Sacubitril/Valsartan in Pediatric Heart Failure (PANORAMA-HF): A Randomized, Multicenter, Double-Blind Trial.

BACKGROUND: Sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), is an established treatment for heart failure (HF) with reduced left ventricular ejection fraction. It has not been rigorously compared with angiotensin-converting enzyme inhibitors in children. PANORAMA-HF (Prospective Trial to Assess the Angiotensin Receptor Blocker Neprilysin Inhibitor LCZ696 Versus Angiotensin-Converting Enzyme Inhibitor for the Medical Treatment of Pediatric HF) is a randomized, double-blind trial that evaluated the pharmacokinetics and pharmacodynamics (PK/PD), safety, and efficacy of sacubitril/valsartan versus enalapril in children 1 month to <18 years of age with HF attributable to systemic left ventricular systolic dysfunction (LVSD). METHODS: Children with HF attributable to LVSD were randomized to sacubitril/valsartan versus enalapril to assess the efficacy and safety of sacubitril/valsartan at 52 weeks of follow-up. The primary end point of the study was to determine whether sacubitril/valsartan was superior to enalapril for the treatment of pediatric patients with HF attributable to systemic LVSD, assessed using a primary global rank end point consisting of ranking patients from worst to best on the basis of clinical events such as death, listing for urgent heart transplant, mechanical life support requirement, worsening HF, New York Heart Association (NYHA)/Ross class, Patient Global Impression of Severity (PGIS), and Pediatric Quality of Life Inventory physical functioning domain. The change from baseline to 52 weeks in NT-proBNP (N-terminal pro-B-type natriuretic peptide) was an exploratory end point. RESULTS: A total of 375 children (mean age, 8.1±5.6 years; 52% female) were randomized to sacubitril/valsartan (n=187) or enalapril (n=188). At week 52, no significant difference was observed between the 2 treatment arms in the global rank end point (Mann-Whitney probability, 0.52 [95% CI, 0.47-0.58]; Mann-Whitney odds, 0.91 [95% CI, 0.72-1.14]; P=0.42). At week 52, clinically meaningful reductions were observed in both treatment arms in NYHA/Ross, PGIS, Patient Global Impression of Change, and NT-proBNP, without significant differences between groups. Adverse events were similar between treatment arms (incidence: sacubitril/valsartan, 88.8%; enalapril, 87.8%), and the safety profile of sacubitril/valsartan was acceptable in children. CONCLUSIONS: In this study, sacubitril/valsartan did not show superiority over enalapril in the treatment of children with HF attributable to systemic LVSD using the prespecified global rank end point. However, both treatment arms showed clinically meaningful improvements over 52 weeks. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02678312.

Long-term outcomes for pediatric heart transplant recipients transitioning to adult care teams.

BACKGROUND: There are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams. METHODS: We retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow-up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition. RESULTS: Seventy-two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0-.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144-333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high-risk individuals prior to the transition of care. CONCLUSIONS: Transition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high-risk patients, including those with psychiatric comorbidities, may favorably influence outcomes.

Trends in pediatric donor heart discard rates and the potential use of unallocated hearts for allogeneic valve transplantation.

Objectives: Allogeneic valve transplantation is an emerging therapy that delivers a living valve from a donor heart. We reviewed the national discard rate of pediatric and young adult (aged 25 years or younger) donor grafts to estimate the number of hearts potentially available to source valve allotransplantation. Methods: We queried the United Network for Organ Sharing database to identify pediatric and young adult heart donors from 1987 to 2022. Donor heart discard was defined as nontransplantation of the allograft. Results: Of 72,460 pediatric/young adult heart donations, 41,065 (56.7%) were transplanted and 31,395 (43.3%) were unutilized. The average annual number of discarded hearts in era 1 (1987-2000), era 2 (2000-2010), and era 3 (2010-2022) was 791 (42.8%), 1035 (46.3%), and 843 (41.2%), respectively. From 2017 to 2021, the average annual number of discards by age was: 39 (31.8%) neonates/infants, 78 (38.0%) toddlers, 41 (49.4%) young children, 240 (38.0%) adolescents, and 498 (40.1%) young adults. High-volume procurement regions had the greatest proportion of nonutilization, with the national average discard rate ranging from 39% to 49%. The most frequently documented reasons for nonallocation were distribution to the heart valve industry (26.5%), presumably due to suboptimal graft function, poor organ function (22.7%), and logistical challenges (10.8%). Conclusions: With ∼900 pediatric/young adult donor hearts discarded annually, unutilized grafts represent a potential source of valves for allogeneic valve transplant to supplement current conduit and valve replacement surgery. The limited availability of neonatal and infant hearts may limit this technique in the youngest patients, for whom cryopreserved homografts or xenografts will likely remain the primary valve substitute.

Impact of donor-specific anti-HLA antibody on cardiac hemodynamics and graft function 3 years after pediatric heart transplantation: First results from the CTOTC-09 multi-institutional study.

The aim of this study (CTOTC-09) was to assess the impact of "preformed" (at transplant) donor-specific anti-HLA antibody (DSA) and first year newly detected DSA (ndDSA) on allograft function at 3 years after pediatric heart transplantation (PHTx). We enrolled children listed at 9 North American centers. The primary end point was pulmonary capillary wedge pressure (PCWP) at 3 years posttransplant. Of 407 enrolled subjects, 370 achieved PHTx (mean age, 7.7 years; 57% male). Pre-PHTx sensitization status was nonsensitized (n = 163, 44%), sensitized/no DSA (n = 115, 31%), sensitized/DSA (n = 87, 24%), and insufficient DSA data (n = 5, 1%); 131 (35%) subjects developed ndDSA. Subjects with any DSA had comparable PCWP at 3 years to those with no DSA. There were also no significant differences overall between the 2 groups for other invasive hemodynamic measurements, systolic graft function by echocardiography, and serum brain natriuretic peptide concentration. However, in the multivariable analysis, persistent first-year DSA was a risk factor for 3-year abnormal graft function. Graft and patient survival did not differ between groups. In summary, overall, DSA status was not associated with worse allograft function or inferior patient and graft survival at 3 years, but persistent first-year DSA was a risk factor for late graft dysfunction.

Safety and Efficacy of Sildenafil for Group 2 Pulmonary Hypertension in Left Heart Failure.

Pulmonary hypertension (PH) is a multifactorial, progressive disease with poor outcomes. Group 2 PH is defined by pulmonary vascular disease with elevated pulmonary capillary wedge pressure including both left-sided obstructive lesions and diastolic heart failure (HF). Sildenafil was historically discouraged in this population as pulmonary vasodilation can lead to pulmonary edema. However, evidence suggests that sildenafil can help to treat the precapillary component of PH. This is a single center, retrospective pilot study of pediatric PH patients with left-sided HF who were treated with sildenafil for ≥ 4 weeks. HF patients without mechanical support (HF group) and HF patients with a left ventricular assist device (HF-VAD) were analyzed. The exploratory analysis described the safety and side effects of the drug. Echocardiographic parameters were compared before and after sildenafil treatment in a paired analysis. The changes in medical therapy during treatment, mechanical support, and mortality was reported; 19/22 patients tolerated sildenafil. Pulmonary edema in two patients resolved upon discontinuation of sildenafil. In the HF group, both the right atrial volume and right ventricular diastolic area decreased, and the tricuspid regurgitation (TR) S/D ratio decreased after therapy (p = 0.02). Across both the groups, four patients weaned off milrinone and seven weaned off inhaled nitric oxide. Of the thirteen HF patients, four received a transplant, and all of the nine HF-VAD patients received a transplant. Sildenafil can be safely used in carefully selected patients with HF and mixed pre/postcapillary PH with judicious titration and inpatient surveillance, with patients showing improvements in echocardiographic parameters.

Long-term outcomes of surgery for obstructive hypertrophic cardiomyopathy in a pediatric cohort.

Background: Septal reduction therapy via septal myectomy or a modified Konno procedure is the mainstay of therapy for drug-refractory obstructive hypertrophic cardiomyopathy (HCM), although outcomes data on septal myectomy in pediatric patients are limited. We evaluated long-term outcomes following surgery for obstructive HCM in a pediatric cohort. Methods: We retrospectively reviewed patients age ≤18 years with obstructive HCM who underwent a left and/or right ventricular septal myectomy at our institution between 1992 and 2022. Primary endpoints were transplantation-free survival, freedom from HCM-related death, and cumulative probability of HCM-related reintervention. We further evaluated outcomes in patients with and without Noonan syndrome or other RASopathies. Results: Thirty-seven patients (median age, 7.4 years; interquartile range [IQR], 3.4-12.9 years) underwent transaortic septal myectomy. A combined modified Konno procedure was performed in 5 patients (13.9%). Sixteen patients (43.2%) had a RASopathy. A concomitant right ventricular outflow tract resection was performed in 9 patients (24.3%). There was 1 (2.7%) in-hospital death and 4 late deaths at a median follow-up of 10.5 years (IQR, 0.1-29.3). Twenty-year transplant-free survival and freedom from HCM-related death were 80.6% (95% confidence interval [CI], 64.2%-100%) and 87.1% (95% CI, 71.8%-100%), respectively. The 20-year cumulative probability of HCM-related reintervention was 34.2% (95% CI, 12.8%-57.1%). Seven patients required a septal reintervention. There was no difference in any primary endpoints between patients with and without a RASopathy. Conclusions: Surgery for obstructive HCM, including septal myectomy with and without a modified Konno procedure, may be performed with low morbidity and good long-term outcomes in pediatric patients. Recurrent outflow tract obstruction is not uncommon.

Quality of life and lifetime achievement in adult survivors of pediatric heart transplant.

BACKGROUND: Survival in pediatric heart transplantation has improved since the first successful transplant over 35 years ago leading to increasing numbers of patients entering adulthood. We sought to examine quality of life and various lifetime achievements in our institutional population of long-term adult survivors of pediatric heart transplant. METHODS: Participants ≥18 years of age who received a heart transplant as a pediatric patient (<18 years old), and who have survived ≥10 years post-transplant, completed two self-report surveys: (1) Ferrans and Powers QLI cardiac version which reports a measure of life satisfaction with a range of 0 (very dissatisfied) to 1 (very satisfied); and (2) CHONY Pediatric Heart Transplant Life Achievement Survey to examine lifetime achievement. RESULTS: Sixty-two and sixty-five participants completed the Ferrans and Powers QLI cardiac version and CHONY Pediatric Heart Transplant Life Achievement Survey. The mean overall QLI was 0.75 ± 0.14 with the most satisfaction in the family domain. QLI scores were analyzed by age at initial transplant, gender, indication for transplant, and whether patients currently followed by pediatric or adult providers, with no statistically significant differences noted. Seventy-two percent of participants demonstrated stable employment or schooling. Around thirty percent of participants showed the ability to reach academic milestones including college and post-graduate education and ten percent to start their own families. CONCLUSIONS: Our cohort of long-term adult survivors of pediatric heart transplant report a quality of life with scores thought to be reflective of a satisfactory quality of life, and many demonstrate achievement of major life milestones.

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.

Cardiac allograft vasculopathy in pediatric heart transplant recipients does early-onset portend a worse prognosis?

PURPOSE: We sought to evaluate the association between timing of cardiac allograft vasculopathy (CAV) occurrence post-heart transplant (HT) with graft survival and progression of CAV severity in pediatric HT recipients. METHODS: Data from the Pediatric Heart Transplant Society for pediatric (<18 years old) HT recipients between 1993-2019 with available angiographic data were obtained (N = 5,075). The timing of CAV diagnosis (<3; 3-<5; 5-<10; and ≥10 years post-HT) and severity of disease at each assessment (CAV 1-3) was determined. Associations between CAV timing, graft survival, and CAV progression were evaluated using Kaplan-Meier survival curves, multivariable COX proportional hazard regression analyses, and competing risk analyses. RESULTS: Over a median follow-up period of 4.1 (IQR 1.3-8.3) years, CAV was identified in 17% (885/5,075), 28% (252/885) of which were early-onset CAV. Compared with late onset CAV ≥10 years post-HT, patients with early CAV were older at the time of transplant (8.3 ± 6.2 vs. 3.8 ± 4.8 years, p < .0001). While the five-year graft-survival in the ≥10-year group (79.2%, p = 0.03) was significantly higher than the <3, 3-<5, and 5-<10 years post-HT groups (65.0%-67%) (p = 0.03), overall post-CAV graft survival was not significantly different across the CAV time-points. CAV disease progression did not vary with CAV timing post-HT, with an overall five-year freedom from CAV ≥2 of 75.4% (73.1%-77.6%). CONCLUSION: Later onset CAV (≥10-years post-HT) was associated with improved five-year graft survival compared with CAV onset at earlier time-points, but similar and poor long-term outcomes. CAV timing post-HT was not associated with progression of CAV disease severity.

Association between homograft tissue exposure and allosensitization prior to heart transplant in patients with congenital heart disease.

BACKGROUND: Surgical repair for patients with congenital heart disease (CHD) often incorporates homograft tissue or other foreign material that can lead to allosensitization. We sought to identify the relationship between pre-sensitization prior to heart transplant and exposure to homograft tissue in CHD patients. METHODS: Retrospective chart review of all CHD patients who underwent heart transplant at a major pediatric transplant center between 1/1/2011-3/31/18. Operative records determined use of homograft tissue or foreign material. Panel reactive antibody (PRA) and LuminexTM single-antigen bead (SAB) testing results were reviewed. Statistical analysis determined odds of pre-sensitization in patients exposed to homograft tissue. RESULTS: Fifty-six CHD patients underwent transplant during the review period. Thirteen patients (23%) were pre-sensitized by PRA>10%. By SAB testing, 33 patients (59%) developed any anti-HLA antibody >0 MFI, 30 patients (54%) >2000 MFI, and 19 patients (34%) >6000 MFI. Patients with homografts were more likely to be pre-sensitized by PRA (OR = 7.31, p = .007), and to have developed any anti-HLA antibody at various levels, >0 (OR = 4.52, p = .034), >2000 (OR = 8.59, p = .003), and >6000 (OR = 8.50, p = .004). Of patients with homografts, those pre-sensitized by PRA had longer exposure times (9.80 vs 4.96 years, p = .025). There was no difference in exposure time with relation to pre-sensitization by SAB testing. CONCLUSIONS: Previous exposure to homograft tissue appears to increase the odds of pre-sensitization by either the PRA or SAB testing. Longer exposure time to homograft tissue prior to transplant is associated with increased pre-sensitization at transplant as determined by PRA, though not by SAB testing.

Efficacy of Distraction for Reducing Pain and Distress Associated With Venipuncture in the Pediatric Posttransplant Population: A Randomized Controlled Trial.

OBJECTIVE: Distraction can reduce pain and distress associated with painful procedures but has never been studied in children with solid organ transplants. We aimed to determine whether there is a difference in pain and distress associated with venipuncture in pediatric posttransplant patients who receive distraction compared with those who do not. METHODS: Randomized controlled trial of children aged 4 to 17 years with solid organ transplants undergoing venipuncture in the outpatient setting. Patients were randomized to receive distraction or no distraction. The primary outcome was the Faces Pain Scale-Revised. Secondary outcomes were the Observational Scale of Behavioral Distress-Revised; Faces, Leg, Activity, Cry, Consolability; and Children's Hospital of Eastern Ontario Pain Scale. Exploratory outcomes included the number of venipuncture attempts, time to successful venipuncture, and satisfaction of phlebotomists and parents. RESULTS: Median age of the 40 children enrolled was 11.5 years. Type of transplants included the heart (67.5%), kidney (22.5%), liver (7.5%), and more than 1 organ (2.5%). There was no difference between the Faces Pain Scale-Revised scores in distraction and no distraction groups (1.4; 95% confidence interval, 0.9-1.9; and 1.3, 95% confidence interval, 0.5-2.1, respectively). There was also no difference in the Observational Scale of Behavioral Distress-Revised; Faces, Leg, Activity, Cry, Consolability; and Children's Hospital of Eastern Ontario Pain Scale scores, number of venipuncture attempts, or time to successful venipuncture. Phlebotomists were more satisfied with the venipuncture when distraction was implemented. CONCLUSIONS: In children with solid organ transplants, there was no difference in pain and distress associated with venipuncture between those who did and did not receive distraction. There was also no difference in other procedure-related outcomes except for greater phlebotomist satisfaction when distraction was implemented.

Clinical outcomes of children receiving ABO-incompatible versus ABO-compatible heart transplantation: a multicentre cohort study.

BACKGROUND: ABO-incompatible heart transplantation increases donor availability in young children and is evolving into standard of care in children younger than 2 years. Previous smaller studies suggest similar outcomes to ABO-compatible heart transplantation, but persisting alterations of the immune system in ABO-incompatible recipients might increase the risk of some infections or benefit the graft owing to reduced HLA reactivity. We aimed to assess long-term outcomes in young children after they received ABO-incompatible or ABO-compatible heart transplantation. METHODS: In this multicentre, prospective cohort study, we analysed data from the Pediatric Heart Transplant Society registry to compare children who received ABO-incompatible or ABO-compatible heart transplantation before age 2 years between Jan 1, 1999, and June 30, 2018. Given significantly different clinical demographics between the two groups, we also matched each ABO-incompatible recipient to two ABO-compatible recipients using propensity score matching. We assessed patient and graft survival, coronary allograft vasculopathy, malignancy, acute rejection (any episode resulting in augmentation of immunosuppression), and infections (requiring intravenous antibiotic or antiviral therapy or life-threatening infections treated with oral therapy). FINDINGS: We included 2206 children who received a heart transplant before age 2 years, with 11 332·6 patient-years of cumulative observation time. Children who received an ABO-incompatible transplant (n=364) were younger and a larger proportion had congenital heart disease and ventilator and mechanical circulatory support than the ABO-compatible recipients (n=1842). After matching, only differences in blood group (more O in ABO-incompatible and more AB in ABO-compatible groups) and use of polyclonal induction therapy with anti-thymocyte globulins persisted. The two matched groups had similar post-transplantation graft survival (p=0·74), freedom from coronary allograft vasculopathy (p=0·75), and malignancy (p=0·51). ABO-incompatible recipients showed longer freedom from rejection (p=0·0021) in the overall cohort, but not after matching (p=0·48). Severe infections (p=0·0007), bacterial infections (p=0·0005), and infections with polysaccharide encapsulated bacteria (p=0·0005) that share immunological properties with blood group antigens occurred less frequently after ABO-incompatible heart transplantation. INTERPRETATION: ABO-incompatible heart transplantation for children younger than 2 years is a clinically safe approach, with similar survival and incidences of rejection, coronary allograft vasculopathy, and malignancy to ABO-compatible recipients, despite higher-risk pre-transplant profiles. ABO-incompatible transplantation was associated with less bacterial infection, particularly encapsulated bacteria, suggesting that the acquired immunological changes accompanying ABO tolerance might benefit rather than jeopardise transplanted children. FUNDING: Pediatric Heart Transplant Society.

Anti-hypertensive treatment in the immediate post-operative period and 1 year after pediatric heart transplantation.

Hypertension is a known complication of pediatric heart transplantation. We sought to identify factors associated with anti-hypertensive use in pediatric heart transplant recipients immediately post-transplant and oral anti-hypertensive use at discharge and 1-year post-transplant. Retrospective chart review was conducted of patients ≤18 years who underwent heart transplantation at two major heart transplant centers between August 1, 2009 and December 31, 2017 with ≥1-year follow-up. Exclusion criteria included re-transplant, multi-organ recipients, survival <1 year, and comorbidities associated with hypertension. Anti-hypertensive use was recorded during initial ICU stay, at discharge, and 1-year post-transplant. Univariate and multivariate analyses determined associations of demographic and diagnostic factors and need for anti-hypertensives. There were 188 patients that met inclusion criteria. Anti-hypertensive infusions were required in the ICU post-transplant in 46 patients (24.5%) for a median of 3 days (1-21 days). Oral anti-hypertensives were required in 58 patients (30.9%) at discharge and 1-year post-transplant. Anti-hypertensive infusion in the ICU post-transplant was associated with donor-to-recipient weight ratio. Oral anti-hypertensive use at discharge was associated with weight ratio and pretransplant VAD use, and at 1-year, post-transplant was associated with age at transplant, steroid use at discharge, and oral anti-hypertensive use at discharge. Hypertension is common immediately following and 1-year post-transplant. Weight ratio was the only independent predictor of anti-hypertensive use in the early post-transplant period, whereas VAD use was also associated with anti-hypertensive use at discharge. Anti-hypertensive use 1-year post-transplant was not associated with those factors, but rather with age at transplant and steroid use.

Varying presentations of COVID-19 in young heart transplant recipients: A case series.

BACKGROUND: Immunosuppression is considered a risk factor for more severe clinical presentation of COVID-19. Limited data regarding clinical outcome exist in adults, whereas very little is known about the spectrum of the disease in pediatric heart transplant recipients. METHODS: We retrospectively reviewed the charts of young heart transplant patients from our tertiary care center during the coronavirus pandemic in New York City and identified patients infected with SARS-CoV-2. RESULTS: We present four cases with COVID-19 disease and elaborate on their presentation and clinical course. CONCLUSIONS: Although far from conclusive and limited by the small sample size and selection bias, these cases demonstrate mild and self-limited disease despite immunosuppressive therapy and various comorbidities that are expected to increase the severity of the clinical picture based on extrapolation from the adult experience with this novel disease.

Evolution of pediatric ventricular assist devices and their neurologic and renal complications-A 24-year single-center experience.

Utilization of ventricular assist devices (VADs) in adult populations with severe heart failure as a bridge to transplant has become the standard of care over the past two decades. Analogously, the use of VADs in pediatric populations has become more commonplace as pediatric heart transplantation has become more prevalent. We still have much to learn, however, about the complications after VAD placement in pediatric patients, their impact on transplantation and, in particular, how outcomes have changed over time. The objectives of this study were to (a) review the experience of a single pediatric VAD center, (b) identify risk factors that could lead to poor outcomes in patients on the transplant waitlist after VAD implantation and (c) demonstrate changes in outcomes over time. A retrospective cohort analysis was performed comparing death as a primary outcome and stroke and acute kidney injury (AKI) as secondary outcomes, across the study period divided into three timed eras. We analyzed 88 patients supported by a VAD over a 24-year timeframe. The duration, age at implant and indication for VAD support did not change significantly across the eras. We found that the incidence of stroke decreased over the study period and, while the rates of AKI did not change over the study period, those who developed AKI, while supported on VAD, had an increased risk of death.

Impact of dipyridamole on adenosine dosing in pediatric and young adult patients after heart transplantation.

BACKGROUND: Relative contraindications to adenosine use have included heart transplant and dipyridamole. We previously demonstrated the safety and efficacy of adenosine-induced atrioventricular (AV) block in healthy young heart transplant recipients while suspending dipyridamole therapy (dual antiplatelet agent). This prospective follow-up study evaluated the safety and efficacy of adenosine use in the same cohort of heart transplant recipients while on dipyridamole. METHODS: Adenosine was incrementally dosed until AV block occurred (maximum 200 mcg/kg up to 12 mg). The primary outcome was clinically significant asystole (≥12 seconds). Secondary outcomes included maximal adenosine dose, AV block duration, dysrhythmias, and clinical symptoms. Outcomes were compared to the parent study. RESULTS: Thirty of 39 eligible patients (5-24 years) were tested. No patient (0%, CI 0%-8%) experienced clinically significant asystole. AV block occurred in 29/30 patients (97%, CI 86%-100%). The median dose causing AV block was 50mcg/kg (vs 100 mcg/kg off dipyridamole; P = .011). Seventeen patients (57%, CI 39%-72%) required less adenosine to achieve AV block on dipyridamole; six (20%) required more. AV block occurred at doses ≥25 mcg/kg in all patients. In pairwise comparison to prior testing off dipyridamole, no significant change occurred in AV block duration, frequency of cardiac ectopy, or incidence of reported symptoms. No atrial fibrillation/flutter occurred. CONCLUSIONS: AV block often occurs at twofold lower adenosine doses in healthy young heart transplant recipients taking oral dipyridamole, compared with previous testing of this cohort off dipyridamole. Results suggest that initial dosing of 25 mcg/kg (maximum 0.8 mg) with stepwise escalation poses low risk of prolonged asystole on dipyridamole.

A current era analysis of ABO incompatible listing practice and impact on outcomes in young children requiring heart transplantation.

BACKGROUND: Heart transplantation from ABO incompatible (ABOi) donors has evolved into a progressively accepted therapy in young children. We assessed the recent practice of ABOi listing impact on waitlist and post-transplant outcomes. METHODS: Using the Pediatric Heart Transplant Society registry, we compared clinical presentation, waitlist parameters, and post-transplant survival of children < 2 years of age listed for ABOi vs ABO compatible (ABOc) heart transplant between January 2010 and June 2018 with sub-analysis of blood group O recipients. RESULTS: Among 2,039 patients, ABOi listing increased significantly with time from 49% (2010) to 72% (2017). ABOi-listed patients had lower age and body surface area, and higher proportion of congenital heart disease, mechanical ventilation, and high urgency status (all p < 0.01). Use of mechanical circulatory support was similar between groups. Of 1,288 patients reaching transplant, 239 (18.6%) received an ABOi organ (15%-40%/year). Death while waiting, removal from the waitlist, and waitlist survival were similar between groups. Time to transplant was significantly shorter for ABOi listing in blood group O patients (p < 0.02), approaching significance (p = 0.057) for all blood groups. Post-transplant survival was similar except for lower survival of patients listed ABOc but transplanted ABOi. These patients showed increasing need for mechanical circulatory support and high urgency listing while waiting. CONCLUSIONS: In the current era, primary listing for ABOi heart transplant has become routine for the majority of children < 2 years old, resulting in shorter waitlist time, especially in blood group O. Post-transplant survival is similar despite ABOi-listed children still showing a higher risk profile.

Effects of donor cause of death, ischemia time, inotrope exposure, troponin values, cardiopulmonary resuscitation, electrocardiographic and echocardiographic data on recipient outcomes: A review of the literature.

BACKGROUND: Heart transplantation has become standard of care for pediatric patients with either end-stage heart failure or inoperable congenital heart defects. Despite increasing surgical complexity and overall volume, however, annual transplant rates remain largely unchanged. Data demonstrating pediatric donor heart refusal rates of 50% suggest optimizing donor utilization is critical. This review evaluated the impact of donor characteristics surrounding the time of death on pediatric heart transplant recipient outcomes. METHODS: An extensive literature review was performed to identify articles focused on donor characteristics surrounding the time of death and their impact on pediatric heart transplant recipient outcomes. RESULTS: Potential pediatric heart transplant recipient institutions commonly receive data from seven different donor death-related categories with which to determine organ acceptance: cause of death, need for CPR, serum troponin, inotrope exposure, projected donor ischemia time, electrocardiographic, and echocardiographic results. Although DITs up to 8 hours have been reported with comparable recipient outcomes, most data support minimizing this period to <4 hours. CVA as a cause of death may be associated with decreased recipient survival but is rare in the pediatric population. Otherwise, however, in the setting of an acceptable donor heart with a normal echocardiogram, none of the other data categories surrounding donor death negatively impact pediatric heart transplant recipient survival. CONCLUSIONS: Echocardiographic evaluation is the most important donor clinical information following declaration of brain death provided to potential recipient institutions. Considering its relative importance, every effort should be made to allow direct image visualization.

Biventricular Impella use in pediatric patients with severe graft dysfunction from acute rejection after heart transplantation.

Rejection with severe hemodynamic compromise is a significant source of morbidity and mortality for pediatric heart transplant patients. Traditionally, treatment for these patients includes inotropes and escalation to extracorporeal membrane oxygenation (ECMO) when necessary. There is increasing interest in using percutaneous ventricular assistive devices in the pediatric population as a less invasive alternative to ECMO. We report the largest case series to date of biventricular support using percutaneous Impella devices. Retrospective case series was performed by chart review. Hemodynamics, left ventricular ejection fraction (LVEF), and indices of end organ function were collected before and after Impella placement. A 14-year-old male, 18-year-old male, and 19-year-old female, all status post heart transplant, presented with severely decreased biventricular function due to presumed clinical rejection, requiring maximal inotropic support without improvement. In all the three cases, simultaneous Impella CP and RP devices were placed percutaneously. Prior to implantation, LVEFs were 40%, 23%, and 25%, respectively. Hemodynamics measured invasively prior to device placement showed elevated filling pressures. Adverse events while on support included bleeding, hemolysis, and right femoral arterial dissection during implantation. All patients were successfully weaned from the devices and survived to discharge. The average time of right-sided support and total support was 11 days and 13 days, respectively. After device removal, right-sided pressures and echocardiographic measurements showed improvement in all patients. Bilateral Impella configuration (BiPella) is a viable option for temporary mechanical circulatory support in pediatric patients with significant graft dysfunction.