Heart transplantation in neonatal Marfan syndrome: Saving life in a rare and fatal condition.

BACKGROUND: Neonatal Marfan syndrome is a rare disease with mortality in the first year of life reported as high as 95% predominantly due to progressive heart failure from valvar regurgitation and cardiomyopathy. Multisystem involvement and uncertain prognosis have historically precluded transplant candidacy, and current management options are of limited success. CASE REPORT: We present a baby girl with a postnatal diagnosis of neonatal Marfan syndrome who at 1 year of age underwent mitral valve and tricuspid valve repair with postoperative profound left ventricular and moderate right ventricular dysfunction necessitating biventricular assist device (BiVAD) support and subsequent heart transplant. A number of noncardiac issues persisted in our patient; however, she enjoyed a good quality of life for the initial 3 years posttransplant. Unfortunately, she subsequently developed rapidly progressive coronary allograft vasculopathy (CAV) with progressive deterioration in function and cardiac arrest. CONCLUSION: To our best knowledge, this is only the second case of neonatal Marfan syndrome to undergo heart transplant reported in the literature and the first with BiVAD support as a bridge to candidacy. This is also the first case of neonatal Marfan syndrome associated with intragenic duplication. This case though demonstrating that earlier listing, ventricular assist device (VAD) support and even primary transplant as treatment in neonatal Marfan syndrome should all be considered viable options but also portends a cautionary tale given the spectrum of comorbidities in this rare and severe disorder.

When is enough, enough? Exploring ethical and team considerations in paediatric cardiac care dilemmas.

PURPOSE OF REVIEW: Therapies for paediatric congenital and acquired heart disease continue to evolve and the appropriateness of pursuing life sustaining interventions at margins of standard therapy is ethically challenging. RECENT FINDINGS: With ongoing emphasis on shared decision making, recent literature explored physician and parental perspectives on communication with families and offering interventions for complex congenital heart disease and advanced heart failure. The inclusion of parental values and views in this process is now widely accepted. Identified outstanding challenges include difficulty with prognostication from the outset, adjusting long-term goals of care to changes in clinical parameters, need for consistency in communication including regular review meetings with family or surrogate decision-makers. Bioethics consultation and multidisciplinary team reviews may be helpful supports. Palliative care involvement in this population improves quality of life and alleviates parental distress but this collaboration is not optimized. SUMMARY: Decision to offer, forgo, or discontinue life-sustaining therapies for children with heart disease has nuanced and context-specific considerations, and must integrate burdens of interventions with patient and family values. Thus, decision making remains complex and demands thoughtful review of not only risks and benefits, but views and values, clearly communicated to team and family.

"Acquired" Brugada syndrome in a cardiac allograft.

INTRODUCTION: Brugada syndrome is an inherited channelopathy characterized by arrhythmia and an increased risk of sudden cardiac death (SCD). Implantation of a defibrillator for primary or secondary prevention is the only effective strategy to decrease the risk of SCD in Brugada syndrome. We present a case in which a cardiac donor had a pathogenic variant for Brugada syndrome, discovered on genetic testing after transplantation. CASE REPORT: A young child with dilated cardiomyopathy underwent orthotopic heart transplantation from a donor with in-hospital cardiac arrest in the context of fever and a normal ECG. Approximately 1 month after transplant, the donor's post mortem genetic testing revealed a pathogenic loss-of-function SCN5A variant associated with Brugada syndrome, which was confirmed on genetic testing on a post-transplant endomyocardial biopsy from the recipient. The recipient's post-transplant electrocardiographic monitoring revealed persistent right bundle branch block and progressive, asymptomatic sinus node dysfunction. The recipient was managed with precautionary measures including aggressive fever management, avoidance of drugs that increase arrhythmia risk in Brugada syndrome, and increased frequency of arrhythmia surveillance. The recipient remains asymptomatic at over 3 years post-transplant with preserved graft function and no documented ventricular arrhythmias. CONCLUSION: We describe the clinical course of "acquired" Brugada syndrome in a cardiac allograft recipient, which has not been previously reported. The time-sensitive nature of donor organ selection, especially in critically ill recipients, combined with the growing use of molecular autopsies in patients with unexplained etiologies for death may increasingly result in important donor genetic information being made available after transplantation.

Barriers to effective, safe communication and workflow between nurses and non-consultant hospital doctors during out-of-hours.

OBJECTIVE: This study aimed to evaluate the nature and type of communication and workflow arrangements between nurses and doctors out-of-hours (OOH). Effective communication and workflow arrangements between nurses and doctors are essential to minimize risk in hospital settings, particularly in the out-of-hour's period. Timely patient flow is a priority for all healthcare organizations and the quality of communication and workflow arrangements influences patient safety. DESIGN: Qualitative descriptive design and data collection methods included focus groups and individual interviews. SETTING: A 500 bed tertiary referral acute hospital in Ireland. PARTICIPANTS: Junior and senior Non-Consultant Hospital Doctors, staff nurses and nurse managers. RESULTS: Both nurses and doctors acknowledged the importance of good interdisciplinary communication and collaborative working, in sustaining effective workflow and enabling a supportive working environment and patient safety. Indeed, issues of safety and missed care OOH were found to be primarily due to difficulties of communication and workflow. Medical workflow OOH is often dependent on cues and communication to/from nursing. However, communication systems and, in particular the bleep system, considered central to the process of communication between doctors and nurses OOH, can contribute to workflow challenges and increased staff stress. It was reported as commonplace for routine work, that should be completed during normal hours, to fall into OOH when resources were most limited, further compounding risk to patient safety. CONCLUSION: Enhancement of communication strategies between nurses and doctors has the potential to remove barriers to effective decision-making and patient flow.

Outcomes of Children With Hypoplastic Left Heart Syndrome and Heart Failure on Medical Therapy.

Background: Systemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. Objectives: The authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. Methods: The SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. Results: Of 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. Conclusions: Our cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.

Pitfalls and Possibilities of Ventricular Assist Device Support in Congenitally Corrected Transposition of the Great Arteries in Children.

Congenitally corrected transposition of the great arteries (ccTGAs) represents a complex form of congenital heart disease that is associated with several cardiac complications. Herein is a case series of three children with ccTGA and ventricular assist device (VAD) inserted for systemic right ventricle failure at a single institution. All patients remained hemodynamically stable postimplant and were successfully discharged from the intensive care unit to undergo postoperative rehabilitation. All three patients received an orthotopic heart transplant with uneventful posttransplant courses. This case series provides insight into the medical management and technical feasibility of VAD support in children with ccTGA with end-stage heart failure.

Symptomatic presentation influences outcomes in pediatric restrictive cardiomyopathy.

Introduction: Children with restrictive cardiomyopathy (RCM) traditionally have a poor prognosis, with most patients either dying or requiring heart transplantation within 2 years of diagnosis. The development of symptoms in RCM suggests advanced disease. However, as screening practices evolve and lead to diagnosis of early disease, identifying appropriate timing of transplant listing becomes increasingly important. In this context we compared outcomes of children with RCM presenting with clinical symptoms to those asymptomatic at initial presentation. Methods: This retrospective cohort study included 25 patients with RCM presenting to a quaternary care center between 2001 and 2018. Times to transplantation, death, and a composite outcome of adverse cardiac events (CPR, cardioversion, inotropic support, mechanical ventilation, mechanical support, or heart transplant) were compared between those symptomatic and asymptomatic at presentation. Results: At 2 years following diagnosis, patients asymptomatic at presentation had a significantly better transplant-free survival at 57% compared to 17% for symptomatic patients (p = 0.03). Those asymptomatic at diagnosis also had significantly improved cardiac event-free survival at 71% compared to symptomatic patients at 25% (p = 0.01). In multivariable analysis, cardiac symptoms at presentation remained an independent risk factor for heart-transplant or death [hazard ratio 5.17 (1.28-20.85), p = 0.02]. Conclusion: Patients with RCM who are symptomatic at time of diagnosis have significantly worse transplant-free survival and cardiac event-free survival. Given current practice variability in timing of transplant listing, the presence of any cardiac symptoms is an important negative prognostic marker and should prompt urgent transplant listing.

Risk of Sudden Death in Patients With RASopathy Hypertrophic Cardiomyopathy.

BACKGROUND: Genetic defects in the RAS/mitogen-activated protein kinase pathway are an important cause of hypertrophic cardiomyopathy (RAS-HCM). Unlike primary HCM (P-HCM), the risk of sudden cardiac death (SCD) and long-term survival in RAS-HCM are poorly understood. OBJECTIVES: The study's objective was to compare transplant-free survival, incidence of SCD, and implantable cardioverter-defibrillator (ICD) use between RAS-HCM and P-HCM patients. METHODS: In an international, 21-center cohort study, we analyzed phenotype-positive pediatric RAS-HCM (n = 188) and P-HCM (n = 567) patients. The between-group differences in cumulative incidence of all outcomes from first evaluation were compared using Gray's tests, and age-related hazard of all-cause mortality was determined. RESULTS: RAS-HCM patients had a lower median age at diagnosis compared to P-HCM (0.9 years [IQR: 0.2-5.0 years] vs 9.8 years [IQR: 2.0-13.9 years], respectively) (P < 0.001). The 10-year cumulative incidence of SCD from first evaluation was not different between RAS-HCM and P-HCM (4.7% vs 4.2%, respectively; P = 0.59). The 10-year cumulative incidence of nonarrhythmic deaths or transplant was higher in RAS-HCM compared with P-HCM (11.0% vs 5.4%, respectively; P = 0.011). The 10-year cumulative incidence of ICD insertions, however, was 5-fold lower in RAS-HCM compared with P-HCM (6.9% vs 36.6%; P < 0.001). Nonarrhythmic deaths occurred primarily in infancy and SCD primarily in adolescence. CONCLUSIONS: RAS-HCM was associated with a higher incidence of nonarrhythmic death or transplant but similar incidence of SCD as P-HCM. However, ICDs were used less frequently in RAS-HCM compared to P-HCM. In addition to monitoring for heart failure and timely consideration of advanced heart failure therapies, better risk stratification is needed to guide ICD practices in RAS-HCM.

Left Ventricular Noncompaction Cardiomyopathy: Left Ventricular Dilation and Dysfunction at Baseline Portend the Risk of Death or Heart Transplantation.

BACKGROUND: Left ventricular noncompaction (LVNC) is associated with genetic and phenotypic variability that influences outcomes. We aimed to identify risk factors for death or heart transplantation (HTx) in a paediatric LVNC cohort. METHODS: We reviewed patients < 18 years of age (2001-2018) with LVNC, either isolated (I-LVNC) or with dilated phenotype (D-LVNC), and at least mildly reduced left ventricular ejection fraction (EF). Patients with dilated cardiomyopathy (DCM) were included as control subjects. Descriptive statistics, multivariate analysis, and time-to-event analysis were used. RESULTS: We included 188 patients, 34 (18%) with I-LVNC, 37 (20%) with D-LVNC, and 117 (62%) with DCM. Overall median age at diagnosis was 1.08 years (interquartile range [IQR] 0.22-10.65) and median follow-up was 1.4 years (IQR 0.2-5.2) years. I-LVNC patients' median baseline LVEF was 47%, compared with 33% for D-LVNC, and 21% for DCM (P < 0.0001); 62% of I-LVNC patients developed moderate to severe LV dysfunction during follow-up. The incidence of death or transplantation was 43.6% in the overall cohort. Freedom from death or HTx at 10 years after diagnosis was 88.6% (95% CI 76%-100%) for I-LVNC, 47% (95% CI 29%-65%) for D-LVNC, and 42.3% (95% CI 33%-52%) for DCM. On multivariable analysis, baseline LVEF and LV end-diastolic diameter (LVEDD) z-score were associated with death or transplantation. Patients with a baseline LVEDD z-score > 4 and moderate to severe LV dysfunction had a transplantation-free survival of 38%. CONCLUSIONS: Baseline LV dilation and systolic dysfunction were independently associated with progression to death or HTx in LVNC patients.