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OBJECTIVE: To assess the diagnostic yield of exome sequencing (ES) in pediatric cardiomyopathy. STUDY DESIGN: A single-institution, retrospective chart review of 91 patients with pediatric cardiomyopathy was performed. While pediatric cardiomyopathy is often genetic in nature, no genetic test is recommended as standard of care. All our patients were diagnosed with cardiomyopathy and evaluated by a medical geneticist between January 2010 through September 2022. Demographic information and clinical data were abstracted. RESULTS: Of 91 patients with pediatric cardiomyopathy, 36 (39.6%) received a diagnosis by ES. Twenty-two (61.1%) of these diagnoses would have been missed on cardiac multigene panel testing. The diagnostic yield for cardiomyopathy presenting under 1 year of age was 38.3%, while the yield for patients over 1 year of age was 41.9%. CONCLUSIONS: ES has a high diagnostic yield in pediatric cardiomyopathy compared with a gene panel. Over 60% of patients with diagnosis by ES would not have received their molecular genetic diagnosis if only multigene panel testing was sent. Diagnostic yield did not vary significantly between the subtypes of cardiomyopathy and patient age groups, highlighting the likely clinical utility of ES for all pediatric cardiomyopathy patients.
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Cardiomiopatias , Médicos , Humanos , Criança , Sequenciamento do Exoma , Estudos Retrospectivos , Testes Genéticos , Cardiomiopatias/diagnóstico , Cardiomiopatias/genéticaRESUMO
OBJECTIVE: To evaluate the effectiveness of patient education, physician counseling, and point-of-care (POC) testing on improving adherence to lipid screening national guidelines in a general pediatric cardiology practice (2017-2023). STUDY DESIGN: Regional primary care providers were surveyed regarding lipid screening practices. Key drivers were categorized (physician, patient, and system) with corresponding interventions. Pediatric cardiologists started offering lipid screening during regular visits by providing families with preventive cardiovascular education materials and lab phlebotomy testing. System redesign included educational posters, clinical intake protocol, physician counseling, electronic health record integration, and POC testing. Run charts and statistical process control charts measured screening rates and key processes. RESULTS: The primary care survey response rate was 32% (95/294); 97% supported pediatric cardiologists conducting routine lipid screening. Pediatric cardiology mean baseline lipid screening rate was 0%, increased to 7% with patient education, and to 61% after system redesign including POC testing. Screening rates among 1467 patients were similar across age groups (P = .98). More patients received lipid screening by POC (91.7%) compared with phlebotomy (8.3%). Lipid abnormalities detected did not differ by screening methodology (P = .49). CONCLUSION: Patient education, counseling, and POC testing improved adherence to national lipid screening guidelines, providing a possible model for primary care implementation.
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Cardiac dysfunction due to hypertension (CDHTN) in pediatrics is not well described. We aimed to describe the presentation and outcomes of pediatric CDHTN and identify clinical features associated with resolution of dysfunction. A single-center retrospective cohort study of patients ≤ 21 years with CDHTN from January 2005-September 2020 was performed. Patients with systolic dysfunction without another cause, blood pressure > 95th percentile, and physician judgment that dysfunction was secondary to hypertension were included. Demographics, clinical characteristics, echocardiographic findings, and outcomes were examined using Fisher's exact and Mann-Whitney U tests. Multiple correspondence analysis was used to explore the relationship of resolution of dysfunction to clinical features. Thirty-four patients were analyzed at a median age of 10.9 (IQR 0.3-16.9) years. Patients were divided into groups < 1 year (n = 12) and ≥ 1 year (n = 22). Causes of hypertension were varied by age, with renovascular disease most common in infants (42%) and medical renal disease most common in older patients (77%). Echocardiography demonstrated mild LV dilation (median LV end-diastolic z-score 2.6) and mild LV hypertrophy (median LV mass z-score 2.4). Most patients (81%) had resolution of dysfunction, particularly infants (92%). One patient died and one patient was listed for heart transplant. None required mechanical circulatory support (MCS). No clinical features were statistically associated with resolution of dysfunction. Hypertension is an important but reversible cause of systolic dysfunction in children. Patients are likely to recover with low mortality and low utilization of MCS or transplantation. Further studies are needed to confirm features associated with resolution of dysfunction.
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Cardiomiopatias , Hipertensão , Disfunção Ventricular Esquerda , Lactente , Humanos , Criança , Idoso , Pré-Escolar , Adolescente , Estudos Retrospectivos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Hipertensão/complicações , Cardiomiopatias/complicações , EcocardiografiaRESUMO
Outcomes in patients requiring prolonged inotropes (PI) following surgery for congenital heart disease (CHD) have not been well studied. We aimed to describe the burden of PI use in the immediate postoperative period after CHD surgery and identify risk factors for in-hospital mortality. We conducted a retrospective cohort study using the Pediatric Health Information System® (PHIS) database. Patients 0-18 years with CHD who underwent cardiovascular surgery from 2010 to 2020 were included. Patients who received inotropic medications for > 7 consecutive days after surgery were in the PI group and all others in the control group. Patients who died before 7 days were excluded. Multivariable mixed-effect logistic regression was used to examine risk factors for in-hospital mortality. There were 110,271 patients from 48 centers included, 10,292 in the PI group and 99,979 in the control group. In-hospital mortality was significantly higher in the PI group (24.9% vs. 4.6%, p < 0.001). Ventricular assist device use was rare (1.6%). After adjustment, odds of in-hospital mortality in the PI group was 3.5 (95% CI 3.3-3.8) times higher than in controls. Independent risk factors for in-hospital mortality were age, non-White race, class of CHD, number of complex chronic conditions, preoperative inotrope, preoperative extracorporeal membrane oxygenation, sepsis, stroke, renal failure, number of inotropes at 7 days, and discharge year (p < 0.01 for all). Postoperative PI use in CHD is common and carries a considerable burden of mortality. Additional work is needed to understand which risk factors are modifiable and which patients may benefit from reintervention or advanced heart failure therapies.
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In children with hypertrophic cardiomyopathy (HCM), the genotype-phenotype association of abnormal electrocardiographic (ECG) features in the backdrop of gene positivity has not been well described. This study aimed to describe the abnormal ECG findings in children with HCM harboring who have genetic variants and determine the association with major adverse cardiac events (MACE). We retrospectively analyzed 81 variants-positive, phenotype-positive (V+P+), 66 variant-positive, phenotype-negative (V+P-), and 85 non-sarcomeric subjects. We analyzed ECG findings and clinical outcomes in the three groups of subjects. Repolarization abnormalities (ST and T wave changes) and pathologic Q waves were the most common abnormalities in variant and non-sarcomeric subjects. The V+P+ group showed higher occurrence of ST segment changes and T wave abnormalities compared to V+P- group. Independent predictors of MACE included ST segment changes (OR 3.54, CI 1.20-10.47, p = 0.022). T wave changes alone did not predict outcome (OR 2.13, CI 0.75-6.07, p = 0.157), but combined repolarization abnormalities (ST+T changes) were strong predictors of MACE (OR 5.84, CI 1.43-23.7, p = 0.014) than ST segment changes alone. Maximal wall z score by echocardiography was a predictor of MACE (OR 1.21, CI 1.07-1.37, p = 0.002). Despite the presence of significant myocardial hypertrophy (z score > 4.7), voltage criteria for LVH were much less predictive. In the non-sarcomeric group, RVH was significantly associated with MACE (OR 3.85, CI 1.08-13.73, p = 0.038). These abnormal ECG findings described on the platform of known genetic status and known myocardial hypertrophy may add incremental value to the diagnosis and surveillance of disease progression in children with HCM. Select ECG findings, particularly repolarization abnormalities, may serve as predictors of MACE in children.
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Noonan syndrome is an inherited disorder caused by alterations in the RAS-MAPK pathway. There have been several identified genotype-phenotype associations made with respect to congenital cardiac lesions and Noonan syndrome variants, but limited data exist regarding single ventricle disease in this population. Here, we report two patients with PTPN11-related Noonan syndrome and hypoplastic left heart syndrome variants.
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Síndrome do Coração Esquerdo Hipoplásico , Síndrome de Noonan , Humanos , Síndrome de Noonan/complicações , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Síndrome do Coração Esquerdo Hipoplásico/complicações , Síndrome do Coração Esquerdo Hipoplásico/genética , Mutação , Estudos de Associação Genética , FenótipoRESUMO
The relationship between center-specific variation in indication for pediatric heart transplantation and short-term outcomes after heart transplantation is not well described. We used merged patient- and hospital-level data from the United Network for Organ Sharing and the Pediatric Health Information Systems to analyze outcomes according to transplant indication for a cohort of children (≤ 21 years old) who underwent heart transplantation between 2004 and 2015. Outcomes included 30-day mortality, transplant hospital admission mortality, and hospital length of stay, with multivariable adjustment performed according to patient and center characteristics. The merged cohort reflected 2169 heart transplants at 20 U.S. centers. The median number of transplants annually at each center was 11.6, but ranged from 3.5 to 22.6 transplants/year. Congenital heart disease was the indication in the plurality of cases (49.2%), with cardiomyopathy (46%) and myocarditis (4.8%) accounting for the remainder. There was significant center-to-center variability in congenital heart disease as the principal indication, ranging from 15% to 66% (P < 0.0001). After adjustment, neither center volume nor proportion of indications for transplantation were associated with 30-day or transplant hospital admission mortality. In this large, merged pediatric cohort, variation was observed at center level in annual transplant volume and prevalence of indications for heart transplantation. Despite this variability, center volume and proportion of indications represented at a given center did not appear to impact short-term outcomes.
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Sistemas de Informação em Saúde , Cardiopatias Congênitas , Transplante de Coração , Adulto , Criança , Estudos de Coortes , Cardiopatias Congênitas/cirurgia , Hospitalização , Humanos , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Children with advanced heart failure may require ventricular assist devices (VAD) while awaiting heart transplantation. Currently, no data exist regarding the safety of exercise rehabilitation (ER) in children on VAD support. The purpose of this study was to determine the safety and feasibility of ER in children on VAD support awaiting heart transplantation. Eligible patients underwent VAD placement between 1998 and 2019; both inpatient and outpatient participants were included. After VAD implantation and when ambulatory, patients were enrolled in ER. Exercise sessions were scheduled three times a week and consisted of aerobic and musculoskeletal conditioning. A total of 29 patients (59% male, mean age 14 ± 3.2 years) were included with a median VAD duration of 120 ± 109 days. Cardiac diagnoses included cardiomyopathy (81%) and congenital heart disease (19%). VAD type included pulsatile (59%) and continuous-flow devices (41%). Eight hundred and sixty-four (85%) ER sessions were successfully completed and began at a mean of 49 days (range 19-108) after VAD implant. No adverse events, including episodes of hypotension, significant complex arrhythmia, or VAD malfunction occurred during exercise testing or ER, and no sessions were discontinued prematurely. Pediatric patients on VAD support can safely participate in ER with relatively high compliance, and sessions can be implemented early after VAD implantation. Given the safety profile, ER in pediatric VAD recipients, which is a modifiable pre-transplant risk factor that may improve functional capacity, warrants further study as a potential modality to improve post-transplant outcomes.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Adolescente , Criança , Estudos de Viabilidade , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Cardiac disease in pediatric patients due to coronavirus SARS-CoV-2 disease (COVID-19) includes myocarditis and multisystem inflammatory syndrome, both of which can present with a broad range in severity. Here we describe an infant with COVID-19 causing fulminant myocarditis with inotrope-resistant acute heart failure requiring extracorporeal membrane oxygenation. The patient demonstrated an atypical finding of localized septal thickening suggestive of hypertrophic cardiomyopathy, but the diagnosis of myocarditis was confirmed by cardiac MRI. Serial echocardiography illustrated complete resolution of septal hypertrophy and normalized cardiac function. The current report highlights the potential severity of COVID-19 associated myocarditis, the potential for recovery, and the utility of cardiac MRI in confirming the mechanism.
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There are limited data describing the prevalence of mental health disorders (MHDOs) in patients with ventricular assist devices (VADs), or associations between MHDOs and resource use or outcomes. We used the Nationwide Emergency Department Sample administrative database to analyze 44,041 ED encounters for VAD-supported adults from 2010 to 2017, to assess the relationship between MHDOs and outcomes in this population. MHDO diagnoses were present for 23% of encounters, and were associated with higher charges and rates of admission, but lower mortality.
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Serviço Hospitalar de Emergência/estatística & dados numéricos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Transtornos Mentais/epidemiologia , Adolescente , Adulto , Idoso , Comorbidade , Utilização de Instalações e Serviços , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: To provide sex, age, and race specific reference values for ramp cycle ergometer cardiopulmonary exercise test (CPET) in children in the US. STUDY DESIGN: Retrospective review was conducted of all cardiopulmonary CPET data from our Exercise Physiology Laboratory on healthy children and adolescents (6-18 years) with body mass index between the 5th and 95th percentiles and structurally normal hearts who performed a ramp cycle ergometry stress test between 1999 and 2015. Twenty-eight exercise variables were included: peak oxygen consumption, oxygen consumption at ventilatory anaerobic threshold, peak work rate, resting and peak heart rate and blood pressure, resting pulmonary function testing, and ventilatory responses to progressive exercise using breath-by-breath gas exchange. Owing to the nonlinear association between CPET results and age, fractional polynomials were used in the mixed-effects regression models to describe the sex- and age-specific normative values with 95% CIs, after adjusting for race and body mass index. RESULTS: We analyzed data on 1829 children (average age, 13.6 ± 2.6 years; 52% male). After 12 years of age, males generally had higher peak values for aerobic capacity and work rate. There were progressive increases with age for both sexes in resting pulmonary function and ventilatory response to exercise, peak aerobic and work rate, and oxygen pulse. Notably, there was an age-related decrease in ventilatory equivalents of oxygen and carbon dioxide at the ventilatory anaerobic threshold. CONCLUSIONS: Future research using prospective, inclusive, and statistically planned cohorts with standardized laboratory approaches and confirmed interoperability should be considered as a focus for validating normative pediatric CPET values in the future.
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Aptidão Cardiorrespiratória , Teste de Esforço , Adolescente , Limiar Anaeróbio , Pressão Sanguínea , Criança , Tolerância ao Exercício , Feminino , Frequência Cardíaca , Humanos , Masculino , Consumo de Oxigênio , Troca Gasosa Pulmonar , Valores de Referência , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
BACKGROUND: Previous genetic research in pediatric cardiomyopathy (CM) has focused on pathogenic variants for diagnostic purposes, with limited data evaluating genotype-outcome correlations. We explored whether greater genetic variant burden (pathogenic or variants of unknown significance, VUS) correlates with worse outcomes. METHODS: Children with dilated CM (DCM) and hypertrophic CM (HCM) who underwent multigene testing between 2010 and 2018 were included. Composite endpoint was freedom from major adverse cardiac event (MACE). RESULTS: Three hundred and thirty-eight subjects were included [49% DCM, median age 5.7 (interquartile range (IQR) 0.2-13.4) years, 51% HCM, median age 3.0 (IQR 0.1-12.5) years]. Pathogenic variants alone were not associated with MACE in either cohort (DCM p = 0.44; HCM p = 0.46). In DCM, VUS alone [odds ratio (OR) 4.0, 95% confidence interval (CI) 1.9-8.3] and in addition to pathogenic variants (OR 5.2, 95% CI 1.7-15.9) was associated with MACE. The presence of VUS alone or in addition to pathogenic variants were not associated with MACE in HCM (p = 0.22 and p = 0.33, respectively). CONCLUSION: Increased genetic variant burden (pathogenic variants and VUS) is associated with worse clinical outcomes in DCM but not HCM. Genomic variants that influence DCM onset may be distinct from those driving disease progression, highlighting the potential value of universal genetic testing to improve risk stratification. IMPACT: In pediatric CM, inconsistent findings historically have been shown between genotype and phenotype severity when only pathogenic variants have been considered. Increased genetic variant burden (including both pathogenic variants and VUS) is associated with worse clinical outcomes in DCM but not HCM. Genomic variants that influence CM onset may be distinct from those variants that drive disease progression and influence outcomes in phenotype-positive individuals. Incorporation of both pathogenic variants and VUS may improve risk stratification models in pediatric CM.
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Cardiomiopatias/genética , Adolescente , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
Heart failure metrics specific to the pediatric population are required to successfully implement quality improvement initiatives in children with heart failure. Medication use at the time of discharge following admission for decompensated heart failure has been identified as a potential quality metric in this population. This study aimed to report medication use at discharge in the current era for children admitted with acute decompensated heart failure. All patients < 21 years of age with an index admission (1/1/2011-12/31/2019) for acute heart failure and a coexisting diagnosis of cardiomyopathy were identified from the Pediatric Health Information System. Medication use patterns were described and compared across age groups and centers. A total of 2288 patients were identified for inclusion. An angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker (ACEi/ARB) was prescribed in 1479 (64.6%), beta blocker in 1132 (49.5%), and mineralocorticoid receptor antagonist (MRA) in 864 (37.8%) patients at discharge. The use of ACEi/ARB at discharge has decreased over time (64.6% vs. 69.6%, p = 0.001) and the use of beta blockers has increased (49.5% vs. 36.8%, p < 0.001) compared to a historical cohort (2001-2010). There is considerable variability in medication use across centers with an overall increase in beta blocker and decrease in ACEi/ARB use over time. Collaborative efforts are needed to standardize care and define quality metrics to identify best practices in the management of pediatric heart failure.
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Antagonistas Adrenérgicos beta/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Adolescente , Benchmarking , Cardiomiopatias/epidemiologia , Fármacos Cardiovasculares/uso terapêutico , Criança , Pré-Escolar , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Alta do Paciente/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Qualidade de Vida , Adulto JovemRESUMO
Congenital heart disease (CHD)-related heart failure is common and associated with significant morbidity, mortality, and resource utilization. In adults with CHD (ACHD), exercise limitation is often underestimated. Quantitative assessment with cardiopulmonary exercise testing (CPET) provides a comprehensive evaluation of exercise capacity and can help risk stratify patients, particularly across serial testing. CPET parameters must be interpreted within the context of the underlying anatomy, specifically for patients with either single ventricle physiology and/or cyanosis. Acknowledging differences in CPET parameters between ACHD and non-ACHD patients with heart failure are also important considerations when evaluating the overall benefit of advanced heart failure therapies. CPET testing can also guide safe exercise recommendation, including those with ACHD-related heart failure.
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Teste de Esforço/métodos , Exercício Físico/fisiologia , Cardiopatias Congênitas/complicações , Insuficiência Cardíaca/diagnóstico , Adulto , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , HumanosRESUMO
Hypertrophic cardiomyopathy (HCM) is a prevalent cardiomyopathy in children, with variable etiologies, phenotypes, and associated syndromic genetic disorders (GD). The spectrum of evaluation in this heterogeneous population has not been well described. We aimed to describe mortality and medical management in the pediatric HCM population, and compare HCM pediatric patients with GD to those without GD. Children (< 18 years) with HCM from the claims-based Truven Health Analytics MarketScan Research Database for years 2013-2016 were identified. Outcomes, including patient visits, diagnostic tests, procedures, medications, and mortality, were reported across demographic and clinical characteristics. Multivariable negative binomial, logistic, and survival models were utilized to test the association between those with and without GD by outcomes. 4460 patients were included, with a median age of 11 years (IQR 3-16), 61.7% male, 17.7% with GD, and 2.1% who died during the study period. There were 0.36 inpatient admissions per patient-year. Patients with GD were younger [8 years (IQR 1-14) vs 12 years (IQR 3-16) (p < 0.0001)], had more echocardiograms (1.77 vs 0.93) p < 0.0001; and ambulatory cardiac monitoring per year (0.32 vs 0.24); p = 0.0002. Adjusting for potential confounders including age, other chronic medical conditions, procedures, and heart failure, GD had increased risk of mortality [HR 2.46 (95% CI 1.62, 3.74)], myectomy [HR 1.59 (95% CI 1.08, 2.35)], and more annual admissions [OR 1.36 (CI 1.27, 1.45]. Patients with HCM show higher rates of death, admission, testing, and myectomy when concomitant syndromic genetic disorders are present, suggesting that the disease profile and resource utilization are different from HCM patients without GD.
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Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/mortalidade , Doenças Genéticas Inatas/complicações , Adolescente , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/terapia , Criança , Pré-Escolar , Ecocardiografia , Feminino , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Masculino , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Children with congenital heart disease (CHD) are at risk for advanced heart failure (AHF). We sought to define the mortality and resource utilization in CHD-related AHF in children and young adults. METHODS: All hospitalizations in the Pediatric Health Information System database involving patients ≤21 years old with a CHD diagnosis and heart failure requiring at least 7 days of continuous inotropic support between 2004 and 2015 were included. Hospitalizations including CHD surgery were excluded. RESULTS: Of 465,482 CHD hospitalizations, AHF was present in 2,712 (0.6%) [58% infant, 55% male, 30% single ventricle]. AHF therapies frequently used included extracorporeal membrane oxygenation (ECMO) (15%) and cardiac transplant (16%). Ventricular assist device (VAD) support was rare (3%), although VAD use significantly increased from 2004 to 2015 (P < .0010). Hospital mortality in CHD with AHF was 26%, with higher mortality associated with single ventricle heart disease (OR 1.64, 95% CI 1.23-2.19; P = .0009), infancy (OR 1.71, 95% CI 1.17-2.5; P = .0057), non-white race (OR 1.28, 95% CI 1.04-1.59; p=0.0234), and chronic complex comorbidities (OR 1.76, 95% CI 1.34-2.30; P < .0001). Over the 11-year study period, despite the significant increase in CHD-related AHF hospitalizations (P < .0001), hospital mortality improved (P = .0011). Median hospital costs were $252,000, a 6-fold increase above those without AHF, and was primarily driven by hospital length of stay (P < .0001). CONCLUSION: AHF in children with CHD in uncommon but increasing and is associated with significant morbidity, mortality and resource utilization. Approximately 1 in 5 children do not survive to hospital discharge. Many risk factors for mortality may not be modifiable, and further study is needed to identify modifiable risk factors and improve care for this complex population.
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Recursos em Saúde/estatística & dados numéricos , Cardiopatias Congênitas/complicações , Insuficiência Cardíaca/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Cardiopatias Congênitas/epidemiologia , Insuficiência Cardíaca/etiologia , Mortalidade Hospitalar/tendências , Humanos , Lactente , Masculino , Morbidade/tendências , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Merging United Network for Organ Sharing (UNOS) and Pediatric Health Information Systems databases has enabled a more granular analysis of pediatric heart transplant outcomes and resource utilization. We evaluated whether transplant indication at time of transplantation was associated with mortality, resource utilization, and inpatient costs during the first year after transplantation. METHODS AND RESULTS: We analyzed transplant outcomes and resource utilization from 2004 to 2015. Patients were categorized as congenital (CHD), myocarditis, or cardiomyopathy based on UNOS-defined primary indication. CHD complexity subgroup analyses (single-ventricle, complex, and simple biventricular CHD) were also performed. Of 2251 transplants (49% CHD, 5% myocarditis, 46% cardiomyopathy), CHD recipients were younger (2 [IQR 0-10], 6 [IQR 0-12], and 7 [IQR 1-14] years, respectively; P < .001) and less likely to have a ventricular assist device (VAD) at transplantation (3%, 27%, and 13%, respectively; P < .001). Patients with single-ventricle CHD had the longest time on the waitlist and were least likely to receive a VAD before transplantation. After adjusting for patient-level factors, transplant recipients with single-ventricle CHD had the greatest mortality during transplantation admission and within 1 year (odds ratio [OR] 11.8 [95% confidence interval (CI) 5.9-23.6] and OR 6.0 [95% CI 3.6-10.2], respectively, vs cardiomyopathy). Mortality was similar between patients with myocarditis and cardiomyopathy. Post-transplantation length of stay (LOS) was longer in transplant recipients with CHD than myocarditis or cardiomyopathy (25 [interquartile range [IQR] 15-45] vs 21 [IQR 12-35] vs 16 [IQR 12-25] days; P < .001), related in part to longer duration of intensive care unit-level care (ICU LOS 8 [IQR 4-20] vs 6 [IQR 4-13] vs 5 [IQR 3-8] days; P < .001). Similarly, patients with CHD had higher median post-transplantation costs than myocarditis or cardiomyopathy ($415K [IQR $201K-503K] vs $354K [IQR $179K-390K] vs $284K [IQR $145K-319K]; P < .001) that persisted after adjusting for patient-level factors (adjusted cost ratio 1.4 [95% CI 1.4-1.5], CHD vs cardiomyopathy) and was primarily driven by longer LOS. More than 50% were readmitted during the first year after transplantation, although readmission rates were similar across transplant indications (Pâ¯=â¯.42). CONCLUSIONS: Children with CHD, particularly single-ventricle patients, require substantially greater hospital resource utilization and have significantly worse outcomes during the first year after heart transplantation compared with other indications. Further work is aimed at identifying modifiable pre-transplantation risk factors, such as pre-transplantation conditioning with VAD support and cardiac rehabilitation, to improve post-transplantation outcomes and reduce resource utilization in this complex population.
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Bases de Dados Factuais , Sistemas de Informação em Saúde , Insuficiência Cardíaca/mortalidade , Transplante de Coração/mortalidade , Custos Hospitalares , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Criança , Pré-Escolar , Análise de Dados , Bases de Dados Factuais/economia , Bases de Dados Factuais/tendências , Feminino , Sistemas de Informação em Saúde/economia , Sistemas de Informação em Saúde/tendências , Recursos em Saúde/economia , Recursos em Saúde/tendências , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/terapia , Transplante de Coração/economia , Transplante de Coração/tendências , Custos Hospitalares/tendências , Hospitalização/economia , Humanos , Lactente , Masculino , Mortalidade/tendências , Estudos RetrospectivosRESUMO
In complete atrioventricular canal defect (CAVC), there are limited data on preoperative clinical and echocardiographic predictors of operative timing and postoperative outcomes. A retrospective, single-center analysis of all patients who underwent primary biventricular repair of CAVC between 2006 and 2015 was performed. Associated cardiac anomalies (tetralogy of Fallot, double outlet right ventricle) and arch operation were excluded. Echocardiographic findings on first postnatal echocardiogram were correlated with surgical timing and postoperative outcomes using bivariate descriptive statistics and multivariable logistic regression. 153 subjects (40% male, 84% Down syndrome) underwent primary CAVC repair at a median age of 3.3 (IQR 2.5-4.2) months. Median postoperative length of stay (LOS) was 7 (IQR 5-15) days. Eight patients (5%) died postoperatively and 24 (16%) required reoperation within 1 year. On multivariable analysis, small aortic isthmus (z score < - 2) was associated with early primary repair at < 3 months (OR 2.75, 95% CI 1.283-5.91) and need for early reoperation (OR 3.79, 95% CI 1.27-11.34). Preoperative ventricular dysfunction was associated with higher postoperative mortality (OR 7.71, 95% CI 1.76-33.69). Other factors associated with mortality and longer postoperative LOS were prematurity (OR 5.30, 95% CI 1.24-22.47 and OR 5.50, 95% CI 2.07-14.59, respectively) and lower weight at surgery (OR 0.17, 95% CI 0.04-0.75 and OR 0.55, 95% CI 0.35-0.85, respectively). Notably, preoperative atrioventricular valve regurgitation and Down syndrome were not associated with surgical timing, postoperative outcomes or reoperation, and there were no echocardiographic characteristics associated with late reoperation beyond 1 year after repair. Key preoperative echocardiographic parameters helped predict operative timing and postoperative outcomes in infants undergoing primary CAVC repair. Aortic isthmus z score < - 2 was associated with early surgical repair and need for reoperation, while preoperative ventricular dysfunction was associated with increased mortality. These echocardiographic findings may help risk-stratified patients undergoing CAVC repair and improve preoperative counseling and surgical planning.
Assuntos
Defeitos dos Septos Cardíacos/cirurgia , Tempo para o Tratamento , Síndrome de Down/complicações , Ecocardiografia , Feminino , Defeitos dos Septos Cardíacos/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido Prematuro , Masculino , Reoperação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Lung Doppler signals (LDS) acquired via transthoracic echocardiography is a novel technology previously reported in adults for use in detecting pulmonary hypertension. The aim of this study was to characterize LDS in healthy children to establish normative pediatric LDS data, and compare the pediatric data to the previously published healthy adult LDS. In this prospective, two-center study, LDS were acquired in children without cardiopulmonary disease using a 2 MHz transthoracic pulsed Doppler transducer. The data were processed to obtain Doppler velocity patterns corresponding to phases of the cardiac cycle. Signals were analyzed using a parametric Doppler signal-processing package and performance evaluation of the trained classifiers was performed using cross validation method. Pediatric signals were then compared to a retrospective cohort of healthy adults. Eighty-six healthy pediatric subjects (mean age 9.1 ± 5.1 years) and 79 healthy adult controls (mean age 59.7 ± 10.7 years) were included. The normative LDS velocity profiles were defined for pediatric subjects and then compared to adults; the highest discriminating LDS parameters between healthy children and adults were acceleration of atrial (A) signal contraction (46 ± 18 vs. 90 ± 34; p < 0.001), peak systolic (S) signal velocity (10.0 ± 3.5 vs. 11.7 ± 3.5; p < 0.001), and ratio of peak diastolic (D)-to-atrial (A) signal velocity (1.4 ± 0.5 vs. 0.4 ± 0.3; p < 0.001). The sensitivity and specificity of this LDS based method to discern between healthy children and adult subjects was 98.6% and 97.4%, respectively. Subgroup analyses between younger (2-8 years) and older (9-18 years) pediatric LDS yielded significant differences between atrial (A) acceleration (43.7 ± 33.9 vs. 47.7 ± 42.1; p = 0.04) and diastolic (D)-to-atrial (A) signal velocity (1.2 ± 0.5 vs. 1.5 ± 0.5; p = 0.01) but not systolic (S) signals (0.14 ± 0.05 vs. 0.14 ± 0.05; p = 0.97). In this study, we defined the normal LDS profile for healthy children and have demonstrated differences in LDS between children and adults. Specifically, healthy children had lower atrial contraction power, differences in ventricular compliance and increased chronotropic response. Further studies are warranted to investigate the application of this technology, for example as a tool to aid in the detection of pulmonary hypertension in children.
Assuntos
Doenças Cardiovasculares/diagnóstico por imagem , Ecocardiografia , Pneumopatias/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Ultrassonografia Doppler , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Pediatria , Estudos Prospectivos , Artéria Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Sensibilidade e Especificidade , SístoleRESUMO
Immunotherapy with chimeric antigen receptor (CAR)-modified T cells targeting CD19 for pediatric acute lymphoblastic leukemia (ALL) has demonstrated significant efficacy. The principle toxicity is cytokine release syndrome with resultant hypotension. However, the spectrum of cardiovascular effects associated with CAR T cell therapy has not been systematically evaluated. We reviewed all patients who received CD19-directed CAR T cells at the Children's Hospital of Philadelphia between April 2012 and September 2016. The primary endpoint was hypotension-requiring inotropic support. Secondary endpoints included echocardiographic dysfunction at discharge and 6-month follow-up. Descriptive and univariate analyses were performed, and 98 encounters were included (55% male patients; mean age, 11.8 years [range, 1.7 to 27.1]); 98% had B-ALL. Before infusion 10 had cardiomyopathy and 1 had single-ventricle physiology. Primary endpoint occurred in 24 patients with mean onset 4.6 days (range, 1 to 9) after CAR T cell infusion, including 6 patients receiving milrinone. Worsened systolic function occurred in 10 patients; there were no cardiac-related deaths. Pretreatment factors associated with primary endpoint included higher pretreatment blast percentage on bone marrow biopsy (blast > 25%: odds ratio, 15.5; 95% confidence interval, 5.1 to 47.1; P < .001) and baseline lower ejection fraction (P = .019) or diastolic dysfunction (P = .021); neither pre-existing cardiomyopathy (P = .062), total body irradiation (P = .629), nor anthracycline dose (P = .444) were associated. At discharge, 7 patients had worsened echocardiographic function, but persistent dysfunction by the 6-month follow-up was rare. Pretreatment factors were not associated with persistent dysfunction at discharge. This is the first study to describe the cardiovascular effects of pediatric CAR T cell therapy. Although 10% had new systolic dysfunction after treatment, persistence was rare. Pretreatment blast count > 25% or pre-existing cardiac dysfunction increased the risk for hypotension-requiring inotropic support; these patients may warrant close observation.