Adult Congenital Heart Disease Transplantation: Does Univentricle Physiology Impact Early Mortality?

BACKGROUND: With patients with congenital heart disease increasingly living into adulthood, there is a growing population of patients with adult congenital heart disease (ACHD) who have heart failure. Limited data exist on evaluating heart transplantation in this population. METHODS: A retrospective review was performed of patients with ACHD who underwent heart transplantation from November 1990 to January 2023. Kaplan-Meier, cumulative incidence accounting for competing risk of death, and subgroup analyses comparing those patients with biventricular (BiV) and univentricular (UniV) physiology were performed. Data are presented as median (interquartile range [IQR]) or counts (%). RESULTS: A total of 77 patients with a median age of 36 years (IQR, 27-45 years) were identified, including 57 (74%) BiV and 20 (26%) UniV patients. Preoperatively, UniV patients were more likely to have cirrhosis (9 of 20 [45.0%] vs 4 of 57 [7.0%]; P < .001) and protein losing enteropathy (4 of 20 [20.0%] vs 1 of 57 [1.8%]; P = .015). Multiorgan transplantation was performed in 23 patients (30%) and more frequently in UniV patients (10 [50%] vs 13 [23%]; P = .04). Operative mortality was 6.5%, 2 of 20 (10%) among UniV patients and 2 of 57 (4%) among BiV patients (P = .276). Median clinical follow-up was 6.0 years (IQR, 1.4-13.1 years). Survival tended to be lower among UniV patients compared with BiV patients, particularly within the first year (P = .09), but it was similar for survivors beyond 1 year. At 5 years, the incidence of rejection was 28% (IQR, 17%-38%) and that of coronary allograft vasculopathy was 16% (IQR, 7%-24%). CONCLUSIONS: Underlying liver disease and the need for heart-liver transplantation were significantly higher among UniV patients. Survival tended to be lower among UniV patients, particularly within the first year, but it was similar for survivors beyond 1 year.

Prevalence and spectrum of infectious and inflammatory dermatologic conditions occurring in pediatric heart transplant patients on a predominantly mTOR-based immune suppressive regimen: A retrospective chart review.

INTRODUCTION: Pediatric heart transplant patients are routinely followed in dermatology clinics due to elevated risk of cutaneous malignancy. However, transplant patients may experience other, non-cancer-related dermatologic conditions including skin infections, inflammatory diseases, and drug eruptions that can cause significant medical and psychosocial comorbidity. METHODS: A retrospective chart review of all pediatric heart transplant patients at Mayo Clinic Children's Center in Rochester, MN, was performed to determine the prevalence and spectrum of non-cancer dermatologic conditions. Statistical analysis was conducted to look for associations between episodes of rejection and skin condition development. RESULTS: Of the 65 patients who received heart transplants under the age of 18 and were followed at Mayo Clinic, 69% (N = 45) were diagnosed with at least one skin condition between transplant and the time of most recent follow-up. Sixty-two percent (N = 40) of patients were diagnosed with an inflammatory skin condition (most commonly acne and atopic dermatitis), 45% (N = 29) with an infectious skin condition (most commonly warts and dermatophyte infection), and 32% (N = 21) with a drug eruption (most commonly unspecified rash and urticaria). No association was found between presence of skin disease and number of rejection episodes. CONCLUSIONS: Non-cancer dermatologic conditions are prevalent within pediatric heart transplant recipients and may directly impact their medical needs and quality of life. Dermatologist involvement in the care of post-transplant pediatric patients is important, not only for cancer screening but also for diagnosis and treatment of common infectious and inflammatory skin conditions.

Optimizing Referral Timing of Patients With Fontan Circulatory Failure for Heart Transplant.

BACKGROUND: There are no criteria guiding the timing of heart transplant referral for Fontan patients, nor are there any characteristics of those deferred or declined listing reported. This study examines comprehensive transplant evaluations for Fontan patients of all ages, listing decisions, and outcomes to inform referral practices. METHODS: Retrospective review of 63 Fontan patients formally assessed by the advanced heart failure service and presented at Mayo Clinic transplant selection committee meetings (TSM) January 2006 to April 2021. The study is compliant with the Helsinki Congress and Declaration of Istanbul and included no prisoners. Statistical analysis was performed with Wilcoxon Rank Sum and Fisher's Exact tests. RESULTS: Median age at TSM was 26 years (17.5, 36.5). Most were approved (38/63 [60%]); 9 of 63 (14%) were deferred and 16 of 63 (25%) were declined. Approved patients more commonly were <18 years old at TSM (15/38 [40%] vs 1/25 [4%], P = .002) compared with those deferred/declined. Complications of Fontan circulatory failure were less common in approved vs deferred/declined patients: ascites (15/38 [40%] vs 17/25 [68%], P = .039), cirrhosis (16/38 [42%] vs 19/25 [76%], P = .01), and renal insufficiency (6/38 [16%] vs 11/25 [44%], P = .02). Ejection fraction and atrioventricular valve regurgitation did not differ between groups. Pulmonary artery wedge pressure was overall high normal (12 mm Hg [9,16]) but higher in deferred/declined vs approved patients, 14.5 (11, 19) vs 10 (8, 13.5) mm Hg, P = .015. Overall survival was significantly lower in deferred/declined patients (P = .0018). CONCLUSION: Fontan patient referral for heart transplant at younger age and before the onset of end-organ complications is associated with increased approval for transplant listing.

Correlation between non-invasive to invasive right-heart data in paediatric heart transplant patients.

BACKGROUND: Paediatric studies have shown serum N-terminal pro b-type natriuretic peptide levels to be a valuable tool in the surveillance of myocardial function and an early biomarker for rejection in transplant patients. The correlation between low mean right atrial pressure and increased inferior vena cava collapsibility index is well studied in adults. Our study aims to assess correlation between non-invasive measurements (serum N-terminal pro b-type natriuretic peptide, inferior vena cava dimensions collapsibility, tricuspid regurgitation, and left ventricular remodelling index to invasive mean right atrial pressure in paediatric heart transplant patients). METHODS: A single centre, retrospective chart review of the paediatric transplant patients from 0 to 21 years of age was performed between 2015 and 2017. Thirty-nine patients had complete data which includes cardiac catheterisation, transthoracic echocardiogram, and serum N-terminal pro b-type natriuretic peptide levels done within a two weeks of interval. RESULTS: A higher inferior vena cava collapsibility index correlated with a lower mean right atrial pressure (r = -0.21, p = 0.04) and a larger inferior vena cava diameter in expiration indexed to body surface area (IVCmax/BSA0.5) correlated with a higher mean right atrial pressure (r = 0.29, p = 0.01). There was a correlation between elevated N-terminal pro b-type natriuretic peptide and inferior vena cava collapsibility index (r = -0.38, p = 0.0001), IVCmax/BSA0.5 (r = 0.25, p = 0.0002), and mean right atrial pressure (r = 0.6, p = 0.0001). CONCLUSION: Serum N-terminal pro b-type natriuretic peptide levels correlated to non-invasive measurements (inferior vena cava collapsibility index and IVCmax/BSA0.5) and to the invasive mean right atrial pressure. Non-invasive (IVC-CI IVCmax/BSA0.5) correlates with elevated mean right atrial pressure in this population. Together, these may serve as a reliable surveillance tool in assessing right heart filling pressures and cardiac function within the paediatric heart transplant patient.

Early aspirin use and the development of cardiac allograft vasculopathy in pediatric heart transplant recipients: A pediatric heart transplant society analysis.

BACKGROUND: Cardiac allograft vasculopathy (CAV) remains a leading cause of graft loss in pediatric heart transplant (HTx) recipients. Adult literature suggests that aspirin (ASA) use in the early post-HTx period may reduce the risk of CAV. This study aimed to determine the impact of early ASA use on the development of CAV in pediatric HTx recipients. METHODS: All subjects <17 years of age at time of primary HTx who survived ≥3 years without evidence of CAV were identified for inclusion from the Pediatric Heart Transplant Society database (1996-2019). Early ASA use was defined as ASA started within the first 3 years post-HTx and was classified as continuous or intermittent. Frequency of ASA use was described across centers. Kaplan-Meier method assessed freedom from CAV and overall graft survival. Multiphase parametric hazard analyses and propensity score matched analysis were used to identify independent risk factors. RESULTS: 3,011 patients were included with 387 (13%) receiving continuous ASA, 676 (22%) receiving intermittent ASA, and 1,948 (65%) receiving no ASA. ASA use was highly variable across centers (0%-100%). At baseline patients receiving continuous ASA therapy demonstrated inferior graft survival (p < 0.001) and worse freedom from CAV (p = 0.002), but with lower CAV grades (p = 0.05). In multiphase parametric hazard modeling continuous ASA use was not independently associated with CAV, but remained associated with inferior graft survival. Propensity-matched sub-analysis between continuous and no ASA groups demonstrated no difference in freedom from CAV or overall graft loss. CONCLUSIONS: ASA use varies widely across pediatric HTx centers. Early ASA use did not reduce the risk of CAV or graft loss in pediatric heart transplant recipients.

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.

Heart Transplantation in Children With Down Syndrome.

Background Children with Down syndrome (DS) have a high risk of cardiac disease that may prompt consideration for heart transplantation (HTx). However, transplantation in patients with DS is rarely reported. This project aimed to collect and describe waitlist and post- HTx outcomes in children with DS. Methods and Results This is a retrospective case series of children with DS listed for HTx. Pediatric HTx centers were identified by their participation in 2 international registries with centers reporting HTx in a patient with DS providing detailed demographic, medical, surgical, and posttransplant outcome data for analysis. A total of 26 patients with DS were listed for HTx from 1992 to 2020 (median age, 8.5 years; 46% male). High-risk or failed repair of congenital heart disease was the most common indication for transplant (N=18, 69%). A total of 23 (88%) patients survived to transplant. All transplanted patients survived to hospital discharge with a median posttransplant length of stay of 22 days. At a median posttransplant follow-up of 2.8 years, 20 (87%) patients were alive, 2 (9%) developed posttransplant lymphoproliferative disorder, and 8 (35%) were hospitalized for infection within the first year. Waitlist and posttransplant outcomes were similar in patients with and without DS (P=non-significant for all). Conclusions Waitlist and post-HTx outcomes in children with DS selected for transplant listing are comparable to pediatric HTx recipients overall. Given acceptable outcomes, the presence of DS alone should not be considered an absolute contraindication to HTx.

Eisenmenger Syndrome: JACC State-of-the-Art Review.

Although major breakthroughs in the field of pediatric cardiology, cardiac surgery, intervention, and overall care improved the outlook of congenital heart disease, Eisenmenger syndrome (ES) is still encountered and remains a complex clinical entity with multisystem involvement, including secondary erythrocytosis, increased thrombotic and bleeding diathesis, high arrhythmogenic risk, progressive heart failure, and premature death. Clearly, care for ES is best delivered in multidisciplinary expert centers. In this review, we discuss the considerable recent progress in understanding the complex pathophysiology of ES, means of prognostication, and improvement in clinical outcomes achieved with pulmonary arterial hypertension-targeted therapies. Additionally, we delineate areas of uncertainty in various aspects of care, discuss gaps in current evidence, and review current status in less privileged countries and propose initiatives to reduce disease burden. Finally, we propose the application of emerging technologies to enhance the delivery and quality of health care related to ES and beyond.

Obesity and dyslipidemia predict cardiac allograft vasculopathy and graft loss in children and adolescents post-heart transplant: A PHTS multi-institutional analysis.

BACKGROUND: Obesity and dyslipidemia afflict children of all ages. We explored the prevalence of obesity and dyslipidemia in pediatric heart transplant (HT) recipients and its effects on cardiac allograft vasculopathy (CAV) and survival. METHODS: This study included primary HT recipients (≤18 years) transplanted between 01/1996 and 12/2018 included in the Pediatric Heart Transplant Society database. Obesity was categorized according to WHO/CDC guidelines and dyslipidemia according to the National Cholesterol Education Program. Kaplan-Meier analyses for CAV and graft loss stratified for BMI and lipid panels were generated and risk factors identified using multivariate analyses. RESULTS: Among 6291 HT patients (median age [range] at HT = 4.3 [0.6-12.8] years; 45% Female; 68% White), 56% had a normal BMI at HT. Obese patients at HT had an increased risk for graft loss (HR 1.19, 95% CI 1.01-1.4, p = .04). Poor total cholesterol (TC), LDL-C, and TG were associated with the risk of both CAV (HR 1.79, p < .0001; HR 1.65, p = .0015; HR 1.53, p < .0001, respectively) and graft loss (HR 1.58, p = .0008; HR 1.22, p = .04; HR 1.43, p = .0007, respectively). CONCLUSIONS: Pediatric patients who are obese at the time of HT and dyslipidemic at 1 year post-HT are at an increased risk for CAV and graft loss. Preventative interventions may reduce morbidity and mortality among this cohort.

Successful management of an arteriovenous malformation with trametinib in a patient with capillary-malformation arteriovenous malformation syndrome and cardiac compromise.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is an autosomal dominant condition characterized by multifocal, noncontiguous pink patches on the skin that often have a surrounding pale halo. In some cases, an association with a fast flow, arteriovenous malformation (AVM) can be identified. Here, we describe a case report of a 16-year-old woman with CM-AVM syndrome and significant cardiac compromise successfully treated with trametinib, a mitogen-activated protein kinase (MEK) inhibitor.

Clinical and hemodynamic characteristics of the pediatric failing Fontan.

AIM: To describe the clinical and hemodynamic characteristics of Fontan failure in children listed for heart transplant. METHODS: In a nested study of the Pediatric Heart Transplant Society, 16 centers contributed information on Fontan patients listed for heart transplant between 2005and 2013. Patients were classified into four mutually exclusive phenotypes: Fontan with abnormal lymphatics (FAL), Fontan with reduced systolic function (FRF), Fontan with preserved systolic function (FPF), and Fontan with "normal" hearts (FNH). Primary outcome was waitlist and post-transplant mortality. RESULTS: 177 children listed for transplant were followed over a median 13 (IQR 4-31) months, 84 (47%) were FAL, 57 (32%) FRF, 22 (12%) FNH, and 14 (8%) FPF. Hemodynamic characteristics differed between the 4 groups: Fontan pressure (FP) was most elevated with FPF (median 22, IQR 18-23, mmHg) and lowest with FAL (16, 14-20, mmHg); cardiac index (CI) was lowest with FRF (2.8, 2.3-3.4, L/min/m2). In the entire cohort, 66% had FP >15 mmHg, 21% had FP >20 mmHg, and 10% had CI <2.2 L/min/m2. FRF had the highest risk of waitlist mortality (21%) and FNH had the highest risk of post-transplant mortality (36%). CONCLUSIONS: Elevated Fontan pressure is more common than low cardiac output in pediatric failing Fontan patients listed for transplant. Subtle hemodynamic differences exist between the various phenotypes of pediatric Fontan failure. Waitlist and post-transplant mortality risks differ by phenotype.

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.

1p36 Deletion Syndrome and Left Ventricular Non-compaction Cardiomyopathy-Two Cases Report.

1p36 deletion is the most common terminal deletion syndrome in humans. Herein, we report two cases, a 5-month-old female and a 14.5-year-old female, both with 1p36 deletion and left ventricular non-compaction cardiomyopathy. They presented with severely depressed left ventricle function and underwent heart transplantation with excellent outcomes. Given the incidence of heart defects and cardiomyopathy in 1p36 deletion syndrome, it should be recommended that children with this genetic condition have screening for cardiac disease. These cases add to the current literature by demonstrating the potential therapeutic options for non-compaction in 1p36 deletion syndrome and showed the favorable outcomes.

Safety of a Noninvasive Expandable Electromagnetic Prosthesis with an In Situ Ventricular Assist Device: A Case Report.

CASE: An 8-year-old girl was diagnosed with osteosarcoma of the distal femur. She underwent chemotherapy and wide resection with implantation of a noninvasive electromagnetic expandable distal femur prosthesis. Ninety-three days after chemotherapy, she developed anthracycline-induced cardiomyopathy with heart failure for which a ventricular assist device was placed. Device compatibility was tested, and she was successfully lengthened. CONCLUSION: Expandable prostheses allow limb length maintenance in skeletally immature patients who undergo limb salvage. Chemotherapy for osteosarcoma involves anthracyclines with a dose-dependent side effect of cardiotoxicity. Patients can be successfully and safely lengthened with expandable electromagnetic prostheses with in situ ventricular assist devices.

Berlin Heart EXCOR and ACTION post-approval surveillance study report.

BACKGROUND: The Berlin Heart EXCOR Pediatric (EXCOR) ventricular assist device (VAD) was introduced in North America nearly 2 decades ago. The EXCOR was approved under Humanitarian Device Exemption status in 2011 and received post-market approval (PMA) in 2017 from Food and Drug Administration. Since the initial approval, the field of pediatric mechanical circulatory support has changed, specifically with regard to available devices, anticoagulation strategies, and the types of patients supported. This report summarizes the outcomes of patients supported with EXCOR from the Advanced Cardiac Therapies Improving Outcomes Network (ACTION) registry. These data were part of the PMA surveillance study (PSS) required by the Food and Drug Administration. METHODS: ACTION is a learning collaborative of over 40 pediatric heart failure programs worldwide, which collects data for all VAD implantations as one of its initiatives. All patients in North America with EXCOR implants reported to ACTION from 2018 to 2020 (n = 72) who had met an outcome were included in the EXCOR PSS group. This was compared with a historical, previously reported Berlin Heart EXCOR study group (Berlin Heart study [BHS] group, n = 320, 2007‒2014). RESULTS: Patients in the PSS group were younger, were smaller in weight/body surface area, were more likely to have congenital heart disease, and were less likely to receive a bi-VAD than those in the BHS group. Patients in the PSS group were less likely to be in Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 and were supported for a longer duration. The primary anticoagulation therapy for 92% of patients in the PSS group was bivalirudin. Success, defined as being transplanted, being weaned for recovery, or being alive on a device at 180 days after implantation, was 86% in the PSS group compared with 76% in the BHS group. Incidence of stroke was reduced by 44% and the frequency of pump exchange by 40% in the PSS group compared with those in the BHS group. Similarly, all other adverse events, including major bleeding, were reduced in the PSS group. CONCLUSIONS: The PSS data, collected through ACTION, highlight the improvement in outcomes for patients supported with EXCOR compared with the outcomes in a historical cohort. These findings may be the result of changes in patient care practices over time and collaborative learning.

Angiographic evidence of backward compression wave: systolic compression of septal perforators in a child with hypertrophic cardiomyopathy.

Intracoronary wave intensity analysis in hypertrophic cardiomyopathy has shown a large backward compression wave due to compressive deformation of the intramyocardial coronary arteries in systole. The authors describe the angiographic evidence of this backward compression wave, which has not been described in this physiological context and can be a marker of poor prognosis.

Berlin Excor Cannulation of Left Atrial Appendage in Left Ventricular Restrictive Physiology: A Novel Bailout Strategy.

Ventricular assist device (VAD) management continues to be a challenge in the presence of restrictive physiology. Left atrial (LA) decompression is not satisfactory even with good function and position of the left ventricular cannula. We describe an alternate approach with LA cannulation via the left atrial appendage (LAA) as a rescue strategy in a patient who had restrictive physiology, in our case was secondary to viral myocarditis acute systolic heart failure with subsequent insidious diffuse endomyocardial fibrosis and superimposed massive calcification, causing inadequate emptying of the left ventricle despite optimal VAD apical cannula position.

Pediatric SubQ-ICD implantation, a single center review of the inter-muscular technique.

INTRODUCTION: Pediatric patients with cardiomyopathies are at risk for sudden death and may need implantable cardioverter defibrillators (ICD's), but given their small size and duration of use, children are at increased risk for complications associated with ICD use. The subcutaneous ICD presents a favorable option for children without pacing indications. Unfortunately, initial pediatric studies have demonstrated a high complication rate, likely due to the 3-incision technique employed. MATERIAL AND METHODS: Patients with ICD but no pacing indication were retrospectively reviewed after implantation of subcutaneous ICD via the two-incision technique. In half of the patients, 10-J impedance test was also performed to compare with impedance obtained after defibrillation threshold testing with 65-J. RESULTS: Twelve patients were included. The median age was 14 years (range 10-16 years) with eight males included (72.7%). The median weight was 55 kg (range 29 kg-75.1 kg). Follow-up had a median of 11.5 months (range 2-27 months). The median body mass index was 18.4 kg/m squared (range 15.5-27.9 kg/m squared). One patient suffered a minor complication after tearing off the incisional adhesive strips early and required a non-invasive repair in clinic. Shock impedance had a median of 55 J (range 48-68 J). There was one appropriate shock/charge and no inappropriate shocks during follow-up. CONCLUSION: The two-incision, intermuscular technique appears to have a lower acute complication rate than prior reports, in our cohort of 12 pediatric patients.

Orthotopic Heart Transplantation in a Child with Single Ventricle after Pneumonectomy.

We report a 6-year-old with single ventricle physiology secondary to tricuspid atresia who had cardiorespiratory failure who was not a candidate for further single ventricle palliation. The patient underwent planned staged left pneumonectomy for recurrent pneumonias secondary to bronchomalacia followed by orthotopic heart transplantation. This aggressive approach improved the patient candidacy for heart transplantation by removing the source of recurrent infection and respiratory failure (left lung).

Cardiac transplantation in children with Noonan syndrome.

NS and related RAS/MAPK pathway (RASopathy) disorders are the leading genetic cause of HCM presenting in infancy. HCM is a major cause of morbidity and mortality in children with Noonan spectrum disorders, especially in the first year of life. Previously, there have been only isolated reports of heart transplantation as a treatment for heart failure in NS. We report on 18 patients with NS disorders who underwent heart transplantation at seven US pediatric heart transplant centers. All patients carried a NS diagnosis: 15 were diagnosed with NS and three with NSML. Sixteen of eighteen patients had comprehensive molecular genetic testing for RAS pathway mutations, with 15 having confirmed pathogenic mutations in PTPN11, RAF1, and RIT1 genes. Medical aspects of transplantation are reported as well as NS-specific medical issues. Twelve of eighteen patients described in this series were surviving at the time of data collection. Three patients died following transplantation prior to discharge from the hospital, and another three died post-discharge. Heart transplantation in NS may be a more frequent occurrence than is evident from the literature or registry data. A mortality rate of 33% is consistent with previous reports of patients with HCM transplanted in infancy and early childhood. Specific considerations may be important in evaluation of this population for heart transplant, including a potentially increased risk for malignancies as well as lymphatic, bleeding, and coagulopathy complications.