Cardiac Retransplantation Research Articles

Clonal Hematopoiesis of Indeterminate Potential and Long-term Outcomes in Heart Transplantation

BackgroundClonal hematopoiesis of indeterminate potential (CHIP) mutations, an aging trait, has been associated with progression of cardiovascular disease and development of malignancy. Uncertainty prevails regarding a robust association between CHIP and heart transplantation outcomes. ObjectivesTo determine prevalence of CHIP mutations in heart transplantation and their association with long-term outcomes including cardiac allograft vasculopathy (CAV), graft failure, malignancy, and all-cause mortality. MethodsWe conducted a mixed retrospective-prospective observational study of heart transplant recipients with targeted sequencing for CHIP mutations (Variant allele frequency (VAF) of ≥2%). The primary composite outcome was first occurrence of CAV grade ≥2, graft failure, malignancy, cardiac re-transplantation, or all-cause death. Secondary outcomes were the individual components of the composite primary outcome. Sensitivity analyses with base-case and extreme scenarios were performed. ResultsAmong 95 HT recipients, 30 had CHIP mutations (31.6%). DNMT3A mutations were most common (44.7%) followed by PPM1D (13.2%), SF3B1 (10.5%), TET2 (7.9%) and TP53 (7.9%). The only significant independent predictor of CHIP was age at enrollment or age at transplantation. After multivariable adjustment, CHIP was not associated with the primary outcome which occurred in 44 (46.3%) patients (HR=0.487; 95%CI:0.197-1.204; p=0.119), malignancy alone or death. ConclusionWe demonstrated no association between CHIP mutations and post-transplant outcomes including CAV, graft failure, malignancy, and all-cause mortality. In line with previously published data, our analysis provides additional evidence on the lack of clinical value of using CHIP mutations as a biomarker for surveillance in outcomes after heart transplantation.

(1138) - Interatrial Shunt: A “Hole in Time” to Delay Cardiac Retransplantation in Late Graft Dysfunction

(1138) - Interatrial Shunt: A “Hole in Time” to Delay Cardiac Retransplantation in Late Graft Dysfunction

A change of heart: Characteristics and outcomes of multiple cardiac retransplant recipients.

Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described. Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p<.001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p<.001). Mortality was highest amongst recipients aged>60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher. Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup.

A case of successful orthotopic heart retransplantation in an 11-year-old child

Objective: to present a clinical case of an 11-year-old child who underwent repeat heart transplantation (HT) at Almazov National Medical Research Centre in St. Petersburg, Russia.Materials and methods. A case of successful heart retransplantation in an 11-year-old child with cardiac allograft vasculopathy (CAV) is presented.Results. The postoperative period after heart retransplantation had no significant differences with the postoperative period of primary heart recipients. The complexity of the intraoperative stage was determined by pronounced adhesions. As part of preoperative preparation, the patient underwent chest CT scan, which, in our experience, allows us to evaluate the heart syntopy and, in turn, is an important preparatory stage in planning repeat interventions.Conclusion. Our first experience of cardiac retransplantation in pediatric patients suggests that repeat HT is the most optimal treatment for pediatric patients with CAV and requires more thorough preoperative preparation.

Elective cardiac retransplantation. First case in Mexico

Elective cardiac retransplantation. First case in Mexico

Predictors of 1‐year outcome after cardiac re‐transplantation: Machine learning analysis

As cardiac re-transplantation is associated with inferior outcomes compared with primary transplantation, allocating scarce resources to appropriate re-transplant candidates is important. The aim of this study is to elucidate the factors associated with 1-year mortality in cardiac re-transplantation using the random forests algorithm for survival analysis. We retrospectively reviewed the United Network for Organ Sharing registry and identified all adult (>17 years old) recipients who underwent cardiac re-transplantation between January 2000 and March 2020. The random forest algorithm on Cox modeling was used to calculate the variable importance (VIMP) of independent variables for contributing to 1-year mortality. A total of 1294 patients underwent cardiac re-transplantation. Of these, 137 patients were re-transplanted within 1year of their first transplant, while 1157 patients were re-transplanted more than 1year after their first transplant. One-year mortality was significantly higher for patients receiving early transplantation compared with those receiving late transplantation (Early 40.6%vs. Late 13.6%, log-rank P<.001). Machine learning analysis showed that total bilirubin (>2mg/dl) (VIMP, 2.99%) was an independent predictor of 1-year mortality after early re-transplant. High BMI (>30.0kg/m2 ) (VIMP, 1.43%) and ventilator dependence (VIMP, 1.47%) were independent predictors of 1-year mortality for the late re-transplantation group. Machine learning showed that optimal 1-year survival following cardiac re-transplantation was significantly related to liver function in early re-transplantation, and to obesity and preoperative ventilator dependence in late re-transplantation.

Predictors of One-Year Outcome in Patients Undergoing Cardiac Re-Transplantation: Machine Learning Analysis

<h3>Purpose</h3> As cardiac re-transplantation is associated with inferior outcomes compared with primary transplantation, allocating scarce resources to appropriate re-transplant candidates is important. The aim of this study is to elucidate the factors of 1-year mortality in cardiac re-transplantation using random survival forests. <h3>Methods</h3> We retrospectively reviewed the United Network for Organ registry and identified all adult (>17 years old) recipients underwent cardiac re-transplantation between January 2000 and March 2020. Recipients were divided into early (≦1 year after previous transplant) and late (>1 year after previous transplant) groups based on the timing of re-transplantation. The random forest algorithm on Cox modeling was used to calculate the variable importance (VIMP) of the independent variables for the time to one-year mortality. <h3>Results</h3> There were 1157 patients in the late re-transplantation and 137 patients in the early re-transplantation. Recipients in the late cardiac re-transplantation were younger (p=0.004), more sensitized (p=0.012), higher creatine (p=0.045) and had a lower total bilirubin (p<0.001), pulmonary vascular resistance (p=0.003), and percentage of worse functional status (p<0.001). Recipients in the late cardiac re-transplantation were less likely to be ventilator dependent (p<0.001), treated with ECMO (p<0.001), and intra-aortic balloon pumps (p<0.001), have an inotrope support (p<0.001), left ventricular assist device (p<0.001), dialysis (p<0.001), and blood transfusion after listing (p<0.001), and stay in intensive care unit (p<0.001). 1-year mortality was significantly higher in the early transplantation compared with the late transplantation (13.6% vs. 40.6%, log-rank P<0.001). Machine learning showed that BMI (>30.0 kg/m2) (VIMP, 1.43%) and ventilator dependence (VIMP, 1.47%) in the late re-transplantation, and total bilirubin (>2 mg/dl) (VIMP, 2.99%) in the early re-transplantation were significantly associated with increased 1-year mortality. <h3>Conclusion</h3> Machine learning showed that optimal 1-year survival following cardiac re-transplantation was significantly related to obesity and preoperative ventilator dependence in late re-transplantation and liver function in early re-transplantation.

Should Age-Based Eligibility Thresholds Differ for Repeat Heart Transplantation? Analysis of the United Network of Organ Sharing Database

<h3>Purpose</h3> Risk-adjusted survival after cardiac re-transplantation may be comparable to primary transplant, but the efficacy of re-transplantation in older candidates is not established. We evaluated outcomes after re-transplantation in recipients > 60 years. <h3>Methods</h3> The United Network for Organ Sharing Database identified 1295 adult patients undergoing heart re-transplants between 2003 and 2020 (excluding heart-lung transplants). Unadjusted 5-year survival of older recipients (> 60 years, n=212) was compared to younger recipients (<= 60 years, n=1083). Adjusted Cox model using restricted cubic splines explored the non-linear relationship between recipient age and mortality risk after re-transplantation. A separate multivariate Cox model analyzed recipients>60 years undergoing either primary transplant (n=12826) or re-transplantation (n=181, excluding re-transplants for acute/hyperacute rejection or primary graft dysfunction) to evaluate the impact of re-transplantation on mortality. <h3>Results</h3> In patients undergoing re-transplantation, older recipients had more pre-transplant ECMO use (9.9% vs. 5.8%, p=0.027) and received grafts from older donors (34, IQR 24-46 vs. 28, IQR 21-38 years, p<0.0001). Recipient age >60 was associated with inferior unadjusted survival (Figure 1A). Restricted cubic spline (Figure 1B) showed a significant increase in mortality risk when recipient age becomes older than 61.8 years (corresponding HR 1.35, 95% CI 1.01-1.79). In recipients >60 years undergoing either primary transplant or re-transplantation, re-transplantation was independently associated with increased risk of mortality (HR 1.33, 95% CI 1.07-1.65, p=0.01) compared to primary transplant. <h3>Conclusion</h3> Re-transplanting patients greater than 60 years old is independently associated with increased risk of mortality. More conservative age-based thresholds for re-transplantation may be appropriate.

A Single Center Look at Pediatric Heart Re-Transplantation

<h3>Purpose</h3> Cardiac re-transplantation (reTX) in pediatrics remains a rare occurrence, representing only 2% of all pediatric heart transplants (HT). The purpose of this study was to describe the pre-transplant characteristics, waitlist outcomes and post-HT outcomes for reTX at our center. <h3>Methods</h3> Retrospective review of all patients listed for heart transplantation (HT) from 1/1/2014-10/18/2021. Pre-transplant characteristics and post-transplant outcomes are compared to primary HT. <h3>Results</h3> Of 215 total listings, 14 (7%) were for reTX. Of these, 1 (7%) died on waitlist, 1 (7%) remains listed and 12 (92%) survived to reTX, at a median of 140 (62, 454) waitlist days and 7 (4,11) years after primary HT. Three (21%) were bridged to reTX with a ventricular assist device (VAD). One patient received a concurrent kidney transplant. When compared to primary HT, reTX patients were older at listing and transplant (P= 0.01 and 0.008) and less likely to be status 1A at transplant (42% vs. 70%, P=0.05). Post transplant tracheostomy and dialysis were more common after reTX than primary transplant, though not statistically significant (Table 1). At a median follow up of 667 (364, 1330) days, 9 (75%) reTX and 83% primary HT patients were still alive (P=0.2), (Figure 1). <h3>Conclusion</h3> We describe the retransplant experience in a contemporary single center cohort. Pre-HT characteristics are similar, though reTX patients are more often transplanted from a lower UNOS listing status. Long-term outcomes of patients with reTX were not significantly worse than primary HT in this cohort. Patients and families should be counseled at time of listing for reTX complications including tracheostomy and dialysis.

Outcome of Paediatric Cardiac Re-Transplantation in the Mechanical Support Era

<h3>Purpose</h3> To review the outcome of paediatric cardiac re-transplantation (reOHTx) in the mechanical cardiac support (MCS) era. <h3>Methods</h3> A retrospective study of patients less than 18 years of age who underwent reOHTx in our Institution. Data were obtained from departmental databases and hospital medical records. <h3>Results</h3> From 1987 to 2021, 21 patients underwent reOHTx. Diagnoses leading to first transplant were dilated cardiomyopathy in 12 (10 idiopathic, 1 post-chemotherapy, 1 related to viral myocarditis), restrictive cardiomyopathy in 1, hypertrophic cardiomyopathy in 1 and congenital heart disease in 7 patients. Mean age at first OHTx was 8 years. Prior to primary transplant, one patient was supported with Levitronix Centrimag LVAD, one with BIVAD, a child with VA-ECMO followed by Berlin Heart EXCOR LVAD and one child with VA-ECMO only. Mean time course between first and second OHTx was 82 months. Eleven patients were mechanically supported as a bridge to reOHTx: 8 with Levitronix Centrimag BIVAD (2 from VA-ECMO), 4 with VA-ECMO, 2 with Berlin Heart EXCOR BIVAD, 2 with Berlin Heart EXCOR LVAD and 1 with Heartware. Mean time on support was 54 days (1-275). There was only one early death after reOHTx. This patient received the second heart 8 days after the first transplant and died from 2 days post reOHTx due to brain hemorrhage. One patient required 2 VA-ECMO runs due to acute graft failure. Two patients required VA-ECMO post reOHTx. Eight patients required renal replacement therapy. Five suffered a cerebrovascular accident. Mean follow up is 112 months. There were 7 late deaths in this period of 34 years, 2 of them related to rejection due to poor compliance with immunosuppressive treatment. <h3>Conclusion</h3> Re-transplantation in children carries a very good outcome. With mechanical cardiac support we can bridge children to reOHTx more effectively. Furthermore, MCS can be also used in acute graft failure or for immunological manipulation in acute rejection.

When Third Time's a Charm: Successful Outcome after Third Orthotopic Heart Transplantation

IntroductionCardiac re-transplantation represents a small but growing proportion of total transplants being performed. Medical, ethical, moral and social dynamics continue to remain individualized and highly debated but more evolved with advancement in medicine for patients needing cardiac re-transplantation. We describe a case of a successful outcome in a patient requiring her third orthotopic heart transplant.CaseA 26 year old female with history of orthotopic heart transplant at age 11 for hypertrophic cardiomyopathy and subsequent re-transplantation for cardiac allograft vasculopathy (CAV) ten years later presented to our emergency room with cardiac arrest. Prior to the index hospitalization, the patient had an echocardiogram with a mildly reduced ejection fraction and an angiogram with chronic total occlusions of the right coronary artery and left circumflex artery with excellent collaterals and preserved cardiac output. Nuclear stress test showed no evidence of ischemia. Cardiac allograft vasculopathy prophylaxis with aspirin and pravastatin in addition to a triple regimen of immunosuppression of tacrolimus, sirolimus and mycophenolate mofetil were verified.The hospitalization was complicated by rapidly deteriorating biventricular function and three more episodes of cardiac arrest ultimately requiring extracorporeal membrane oxygenation (ECMO). Fortunately, the patient had negative HLAs with 0% CPRA and preserved end organ function. The selection committee thoughtfully considered her history of intermittent social marijuana use, active COVID 19 precautions in the hospital and a third sternotomy at such a young age, with likely need of possible 4th heart transplant in the future, but ultimately approved the patient for listing. Despite being Status 1, the patient had near daily loss of pulsatility for greater than 10-15 minutes which made us consider the possibility of total artificial heart. Fortunately, the patient received a local heart due to the COVID travel restrictions with total ischemic time of 98 minutes. She was induced with basiliximab and had negative retrospective and prospective crossmatches. There were no intra-op complications and post-op the patient had mild RV dysfunction requiring 4 days of inotropes. Patient was successfully discharged 9 days following her third OHT.ConclusionPatients undergoing re-transplantation have overall poorer outcomes than those undergoing primary transplantation. Several factors influence these outcomes including timing from prior transplant, previous sternotomy, sensitization status, and renal dysfunction. With advances in medicine and pediatric patients living well into adulthood, there will be more patients requiring re-transplantation. As these trends emerge, individualized patient selection remains the key factor to improved outcomes. Our case presents an otherwise healthy young woman with graft failure without evidence of sensitization who underwent a successful third transplantation.

Nuclear Osteopontin Is a Marker of Advanced Heart Failure and Cardiac Allograft Vasculopathy: Evidence From Transplant and Retransplant Hearts

BackgroundHeart transplant is the gold standard therapy for patients with advanced heart failure. Over 5,500 heart transplants are performed every year worldwide. Cardiac allograft vasculopathy (CAV) is a common complication post-heart transplant which reduces survival and often necessitates heart retransplantation. Post-transplant follow-up requires serial coronary angiography and endomyocardial biopsy (EMB) for CAV and allograft rejection screening, respectively; both of which are invasive procedures. This study aims to determine whether osteopontin (OPN) protein, a fibrosis marker often present in chronic heart disease, represents a novel biomarker for CAV.MethodsExpression of OPN was analyzed in cardiac tissue obtained from patients undergoing heart retransplantation using immunofluorescence imaging (n = 20). Tissues from native explanted hearts and three serial follow-up EMB samples of transplanted hearts were also analyzed in five of these patients.ResultsFifteen out of 20 patients undergoing retransplantation had CAV. 13/15 patients with CAV expressed nuclear OPN. 5/5 patients with multiple tissue samples expressed nuclear OPN in both 1st and 2nd explanted hearts, while 0/5 expressed nuclear OPN in any of the follow-up EMBs. 4/5 of these patients had an initial diagnosis of dilated cardiomyopathy (DCM).ConclusionNuclear localization of OPN in cardiomyocytes of patients with CAV was evident at the time of cardiac retransplant as well as in patients with DCM at the time of the 1st transplant. The results implicate nuclear OPN as a novel biomarker for severe CAV and DCM.

Upper-body cannulation for midterm mechanical circulatory support: A novel bridging strategy to cardiac retransplantation.

Heart retransplantation remains a controversial issue, due to the overall shortage of donor organs. Many patients put on the waiting list for retransplantation, decompensate rapidly, and do not survive. The use of veno-arterial extracorporeal life support remains an option in such emergency situations as bridge-to-recovery or bridge-to-transplantation therapy. In peripheral femoral configuration, veno-arterial extracorporeal life support improves the patient's condition by relieving low-cardiac output but immobilizes him or her for an uncertain period of time. The upper-body cannulation is an alternative approach, which allows to maintain the patient awake and mobile. We present two cases of midterm circulatory support as a bridge to heart retransplantation, using upper-body cannulation veno-arterial extracorporeal life support. Two male patients, presenting with progressive cardiac decompensation due to severe graft rejection, were placed on upper-body veno-arterial extracorporeal life support. The stabilization of hemodynamics and improvement of end-organ perfusion could be achieved after extracorporeal life support initiation. After 48 and 40 days, respectively, on extracorporeal life support with active physical therapy and no major adverse events, both patients received a cardiac retransplantation and were eventually discharged home. The presented cases are the first reported where a successful cardiac retransplant was performed following prolonged upper-body extracorporeal life support.

Cardiac Re-Transplantation - A Reasonable Treatment Option in Selected Patients with Severe Graft Failure?

Heart re-transplantation (re-HTx) has been considered controversial due to shortage of donor organs and suboptimal results. We studied the results of cardiac re-Tx and compared it with primary heart transplantation (HTx) at our center. A total of 708 heart transplantations were carried out at our center between 1984 and 2017. 21 of those were re-HTx. One patient had been re-transplanted twice and two other patients had their primary transplantation in London before our program started. In a retrospective study, we evaluated pre-operative characteristics, cause of graft-loss, immunology and outcome among patients undergoing cardiac re-Tx and compared them with the primary HTx population. A total of 20 patients (14 male, 5 female) received a second HTx (n=20) or a third HTx (n=1) at Sahlgrenska University Hospital. Mean age at re-HTx was 35 as compared to 45 years for the primary HTx group. Mean donor age in the re-HTx and primary HTx groups was 42 and 37 years, respectively. The primary cardiac diagnosis for re-HTx patients was DCM (n=11), myocarditis (n=3), IHD (n=2), CHD (n=2) and unknown (n=1). The causes of graft failure and re-HTx were acute rejection (n=5), coronary allograft vasculopathy (CAV) (n=5), and unexplained graft failure (n=10). The median time interval between primary and re-Tx was 49 months (range 0 - 305 months). Patients undergoing re-HTx were more often in need of pre-operative dialysis (37%) as compared with primary HTx (1.5%). Also, the re-HTx group was more often treated with a short-term MCS (37 %; 6 ECMO, 1 BiVAD) than those receiving a primary HTx (19%). The 1-, 5- and 10-year survival rates for re-HTx and primary HTx were 85% (95%CI:60-95) / 58% (95%CI:33-76) / 45% (95%CI:22-66) and 88% (95%CI:86-90) / 80% (95%CI:77-83) / 68% (95%CI:63-71), respectively. Causes of death in the re-Tx group included acute transplant related death (n=1), cardiac death (n=2) and non-cardiac causes (infection/ malignancy, n=3). During a 30-year period, 3% of our HTx population underwent a re-HTx. The most common cause for re-HTx was unexplained graft failure, followed by acute rejection and CAV. Although inferior to primary HTx, cardiac re-HTx offers a reasonable long-term outcome and should therefore be offered to selected patients.

Characteristics of patients with preeclampsia and eclampsia in a tertiary teaching hospital in India

The aim of our study was to identify preoperative risk factors affecting overall survival after cardiac retransplantation (ReTX) in a contemporary era.The United Network for Organ Sharing database was used to identify patients undergoing ReTX between 1995 and 2012. Of the total 28,464 primary transplants performed, 987 (3.5%) were retransplants. The primary outcome investigated was overall survival. The influence of preoperative donor and recipient characteristics on survival were then tested with univariate logistic regression and multivariate Cox regression models.Of 987 patients who underwent ReTX, median survival was 9 years. Estimated survival at 1, 3, 5, 10, and 15 years following retransplant was 80% (95% confidence interval [CI], 78%-83%), 70% (95% CI, 67%-73%), 64% (95% CI, 61%-67%), 47% (95% CI, 43%-51%), and 30% (95% CI, 25%-37%), respectively. Clinical predictors of survival using multivariable analysis included donor age (relative risk [RR], 1.14; P = .004), ischemic time > 4 hours (RR, 1.48; P = .004); preoperative support with extracorporeal membrane oxygenator (RR, 3.91; P < .001), and the time between previous and current transplant (P = .004). Patients with ReTX have 1.27 times higher relative risk of death compared with patients undergoing primary transplant only (RR, 1.27; 95% CI, 1.13-1.42; P < .001).Patients who undergo cardiac ReTX can expect to have a 1-year survival less than a patient undergoing primary transplant with an acceptable median overall survival. Both donor and recipient preoperative factors contribute to overall survival following cardiac ReTx. Donor characteristics include age of the donor and ischemic time. Recipient factors include the need for extracorporeal membrane oxygenator and the number of days between the first and second transplant. Optimal survival following cardiac ReTX can best be predicted by choosing patients who are farther out from their initial transplant, not dependent upon preoperative extracorporeal support, and by choosing donor hearts younger in age and those likely to have shorter ischemic times.

Outcomes in patients undergoing cardiac retransplantation: A propensity matched cohort analysis of the UNOS Registry

Cardiac retransplantation accounts for approximately 3% of cardiac transplantation and is considered a risk factor for increased mortality. However, factors inherent to retransplantation including previous sternotomy, sensitization, and renal dysfunction may account for the increased mortality. We assessed whether retransplantation was associated with all-cause mortality after adjusting for such patient risk factors. We conducted a retrospective cohort study of adult and pediatric patients enrolled in the United Network for Organ Sharing database. We identified patients undergoing cardiac retransplantation based on transplant listing diagnosis and history of previous transplant. We used propensity-score matching to identify a matched cohort undergoing initial heart transplantation. In total, 62,112 heart transplant recipients were identified, with a mean age 46.6 ± 19.1 years. Of these, 2,202 (3.4%) underwent late cardiac retransplantation (>1 year after initial transplant and not for acute rejection). Compared with a matched group of patients undergoing initial heart transplantation, patients undergoing late retransplantation had comparable rates of all-cause mortality at 1 year (13.6% vs 13.8%, p = 0.733). In addition, overall mortality was not significantly different after matching (unadjusted hazard ratio [HR] 1.08, p = 0.084). In contrast, patients undergoing retransplantation within 1 year of initial transplant or for acute rejection remained at increased risk of mortality post-transplant after similar matching (unadjusted HR 1.79, p < 0.001). After matching for comorbidities, late retransplantation in the adult population was not associated with an increase in all-cause mortality. Our findings highlight the importance of assessing indication acuity and comorbid conditions when considering retransplant candidacy.

Efficacy of HTK Solution in the Preservation of Donor Hearts

Purpose Various preservation solutions for donor hearts are used nationally. We examined transplant outcomes where we used Histidine-tryptophan-ketoglutarate (HTK) solution exclusively since 2004. Methods Retrospective review of UNOS registry comparing our heart transplant outcomes with national outcomes since 2004. Propensity matching (1:3) was performed for donor and recipient age, gender, size, ischemic time , ejection fraction , prior cardiac surgery, heart failure etiology, concomitant kidney/liver transplantation, preop creatinine and preop mechanical support. Survival and postoperative outcomes were examined. We excluded pre-transplant extra-corporeal membrane oxygenation (ECMO), cardiac re-transplantation , heart-lung transplantation , and age less than 18. Results Our heart transplant population had a higher portion of patients with preoperative left ventricular assist device (56.9% vs 32.7%, P 0.05). There was no difference in survival between our institution and the national cohort (figure, P=0.649). Survival at 1, 5 and 10 years at our institution was 92.2%, 81.3%, and 70.8%, and for the UNOS population was 91.5%, 80.2%, and 62.0%. Our institution had a lower incidence of postoperative stroke (1.1% vs 3.1%, P=0.043) and new postoperative dialysis (5.6% vs 9.3%, P=0.028). The Michigan primary graft dysfunction (PGD) rate requiring mechanical support was 4.2%. Postoperative mechanical support utilized for PGD included ECMO (60.0%), right ventricular assist device (33.3%), intra-aortic balloon pump (20.0%), LVAD (13.3%), and biventricular support (13.3%). Conclusion Our exclusive use of HTK solution for donor heart preservation was associated with a low rate of PGD requiring mechanical support. Survival was non-inferior to the national outcomes. HTK is efficacious in preserving donor heart function.

Outcomes of bridge to cardiac retransplantation in the contemporary mechanical circulatory support era

BackgroundOutcomes have improved in patients bridged to heart transplant on contemporary continuous-flow ventricular assist devices over the past decade. We evaluated mechanical circulatory support as a means to bridge patients to cardiac retransplantation. MethodsWe retrospectively reviewed 464 patients who underwent cardiac retransplant from the United Network for Organ Sharing database between January 2006 and November 2016. Pre- and post-transplant data were compared between patients bridged to retransplant with mechanical circulatory support (n = 81) and those without mechanical circulatory support (n = 383). ResultsThe mean ages for the patients in the mechanical circulatory support and nonmechanical circulatory support cohorts were 41.2 ± 16 years and 42.1 ± 15.7 years, respectively (P = .64). Patients bridged with mechanical circulatory support were placed on extracorporeal membrane oxygenation (n = 29, 35.8%), a total artificial heart (n = 13, 16.0%), or a temporary or durable ventricular assist device (n = 39, 48.1%). Twelve patients (14.8%) were placed on a second device before retransplant. Thirty-nine percent of the mechanical circulatory support group were indicated for listing because of primary graft dysfunction or acute rejection versus 6% of the nonmechanical circulatory support group (P < .01). Likewise, 30% of patients in the mechanical circulatory support group were listed for cardiac allograft vasculopathy compared with 59% of the nonmechanical circulatory support group (P < .01). Thirty-day mortality was significantly higher in the mechanical circulatory support group (17.8% vs 4.8%, P < .01). However, patients who were bridged with a ventricular assist device or total artificial heart had comparable midterm outcomes to the nonmechanical circulatory support group. ConclusionsPatients who require mechanical circulatory support bridge to retransplantation belong to a high-risk cohort. Comparable midterm outcomes to the nonmechanical circulatory support cohort were demonstrated when patients' conditions allow for bridge with a ventricular assist device or total artificial heart. Bridging to retransplantation with extracorporeal membrane oxygenation remains a relative contraindication.

Effect of recipient gender and donor-specific antibodies on antibody-mediated rejection after heart transplantation.

Gender-difference regarding antibody-mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor-specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single-institution 6-year cohort (2010-2015), time to AMR was assessed, comparing men with women by survival analysis with a 1-year death-censored follow-up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA-, size- and sex-mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard-ratio [adj. HR]=1.78 [1.06-2.99]), P=.03) and the presence of pfDSA (adj. HR=3.20 [1.80-5.70], P<.001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR=2.2 (P=.026) and MFI of pfDSA (per 1 MFI-increase) adj. HR=1.0002 (P<.0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender-related difference in the severity of pfDSA.

Inhibition of C-X-C motif chemokine 10 reduces graft loss mediated by memory CD8+ T cells in a rat cardiac re-transplant model.

The interaction of chemokine (C-X-C motif) ligand 10 (CXCL10) with its receptor (CXCR3) is a critical process in recruiting donor reactive T cells to a graft and alloantigen-specific memory T (Tm) cells exert a principal function in promoting graft dysfunction during accelerated cardiac rejection. However, whether CXCL10 chemokine exerts any effects on acute accelerated rejection mediated by CD8+ Tm cells in a re-transplant model has remained elusive. The present study established a cardiac transplant model by advanced microsurgery technology and improved organ storage. A novel rat model of cardiac re-transplantation was established at 40 days following primary heart transplant. The experiment included two parts, and when models were established, the rats were divided into two groups: Primary cardiac transplant (HTx) and re-transplantation without treatment (HRTx). In part 1, recipients from part 2, including re-transplantation without treatment (HRTx+NS) and re-transplantation treated with anti-CXCL10 antibodies (500 µg every other day by intraperitoneal injection; HRTx+CXCL10 Abs group). The graft survival time was observed and graft infiltration by inflammatory cells was assessed via histology of cardiac graft sections; in addition, the gene expression and the serum concentration of CXCL10 in each group was assessed. Indexes such as rejection-associated cytokines were assayed by reverse-transcription quantitative PCR and ELISA kits, and flow cytometry of splenocytes was used to detect Tm cells in the re-transplantation groups. The results demonstrated that level of CXCL10 was significantly increased and the graft mean survival time was shortened accompanied with aggravated lymphocyte cell infiltration in the HRTx group when compared that in the HTx group; in addition, the serum levels and mRNA expression of interleukin (IL)-2 and interferon (IFN)-γ were increased, while transforming growth factor (TGF)-β was decreased in the HRTx group. Furthermore, neutralization of CXCL10 prolonged the graft mean survival time and delayed accelerated rejection. Compared with that in the HRTx+NS group, serum levels and graft tissue mRNA expression of IFN-γ and IL-2 were decreased in the HRTx+CXCL10 Abs group, while TGF-β mRNA was significantly increased but the serum concentration was not significantly affected. In addition, there was no difference in IL-10 between the two groups, while delayed accelerated rejection paralleled with inflammatory cell infiltration decreased and the proliferation and differentiation of CD8+ Tm cells in secondary lymphoid organs were reduced in the HRTx+CXCL10 Abs group vs. those in the HRTx+NS group. The present study demonstrated that CXCL10 had a crucial role in cardiac transplantation and re-transplantation, and that treatment with CXCL10 antibodies delays accelerated acute rejection mediated by Tm cells in a rat model of cardiac re-transplantation.