Heterogeneous outcomes of liver disease after heart transplantation for a failed Fontan procedure.

BACKGROUND: Fontan-associated liver disease (FALD) uniformly affects patients with long-term Fontan physiology. The effect of isolated heart transplant (HT) on the course of FALD post-HT is not well understood. METHODS: We evaluated serial liver imaging pre- and post-HT to assess liver changes over time in a single-center retrospective analysis of Fontan HT recipients who had pre- and ≥1-year post-HT liver imaging. Available patient demographic and clinical data were reviewed, including available liver biopsy results. RESULTS: Serial liver imaging was available in 19 patients with a median age at HT of 12 years (range 3-23), the median age from Fontan to HT of 5.7 years (range 0.8-16), and the median time from imaging to follow up of 27 months (range 12-136 months). Pre-HT liver imaging was classified as follows: normal (n=1), congested (n=9), fibrotic (n=7), and cirrhotic (n=2). The majority of transplanted patients (15/19) had improvement in their post-HT liver imaging, including 13 patients with initially abnormal imaging pre-HT having normal liver imaging at follow-up. One patient had persistent cirrhosis at 26-month follow-up, one patient had unchanged fibrosis at 18-month follow-up, and one patient progressed from fibrosis pre-HT to cirrhosis post-HT at 136 months. No patients had overt isolated liver failure during pre- or post-HT follow-up. Liver biopsy did not consistently correlate with imaging findings. CONCLUSIONS: Post-HT liver imaging evaluation in Fontan patients reveals heterogeneous liver outcomes. These results not only provide evidence for the improvement of FALD post-HT but also show the need for serial liver imaging follow-up post-HT.

Early outcomes for low-risk pediatric heart transplant recipients and steroid avoidance: A multicenter cohort study (Clinical Trials in Organ Transplantation in Children - CTOTC-04).

BACKGROUND: Immunosuppression strategies have changed over time in pediatric heart transplantation. Thus, comorbidity profiles may have evolved. Clinical Trials in Organ Transplantation in Children-04 is a multicenter, prospective, cohort study assessing the impact of pre-transplant sensitization on outcomes after pediatric heart transplantation. This sub-study reports 1-year outcomes among recipients without pre-transplant donor-specific antibodies (DSAs). METHODS: We recruited consecutive candidates (<21 years) at 8 centers. Sensitization status was determined by a core laboratory. Immunosuppression was standardized as follows: Thymoglobulin induction with tacrolimus and/or mycophenolate mofetil maintenance. Steroids were not used beyond 1 week. Rejection surveillance was by serial biopsy. RESULTS: There were 240 transplants. Subjects for this sub-study (n = 186) were non-sensitized (n = 108) or had no DSAs (n = 78). Median age was 6 years, 48.4% were male, and 38.2% had congenital heart disease. Patient survival was 94.5% (95% confidence interval, 90.1-97.0%). Freedom from any type of rejection was 67.5%. Risk factors for rejection were older age at transplant and presence of non-DSAs pre-transplant. Freedom from infection requiring hospitalization/intravenous anti-microbials was 75.4%. Freedom from rehospitalization was 40.3%. New-onset diabetes mellitus and post-transplant lymphoproliferative disorder (PTLD) occurred in 1.6% and 1.1% of subjects, respectively. There was no decline in renal function over the first year. Corticosteroids were used in 14.5% at 1 year. CONCLUSIONS: Pediatric heart transplantation recipients without DSAs at transplant and managed with a steroid avoidance regimen have excellent short-term survival and a low risk of first-year diabetes mellitus and PTLD. Rehospitalization remains common. These contemporary observations allow for improved caregiver and/or patient counseling and provide the necessary outcomes data to help design future randomized controlled trials.

Current Topics and Controversies in Pediatric Heart Transplantation: Proceedings of the Pediatric Heart Transplantation Summit 2017.

In October 2017, a pediatric heart transplant summit was held in Seattle-the first of its kind internationally-which focused solely upon controversies in pediatric end-stage heart failure management and pediatric heart transplantation. We selected five of the most popular and contentious topics and asked the speakers to provide a position paper. Worldwide, the vast majority of programs perform only a handful of pediatric heart transplants a year. Because of this, these "orphan" areas of investigation provide an opportunity for us as a community to aggregate our collective knowledge, which may represent the only viable way that we might sort through these complex and controversial issues in the field. We hope this represents the first of many such conferences and that this initial selection of papers encourages us to begin this collaborative process.

Impact of routine surveillance biopsy intensity on the diagnosis of moderate to severe cellular rejection and survival after pediatric heart transplantation.

Data are lacking on RSB intensity and outcomes after pediatric heart transplantation. PHTS centers received a survey on RSB practices from 2005 to present. PHTS data were obtained for 2010-2013 and integrated with center-matched survey responses for analysis. Survey response rate was 82.6% (38/46). Centers were classified as low-, moderate-, and high-intensity programs based on RSB frequency (0-more than 8 RSB/y). RSB intensity decreased with increasing time from HT. Age at HT impacted RSB intensity mostly in year 1, with little to no impact in later years. Most centers have not replaced RSB with non-invasive methods, but many added ECHO and biomarker monitoring. Higher RSB intensity was not associated with decreased 4-year mortality (P=.63) or earlier detection of moderate to severe (ISHLT grade 2R/3R) cellular rejection (RSBMSR) in the first year (P=.87). First-year RSBMSR incidence did not differ with intensity or age at HT. Significant variability exists in RSB intensity, but with no impact on timing and incidence of RSBMSR or 4-year mortality. Reduction in RSB frequency may be safe in certain patients after pediatric HT.

A Novel Surgical Approach to Mechanical Circulatory Support in Univentricular Infants.

BACKGROUND: Historically, the options for mechanical circulatory support in infants, particularly those with single-ventricle physiology, have been limited and outcomes have generally been poor. We report a new approach implemented for long-term support in a series of such patients. METHODS: This study is a single-center case series of 7 patients with single-ventricle physiology after stage 1 palliation supported with mechanical circulatory support using a novel technique, between May 2014 and September 2015. Our technique included modification and implantation of commercially available pediatric cannulae into the common atrium and the ascending aorta or reconstructed neoaorta and utilization of a centrifugal extracorporeal pump. RESULTS: Median circulatory support duration was 64 days (range, 35 to 99). One adverse neurologic event was observed in 1 patient, and bleeding requiring reoperation in 2 patients. Support to recovery, decision, or heart transplantation was accomplished in all cases. Of all patients, 43% were successfully discharged home. CONCLUSIONS: Our experience shows that long-term extracorporeal mechanical circulatory support of patients with underlying single-ventricle physiology after stage 1 palliation is feasible utilizing our technique. This approach overcomes several major challenges encountered in these patients, such as high flow requirement and stability of the cannulae, and allows extubation, rehabilitation, and at times, myocardial recovery.

Berlin Heart EXCOR use in patients with congenital heart disease.

BACKGROUND: Management of mechanical circulatory support in children with congenital heart disease (CHD) is challenging due to physiologic variations and anatomic limitations to device placement. In this study we examine the use of Berlin Heart EXCOR in CHD patients. METHODS: CHD patients were identified from the EXCOR Pediatric Study data set (2007 to 2010). Mortality and serious adverse events were compared between CHD and non-CHD cohorts, and predictors of poor outcomes in the CHD cohort were identified. RESULTS: CHD was present in 29% (n = 59, 18 with 1-ventricle physiology) of all EXCOR patients (N = 204). Successful bridge (transplant or wean) was less likely in CHD patients compared with non-CHD patients (48% vs 80%; p < 0.01). Among CHD patients, no neonates, 25% of infants (30 days to 1 year) and 65% of children (>1 year) were successfully bridged. Pre-implant congenital heart surgery (CHS) and extracorporeal membrane oxygenation (ECMO) on the same admission occurred in 60% of children ≤1 year of age (83% of neonates, 50% of infants), with 8% survival. Regardless of age, patients who did not have CHS and ECMO had 61% survival. Smaller pump, pre-implant bilirubin >1.2 mg/dl and renal dysfunction were independently associated with mortality. CONCLUSIONS: End-organ function at implant reliably predicts adverse outcomes and should be considered when making implant decisions. EXCOR use in neonates and infants with CHD should be approached cautiously. If patients have undergone pre-implant CHS and ECMO, EXCOR support may not provide any survival benefit. EXCOR support in non-infants with CHD is challenging but can be consistently successful with appropriate patient selection.

Impact of age on incidence and prevalence of moderate-to-severe cellular rejection detected by routine surveillance biopsy in pediatric heart transplantation.

BACKGROUND: The effect of age at transplant on rejection detected by routine surveillance biopsy (RSB) in pediatric heart transplant (HT) recipients is unknown. We hypothesized there would be low diagnostic yield and decreased prevalence of rejection detected on RSB in infants (age <1 year) when compared with children (age 1 to 9 years) and adolescents (age 10 to 18 years). METHODS: We utilized Pediatric Heart Transplant Study (PHTS) data from 2010 to 2013 to analyze moderate-to-severe (ISHLT Grade 2R/3R) cellular rejection (MSR) detected only on RSB (RSBMSR). RESULTS: RSB detected 280 of 343 (81.6%) episodes of MSR. RSBMSR was detected in all age groups even >5 years after HT. Infant RSBMSR had a greater proportion (p = 0.0025) occurring >5 years after HT (39.2 vs 18.4 vs 10.8%) and a lower proportion (p = 0.0009) occurring in the first year after HT (25.5 vs 60.6 vs 51.7%) compared with children and adolescents, respectively. Freedom from RSBMSR was 87 ± 7% in infants, 76 ± 6% in children and 73 ± 7% in adolescents 4 years after HT. In 1-year survivors who had RSBMSR in the first year after HT, the risk of RSBMSR occurring in Years 2 to 4 was significantly (p < 0.0001) greater than patients without RSBMSR in the first year (hazard ratio 21.28, 95% confidence interval 10.87 to 41.66), regardless of recipient age. CONCLUSIONS: RSBMSR exists in all age groups after pediatric HT with long-term follow-up. The prevalence in infant recipients is highest >5 years after HT. Those with RSBMSR in the first year after HT are at a high risk for recurrent rejection regardless of age at HT.

Fontan Patient Survival After Pediatric Heart Transplantation Has Improved in the Current Era.

BACKGROUND: Historically, patients with a prior Fontan procedure for complex congenital heart disease (CHD) have been considered at higher risk for death after heart transplant (HT) compared with other HT transplant candidates. With the overall trend of improved survival of pediatric HT recipients, it is unclear of Fontan patient post-HT survival has also improved in the current era. METHODS: Data from the Pediatric Heart Transplant Study database for Fontan patients who underwent HT was compared between the early era (1993 to 2006, n = 150) and late era (2007 to 2014, n = 252). Post-HT survival and pre-HT characteristics were compared among eras and also with non-Fontan CHD patients. RESULTS: At time of HT, Fontan patients in the late era were more likely to require inotropic support, have protein-losing enteropathy, have failure to thrive, and be further from time of Fontan, although less likely to be on ventilator support. Only ventilator support and earlier year of HT were significant risk factors for death in the multivariate analysis. Post-HT Fontan patient survival significantly improved from the early to late era (p = 0.02), particularly in the early phase, with 1-year survival of 77% in the early era and 89% in the late era. Late era non-Fontan CHD patient 1-year post-HT survival was similar to Fontan patients at 92%. CONCLUSIONS: Survival of Fontan patients after HT has significantly improved in the current era. Currently, expected post-HT survival for Fontan patients is on par with other CHD patients. Fontan patients should not be excluded from consideration for HT solely on a history of Fontan.

Is Endomyocardial Biopsy a Safe and Useful Procedure in Children with Suspected Cardiomyopathy?

Endomyocardial biopsy (EMB) is a common procedure used to aid in the diagnosis, prognosis and treatment of suspected pediatric cardiomyopathy. In suspected cardiomyopathy, no multicenter experience has previously reported on the safety and utility of EMBs. Retrospectively, adverse event (AE) and patient and procedural characteristics were obtained at seven institutions participating in the Congenital Cardiac Catheterization Outcomes Project for both a cardiomyopathy (n = 158) and a post-transplant surveillance (n = 2665) cohort. Descriptive information regarding biopsy indication, pathology and clinical management based on EMB findings were retrospectively obtained. High-severity AEs were more common in the cardiomyopathy cohort when compared to the post-transplant surveillance cohort. The cardiomyopathy cohort was younger, more hemodynamically vulnerable and required more cardiorespiratory support during the procedure. The eight high-severity AEs in the cardiomyopathy group included one myocardial perforation, two ECMO cannulations and three deaths following the EMB. Factors associated with high-severity AEs included performing another catheter-based intervention during the EMB and longer fluoroscopy time. Notably, an increased number of biopsy attempts did not increase the risk of an AE. Suspected myocarditis was the most common indication. Diagnostic EMB pathology and thus alteration to clinical management based on pathology occurred more frequently in patients with suspected myocarditis. In conclusion, there is an increased incidence of high-severity AEs in patients undergoing EMB for suspected cardiomyopathy. EMB may be more clinically useful in the management of suspected myocarditis. The increased risk of high-severity AEs when additional interventions are performed highlights the hemodynamic vulnerability in patients with suspected cardiomyopathy.

Autoimmunity Against the Heart and Cardiac Myosin in Children With Myocarditis.

BACKGROUND: Host autoimmune activity in myocarditis has been proposed to play a role in development of cardiac disease, but evidence of autoimmunity and relationship to outcomes have not been evaluated in pediatric myocarditis. METHODS: We performed a multi-institutional study of children with clinical myocarditis. Newly diagnosed patients were followed for up to 12 months and previously diagnosed patients at a single follow-up for serum levels of autoantibodies to human cardiac myosin, beta-adrenergic receptors 1 and 2, muscarinic-2 receptors, and antibody-mediated protein kinase A (PKA) activation in heart cells in culture. Results were compared with those of healthy control children. RESULTS: Both previously diagnosed patient at follow-up (P = .0061) and newly diagnosed patients at presentation (P = .0127) had elevated cardiac myosin antibodies compared with control subjects. Antibody levels were not associated with recovery status at follow-up in either group. PKA activation was higher at presentation in the newly diagnosed patients who did not recovery normal function (P = .042). CONCLUSIONS: Children with myocarditis have evidence of autoantibodies against human cardiac myosin at diagnosis and follow-up compared with control subjects. Differences in antibody-mediated cell signaling may contribute to differences in patient outcomes, as suggested by elevated antibody-mediated PKA activation in heart cells by the serum from nonrecovered patients.

High Frequency of Detection by PCR of Viral Nucleic Acid in The Blood of Infants Presenting with Clinical Myocarditis.

Specific viruses are associated with pediatric myocarditis, but the prevalence of viral DNAemia detected by blood polymerase chain reaction (PCR) is unknown. We evaluated the prevalence of known cardiotropic viruses (enterovirus, adenovirus, human herpesvirus 6, and parvovirus B19) in children with clinical myocarditis (n = 21). Results were compared to pediatric controls with similar viral PCR testing. The majority of positive PCR (89 %) was noted in children ≤12 months of age at diagnosis compared to older children. Infant myocarditis patients (8/10) had increased the prevalence of PCR positivity compared to infant pediatric controls (4/114) (p < 0.0001). Other than age, patient characteristics at diagnosis were similar between PCR-positive and PCR-negative patients. Both PCR-negative myocarditis infants had clinical recovery at follow-up. Of the PCR-positive myocarditis infants, 4 had clinical recovery, 2 developed chronic cardiomyopathy, 1 underwent heart transplant, and 1 died. Infants with clinical myocarditis have a high rate of blood viral positivity, which is higher compared to older children with myocarditis and healthy infant controls. Age-related differences in PCR positivity may be due to differences in host and/or virus characteristics. Our findings suggest that viral blood PCR may be a useful diagnostic tool and identify patients who would potentially benefit from virus-specific therapy.

Successful bridge through transplantation with berlin heart ventricular assist device in a child with failing fontan.

In patients with failed Fontan circulation, end-stage heart failure can develop or Fontan physiology failure requiring transplantation. Experience with ventricular assist device support for these patients as a bridge to heart transplantation has been limited and often not resulted in successful hospital discharge. We report the successful use of the Berlin Heart EXCOR (Berlin Heart, The Woodlands, TX) ventricular assist device in bridging a child with Fontan circulation and systolic dysfunction to heart transplantation and discharge home.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.

BACKGROUND: Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. METHODS: We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. RESULTS: CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. CONCLUSIONS: Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population.

Post-transplant outcomes of children bridged to transplant with the Berlin Heart EXCOR Pediatric ventricular assist device.

BACKGROUND: Recent data suggest that Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device improves waiting list survival for pediatric heart transplant candidates. Little is known about their post-transplant outcomes. The aim of this analysis was to determine whether there was a difference in early survival for children bridged to transplant with EXCOR versus status 1A pediatric heart transplant patients not transplanted with ventricular assist device support. METHODS AND RESULTS: Pediatric heart transplant patients (n=106) bridged to transplantation with EXCOR were compared with a similarly aged cohort (n=1021) within the Organ Procurement and Transplant Network (OPTN) database (both cohorts from May 2007 to December 2010). In the EXCOR group, 12-month post-transplant survival (88.7%) was similar to OPTN patients listed status 1A who were not on ventricular assist device support at transplant (89.3%; P=0.85) and significantly better than 12-month survival in OPTN patients on extracorporeal membrane oxygenation at transplant (60.3%; P<0.001). Rejection (50%) was a significantly (P=0.005) higher cause of 12-month post-transplant mortality in the EXCOR compared with the OPTN group. Death after transplant was also higher in EXCOR patients with congenital heart disease compared with those with cardiomyopathy (26.1% versus 7.2%; P=0.02). Post-transplant survival was similar in EXCOR patients with ≥1 serious adverse event during ventricular assist device support as those without an event during support. CONCLUSIONS: The 12-month post-transplant survival with EXCOR is comparable with overall pediatric heart transplant survival and superior to survival after extracorporeal membrane oxygenation. Neither adverse events during support nor factors associated with mortality during support influence post-transplant survival. Rejection was a significantly greater cause of post-transplant mortality in EXCOR than in OPTN patients.

Human polyomaviruses in children undergoing transplantation, United States, 2008-2010.

Immunocompromised patients are at risk for disease caused by infection by some polyomaviruses. To define the prevalence of polyomaviruses in children undergoing transplantation, we collected samples from a longitudinal cohort and tested for the 9 known human polyomaviruses. All were detected; several were present in previously unreported specimen types.

Early predictors of survival to and after heart transplantation in children with dilated cardiomyopathy.

BACKGROUND: The importance of clinical presentation and pretransplantation course on outcome in children with dilated cardiomyopathy listed for heart transplantation is not well defined. METHODS AND RESULTS: The impact of age, duration of illness, sex, race, ventricular geometry, and diagnosis of myocarditis on outcome in 261 children with dilated cardiomyopathy enrolled in the Pediatric Cardiomyopathy Registry and Pediatric Heart Transplant Study was studied. End points included listing as United Network for Organ Sharing status 1, death while waiting, and death after transplantation. The median age at the time of diagnosis was 3.4 years, and the mean time from diagnosis to listing was 0.62±1.3 years. Risk factors associated with death while waiting were ventilator use and older age at listing in patients not mechanically ventilated (P=0.0006 and P=0.03, respectively). Shorter duration of illness (P=0.04) was associated with listing as United Network for Organ Sharing status 1. Death after transplantation was associated with myocarditis at presentation (P=0.009), nonwhite race (P<0.0001), and a lower left ventricular end-diastolic dimension z score at presentation (P=0.04). In the myocarditis group, 17% (4 of 23) died of acute rejection after transplantation. CONCLUSIONS: Mechanical ventilator use and older age at listing predicted death while waiting, whereas nonwhite race, smaller left ventricular dimension, and myocarditis were associated with death after transplantation. Although 97% of children with clinically or biopsy-diagnosed myocarditis at presentation survived to transplantation, they had significantly higher posttransplantation mortality compared with children without myocarditis, raising the possibility that preexisting viral infection or inflammation adversely affects graft survival.

Trends in the indications and survival in pediatric heart transplants: a 24-year single-center experience in 307 patients.

BACKGROUND: Heart transplantation is the only viable treatment for children with end-stage heart failure due to congenital heart disease (CHD) or cardiomyopathy. This study reviewed the trends in the indications for transplant and survival after transplant during the past 24 years. METHODS: A retrospective review was performed of the 307 heart transplants performed at our center since 1986. To analyze the trends in the indications for transplant as well as operative death and late-survival, the data were divided into three periods in 8-year increments: 1986 to 1993 (50 patients), 1994 to 2001 (116 patients), and 2002 to 2009 (141 patients). RESULTS: The indications for transplantation were 39% cardiomyopathy, 57% CHD, and 4% retransplant. Of the 173 with CHD, 139 (80%) had single-ventricle (SV) anomalies. In the CHD group, transplantation for failed SV palliation, including Fontan procedure, became the predominant indication in the last 8-year interval of our program. Survival after transplant was the best in patients with cardiomyopathy and the worst in patients with failed palliations for SV anomalies, including failed Fontan procedures. CONCLUSIONS: Transplantation for heart failure related to failed SV palliation has become the most common indication for patients with CHD. The high-risk nature of these transplants will have significant implications for heart transplant programs as more infants with SV anomalies survive palliative procedures performed during infancy.

Early survival after heart transplant in young infants is lowest after failed single-ventricle palliation: a multi-institutional study.

BACKGROUND: Infant heart transplant (HT) recipients have the best long-term survival of any age group, but the small donor pool and high early mortality limit the therapeutic effectiveness. We sought to determine the relationship between pre-HT diagnosis and early HT outcome to better define the mortality risk associated with a diagnosis of congenital heart disease (CHD) and to examine differences between early and current HT eras. METHODS: The Pediatric Heart Transplant Study (PHTS) database was used to identify 739 infant HT recipients at age ≤ 6 months between 1993 and 2008 divided into the following etiologic groups: cardiomyopathy (CM), 18%; hypoplastic left heart syndrome (HLHS) without surgery, 41%; HLHS with surgery, 9%; other CHD without surgery, 16%; and other CHD with surgery, 15%. Severity of illness at HT, post-HT survival, and era effects were compared. RESULTS: At 1 year after HT, survival was 89% for the CM group, which was the best, 79% for CHD without surgery, 82% for CHD with surgery, 79% for HLHS without surgery, and 70% for HLHS with surgery, which was the worst outcome. Hazard function analysis demonstrated the difference occurred within the first 3 months after HT. After adjusting for illness severity, differences in mortality risk persisted across etiologic groups. HT survival was similar in the current surgical era for HLHS with surgery, 71% (1993-1998) vs 70% (1999-2008). CONCLUSIONS: Infant HT recipients with different pre-HT diagnoses have significantly different post-HT outcomes. HLHS infants with surgery have the lowest survival and their outcome is unchanged in the current era.

Endomyocardial biopsy and selective coronary angiography are low-risk procedures in pediatric heart transplant recipients: results of a multicenter experience.

BACKGROUND: No prior reports documenting the safety and diagnostic yield of cardiac catheterization and endomyocardial biopsy (EMB) in heart transplant recipients include multicenter data. METHODS: Data on the safety and diagnostic yield of EMB procedures performed in heart transplant recipients were recorded in the Congenital Cardiac Catheterization Outcomes Project database at 8 pediatric centers during a 3-year period. Adverse events (AEs) were classified according to a 5-level severity scale. Generalized estimating equation models identified risk factors for high-severity AEs (HSAEs; Levels 3-5) and non-diagnostic biopsy samples. RESULTS: A total of 2,665 EMB cases were performed in 744 pediatric heart transplant recipients (median age, 12 years [interquartile range, 4.8, 16.7]; 54% male). AEs occurred in 88 cases (3.3%), of which 28 (1.1%) were HSAEs. AEs attributable to EMB included tricuspid valve injury, transient complete heart block, and right bundle branch block. Amongst 822 cases involving coronary angiography, 10 (1.2%) resulted in a coronary-related AE. There were no myocardial perforations or deaths. Multivariable risk factors for HSAEs included fewer prior catheterizations (p = 0.006) and longer case length (p < 0.001). EMB yielded sufficient tissue for diagnosis in 99% of cases. Longer time since heart transplant was the most significant predictor of a non-diagnostic biopsy sample (p < 0.001). CONCLUSIONS: In the current era, cardiac catheterizations involving EMB can be performed in pediatric heart transplant recipients with a low AE rate and high diagnostic yield. Risk of HSAEs is increased in early post-transplant biopsies and with longer case length. Longer time since heart transplant is associated with non-diagnostic EMB samples.

The impact of heart failure severity at time of listing for cardiac transplantation on survival in pediatric cardiomyopathy.

BACKGROUND: The survival benefit of heart transplantation in adult heart failure is greatest for the sickest patients and negligible for patients not requiring inotropic or mechanical support. We hypothesized a similar survival benefit of heart transplantation for childhood cardiomyopathies with heart failure. METHODS: A merged data set of children registered in both the Pediatric Cardiomyopathy Registry and the Pediatric Heart Transplant Study was used to assess differences in mortality before and after transplant in patients with different levels of heart failure severity. Severity was scored 2 if mechanical ventilatory or circulatory support was required, 1 if intravenous inotropes were required, or 0 if no support was required. RESULTS: For 332 eligible children, 12-month mortality after listing was 9% for those with a severity score of 0 (n = 105), 16% with a score of 1 (n = 118), and 26% with a score of 2 (n = 109; p = 0.002) with a 3%, 8%, and 20% mortality with severity scores at listing of 0, 1, and 2, respectively, occurring before transplant. Patients listed with a score of 0 frequently deteriorated: 50% received an allograft or died before transplant with severity scores of 1 or 2. The risk of deterioration increased with previous surgery (relative risk, 3.84; p = 0.03) in the short-term and with lower left ventricular mass z-score at time of presentation (relative risk, 1.74; p = 0.003) in the longer-term. CONCLUSION: Pediatric cardiomyopathy patients who require high levels of support receive a survival benefit from heart transplantation that is not shared by patients not requiring intravenous inotropic or mechanical support.