Abstract
Objective
To analyze our institution’s experience with extracorporeal membrane oxygenation (ECMO) support after orthotopic heart transplantation (OHT) in the pediatric population.
Background
Mechanical circulatory support has been used for more than 30 years to allow the heart to recover from ischemia and injury. There are limited pediatric data, however, on the efficacy of ECMO in the setting of post-transplantation support for primary graft dysfunction or rejection.
Methods
Data from all patients at our university-affiliated, tertiary care children’s hospital who underwent OHT between 1998 and 2010 and required subsequent ECMO support were analyzed. The primary outcome measure was survival to hospital discharge.
Results
203 pediatric patients underwent OHT between 1998 and 2010 at our institution. Twenty-nine of these patients experienced post-transplantation cardiac failure requiring ECMO support, eighteen of whom survived to hospital discharge (62%). Survival in the rejection and allograft vasculopathy group was 75%, and survival in patients with primary graft failure was 53% after ECMO support (P = 0.273). Patient survival to hospital discharge was not associated with ischemic time or duration of ECMO.
Conclusions
ECMO provides hemodynamic support in the setting of cardiac failure and can be used successfully after pediatric OHT for primary graft dysfunction or rejection.
Keywords: Extracorporeal membrane oxygenation, mechanical circulatory support, orthotopic heart transplantation, pediatric
Introduction
In an era of rapid technological and surgical advancement, an increasing number of children with complex cardiac disease are surviving to adulthood. In severe cases that are not amenable to surgical correction or palliation, heart transplantation remains a final option (1). Pediatric cardiac transplantation has evolved substantially over the past four decades, with improving long-term outcomes (2). Postoperatively, orthotopic heart transplantation (OHT) requires close monitoring, cardiac intensivist management, and pharmacologic support. If a graft is unable to maintain adequate cardiac output despite conventional post-operative management, mechanical circulatory support may be considered as a bridge to recovery of cardiac function.
There has been much advancement in the field of mechanical circulatory support in the past decade, which has broadened its application as well as improved survival and outcomes. In the setting of post-cardiac transplantation, extracorporeal membrane oxygenation (ECMO) remains the most feasible form of mechanical circulatory support because of its ability for rapid initiation as well as portability. ECMO may be applied in many clinical situations, for both cardiac and respiratory support. ECMO has been used successfully in cardiac disease in cases of inadequate cardiac output, extracorporeal cardiopulmonary resuscitation, bridging to heart transplantation or retransplantation, and postoperatively in cases of postcardiotomy cardiogenic shock (3-7). In our experience, ECMO can also be effectively implemented in pediatric patients in cases of primary graft failure or rejection as a bridge to recovery after heart transplantation. The primary objective of our study is to report our institution’s survival to hospital discharge for pediatric patients receiving ECMO support after OHT. Our secondary objective is to analyze whether our center’s survival was associated with any particular demographic or clinical variables. We hypothesized that longer graft ischemic time and longer duration of ECMO would be associated with worse survival among pediatric patients receiving ECMO support.
Methods
Our university’s institutional review board approved this study and waived the need for informed consent.
Patient population
Records of all pediatric heart transplantation recipients less than 21 years of age at the time of OHT at our tertiary-care children’s hospital between January 1, 1998 and December 31, 2010 were reviewed. We identified and evaluated all patients who required ECMO support after cardiac transplantation. Variables examined included demographic data, pre-OHT diagnosis, indication for ECMO, donor ischemic time, total cardiopulmonary bypass (CPB) time, past cardiac surgical history, ECMO initiation location, time between OHT and ECMO initiation, ECMO duration and survival to hospital discharge.
We separated our cohort into two groups based on their underlying reason for requiring ECMO support: (1) patients with primary graft dysfunction, and (2) patients with transplant rejection. Patients experiencing hemodynamic compromise occurring within 24 hours of OHT without evidence of elevated panel-reactive antibodies were considered to experience primary graft dysfunction. Patients were presumed to have transplant rejection if they had normalized cardiac function after transplantation that subsequently deteriorated by quantitative measurement of shortening fraction via echocardiogram, and one of the following: (1) a biopsy demonstrating cellular or antibody-mediated rejection greater than 1R based on the International Society for Heart and Lung Transplantation classification; (2) evidence of clinical improvement with empiric anti-rejection therapy; or (3) autopsy-demonstrated cellular or antibody-mediated rejection. Also included in this late ECMO support group was any patient with cardiac allograft vasculopathy (CAV) who required mechanical circulatory support. CAV is considered to be a manifestation of transplant rejection. None of the patients who experienced transplant rejection or CAV had previously been on ECMO support following their transplantation.
Immunosuppression
During our study period, routine immunosuppression consisted of a combination of tacrolimus (Astellas), mycophenolate mofetil (Roche) and corticosteroids. Mycophenolate mofetil dose was initiated at 1500 mg/m2 divided twice a day, and was titrated to maintain mycophenolic acid levels between 2 to 4 μg/dL. Tacrolimus dose was titrated to achieve levels of 12 to 15 ng/mL in the first month after transplant, then 8 to 10 ng/mL from 1 to 6 months post-OHT, 6 to 10 ng/mL from 6 months to 5 years post-OHT, and finally 4 to 8 ng/mL for patients who were more than 5 years post-OHT. After the immediate post-transplantation period, intravenous methylprednisolone was converted to prednisone, which was tapered off over 12 months as clinically appropriate. Sirolimus (Pfizer) was in certain cases utilized to replace mycophenolate mofetil for high-risk patients such as those with congenital heart disease, elevated panel-reactive antibodies, multiple blood transfusions, and patients who previously required mechanical circulatory support. Sirolimus was also utilized in patients with evidence of humoral graft rejection and coronary artery vasculopathy. These high-risk patients and patients with renal compromise received induction therapy with anti-thymocyte globulin (ATG) (Sanofi-Aventis) for the first five days postoperatively. These patients were then transitioned to standard immunosuppression protocol at our institution. Patients who experienced episodes of biopsy-proven rejection or suspected rejection (based on history, physical examination and echocardiography) were treated with intravenous pulse methylprednisolone, or an advanced protocol including plasmapheresis, rituximab (Genentech) and/or ATG.
ECMO
A standardized ECMO circuit was implemented with appropriate cannulas according to patient size. Cannulation sites for ECMO depended on the adequacy of vessels. All patients were cannulated for venoarterial ECMO, either via a transthoracic approach or via peripheral arteries and veins. Standard anticoagulation at our institution is achieved with heparin. Our institutional preference for initial cardiac support is a centrifugal pump due to the ease of deployment and smaller size. A common indication for changing to a roller pump at our institution is hemolysis.
Statistical analysis
The distribution of patient demographics and transplantation variables were compared between survivors and non-survivors to hospital discharge. For categorical variables, differences between the two groups were examined using Fisher’s exact test. Wilcoxon rank sum tests were utilized to compare continuous variables between groups. Kaplan Meier curves were constructed to visualize overall survival rates between the late rejection and graft dysfunction subgroups. The differences in overall survival were formally tested using the log-rank test. A P-value less than 0.05 was considered significant. All statistical analyses were performed using SAS (version 9.2; SAS Institute, Cary, NC) and R (version 2.15.0; www.rproject.org).
Results
Transplantation Demographics
There were 203 pediatric patients who underwent heart transplantation between 1998 and 2010 at our institution. Twenty-nine of these patients experienced cardiac failure following OHT requiring ECMO support. Patients ranged in age from 2 months to 21 years (mean, 8.8 years; median, 9.9 years). Nineteen patients were male, and ten were female. Patient weight ranged from 2.5 to 94 kg (mean 37.3 kg; median 35.2 kg). Of these patients, indications for transplantation were cardiomyopathy in 18, congenital heart disease (CHD) in 7, and graft failure (re-transplantation) in 4. The cardiomyopathy group included 13 patients with dilated cardiomyopathy, 3 with restrictive cardiomyopathy, 1 with noncompaction, and 1 with hypertrophic cardiomyopathy. The CHD group was heterogeneous, and all patients in this group had previous failed corrective or palliative heart surgery (2 hypoplastic left heart syndrome, 2 pulmonary atresia with intact ventricular septum, 1 total anomalous pulmonary venous return, 1 truncus arteriosus, and 1 double-outlet right ventricle).
Indications for ECMO
ECMO was initiated because of primary graft dysfunction in 17 patients (59%). These patients were either cannulated in the operating room, intensive care unit, or post-anesthesia care unit. They were all cannulated within 24 hours of cardiac transplantation (Table 1). The remaining patients required ECMO support after transplantation because of transplant rejection (11 patients), or CAV established by coronary angiography (1 patient). All patients who were deemed to have rejection or CAV requiring ECMO support had recovered during the initial postoperative period and were re-hospitalized remote from their heart transplantation (Table 1).
Table 1.
Early Outcome of Post-transplantation ECMO
|
ECMO for graft
dysfunction |
|||
|
| |||
| Initial diagnosis |
Post-operative day to
ECMO |
Days on
ECMO |
Survival to hospital
discharge |
|
| |||
| Cardiomyopathy | 0 | 2 | Survived |
| Cardiomyopathy | 0 | 8 | Survived |
| Cardiomyopathy | 0 | 5 | Survived |
| Cardiomyopathy | 0 | 4 | Survived |
| Cardiomyopathy | 0 | 31 | Survived |
| Cardiomyopathy | 0 | 2 | Survived |
| Cardiomyopathy | 0 | 2 | Survived |
| CHD | 1 | 6 | Survived |
| CHD | 1 | 3 | Survived |
| Cardiomyopathy | 1 | 12 | Died |
| Cardiomyopathy | 0 | 2 | Died |
| Cardiomyopathy | 1 | 6 | Died |
| CHD | 0 | 2 | Died |
| CHD | 0 | 7 | Died |
| CHD | 0 | 4 | Died |
| Retransplantation | 0 | 24 | Died |
| Retransplantation | 0 | 10 | Died |
|
| |||
| ECMO for late rejection | |||
|
| |||
| Initial diagnosis |
Post-operative day to
ECMO |
Days on
ECMO |
Survival to hospital
discharge |
|
| |||
| Cardiomyopathy | 23 | 5 | Survived |
| Cardiomyopathy | 304 | 1 | Survived |
| Cardiomyopathy | 214 | 3 | Survived |
| Cardiomyopathy | 1147 | 8 | Survived |
| Retransplantation | 2763 | 34 | Survived |
| Cardiomyopathy | 326 | 16 | Survived |
| CHD | 711 | 8 | Survived |
| CHD | 203 | 4 | Survived |
| Cardiomyopathy | 68 | 6 | Survived |
| Re-transplantation | 649 | 4 | Died |
| Cardiomyopathy | 145 | 15 | Died |
|
| |||
| ECMO for CAV | |||
|
| |||
| Initial diagnosis |
Post-operative day to
ECMO |
Days on
ECMO |
Survival to hospital
discharge |
|
| |||
| Cardiomyopathy | 677 | 11 | Died |
CAV = cardiac allograft vasculopathy; CHD = congenital heart disease; ECMO = extracorporeal membrane oxygenation; POD = postoperative day
Outcomes
The length of ECMO support ranged from 1 to 34 days, (mean 8.4 days, median 6 days). There was not a significant difference in length of ECMO support between the patients with primary graft dysfunction and patients with transplantation rejection/CAV (interquartile range 2 to 9 days vs. 4 to 15 days; P = 0.244). Of these 29 patients, 18 survived to hospital discharge (62%). Survival was similar among patients with transplantation rejection/CAV compared to those who required ECMO due to primary graft dysfunction (75% vs. 53%; P = 0.14) (Figure 1). Of those patients who died prior to discharge, 4 patients experienced multi-organ system failure, 2 experienced cardiac failure, 1 experienced central nervous system failure, and 2 died of septic shock. In 5 cases, ECMO was withdrawn upon the family’s request (Table 1). In both groups, patient survival to hospital discharge was not associated with gender, age, indication for OHT, past surgical history, ischemic time, CBP time, intraoperative or postoperative ECMO cannulation, time between OHT and ECMO, or duration of ECMO (Tables 2 and 3). Patient weight was not associated with survival in patients who required ECMO for support of primary graft dysfunction, but increased weight was inversely associated with survival in patients suffering from late rejection (P = 0.009) (Tables 2 and 3).
Figure 1.
Survival trends for post-OHT patients requiring ECMO for primary graft dysfunction versus rejection
Table 2.
Pediatric heart transplantation recipients who required ECMO support post-operatively for primary graft dysfunction (N = 17)
| All patients (N=17) | Survivors (N= 9) | Nonsurvivors (N= 8) | ||
|---|---|---|---|---|
| Data | Mean ± SD Frequency |
Mean ± SD Frequency |
Mean ± SD Frequency |
P-value |
| Demographics | ||||
| Recipient weight (kg) | 24.9 ± 22.9 | 17.1 ± 18.9 | 33.6 ± 25.0 | 0.277 |
| Age at OHT (years) | 6.7 ± 7.5 | 4.3 ± 6.9 | 8.9 ± 7.8 | 0.2 |
|
| ||||
| Gender | 0.637 | |||
| Male | 9 | 4 | 5 | |
| Female | 8 | 5 | 3 | |
|
| ||||
| Indications for OHT | 0.205 | |||
| Cardiomyopathy | 10 | 7 | 3 | |
| CHD | 5 | 2 | 3 | |
| Re-transplantation | 2 | 0 | 2 | |
|
| ||||
| Past surgical history | 0.185 | |||
| Previous OHT | 1 | 1 | 0 | |
| Previous palliative surgery | 5 | 1 | 4 | |
| No past surgeries | 8 | 6 | 2 | |
| Both | 3 | 1 | 2 | |
|
| ||||
| Transplantation | ||||
| Ischemic time (min) | 239.3 ± 87.1 | 245.2 ± 77.9 | 233.3 ± 102.6 | >0.99 |
| Total CBP time (min) | 202.7 ± 90.2 | 191.2 ± 87.9 | 214.2 ± 99.3 | 0.699 |
|
| ||||
| ECMO cannulation | >0.99 | |||
| Intraoperative | 6 | 1 | 5 | |
| Postoperative | 11 | 8 | 3 | |
|
| ||||
| Days b/w OHT and ECMO | 0.3 ± 0.4 | 0.2 ± 0.4 | 0.3 ±0.5 | >99 |
| ECMO duration (days) | 7.6 ± 8.1 | 7.0 ±9.2 | 8.4 ±7.2 | 0.423 |
Table 3.
Pediatric heart transplantation recipients who required ECMO support post-operatively for clinical evidence of rejection (N= 12)
| All patients (N=12) | Survivors (N= 9) | Nonsurvivors (N= 3) | ||
|---|---|---|---|---|
| Data | Mean ± SD Frequency |
Mean ± SD Frequency |
Mean ± SD Frequency |
P-value |
| Demographics | ||||
| Recipient weight (kg) | 46.5 ± 20.9 | 38.19 ± 13.90 | 71.33 ± 19.63 | 0.009 |
| Age at OHT (years) | 12.0 ± 4.1 | 12.65 ± 4.08 | 9.97 ± 4.46 | 0.373 |
|
| ||||
| Gender | ||||
| Male | 10 | 8 | 2 | |
| Female | 2 | 1 | 1 | |
|
| ||||
| Indications for OHT | ||||
| Cardiomyopathy | 7 | 5 | 2 | 0.714 |
| CHD | 3 | 3 | 0 | |
| Re-transplantation | 2 | 1 | 1 | |
|
| ||||
| Past surgical history | ||||
| Previous OHT | 3 | 2 | 1 | 0.755 |
| Previous palliative surgery | 3 | 3 | 0 | |
| No past surgeries | 6 | 4 | 2 | |
| Both | ||||
|
| ||||
| Transplantation | ||||
| Ischemic time (min) | 189.4 ± 58.3 | 199.4 ± 55.9 | 166.0 ± 68.4 | 0.517 |
| Total CBP time (min) | 138.4 ± 57.3 | 135.3 ± 64.2 | 145.7 ± 47.7 | 0.833 |
|
| ||||
| ECMO cannulation | ||||
| Intraoperative | 1 | 1 | 0 | >0.99 |
| Postoperative | 11 | 8 | 3 | |
|
| ||||
| Days b/w OHT and ECMO | 602.6 ± 756.3 | 691.4 ± 855.7 | 336.0 ± 273.3 | 0.600 |
| ECMO duration (days) | 9.6 ± 9.0 | 10.3 ± 9.9 | 7.3 ± 6.7 | 0.482 |
Discussion
There has been much advancement in the field of mechanical circulatory support since ECMO was first introduced in the early 1970s (8). From 2000 to 2013, implementation of ECMO for cardiac indications in the pediatric population has grown (9). ECMO is now widely used for maintenance of cardiac output in pediatric patients with cardiogenic shock or cardiopulmonary resuscitation failure as a bridge to recovery, ventricular assist device implantation or cardiac transplantation (6, 7, 10). ECMO has also been implemented postoperatively in patients who are unable to wean from CPB or who develop post-cardiotomy low cardiac output syndrome (11). Similarly, ECMO is a practical option for pediatric OHT patients with depressed postoperative cardiac output, allowing time for graft recovery from stress of organ recovery and surgery, as well as gradual adaptation to a new hemodynamic environment (12-14).
Our recent data over a 12-year period confirms that ECMO can be lifesaving in the pediatric post-cardiac transplantation population, as both a bridge to graft recovery or re-transplantation. Currently, overall survival after heart transplantation in the pediatric population is approximately 90% at one year and 78% at five years (15). Primary graft failure and rejection are complications that significantly affect morbidity and mortality, with primary graft failure accounting for 35% of deaths within the first 30 days after transplantation, and the combination of primary graft failure and rejection accounting for more than half of all deaths in the first three years following transplantation (15). Of our 203 pediatric patients who received OHT, we found that 29 required ECMO for cardiac support after their transplantation (14%), either in the immediate postoperative period for primary graft failure (17 patients), or remotely due to clinical findings of rejection and CAV (12 patients) (Table 1). Our cohort included young patients and those with congenital heart disease. In one report, 17% of patients < 1 year of age required ECMO for primary graft failure. In another report, primary graft failure as the cause of death among pediatric and adult patients with congenital heart disease dying within 30 days of transplantation has been reported to be 9%. We speculate that the relatively high incidence of post-OHT requirement for ECMO encountered at our institution is in part due to our large congenital heart disease population, as well as our acceptance of high-risk transplantation patients from referring centers. These populations are known to experience significantly increased early post-OHT complications and mortality (16). Our center also transplants young patients. We, therefore, believe that our experience is similar to other centers with regard to the incidence of primary graft dysfunction and not related to a specific institutional factor at our center (such as a surgical technique or medical practice). In our post-transplantation population who experienced these life-threatening complications, 9 of 12 patients with rejection survived to hospital discharge after ECMO (75%), and 9 of 17 patients with primary graft dysfunction survived to hospital discharge after ECMO (53%). Although we did not randomize our patients to ECMO, leading to possible selection bias, the utilization of ECMO at our institution for this patient population may have improved the survival of this high-risk group.
Primary graft dysfunction versus late rejection
We recognize that our cohort of patients who required ECMO for post-transplantation hemodynamic support represent two distinct populations requiring mechanical circulatory support under different circumstances. Among our 29 patients, 17 required ECMO soon after transplantation for primary graft failure. All of these patients were cannulated for ECMO within 24 hours of their heart transplantation. In contrast, the remainder of our cohort required mechanical circulatory support for clinical evidence of rejection and CAV. These patients did not require ECMO support until months to years after their initial heart transplantation. These two groups were thus analyzed separately because of their inherent differences. Although we did not find that survival was significantly impacted by any of our examined clinical or demographic variables, we made several observations.
First, we found that in patients who required ECMO for graft dysfunction, there was a trend toward improved survival in patients who had no past surgical history (Table 2). Specifically, patients who had previously undergone surgical palliation prior to heart transplantation appeared to have a lower survival rate when cannulated for ECMO. While this finding did not reach statistical significance in our study, we speculate that this possible association may be related to increased technical difficulty in transplanting a patient who has had previous surgery, including previous anatomic manipulation and associated comorbidities such as end-organ injury and pulmonary vascular disease. Our observation is consistent with the knowledge that congenital heart disease, for which previous palliation may have been attempted, is an individual risk factor for post-heart transplantation mortality (17-18).
Second, we found that survival may be improved in patients who required ECMO support for rejection compared with those who were cannulated for ECMO for primary graft failure, although we were not able to reach statistical significance in our limited cohort (Figure 1). A similar observation was noted in 2011 by Chen and colleagues who found that 70% of patients requiring ECMO for support of cardiac rejection survived to wean off of mechanical circulatory support or re-transplantation, compared with only 50% of patients requiring ECMO for primary graft dysfunction (18).
We speculate that this is partially reflective of the inherently fragile hemodynamic state of patients who are immediately post-cardiac transplantation. Not only have these patients failed medical management to require heart transplantation, they have also undergone CPB. In addition, primary graft failure may occur due to recipient and donor risk factors. Recipient risk factors may include the need for mechanical support prior to transplantation, a history of congenital heart disease, increased pulmonary vascular resistance, and renal dysfunction. Donor risk factors may include increased donor-recipient size discrepancy, prolonged graft ischemic time, and administration of cardiopulmonary resuscitation and/or anoxic damage to the donor prior to organ recovery (17-18). Beyond implementation of ECMO to support a graft that may have impaired function post-operatively, many of these risk factors are not amenable to specific treatment. In contrast, patients who experience rejection profound enough to require mechanical circulatory support will undergo aggressive and protocolized anti-rejection therapy. The ability to direct treatment while concurrently supporting cardiac output with ECMO allows for improved recovery in patients who experience graft failure from rejection.
Length of support
An extended requirement for mechanical circulatory support is reflective of poor clinical status, and such an extension exposes patients to a continual risk of secondary complications (12, 19). There have been conflicting findings as to whether prolonged support with ECMO affects survival outcome. Several studies have found that a requirement for mechanical circulatory support greater than four days was associated with a significantly decreased survival outcome, while others have found no such correlation (12, 14, 19, 20). We did not find patient survival to be associated with duration of ECMO (Tables 2 and 3). In fact, one survivor in our cohort was supported with ECMO for 34 days prior to decannulation. Patients with primary graft dysfunction who were started on ECMO intraoperatively did not have a significantly higher mortality compared to those who were cannulated postoperatively. We speculate that ECMO complications and individual patient pre-cannulation end-organ condition may play a role in ultimate survival to discharge. Future studies would be required to confirm these hypotheses. Our findings support the use of ECMO for primary graft dysfunction and for prolonged need.
Patient age and size
We did not find any significant association between patient age and survival to discharge (Tables 2 and 3). Although smaller and younger patients may be technically difficult surgical patients, our findings show that weight and age are not associated with survival in post-transplantation patients requiring ECMO for support of primary graft dysfunction. Our observations are consistent with recent pediatric post-transplantation data among patients greater than one year of age showing no significant association between age and early survival (15). In our transplant patients who required ECMO support for late rejection, however, we found an unexpected and unexplained association between weight and mortality (P = 0.009) (Table 3). Further investigation of this population is required to identify potential causality.
Although ventricular assist device (VAD) support in this population is conceptually possible, only certain children may benefit from such devices. Two limitations to VAD support in the pediatric population are the small size of pediatric patients and the potential for urgent deployment need. Until the recent approval of the EXCOR Pediatric Ventricular Assist Device (Berlin Heart GmbH, Berlin), no known VAD small enough for young children was available. In addition, deployment of a VAD is impractical in emergent situations such as cardiac failure or resuscitation.
Limitations
Limitations of our study include our small sample size as well as a lack of clearly defined criteria for the use of ECMO after OHT at our center. Furthermore, our patients were not randomized to receive ECMO, therefore introducing likely selection bias. In addition, institutional differences in graft preservation after recovery as well as immunosuppressant regimens may affect the ability to generalize our results to other institutions, providers and patients. Also, institutional ECMO familiarity and expertise likely varies. A larger sample size may be required to see larger or additional differences between survivors to hospital discharge and nonsurvivors. Our study is retrospective and observational in nature, potentially affecting the ability to generalize our findings to other institutions, providers, and patients.
Conclusion
To date, this is the largest single-center pediatric series examining the impact of ECMO in post-heart transplantation patients over a 12-year period. In our experience, ECMO provides hemodynamic support in the setting of cardiac failure and can be used successfully after pediatric OHT for primary graft dysfunction or rejection. Our study serves to help inform pediatric cardiothoracic surgery, cardiology and critical care providers that ECMO can be used successfully after pediatric OHT for primary graft dysfunction or rejection/CAV with acceptable survival. While describing and distinguishing two distinct patient populations who may require ECMO support following transplantation, namely, those with primary graft dysfunction and rejection/CAV, our experience may help to preserve scarce cardiac grafts. We believe that a large, multicenter, prospective cohort study will be useful to clearly define criteria for the use of ECMO after OHT to maximize survival.
Acknowledgements
Statistical analyses for this research were supported by NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number UL1TR000124.
Footnotes
Author Contributions:
Jennifer Su, MD is the primary researcher and principal investigator of this project. She was involved in development the research question, reviewed the available databases and organized the information for analysis, and drafted the manuscript.
Robert Kelly, MD is the faculty sponsor and primary advisor of this project. He supervised the development of the project, provided research mentorship and advice throughout the project, and closely reviewed and revised the manuscript.
Tristan Grogan, MS was the primary statistician involved with the project. Together with David Elashoff, he drafted the statistics section of the manuscript and provided the statistical analyses of the data.
David Elashoff, PhD was the overseeing statistician involved with the project. Together with Tristan Grogan, he drafted the statistics section of the manuscript and provided the statistical analyses of the data.
Juan Alejos, MD is a faculty advisor from the Pediatric Cardiology division, providing access to the heart transplantation and ECMO databases at UCLA. He also contributed to development of the project, detailed the immunosuppression and transplantation protocols, and revised the manuscript.
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