Ivan Wilmot

Pediatric heart transplant waiting list mortality in the era of ventricular assist devices

BACKGROUND Earlier reviews have reported unacceptably high incidence of pediatric heart transplant (PHT) waiting list mortality. An increase in ventricular assist devices (VAD) suggests a potential positive effect. This study evaluated PHT waiting list mortality in the era of pediatric VADs. METHODS United Network of Organ Sharing (UNOS) database from 1999 to 2012 showed 5,532 pediatric candidates (aged ≤ 18 years) actively listed for PHT: 2,191 were listed in 1999 to 2004 (Era 1) and 3,341 were listed in 2005 to 2012 (Era 2). RESULTS Waiting list mortality was lower in Era 2 (8%) vs Era 1 (16%; p < 0.001). VAD therapy was used more frequently in Era 2 (16%) than in Era 1 (6%; p < 0.001) and was associated with better waiting list survival (p < 0.001). There were more UNOS Status 1A patients in Era 2 (80%) vs Era 1 (68%; p < 0.001). Independent predictors of waiting list mortality included weight < 10 kg (odds ratio [OR], 2.7 95% confidence interval [CI], 1.1-6.9), congenital heart disease diagnosis (OR, 2.4; 95% CI, 1.9-3.0), blood type O (OR, 2.2; 95% CI, 1.8-2.8)], extracorporeal membrane oxygenation (OR, 1.5; 95% CI, 1.1-2.2), mechanical ventilation (OR, 1.8; 95% CI, 1.4-2.3), and renal dysfunction (OR 1.6; 95% CI, 1.2-2.0). Independent predictors of survival on the waiting list included VAD therapy (OR 4.2; 95% CI, 2.4-7.6), cardiomyopathy diagnosis (OR 3.3; 95% CI, 2.4-4.6), blood type A (OR, 2.2; 95% CI, 1.8-2.8), UNOS list Status 1B (OR, 1.9; 95% CI, 1.2-3.0), listed in Era 2 (OR 1.8; 95% CI, 1.4-2.2), and white race (OR 1.3; 95% CI, 1.1-1.6). CONCLUSIONS Despite an increase in the number of children listed as Status 1A, there was more than a 50% reduction in waiting list mortality in the new era. Irrespective of other factors, patients supported with a VAD were 4 times more likely to survive to transplant.

Pediatric Mechanical Circulatory Support

Mechanical circulatory support (MCS) in the pediatric heart failure population has a limited history especially for infants, and neonates. It has been increasingly recognized that there is a rapidly expanding population of children diagnosed and living with heart failure. This expanding population has resulted in increasing numbers of children with medically resistant end-stage heart failure. The traditional therapy for these children has been heart transplantation. However, children with heart failure unlike adults do not have symptoms until they present with end-stage heart failure and therefore, cannot safely wait for transplantation. Many of these children were bridged to heart transplantation utilizing extracorporeal membranous oxygenation as a bridge to transplant which has yielded poor results. As such, industry, clinicians, and the government have refocused interest in developing increasing numbers of MCS options for children living with heart failure as a bridge to transplantation and as a chronic therapy. In this review, we discuss MCS options for short and long-term support that are currently available for infants and children with end-stage heart failure.

Health-related quality of life in children with heart failure as perceived by children and parents.

Advancements in paediatric heart failure management have resulted in improved survival and a focus on long-term outcomes including health-related quality of life. We compared health-related quality of life in children with heart failure with healthy patients, children with chronic conditions, and children with cardiovascular disease. Families (n=63) and children (n=73) aged 2-20 years with heart failure were enrolled and compared with data previously published for healthy patients (n=5480), those with chronic conditions (n=247), and those with cardiovascular disease (n=347). Patients and parents completed the PedsQL 4.0 and the Cardiac 3.0 Module health-related quality-of-life questionnaires. PedsQL scores including Total, Psychosocial Health Summary, and Physical were compared between groups. In general, patients with heart failure had lower scores than the healthy population (p=0.001), and comparable scores with those with chronic conditions. Parents perceived no difference in physical scores for children with heart failure when compared with healthy children, and perceived higher scores for children with heart failure when compared with those with chronic conditions (p⩽0.003). Furthermore, children with heart failure had decremental health-related quality-of-life scores as the American Heart Association stage of heart failure increased, such that patients with stage C heart failure had scores similar to children with severe cardiovascular disease. Children with heart failure reported significantly impaired health-related quality of life compared with healthy children and similar scores compared with children with chronic conditions. Parental perceptions appear to underestimate these impairments. Children with heart failure appear to have progressive impairment of health-related quality of life with advancing stage of heart failure.

Outcomes, Arrhythmic Burden and Ambulatory Monitoring of Pediatric Patients With Left Ventricular Non-Compaction and Preserved Left Ventricular Function

Pediatric patients with left ventricular noncompaction (LVNC) and severe ventricular dysfunction are at risk for sudden death. The aims of this study were to (1) evaluate outcomes, (2) describe arrhythmic burden on Holter monitoring, and (3) analyze the utility of Holter monitoring and its impact on care in pediatric patients with LVNC and preserved or mild ventricular dysfunction. This was a retrospective study including patients <21 years of age with LVNC and ejection fractions ≥45%. Demographic and outcome data were analyzed. Individual and cumulative Holter data were evaluated for all patients. Arrhythmias, conduction system disease, and symptoms were analyzed for each Holter recording. The incidence of significant findings and the impact on care were determined for each study. Outcome and Holter data were compared between patients on the basis of the ejection fraction (≥55% [normal] or ≥45% to <55% [mild]). This study included 72 patients, 65 with normal function and 7 with mild dysfunction (mean age 13 years). There was a single death in the cohort, which was sudden in nature. Simple ventricular ectopy was common on Holter monitoring and more common in patients with mild dysfunction (86% vs 27%, p = 0.005). Significant Holter findings (4% vs 6%) and changes to patient care (2% vs 4%) improved with cumulative Holter monitoring. In conclusion, in contrast to patients with severe dysfunction, pediatric patients with LVNC and normal or mild dysfunction have significantly better outcomes. However, worsening LV systolic function was correlated with increasing ventricular ectopy. The role of Holter monitoring is unknown, but it may have utility in patient care if used as part of ongoing screening.

The use of a Berlin Heart EXCOR LVAD in a child receiving chemotherapy for Castleman's disease

We present the unique case of a pediatric patient who received chemotherapy for a diagnosis of CD, while mechanically supported with a Berlin EXCOR LVAD secondary to restrictive cardiomyopathy. A four‐yr‐old previously healthy male with restrictive cardiomyopathy required MCS after cardiac arrest but was diagnosed with multicentric CD, a non‐malignant lymphoproliferative disorder fueled by excessive IL‐6 production. Treatment with IL‐6 blockade (tocilizumab) every two wk and methylprednisolone had no effect on his lymph nodes or cardiac function while on temporary RotaFlow. A Berlin LVAD was placed for treatment with rituximab, COP, vincristine, and methylprednisolone. After three courses of chemotherapy, his inflammatory markers normalized and his lymphadenopathy decreased but cardiac function remained severely depressed. He tolerated chemotherapy on the Berlin but required frequent titrations of his anti‐coagulation regimen and he did suffer a hemorrhagic stroke. His clinical status improved significantly with rehabilitation, and he tolerated heart transplantation without further complications. MCS is a feasible option as a bridge to recovery or heart transplant eligibility for patients with hemodynamic collapse requiring chemotherapy but it does necessitate close titration of the anti‐coagulation regimen to coincide with changes in the inflammatory state.

Preventing pediatric cardiomyopathy: a 2015 outlook

ABSTRACT Cardiomyopathies in children encompass a broad range of diseases, both genetic and acquired, which manifest as a primary cardiac disorder or as a cardiomyopathy secondary to systemic disease. The burden of this group of disorders is substantial, and growing on a global scale. The availability of disease altering treatments is limited, and therefore a focused review on the prevention of cardiomyopathies is justified. In this review, we address the prevention of cardiomyopathy in children by dealing with the root causes of disease at a molecular, clinical and population level. Recent years have yielded promising returns in basic research related to gene-targeted therapy, specific anti-viral therapies and modification of the effects of cardiotoxic drugs. Much work remains to be done in the fields of vaccine development, public health and adoption of available treatments. Effective research in this field will require that diagnostic methods are both refined, and made available more broadly, from imaging to gene testing. Much of our knowledge today is derived from the use of registries, which have successfully catalogued the detailed phenotype of affected patients, and provided long-term longitudinal follow up of affected individuals.

Quality of Life and Psychosocial Care in Pediatric Heart Failure

Abstract Advances in both medical and surgical management of children living with cardiovascular disease have resulted in improved survival in this population. However, children living with cardiovascular disease are often required to abide by physical activity restrictions, medications, and chronic long-term follow-up, which can impair health-related quality of life (HRQOL). Additionally, advanced therapies including implantable cardioverter–defibrillators (ICDs), cardiac resynchronization therapy (CRT), and increasingly utilized mechanical circulatory support (MCS) in this population can further affect HRQOL. Additionally, heart failure (HF) is increasingly appreciated as a syndrome affecting many organ systems including the brain, mental health, and HRQOL. HRQOL is appreciated as an important long-term outcome measure in the management of adults living with HF and is increasingly appreciated as such in the pediatric HF population.

Fontan-associated protein-losing enteropathy and post-heart transplant outcomes: a multicenter study

BACKGROUND The influence of Fontan-associated protein-losing enteropathys (PLE) severity, duration, and treatment on heart transplant (HTx) outcomes is unknown. We hypothesized that long-standing PLE and PLE requiring more intensive therapy are associated with increased post-HTx mortality. METHODS This 12-center, retrospective cohort study of post-Fontan patients with PLE referred for HTx from 2003 to 2015 involved collection of demographic, medical, surgical, and catheterization data, as well as PLE-specific data, including duration of disease, intensity/details of treatment, hospitalizations, and complications. Factors associated with waitlist and post-HTx outcomes and PLE resolution were sought. RESULTS Eighty patients (median of 5 per center) were referred for HTx evaluation. Of 68 patients listed for HTx, 8 were removed due to deterioration, 4 died waiting, and 4 remain listed. In 52 patients undergoing HTx, post-HTx 1-month survival was 92% and 1-year survival was 83%. PLE-specific factors, including duration of PLE pre-HTx, pre-HTx hospitalizations, need for/frequency of albumin replacement, PLE therapies, and growth parameters had no association with post-HTx mortality. Immunosuppressant regimen was associated with mortality; standard mycophenolate mofetil immunotherapy was used in 95% of survivors compared with only 44% of non-survivors (p = 0.03). Rejection (53%) and infection (42%) post-HTx were common, but not associated with PLE-specific factors. PLE resolved completely in all but 1 HTx survivor at a median of 1 month (interquartile range 1 to 3 months); resolution was not affected by PLE-specific factors. CONCLUSIONS PLE severity, duration, and treatment do not influence post-HTx outcome, but immunosuppressive regimen may have an impact on survival. PLE resolves in nearly all survivors.

Pediatric Heart Transplantation Long-Term Survival in Different Age and Diagnostic Groups: Analysis of a National Database

Background: The purpose of this study was to evaluate differences in long-term survival without the influence of early mortality, and to identify factors associated with one-year conditional ten-year survival after heart transplantation (HTx) across different age and diagnostic groups. Methods: Organ Procurement and Transplant Network data from January 1990 to December 2005 were used. Cohort was divided according to age (infants [<1 year], children [>1-10 years], and adolescents [11-18 years]) and diagnosis (cardiomyopathy and congenital heart disease [CHD]). Factors associated with one-year conditional ten-year survival were identified using multivariable logistic regression and using a case–control design. Results: One-year conditional ten-year survivors included 1,790 patients compared to 1,114 patients who died after the first posttransplant year and within ten years of transplant with a median follow-up of 4.8 years. Predictors of one-year conditional ten-year survival for infants were recipient’s Caucasian race (odds ratio [OR]: 1.9, 95% confidence interval [CI]: 1.3-2.7) and donor–recipient weight ratio (OR: 0.8, 95% CI: 0.6-1); for children: Caucasian race (OR: 1.6, 95% CI: 1.2-2.1), retransplantation (OR: 0.4, 95% CI: 0.2-0.6), and transplantation after the year 2000 (OR: 1.5, 95% CI: 1.1-2.1); for adolescents only Caucasian race (OR: 2.5, 95% CI: 1.9-2.3). In both CHD and cardiomyopathy, adolescents had worse survival compared to infants and children. There was an era effect with improved survival after 2000. Male gender was a predictor of survival in cardiomyopathy group. Conclusion: Predictors of one-year conditional ten-year survival varied among groups. These data and analyses provide important information that may be useful to clinicians, particularly when counseling patients and families regarding expectations of survival after pediatric HTx.

Dilated Cardiomyopathy and Cardioskeletal Involvement

Dilated cardiomyopathy encompasses a large heterogeneous group of genetically triggered and acquired etiologies. Cardioskeletal involvement in this population is increasingly identified. Recognition of multifactorial causes such as genetics, proteomics, and inflammation offer a more overarching and unifying explanation for cardioskeletal disease. The neuromuscular patient with Duchene muscular dystrophy provides a vivid example of cardioskeletal disease. In such patients the heritable defect in dystrophin leads to abnormal protein formation, inflammation in both cardiac and skeletal myocytes, and ultimately cardioskeletal disease. Similarly, acquired autoimmune inflammatory processes such as dermatomyositis are associated with inflammation and injury of myocytes and can result in cardioskeletal disease. In this chapter we discuss both heritable and acquired etiologies of dilated cardiomyopathy and explain some of the links to cardioskeletal disease. We discuss the evaluation and diagnosis of dilated cardiomyopathy and the subsequent management. Finally, we explore future directions that may further clarify the relationship between dilated cardiomyopathy and cardioskeletal disease.