Hybrid delivery of behavioral health screening and prevention intervention for pediatric heart transplant recipients and families: A randomized pilot study.

BACKGROUND: A significant number of pediatric heart transplant recipients and their families experience post-traumatic stress symptoms following transplantation, which can impact recipient behavioral and medical health outcomes. Preventive behavioral health interventions may improve outcomes, especially if interventions can be delivered at a distance to decrease barriers to mental health care. This pilot study examined the acceptability and accessibility of an evidence-informed resilience training program delivered using a video telehealth platform. A secondary aim was to assess the preliminary efficacy of the intervention on recipient behavioral health outcomes, perceived barriers to recipient medication adherence, parent behavioral health outcomes, and family functioning. METHODS: Seventeen heart transplant recipients (8-18 years old) and their families were recruited and randomly assigned to a treatment as usual (n = 8) or an intervention group (n = 9). Baseline assessment data collected included demographic information and validated behavioral health measures. Follow-up assessments included the validated measures and acceptability and satisfaction ratings. RESULTS: The study demonstrated that the program has high acceptability by recipients and parents, and a positive impact on recipients and parents, including significant reductions in youth behavioral difficulties as well as parent depression and post-traumatic stress symptoms. CONCLUSIONS: Results of this study are promising and call for further evaluation of hybrid delivery models for behavioral health screening and prevention interventions for pediatric heart transplant recipients and their families.

Deceased donor organ allocation in pediatric transplantation: A historical narrative.

BACKGROUND: Since the earliest clinical successes in solid organ transplantation, the proper method of organ allocation for children has been a contentious subject. Over the past 30-35 years, the medical and social establishments of various countries have favored some degree of preference for children on the respective waiting lists. However, the specific policies to accomplish this have varied widely and changed frequently between organ type and country. METHODS: Organ allocation policies over time were examined. This review traces the reasons behind and the measures/principles put in place to promote early deceased donor transplantation in children. RESULTS: Preferred allocation in children has been approached in a variety of ways and with varying degrees of commitment in different solid organ transplant disciplines and national medical systems. CONCLUSION: The success of policies to advantage children has varied significantly by both organ and medical system. Further work is needed to optimize allocation strategies for pediatric candidates.

Fontan-associated liver disease after heart transplant.

BACKGROUND: Fontan associated liver disease (FALD) potentially impacts Fontan patients undergoing heart transplant. This multi-center study sought to identify pre-transplant risk factors and characterize any post-transplant liver recovery in those patients undergoing heart-alone transplant. METHODS: Review of Fontan patients at 12 pediatric institutions who underwent heart transplant between 2001-2019. Radiologists reviewed pre and post-transplant liver imaging for fibrosis. Laboratory, pathology and endoscopy studies were reviewed. RESULTS: 156 patients underwent transplant due to decreased ventricular function (49%), protein losing enteropathy (31%) or plastic bronchitis (10%); median age at transplant was 13.6 years (interquartile range IQR 7.8, 17.2) with a median of 9.3 years (IQR 3.2, 13.4) between the Fontan operation and transplant. Few patients had pre-transplant endoscopy (18%), and liver biopsy (19%). There were 31 deaths (20%). The median time from transplant to death was 0.5 years (95% Confidence Interval CI 0.0, 3.6). The five-year survival was 73% (95% CI 64%, 83%). Deaths were related to cardiac causes in 68% (21/31) and infection in 6 (19%). A pre-transplant elevation in bilirubin was a predictor of death. Higher platelet levels were protective. Immediate post-transplant elevations in creatinine, AST, ALT, and INR were predictive of death. Advanced liver fibrosis identified on ultrasound, computed tomography, or magnetic resonance imaging was not predictive of death. Liver imaging suggested some improvement in liver congestion post-transplant. CONCLUSIONS: Elevated bilirubin, but not fibrosis on liver imaging, was associated with post-heart transplant mortality in Fontan patients in this multicenter retrospective study. Additionally, heart transplant may alter the progression of FALD.

Outcomes of infants with pulmonary atresia with intact ventricular septum listed for heart transplantation: A multi-institutional study.

BACKGROUND: Management of infants with pulmonary atresia/intact ventricular septum (PA/IVS) is variable. Because of higher mortality in more severe forms, heart transplant (HT) is an acceptable approach, but waitlist and post-transplant outcomes are unclear. This study compared outcomes of infants with PA/IVS vs. other single ventricle (SV) anatomies listed for HT. METHODS: Data from the Pediatric Heart Transplant Society (1993-2018) were analyzed for survival and risk factors for mortality. RESULTS: Of 1617 SV infants, 300 had PA/IVS (19%) and 1317 had other SV (81%). Overall, 1-, 5-, and 10-year survival was higher among PA/IVS (74%, 65%, 61%) versus other SV infants (62%, 54%, 50%, p = .004). While waitlist mortality was similar between groups (p = .09), PA/IVS was an independent predictor of improved waitlist survival (HR 0.68, p = .03), and PA/IVS infants had higher incidence of waitlist removal (8% vs. 5.5%, p = .03), most commonly for being "too well." Post-transplant survival was superior among PA/IVS versus other SV infants (1- and 5-year survival 93% and 81% vs. 80% and 71%, p < .0001). Risk factors for PA/IVS waitlist mortality (2008-2018) included extracorporeal membrane oxygenation and mechanical ventilation. Prior aortopulmonary (AP) shunt among PA/IVS infants was associated with improved waitlist survival. CONCLUSIONS: Overall survival among PA/IVS infants listed for HT exceeds that of other SV infants with PA/IVS identified as an independent predictor of improved waitlist and post-transplant survival. Prior AP shunt among listed PA/IVS infants was associated with improved waitlist outcomes, though, which may reflect a listing selection bias.

The Effect of Infectious Complications During Ventricular Assist Device Use on Outcomes of Pediatric Heart Transplantation.

To describe the impact of infectious adverse events (IAEs) during ventricular assist device (VAD) support on graft loss, infection, and rejection after pediatric heart transplant (HT). Pedimacs data were linked to Pediatric Heart Transplant Society (PHTS) data for patients receiving a VAD followed by HT between September 2012 and December 2016. Linked patients were categorized into IAE on VAD (group A) and no IAE on VAD (group B). Infectious adverse event locations included nondevice, device (external or internal), and sepsis. Post-HT outcomes for analysis were graft loss, infection, and rejection. Time-dependent analysis included Kaplan-Meier and multiphase parametric hazard function analysis. We linked 207 patients (age 9.4 ± 6.3 years). Post-HT follow-up was 19.4 patient-months (<8 days-4.1 years). Group A included 42 patients (20%) with 62 IAEs. Group B included 165 patients without an IAE. Group A patients were younger (7.4 ± 6.1 vs. 9.5 ± 6.3 years; p = 0.03), waited longer for HT (5.3 ± 4.1 vs. 2.9 ± 2.5 months; p = 0.0005), and were hospitalized longer post-HT (42 ± 59 vs. 23 ± 22 days; p = 0.05). VAD-related IAEs were rare (N = 11). Groups A and B had similar freedom from first post-HT infection, rejection, and graft loss (all p > 0.1). However, patients with VAD-related IAE were somewhat more likely to experience rejection (p = 0.03) and graft loss (p = 0.01). Children with an IAE on VAD who survive to HT are younger, wait longer for HT, and remain hospitalized longer than those without an IAE on VAD. Overall, IAE on VAD did not impact post-HT outcomes, but VAD-related IAE may be associated with graft loss and rejection.

Recessive ciliopathy mutations in primary endocardial fibroelastosis: a rare neonatal cardiomyopathy in a case of Alstrom syndrome.

Among neonatal cardiomyopathies, primary endocardial fibroelastosis (pEFE) remains a mysterious disease of the endomyocardium that is poorly genetically characterized, affecting 1/5000 live births and accounting for 25% of the entire pediatric dilated cardiomyopathy (DCM) with a devastating course and grave prognosis. To investigate the potential genetic contribution to pEFE, we performed integrative genomic analysis, using whole exome sequencing (WES) and RNA-seq in a female infant with confirmed pathological diagnosis of pEFE. Within regions of homozygosity in the proband genome, WES analysis revealed novel parent-transmitted homozygous mutations affecting three genes with known roles in cilia assembly or function. Among them, a novel homozygous variant [c.1943delA] of uncertain significance in ALMS1 was prioritized for functional genomic and mechanistic analysis. Loss of function mutations of ALMS1 have been implicated in Alstrom syndrome (AS) [OMIM 203800], a rare recessive ciliopathy that has been associated with cardiomyopathy. The variant of interest results in a frameshift introducing a premature stop codon. RNA-seq of the proband's dermal fibroblasts confirmed the impact of the novel ALMS1 variant on RNA-seq reads and revealed dysregulated cellular signaling and function, including the induction of epithelial mesenchymal transition (EMT) and activation of TGFß signaling. ALMS1 loss enhanced cellular migration in patient fibroblasts as well as neonatal cardiac fibroblasts, while ALMS1-depleted cardiomyocytes exhibited enhanced proliferation activity. Herein, we present the unique pathological features of pEFE compared to DCM and utilize integrated genomic analysis to elucidate the molecular impact of a novel mutation in ALMS1 gene in an AS case. Our report provides insights into pEFE etiology and suggests, for the first time to our knowledge, ciliopathy as a potential underlying mechanism for this poorly understood and incurable form of neonatal cardiomyopathy. KEY MESSAGE: Primary endocardial fibroelastosis (pEFE) is a rare form of neonatal cardiomyopathy that occurs in 1/5000 live births with significant consequences but unknown etiology. Integrated genomics analysis (whole exome sequencing and RNA sequencing) elucidates novel genetic contribution to pEFE etiology. In this case, the cardiac manifestation in Alstrom syndrome is pEFE. To our knowledge, this report provides the first evidence linking ciliopathy to pEFE etiology. Infants with pEFE should be examined for syndromic features of Alstrom syndrome. Our findings lead to a better understanding of the molecular mechanisms of pEFE, paving the way to potential diagnostic and therapeutic applications.

Case Report: Whole Exome Sequencing Identifies Compound Heterozygous Variants in TSFM Gene Causing Juvenile Hypertrophic Cardiomyopathy.

We report a case of hypertrophic cardiomyopathy and lactic acidosis in a 3-year-old female. Cardiac and skeletal muscles biopsies exhibited mitochondrial hyperplasia with decreased complex IV activity. Whole exome sequencing identified compound heterozygous variants, p.Arg333Trp and p.Val119Leu, in TSFM, a nuclear gene that encodes a mitochondrial translation elongation factor, resulting in impaired oxidative phosphorylation and juvenile hypertrophic cardiomyopathy.

Treatment of post-transplant lymphoproliferative disorder (PTLD) in a heart transplant recipient with chimeric antigen receptor T-cell therapy.

Post-transplant lymphoproliferative disorders (PTLD) are a group of lesions that can complicate solid organ or hematopoietic stem cell transplantation and are often associated with Epstein-Barr virus (EBV). The treatment of PTLD is dependent on the type of lesion and includes a wide range of therapies, but chimeric antigen receptor (CAR) T-cell therapy has not previously been reported as a treatment option for PTLD. We present a patient who developed refractory PTLD in her right retroperitoneum, right inguinal and iliac chains, and right axillary region shortly after heart transplantation and was treated with CAR T-cell therapy. She could not tolerate complete discontinuation of immunosuppression due to the risk of rejection of a life-supporting graft. The patient's PTLD responded to CAR T-cell therapy, and her heart was monitored throughout the treatment course without any signs of rejection or ventricular dysfunction. CAR T-cell therapy may be a viable treatment option in patients who develop PTLD after a solid organ transplant.

Rapidly progressive heart failure requiring transplantation in muscular dystrophy: a need for frequent screening.

Fukuyama congenital muscular dystrophy weakens both skeletal and cardiac muscles, but the rate of cardiomyopathic progression can accelerate faster than that of skeletal muscles. A 14-year-old boy with Fukuyama congenital muscular dystrophy presented with mild skeletal myopathy but severe cardiomyopathy requiring heart transplantation within 1 year of declining heart function. These patients need frequent screening regardless of musculoskeletal symptoms.

Extracorporeal membrane oxygenation support after pediatric orthotopic heart transplantation.

Mechanical circulatory support has been used for more than 30 yr 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. 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. Two hundred and three pediatric patients underwent OHT between 1998 and 2010 at our institution. Twenty-nine of these patients experienced post-transplantation cardiac failure requiring ECMO support, 18 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. ECMO provides hemodynamic support in the setting of cardiac failure and can be used successfully after pediatric OHT for primary graft dysfunction or rejection.

Outcomes of fetal listed patients awaiting heart transplantation.

HTx in neonates is mainstay therapy for those with severe cardiomyopathies and congenital heart disease. Fetal listing for HTx has been proposed as a way to increase the potential window for a donor with outcomes predicted to be similar to the neonatal population. Data from the PHTS, a prospective multicenter study, were used to examine the outcomes of fetuses listed between 1993 and 2009. Four thousand three hundred and sixty-five children were listed for HTx during this period. Fetuses comprised 1% and neonates 19.8% of listed patients. In those patients listed as fetus and transplanted, the median wait time from listing to HTx was 55 days (range 4-255), with a median of 25 days (range 0-233) after birth. By six months post-listing, a higher proportion of fetal listed patients had undergone HTx with a lower waitlist mortality when compared with neonate. There was no significant difference in survival following HTx between the two group (p = 0.4). While the results of this study may be less applicable to current practice due to changes in referrals for fetal listing, they do indicate that fetal listing can be a reasonable option. These results are of particular interest at the present time given the ongoing public discourse on the proposed elimination of fetal listing within UNOS.

Does cytomegalovirus serology impact outcome after pediatric heart transplantation?

BACKGROUND: Cytomegalovirus (CMV) infection has been implicated in a number of complications after heart transplantation. A recent study suggested that children with positive CMV serology (CMV(+)) before transplantation are at increased risk of developing coronary allograft vasculopathy (CAV) and death when compared with CMV(-) recipients. We analyzed data from the Pediatric Heart Transplant Study Group to determine the impact of recipient CMV status and CMV mismatching on outcome. In addition, the use and efficacy of CMV prophylaxis were studied. METHODS: Subjects <18 years of age who underwent heart transplantation during the period from 1993 to 2007 were analyzed. Those transplants in which either the recipient or donor were <6 months of age were excluded due to the confounding effects of maternal antibody. The primary outcome variable was freedom from CAV (mild or greater). Secondary outcomes included freedom from death and freedom from clinical CMV infection. Risk factors were assessed using parametric hazard regression. RESULTS: Of the 1,598 subjects included in the analysis, 637 (40%) were CMV(+) at the time of transplantation. Some form of CMV prophylaxis was administered to 67% of all recipients, most commonly with a CMV mismatch (donor CMV(+)/recipient CMV(-)). Freedom from clinical CMV infection at 5 years was 91%. Pre-transplant CMV serology was not associated with mortality (p = 0.40) or risk of developing CAV (p = 0.10). CMV mismatch was associated with increased risk of clinical CMV disease (p < 0.001). The use of CMV prophylaxis had no association with mortality or development of CAV. There was also no significant association between CMV prophylaxis and the development of clinical CMV infection. CONCLUSIONS: CMV(+) serology at time of pediatric heart transplantation had no demonstrable association with death or development of CAV. CMV(-) recipients who receive a CMV(+) organ are at increased risk of clinical CMV disease. CMV prophylaxis was commonly used, although further studies are needed to establish an optimal approach for prevention of CMV disease in this population.

The corrected QT interval before and after heart transplantation.

Heart donor candidates have severe neurologic injuries that have been associated with significant prolongation of the corrected QT (QTc) interval. Screening for an underlying abnormality of cardiac repolarization such as the long-QT syndrome thus becomes difficult. The aims of this study were to establish normal values and determine factors associated with prolongation of pre- and post-transplantation QTc intervals in a large cohort of heart transplantation donors and recipients. The medical records of 179 donors and 112 recipients were reviewed for historical, electrocardiographic, and neuroimaging data. After linear regression analysis, gunshot wounds were associated with the shortest mean pre-transplantation QTc interval of 447 +/- 51 ms (p = 0.016), whereas all other mechanisms of brain injury were associated with markedly prolonged QTc intervals. Overall, the mean QTc interval decreased from 467 +/- 58 to 446 +/- 47 ms (p <0.001), the mean QRS duration increased from 87 +/- 16 to 98 +/- 21 ms (p <0.001), and the mean QT dispersion did not change significantly after transplantation. The only factor associated with a prolonged QTc interval in the post-transplantation period was hypokalemia, with a mean QTc of 468 +/- 37 ms (p = 0.047). In conclusion, the mechanism of donor brain injury is associated with alterations in the pre-transplantation QTc interval, with the shortest intervals related to gunshot wounds. Fewer than 5% of the donor population was found to have QTc interval > or =580 ms. For those afflicted by gunshot wounds, <5% had QTc intervals > or =550 ms. This information can be used in pre-transplantation donor assessment, and post-transplantation management can be tailored to avoid the occurrence of ventricular arrhythmia.

Nesiritide improves hemodynamics in children with dilated cardiomyopathy: a pilot study.

BACKGROUND: This study aimed to obtain hemodynamic measurements of nesiritide in children with dilated cardiomyopathy. METHODS: A prospective, randomized, double-blinded, placebo-controlled pilot study was conducted in the pediatric intensive care unit at the University of California, Los Angeles. All subjects younger than 21 years admitted to the pediatric intensive care unit with a diagnosis of dilated cardiomyopathy and submitted to cardiac catheterization were randomized to receive either nesiritide or placebo. Right heart catheterization with Swan-Ganz catheter placement was performed. Nesiritide was infused over 24 h. Hemodynamic data were obtained before, during, and after the 24-h nesiritide infusion. The measures obtained included pulmonary capillary wedge pressure (PCWP), central venous pressure, mean pulmonary arterial pressure (MPAP), systolic arterial blood pressure (SBP), cardiac index, and systemic vascular resistance. RESULTS: The study included 20 children: 9 randomized to nesiritide and 11 to placebo. At 24 h, the mean decreases in PCWP, MPAP, and SBP were significantly greater for nesiritide than for placebo: PCWP (-5.3 vs. 1.2 mmHg; p = 0.02), MPAP (-8.0 vs. 0.4 mmHg; p = 0.006), SBP (-7.9 vs. 2.6 mmHg; p = 0.04). CONCLUSIONS: Nesiritide significantly decreases PCWP, MPAP, and SBP in children with dilated cardiomyopathy.

Growth and weight gain of prepubertal children after cardiac transplantation.

This study evaluated changes in growth parameters after pediatric heart transplantation and identified factors associated with the changes after pediatric heart transplantation (OHT). We retrospectively evaluated the somatic growth of 46 children <11 yr of age who underwent OHT for changes in weight, height, and BMI. The patient age range was 3.5 months to 10.7 yr. Gain in Z score for weight and BMI was significant at six months post-OHT (mean weight Z score changed from -1.1 to -0.1 and mean BMI Z score changed from -0.1 to 1.3; p < 0.001). After six months post-OHT, there was no further significant change in weight or BMI Z score. Height Z score did not show significant change from pre-OHT at six months, one yr, or two yr post-OHT. Eight patients (17%) became overweight during the two-yr follow-up period as evidenced by a BMI Z score > 2. Multivariate analysis showed length of steroid treatment as a predictor for negative height Z score change, and age at transplant as a predictor for positive height Z score change. Post-OHT, weight significantly increases without proportional increases in height, resulting in a significant proportion of these children becoming obese. Length of steroid therapy is negatively related to the "catch-up" linear growth following OHT.

The use of Doppler tissue imaging to predict cellular and antibody-mediated rejection in pediatric heart transplant recipients.

DTI indices have been associated with cellular rejection in adult heart transplant recipients, but their predictive value in pediatric recipients is unknown. The purpose of this study was to evaluate DTI measures in the detection of cellular and AMR in pediatric heart transplant recipients. One hundred and forty-eight pediatric heart transplant recipients who had 267 cardiac catheterization procedures with EMB, echocardiogram with DTI, and BNP level performed on the same day were included in the study. For the mitral and tricuspid valves, the ratios (E/E') between the early diastolic inflow velocity by pulsed Doppler (E, m/s) and the early diastolic annular velocity by DTI (E', m/s) were obtained and compared between subjects with and without rejection. Of the 148 recipients, 30 subjects had a total of 37 episodes of rejection: 10 cellular (>or=1B), 17 AMR, and 10 biopsy-negative clinical rejection. Mitral and tricuspid valve E/E' ratios were significantly higher in rejectors than in non-rejectors (5.5 +/- 1.3 vs. 4.4 +/- 1.4, p < 0.001 and 4.9 +/- 2.1 vs. 4.1 +/- 1.5, p < 0.01, respectively). By multivariate linear regression, mitral valve E/E' was an independent predictor of rejection. Mitral and tricuspid valve E/E' <5.0 had 93% and 89% NPV, respectively, for rejection. Mitral and tricuspid valve E/E' ratios <5.0 may be useful non-invasive screening measures to exclude rejection in pediatric heart transplant recipients.

Danon disease with typical early-onset cardiomyopathy in a male: focus on a novel LAMP-2 mutation.

We report a case of a 16-yr-old male with Danon disease caused by a novel mutation in the LAMP-2 gene. Mutations in the LAMP-2 gene result in the absence of LAMP-2 on immunohistochemical staining of muscle tissue, thus defining Danon disease, a rare X-linked myopathy. It is characterized clinically by HCM or left ventricular hypertrophy, a WPW pattern on ECG, variable degrees of muscular weakness (skeletal myopathy), mental retardation, and retinal changes. The patient presented with severe skeletal muscular weakness and respiratory failure. He also had a history of two OHTs, the first one for severe HCM and the second for allograft rejection. The patient's myopathy was initially presumed to be exclusively related to steroid-induced "critical care myopathy." However, further evaluation with a thigh muscle biopsy revealed autophagic vacuoles with sarcolemnal features suggestive of a lysosomal storage disorder. DNA analysis ultimately identified a previously unreported hemizygous IVS6+3_+6delGAGT splice site deletion mutation in the LAMP-2 gene located within the 5' splice site of intron 6, consistent with Danon disease.

Humoral rejection in pediatric orthotopic heart transplantation.

BACKGROUND: Pediatric heart transplant grafts may fail without evidence of cellular rejection or transplant coronary artery disease. The role of antibody-mediated humoral rejection (HR) in graft failure has not yet been described in the pediatric population. METHODS: We reviewed the medical records of 103 pediatric heart transplantations performed at our institution from July 1997 to June 2004. Biopsy specimens were evaluated for HR histologically and by immunoperoxidase and immunofluorescence staining. Risk factors for HR were determined by statistical analysis. Graft survival curves were constructed and compared for patients testing negative or positive for HR. RESULTS: A total of 358 endomyocardial biopsies (EMBs) from 103 pediatric heart transplant patients (age 3 weeks to 20 years; 52% males) were analyzed for HR. Thirty-six grafts (32%) showed evidence of HR. Grafts with a history of HR during the first year after transplant had a 47% failure rate over 3 years, compared with 29% of those hearts with no evidence of HR (p = 0.06). Although patients with congenital heart disease (CHD) appeared to be at greatest risk for developing HR (p = 0.01), patients with positive donor-specific crossmatch data showed a trend toward more significant risks for HR (p = 0.055). Hemodynamic data (including pulmonary capillary wedge pressure [PCWP] and cardiac index [CI]), left ventricular ejection fraction (LVEF), gender matching, recipient age, race of recipient vs donor and pre-transplant panel-reactive antibody (PRA) were not predictive of HR. CONCLUSIONS: Patients with a pathologic diagnosis of HR have increased graft failure rates and overall mortality. Patients with congenital heart disease and positive cross-match results may be at increased risk for HR.

Cellular rejection of the conduction system after orthotopic heart transplantation for congenital atrioventricular block.

We report a case of severe acute cellular rejection of the cardiac allograft conduction system in a 15-month-old girl who received orthotopic heart transplantation (OHT) for congestive heart failure from a congenital heart block. Post-operatively, the patient was treated for clinical evidence of rejection, but did not have electrocardiographic findings of heart block. Six weeks after transplantation, the patient developed sudden-onset bradycardia and died. Autopsy showed severe acute cellular rejection involving primarily the conduction system. Cellular rejection of the cardiac conduction system is a potentially lethal complication of OHT. Although diagnostic modalities to predict or detect ongoing cellular rejection in the conduction system are limited, recognizing the early signs, such as post-operative heart block, may prevent devastating consequences.