Pre-transplant Mechanical Circulatory Support Research Articles

A comparison of quality-adjusted life years in older adults after heart transplantation versus long-term mechanical support: Findings from the SUSTAIN-IT study

BackgroundThe quality-adjusted life year (QALY) measures disease burden and treatment, combining overall survival and health-related quality of life (HRQOL). We estimated QALYs in three groups of older patients (60-80 years) with heart failure (HF) who underwent heart transplantation (HT, with pre-transplant mechanical circulatory support [HT MCS] or HT without pre-transplant MCS [HT Non-MCS]) or long-term MCS (destination therapy). We also identified factors associated with gains in QALYs through 24 months follow-up. MethodsOf 393 eligible patients enrolled (10/1/15-12/31/18) at 13 U.S. sites, 161 underwent HT (n=68 HT MCS, n=93 HT Non-MCS) and 144 underwent long-term MCS. Survival and HRQOL data were collected through 24 months. QALY health utilities were based on patient self-report of EQ-5D-3L dimensions. Mean-restricted QALYs were compared among groups using generalized linear models. ResultsFor the entire cohort, mean age in years closest to surgery was 67 (standard deviation, SD: 4.7), 78% were male, and 83% were White. By 18 months post-surgery, sustained significant differences in adjusted average+SD QALYs emerged across groups, with the HT Non-MCS group having the highest average QALYs (24-month window: HT Non-MCS=22.58+1.1, HT MCS=19.53+1.33, Long-term MCS=19.49+1.3, p=0.003). At 24 months post-operatively, a lower gain in QALYs was associated with HT MCS, long-term MCS, a lower pre-operative LVEF, NYHA class III or IV before surgery, and an ischemic or other etiology of HF. ConclusionsDetermination of QALYs may provide important information for policy makers and clinicians to consider regarding benefits of HT and long-term MCS as treatment options for older patients with HF.

(399) - Association Between Pre-Transplant Mechanical Circulatory Support Status and Donor-Derived Cell-Free DNA Levels and Gene Expression Profiling Following Heart Transplant

(399) - Association Between Pre-Transplant Mechanical Circulatory Support Status and Donor-Derived Cell-Free DNA Levels and Gene Expression Profiling Following Heart Transplant

Strategy for prophylactic application of peripheral va-ecmo in transplantation involving expected extremely prolonged ischemia time

Heart transplantation (HT) with extremely prolonged (>6 hours) graft ischemia is associated with severe cardiac graft dysfunction. The high efficiency of prophylactic (preoperative initiation) veno-arterial extracorporeal membrane oxygenation (VA-ECMO) to prevent severe hemodynamic disorders during cardiac surgery has been demonstrated. Objective: to determine the effect of prophylactic VA-ECMO on the perioperative period in HT with an expected graft ischemia >6 hours. Materials and methods. Thirty-eight recipients (33 (86.8%) males and 5 (13.2%) females), age 11–66 (44.7 ± 12.0) years (median 48.0 years) were examined. Pre-transplant mechanical circulatory support (MCS) using peripheral VA-ECMO was applied in 15 (39.5%) recipients, in 6 of whom by prophylactic technique. The recipients (n = 38) were divided into 3 groups: 1) «no pre-HT VA-ECMO» (n = 23); 2) «pre-HT VA-ECMO» (n = 9) – pre-transplant VA-ECMO as a bridge to HT; 3) «prophylactic VA-ECMO» (n = 6). Results. In «prophylactic VA-ECMO» group, extracorporeal circulation (ECC) (94.0 [85.5; 102.8] min) and reperfusion time (20.0 [18.3; 27.6] min) were shorter (p < 0.05) compared to «no pre-HT VA-ECMO» (161.0 [122; 191.5] and 60.0 [55.3; 70.5] min) and «pre-HT VA-ECMO» (127.0 [117; 150.3] and 35.0 [27.8; 48.8] min) groups. The vasoactive-inotropic score was lower (p < 0.05) in «pre-HT VA-ECMO» and «prophylactic VAECMO» groups compared to recipients in «no pre-HT VA-ECMO» group, 12.1 [11.2; 14.0] and 12.5 [11.7; 14.8] vs. 16.0 [15.0; 18.5], respectively. The groups did not differ in terms of incidence of severe primary dysfunction. The «pre-HT VA-ECMO» and «prophylactic VA-ECMO» groups were characterized by shorter duration of mechanical ventilation (MV) compared with «no pre-HT VA-ECMO» group (11.7 [10.0; 16.5] and 12.7 [11.3; 18.4], respectively, vs. 14.5 [13.0; 19.3]). The «no pre-HT VA-ECMO» and «prophylactic VA-ECMO» groups did not differ in the need for postoperative MST, 21.7% and 16.7%, respectively. The groups did not differ in terms of length of stay in the intensive care unit (ICU) and in-hospital mortality – 0% («prophylactic VA-ECMO») and 8.7% («no pre-HT VA-ECMO») and 11.1% («pre-HT VA-ECMO»), respectively. Conclusion. Prophylactic VA-ECMO in HT with extremely prolonged cardiac graft ischemia reduces ECC duration, reperfusion period, postoperative mechanical ventilation period, and the need for inotropic therapy.

Necropsy findings in heart transplant recipients with and without primary graft dysfunction: a retrospective study

Abstract Background Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT). Physiopathology of PGD is not clear, and histological findings are not defined in literature. Purpose The objective of this study is to describe the morphological findings in the hearts of patients who died within the first 14 days after HT and to compare findings between 2 groups: a group with the diagnosis of PGD and a group without PGD. Methods We included all adult patients submitted to HT in one center who died within the first 14 days after the procedure and were submitted to necropsy between January 1st, 2013 and March 31st, 2020. Demographic, perioperative, histological and immunohistochemical data on heart slides obtained on necropsy were recorded retrospectively. We retrospectively analyzed if the patients met the ISHLT criteria for PGD, and then we categorized them in two groups: PGD group or non-PGD group. All heart slides were reviewed by an experienced pathologist considering the presence of histological features of acute cellular rejection, antibody-mediated rejection, necrosis and its morphological characteristics if present. Pathologist was blind for each patient group. We considered the necrosis significant if it took more than 10% of the examined area. All findings were compared between groups. Results Among 322 HTs performed, 31 patients died within 14 days after the procedure. Five patients were not subjected to autopsy, and the remaining 26 patients were included. Twelve patients presented PGD, while 14 patients did not. Comparison between groups shows longer ischemia time, higher incidence of pre-transplant mechanical circulatory support, lower post-transplant left ventricular ejection fraction and higher incidence of post-transplant right ventricular dysfunction in PGD group (Table 1). Necropsy findings were similar between groups and four patterns of necrosis were found, namely microcalcified, contraction-band, coagulative and liquefactive necrosis (Table 2). Necrosis was detected in the 80.7% of all cases, taking more than 10% of the myocardial area in 46.1% of them. Seven patients (26.9%) presented signs of mild cellular rejection (1R). One of them had also antibody-mediated rejection. One patient presented hyperacute graft rejection. The cause of death was defined by necropsy in 21 cases. The most common cause of death in PDG group was cardiogenic shock (66.7%), while in non-PGD group septic shock (28.5%) and bleeding (21.4%) were the most common causes. Conclusion While left ventricular ejection fraction was significantly lower in PGD group, necrosis was a frequent finding both groups, raising the hypothesis maybe necrosis is not directly the cause of cardiac dysfunction in PGD. More studies are needed to fully understand PGD pathology.Table 1Table 2

Primary Graft Dysfunction After Heart Transplantation: Incidence and Current Risk Factors

<h3>Purpose</h3> Primary graft dysfunction (PGD) is a leading cause of perioperative mortality in heart transplant (HT). Yet the impact of the current increased use of high-risk recipients and donors for HT on the incidence of PGD is unknown. <h3>Methods</h3> This is a retrospective single-center study of adult patients who underwent isolated heart or heart-kidney transplant from January 2018 to March 2020 to evaluate the incidence and patient characteristics associated with PGD, as defined by the International Society for Heart and Lung Transplantation consensus guidelines. Baseline characteristics and postoperative outcomes were compared between patients with no/mild PGD versus moderate/severe PGD. Multivariate logistic regression was used to determine independent predictors of PGD. <h3>Results</h3> One-hundred seventeen patients were evaluated: 105 (89.7%) had no/mild PGD and 12 (10.3%) had moderate/severe PGD. Patients with moderate/severe PGD were less likely to be bridged to transplant with temporary mechanical circulatory support (MCS) (8.3% versus 55.2%, p=0.002) and were more likely to receive undersized hearts (donor/recipient weight ratio 0.93±0.14 versus 1.12±0.26, p=0.008). Moderate/severe PGD patients had a higher postoperative median vasoactive inotropic score (24.97 versus 6.50, p<0.001) and only one moderate/severe PGD patient required postoperative extracorporeal membrane oxygenation (ECMO). By multivariate analysis, undersized donor (odds ratio [OR] 1.055; 95% confidence interval [CI] 1.003-1.127, p<0.001) was an independent predictor of PGD and pre-transplant temporary MCS was a negative predictor of PGD (OR 0.075; 95% CI 0.003-0.580, p=0.033). <h3>Conclusion</h3> In this experience with HT in high acuity recipients, the incidence of moderate/severe PGD is low and need for post-transplant ECMO is rare. Interestingly, these data suggest that use of pre-transplant temporary MCS may be protective against moderate/severe PGD, and further investigation of this approach is indicated.

Factors Associated with Change in Health-Related Quality of Life from Before to 24 Months After Surgery

<h3>Purpose</h3> We sought to identify factors associated with long-term changes in health-related quality of life (HRQOL) among 3 groups of older patients (pts) with advanced heart failure (HF) undergoing heart transplantation (HT), with or without pre-transplant mechanical circulatory support (MCS), or long-term MCS, if ineligible for HT. <h3>Methods</h3> From 10/1/15-12/31/18, 393 pts (60-80 years) were enrolled from 13 U.S. sites, including 239 pts awaiting HT (118 with and 121 without MCS) and 154 long-term MCS pts. Of these, 151 pts (95 HT pts [34 with MCS and 61 without MCS before HT] and 56 long-term MCS pts) had 24-month follow-up data. The EQ-5D Visual Analog Scale (VAS; 0-100 [worst-best health state]) and KCCQ-12 overall summary score (OSS; 0-100 [poor-excellent health status]) were collected at baseline (closest to surgery) and 24-months. Analyses included ANOVA, paired t-tests, and multivariable linear regression. <h3>Results</h3> Average age at HT or long-term MCS implant (n=151) was 66.8 ±4.5 years, 80% were male, and 81% were white. At baseline, long-term MCS pts, compared with HT pts awaiting HT with MCS and those awaiting HT on medical therapy, had the lowest VAS scores (48.7±20.8 vs 65.9±21.0 vs 51.6±25.4, p=0.002) and KCCQ-12 OSS (37.1±20.9 vs 56.5±25.6 vs 46.4±20.5, p<0.001). HRQOL improved significantly in all 3 groups by 24 months (p<0.001); however, long-term MCS pts, compared with HT pts awaiting HT with MCS and those awaiting HT on medical therapy, still had the lowest VAS scores (70.9±19.7 vs 81.8±14.6 vs 86.2±12.1, p<0.001) and KCCQ-12 OSS (63.3±24.1 vs 85.3±16.0 vs 90.0±14.3, p<0.001). Multivariable models (Table) indicate that baseline HRQOL and undergoing HT, with or without MCS, are the strongest predictors of improvement in HRQOL. <h3>Conclusion</h3> Among pts with advanced HF requiring HT or MCS, improvement in HRQOL was greatest in those undergoing HT with or without MCS pre-HT and those with worse baseline HRQOL. These findings may inform advanced HF pts of anticipated HRQOL outcomes with alternative therapies.

Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support

We evaluated post-heart transplant (HTx) outcomes after use of higher-risk donor hearts for candidates supported with pre-HTx mechanical circulatory support (MCS). In this retrospective analysis of the national United Network for Organ Sharing registry, a total of 9,915 adult candidates on MCS underwent HTx from January 1, 2010 to March 31, 2019. Multi-organ, re-transplant, and congenital heart disease patients were excluded. Higher-risk donor organs met at least one of the following criteria: left ventricular ejection fraction <50%, donor to recipient predicted heart mass ratio <0.86, donor age >55 years, or ischemic time >4 hours. Primary outcome was 1 year post-transplant survival. Among HTx recipients, 3688 (37.2%) received higher-risk donor hearts. Candidates supported with pre-HTx extracorporeal membrane oxygenation or biventricular assist device (n=374, 3.8%) who received higher-risk donor hearts had comparable 1 year survival (HR: 1.14, 95% CI: [0.67-1.93], p=0.64) to recipients of standard-risk donor hearts, when adjusted for recipient age and sex. In candidates supported with intra-aortic balloon pump (n=1391, 14.6%), transplantation of higher-risk donor hearts did not adversely affect 1 year survival (HR: 0.80, 95% CI: [0.52-1.22], p=0.30). Patients on durable left ventricular assist devices (LVAD) who received higher-risk donor hearts had comparable 1 year survival to continued LVAD support on the waitlist, but mortality was increased compared to those who received standard-risk donor hearts (HR: 1.37, 95% CI: [1.11-1.70], p=0.004). Patients requiring pre-HTx temporary MCS who received higher-risk donor hearts had comparable 1 year post-transplant survival to those who received standard-risk donor hearts. Stable patients on durable LVADs may benefit from waiting for standard-risk donor hearts.

Primary Graft Dysfunction in Heart Transplant Recipients-Risk Factors and Longitudinal Outcomes.

Before the 33rd Annual International Society for Heart and Lung Transplantation conference, there was significant intercenter variability in definitions of primary graft dysfunction (PGD). The incidence, risk factors, and outcomes of consensus-defined PGD warrant further investigation. We retrospectively examined 448 adult cardiac transplant recipients at our institution from 2005 to 2017. Patient and procedural characteristics were compared between PGD cases and controls. Multivariable logistic regression was used to model PGD and immediate postoperative high-inotrope requirement for hypothesized risk factors. Patients were followed for a mean 5.3 years to determine longitudinal mortality. The incidence of PGD was 16.5%. No significant differences were found with respect to age, sex, race, body mass index, predicted heart mass mismatch, pretransplant amiodarone therapy, or pretransplant mechanical circulatory support (MCS) between recipients with PGD versus no PGD. Each 10 minute increase in ischemic time was associated with 5% greater odds of PGD (OR = 1.05 [95% CI, 1.00-1.10]; p = 0.049). Pretransplant MCS, predicted heart mass mismatch ≥30%, and pretransplant amiodarone therapy were associated with high-immediate postoperative inotropic requirement. The 30 day, 1 year, and 5 year mortality for patients with PGD were 28.4%, 38.0%, and 45.8%, respectively, compared with 1.9%, 7.1%, and 21.5% for those without PGD (log-rank, p < 0.0001). PGD heralded high 30 day, 1 year, and 5 year mortality. Pretransplant MCS, predicted heart mass mismatch, and amiodarone exposure were associated with high-inotrope requirement, while prolonged ischemic time and multiple perioperative transfusions were associated with consensus-defined PGD, which may have important clinical implications under the revised United Network for Organ Sharing allocation system.

The influence of mechanical Circulatory support on post-transplant outcomes in pediatric patients: A multicenter study from the International Society for Heart and Lung Transplantation (ISHLT) Registry

Mechanical circulatory support (MCS) is increasingly being used as a bridge to transplant in pediatric patients. We compare outcomes in pediatric patients bridged to transplant with MCS from an international cohort. This retrospective cohort study of heart-transplant patients reported to the International Society for Heart and Lung Transplantation (ISHLT) registry from 2005-2017 includes 5,095 patients <18 years. Pretransplant MCS exposure and anatomic diagnosis were derived. Outcomes included mortality, renal failure, and stroke. 26% of patients received MCS prior to transplant: 240 (4.7%) on extracorporeal membrane oxygenation (ECMO), 1,030 (20.2%) on ventricular assist device (VAD), and 54 (1%) both. 29% of patients were <1 year, and 43.8% had congenital heart disease (CHD). After adjusting for clinical characteristics, compared to no-MCS and VAD, ECMO had higher mortality during their transplant hospitalization [OR 3.97 & 2.55; 95% CI 2.43-6.49 & 1.42-4.60] while VAD mortality was similar [OR 1.55; CI 0.99-2.45]. Outcomes of ECMO+VAD were similar to ECMO alone, including increased mortality during transplant hospitalization compared to no-MCS [OR 4.74; CI 1.81-12.36]. Patients with CHD on ECMO had increased 1 year, and 10 year mortality [HR 2.36; CI 1.65-3.39], [HR 1.82; CI 1.33-2.49]; there was no difference in survival in dilated cardiomyopathy (DCM) patients based on pretransplant MCS status. Survival in CHD and DCM is similar in patients with no MCS or VAD prior to transplant, while pretransplant ECMO use is strongly associated with mortality after transplant particularly in children with CHD. In children with DCM, long term survival was equivalent regardless of MCS status.

Heart transplantation from donors with left ventricular ejection fraction under forty percent.

Heart transplantation (HTx) remains the treatment of choice for patients with end-stage advanced heart failure. In 2016, the Shumakov National Medical Research Center commenced performing HTx from donors with abnormal left ventricular systolic function (LVEF<40%). The aim of this study was to evaluate early and late outcomes of recipients after HTx from donors with abnormal LV systolic function. Four hundred eighty seven patients underwent HTx in our institution from January 2016 to December 2018. 27 (5.5%) patients were transplanted using cardiac allografts from donors with LVEF <40%. A total of 47 donors with LVEF <40% were evaluated for potential donation. Most heart donors revealed a left ventricular ejection fraction ranging between 30% and 40%. Twenty-five recipients required urgent HTx. Four recipients presented with early allograft dysfunction. All surviving recipients demonstrated early (85.2%) or delayed (14.8%) recovery of systolic function (LVEF>60%). The use of dysfunctional donor hearts with impaired LV systolic function may be a realistic approach for expanding the donor pool. However, organs from such donors should be used for recipient cohorts requiring an urgent HTx, particularly for those with pretransplant mechanical circulatory support allowing for hemodynamic support in cases of early graft dysfunction in the post-transplant period.

Development of an International Consortium on Primary Graft Dysfunction: Redefining Clinical Risk Factors in the Contemporary Era of Heart Transplantation

<h3>Purpose</h3> Primary Graft Dysfunction (PGD) is a leading cause of short-term mortality after heart transplantation (HT). Available registries lack data to identify PGD based on post-HT hemodynamics and mechanical circulatory support (MCS). Herein, we describe the development of a multicenter International Consortium on PGD: a registry designed to quantify the incidence, risk factors, and impact of PGD, in order to develop contemporary risk prediction models. <h3>Methods</h3> We are currently collecting data from 10 participating sites in Europe and North America which will include clinical data from an estimated 3,826 HT recipients (Table 1). We defined PGD using the ISHLT 2014 consensus criteria. Our complete consortium will include data on baseline donors and recipients demographics, pre and post-HT hemodynamics, and the type and duration of MCS after HT. We will use regression models and supervised machine learning (ML) algorithms to develop risk prediction models that reflect the contemporary landscape of HT. <h3>Endpoints</h3> To date, we have collected preliminary data on 2,178 single-organ HT recipients between 2010 - 2020 (57% of the anticipated final sample size). Our consortium cohort consists of patients with age of 54 ± 12 years, of whom 24.7% (n=537) are female. Pre-transplant MCS included IABP in 3.6% (n=80), ECMO in 1.4% (n=30), and durable LVAD in 8.3% (n=181). Donor age was 37 ± 13 years and ischemic time was 3.4 ± 1.0 hours. A total of 167 (7.7%) recipients met criteria for severe PGD and 76 (6.5%) for moderate PGD. One-year survival was 67% (95% CI 59 - 74%) and 93% (95% CI 92 - 94%) in patients with and without severe PGD, respectively. We aim to develop contemporary tools for risk stratification of HT recipients for incident PGD. Our multicenter, international consortium allows for comprehensive phenotyping of HT recipients based upon a standardized definition of PGD to accurately understand PGD incidence, risk factors, and outcomes in the era of MCS. <h3>Interim Results</h3> To date, we have collected 106 variables on 2,476 single-organ HT recipients from 2010 to 2020 (Figure 1A). Mean age of cohort is 53.9 ± 12.3 years; 25% female, 330 recipients from Canada, 518 from Europe, and 1628 from the US. Pre-transplant MCS included IABP in 8.4% (n=207), ECMO in 1.3% (n=33), and durable LVAD in 32.1% (n=795) (Figure 1B). Average donor age was 36.4 ± 13.0 years with mean ischemic time 3.4 ± 1.1 hours. A total of 214 (8.6%) of recipients met criteria for severe PGD, requiring VA-ECMO (n=186), RVAD (n=28), or both (n=3). Among 1811 patients with adequate follow up data, 1-year survival was 78% (95% CI 72% – 83%) in patients with severe PGD, and 95% (95% CI 94% – 96%) in those without severe PGD (Figure 1C). The previously-published RADIAL PGD risk score performed poorly in our cohort, with an AUC of 0.50 for severe PGD(Figure 1D).

Heart transplantation in diabetic recipients

Introduction . Heart transplantation (HT) in patients with preexisting type 2 diabetes (T2D) is associated with high risk of infectious and non-infectious complications (renal dysfunction, multifocal atherosclerosis, transplant coronary artery disease, etc.) that can negatively affect recipient survival in the early and late periods after HT. Objective: to assess the effect of pre-transplant T2D on early and long-term outcomes of HT based on a singlecenter retrospective study. Materials and methods . The study enrolled 891 recipients who underwent HT within the period 2011 to 2018, and were divided into two groups: main group (T2D) – recipients with pretransplant T2D (n = 80, 9.0%) and the control group (T2D-free) – recipients without T2D (n = 811, 91.0%). Recipients from both groups did not differ in terms of HT urgency (UNOS status) and the need for pre-transplant mechanical circulatory support (MCS). Results . At the time of the HT, recipients from the T2D group were older than the T2D-free recipients (54 [46; 59] years vs 48 [35; 56] years, p &lt; 0.001), they had a higher weight (p &lt; 0.001) and body mass index (p &lt; 0.001), coronary heart disease was more often their main disease (65.0% vs 36.5%, p &lt; 0.001), they had higher transpulmonary gradient (10.0 [7.0; 12.0] mm Hg vs 9.0 [6.0; 12.0] mm Hg, p = 0.024) and pulmonary vascular resistance (2.9 [2.2; 4.0] Wood units vs 2.5 [1.8; 3.4] Wood units, p = 0.038). In the pre-transplant period, the T2D group had pronounced manifestations of renal dysfunction and increased comorbidity. Recipients in both groups did not differ in terms of cardiac donor parameters, graft ischemia time, cardiopulmonary bypass time, and incidence of severe early heart graft dysfunction requiring MCS (12.5% vs 10.7%, p = 0.74). In the early post-transplant period, the T2D group had high requirements (100% vs 28.0%, p &lt; 0.001) and higher doses of insulin therapy. More pronounced manifestations of renal dysfunction and a greater need for renal replacement therapy (51.4% vs 27.9%, p = 0.003) did not affect artificial ventilation and ICU duration (6 [5; 10] days vs 6 [5; 10] days, p = 0.098), as well as hospital mortality ( 8.8% vs 8.5%, p = 0.895). The presence of pre-transplant T2D had no negative effect on the incidence of acute cardiac graft rejection, progression of transmissible coronary atherosclerosis, incidence and severity of cardiac graft vasculopathy, structure and severity of distant infectious and non-infectious complications, and post-transplant survival. Conclusion . With correct selection of recipients and choice of optimal tactics for their post-transplant management, the presence of pre-transplant T2D has no negative effect on early and long-term outcomes of HT.

Temporary mechanical circulatory support: insights and evolving strategies.

The goal of this study is to evaluate the utilization and outcomes of temporary mechanical circulatory support (MCS) among patients listed for cardiac transplantation (CT). There is a constant threat of sudden clinical deterioration in these patients that could necessitate emergent MCS. All advanced heart failure and transplant centers in India are plagued by issues of late referrals, low organ donation rates, and financial constraints. Here, we share our experience and explain our evolving strategies tailored to improve outcomes. Single-center retrospective analysis of temporary MCS implanted in patients listed for CT from January 1, 2015, to December 31, 2019. A total of 35 patients had 41 MCS implantations. Twenty-four cases were pre-transplant and 11 cases were post-transplant. Veno-arterial extracorporeal membrane oxygenator was the most commonly (20 cases, 44.4%) used MCS modality. Primary outcome of in-hospital mortality was noted in 17 patients (48.5%) in this high-risk profile. All but 2 of the 12 patients that underwent pre-transplant MCS, and were bridged to cardiac transplant, survived the index hospitalization accounting for 90% survival in this subset of patients. The secondary outcome of MCS-related vascular injury was observed in 9 patients (25.7%). This single-center observational study demonstrates that early planning and timely institution of MCS improves outcomes in high-risk MCS patients bridged to cardiac transplant. The incidence of MCS-related vascular complications can be improved with development of standard operating protocols.

Self-efficacy, recovery and psychological wellbeing one to five years after heart transplantation: a Swedish cross-sectional study.

Self-efficacy refers to a person´s confidence in carrying out treatment-related activities and constitutes the foundation of self-management as well as long-term follow-up after heart transplantation. Exploring the heart recipients´ experiences by means of self-report instruments provides healthcare professionals with valuable information on how to supply self-management support after heart transplantation. The aim was to explore self-efficacy in relation to the self-reported level of recovery and psychological wellbeing, among adult heart recipients, one to 5 years after transplantation. This cross-sectional study includes 79 heart recipients, due for follow-up one to 5 years after transplantation. Three different self-assessment instruments were employed: the self-efficacy for managing chronic disease 6-item scale; the postoperative recovery profile; and the psychological general wellbeing instrument. The reported level of self-efficacy was high (median 8.3, maximum score 10). Significantly higher self-efficacy was seen among those who had returned to work (P = 0.003) and those without pre-transplant mechanical circulatory support (P = 0.033). In total, 65.5% (n = 52) reported being reasonably recovered, while 18.8% (n = 12) were not recovered. The median total psychological general wellbeing score was 108 (P25 = 24, P75 = 117), suggesting overall good psychological wellbeing in the whole group of heart recipients. The heart transplant recipients in our study had an overall high level of self-efficacy. Low self-efficacy was found among those with a low self-reported level of recovery, pre-transplant treatment with mechanical circulatory support or who had not returned to work. This is important information for transplant professionals when helping heart recipients to balance their expectations about recovery.

Heart Transplantation From Brain Dead Donors: A Systematic Review of Animal Models.

Despite advances in mechanical circulatory devices and pharmacologic therapies, heart transplantation (HTx) is the definitive and most effective therapy for an important proportion of qualifying patients with end-stage heart failure. However, the demand for donor hearts significantly outweighs the supply. Hearts are sourced from donors following brain death, which exposes donor hearts to substantial pathophysiological perturbations that can influence heart transplant success and recipient survival. Although significant advances in recipient selection, donor and HTx recipient management, immunosuppression, and pretransplant mechanical circulatory support have been achieved, primary graft dysfunction after cardiac transplantation continues to be an important cause of morbidity and mortality. Animal models, when appropriate, can guide/inform medical practice, and fill gaps in knowledge that are unattainable in clinical settings. Consequently, we performed a systematic review of existing animal models that incorporate donor brain death and subsequent HTx and assessed studies for scientific rigor and clinical relevance. Following literature screening via the U.S National Library of Medicine bibliographic database (MEDLINE) and Embase, 29 studies were assessed. Analysis of included studies identified marked heterogeneity in animal models of donor brain death coupled to HTx, with few research groups worldwide identified as utilizing these models. General reporting of important determinants of heart transplant success was mixed, and assessment of posttransplant cardiac function was limited to an invasive technique (pressure-volume analysis), which is limitedly applied in clinical settings. This review highlights translational challenges between available animal models and clinical heart transplant settings that are potentially hindering advancement of this field of investigation.

Five Years Experience of Peripheral Veno-Arterial ECMO as Method of Mechanical Circulatory Support in Heart Transplant Candidates

Mechanical circulatory support (MCS) is the only way to save a life for heart transplant candidates and to decrease of waiting list mortality. The choice between short- or long-term pretransplant MCS depends on of type and severity of CHF. One of the most frequently used methods of temporary MSC before orthotopic heart transplantation (OHTx) is veno-arterial extracorporeal membrane oxygenation (VA ECMO). The aim of this study was to analyze own experience of peripheral VA ECMO (pVA ECMO) in heart transplant candidates needed in urgent HT METHODS: This study included 182 pts [160 (87.9%) men and 22 (12.1%) female, age 43±1.2 yrs] supported with pVA ECMO in the period from 01. 01. 2013 to 31. 12. 2017 or 23.2% from all waiting list (n=786) RESULTS: During VA ECMO, 16 (8.8%) of the 182 pts died. In most pts [n=13 (81.3%)] multiorgan failure/sepsis were the cause of death. One hundred and sixty-six (91.2%) pts were successfully bridged to OHTx or 27.9% from all heart transplant recipients (n=594) (2013-2017 yrs). The duration of pVA ECMO before OHTx (n=166) was 5.8±3.2 days. One hundred and forty-three (86.1%) from 166 pts were discharged to home. Post-transplant survival among heart transplant recipient with pre-transplant MCS by pVA ECMO was in comparison with recipients without pretransplant MCS [84.2% vs. 90.1% (6 months), 83.3% vs.91.8% (1 years), 75.1% vs. 86.1% (2 years), 74.2% vs. 85.8% (3 years), 72.3% vs. 84.7% (4 years), 72.3% vs. 83.5% (5 years) respectively (P<0.0001)] CONCLUSION: pVA ECMO is a useful tool of treatment of patients with INTERMACS profile 1/2. Results of OHTx at recipients bridged with VA ECMO are less successful that recipients without pre-transplant MCS. VA ECMO should be considered as a direct bridge to OHTx in conditions of limited financial resources of health care and high availability of donor's hearts.

The Effect of Pre-Transplant Mechanical Circulatory Support Devices on the Post-Transplant dd-cfDNA and GEP in Heart Transplantation

Evidence around sensitization and increased risk of rejection from use of pre-transplant mechanical circulatory support (MCS) devices remains conflicting. Some evidence suggests devices cause inflammation and association with increased antibody production, which has been shown to be associated with AMR, CMR, and early onset of microvasculopathy at one year post-heart transplant. However other evidence suggests no difference or increased risk of adverse outcome using pre-transplant MCS devices. dd-cfDNA (AlloSure) has been shown to rise in advance to the new formation of de-novo anti-HLA antibodies, with changes in AlloMap also seen in patients who become newly sensitized. The aim of this study was to review MCS patients post-transplant with AlloSure and AlloMap to assess if they had different patterns from those who had no MCS, to support suggestion of early post-transplant complications. Patients who were enrolled in Outcomes AlloMap® Registry (OAR) and the dd-cfDNA extension (D-OAR) were included in this analysis if pre-transplant MCS history was recorded and signs or symptoms of rejection during a visit with an accompanying blood draw were absent (i.e. no biopsy accompanied the visit or if a biopsy occurred it yielded Grade 0R). A total of 282 patients met these criteria, 130 had pre-transplant MCS and 152 did not. A total of 652 samples were collected where both AlloSure and AlloMap scores were obtained. The cumulative distribution of AlloSure and AlloMap scores were assessed via a two-sample Kolmogorov-Smirnov test to determine if differences were observed that may be attributed to mechanical assist support prior to transplant. No difference in the distribution of AlloMap scores from patients that received pre-transplant mechanical support versus those that did not was observed, similarly for AlloSure measurements, there was no statistically significant difference in the distribution of AlloSure scores between those that receive pre-transplant mechanical assist support versus those that do not receive support. Pre-transplant MCS does not correlate with increased dd-cfDNA or GEP score, suggesting the adverse outcomes seen early post-transplant are unlikely to be due to MCS devices.

Take the First Available Heart: Use of Higher-Risk Donors in Recipients with Pre-Transplant Mechanical Circulatory Support

Availability of heart transplantation (HTx) is limited by donor supply. We evaluated the post-transplant outcomes of higher-risk organs in recipients supported with pre-HTx mechanical circulatory support (MCS) METHODS: In this retrospective analysis of the UNOS registry, a total of 18,338 adult patients underwent HTx from 1/2010 to 3/2018. Multi-organ transplant patients were excluded. Higher-risk organs were defined as meeting at least one of the following: donor ejection fraction<50%, donor to recipient predicted heart mass ratio<0.86, donor age>55, or ischemic time>240 minutes. The primary outcome was overall 1-year post-transplant survival RESULTS: Among HTx recipients, 4,381 (23.9%) had higher-risk donor hearts, including 3,684 recipients who had donor to recipient predicted heart mass ratio mismatch and 428 recipients with elderly donor age. There were 133 (0.7%) patients supported with pre-HTx extracorporeal membrane oxygenation (ECMO), with 39 and 94 receiving higher-risk and normal-risk organs, respectively. In this subgroup, the higher-risk organ recipients were more likely to be male (82.1 vs. 60.6%; p=0.02) (Figure 1). There was no association between use of higher-risk organs in pre-HTx ECMO patients and overall 1-year survival (71.6% [95% CI: 61.2-79.7] vs. 66.8% [95% CI: 48.8-79.7], p=0.72) (Figure 1). There were 3,776 (20.6%) patients supported with pre-HTx durable left ventricular assist device (LVAD), with 884 and 2,892 receiving higher-risk and normal-risk organs respectively. Similarly, there was no association between use of higher-risk organs in pre-HTx durable LVAD patients and overall 1-year survival (90.6% [95% CI: 88.4-92.4] vs. 90.7% [95% CI: 89.5-91.7], p=0.34) CONCLUSION: In patients supported with pre-HTx ECMO or LVAD, those who received carefully selected higher-risk organs did not have worse overall 1-year post-transplant survival. Utilization of higher-risk organs in HTx may be a feasible option to avoid prolonged MCS.

Five years' experience with a peripheral veno-arterial ECMO for mechanical bridge to heart transplantation.

Mechanical circulatory support (MCS) is the only way to save a life for heart transplant candidates and to decrease of waiting list mortality. The choice between short- or long-term pretransplant MCS depends on of type and severity of CHF. One of the most frequently used methods of temporary MSC before orthotopic heart transplantation (OHTx) is veno-arterial extracorporeal membrane oxygenation (VA ECMO). The aim of this study was to analyze own experience of peripheral VA ECMO (pVA ECMO) in heart transplant candidates needed in urgent HT. This study included 182 pts [160 (87.9%) men and 22 (12.1%) female, age 43±1.2 yrs] supported with pVA ECMO in the period from 01. 01. 2013 to 31. 12. 2017 or 23.2% from all waiting list (n=786). During VA ECMO, 16 (8.8%) of the 182 pts died. In most pts [n=13 (81.3%)] multiorgan failure/sepsis were the cause of death. One hundred and sixty-six (91.2%) pts were successfully bridged to OHTx or 27.9% from all heart transplant recipients (n=594) (2013-2017 yrs). The duration of pVA ECMO before OHTx (n=166) was 5.8±3.2 days. One hundred and forty-three (86.1%) from 166 pts were discharged to home. Post-transplant survival among heart transplant recipient with pre-transplant MCS by pVA ECMO was in comparison with recipients without pretransplant MCS [84.2% vs. 90.1% (6 months), 83.3% vs. 91.8% (1 years), 75.1% vs. 86.1% (2 years), 74.2% vs. 85.8% (3 years), 72.3% vs. 84.7% (4 years), 72.3% vs. 83.5% (5 years) respectively (P<0.0001)]. pVA ECMO is a useful tool of treatment of patients with INTERMACS profile 1/2. Results of OHTx at recipients bridged with VA ECMO are less successful that recipients without pre-transplant MCS. VA ECMO should be considered as a direct bridge to OHTx in conditions of limited financial resources of health care and high availability of donor's hearts.

Risk of dnDSA with Various MCS Devices as Bridge-to-Transplant

Purpose Previous reports have suggested an association between pre-transplant mechanical circulatory support (MCS) and an increased risk for post-transplant de novo donor specific antibodies (dnDSA). However, it is unclear if specific MCS devices pose a greater risk for dnDSA. The present study seeks to better understand the risk of dnDSA posed by a variety of MCS devices in a multicenter, collaborative study. Methods Multicenter, retrospective analysis of 319 heart transplant recipients from 4 U.S. centers between 2011 - 2017. The primary outcome was the development of post-transplant dnDSA. Results 145 of 319 (45%) patients were supported with durable MCS devices prior to transplant, including 47 Heartware (HVAD), 73 Heartmate II (HM2), and 25 total artificial hearts (TAH). MCS patients had a higher risk of dnDSA compared to those transplanted without mechanical support (37% vs. 23%, p = 0.006; Kaplan Meier log rank p Conclusion Pre-transplant MCS is associated with higher risk for dnDSA. Similar risk is seen regardless of device type; however, the risk associated with TAH was not significantly increased compared to no MCS.