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Background Ventricular assist device (VAD) use as a bridge to transplant (BTT) for children with end-stage heart failure and congenital heart disease (CHD), although challenging, has increased, but its effect on posttransplant outcome is unknown. This study describes posttransplant outcomes of CHD patients BTT with a VAD. Methods All heart transplant recipients identified in United Network of Organ Sharing database from 2006 to 2015 (n = 21,865) were divided into four groups by those with (+) and without (–) a diagnosis of CHD and with (+) and without (–) VAD support at transplant: +CHD/+VAD, +CHD/–VAD, +VAD/–CHD, and –VAD/–CHD. Posttransplant survival of +CHD/+VAD was compared with +CHD/–VAD, –CHD/+VAD, and –CHD/–VAD in addition to pretransplant characteristics comparison between +CHD/+VAD and +CHD/–VAD. Results Of 1,871 patients (8.6%) with CHD, 1,348 (72%) were younger than 18 years old, and 143 (7.6%) were BTT with a VAD (+CHD/+VAD). At transplant, +CHD/+VAD compared with +CHD/–VAD were more likely to have worse functional status (<50%: 60% vs 46%, p = 0.004), infections (29% vs 14%, p < 0.001), to be sensitized (47% vs 30%, p < 0.001) and on ventilator support (20% vs 13%, p = 0.029) and dialysis (13% vs 2.5%, p < 0.001). Overall, 1-year (84% vs 87%) and 5-year (72% vs 75%) survival was similar for +CHD/+VAD and +CHD/–VAD ( p = 0.694). Survival was also similar when +CHD/+VAD were compared with –CHD/+VAD (n = 7,363; p = 0.529) and –CHD/–VAD (n = 12,613; p = 0.097). Conclusions Although more ill pretransplant, CHD patients BTT with a VAD have similar posttransplant survival compared with CHD patients without a VAD and with other non–CHD heart transplant patients. VAD support may mitigate certain risk factors for poor posttransplant outcomes in the challenging CHD cohort. [ABSTRACT FROM AUTHOR]

Children of minority race and ethnicity experience inferior outcomes postheart transplantation (HTx). Studies have associated ventricular assist device (VAD) bridge-to-transplant (BTT) with similar-to-superior post-transplant-survival (PTS) compared to no mechanical circulatory support. It is unclear whether racial and ethnic discrepancies exist in VAD utilization and outcomes. The United Network for Organ Sharing (UNOS) database was used to identify 6,121 children (<18 years) listed for HTx between 2006 and 2021: black (B—22% of cohort), Hispanic (H—21%), and white (W—57%). VAD utilization, outcomes, and PTS were compared between race/ethnicity groups. Multivariable Cox proportional analyses were used to study the association of race and ethnicity on PTS with VAD BTT, using backward selection for covariates. Black children were most ill at listing, with greater proportions of UNOS status 1A/1 (p < 0.001 vs H & W), severe functional limitation (p < 0.001 vs H & W), and greater inotrope requirements (p < 0.05 vs H). Non-white children had higher proportions of public insurance. VAD utilization at listing was: B—11%, H—8%, W—8% (p = 0.001 for B vs H & W). VAD at transplant was: B—24%, H—21%, W—19% (p = 0.001 for B vs H). At transplant, all VAD patients had comparable clinical status (functional limitation, renal/hepatic dysfunction, inotropes, mechanical ventilation; all p > 0.05 between groups). Following VAD, hospital outcomes and one-year PTS were equivalent but long-term PTS was significantly worse among non-whites-(p < 0.01 for W vs B & H). On multivariable analysis, black race independently predicted mortality (hazard ratio 1.67 [95% confidence interval 1.22-2.28]) while white race was protective (0.54 [0.40-0.74]). Pediatric VAD use is, seemingly, equitable; the most ill patients receive the most VADs. Despite similar pretransplant and early post-transplant benefits, non-white children experience inferior overall PTS after VAD BTT. [ABSTRACT FROM AUTHOR]

Background: Heart transplant waitlist mortality remains high in infants <1 year of age and among those with CHD. Currently, the median accepted donor‐to‐recipient weight percentage is approximately 130% of the recipient's weight. We hypothesized that patients with CHD may accept a larger organ using novel 3D‐derived imaging data to estimate donor and recipient TCV. Methods: A single‐center, retrospective study was performed using CT data for 13 patients with CHD and 94 control patients. 3D visualization software was used to create digital 3D heart models that provide an estimate of TCV. In addition, echocardiograms obtained prior to cross‐sectional imaging were reviewed for presence of ventricular chamber dilation. Results: Sixty‐two percent (8/13) of patients with CHD had 3D‐derived TCV resulting in a weight that was >130% larger than their actual weight. This was seen in single‐ventricle patients following Blalock‐Taussig shunt and Fontan palliation, and patients with biventricular repair. Of those, 75% (6/8) had reported moderate‐to‐severe ventricular chamber dilation by echocardiogram or cardiac magnetic resonance imaging. Conclusions: In a large portion of patients with CHD, 3D‐derived TCV place the recipient at a higher listing weight than their actual weight. We propose obtaining cross‐sectional imaging to better assess TCV in a recipient, which may increase the donor range for CHD recipients and improve organ utilization in pediatrics. [ABSTRACT FROM AUTHOR]

Abnormal dystrophin production due to mutations in the dystrophin gene causes Duchenne Muscular Dystrophy (DMD). Cases demonstrate considerable genetic and disease progression variability. It is unclear if specific gene mutations are prognostic of outcomes in this population. We conducted a retrospective cohort study of DMD patients followed at 17 centers across the USA and Canada from 2005 to 2015 with goal of understanding the genetic variability of DMD and its impact on clinical outcomes. Cumulative incidence of clinically relevant outcomes was stratified by genetic mutation type, exon mutation location, and extent of exon deletion. Of 436 males with DMD, 324 (74.3%) underwent genetic testing. Deletions were the most common mutation type (256, 79%), followed by point mutations (45, 13.9%) and duplications (23, 7.1%). There were 131 combinations of mutations with most mutations located along exons 45 to 52. The number of exons deleted varied between 1 and 52 with a median of 3 exons deleted (IQR 1-6). Subjects with mutations starting at exon positions 40-54 had a later onset of arrhythmias occurring at median age 25 years (95% CI 18-∞), p = 0.01. Loss of ambulation occurred later at median age of 13 years (95% CI 12-15) in subjects with mutations that started between exons 55-79, p = 0.01. There was no association between mutation type or location and onset of cardiac dysfunction. We report the genetic variability in DMD and its association with timing of clinical outcomes. Genetic modifiers may explain some phenotypic variability., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Clinical outcomes of ventricular assist device (VAD) support for shunted single ventricle patients trail the larger population due in part to the challenges in optimizing VAD support and balancing systemic and pulmonary circulations. We sought to understand the response to VAD titration in the shunted circulation using a lumped-parameter network modeling six patient-specific clinical cases. Hemodynamic data from six patients (mean body surface area = 0.30 m2) with a systemic-to-pulmonary shunt was used to construct simulated cases of heart failure and hemodynamic response to increasing VAD flow from 5 to 10 L/min/m2. With increasing VAD flow, the pulmonary arterial pressure stayed relatively constant in five patient cases and increased in one patient case. The mean VAD flow needed to attain an arterial-venous O2 saturation difference of 30% was 6.5 ± 1.2 L/min/m2, which is higher than that in the equivalent nonshunted scenario due to the partial diversion of flow to the pulmonary circulation. The hemodynamic responses to VAD support can vary significantly between specific patient cases; therefore hemodynamic modeling may help guide an individualized approach to perioperative VAD management in the shunted single-ventricle circulation and to understand the patients who may benefit the most from VAD support., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2021.)

Background: The pediatric heart transplant community uses weight-based donor-to-recipient size matching almost exclusively, despite no evidence to validate weight as a reliable surrogate of cardiac size. Donor size mismatch is the second most common reason for the refusal of donor hearts in current practice (∼30% of all refusals). Whereas case-by-case segmentation of total cardiac volume (TCV) by computed tomography (CT) for direct virtual transplantation is an attractive option, it remains limited by the unavailability of donor chest CT. We sought to establish a predictive model for donor TCV on the basis of anthropomorphic and chest X-ray (CXR) cardiac measures., Methods: Banked imaging studies from 141 subjects with normal CT chest angiograms were obtained and segmented using 3-dimensional modeling to derive TCV. CXR data were available for 62 of those subjects. A total of 3 predictive models of TCV were fit through multiple linear regression using the following variables: Model A (weight only); Model B (weight, height, sex, and age); Model C (weight, height, sex, age, and 1-view anteroposterior CXR maximal horizontal cardiac width)., Results: Model C provided the most accurate prediction of TCV (optimism corrected R 2  = 0.99, testing set R 2  = 0.98, mean absolute percentage error [MAPE] = 8.6%) and outperformed Model A (optimism corrected R 2  = 0.94, testing set R 2  = 0.94, MAPE = 16.1%) and Model B (optimism corrected R 2  = 0.97, testing set R 2  = 0.97, MAPE = 11.1%)., Conclusions: TCV can be predicted accurately using readily available anthropometrics and a 1-view CXR from donor candidates. This simple and scalable method of TCV estimation may provide a reliable and consistent method to improve donor size matching., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Duchenne muscular dystrophy (DMD) is characterized by myocardial fibrosis and left ventricular (LV) dysfunction. Implantable cardioverter defibrillator (ICD) use has not been characterized in this population but is considered for symptomatic patients with severe LV dysfunction (SLVD) receiving guideline-directed medical therapy (GDMT). We evaluated ICD utilization and efficacy in patients with DMD. Retrospective cohort study of DMD patients from 17 centers across North America between January 2, 2005 and December 31, 2015. ICD use and its effect on survival were evaluated in patients with SLVD defined as ejection fraction (EF) < 35% and/ or shortening fraction (SF) < 16% on final echocardiogram. SLVD was present in 57/436 (13.1%) patients, of which 12 (21.1%) died during the study period. Of these 12, (mean EF 20.9 ± 6.2% and SF 13.7 ± 7.2%), 8 received GDMT, 5 received steroids, and none received an ICD. ICDs were placed in 9/57 (15.8%) patients with SLVD (mean EF 31.2 ± 8.5% and SF 10.3 ± 4.9%) at a mean age of 20.4 ± 6.3 years; 8/9 received GDMT, 7 received steroids, and all were alive at study end; mean ICD duration was 36.1 ± 26.2 months. Nine ICDs were implanted at six different institutions, associated with two appropriate shocks for ventricular tachycardia in two patients, no inappropriate shocks, and one lead fracture. ICD use may be associated with improved survival and minimal complications in DMD cardiomyopathy with SLVD. However, inconsistent GDMT utilization may be a significant confounder. Future studies should define optimal indications for ICD implantation in patients with DMD cardiomyopathy.

As survival and neuromuscular function in Duchenne muscular dystrophy (DMD) have improved with glucocorticoid (GC) therapy and ventilatory support, cardiac deaths are increasing. Little is known about risk factors for cardiac and non-cardiac causes of death in DMD. A multi-center retrospective cohort study of 408 males with DMD, followed from January 1, 2005 to December 31, 2015, was conducted to identify risk factors for death. Those dying of cardiac causes were compared to those dying of non-cardiac causes and to those alive at study end. There were 29 (7.1%) deaths at a median age of 19.5 (IQR: 16.9-24.6) years; 8 (27.6%) cardiac, and 21 non-cardiac. Those living were younger [14.9 (IQR: 11.0-19.1) years] than those dying of cardiac [18 (IQR 15.5-24) years, p = 0.03] and non-cardiac [19 (IQR: 16.5-23) years, p = 0.002] causes. GC use was lower for those dying of cardiac causes compared to those living [2/8 (25%) vs. 304/378 (80.4%), p = 0.001]. Last ejection fraction prior to death/study end was lower for those dying of cardiac causes compared to those living (37.5% ± 12.8 vs. 54.5% ± 10.8, p = 0.01) but not compared to those dying of non-cardiac causes (37.5% ± 12.8 vs. 41.2% ± 19.3, p = 0.58). In a large DMD cohort, approximately 30% of deaths were cardiac. Lack of GC use was associated with cardiac causes of death, while systolic dysfunction was associated with death from any cause. Further work is needed to ensure guideline adherence and to define optimal management of systolic dysfunction in males with DMD with hopes of extending survival.

Durable ventricular assist devices (VADs) have significantly improved survival to transplantation among children with advanced stages of heart failure. The fundamental goals of VAD therapy include decreasing mortality, minimizing adverse events, and improving quality of life. As the pediatric VAD experience has evolved with reduced device related complications and improved survival, VAD therapy is being considered not only as a bridge to transplantation (BTT) but also as a bridge to decision (BTD) and as destination therapy (DT). Data regarding pediatric DT VAD are limited to anecdotal or case reports of children being supported for long periods with VADs and by default being classified as DT VAD. This article reviews current trends in the use of DT VAD and adverse events in children vs adults on VAD, and provides a framework for patient selection with the use of a multidisciplinary approach including palliative care. The general approach to determining DT VAD candidacy should include: 1) a reasonable success that the patient will survive the peri- and postoperative state; and 2) a high likelihood that the patient will be able to be discharged out of hospital and have adequate caregiver support. Patients with muscular dystrophy and failing Fontan physiology are examples of pediatric populations for whom DT VAD may be considered and which require unique considerations., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: As survival and neuromuscular function in Duchenne Muscular Dystrophy (DMD) improve with glucocorticoid therapy and respiratory advances, the proportion of cardiac deaths is increasing. Little is known about the use and outcomes of advanced heart failure (HF) therapies in this population., Methods: A retrospective cohort study of 436 males with DMD was performed, from January 1, 2005-January 1, 2018, with the primary outcome being use of advanced HF therapies including: implantable cardioverter defibrillator (ICD), left ventricular assist device (LVAD), and heart transplantation (HTX)., Results: Nine subjects had an ICD placed, 2 of whom (22.2%) had appropriate shocks for ventricular tachycardia; 1 and 968 days after implant, and all of whom were alive at last follow-up; median 18 (IQR: 12.5-25.5) months from implant. Four subjects had a LVAD implanted with post-LVAD survival of 75% at 1 year; 2 remaining on support and 1 undergoing HTX. One subject was bridged to HTX with ICD and LVAD and was alive at last follow-up, 53 months after HTX., Conclusion: Advanced HF therapies may be used effectively in select subjects with DMD. Further studies are needed to better understand risk stratification for ICD use and optimal candidacy for LVAD implantation and HTX, with hopes of improving cardiac outcomes., Competing Interests: Declaration of interest Carol A. Wittlieb-Weber, MD: None. Chet R. Villa, MD: None. Matthew J. Bock, MD: None. Katheryn E. Gambetta, MD: None. Jonathan N. Johnson, MD: None. Ashwin K. Lal, MD: None. Kurt R. Schumacher, MD: None. Sabrina P. Law, MD: None. Shriprasad R. Deshpande, MD, MS: None. Shawn C. West, MD, MSc: None. Joshua M. Friedland-Little, MD: None. Irene D. Lytrivi, MD: None. Michael A. McCulloch, MD: None. Ryan J. Butts, MD: None. David R. Weber, MD, MSCE: Consulted for Marathon Pharmaceuticals. Kenneth R. Knecht, MD: None.

Background: Heart failure results in significant morbidity and mortality in young children with hypoplastic left heart syndrome (HLHS) after the Norwood procedure., Methods: We studied subjects enrolled in the prospective Single Ventricle Reconstruction (SVR) Trial who survived to hospital discharge after a Norwood operation and were followed up to age 6 years. The primary outcome was heart failure, defined as heart transplant listing after Norwood hospitalization, death attributable to heart failure, or symptomatic heart failure (New York Heart Association [NYHA] Class IV). Multivariate modeling was undertaken using Cox regression methodology to determine variables associated with heart failure., Results: Of the 461 subjects discharged home following a Norwood procedure, 66 (14.3%) met the criteria for heart failure. Among these, 15 died from heart failure, 39 were listed for transplant (22 had a transplant, 12 died after listing, and 5 were alive and not yet transplanted), and 12 had NYHA Class IV heart failure but were never listed. The median age at heart failure identification was 1.28 (interquartile range 0.30 to 4.69) years. Factors associated with early heart failure included post-Norwood lower fractional area change, need for extracorporeal membrane oxygenation, non-Hispanic ethnicity, Norwood perfusion type, and total support time (p < 0.05)., Conclusions: By 6 years of age, heart failure developed in nearly 15% of children after the Norwood procedure. Although transplant listing was common, many patients died from heart failure before receiving a transplant or without being listed. Shunt type did not impact the risk of developing heart failure., (Copyright © 2018 International Society for Heart and Lung Transplantation. All rights reserved.)

Background: Historically, the "temporary" or short-term ventricular assist device (VAD) was used only as a quick bridge to recovery for children with an acute process. In the current era, the devices that were originally used for temporary support are now being used to support children for longer durations and for a variety of indications. In this study we aimed to describe the overall use, patients' characteristics and outcomes of "temporary" VAD use in children., Methods: The Pediatric Interagency Registry for Mechanical Circulatory Support (PediMACS) is a National Institutes of Health-supported national registry for United States Food and Drug Administration-approved VADs in patients <19 years of age at the time of VAD implantation (either durable or temporary VAD). Patients undergoing placement of a device classified as a temporary VAD between September 19, 2012 and June 30, 2016 were included., Results: Temporary VADs were implanted in 63 patients at 20 centers, accounting for 19% of all pediatric VAD patients entered into PediMACS. The median age at implantation was 3.7 (range <1 day to 18) years. The underlying diseases were: congenital heart disease in 26 (41%), 20 of whom were classified as single ventricle; cardiomyopathy in 25 (40%); and myocarditis/rejection in 12 (19%). Patients were predominately Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Profile 1 (51%), and 10 patients (16%) had previously been supported with extracorporeal membrane oxygenation. Median duration of support was 15 (range <1 day to 227) days, with 41 patients (65%) being on support for ≥10 days. The most frequent adverse events were bleeding (29% of patients) and neurologic dysfunction (24% of patients). Overall, 71% (45) achieved a positive outcome (defined as bridge to recovery [30%], transplantation [17%], alive on device [2%] or transition to durable VAD [22%]). Eighty-eight percent (n = 22) of the cardiomyopathy patients and 60% (n = 12) of the single-ventricle patients achieved a favorable outcome., Conclusion: Devices historically classified as "temporary" pumps are being used not only as a short-term mechanical circulatory support strategy but also as a longer term support strategy. In this multi-institutional, high-acuity, complex patient cohort, the use of "temporary" VADs resulted in a positive outcome (bridge to transplant, recovery durable device or alive) in 71% of patients., (Copyright © 2018 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with Duchenne Muscular Dystrophy (DMD) develop cardiac fibrosis and dilated cardiomyopathy. We described the frequency of significant Holter findings in DMD, the relationship between cardiac function and arrhythmia burden, and the impact of these findings on clinical management., Methods and Results: A retrospective review was done of patients with DMD who received a Holter from 2010 to 2014. Clinical and arrhythmic outcomes were analyzed. Patients were classified based on left ventricular ejection fraction (LVEF): ≥55%, 35% to 54% and <35%. Significant Holter findings included atrial tachycardia, ventricular tachycardia and atrial fibrillation/flutter. Logistic regression was used to assess predictors of significant Holter findings and change in care. The study included 442 Holters in 235 patients. Mean age was 14±4 years. Patients with cardiac dysfunction were older, and had increased late gadolinium enhancement and left ventricular dilation (P<0.01). There were 3 deaths (1%), all with normal function and none cardiac. Patients with LVEF <35% had more arrhythmias including nonsustained atrial tachycardia (P=0.01), frequent premature ventricular contractions, ventricular couplets/triplets, and nonsustained ventricular tachycardia (P<0.001) compared to the other groups. LVEF <35% (P<0.001) was the only predictor of clinically significant Holter finding. Four patients (40%) had change in medication in the LVEF <35% group compared to 9 (3%) in the ≥55% and 4 (4%) in the 35% to 54% groups (P<0.001)., Conclusions: Sudden cardiac events are rare in DMD patients with an LVEF >35%. Significant Holter findings are rare in patients with DMD who have an LVEF >35%, and cardiac dysfunction appears to predict significant Holter findings. Holter monitoring is highest yield among DMD patients with cardiac dysfunction., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)