomy and bilateral thoracotomy approaches. A review of the best surgical practices for placement of the pump, inflow cannula, and outflow graft provides advice on the best surgical strategies to avoid device malpositioning while optimizing VAD function. Experts' opinions on cardiopulmonary bypass, postoperative management, and approaches for pump exchange and explant are presented. This review also emphasizes the critical need for multidisciplinary teams and specific training. Conclusions. This expert consensus review provides a compact guide to LT for VAD implantation, from patient selection through intraoperative tips and postoperative management. (C) 2021 by The Society of Thoracic Surgeons

Background. Less invasive techniques for left ventricular assist device implantation have been increasingly prevalent over past years and have been associated with improved clinical outcomes. The procedural economic impact of these techniques remains unknown. We sought to study and report economic outcomes associated with the thoracotomy implantation approach. Methods. The LATERAL clinical trial evaluated the safety and efficacy of the thoracotomy approach for implantation of the HeartWare centrifugal-flow ventricular assist device system (HVAD). We collected UB-04 forms in parallel to the trial, allowing analysis of index hospitalization costs. All charges were converted to costs using hospital-specific cost-to-charge ratios and were subsequently compared with Medicare cost data for the same period (2015-2016). Because thoracotomy implants were off-label for all left ventricular assist devices during that period, the Medicare cohort was assumed to consist predominately of traditional sternotomy patients. Results. Thoracotomy patients demonstrated decreased costs compared with sternotomy patients during the index hospitalization. Mean total index hospitalization costs for thoracotomy were $ 204,107 per patient, corresponding to 21.6% reduction (P <.001) and $ 56,385 savings per procedure compared with sternotomy. Across almost all cost categories, thoracotomy implants were less costly. Conclusions. In LATERAL, a clinical trial evaluating the safety and efficacy of the thoracotomy approach for HVAD, costs were lower than those reported in Medicare patient claims occurring over the same period. Because Medicare data can be presumed to consist of predominately sternotomy procedures, thoracotomy appears less expensive than traditional sternotomy. (C) 2020 by The Society of Thoracic Surgeons

This study reports the first analysis regarding cost-effectiveness of left ventricular assist device (LVAD) implantation via thoracotomy. Cost-effectiveness of LVADs implanted via the traditional surgical approach of sternotomy has been improved through the years because of technological advances, along with understanding the importance of patient selection and postimplant management have on positively affecting outcomes. Given the positive clinical outcomes of the thoracotomy approach, we seek to study the cost-effectiveness of a centrifugal LVAD via this less invasive approach. We developed a Markov model. Survival and quality of life inputs (QALY) for the LVAD arm were based on data from the LATERAL clinical trial. For the Medical Management arm, survival was derived from the Seattle Heart Failure Model. The heart transplant probability was derived from INTERMACS. Survival after heart transplantation used International Society for Heart and Lung Transplantation data. Cost inputs were calculated based on Medicare data and past literature. The incremental cost-effectiveness ratio was found to be $64,632 per quality adjusted life year and $57,891 per life year in the bridge to transplant indication. These results demonstrate further improvement in the overall cost-effectiveness of LVAD therapy and confirm implantation of LVADs via a less invasive approach as being cost-effective.

In a Markov model assessing the cost-effectiveness of Thoracotomy Approach for the Implantation of LVADs, we found an ICER of $64,684/QALY. In cases of low heart transplant rates the ICER was below $50,000/QALY. These outcomes demonstrate a significant improvement in the ICER and confirm that implantation via thoracotomy of a small intrapericardial centrifugal LVAD in certain scenarios is cost-effective.

Background: The paucity of available hearts for transplantation means that more patients remain on durable left ventricular support for longer periods of time. The Registry to Evaluate the HeartWare Left Ventricular Assist System was an investigator-initiated multicenter, prospective, single-arm database established to collect post-Conformité Européene mark clinical information on patients receiving the HeartWare ventricular assist device system as a bridge to transplantation. This registry represents the longest multicenter follow-up of primary left ventricular assist device outcomes. Methods: Data were collected on 254 commercial implants performed between February 2009 and March 2012 from 9 centers in Europe (7) and Australia (2). Patients were followed to device explant, heart transplantation, or death. The outcomes of patients through July/August 2018 were analyzed. Summary statistics were used to describe patient demographics, adverse events, length of support, and outcomes for this extended-term cohort. Results: A total of 122 patients were on support for >2 years, and 34 patients were on support for >5 years. Twenty nine patients are still alive on support (support ranging from 1213 to 3396 days), and 23 of those are on their original HeartWare ventricular assist device system. Kaplan–Meier survival through 7 years was 51%. Through 6 years, freedom from any stroke was 82%, while freedom from severely disabling stroke was 89%. Conclusions: Low rates of heart transplant now require longer periods of left ventricular assist device support in patients. This analysis demonstrates that long-term support using a HeartWare ventricular assist device system offers survival of 51% through 7 years.

Purpose Less invasive techniques for Left Ventricular Assist Device (LVAD) implantation have been increasingly prevalent over the last years and have been associated with improved clinical outcomes. The procedural economic impact of these techniques remains unknown. We sought to study and report economic outcomes associated with the thoracotomy implantation approach. Methods LATERAL is the first clinical trial evaluating the safety and efficacy of the thoracotomy approach for implantation of a small intrapericardial centrifugal LVAD. UB-04 forms were collected in parallel to the trial, allowing analysis of index hospitalization costs. All charges were converted to costs using hospital specific cost-to-charge ratios and were subsequently compared to Medicare cost data (Instant Health Data, IHD) for the same time period (2015-2016). Since thoracotomy implants were off-label for all LVADs during that period, the Medicare cohort was assumed to predominately consist of traditional sternotomy patients. Several sensitivity analyses were also conducted. Results Thoracotomy patients (N=97) demonstrated decreased costs compared to sternotomy patients (N=2,831) during the index hospitalization. Mean total index hospitalization costs for thoracotomy were $203,939 (±$87,401) vs. $260,492 (±$153,703) for sternotomy (p<0.0001). Across almost all cost categories, Thoracotomy implants were found less costly. Supply-related costs amounted to $29,445 (±$27,033) for thoracotomy vs. $37,209 (±$36,190) for sternotomy (p<0.0001), days in Intensive Care (both ICU and CCU) cost $28,918 (±$23,742) for thoracotomy cohort against $42,721 (±$51,271) for sternotomy (p<0.0001) and Laboratory-related costs amounted to $20,255 (±$15,215) vs. $25,919 (±$29,048) for sternotomy (p<0.0001). Conclusion In LATERAL, the first clinical trial evaluating the safety and efficacy of thoracotomy of a small intrapericardial centrifugal LVAD, costs were found to be lower than the ones reported in Medicare patient claims occurring over the same time period. Since Medicare data can be presumed to consist of predominately sternotomy procedures, Thoracotomy appears less expensive than traditional sternotomy.

Purpose Heart transplant for patients with left ventricular assist device (LVAD) often requires long cardiopulmonary bypass and increased blood product use. Hypothesis was made that a donor heart should not be undersized so that it can tolerate complicated surgery. We evaluated the impact of donor-to-recipient size matching on outcome after heart transplantation bridged with LVAD. Methods We reviewed UNOS registry data on patients who received heart transplant bridged with continuous flow LVAD (CF-LVAD). Patients were divided into three groups based on donor and recipient weight ratio; <0.8 (Undersized group), 0.8-1.2 (Matched group), and >1.2 (Oversized group). Pre-Transplant characteristics were compared among the groups. The primary outcome was post-transplant survival. Secondary outcomes included graft failure, dialysis requirement post-transplant and stroke. Kaplan-Meier survival curves and the log-rank test was used to predict and compare survival among 3 groups. Cox proportional hazards analysis was used to identify independent predictors of mortality. Results From 2009 to 2015, 4020 patients were bridged to heart transplant with CF-LVAD. Undersized group included 586 patients (14.6%), Matched group included 2699 patients (67.1%) and Oversized group included 735 patients (18.3%). Incidence of post-transplant dialysis was higher in Undersized group (16%) than Matched (11.8%) or Oversized group (10%, p=0.003). Incidence of graft failure was significantly greater in Undersized group (18%) than Matched (13.4%) or Oversized group (15%, p=0.019). On univariate analysis survival of Undersized group was lower than other two groups (p=0.022). Pre-transplant serum creatinine (p=0.001), height (0.002) and weight (p=0.007) were independent predictors of mortality but use of undersized heart was not. Conclusion Survival of heart transplant recipients of undersized donor is lower than that of size matched or oversized donor. Pre-transplant serum creatinine, height and weight were predictors of mortality but use of undersized heart itself was not.

Lowering calcineurin inhibitor (CNI) exposure to avoid toxicity is desirable after solid organ transplantation although the risk of organ rejection is of concern after lung transplantation (LTx). The 4Everlung trial was designed to evaluate the benefit of early everolimus (EVR)-based quadruple low immunosuppressive (IS) regimen on kidney function (RF) after LTx

Mortality of patients with cardiogenic shock remains high. Patients with biventricular failure have higher mortality than those with left ventricular failure. Bridging strategy including selection of device and timing of device insertion is controversial. CentriMag can offer hemodynamic stability when other less invasive support device failed.

The LATERAL Trial was designed to demonstrate the safety and effectiveness of the HVAD System for refractory, end-stage heart failure implanted via a thoracotomy approach. However, the key secondary endpoint of improvement in the mean length of stay and rehospitalizations had not been reported.

Background Preoperative low-dose whole-body irradiation (IRR) with 1.5 and 7 Gy thymic IRR of the recipient, combined with a perioperative donor splenocyte infusion lead to reliable donor specific peripheral tolerance in our allogeneic porcine lung transplantation model. To reduce the toxicity of this preconditioning regime, modifications of the IRR protocol and their impact on allograft survival were assessed.Methods Left-sided single lung transplantation from major histocompatibility complex and sex mismatched donors was performed in 14 adult female minipigs. Recipient animals were exposed to 3 different protocols of nonmyeloablative IRR within 12 hours before transplantation. All animals were administered a donor splenocyte infusion on the day of lung transplantation. Intravenous pharmacologic immunosuppression was withdrawn after 28 postoperative days. Allograft survival was monitored by chest radiographs and bronchoscopy.Results IRR prolonged transplant survival in a dose- and field-dependent manner. Shielding of the bone marrow from IRR (total lymphoid IRR at 1.5 and 7 Gy thymic IRR) significantly reduced protocol toxicity defined as thrombocytopenia and consecutive increased bleeding propensity, but had a less effective impact on graft survival. Whole-body IRR at 0.5 and 7 Gy thymic IRR proved to be ineffective for reliable tolerance induction. Eventually, high levels of circulating CD4(+)CD25(high) regulatory T cells were present in long-term survivors.Conclusions These data show that the infusion of donor-specific alloantigen in combination with IRR is efficient once a threshold dose is exceeded.

BACKGROUND The allocation of donor lungs for transplantation in Germany was changed on 10 December 2011 to a system based on the Lung Allocation Score (LAS). The aim of the present study is to determine whether this change has prolonged the survival of patients on the transplant waiting list and of those who have undergone lung transplantation (LTx). METHODS We retrospectively compared data from the three-year periods before and after the change to an LAS-based allocation system (2009-2011 vs. 2012-2014). RESULTS The number of patients on the active waiting list declined from 606 on 12/31/2011 to 432 on 12/31/2014, a 29% decrease. The number of patients who died while on the waiting list fell from 306 in 2009-2011 to 226 in 2012-2014 (-26%, p = 0.04). Waiting-list mortality declined across all disease groups. Meanwhile, the number of lung transplantation procedures per year increased by 21% over the period of observation, from 865 to 1045. During the period in which the LAS was used, the proportion of transplant recipients with restrictive lung disease (46% vs. 31%; p<0.001) surpassed the proportion of those with a diagnosis of obstructive lung disease (33% vs. 40%; p = 0.003). The percentage of transplantations in patients treated with mechanical ventilation or extracorporeal respiratory support before transplantation rose from 9% to 13%. The one-year survival rate after lung transplantation was 76% in 2009-2011 and 81% in 2012-2014. CONCLUSION The introduction of the LAS in Germany was associated with a decrease in the number of patients on the waiting list, and also in the number of deaths among patients on the waiting list. The distribution of primary diagnoses among transplant recipients shifted away from obstructive and toward restrictive lung diseases. In the future, additional parameters of patients on the waiting list should be considered to enable further improvement of the allocation model.