RESUMO
Impaired exercise following Fontan is a surrogate of morbidity. Single-center longitudinal data exist, but there is a lack of contemporary multi-center data. Ramp cycle ergometry was re-performed in consented participants who had originally participated in the Pediatric Heart Network's Fontan cross-sectional study. Annualized change was evaluated at maximal and submaximal exercise. Associations between these outcomes and patient characteristics were analyzed. There were 336 participants in Fontan 3, mean age 23.2 years. Paired measurements of peak oxygen consumption (peak VO2) were available for 95; peak exercise data at Fontan 3 were available for 275. Percent-predicted peak VO2 declined by 0.8 ± 1.7% per year (p < 0.001). At Fontan 3, the lowest performing peak VO2 tertile had the highest rate of overweight and obesity (p < 0.001). Female gender was more prevalent in the highest performing tertile (p = 0.004). Paired data at the ventilatory anaerobic threshold (VO2 at VAT) were available for 196; VAT data at Fontan 3 were available for 311. Percent-predicted VO2 at VAT decreased by 0.8 ± 2.6% per year (p < 0.001). At Fontan 3, VO2 at VAT was better preserved than peak VO2 across all tertiles, with higher rates of overweight and obesity in the lower performing group (p = 0.001). Female gender (p < 0.001) and left ventricular morphology (p = 0.03) were associated with better performance. Submaximal exercise is better preserved than maximal in the Fontan population, but declined at the same rate over the study period. The overall longitudinal rate of decline in exercise performance is slower than what has been described previously.
Assuntos
Tolerância ao Exercício , Técnica de Fontan/efeitos adversos , Adolescente , Adulto , Estudos Transversais , Teste de Esforço/métodos , Feminino , Seguimentos , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Consumo de Oxigênio , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Treatment-associated cardiomyopathy is a leading cause of morbidity and mortality for childhood cancer survivors (CCS). As evidence is not available to guide the management of CCS at risk for cardiomyopathy, we aim to describe the collective opinion of regional experts for the care of these patients using a consensus-based Delphi methodology. PROCEDURE: Nineteen physicians from the New England region who care for CCS treated with cardiotoxic therapy (anthracyclines, thoracic radiation) participated in a Delphi panel querying their management approach, using three rounds of anonymous questionnaires formatted as five clinical scenarios. Consensus ≥ 89% agreement. RESULTS: The response rate was 100% for the first round and 95% for subsequent rounds. Panelists reached consensus on screening asymptomatic CCS with serial echocardiograms (94%) and electrocardiograms (89%), with some disagreement on frequency during pregnancy (83%). All panelists agreed with exercise promotion, with no restrictions on weight training. Consensus was reached on indications for referrals; cardiology for asymptomatic left ventricular dysfunction (ALVD) (100%) and maternal-fetal medicine for pregnancy (94%). In the scenario of ALVD, there was disagreement on the benefit of additional cardiac testing (50% cardiologists recommended cardiac MRI), and although all panelists endorsed treating with angiotension-converting enzyme (ACE) inhibitors, most adult cardiologists (75%) also recommended therapy with beta blockers, compared with none of the pediatric cardiologists or primary-care physicians. CONCLUSIONS: Despite a lack of evidence to guide the management of CCS at risk for cardiomyopathy, a panel of regional physicians reached consensus on managing most clinical scenarios. A controversial area requiring further study is the medical management of ALVD.
Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antraciclinas , Sobreviventes de Câncer , Cardiomiopatias , Cardiotoxicidade , Cuidadores , Ecocardiografia , Eletrocardiografia , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Adulto , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Cardiomiopatias/induzido quimicamente , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/fisiopatologia , Cardiomiopatias/prevenção & controle , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/fisiopatologia , Cardiotoxicidade/prevenção & controle , Criança , Técnica Delphi , Feminino , Humanos , Disfunção Ventricular Esquerda/induzido quimicamente , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controleRESUMO
BACKGROUND: While echocardiographic parameters are used to quantify ventricular function in infants with single ventricle physiology, there are few data comparing these to invasive measurements. This study correlates echocardiographic measures of diastolic function with ventricular end-diastolic pressure in infants with single ventricle physiology prior to superior cavopulmonary anastomosis. METHODS: Data from 173 patients enrolled in the Pediatric Heart Network Infant Single Ventricle enalapril trial were analysed. Those with mixed ventricular types (n = 17) and one outlier (end-diastolic pressure = 32 mmHg) were excluded from the analysis, leaving a total sample size of 155 patients. Echocardiographic measurements were correlated to end-diastolic pressure using Spearman's test. RESULTS: Median age at echocardiogram was 4.6 (range 2.5-7.4) months. Median ventricular end-diastolic pressure was 7 (range 3-19) mmHg. Median time difference between the echocardiogram and catheterisation was 0 days (range -35 to 59 days). Examining the entire cohort of 155 patients, no echocardiographic diastolic function variable correlated with ventricular end-diastolic pressure. When the analysis was limited to the 86 patients who had similar sedation for both studies, the systolic:diastolic duration ratio had a significant but weak negative correlation with end-diastolic pressure (r = -0.3, p = 0.004). The remaining echocardiographic variables did not correlate with ventricular end-diastolic pressure. CONCLUSION: In this cohort of infants with single ventricle physiology prior to superior cavopulmonary anastomosis, most conventional echocardiographic measures of diastolic function did not correlate with ventricular end-diastolic pressure at cardiac catheterisation. These limitations should be factored into the interpretation of quantitative echo data in this patient population.
Assuntos
Cateterismo Cardíaco/métodos , Ecocardiografia Doppler/métodos , Enalapril/uso terapêutico , Cardiopatias Congênitas/diagnóstico , Ventrículos do Coração/anormalidades , Função Ventricular Esquerda/fisiologia , Pressão Ventricular/fisiologia , Anti-Hipertensivos/uso terapêutico , Diástole , Método Duplo-Cego , Feminino , Seguimentos , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVES: To assess self-reported quality of life (QOL) in a large multicenter cohort of adolescent and young adults surviving Fontan. STUDY DESIGN: Cross-sectional. The Pediatric Quality of Life Inventory (PedsQL) was administered to 408 survivors of Fontan ages 13-25 years enrolled in the Pediatric Heart Network Fontan Follow-up Study. Subjects also completed either the Child Health Questionnaire (age <19 years) or Short Form Health Survey (age ≥ 19 years). PedsQL data were compared with matched controls without a chronic health condition. Correlations between the measures were examined. RESULTS: Mean PedsQL scores for subjects receiving Fontan were significantly lower than those for the control group for physical and psychosocial QOL (P < .001). Overall, 45% of subjects receiving Fontan had scores in the clinically significant impaired range for physical QOL with 30% in the impaired range for psychosocial QOL. For each 1 year increase in age, the physical functioning score decreased by an average of 0.76 points (P = .004) and the emotional functioning score decreased by an average of 0.64 points (P = .03). Among subjects ≥19 years of age, the physical functioning score decreased by an average of 2 points for each year increase in age (P = .02). PedsQL scale scores were significantly correlated with conceptually related Child Health Questionnaire (P < .001) and Short Form Health Survey scores (P < .001). CONCLUSIONS: Survivors of Fontan are at risk for significantly impaired QOL which may decline with advancing age. Routine assessment of QOL is essential to inform interventions to improve health outcomes. The PedsQL allowed QOL assessment from pediatrics to young adulthood. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00132782.
Assuntos
Técnica de Fontan/psicologia , Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Estudos Transversais , Feminino , Seguimentos , Humanos , Masculino , Inquéritos e Questionários , Sobreviventes , Estados Unidos/epidemiologia , Adulto JovemRESUMO
M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement.
Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Função Ventricular Esquerda/fisiologia , Adolescente , Cardiomiopatia Dilatada/fisiopatologia , Criança , Pré-Escolar , Feminino , Ventrículos do Coração/fisiopatologia , Humanos , Lactente , Masculino , Curva ROC , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Data regarding the value of B-type natriuretic peptide (BNP) measurements in infants with a single-ventricle (SV) physiology are lacking. This analysis aimed to describe the BNP level changes in infants with an SV physiology before and after superior cavopulmonary connection (SCPC) surgery. Levels of BNP were measured by a core laboratory before SCPC (at 5.0 ± 1.6 months) and at the age of 14 months during a multicenter trial of angiotensin-converting enzyme inhibition therapy for infants with SV. Multivariable longitudinal analysis was used to model the associations between BNP levels and three sets of grouped variables (echocardiography, catheterization, growth). Multivariable analysis was performed to assess associations with patient characteristics at both visits. Associations between BNP levels and neurodevelopmental variables were investigated at the 14 month visit because neurodevelopmental assessment was performed only at this visit. The BNP level was significantly higher before SCPC (n = 173) than at the age of 14 months (n = 134). The respective median levels were 80.8 pg/ml (interquartile range [IQR], 35-187 pg/ml) and 34.5 pg/ml (IQR, 17-67 pg/ml) (p < 0.01). A BNP level higher than 100 pg/ml was present in 72 subjects (42 %) before SCPC and in 21 subjects (16 %) at the age of 14 months. In the 117 patients who had BNP measurements at both visits, the median BNP level decreased 32 pg/ml (IQR, 1-79 pg/ml) (p < 0.01). In the longitudinal multivariable analysis, higher BNP levels were associated with a higher end-systolic volume z-score (p = 0.01), a greater degree of atrioventricular (AV) valve regurgitation (p < 0.01), a lower weight z-score (p < 0.01), and a lower length z-score (p = 0.02). In multivariable analyses, a higher BNP level at the age of 14 months was associated with arrhythmia after SCPC surgery (p < 0.01), a prior Norwood procedure (p < 0.01), a longer hospital stay after SCPC surgery (p = 0.04), and a lower Bayley psychomotor developmental index (p = 0.02). The levels of BNP decreases in infants with SV from the pre-SCPC visit to the age of 14 months. A higher BNP level is associated with increased ventricular dilation in systole, increased AV valve regurgitation, impaired growth, and poorer neurodevelopmental outcomes. Therefore, BNP level may be a useful seromarker for identifying infants with SV at risk for worse outcomes.
Assuntos
Biomarcadores/sangue , Cardiopatias Congênitas/sangue , Ventrículos do Coração/anormalidades , Peptídeo Natriurético Encefálico/sangue , Ecocardiografia , Feminino , Cardiopatias Congênitas/cirurgia , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , MasculinoRESUMO
BACKGROUND: Reduced long-axis shortening despite enhanced global function has been reported in aortic stenosis. We sought to improve the understanding of this phenomenon using multi-dimensional strain analysis in conjunction with the evaluation of left ventricular rotation and twist - ventricular torsion - using tissue Doppler techniques. METHODS: A total of 57 patients with variable severity of aortic stenosis, aortic regurgitation, or mixed aortic valve disease, subdivided into six groups, were studied. Ventricular morphology was assessed using long-axis/short-axis and mass/volume ratios, afterload using end-systolic meridional wall stress, and global performance using ejection fraction. The circumferential and longitudinal strain was measured from two-dimensional images, and left ventricular rotation and twist were estimated as the difference in rotation between the base and apex of the ventricle. RESULTS: Aortic stenosis was associated with higher mass/volume, ejection fraction, circumferential strain and left ventricular rotation and twist, significantly lower end-systolic wall stress, and a trend towards lower longitudinal strain compared with normal. Myocardial mechanics in aortic regurgitation were normal despite ventricular dilation. Mixed aortic valve disease showed findings similar to aortic stenosis. Left ventricular rotation and twist correlated with midwall circumferential strain (r = 0.62 and p < 0.0001), endocardial circumferential strain (r = 0.61 and p < 0.0001), and end-systolic wall stress (r = 0.48 and p < 0.0001), but not with longitudinal strain (r = 0.18 and p > 0.05). CONCLUSIONS: Myocardial mechanics are normal in patients with aortic regurgitation, independent of abnormalities in cardiac geometry. Conversely, in aortic stenosis and mixed aortic valve disease, significant alterations in the patterns of fibre shortening are found. The effects of stenosis on cardiac function seem to dominate the effect of ventricular remodelling.
Assuntos
Insuficiência da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/diagnóstico por imagem , Ecocardiografia Doppler/métodos , Ventrículos do Coração/diagnóstico por imagem , Contração Miocárdica/fisiologia , Adolescente , Adulto , Insuficiência da Valva Aórtica/complicações , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/fisiopatologia , Estudos de Casos e Controles , Criança , Ventrículos do Coração/fisiopatologia , Humanos , Índice de Gravidade de Doença , Remodelação Ventricular/fisiologia , Adulto JovemRESUMO
PURPOSE: The aim of this study was to compare associations between generic versus disease-specific functional health status assessments and patient and clinical characteristics for patients with severe congenital heart disease. METHODS: This was a cross-sectional observational study involving 325 single ventricle patients, aged 10-18 years, after Fontan procedure. Enrolled patients underwent a medical history review, laboratory testing, and assessment of the functional health status by completion of the generic Child Report Child Health Questionnaire and the disease-specific Congenital Heart Adolescent and Teenage questionnaire. Correlated conceptually equivalent domains from both questionnaires were identified and their associations with patient and clinical variables were compared. RESULTS: From the generic assessment, patients perceived marginally lower physical functioning (p = 0.05) but greater freedom from bodily pain compared with a normal population (p < 0.001). The equivalent physical functioning/limitations domain of the generic instrument, compared with the disease-specific instrument, had similar associations (higher multi-variable model R²) with medical history variables (R² = 0.14 versus R² = 0.12, respectively) and stronger associations with exercise testing variables (R² = 0.22 versus R² = 0.06). Similarly, the corresponding freedom from bodily pain/symptoms domains from both questionnaires showed a greater association for the generic instrument with medical history variables (R² = 0.15 versus R² = 0.09, respectively) and non-cardiac conditions (R² = 0.13 versus R² = 0.06). The associations of each questionnaire with echocardiographic results, cardiac magnetic resonance imaging results, and serum brain natriuretic peptide levels were uniformly weak (R² range <0.01 to 0.04). CONCLUSIONS: Assessment of the physical functional health status using generic and disease-specific instruments yields few differences with regard to associations between conceptually similar domains and patient and clinical characteristics for adolescents after Fontan procedure.
Assuntos
Técnica de Fontan , Nível de Saúde , Cardiopatias Congênitas/cirurgia , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Restrictive cardiomyopathy (RCM) has been associated with poor prognosis in childhood. The goal of the present analysis was to use the Pediatric Cardiomyopathy Registry to analyze outcomes of childhood RCM, with a focus on the impact of phenotype comparing pure RCM with cases that have additional features of hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analyzed the Pediatric Cardiomyopathy Registry database (1990-2008; N=3375) for cases of RCM. Cases were defined as pure when RCM was the only assigned diagnosis. Additional documentation of HCM at any time was used as the criterion for RCM/HCM phenotype. RCM accounted for 4.5% of cases of cardiomyopathy. In 101 (66%), pure RCM was diagnosed; in 51 (34%), there was a mixed phenotype. Age at diagnosis was not different between groups, but 10% of the pure RCM group was diagnosed in infancy versus 24% of the RCM/HCM group. Freedom from death was comparable between groups with 1-, 2-, and 5-year survival of RCM 82%, 80%, and 68% versus RCM/HCM 77%, 74%, and 68%. Transplant-free survival was 48%, 34%, and 22% and 65%, 53%, and 43%, respectively (P=0.011). Independent risk factors at diagnosis for lower transplant-free survival were heart failure (hazard ratio 2.20, P=0.005), lower fractional shortening z score (hazard ratio 1.12 per 1 SD decrease in z score, P=0.014), and higher posterior wall thickness in the RCM/HCM group only (hazard ratio 1.32, P<0.001). Overall, outcomes were worse than for all other forms of cardiomyopathy. CONCLUSIONS: Transplant-free survival is poor for RCM in childhood. Survival is independent of phenotype; however, the RCM/HCM phenotype has significantly better transplant-free survival. CLINICAL TRIALS REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00005391.
Assuntos
Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/fisiopatologia , Cardiomiopatia Restritiva/mortalidade , Cardiomiopatia Restritiva/fisiopatologia , Sistema de Registros/estatística & dados numéricos , Arritmias Cardíacas/mortalidade , Cardiomiopatia Hipertrófica/cirurgia , Cardiomiopatia Restritiva/cirurgia , Criança , Pré-Escolar , Feminino , Fibrinolíticos/uso terapêutico , Seguimentos , Transplante de Coração/mortalidade , Humanos , Lactente , Masculino , Fenótipo , Modelos de Riscos Proporcionais , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidadeRESUMO
Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great arteries, systemic veins, and pulmonary veins were less likely to be adequately imaged than other cardiac structures. Quantitative analysis of ventricular volume was possible in 76% overall, but only 41% of those with mixed ventricular morphology. Factors independently associated with better quality included younger age, levocardia, acquisition of the echocardiogram at a longer time since the beginning of enrollment, absence of a pulmonary artery stent, and clinical site. Patient and center-specific factors are associated with echocardiographic quality after the Fontan procedure. Increased familiarity and experience with a standard imaging protocol is likely to result in improved quality.
Assuntos
Ecocardiografia/métodos , Ecocardiografia/estatística & dados numéricos , Técnica de Fontan/estatística & dados numéricos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Adolescente , Criança , Estudos Transversais , Feminino , Cardiopatias Congênitas/epidemiologia , Humanos , Incidência , Masculino , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: A superior cavopulmonary connection is commonly performed before the Fontan procedure in patients with a functionally univentricular heart. Data are limited regarding associations between a prior superior cavopulmonary connection and functional and ventricular performance late after the Fontan procedure. METHODS: We compared characteristics of those with and without prior superior cavopulmonary connection among 546 subjects enrolled in the Pediatric Heart Network Fontan Cross-Sectional Study. We further compared different superior cavopulmonary connection techniques: bidirectional cavopulmonary anastomosis (n equals 229), bilateral bidirectional cavopulmonary anastomosis (n equals 39), and hemi-Fontan (n equals 114). RESULTS: A prior superior cavopulmonary connection was performed in 408 subjects (75%); the proportion differed by year of Fontan surgery and centre (p-value less than 0.0001 for each). The average age at Fontan was similar, 3.5 years in those with superior cavopulmonary connection versus 3.2 years in those without (p-value equals 0.4). The type of superior cavopulmonary connection varied by site (p-value less than 0.001) and was related to the type of Fontan procedure. Exercise performance, echocardiographic variables, and predominant rhythm did not differ by superior cavopulmonary connection status or among superior cavopulmonary connection types. Using a test of interaction, findings did not vary according to an underlying diagnosis of hypoplastic left heart syndrome. CONCLUSIONS: After controlling for subject and era factors, most long-term outcomes in subjects with a prior superior cavopulmonary connection did not differ substantially from those without this procedure. The type of superior cavopulmonary connection varied significantly by centre, but late outcomes were similar.
Assuntos
Técnica de Fontan , Derivação Cardíaca Direita/métodos , Cardiopatias Congênitas/cirurgia , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Feminino , Cardiopatias Congênitas/fisiopatologia , Testes de Função Cardíaca , Humanos , Masculino , Resultado do TratamentoRESUMO
Importance: Valsartan has shown promise in attenuating cardiac remodeling in patients with early-stage sarcomeric hypertrophic cardiomyopathy (HCM). Genetic testing can identify individuals at risk of HCM in a subclinical stage who could benefit from therapies that prevent disease progression. Objective: To explore the potential for valsartan to modify disease development, and to characterize short-term phenotypic progression in subclinical HCM. Design, Setting, and Participants: The multicenter, double-blind, placebo-controlled Valsartan for Attenuating Disease Evolution in Early Sarcomeric Hypertrophic Cardiomyopathy (VANISH) randomized clinical trial was conducted from April 2014 to July 2019 at 17 sites in 4 countries (Brazil, Canada, Denmark, and the US), with 2 years of follow-up. The prespecified exploratory VANISH cohort studied here included sarcomere variant carriers with subclinical HCM and early phenotypic manifestations (reduced E' velocity, electrocardiographic abnormalities, or an increased left ventricular [LV] wall thickness [LVWT] to cavity diameter ratio) but no LV hypertrophy (LVH). Data were analyzed between March and December 2022. Interventions: Treatment with placebo or valsartan (80 mg/d for children weighing <35 kg, 160 mg/d for children weighing ≥35 kg, or 320 mg/d for adults aged ≥18 years). Main Outcomes and Measures: The primary outcome was a composite z score incorporating changes in 9 parameters of cardiac remodeling (LV cavity volume, LVWT, and LV mass; left atrial [LA] volume; E' velocity and S' velocity; and serum troponin and N-terminal prohormone of brain natriuretic peptide levels). Results: This study included 34 participants, with a mean (SD) age of 16 (5) years (all were White). A total of 18 participants (8 female [44%] and 10 male [56%]) were randomized to valsartan and 16 (9 female [56%] and 7 male [44%]) were randomized to placebo. No statistically significant effects of valsartan on cardiac remodeling were detected (mean change in composite z score compared with placebo: -0.01 [95% CI, -0.29 to 0.26]; P = .92). Overall, 2-year phenotypic progression was modest, with only a mild increase in LA volume detected (increased by 3.5 mL/m2 [95% CI, 1.4-6.0 mL/m2]; P = .002). Nine participants (26%) had increased LVWT, including 6 (18%) who developed clinically overt HCM. Baseline LA volume index (LAVI; 35 vs 28 mL/m2; P = .01) and average interventricular septum thickness (8.5 vs 7.0 mm; P = .009) were higher in participants who developed HCM. Conclusions and Relevance: In this exploratory cohort, valsartan was not proven to slow progression of subclinical HCM. Minimal changes in markers of cardiac remodeling were observed, although nearly one-fifth of patients developed clinically overt HCM. Transition to disease was associated with greater baseline interventricular septum thickness and LAVI. These findings highlight the importance of following sarcomere variant carriers longitudinally and the critical need to improve understanding of factors that drive disease penetrance and progression. Trial Registration: ClinicalTrials.gov Identifier: NCT01912534.
Assuntos
Cardiomiopatia Hipertrófica , Remodelação Ventricular , Adulto , Criança , Humanos , Masculino , Feminino , Adolescente , Predisposição Genética para Doença , Hipertrofia Ventricular Esquerda , Valsartana/uso terapêuticoRESUMO
BACKGROUND: We investigated the effect of polymorphisms in the renin-angiotensin-aldosterone system (RAAS) genes on ventricular remodeling, growth, renal function, and response to enalapril in infants with single ventricle. METHODS AND RESULTS: Single ventricle infants enrolled in a randomized trial of enalapril were genotyped for polymorphisms in 5 genes: angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 receptor, aldosterone synthase, and chymase. Alleles associated with renin-angiotensin-aldosterone system upregulation were classified as risk alleles. Ventricular mass, volume, somatic growth, renal function using estimated glomerular filtration rate, and response to enalapril were compared between patients with ≥2 homozygous risk genotypes (high risk), and those with <2 homozygous risk genotypes (low risk) at 2 time points: before the superior cavopulmonary connection (pre-SCPC) and at age 14 months. Of 230 trial subjects, 154 were genotyped: Thirty-eight were high risk, and 116 were low risk. Ventricular mass and volume were elevated in both groups pre-SCPC. Ventricular mass and volume decreased and estimated glomerular filtration rate increased after SCPC in the low-risk (P<0.05), but not the high-risk group. These responses were independent of enalapril treatment. Weight and height z-scores were lower at baseline, and height remained lower in the high-risk group at 14 months, especially in those receiving enalapril (P<0.05). CONCLUSIONS: Renin-angiotensin-aldosterone system-upregulation genotypes were associated with failure of reverse remodeling after SCPC surgery, less improvement in renal function, and impaired somatic growth, the latter especially in patients receiving enalapril. Renin-angiotensin-aldosterone system genotype may identify a high-risk subgroup of single ventricle patients who fail to fully benefit from volume-unloading surgery. Follow-up is warranted to assess long-term impact. CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00113087.
Assuntos
Ventrículos do Coração/anormalidades , Ventrículos do Coração/metabolismo , Sistema Renina-Angiotensina/genética , Função Ventricular/genética , Remodelação Ventricular/genética , Aldosterona/genética , Angiotensinas/genética , Estudos de Coortes , Método Duplo-Cego , Feminino , Genótipo , Transtornos do Crescimento/genética , Transtornos do Crescimento/metabolismo , Transtornos do Crescimento/fisiopatologia , Humanos , Lactente , Recém-Nascido , Testes de Função Renal , Masculino , Peptidil Dipeptidase A/genética , Polimorfismo Genético/genética , Renina/genética , Regulação para Cima/genéticaRESUMO
Background: Cardiomyopathy is a leading cause of late morbidity and mortality in childhood cancer survivors (CCS). Evidence-based guidelines recommend risk-stratified screening for cardiomyopathy, but the management approach for abnormalities detected when screening asymptomatic young adult CCS is poorly defined. Objectives: The aims of this study were to build upon existing guidelines by describing the expert consensus-based cardiomyopathy screening practices, management approach, and clinical rationale for the management of young adult CCS with screening-detected abnormalities and to identify areas of controversy in practice. Methods: A multispecialty Delphi panel of 40 physicians with expertise in cancer survivorship completed 3 iterative rounds of semi-open-ended questionnaires regarding their approaches to the management of asymptomatic young adult CCS at risk for cardiomyopathy (screening practices, referrals, cardiac testing, laboratory studies, medications). Consensus was defined as ≥90% panelist agreement with recommendation. Results: The response rate was 100% for all 3 rounds. Panelists reached consensus on the timing and frequency of echocardiographic screening for anthracycline-associated cardiomyopathy, monitoring during pregnancy, laboratory testing for modifiable cardiac risk factors, and referral to cardiology for ejection fraction ≤50% or preserved ejection fraction with diastolic dysfunction. Controversial areas (<75% agreement) included chest radiation dose threshold to merit screening, indications for advanced cardiac imaging and cardiac serum biomarkers for follow-up of abnormal echocardiographic findings, and medical management of asymptomatic left ventricular systolic dysfunction. Conclusions: Expert practice is largely consistent with existing risk-based screening guidelines. Some recommendations for managing abnormalities detected on screening echocardiography remain controversial. The rationale offered by experts for divergent approaches may help guide clinical decisions in the absence of guidelines specific to young adult CCS.
RESUMO
BACKGROUND: Patients after the Fontan procedure are at risk for suboptimal functional health status, and associations with laboratory measures are important for planning interventions and outcome measures for clinical trials. METHODS AND RESULTS: Parents completed the generic Child Health Questionnaire for 511 Fontan Cross-Sectional Study patients 6 to 18 years of age (61% male). Associations of Child Health Questionnaire Physical and Psychosocial Functioning Summary Scores (FSS) with standardized measurements from prospective exercise testing, echocardiography, magnetic resonance imaging, and measurement of brain natriuretic peptide were determined by regression analyses. For exercise variables for maximal effort patients only, the final model showed that higher Physical FSS was associated only with higher maximum work rate, accounting for 9% of variation in Physical FSS. For echocardiography, lower Tei index (particularly for patients with extracardiac lateral tunnel connections), lower indexed end-systolic volume, and the absence of atrioventricular valve regurgitation for patients having Fontan procedure at age <2 years were associated with higher Physical FSS, accounting for 14% of variation in Physical FSS. For magnetic resonance imaging, ratio of lower mass to end-diastolic volume and midquartiles of indexed end-systolic volume (nonlinear) were associated with higher Physical FSS, accounting for 11% of variation. Lower brain natriuretic peptide was significantly but weakly associated with higher Physical FSS (1% of variation). Significant associations for Psychosocial FSS with laboratory measures were fewer and weaker than for Physical FSS. CONCLUSIONS: In relatively healthy Fontan patients, laboratory measures account for a small proportion of the variation in functional health status and therefore may not be optimal surrogate end points for trials of therapeutic interventions.
Assuntos
Tolerância ao Exercício/fisiologia , Técnica de Fontan , Nível de Saúde , Cardiopatias Congênitas/cirurgia , Complicações Pós-Operatórias/fisiopatologia , Disfunção Ventricular/fisiopatologia , Adolescente , Volume Cardíaco , Criança , Estudos Transversais , Ecocardiografia , Teste de Esforço , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Peptídeo Natriurético Encefálico/sangue , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Inquéritos e Questionários , Disfunção Ventricular/diagnóstico por imagem , Disfunção Ventricular/patologiaRESUMO
BACKGROUND: Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown. METHODS AND RESULTS: The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg . kg(-1) . d(-1)) or placebo who were followed up until 14 months of age. The primary end point was weight-for-age z score at 14 months. The primary analysis was intention to treat. A total of 185 infants completed the study. There were 24 and 21 withdrawals or deaths in the enalapril and placebo groups, respectively (P=0.74). Weight-for-age z score was not different between the enalapril and placebo groups (mean+/-SE -0.62+/-0.13 versus -0.42+/-0.13, P=0.28). There were no significant group differences in height-for-age z score, Ross heart failure class, brain natriuretic peptide concentration, Bayley scores of infant development, or ventricular ejection fraction. The incidence of death or transplantation was 13% and did not differ between groups. Serious adverse events occurred in 88 patients in the enalapril group and 87 in the placebo group. CONCLUSIONS: Administration of enalapril to infants with single-ventricle physiology in the first year of life did not improve somatic growth, ventricular function, or heart failure severity. The results of this randomized trial do not support the routine use of enalapril in this population.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Insuficiência Cardíaca/epidemiologia , Ventrículos do Coração/anormalidades , Aldosterona/sangue , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Método Duplo-Cego , Enalapril/efeitos adversos , Endotélio Vascular/fisiopatologia , Taxa de Filtração Glomerular/fisiologia , Humanos , Lactente , Volume SistólicoRESUMO
Barth syndrome (BTHS) is a mitochondrial myopathy characterized by reports of exercise intolerance. We sought to determine if 1) BTHS leads to abnormalities of skeletal muscle O(2) extraction/utilization and 2) exercise intolerance in BTHS is related to impaired O(2) extraction/utilization, impaired cardiac function, or both. Participants with BTHS (age: 17 ± 5 yr, n = 15) and control participants (age: 13 ± 4 yr, n = 9) underwent graded exercise testing on a cycle ergometer with continuous ECG and metabolic measurements. Echocardiography was performed at rest and at peak exercise. Near-infrared spectroscopy of the vastus lateralis muscle was continuously recorded for measurements of skeletal muscle O(2) extraction. Adjusting for age, peak O(2) consumption (16.5 ± 4.0 vs. 39.5 ± 12.3 ml·kg(-1)·min(-1), P < 0.001) and peak work rate (58 ± 19 vs. 166 ± 60 W, P < 0.001) were significantly lower in BTHS than control participants. The percent increase from rest to peak exercise in ejection fraction (BTHS: 3 ± 10 vs. control: 19 ± 4%, P < 0.01) was blunted in BTHS compared with control participants. The muscle tissue O(2) saturation change from rest to peak exercise was paradoxically opposite (BTHS: 8 ± 16 vs. control: -5 ± 9, P < 0.01), and the deoxyhemoglobin change was blunted (BTHS: 0 ± 12 vs. control: 10 ± 8, P < 0.09) in BTHS compared with control participants, indicating impaired skeletal muscle extraction in BTHS. In conclusion, severe exercise intolerance in BTHS is due to both cardiac and skeletal muscle impairments that are consistent with cardiac and skeletal mitochondrial myopathy. These findings provide further insight to the pathophysiology of BTHS.
Assuntos
Síndrome de Barth/complicações , Cardiomiopatia Dilatada/etiologia , Tolerância ao Exercício , Contração Muscular , Consumo de Oxigênio , Oxigênio/metabolismo , Músculo Quadríceps/metabolismo , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Análise de Variância , Síndrome de Barth/diagnóstico , Síndrome de Barth/metabolismo , Síndrome de Barth/fisiopatologia , Biomarcadores/sangue , Pressão Sanguínea , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Criança , Estudos Transversais , Ecocardiografia , Eletrocardiografia , Teste de Esforço , Frequência Cardíaca , Hemoglobinas/metabolismo , Humanos , Masculino , Oxigênio/sangue , Músculo Quadríceps/fisiopatologia , Mecânica Respiratória , Espectroscopia de Luz Próxima ao Infravermelho , Função Ventricular Esquerda , Adulto JovemRESUMO
BACKGROUND: The practice of coiling aortopulmonary collaterals (APCs) before Fontan completion is controversial, and published data are limited. We sought to compare outcomes in subjects with and without pre-Fontan coil embolization of APCs using the Pediatric Heart Network Fontan Cross-Sectional Study database which enrolled survivors of prior Fontan palliation. METHODS: We compared hospital length of stay after Fontan in 80 subjects who underwent APC coiling with 459 subjects who did not. Secondary outcomes included post-Fontan complications and assessment of health status and ventricular performance at cross-sectional evaluation (mean 8.6 ± 3.4 years after Fontan). RESULTS: Centers varied markedly in frequency of pre-Fontan APC coiling (range 0%-30% of subjects, P < .001). The coil group was older at Fontan (P = .004) and more likely to have single right ventricular morphology (P = .054) and pre-Fontan atrioventricular valve regurgitation (P = .03). The coil group underwent Fontan surgery more recently (P < .001), was more likely to have a prior superior cavopulmonary anastomosis (P < .001), and more likely to undergo extracardiac Fontan connection (P < .001) and surgical fenestration (P < .001). In multivariable analyses, APC coiling was not associated with length of stay (hazard ratio for remaining in-hospital 0.91, 95% CI 0.70-1.18, P = .48) or postoperative complications, except more post-Fontan catheter interventions (hazard ratio 1.74, 95% CI 1.04-2.91, P = .03), primarily additional APC coils. The groups had similar outcomes at cross-sectional evaluation. CONCLUSION: Management of APCs before Fontan shows marked practice variation. We did not find an association between pre-Fontan coiling of APCs and shorter postoperative hospital stay or with better late outcomes. Prospective studies of this practice are needed.
Assuntos
Embolização Terapêutica/métodos , Técnica de Fontan , Cardiopatias Congênitas/cirurgia , Cuidados Pré-Operatórios/métodos , Artéria Pulmonar , Artérias Torácicas , Função Ventricular Esquerda , Adolescente , Cateterismo Cardíaco , Criança , Pré-Escolar , Circulação Colateral , Estudos Transversais , Ecocardiografia , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: To describe growth patterns in infants with single ventricle physiology and determine factors influencing growth. STUDY DESIGN: Data from 230 subjects enrolled in the Pediatric Heart Network Infant Single Ventricle Enalapril Trial were used to assess factors influencing change in weight-for-age z-score (z) from study enrollment (0.7 ± 0.4 months) to pre-superior cavopulmonary connection (SCPC; 5.1 ± 1.8 months, period 1) and pre-SCPC to final study visit (14.1 ± 0.9 months, period 2). Predictor variables included patient characteristics, feeding regimen, clinical center, and medical factors during neonatal (period 1) and SCPC hospitalizations (period 2). Univariate regression analysis was performed, followed by backward stepwise regression and bootstrapping reliability to inform a final multivariable model. RESULTS: Weights were available for 197 of 230 subjects for period 1 and 173 of 197 subjects for period 2. For period 1, greater gestational age, younger age at study enrollment, tube feeding at neonatal hospitalization discharge, and clinical center were associated with a greater negative z (poorer growth) in multivariable modeling (adjusted R(2) = 0.39, P < .001). For period 2, younger age at SCPC and greater daily caloric intake were associated with greater positive z (better growth; R(2) = 0.10, P = .002). CONCLUSIONS: Aggressive nutritional support and earlier SCPC are modifiable factors associated with a favorable change in weight-for-age z-score.
Assuntos
Transtornos do Crescimento/etiologia , Cardiopatias Congênitas/complicações , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
CHD is the most commonly occurring birth defect in the United States. Improvements in supportive care for CHD result in increasing numbers of survivors who may develop benign or malignant conditions for which HSCT is indicated. However, the ability of individuals with CHD to tolerate HSCT is unknown. Retrospective medical record review of 1031 patients who underwent HSCT at Children's Hospital Boston between 1989 and 2007 identified those with CHD. Ten patients with CHD that required repair or palliation before or after HSCT, or with CHD that would have required repair had they survived HSCT, were identified. These patients tolerated chemotherapy and/or radiation therapy uneventfully. Although half experienced febrile neutropenia and two had documented bacteremia, no endocarditis was observed. During the first 100 days post-HSCT, combined rates of grade 3, 4, and 5 cardiac, renal, and pulmonary toxicity for these patients were 10%, 0%, and 10%, respectively. In children with underlying CHD, there was no clinical evidence of impaired ability to tolerate febrile neutropenia, volume challenge, or other regimen-related toxicities that might require significant cardiac reserve. CHD alone should not be considered an absolute contraindication for indicated HSCT.