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1.
Heart ; 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32748799

RESUMO

OBJECTIVES: Although a life-preserving surgery for children with single ventricle physiology, the Fontan palliation is associated with striking morbidity and mortality with advancing age. Our primary objective was to evaluate the impact of non-invasive, external, thoraco-abdominal ventilation on pulmonary blood flow (PBF) and cardiac output (CO) as measured by cardiovascular magnetic resonance (CMR) imaging in adult Fontan subjects. METHODS: Adults with a dominant left ventricle post-Fontan palliation (lateral tunnel or extracardiac connections) and healthy controls matched by sex and age were studied. We evaluated vascular flows using phase-contrast CMR imaging during unassisted breathing, negative pressure ventilation (NPV) and biphasic ventilation (BPV). Measurements were made within target vessels (aorta, pulmonary arteries, vena cavae and Fontan circuit) at baseline and during each ventilation mode. RESULTS: Ten Fontan subjects (50% male, 24.5 years (IQR 20.8-34.0)) and 10 matched controls were studied. Changes in PBF and CO, respectively, were greater following BPV as compared with NPV. In subjects during NPV, PBF increased by 8% (Δ0.20 L/min/m2 (0.10-0.53), p=0.011) while CO did not change significantly (Δ0.17 L/min/m2 (-0.11-0.23), p=0.432); during BPV, PBF increased by 25% (Δ0.61 L/min/m2 (0.20-0.84), p=0.002) and CO increased by 16% (Δ0.47 L/min/m2 (0.21-0.71), p=0.010). Following BPV, change in PBF and CO were both significantly higher in subjects versus controls (0.61 L/min/m2 (0.2-0.84) vs -0.27 L/min/m2 (-0.55-0.13), p=0.001; and 0.47 L/min/m2 (0.21-0.71) vs 0.07 L/min/m2 (-0.47-0.33), p=0.034, respectively). CONCLUSION: External ventilation acutely augments PBF and CO in adult Fontan subjects. Confirmation of these findings in larger populations with longer duration of ventilation and extended follow-up will be required to determine sustainability of haemodynamic effects.

2.
Pediatr Res ; 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375165

RESUMO

BACKGROUND: Information on genetic etiology of pediatric hypertrophic cardiomyopathy (HCM) rarely aids in risk stratification and prediction of disease onset. Little data exist on the association between genetic modifiers and phenotypic expression of myocardial performance, hampering an individual precision medicine approach. METHODS: Single-nucleotide polymorphism genotyping for six previously established disease risk alleles in the hypoxia-inducible factor-1α-vascular endothelial growth factor pathway was performed in a pediatric cohort with HCM. Findings were correlated with echocardiographic parameters of systolic and diastolic myocardial deformation measured by two-dimensional (2-D) speckle-tracking strain. RESULTS: Twenty-five children (6.1 ± 4.5 years; 69% male) with phenotypic and genotypic (60%) HCM were included. Out of six risk alleles tested, one, VEGF1 963GG, showed an association with reduced regional systolic and diastolic left ventricular (LV) myocardial deformation. Moreover, LV average and segmental systolic and diastolic strain and strain rate were significantly reduced, as assessed by the standardized difference, in patients harboring the risk allele. CONCLUSIONS: This is the first study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial function, with the VEGF1 963GG allele associated with reduced LV systolic and diastolic myocardial performance. While studies are needed to link this information to adverse clinical outcomes, this knowledge may help in risk stratification and patient management in HCM. IMPACT: Risk allele in the VEGF gene impacts on LV myocardial deformation phenotype in children with HCM.LV 2-D strain is significantly reduced in patients with risk allele compared to non-risk allele patients within HCM patient groups.Describes that deficiencies in LV myocardial performance in children with HCM are associated with a previously identified risk allele in the angiogenic transcription factor VEGF.First study to identify an association between a risk allele in the VEGF pathway and regional LV myocardial deformation measured by 2-D strain in children with HCM.

3.
Eur Heart J ; 40(45): 3672-3681, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31170284

RESUMO

AIMS: Current guidelines recommend initiating family screening for hypertrophic cardiomyopathy (HCM) after age 10 or 12 years unless early screening criteria are met. The aim was to evaluate if current screening guidelines miss early onset disease. METHODS AND RESULTS: Children who underwent family screening for HCM before age 18 years were analysed. Major cardiac events (MaCEs) were defined as death, sudden cardiac death (SCD), or need for major cardiac interventions (myectomy, implantable cardioverter-defibrillator insertion, transplantation). Of 524 children screened, 331 were under 10 years of age, 9.9% had echocardiographic evidence of HCM, and 1.1% were symptomatic at first screening. The median (interquartile range) age at HCM onset was 8.9 (4.7-13.4) years, and at MaCE was 10.9 (8.5-14.3) years with a median time to MaCE from HCM onset of 1.5 (0.5-4.1) years. About 52.5% phenotype-positive children and 41% with MaCEs were <10 years old. Only 69% children with early HCM met early screening criteria. Cox regression identified male gender, family history of SCD, and pathogenic variants in MYH7/MYBPC3 as a predictor of early onset HCM and MaCEs. CONCLUSION: A third of children not eligible for early screening by current guidelines had phenotype-positive HCM. MYH7 and MYBC3 mutation-positive patients were at highest risk for developing early HCM and experiencing an event or requiring a major intervention. Our findings suggest that younger family members should be considered for early clinical and genetic screening to identify the subset in need of closer monitoring and interventions.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Morte Súbita Cardíaca/epidemiologia , Desfibriladores Implantáveis/estatística & dados numéricos , Testes Genéticos/métodos , Transplante de Coração/estatística & dados numéricos , Adolescente , Miosinas Cardíacas/genética , Cardiomiopatia Hipertrófica/complicações , Doenças Cardiovasculares/epidemiologia , Proteínas de Transporte/genética , Criança , Pré-Escolar , Morte Súbita Cardíaca/prevenção & controle , Ecocardiografia/métodos , Família , Feminino , Transplante de Coração/métodos , Humanos , Masculino , Mutação , Cadeias Pesadas de Miosina/genética , Fenótipo , Guias de Prática Clínica como Assunto , Estudos Retrospectivos
4.
Pediatr Res ; 72(6): 583-92, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23007030

RESUMO

BACKGROUND: Risk factors for diastolic dysfunction in hypertrophic cardiomyopathy (HCM) are poorly understood. We investigated the association of variants in hypoxia-response genes with phenotype severity in pediatric HCM. METHODS: A total of 80 unrelated patients <21 y and 14 related members from eight families with HCM were genotyped for six variants associated with vascular endothelial growth factor A (VEGFA) downregulation, or hypoxia-inducible factor A (HIF1A) upregulation. Associations between risk genotypes and left-ventricular (LV) hypertrophy, LV dysfunction, and freedom from myectomy were assessed. Tissue expression was measured in myocardial samples from 17 patients with HCM and 20 patients without HCM. RESULTS: Age at enrollment was 9 ± 5 y (follow-up, 3.1 ± 3.6 y). Risk allele frequency was 67% VEGFA and 92% HIF1A. Risk genotypes were associated with younger age at diagnosis (P < 0.001), septal hypertrophy (P < 0.01), prolonged E-wave deceleration time (EWDT) (P < 0.0001) and isovolumic relaxation time (IVRT) (P < 0.0001), and lower freedom from myectomy (P < 0.05). These associations were seen in sporadic and familial HCM independent of the disease-causing mutation. Risk genotypes were associated with higher myocardial HIF1A and transforming growth factor B1 (TGFB1) expression and increased endothelial-fibroblast transformation (P < 0.05). CONCLUSION: HIF1A-upregulation and/or VEGFA-downregulation genotypes were associated with more severe septal hypertrophy and diastolic dysfunction and may provide genetic markers to improve risk prediction in HCM.


Assuntos
Cardiomiopatia Hipertrófica/genética , Variação Genética , Hipóxia/genética , Criança , Pré-Escolar , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único
5.
Heart ; 97(16): 1343-8, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21646245

RESUMO

BACKGROUND: The bidirectional cavopulmonary connection (BCPC) is used in the staged palliation of univentricular hearts and places the cerebral and pulmonary vascular beds in series. Angiotensin-converting enzyme inhibitors (ACEI) are often used in this complex circulation, but the effects of their vasodilation are unclear. OBJECTIVE: Assessment of the acute response of perfusion pressure, flow and resistance across the systemic, cerebral and pulmonary vascular beds to ACEI in patients with a BCPC. DESIGN: Prospective interventional study. SETTING: Single tertiary care centre. PATIENTS: 12 patients with a BCPC (median age 28 months, weight 11.8 kg) undergoing a pre-Fontan catheterisation with MRI measurement of flows. INTERVENTION: Intravenous enalaprilat 0.005 or 0.01 mg/kg. RESULTS: Enalaprilat increased descending aorta flow (median 21.6%, p=0.0005), decreased total pulmonary vein flow (median 10.6%, p=0.025), and both superior caval vein flow (median 8.6%, p=0.065) and aortopulmonary collateral flow (median 15.5%, p=0.077) tended to decrease. Total cardiac output was unchanged (p=0.57). Systemic vascular resistance (median 41.9%, p=0.0005) and cerebral vascular resistance (median 23.4%, p=0.0005) decreased, but pulmonary vascular resistance (p=0.73) showed little change. There was evidence of autoregulation of cerebral blood flow. The proportion of descending aortic flow to total cardiac output increased (median 27 to 35%, p=0.001). Systemic oxygen saturation decreased from 87% to 83% (p=0.02). CONCLUSION: Enalaprilat did not increase total cardiac output but redistributed flow to the lower body, with a concomitant decrease in arterial oxygen saturation. It is difficult to increase cardiac output in patients with a BCPC and ACEI should be used with caution in those with borderline aortic saturations.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Enalaprilato/farmacologia , Derivação Cardíaca Direita , Cardiopatias Congênitas/cirurgia , Hemodinâmica/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Cateterismo Cardíaco/métodos , Débito Cardíaco/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Pré-Escolar , Enalaprilato/administração & dosagem , Feminino , Cardiopatias Congênitas/fisiopatologia , Ventrículos do Coração/anormalidades , Humanos , Lactente , Angiografia por Ressonância Magnética/métodos , Masculino , Cuidados Pós-Operatórios/métodos , Estudos Prospectivos , Circulação Pulmonar/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos
6.
Am J Cardiol ; 104(6): 862-7, 2009 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-19733725

RESUMO

Transcatheter pulmonary valve implantation (PVI) is an emerging therapy for right ventricular (RV) outflow dysfunction in congenital heart disease. We investigated, for the first time in children after surgery for congenital heart disease, the short-term effects of PVI on RV and left ventricular (LV) function using 2-dimensional speckle tracking echocardiography and tissue Doppler imaging. We hypothesized that the short-term RV and LV function would improve. Two-dimensional speckle tracking echocardiograms and pulsed tissue Doppler images were obtained before and 1 to 2 days after PVI (18-mm Melody valve). The catheter right heart hemodynamics were recorded. The strain and strain rate of the basal lateral left ventricle, lateral right ventricle, and interventricular septum were measured by 2-dimensional speckle tracking echo, and the pre- and postprocedure values were compared. Of the 16 eligible patients (age 16 +/- 2 years), the scans of 10 had correct image format and adequate quality. PVI was performed for volume (n = 4) or combined pressure-volume (n = 6) loading. After PVI, the RV to pulmonary artery pressure gradient (33 +/- 22 to 12 +/- 4 mm Hg, p = 0.02), pulmonary regurgitation, and RV end-diastolic volume (3.2 +/- 0.8 to 2.8 +/- 0.6 cm, p = 0.02) decreased, and the septal systolic velocities (3.5 +/- 1.1 to 4.7 +/- 1.1 cm/s, p = 0.04), strain (-7.6 +/- 9.3% to -15.6% +/- 6.7%, p = 0.01) and strain rate (-0.3 +/- 1.1 to -1.1 +/- 0.5 1/s, p = 0.04) and RV free wall strain increased (-17.4 +/- 8.6% to -23.4% +/- 6.2%, p = 0.03). The LV tissue velocities, strain, and strain rate were unchanged. In conclusion, PVI leads to RV unloading and acutely improves RV and septal function.


Assuntos
Ecocardiografia Doppler/métodos , Cardiopatias Congênitas/cirurgia , Valva Pulmonar/cirurgia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/cirurgia , Adolescente , Cateterismo Cardíaco , Criança , Ecocardiografia Doppler de Pulso/métodos , Feminino , Cardiopatias Congênitas/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Variações Dependentes do Observador , Estudos Retrospectivos , Sensibilidade e Especificidade , Tetralogia de Fallot/fisiopatologia , Tetralogia de Fallot/cirurgia , Função Ventricular Esquerda , Função Ventricular Direita , Pressão Ventricular
7.
Circulation ; 119(15): 2078-85, 2009 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-19349326

RESUMO

BACKGROUND: Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct. METHODS AND RESULTS: Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (n=14) or bare metal (n=14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct-derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [(3)H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (P=0.009), 54% (P=0.004), and 77% (P=0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (P=0.18), 5% (P=0.25), and 61% (P=0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (P<0.001). CONCLUSIONS: Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.


Assuntos
Stents Farmacológicos , Canal Arterial/efeitos dos fármacos , Sirolimo/uso terapêutico , Animais , Animais Recém-Nascidos , Divisão Celular/efeitos dos fármacos , Células Cultivadas/efeitos dos fármacos , Canal Arterial/diagnóstico por imagem , Canal Arterial/cirurgia , Canal Arterial/ultraestrutura , Elastina/biossíntese , Cardiopatias Congênitas/cirurgia , Hiperplasia , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Sirolimo/administração & dosagem , Sus scrofa , Túnica Íntima/ultraestrutura , Ultrassonografia
8.
J Am Coll Cardiol ; 49(9): 993-1002, 2007 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-17336724

RESUMO

Pulmonary vein pathologies often present a diagnostic challenge. Among the different imaging modalities used for the evaluation of pulmonary veins, magnetic resonance is the most comprehensive in assessing anatomy and pathophysiology at the same time. Bright blood cine sequences and contrast-enhanced magnetic resonance angiography outline the course and connections of the pulmonary veins. Phase-contrast velocity mapping measures flow patterns, velocities, and volumes throughout the pulmonary circulation. This paper reviews contemporary utilization of magnetic resonance in the evaluation of pulmonary venous abnormalities in children, based on our experience over the last 5 years and on that of other investigators. We summarize how magnetic resonance imaging enhances our understanding of pulmonary vein physiology and how it can influence the diagnostic approach to children and adults with a pulmonary venous pathology, and we discuss its limitations.


Assuntos
Angiografia por Ressonância Magnética/métodos , Veias Pulmonares/patologia , Veias Pulmonares/fisiopatologia , Velocidade do Fluxo Sanguíneo , Anormalidades Cardiovasculares/diagnóstico , Ablação por Cateter , Criança , Pré-Escolar , Constrição Patológica/diagnóstico , Feminino , Humanos , Lactente , Masculino , Oximetria/métodos , Circulação Pulmonar , Veias Pulmonares/anormalidades , Veias Pulmonares/cirurgia
9.
Cardiol Young ; 16(3): 305-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16725071

RESUMO

We report an unusual case in which the peripheral part of the otherwise normal left lung was supplied by major systemic arteries arising from the left subclavian, internal mammary and coeliac arteries. Unlike most cases with systemic arterial supply to a normal or sequestered lung, where the systemic arterial branches get access to the lung through the pulmonary hilum or inferior pulmonary ligament, in our patient the systemic arterial branches entered the lung through the transpleural routes.


Assuntos
Sequestro Broncopulmonar/diagnóstico por imagem , Artéria Pulmonar/anormalidades , Angiografia , Criança , Diagnóstico Diferencial , Humanos , Masculino , Artéria Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X
10.
Circulation ; 107(23): 2938-43, 2003 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-12771012

RESUMO

BACKGROUND: The importance of pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) is increasingly recognized, but little is known regarding its underlying mechanisms. This phase-contrast cine magnetic resonance (PC MR) study was performed to evaluate the relative contribution of each lung to total regurgitant volume. METHODS AND RESULTS: Twenty-two patients with significant PR underwent a PC MR 3 to 16 years after repair of TOF. Regurgitant fraction of the main pulmonary artery was 39+/-10%. Regurgitant fraction of the left pulmonary artery (LPA; 46+/-18%) was greater than that of the right pulmonary artery (34+/-16%; P=0.002). The average contribution of the LPA to the total regurgitant flow volume was 54+/-19%, whereas its average contribution to the total forward flow volume was 44+/-13% (P=0.002). In 4 patients, regurgitant flow in the LPA accounted for 75% to 100% of the total regurgitant flow. There was a linear relationship between regurgitant fraction and fraction of the regurgitant flow duration in the main pulmonary artery (P<0.001) and right pulmonary artery (P=0.001) but not in the LPA (P=0.129). CONCLUSIONS: PR after repair of TOF is commonly associated with differential regurgitation in the branch pulmonary arteries, which is usually greater in the LPA. Although the cause of this disparity requires further investigation, those patients with a significant unilateral contribution to total PR may be amenable to localized techniques to reduce regurgitation.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Imagem Cinética por Ressonância Magnética , Insuficiência da Valva Pulmonar/diagnóstico , Insuficiência da Valva Pulmonar/etiologia , Tetralogia de Fallot/cirurgia , Adolescente , Velocidade do Fluxo Sanguíneo , Criança , Pré-Escolar , Feminino , Humanos , Pulmão/irrigação sanguínea , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Insuficiência da Valva Pulmonar/fisiopatologia , Grau de Desobstrução Vascular
11.
J Am Coll Cardiol ; 40(4): 796-802, 2002 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-12204513

RESUMO

OBJECTIVES: This study was designed to document the association of endocardial fibroelastosis (EFE) and maternal autoantibodies. BACKGROUND: Neonatal lupus erythematosus is associated with the transplacental passage of maternal anti-Ro and anti-La antibodies, leading to complete atrioventricular block (CAVB). In some cases, CAVB is associated with EFE. Isolated EFE may be independently related to maternal anti-Ro and anti-La antibodies. METHODS: We identified three cases (one fetus and two infants, all female) of isolated EFE in infants born to autoantibody-positive mothers in the absence of CAVB. Demographics, echocardiograms, and pathology were reviewed. Immunohistochemical analyses for immunoglobulin (Ig)G, IgM, IgA, T-cell, B-cell, and terminal deoxynucleoleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) (test for cell apoptosis) staining were performed on multiple sections of the heart in each case and compared with negative controls. RESULTS: Two cases died and one received a cardiac transplant. All three cases had histologically confirmed EFE. All cases demonstrated significant diffuse IgG infiltration. To a lesser extent, myocardial tissue was also positive for IgM, CD43, and Granzyme B. None of the specimens were TUNEL positive. CONCLUSIONS: These are the first reported cases of isolated EFE associated with maternal anti-Ro and anti-La antibodies in the absence of CAVB. The diffuse deposition of IgG and the presence of a T-cell infiltrate throughout the myocardium suggest that the transplacental passage of maternal autoantibodies induces an immune reaction within the myocardium, leading to isolated EFE. Autoantibody-mediated EFE may be an etiologic factor in cases of fetal and neonatal "idiopathic" dilated cardiomyopathy.


Assuntos
Autoanticorpos , Autoantígenos/imunologia , Fibroelastose Endocárdica/imunologia , Feto/imunologia , Miocárdio/imunologia , Ribonucleoproteínas/imunologia , Anticorpos Antinucleares , Fibroelastose Endocárdica/patologia , Feminino , Humanos , Lactente , Lúpus Eritematoso Sistêmico/imunologia , Troca Materno-Fetal , Miocárdio/patologia , Gravidez
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