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BACKGROUND: Heterotaxy syndrome (HS) is a defect in lateralization which often results in complex intra and extracardiac abnormalities. Orthotropic heart transplantation (OHT) in HS involves intricate and individualized modifications to surgical technique. Post-OHT outcomes are worse in patients with HS, however, the impact of post-OHT residual lesions has not yet been characterized. METHODS: Patients with HS who underwent OHT at Ann & Robert H. Lurie Children's Hospital of Chicago between January 2012 and June 2023 were identified. Patients were excluded if follow-up data was not available due to follow up at a different institution of early mortality. Pre-OHT clinical data, surgical data, and post-OHT surgical and catheterization data were collected. RESULTS: Two early mortalities were excluded from analysis, leaving 15 patients in the study cohort. Median age at OHT was 3.7 years (range: 0.7-15.4). Nine out of 15 patients were diagnosed with residual lesions requiring intervention at a median of 188 days post transplantation. All interventions on residual lesions occurred via catheterization. Overall mortality rate was 27% (4/15) with all deaths occurring in patients with residual lesions (4/9 patients, 44%). 83% (10/12) of lesions were diagnosed via catheterization, and 83% (10/12) of lesions of occurred in the first year after transplant. CONCLUSIONS: Patients with HS are at high risk for residual lesions after OHT, which may contribute to increased mortality. Comprehensive invasive diagnostics were required to diagnose residual lesions, which were all addressed percutaneously.
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Transplante de Coração , Síndrome de Heterotaxia , Criança , Humanos , Lactente , Pré-Escolar , Adolescente , Síndrome de Heterotaxia/complicações , Síndrome de Heterotaxia/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Pulmonary vein stenosis (PVS) is a rare condition in which neointimal proliferation leads to venous and arterial hypertension. Little is known about PVS after heart transplant (HTx) in children. We sought to describe the characteristics and outcomes of children who develop PVS after HTx. METHODS: We performed a retrospective review of patients ≤18 years old who underwent HTx at two HTx centers between April 2012 and October 2023. Patients with PVS were identified via database queries. Cardiac diagnosis, PVS location and extent, and outcomes were recorded. RESULTS: Over 11.5 years, 422 patients underwent HTx across both centers. Nineteen patients with PVS (10 male) were identified, 15 with de novo PVS. Sixteen had underlying congenital heart disease (CHD), two with anomalous pulmonary venous return. PVS was diagnosed at a median of 2 months (range 2 weeks to 14 years) after HTx. At time of initial diagnosis, 13 patients had one-vessel PVS. At final follow-up, 7/19 (37%) had increases in the number of vessels involved. Six patients underwent surgery, and nine patients had stent or balloon angioplasty. Two patients were treated for pulmonary hypertension following PVS diagnosis. Three patients died from right heart failure secondary to PVS. CONCLUSIONS: This is the largest study to describe the characteristics of post-HTx PVS in children. PVS occurs in 4.5% of HTx, and underlying CHD is a strong risk factor. Multiple vessels can be involved and may require catheter-based or surgical intervention. Clinicians must be vigilant in monitoring the development of PVS in this population.
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Transplante de Coração , Complicações Pós-Operatórias , Estenose de Veia Pulmonar , Humanos , Estudos Retrospectivos , Masculino , Transplante de Coração/efeitos adversos , Feminino , Criança , Pré-Escolar , Estenose de Veia Pulmonar/etiologia , Lactente , Adolescente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Recém-Nascido , Progressão da Doença , Cardiopatias Congênitas/cirurgia , Cardiopatias Congênitas/complicações , SeguimentosRESUMO
BACKGROUND: Chronic graft failure (CGF) in pediatric heart transplant (PHT) is multifactorial and may present with findings of fibrosis and microvessel disease (MVD) on endomyocardial biopsy (EMB). There is no optimal CGF surveillance method. We evaluated associations between cardiac magnetic resonance imaging (CMR) and historical/EMB correlates of CGF to assess CMR's utility as a surveillance method. METHODS: Retrospective analysis of PHT undergoing comprehensive CMR between September 2015 and January 2022 was performed. EMB within 6 months was graded for fibrosis (scale 0-5) and MVD (number of capillaries with stenotic wall thickening per field of view). Correlation analysis and logistic regression were performed. RESULTS: Forty-seven PHT with median age at CMR of 15.7 years (11.6, 19.3) and time from transplant of 6.4 years (4.1, 11.0) were studied. Cardiac allograft vasculopathy (CAV) was present in 11/44 (22.0%) and historical rejection in 14/41 (34.2%). CAV was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.038) and peak T2 (57.0 vs. 53.0 ms; p = 0.013) on CMR. Historical rejection was associated with higher global T2 (49.0 vs. 47.0 ms; p = 0.007) and peak T2 (57.0 vs. 53.0 ms; p = 0.03) as well as global extracellular volume (31.0 vs. 26.3%; p = 0.03). Higher fibrosis score on EMB correlated with smaller indexed left ventricular mass (rho = -0.34; p = 0.019) and greater degree of MVD with lower indexed left ventricular end-diastolic volume (rho = -0.35; p = 0.017). CONCLUSION: Adverse ventricular remodeling and abnormal myocardial characteristics on CMR are present in PHT with CAV, historical rejection, as well as greater fibrosis and MVD on EMB. CMR has the potential use for screening of CGF.
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Transplante de Coração , Miocárdio , Humanos , Criança , Miocárdio/patologia , Estudos Retrospectivos , Transplante de Coração/efeitos adversos , Imageamento por Ressonância Magnética , Fibrose , Valor Preditivo dos Testes , Rejeição de Enxerto/patologiaRESUMO
BACKGROUND: The relationship between histopathologic and molecular ("MMDx"®) assessments of endomyocardial biopsy (EMB) and serum donor-derived cell-free DNA (ddcfDNA) in acute rejection (AR) assessment following pediatric heart transplantation (HT) is unknown. METHODS: EMB sent for MMDx and histopathology from November 2021 to September 2022 were reviewed. MMDx and histopathology results were compared. DdcfDNA obtained ≤1 week prior to EMB were compared with histopathology and MMDx results. The discrimination of ddcfDNA for AR was assessed using receiver-operating curves. FINDINGS: In this study, 177 EMBs were obtained for histopathology and MMDx, 101 had time-matched ddcfDNA values. MMDx and Histopathology displayed moderate agreement for T-cell-mediated rejection (TCMR, Kappa = 0.52, p < .001) and antibody-mediated rejection (ABMR, Kappa = 0.41, p < .001). Discordant results occurred in 24% of cases, most often with ABMR. Compared with no AR, ddcfDNA values were elevated in cases of AR diagnosed by both histopathology and MMDx (p < .01 for all). Additionally, ddcfDNA values were elevated in injury patterns on MMDx, even when AR was not present (p = .01). DdcfDNA displayed excellent discrimination (AUC 0.83) for AR by MMDx and/or histopathology. Using a threshold of ≥0.135%, ddcfDNA had a sensitivity of 90%, specificity of 63%, PPV of 52%, and NPV of 94%. CONCLUSIONS: Histopathology and MMDx displayed moderate agreement in diagnosing AR following pediatric HT, with most discrepancies noted in the presence of ABMR. DdcfDNA is elevated with AR, with excellent discrimination and high NPV particularly when utilizing MMDx. A combination of all three tests may be necessary in some cases.
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Ácidos Nucleicos Livres , Doxorrubicina/análogos & derivados , Transplante de Coração , Humanos , Criança , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/genética , Biópsia , RNA MensageiroRESUMO
The United States (US) Food and Drug Administration (FDA) has issued multiple statements and guidelines since 2015 on the topic of thyroid function testing in babies and children through 3 years old after receiving iodinated contrast media for medical imaging exams. In April 2023, the FDA adjusted this recommendation to target babies and young children younger than 4 years of age who have a history of prematurity, very low birth weight, or underlying conditions which affect thyroid gland function, largely in response to solid arguments from expert statements from the American College of Radiology (ACR) which is endorsed by the Society for Pediatric Radiology (SPR), Pediatric Endocrinology Society (PES), and the Society for Cardiovascular Angiography & Intervention (SCAI). Herein we describe our approach and development of a clinical care guideline along with the steps necessary for implementation of the plan including alterations in ordering exams requiring iodinated contrast media, automatic triggering of lab orders, reporting, and follow-up, to address the 2022 FDA guidance statement to monitor thyroid function in children after receiving iodinated contrast media. The newly implemented clinical care guideline at Ann and Robert H. Lurie Children's Hospital of Chicago remains applicable following the 2023 updated recommendation from the FDA. We will track patients less than 3 months of age who undergo thyroid function testing following computed tomography (CT), interventional radiology, and cardiac catheterization exams for which an iodinated contrast media is administered as a clinical care quality initiative.
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Planejamento Hospitalar , Iodo , Lactente , Criança , Estados Unidos , Humanos , Pré-Escolar , Glândula Tireoide/diagnóstico por imagem , Meios de Contraste/efeitos adversos , United States Food and Drug Administration , Angiografia , Iodo/efeitos adversosRESUMO
Cardiac index (CI) may be derived from the Fick method, using measured or estimated oxygen consumption (VO2), or from thermodilution. In children, LaFarge VO2 estimates correlate poorly with measured VO2 values. In a large adult cohort, there was only modest correlation between estimated Fick CI (eFick CI) and thermodilution CI (TDCI). We evaluated the extent of agreement between eFick CI using LaFarge estimates of VO2 and TDCI in a pediatric cohort. A retrospective, single-center chart review of patients 3-18 years of age who underwent cardiac catheterization with documented eFick CI and TDCI from 2004 to 2020 included 201 catheterizations from 161 unique patients. The mean patient age at catheterization was 12.2y (SD 4.4y). The most frequent diagnosis was cardiomyopathy, followed by congenital heart disease and pulmonary hypertension. TDCI and eFick CI differed by > 20% in 49% of catheterizations. eFick CI systematically exceeded TDCI by a mean percentage difference of 24% (SD 31%). Higher mean CI ((eFick CI + TDCI)/2) and older age were predictive of greater percent difference between eFick CI and TDCI. For each increase in mean CI by 1.0 L/min/m2, the expected percent difference in CI increased by 9.9% (p < 0.001). In pediatric patients undergoing cardiac catheterization, eFick CI with LaFarge VO2 systematically exceeds TDCI. The difference between methods is frequently > 20%, which may have clinically significant implications. Discrepancies between eFick CI and TDCI increase at higher mean CI.
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Balloon aortic valvuloplasty (BAV) is performed in children with significant aortic stenosis (AS). Traditionally, contrast angiography measures the annulus and assesses aortic regurgitation (AR) after each dilation. Echocardiographic guidance is hypothesized to reduce contrast and radiation exposure, without compromising efficacy or safety. Patients < 10 kg undergoing BAV from 2013 to 2022 were retrospectively investigated. Agreement between echocardiographic and angiographic annulus measurements was assessed. Echocardiogram-guided (eBAV) and traditional angiogram-guided (tBAV) outcomes were compared controlling for weight, critical AS, and other congenital heart disease (CHD). Twelve eBAV and 19 tBAV procedures were performed. The median age was 33 days, median weight was 4.3 kg, 7 patients (23%) had critical AS, and 9 patients (29%) had other CHD. Annulus measurements by intraprocedural echocardiography and angiography displayed excellent correlation (ICC 0.95, p < 0.001). eBAV patients received less contrast (0.5 vs 3.5 ml/kg, p < 0.01). Five recent eBAV procedures were performed contrast free. Radiation exposure was not statistically different between the eBAV and tBAV groups (155 vs 313 µGy·M2, p = 0.12). One eBAV patient (8%) and 3 tBAV patients (16%, p = 0.62) experienced serious adverse events. Technical success (gradient < 35 mmHg and increase in AR by ≤ 1 grade) occurred in 11 eBAV patients (92%) and 16 tBAV patients (84%, p = 0.22). AR increased in 2 eBAV patients (17%) and 8 tBAV patients (44%, p = 0.02). eBAV was associated with similar efficacy and significantly lower contrast exposure and risk of aortic regurgitation. There was strong agreement between aortic valve annulus measurements by intraprocedural echocardiography and angiography, ultimately permitting contrast free BAV.
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Percutaneous balloon pulmonary valvuloplasty (PBPV) is the treatment of choice for isolated pulmonary valve stenosis. While this procedure is highly efficacious and has an excellent safety profile, as currently practiced, patients are obligatorily exposed to the secondary risks of ionizing radiation and contrast media. To mitigate these risks, we developed a protocol which utilized echo guidance for portions of the procedure which typically require fluoroscopy and/or angiography. Ten cases of echo-guided pulmonary valvuloplasty (EG-PBPV) for isolated pulmonary stenosis in children less than a year of age were compared to a historical cohort of nineteen standard cases using fluoroscopy/angiography alone, which demonstrated equivalent procedural outcomes and safety, while achieving a median reduction in radiation (total dose area product) and contrast load of 80% and 84%, respectively. Our early experience demonstrates that EG-PBPV in neonates and infants has results equivalent to standard valvuloplasty but with less radiation and contrast.
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Valvuloplastia com Balão , Procedimentos Cirúrgicos Cardíacos , Estenose da Valva Pulmonar , Valvuloplastia com Balão/métodos , Criança , Fluoroscopia , Humanos , Lactente , Recém-Nascido , Estenose da Valva Pulmonar/diagnóstico por imagem , Estenose da Valva Pulmonar/etiologia , Estenose da Valva Pulmonar/terapia , Resultado do TratamentoRESUMO
The GORE® CARDIOFORM ASD occluder (ASDO) is approved for closure of ASDs up to 35 mm diameter. With an adaptable central waist, each device size is suitable over a range of defect diameters. Understanding deployed dimensions across various defect sizes will assist operators. Therefore, this study investigates the deployed dimensions of the ASDO as a function of defect size. A 2-mm-thick ASD model with circular defects ranging from 5 to 35 mm was 3D printed. Diameter, width, and left-right disc diameter were measured by fluoroscopy after ASDO devices were deployed in applicable defects. Linear regression evaluated relationships between device size, defect size, and deployed dimensions. Six ASDOs of each size (27, 32, 37, 44, and 48 mm) were deployed in all applicable defects. There was significant ASDO size-defect size interaction in determining deployed ASDO diameter. Diameter was positively associated with defect size for 48-mm (B = 0.13, p < 0.001) and 44-mm (B = 0.11, p < 0.001) ASDOs, while no association was seen for 27-mm, 32-mm, or 37-mm ASDOs. No such interaction existed for deployed width or left-right disc difference. Controlling for ASDO size, width (B = - 0.12, p < 0.001) and left-right disc difference (B = - 0.06, p < 0.001) were negatively associated with defect size. In smaller defects, the 44-mm and 48-mm ASDOs display progressive diameter foreshortening, and all devices display progressive increase in width and left-right disc asymmetry. Anticipating the degree of diameter foreshortening may be critical when attempting closure of fenestrated lesions and/or in patients with limited total atrial septal length.
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Comunicação Interatrial/patologia , Desenho de Prótese/métodos , Dispositivo para Oclusão Septal , Cateterismo Cardíaco/instrumentação , Comunicação Interatrial/cirurgia , Humanos , Fatores de TempoRESUMO
Covered stents have a continually expanding spectrum of applications for patients with congenital heart disease. Here we report use of covered stents to successfully perform a first-in-human percutaneous biventricular conversion of a 1.5 ventricle Glenn palliation in an adult born with pulmonary atresia. This case demonstrates that in patients considered borderline for biventricular repair, surgery can potentially be modified to promote growth of underdeveloped structures and setup for transcatheter biventricular conversion.
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Procedimentos Endovasculares , Técnica de Fontan , Cardiopatias Congênitas/cirurgia , Cuidados Paliativos , Síndrome da Veia Cava Superior/terapia , Adulto , Procedimentos Endovasculares/instrumentação , Feminino , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica , Humanos , Stents , Síndrome da Veia Cava Superior/diagnóstico por imagem , Síndrome da Veia Cava Superior/etiologia , Síndrome da Veia Cava Superior/fisiopatologia , Resultado do TratamentoRESUMO
AIM: Paediatric vitamin D (25-hydroxyvitamin D (25OHD)) deficiency can lead to nutritional rickets and extra-skeletal complications. Compliance with daily therapy can be difficult, making high-dose, short-term vitamin D (stoss) therapy attractive to correct vitamin D deficiency. We compared the effectiveness and safety of standard versus stoss therapy in treating childhood 25OHD deficiency. METHODS: Children aged 2-16 years with 25OHD <50 nmol/L were randomised to either standard (5000 IU daily for 80 days) or stoss (100 000 IU weekly for 4 weeks) cholecalciferol. Participants underwent an evaluation of effectiveness and safety. The 25OHD level, random spot calcium: creatinine ratio (Ca:Cr) and compliance were measured at 12 weeks. RESULTS: A total of 151 children were enrolled in the study (68 standard and 83 stoss), median age 9 years (inter-quartile range (IQR): 6-12 years). Baseline 25OHD levels were 26 nmol/L (IQR: 19-35 nmol/L) and 32 nmol/L (IQR: 24-39 nmol/L) in the standard and stoss groups, respectively. At 12 weeks, the median 25OHD level was significantly greater in the standard versus stoss group (81 vs. 67 nmol/L; P = 0.005); however, >80% of participants in both groups achieved sufficiency (25OHD > 50 nmol/L) and had normal urinary Ca:Cr, with no significant difference seen between groups. Compliance was similar in the two groups. CONCLUSIONS: Compared to stoss, standard therapy achieved higher 25OHD levels at 12 weeks; however, in both groups, there was a similar proportion of participants who achieved 25OHD sufficiency, with no evidence of toxicity. Unlike other studies, simplifying the treatment regimen did not improve compliance. These results support stoss therapy as an effective and safe alternative therapy for the treatment of paediatric vitamin D deficiency.
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Deficiência de Vitamina D , Adolescente , Calcifediol , Cálcio , Criança , Pré-Escolar , Colecalciferol , Humanos , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , VitaminasRESUMO
Anomalous origin of the left anterior descending coronary artery from the pulmonary artery is a rare variant of anomalous origin of the left main coronary artery from the pulmonary artery. We report on a seemingly asymptomatic patient with ALADCAPA and a small restrictive muscular ventricular septal defect diagnosed by echocardiogram in the neonatal period. Our patient underwent elective repair at 3.5 months of age after which feeding and growth improved dramatically. Multimodality imaging is helpful to confirm this rare anomaly; however, echocardiographic clues including lack of left coronary branching or an abnormal coronary course should raise suspicion for ALADCAPA. This case provides support for early repair in children with an incidental finding of this anomaly as subclinical ischemia may be under-recognized by available testing but may lead to symptoms later in life.
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Anomalias dos Vasos Coronários/diagnóstico por imagem , Comunicação Interventricular/diagnóstico , Artéria Pulmonar/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária , Ecocardiografia/métodos , Feminino , Comunicação Interventricular/cirurgia , Humanos , Achados Incidentais , Recém-Nascido , Imagem MultimodalRESUMO
Introduction New paediatric cardiology trainees are required to rapidly assimilate knowledge and gain clinical skills to which they have limited or no exposure during residency. The Pediatric Cardiology Fellowship Boot Camp (PCBC) at Boston Children's Hospital was designed to provide incoming fellows with an intensive exposure to congenital cardiac pathology and a broad overview of major areas of paediatric cardiology practice. METHODS: The PCBC curriculum was designed by core faculty in cardiac pathology, echocardiography, electrophysiology, interventional cardiology, exercise physiology, and cardiac intensive care. Individual faculty contributed learning objectives, which were refined by fellowship directors and used to build a programme of didactics, hands-on/simulation-based activities, and self-guided learning opportunities. RESULTS: A total of 16 incoming fellows participated in the 4-week boot camp, with no concurrent clinical responsibilities, over 2 years. On the basis of pre- and post-PCBC surveys, 80% of trainees strongly agreed that they felt more prepared for clinical responsibilities, and a similar percentage felt that PCBC should be offered to future incoming fellows. Fellows showed significant increase in their confidence in all specific knowledge and skills related to the learning objectives. Fellows rated hands-on learning experiences and simulation-based exercises most highly. CONCLUSIONS: We describe a novel 4-week-long boot camp designed to expose incoming paediatric cardiology fellows to the broad spectrum of knowledge and skills required for the practice of paediatric cardiology. The experience increased trainee confidence and sense of preparedness to begin fellowship-related responsibilities. Given that highly interactive activities were rated most highly, boot camps in paediatric cardiology should strongly emphasise these elements.
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Cardiologia/educação , Competência Clínica/normas , Bolsas de Estudo/normas , Pediatria/educação , Avaliação de Programas e Projetos de Saúde/normas , Currículo , Educação Médica , HumanosRESUMO
RATIONALE: Studies to dissect the role of calcineurin in pathological cardiac remodeling have relied heavily on murine models, in which genetic gain- and loss-of-function manipulations are initiated at or before birth. However, the great majority of clinical cardiac pathology occurs in adults. Yet nothing is known about the effects of calcineurin when its activation commences in adulthood. Furthermore, despite the fact that ventricular hypertrophy is a well-established risk factor for heart failure, the relative pace and progression of these 2 major phenotypic features of heart disease are unknown. Finally, even though therapeutic interventions in adults are designed to slow, arrest, or reverse disease pathogenesis, little is known about the capacity for spontaneous reversibility of calcineurin-dependent pathological remodeling. OBJECTIVE: We set out to address these 3 questions by studying mice engineered to harbor in cardiomyocytes a constitutively active calcineurin transgene driven by a tetracycline-responsive promoter element. METHODS AND RESULTS: Expression of the mutant calcineurin transgene was initiated for variable lengths of time to determine the natural history of disease pathogenesis, and to determine when, if ever, these events are reversible. Activation of the calcineurin transgene in adult mice triggered rapid and robust cardiac growth with features characteristic of pathological hypertrophy. Concentric hypertrophy preceded the development of systolic dysfunction, fetal gene activation, fibrosis, and clinical heart failure. Furthermore, cardiac hypertrophy reversed spontaneously when calcineurin activity was turned off, and expression of fetal genes reverted to baseline. Fibrosis, a prominent feature of pathological cardiac remodeling, manifested partial reversibility. CONCLUSIONS: Together, these data establish and define the deleterious effects of calcineurin signaling in the adult heart and reveal that calcineurin-dependent hypertrophy with concentric geometry precedes systolic dysfunction and heart failure. Furthermore, these findings demonstrate that during much of the disease process, calcineurin-dependent remodeling remains reversible.
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Calcineurina/metabolismo , Cardiomegalia/enzimologia , Insuficiência Cardíaca/enzimologia , Miócitos Cardíacos/enzimologia , Disfunção Ventricular Esquerda/enzimologia , Remodelação Ventricular , Animais , Calcineurina/genética , Cardiomegalia/diagnóstico por imagem , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Progressão da Doença , Doxiciclina/farmacologia , Feminino , Fibrose , Regulação Enzimológica da Expressão Gênica , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mutação , Contração Miocárdica , Miócitos Cardíacos/patologia , Regiões Promotoras Genéticas/genética , Fatores de Tempo , Ultrassonografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/genética , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular EsquerdaRESUMO
A 33-year-old woman with aortic valve stenosis status-post Ross at age 6 years developed symptomatic right heart failure from right ventricle to pulmonary artery conduit stenosis. Conduit rehabilitation and transcatheter pulmonary valve replacement resulted in acute left atrial hypertension and respiratory failure requiring venoarterial extracorporeal membrane oxygenation and atrial septal defect creation as a bridge to recovery.
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Children with postpericardiotomy syndrome may develop hemodynamically significant pericardial effusions warranting drainage by surgical pericardial window or pericardiocentesis. The optimal approach is unknown. We performed a retrospective observational study at two pediatric cardiac centers. We included 42 children aged <18 years who developed postpericardiotomy syndrome following cardiac surgery between 2014 and 2021. Thirty-two patients underwent pericardial window and 10 underwent pericardiocentesis. Patients in the pericardial window group presented with postpericardiotomy syndrome sooner than those who underwent pericardiocentesis (median 7.5 days vs. 14.5 days, P = 0.03) and tended to undergo earlier intervention (median 8 days vs. 16 days, P = 0.16). No patient required subsequent drainage. There were no differences between groups in days of pericardial tube duration (median 4 days), complications, and subsequent days of intensive care or hospitalization. For children with postpericardiotomy syndrome with a pericardial effusion warranting drainage, these data suggest that pericardial window and pericardiocentesis have similar efficacy, safety, and resource utilization.
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A healthy 11-year-old girl presented with exercise intolerance of unclear etiology, and her physical exam was notable for a 3/6 systolic ejection murmur at the left upper sternal border with radiation to the back. Extensive noninvasive workup consisted of ECG, transthoracic echocardiogram, and cardiac MRI/MRA, which were all nondiagnostic. She was ultimately referred for cardiac catheterization. Baseline invasive hemodynamics demonstrated a normal cardiac index and pulmonary vascular resistance but was notable for mildly elevated right and left end-diastolic pressures. A diagnosis remained elusive, so a 500 mL volume challenge was performed, which unmasked right and left ventricular waveform transformations to reveal the pathognomonic "square root sign" of restrictive cardiomyopathy with concordant RV/LV respirophasic variation. These findings and her clinical history allowed for the rare pediatric diagnosis of restrictive cardiomyopathy early in her clinical course, prior to the development of overt signs of pathologic myocardial remodeling, such as pulmonary hypertension and biatrial enlargement.
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A missense mutation in the alphaB-crystallin (CryAB) gene triggers a severe form of desmin-related cardiomyopathy (DRCM) characterized by accumulation of misfolded proteins. We hypothesized that autophagy increases in response to protein aggregates and that this autophagic activity is adaptive. Mutant CryAB (CryAB(R120G)) triggered a >2-fold increase in cardiomyocyte autophagic activity, and blunting autophagy increased the rate of aggregate accumulation and the abundance of insoluble CryAB(R120G)-associated aggregates. Cardiomyocyte-restricted overexpression of CryAB(R120G) in mice induced intracellular aggregate accumulation and systolic heart failure by 12 months. As early as 2 months (well before the earliest declines in cardiac function), we detected robust autophagic activity. To test the functional significance of autophagic activation, we crossed CryAB(R120G) mice with animals harboring heterozygous inactivation of beclin 1, a gene required for autophagy. Blunting autophagy in vivo dramatically hastened heart failure progression with a 3-fold increase in interstitial fibrosis, greater accumulation of polyubiquitinated proteins, larger and more extensive intracellular aggregates, accelerated ventricular dysfunction, and early mortality. This study reports activation of autophagy in DRCM. Further, our findings point to autophagy as an adaptive response in this proteotoxic form of heart disease.
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Autofagia/fisiologia , Cardiomiopatias/etiologia , Desmina , Cadeia B de alfa-Cristalina/genética , Animais , Fibrose , Camundongos , Camundongos Mutantes , Mutação de Sentido Incorreto , Miócitos Cardíacos , PoliubiquitinaRESUMO
Cardiac hypertrophy is a major predictor of heart failure and a prevalent disorder with high mortality. Little is known, however, regarding mechanisms governing the transition from stable cardiac hypertrophy to decompensated heart failure. Here, we tested the role of autophagy, a conserved pathway mediating bulk degradation of long-lived proteins and cellular organelles that can lead to cell death. To quantify autophagic activity, we engineered a line of "autophagy reporter" mice and confirmed that cardiomyocyte autophagy can be induced by short-term nutrient deprivation in vivo. Pressure overload induced by aortic banding induced heart failure and greatly increased cardiac autophagy. Load-induced autophagic activity peaked at 48 hours and remained significantly elevated for at least 3 weeks. In addition, autophagic activity was not spatially homogeneous but rather was seen at particularly high levels in basal septum. Heterozygous disruption of the gene coding for Beclin 1, a protein required for early autophagosome formation, decreased cardiomyocyte autophagy and diminished pathological remodeling induced by severe pressure stress. Conversely, Beclin 1 overexpression heightened autophagic activity and accentuated pathological remodeling. Taken together, these findings implicate autophagy in the pathogenesis of load-induced heart failure and suggest it may be a target for novel therapeutic intervention.
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Adaptação Biológica , Autofagia , Cardiopatias/patologia , Miocárdio/patologia , Ração Animal , Animais , Aorta/metabolismo , Aorta/cirurgia , Proteínas Reguladoras de Apoptose , Proteína Beclina-1 , Biomarcadores , Linhagem Celular , Heterozigoto , Lisossomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia Eletrônica de Transmissão , Miocárdio/metabolismo , Proteínas/genética , Proteínas/metabolismo , RatosRESUMO
Surgically paced prosthetic conduits are commonly used in the treatment of congenital heart disease. A major limitation of available prosthetic grafts is that they do not grow with the patient. We describe a human case of percutaneous balloon dilation of a surgically placed exGraft conduit (PECA Labs, Inc, Pittsburgh, PA) in a neonate with single-ventricle disease. The use of dilatable conduits could change the management of many congenital heart defects and greatly reduce both the morbidity of repeat cardiac reoperations and the deleterious effects of prolonged conduit dysfunction that accrue between surgical conduit revisions.