Pre-transplant Mechanical Circulatory Support Research Articles

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.

Cost-effectiveness of the National Pediatric Heart Transplantation Program in Australia

ObjectivesCost data for pediatric heart transplantation are scarce. We examined hospital cost of the national pediatric heart transplantation program in Australia and assessed factors associated with increased costs. MethodsThe hospital cost of all children who underwent heart transplantation at a national referral center between January 2003 and June 2015 and were followed more than 1 year was retrospectively analyzed. Lifetime follow-up costs were adjusted for quality of life and projected to life expectancy. All costs were reported in 2016 US dollars. ResultsOf 70 children who underwent heart transplantation in the study period, 61 were followed more than 1 year after transplantation (mean, 4.3 ± 2.5 years). Mean cost of primary heart transplantation was $278,480 (95% confidence interval, 219,282-337,679) and did not change over time. Pretransplant mechanical circulatory support was required in 36% (22/61) of children. On multivariable analysis, greater admission costs were associated with ventricular assist device and pretransplant length of stay. Mean annual follow-up cost after discharge was $55,823 (95% confidence interval, 47,631-64,015) in the first year and $12,119 (95% confidence interval, 8578-15,661) thereafter. Increased first-year follow-up costs were associated with endomyocardial biopsies and length of readmissions. Cost per quality-adjusted life-year gained varied from $29,161 to $44,481 on sensitivity analysis. Freedom from treated rejections was 65.5% at 1 year, 63.2% at 3 years, and 59.5% at 5 years. Endomyocardial biopsies contributed to 52% of first-year follow-up costs. ConclusionsPrimary pediatric heart transplantation in Australia is cost-effective for long-term survivors, even for those supported by ventricular assist device. Surveillance endomyocardial biopsy was a major contributor to post-transplantation costs. Selective targeting of surveillance biopsies may be cost-saving.

Spanish Heart Transplant Registry. 29th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure

Introduction and objectivesThe present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. MethodsWe describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. ResultsA total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P <.001 for trend). In the last decade, there was a trend to better survival. ConclusionsAround 300 transplants per year were performed in Spain in the last decade. There was a significant increase in the use of pretransplant mechanical circulatory support and a trend to improved survival.

Registro Español de Trasplante Cardiaco. XXIX Informe Oficial de la Sección de Insuficiencia Cardiaca de la Sociedad Española de Cardiología (1984-2017)

Introducción y objetivosThe present report updates the characteristics and results of heart transplantation in Spain, mainly focused in the 2008-2017 period. MethodsWe describe the recipient and donor characteristics, surgical procedures, and outcomes of heart transplants performed in 2017. The 2017 data were compared with those obtained from 2008 to 2016. ResultsA total of 304 cardiac transplants were performed in 2017. Between 1984 and 2017, 8173 procedures were performed, 2689 of them after 2008. Significant temporal trends were observed in recipient characteristics (lower pulmonary vascular resistance, lower use of mechanical ventilation, and a higher percentage of diabetic patients and those with previous cardiac surgery), donor characteristics (older donor age and a higher percentage of female donors and those with a prior cardiac arrest) and procedures (lower ischemia time). In 2017, 27% of patients were transplanted after undergoing mechanical ventricular assistance (P <.001 for trend). In the last decade, there was a trend to better survival. ConclusionsAround 300 transplants per year were performed in Spain in the last decade. There was a significant increase in the use of pretransplant mechanical circulatory support and a trend to improved survival.

Risk Factors for Survival After Heart Transplantation in Children and Young Adults: A 22-Year Study of 179 Transplants.

This article reviews all patients who underwent heart transplantation (HTx) within a single institution (172 patients underwent 179 HTx [167 first-time HTxs, 10 second HTxs, 2 third HTxs]) to describe diagnostic characteristics, management protocols, and risk factors for mortality. Descriptive analysis was performed for the entire cohort using mean, standard deviation, median, interquartile range, and overall range, as appropriate. Univariable and multivariable Cox proportional hazards models were performed to identify prognostic factors for outcomes over time. The primary outcome of interest was mortality, which was modeled by Kaplan-Meier analysis. Median age at HTx was 263 days (range, 5 days to 24 years; mean = 4.63 ± 5.95 years; 18 neonates, 79 infants). Median weight at HTx was 7.5 kg (range, 2.2-113 kg; mean = 19.36 ± 23.54). Diagnostic categories were cardiomyopathy (n = 62), primary transplantation for hypoplastic left heart syndrome (HLHS) or HLHS-related malformation (n = 33), transplantation after cardiac surgery for HLHS or HLHS-related malformation (n = 17), non-HLHS congenital heart disease (n = 55), and retransplant (n = 12). Operative mortality was 10.1% (18 patients). Cumulative total follow-up is 1,355 years. Late mortality was 18.4% (33 patients). Overall Kaplan-Meier five-year survival was 76.2%. One hundred twenty-one patients are alive with a mean follow-up of 7.61 ± 6.46 years. No survival differences were seen among the five diagnostic subgroups ( P = .064) or between immunosensitized patients (n = 31) and nonimmunosensitized patients (n = 141; P = .422). Excellent results are expected for children undergoing HTx with comparable results among diagnostic groups. Pretransplant mechanical circulatory support and posttransplant mechanical circulatory support are risk factors for decreased survival. Survival after transplantation for HLHS or HLHS-related malformation is better with primary HTx in comparison to HTx after prior cardiac surgery.

Mechanical Circulatory Support Before And After Heart Transplantation

Objective To investigate the impact on survival of pre and post heart transplant (HT) use of mechanical circulatory support (MCS).Methods Data were collected retrospectively. ECMO was the MCS used to treat severe early graft failure (EGF). Log-rank test was used to compare Kaplan-Meier survival curves. A p-value <0.05 was considered statistically significant. Results 147 HT were done from 2004 to October 2016. The average male and female recipient’s age was 50±13 years and 47±14 years, respectively. Percentage of use of MCS and IABP to bridge patients to HT were 16% and 7%, respectively. MCS included: 8 HeartWare LVAD (5.4%), 6 ECMO (4.1%), 6 Levitronix BiVAD (4.1%), 2 Thoratec LVAD (1.4%) and 2 Levitronix LVAD (1.4%). Hospital mortality was 14.3% (21pt). 1-year survival was 82% and 5-year survival was 75%. Overall pre-transplant MCS was not correlated to worse post-transplant prognosis, p=0.822. Left sided MCS showed a worse survival compared to the no-MCS group (p=0.045) and to the ECMO and BiVAD (p=0.02). Severe primary EGF strongly impact the early mortality after heart transplantation (p<0.001). Excluding the 90 day mortality, the survival between patients with EGF and those without is similar (p=0.874).The risk of mortality increased almost 2 fold according each hour of ischemic time [OR=1.7, 95% IC, 1.1-2.7, p=0.017].Conclusions ECMO because of severe EGF remains associated with worse post-transplant outcomes however, patients discharged after severe EGF, showed a long term survival comparable to those without EGF. A LVAD before HT seems to affect the hospital mortality.

The impact of multidisciplinary care on early morbidity and mortality after heart transplantation.

The impact of multidisciplinary care on outcome after heart transplantation (HTx) remains unclear. This retrospective study investigates the impact of multidisciplinary care on the primary end point 1-year all-cause mortality (ACM) and the secondary end point mean acute cellular rejection (ACR) grade within the first postoperative year. This study includes a total 140 HTx recipients (median age: 53.5 years; males: 80%; donor/recipient gender mismatch: 38.3%; mean length of in-hospital stay: 34 days; mean donor age: 41 years). Multidisciplinary care was implemented in 2008, 66 HTx recipients had operation in 2000-07 and 74 patients had HTx thereafter (2008-14). Non-ischaemic dilated cardiomyopathy was more prevalent in HTx recipients of 2000-07 (63.6 vs 43.2%; P = 0.024). Pre-transplant mechanical circulatory support was more frequent in 2008-14 (9.1 vs 24.3%; P = 0.030). Groups were not different for pre-transplant cardiovascular risk factors or other comorbidity, invasive haemodynamics or echocardiographic parameters. In-hospital and 1-year ACM were numerically lower in 2008-14 (16.2 vs 22.2%; 18.9% vs 25.8%; P = 0.47/0.47, respectively). In 2000-07, pre-transplant weight and diabetes mellitus predicted in-hospital ACM (odds ratio -0.14, P = 0.02; OR 5.24, P = 0.01, respectively) while post-transplant length of in-hospital stay was related with in-hospital ACM (odds ratio -0.10; P = 0.016) and 1-year ACM (odds ratio -0.07; P = 0.007). In 2000-07, the mean grade of ACR within the first postoperative year was higher (0.65 vs 0.20; P < 0.0001) and ≥moderate ACR was associated with in-hospital mortality (χ2 = 3.92; P = 0.048). Multidisciplinary care in HTx compensates post-transplant risk associated with pre-transplant disease and has beneficial impact on the incidence of ACR and ACR-associated early mortality.

FIVE-YEAR EXPERIENCE IN PERIPHERAL VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION AS A METHOD OF MECHANICAL CIRCULATORY SUPPORT IN POTENTIAL HEART TRANSPLANT RECIPIENTS

Introduction.Venoarterial extracorporeal membrane oxygenation (VA ECMO) is one of the most widely used methods of temporary mechanical circulatory support (MCS) during the preparation and performance of heart transplant surgery (HT) [Barth E. et al., 2012; Kittleson M.M. et al., 2011].Aimof this study was to assess the effectiveness of using peripheral VA ECMO as a method of mechanical circulatory support in potential heart transplant recipients that urgently required transplantation.Materials and methods. The study included 125 potential heart transplant recipients (107 (86%) men and 18 (14%) women) aged from 12 to 72 (43 ± 1.2) years with a peripheral VA ECMO system installed within the period from April 01, 2011 till August 12, 2016. The indication for the start of its use was rapidly progressing congestive heart failure (CHF) of level 1 or 2 by the INTERMACS scale. Femoral blood vessel cannulation was performed using both open (surgical) and closed (puncture) methods. 23 and 25 F venous cannulae were utilized for femoral vein cannulation, and 15 and 17 F arterial cannulae were utilized for femoral artery cannulation. In all cases superfi cial femoral artery catheterization (14 F single-lumen catheter) or cannulation (8 or 10 F arterial cannula) was performed in the descending (anterograde) direction for the prevention of lower limb ischemia on the side of the femoral artery cannulation.Results.The peripheral cannulation method was used to perform VA ECMO in 100% (n = 125) observations. In 69 (55.2%) patients the severity of progressive CHF corresponded to INTERMACS level 1; in 51 (40.8%) cases it corresponded to INTERMACS level 2. During VA ECMO the average volumetric extracorporeal circulation fl ow rate ranged from 2.2 to 4.5 (3.2 ± 0.4 l/min) or 1.6 ± 0.2 l/min/m2 with the average rotation speed of the centrifugal pump of 3.216 ± 105 rpm. 113 (90.4%) of 125 potential recipients underwent HT. The duration of VA ECMO prior to HT (n = 113) was from 8 hours to 40 (7.1 ± 2.7) days: in 37 (32.7%) of 113 patients – up to 3 days, in 43 (38.1%) cases – from 4 to 7 days, in 21 (18.6%) cases – from 8 to 14 days, in 8 (7.1%) cases from 15 to 21 days, in 4 (3.5%) cases – more than 3 weeks. In the course of VA ECMO, 12 (9.6%) of 125 potential recipients (11 men and 1 women aged from 21 to 63 (40 ± 4) died before they could receive HT. In 2 (16.7%) of 12 cases the cause of death was brain death associated with a thromboembolic cerebrovascular event. The majority of patients (n = 10; 83.3%) died of progressive multiple organ failure and sepsis. 6 of 12 patients showed clinical and instrumental signs of acute unilateral (n = 2) or bilateral (n = 4) polysegmental pneumonia.Conclusion. Peripheral VA ECMO provides a successful bridge to heart transplant procedure in 90% of potential recipients who need pre-transplant MCS. The timely initiation of VA ECMO before the development of pronounced hemodynamic, organ, electrolyte and metabolic disorders creates the conditions for a successful use of MCS in potential heart transplant recipients.

Transplant Survival After Berlin Heart EXCOR Support.

The Berlin Heart EXCOR pediatric ventricular assist device (VAD) is approved by the Food and Drug Administration for bridge to cardiac transplantation (BTT) in children. As the clinical outcomes of the EXCOR continue to be evaluated in the United States, data on post-transplant survival are needed. The UNOS database was used to identify patients <18 years old undergoing orthotopic heart transplantation (OHT) from June 2004 to June 2014. Patients undergoing BTT with the EXCOR were identified. A matched cohort of (358) patients undergoing OHT without pretransplant mechanical circulatory support (no-MCS) was also identified as control subjects. The post-transplant survival between the two groups was compared. There were 2,885 pediatric OHT during the study period. Of these, 358 (50%) patients were BTT with the EXCOR. At time of listing, inotrope use was 51.7% vs. 53.4%, (p = 0.653) in the EXCOR cohort and the no-MCS cohort, respectively. At the time of transplantation, end-organ function was equivalent with same median creatinine levels (0.4, p = 0.203) and median total bilirubin (0.5, p = 0.682) for the EXCOR and the no-MCS cohorts. Kaplan-Meier post-transplantation survival did not differ between the two cohorts (30 day, 1 year, and 5 year post-transplant survival was 94%, 90%, and 72% [EXCOR cohort] vs. 98%, 91%, and 77% [no-MCS cohort]; p = 0.160). Short- and mid-term post-transplant survival using the EXCOR Pediatric VAD as a BTT in children is equivalent to patients who underwent OHT without pretransplant MCS.

Heart transplant program at IRCCS-ISMETT: Impact of mechanical circulatory support on pre- and post -transplant survival

BackgroundHeart transplantation (HTx) improves the quality of life and survival in patients affected by end-stage heart failure. The purpose of the current study is to present the patients' clinical data and results of HTx in a single Center of Sicily. Focus on survival after pre and post HTx mechanical circulatory support use will be performed. Methods. 133 HTx were done from 2004 to the end of 2015.The average donor age was 34±13.5years and the proportion of male donors was 67%. Percentage of use of mechanical circulatory support to bridge patients to HTx was 18%. Results. Overall pre-transplant mechanical circulatory support was not correlated to worse post-transplant prognosis, p=0.757. Severe primary early graft failure requiring extra corporeal membrane oxygenator support strongly impact the early mortality after heart transplantation (p<0.001). Conclusions. The results of HTx at ISMETT are comparable to those reported in high volume Italian transplant centers as well as in the ISHLT registry. The favorable outcome can be related to focus on multidisciplinary approach, strict recipients' selection and young donor population. Post HTx mechanical circulatory support use in general remains associated with worse post-transplant outcomes. This does not apply to pre-op mechanical circulatory support population.

Mechanical circulatory support and simultaneous heart-kidney transplantation: An outcome analysis

Single-donor simultaneous heart-kidney transplantation (SHKT) can significantly improve the survival of those with advanced heart failure and advanced renal insufficiency. Data on pre-transplant use of mechanical circulatory support (MCS) devices and outcomes after SHKT are limited and conflicting. Using the United Network for Organ Sharing registry data, we evaluated 749 adults undergoing SHKT after January 1, 2000. Patients were categorized into the following groups according to their type of pre-transplant MCS device: none (n = 568), pulsatile-flow left (n = 28), continuous-flow left (n = 68), temporary (n = 12), biventricular (n = 19), total artificial heart (n = 20), and unknown (n = 34). Regression analyses were performed to assess the association between types of MCS and post-transplant outcomes. Pre-transplant MCS was not associated with in-hospital mortality (univariate odds ratio [OR], 1.57; 95% confidence interval [CI], 0.82-2.97; p = 0.170) or post-discharge mortality (univariate hazard ratio, 0.92; 95% CI, 0.58-1.47; p = 0.733). Patients supported with pre-transplant temporary MCS devices were more likely to suffer from serious complications (composite of cardiac or non-cardiac surgeries, stroke, any drug-treated infection, and permanent pacemaker; multivariable adjusted OR, 10.0; 95% CI, 2.77-36.0; p < 0.001) after SHKT. Pre-transplant MCS did not increase risk of post-transplant dialysis (multivariable adjusted OR, 1.19; 95% CI, 0.81-1.75; p = 0.375) or cardiac rejection (univariate OR, 0.71; 95% CI, 0.34-1.51; p = 0.382), and did not prolong the length of hospital stay (≥ 4 weeks; multivariable adjusted OR, 1.05; 95% CI, 0.69-1.59; p = 0.832). Post-transplant dialysis status was a major determinant of adverse in-hospital (multivariable adjusted OR, 6.17; 95% CI, 3.14-12.1; p < 0.001) and post-discharge (multivariable adjusted hazard ratio, 1.56; 95% CI, 1.02-2.39; p = 0.041) mortality after SHKT. In the current transplant era, survival after SHKT in patients with pre-transplant MCS was equivalent to that of conventional SHKT. Pre-transplant dialysis, and not MCS status, determined the need for post-SHKT dialysis, which in-turn was a major risk factor for in-hospital and long-term mortality.

(780) - Effect of Pre-Transplant Mechanical Circulatory Support on Early Cellular Rejection and Subsequent Risk of Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) remains the leading cause of mortality following heart transplantation (HTx). Acute cellular rejection (CR) causes immune activation leading to an inflammatory process in the vascular endothelium thus contributing to CAV. The aim of the present study was to analyze the effect of pre-HTx mechanical circulatory support (MCS) on subsequent CR and the development of significant CAV.

Heart transplantation with or without prior mechanical circulatory support in adults with congenital heart disease

Recent analyses establish that heart transplantation is increasing among adults with congenital heart disease (ACHD), but the effects of pretransplant mechanical circulatory support (MCS) on perioperative and post-transplant outcomes have not been examined in the ACHD population. Scientific Registry of Transplant Recipients data on all adult heart transplants from September 1987 to September 2012 (n = 47 160) were classified based on primary diagnosis codes as CHD or non-CHD and MCS or non-MCS. Demographic, procedural, outcome and survival variables were compared between MCS and non-MCS ACHD patient groups. MCS was used in 83 (6.8%) ACHD patients compared with 8625 (18.8%) patients without CHD (P < 0.001). MCS as a fraction of ACHD transplants increased over time (P = 0.002). MCS patients spent more time on the wait list, had a higher baseline serum creatinine and were more likely to be male, status 1A, hospitalized, in the ICU and/or on a ventilator prior to transplant. However, MCS patients experienced equivalent short-term survival (30-day mortality = 10.8% in MCS vs 13.5% in non-MCS, P = 0.62) and overall survival by Kaplan-Meier analysis (P = 0.57). MCS patients had a longer post-transplant length of stay and were more likely to be transfused, but otherwise had no significant differences in adverse outcomes. MCS is less commonly used in adult CHD patients compared with all patients undergoing heart transplant, but has been increasing over time. Within the ACHD population, patients with MCS have a higher risk profile, but except for increased transfusion rate and longer length of stay, do not experience less favourable post-transplant outcomes.

ABO-incompatible heart transplantation in early childhood: An international multicenter study of clinical experiences and limits

Intentional blood group (BG)-incompatible (ABOi) heart transplantation in childhood is emerging in many centers. Safety limits remain undetermined. In this multicenter study we have compiled experience on clinical and immunologic boundaries. Data from six centers in Europe and North America on ABOi transplantation were collected in a standardized survey. Fifty-eight ABOi transplants were performed in 57 patients. Median age at transplant was 6.8 months (0.03 to 90 months); post-transplant follow-up was 37.7 months (0.46 to 117 months), accumulating 188 patient-years. Forty-seven percent of the patients received pretransplant mechanical circulatory support. Donors were either blood group A (n = 25), B (n = 18) or AB (n = 15). The median peak antibody titer to the donor BG pretransplant was 1:8 (0 to 1:64) for anti-A and 1:4 (0 to 1:32) for anti-B. Titers against the donor BG were lower post- than pretransplant in B recipients (p = 0.02), whereas third-party antibodies in BG O recipients developed normally post-transplant. Induction immunosuppression included anti-thymocyte globulin (61%), basiliximab (32%) or none (7%). All patients received calcineurin inhibitors, including 62% with mycophenolate mofetil, 10% with azathioprine, 2% with everolimus and 24% with steroids. There were 4 episodes of cellular rejection (Grade≥2R) and 7 antibody-mediated rejections. Five patients underwent antibody removal post-transplant. One patient developed severe graft vasculopathy. Freedom from death or retransplantation was 100%/96%/69% at 1/5/10 years. No graft loss was attributed to BG antibodies. Successful ABOi heart transplantation can be performed at an older age and with higher isohemagglutinin titers than initially assumed and using similar immunosuppressive regimens as for ABO-compatible transplants. Rejection and graft vasculopathy are rare. Persistently low titers of antibodies to the donor BG post-transplant suggest elements of tolerance and/or accommodation.

607 Which T-Cell Crossmatch Method Best Predicts Allograft Loss in Pediatric Heart Transplant Recipients?

Purpose: Several methods are currently available for performing a T-cell crossmatch (CM). No national cohort studies have explored the relationship between T-cell CM, CM methodology, and allograft survival after pediatric heart transplantation. Methods and Materials: All children 18 years old transplanted between 1/1999 and 12/2010 with an interpretable T-cell CM result, either by compliment dependent cytotoxicity (CDC) or flow cytometry, were identified using OPTN data. Children with a CDC-positive CM (N 83) and those with a CDC-neg/flow-pos CM (N 37) were compared with CDCneg/flow-neg controls (N 1225). Cox proportional hazard analysis was used to identify multivariable risk factors for time to graft loss. Results: During the past decade, utilization of CDC-CM has decreased significantly whereas the use of flow CM has increased (both P 0.01). Currently 1 in 10 pediatric heart transplants are performed in the context of a positive T-cell CM. Compared to CDC-neg/flow-neg controls, patients with a CDC-pos CM were more likely to be listed UNOS status 1A, have a pre-transplant diagnosis of congenital heart disease or re-transplant, and have a positive PRA (both class I and II). Utilization of pre-transplant mechanical circulatory support was not associated with CM result. CDCpos CM was associated with an increased prevalence of treated allograft rejection by 1 year compared to CDC-neg/flow-pos patients and CMnegative patients (48% vs. 19% and 23%; P 0.001). In multivariable analysis, patients with a CDC-pos CM were more likely to have graft loss than controls (HR 1.9; CI 1.3-2.6) while those with a CDC-neg/flow-neg CM did not show increased risk (HR 0.9; CI 0.4-2.0). Conclusions: Amongst a population of pediatric heart transplant recipients, CDC-pos T-cell CM was strongly associated with an increased risk of death or allograft loss. While the utilization of flow based assays has become more common, a positive flow CM may perform less well in identifying patients at risk for graft loss than the traditional CDC method.

Lessons Learned From 119 Consecutive Cardiac Transplants for Pediatric and Congenital Heart Disease

This manuscript reviews all patients who underwent orthotopic heart transplantations (OHT) at our program (116 patients underwent 119 OHT) to describe their diagnostic characteristics and to assess risk factors for mortality. Median age at OHT was 179 days (mean, 1,446.6 ± 188.9 days [4.0 ± 0.5 years]; range, 5 days to 7,125 days [19.5 years]; 15 neonates, 68 infants). Median weight at OHT was 5.5 kg (mean, 17.2 ± 2.1 kg; range, 2.2 to 113 kg). Diagnoses were cardiomyopathy (n = 37), primary transplantation for hypoplastic left heart syndrome (HLHS) or HLHS-related malformation (n = 29), transplantation after prior cardiac surgery for HLHS or HLHS-related malformation (n = 9), non-HLHS congenital heart disease (n = 39), and retransplant (n = 5). Overall Kaplan-Meier 5-year survival was 72.7%. Operative mortality was 12.6% (15 patients). Late mortality was 13.4% (16 patients). Eighty-five patients survived, with a mean follow-up of 5.76 ± 0.48 years (median, 5.1 years; range, 0.12 to 14.0 years). Total follow-up was 507.0 years. No survival difference was seen among the five diagnostic subgroups (p = 0.20). Univariate association between risk factors and survival was assessed for the following variables: age (p = 0.91), weight (p = 0.86), sex (p = 0.47), race (p = 0.40), insurance classification (p = 0.42), high PRA (p = 0.20), pretransplant mechanical circulatory support (p < 0.001), posttransplant mechanical circulatory support (p < 0.001), redo sternotomy (p = 0.07), heterotaxy (p = 0.02), cardiopulmonary bypass time (p = 0.01), and donor heart cross-clamp time (p = 0.02). Excellent results are expected for children undergoing OHT regardless of diagnostic classification. Pretransplant mechanical circulatory support, posttransplant mechanical circulatory support, cardiopulmonary bypass time, donor heart cross-clamp time, and heterotaxy are risk factors for decreased survival.

Pediatric Heart Transplant Candidates With Failed Donor Heart Allocation After Eurotransplant Urgency Listing Profit From Pretransplant Mechanical Circulatory Support Bridging

Due to the Eurotransplant organ allocation policy, urgency listing for heart transplantation (HTx) remains in force until ventricular assist device (VAD) implantation in Germany. We studied the prognosis of HTx candidates after failed donor heart allocation in urgent status. We studied all adult and pediatric (<18 years) HTx candidates who underwent primary HTx after Eurotransplant urgency listing between January 2001 and December 2006 (Group A-uHTx [A-"u"rgent status "HTx"], n = 99; Group P-uHTx [P-"u"rgent status "HTx"], n = 24) and those to whom donor heart was not urgently allocated before VAD implantation or death in the same period (Group A-fHA [A-"f"ailed "H"eart "A"llocation], n = 21, Group P-fHA [P-"f"ailed "H"eart "A"llocation], n = 10). Mortality rate after urgency listing or primary VAD implantation was studied in each group. In adult patients, 1-year mortality rate after urgency listing in Group A-fHA was 56.8% and significantly higher than in Group A-uHTx (30.6%, P < 0.001, log-rank test). After failed urgent heart allocation, 15 out of 21 patients in Group A-fHA had VAD implantation and two patients (9.5%) underwent HTx after VAD implantation. In pediatric patients, 1-year mortality rate in Group P-fHA was 40.0% and significantly higher than in Group P-uHTx (8.5%, P < 0.05). In Group P-fHA, all 10 patients underwent VAD implantation after failed urgent heart allocation and six patients (60.0%, P < 0.01 vs. Group A-fHA, Fisher's exact test) underwent HTx after VAD implantation. After failed urgent donor heart allocation, pediatric HTx candidates seem to profit more from mechanical circulatory support than adults.

Multivariate Predictors of Heart Transplantation Outcomes in the Era of Chronic Mechanical Circulatory Support

Determining which pretransplantation (TX) characteristics predict the development of chronic renal dysfunction (CRD) or death after heart TX would enable more accurate risk assessment at the time of candidate evaluation. A cohort of 278 patients underwent TX in three hospitals between 1993 and 2002. Predictive models for CRD (serum creatinine consistently above 2 mg/dL) and allograft loss (death or re-TX) were constructed using logistic and Cox regression, respectively. Using logistic regression, CRD was more likely to develop in TX patients if they had a larger body surface area (odds ratio [OR] = 5.8 per m2, 95% confidence interval [CI] = 1.04 to 31.9, p = 0.04) or were inotrope dependent (OR = 1.8, 95% CI = 0.90 to 3.7, p = 0.09). Notably, the implementation of mechanical circulatory support as bridge to transplantation decreased the risk of CRD (OR = 0.30, 95% CI = 0.12 to 0.72, p = 0.007). Cox analysis demonstrated independent predictive ability of improved survival for males (hazard ratio [HR] = 0.42, 95% CI = 0.21 to 0.83, p = 0.01). Worse survival was observed with prior sternotomy (HR = 3.5, 95% CI = 2.0 to 6.0, p < 0.001), diabetes mellitus (HR = 1.9, 95% CI = 0.98 to 3.9, p = 0.06), and elevated serum creatinine (HR = 2.8 per mg/dL, 95% CI = 1.3 to 5.8, p = 0.007). Certain pretransplant characteristics clearly predispose a patient to the development of CRD or increased mortality after heart transplantation. Interestingly, the risk of CRD after heart transplantation is greater for patients bridged to transplant with inotropes than with mechanical circulatory support. When hemodynamically indicated, timely implementation of pretransplant mechanical circulatory support should be considered.

Effect of Mechanical Circulatory Support on Outcomes After Heart Transplantation

Mechanical circulatory support (MCS) before heart transplantation was previously associated with worse post-transplant outcomes than when MCS was not required. Given the changes in technology, expertise, patient selection, and timing of subsequent transplantation, we hypothesized that patients who require MCS before heart transplantation have similar outcomes after transplantation as those not requiring pre-transplant MCS. We retrospectively reviewed 278 patients who underwent cardiac transplantation from 1993 to 2002. MCS was required in 72 patients (HeartMate LVAS in 66, CardioWest Total Artificial Heart in 6) and was not required in 206 patients. The influence of pre-transplant MCS on post-transplant outcomes was assessed in the 2 groups. Baseline clinical characteristics (age, gender, etiology of heart failure, history of diabetes mellitus, and donor age and gender) were similar in the 2 groups. One-month and 1-year survival after transplantation did not differ between the groups (MCS, 92% and 85%, respectively vs no MCS, 97% and 92%, respectively). Similar proportions of patients were free from rejection (International Society for Heart and Lung Transplantation score >or=3A) at 1 year of follow-up (MCS, 56% vs no MCS, 52%, p = 0.60). No difference was observed between MCS and no MCS patients in other post-transplant events such as hospital stay, intensive care unit stay, extubation time, acute allograft dysfunction, reoperation rates, acute renal dysfunction, acute hepatic dysfunction, infections, arrhythmias, thromboembolic complications, neurologic complications, gastrointestinal complications and the development of cardiac allograft vasculopathy. The incidence of chronic renal insufficiency was actually lower in the MCS Group (15.3% vs 37.9%, p = .001). Post-transplant outcomes after pre-transplant use of MCS are similar to those when MCS is not required.