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The transcatheter edge-to-edge mitral valve repair (TEER) has been recommended as a reliable treatment option for selected patients with severe degenerative and functional mitral regurgitation (MR). Although MR patients with rheumatic etiology were excluded from two significant trials (EVEREST II and COAPT) that established a role for the TEER in degenerative and functional MR. However, it has been reported that the TEER procedure could be safely and effectively performed in carefully selected rheumatic MR patients. Therefore, we share a case report of successfully treating severe rheumatic MR using a novel-designed TEER system (JensClipTM).
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Cateterismo Cardíaco , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Válvula Mitral , Cardiopatía Reumática , Índice de Severidad de la Enfermedad , Humanos , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/fisiopatología , Insuficiencia de la Válvula Mitral/etiología , Cateterismo Cardíaco/instrumentación , Resultado del Tratamiento , Cardiopatía Reumática/diagnóstico por imagen , Cardiopatía Reumática/cirugía , Cardiopatía Reumática/fisiopatología , Cardiopatía Reumática/terapia , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Válvula Mitral/fisiopatología , Implantación de Prótesis de Válvulas Cardíacas/instrumentación , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Femenino , Ecocardiografía Transesofágica , Ecocardiografía Doppler en Color , Diseño de Prótesis , Prótesis Valvulares Cardíacas , Persona de Mediana Edad , MasculinoAsunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Enfermedades Vasculares , Humanos , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/métodos , Resultado del TratamientoRESUMEN
(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 (p = 0.006), but fewer G3 (p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations.
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Background: Balloon-expandable valves (BEV) and self-expanding valves (SEV) for transcatheter aortic valve replacement (TAVR) have shown promising results in Western populations. Herein, we comparatively evaluated their hemodynamics and early clinical outcomes in a Chinese population. Methods: One hundred seventy-eight patients with symptomatic aortic stenosis who had undergone transfemoral TAVR using SEV (n=153; Venus-A, 97; VitaFlow, 56) or BEV (n=25; Sapien3) from September 2020 to April 2021 were retrospectively enrolled, and 25 pairs were propensity-score matched for 10 baseline variables. The primary study outcomes were aortic valve hemodynamics and postoperative complications at discharge and 3-month follow-up. Results: TAVR was successful in all patients. Compared with SEV group, the BEV group had similarly distributed baseline characteristics, procedural time, hospital stay, new pacemaker implantation, and paravalvular regurgitation grade. We also observed that the BEV group had lower rates of balloon pre-dilation (60% vs. 92%, P=0.018), post-dilation (0 vs. 20%, P=0.050) and second valve implantation (0 vs. 24%, P=0.022); higher mean transaortic gradient (14.3±6.1 vs. 10.8±4.9, P=0.030) and proportion of patients with elevated gradients (20% vs. 0, P=0.050) at discharge; and similar rehospitalization, mean transaortic gradient, new pacemaker implantation, and paravalvular regurgitation grade than the SEV group at the 3-month follow-up. There were no deaths in either group. However, the proportion of patients with elevated gradients in SEV group was higher at 3 months than before discharge (24% vs. 0, P=0.022). Conclusions: BEV and SEV for transfemoral TAVR appear comparably safe and effective, with high device success and favorable 3-month clinical outcomes. However, the transaortic gradient and new pacemaker implantation in the SEV group increased during follow-up, warranting larger studies with longer-term follow-up.
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BACKGROUND: Chemotherapy has improved the survival of non-small cell lung cancer (NSCLC) patients over the past few decades. However, there have not been any epidemiological studies on chemotherapy for Chinese NSCLC patients. PATIENTS AND METHODS: The patients diagnosed as primary lung cancer between January 1, 2005, and December 31, 2014, in eight hospitals from eight provinces in China were retrospectively reviewed. Demographic and clinical data were extracted from medical history systems. Chi-square test and logistic regression were used to analyze the changes of chemotherapy usage and influential factors. RESULTS: A total of 7184 lung cancer cases were eligible, among which 6481 NSCLC cases were included in this analysis. Among stage I/II patients, the percentages of receiving adjuvant chemotherapy did not change significantly between the earlier (28.5%) and the latter five years (25.7%) (p = 0.1288). Among stage IIIA patients, the percentages of chemotherapy usage did not change significantly between the earlier and the latter five years in neo-adjuvant (7.5% vs 5.6%, p = 0.1478) and adjuvant (23.1% vs 26.8%, p = 0.1129) treatment. The proportions of first-line platinum-based doublets for stage IIIB/IV patients changed significantly over the 10 years (p < 0.0001). Patients from provinces with inferior gross domestic product, with lower medical reimbursement rates and without smoking history were more likely to use the docetaxel/paclitaxel doublets, comparing with the gemcitabine doublets. CONCLUSION: From 2005 to 2014, there was no significant change in the chemotherapy pattern of early NSCLC. Economic factors mainly contributed to the significant changes in the first-line chemotherapy regimen selection for advanced patients.
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BACKGROUND: Percutaneous balloon pulmonary valvuloplasty (PBPV) is the procedure of choice for uncomplicated severe or symptomatic pulmonary stenosis. Echocardiography (echo)-guided PBPV can completely avoid the use of radiation and contrast agents compared to fluoroscopy-guided PBPV. Although we have confirmed that echo-guided PBPV is feasible in humans, the poor visibility of the traditional catheter under echo greatly limits the promotion of this new technology. METHODS: We produced a novel double-balloon catheter to make the catheter easy to be detected by echo through adding a guiding balloon at the distal end of the catheter. Echo-guided PBPV was performed on thirty healthy swine using either a novel catheter or a traditional catheter to evaluate the feasibility and safety of the novel double-balloon catheter. The feasibility was evaluated by the success rate of balloon inflation at the pulmonary valve annulus and the operating time. The safety was evaluated by the frequency of balloon slippage and the incidence of complications. RESULTS: There were no significant between-group differences in terms of weight and the ratio of balloon diameter to pulmonary annulus diameter. The success rate was 93.3% and 60% in the novel and traditional groups, respectively. The novel group had significantly (p<0.05) lower mean procedure time (6.33±6.86min vs 24.8±9.79min) and lower frequency of balloon slippage (0.07±0.26 vs 0.53±0.52), arrhythmia (0.07±0.26 vs 0.47±0.52), and tricuspid regurgitation (6.7% vs 40%) than the traditional group. No myocardial hematoma or pericardial tamponade occurred in the novel catheter group. CONCLUSION: Although further studies and improvements are required, the study results indicate that the novel double-balloon catheter for echo-guided PBPV is feasible and safe.
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Valvuloplastia con Balón/instrumentación , Catéteres , Ecocardiografía/métodos , Válvula Pulmonar/cirugía , Cirugía Asistida por Computador/métodos , Animales , Valvuloplastia con Balón/métodos , Diseño de Equipo , Estudios de Factibilidad , Modelos Animales , Estenosis de la Válvula Pulmonar/cirugía , Porcinos , Resultado del TratamientoRESUMEN
BACKGROUND: A percutaneous approach for pulmonary valve replacement (PVR) is a feasible alternative to surgical PVR in selected patients with severe pulmonary regurgitation after repair of tetralogy of Fallot. However, large right ventricular outflow tract (diameter ≥ 25 mm) remains challenging. METHODS: This retrospective multicenter study enrolled consecutive patients with large right ventricular outflow tract who underwent percutaneous PVR (Venus P-valve, Venus MedTech Inc, Hangzhou, China) (n = 35) or surgical PVR (homograft valve; n = 30) between May 2014 and April 2017. Patients were followed up at 1, 3, 6, and 12 months, and yearly thereafter. Main study outcomes were pulmonary valve function and right ventricular function at discharge and midterm follow-up. RESULTS: PVR was successful in all patients. Percutaneous compared with surgical PVR group had: similarly distributed baseline characteristics; shorter hospitalization, intensive care unit stay, and endotracheal intubation duration; lower cost; lower pulmonary valve gradient before discharge; lower pulmonary valve regurgitant grade (mean difference, -0.63; 95% CI -1.11 to -0.20, P = .022), pulmonary valve gradient (mean difference, -5.7 mm Hg; 95% CI -9.4 to -2.2 mm Hg, P = .005), and right ventricular end-diastolic volume index (mean difference, -9.5 mL/m2; 95% CI -16.9 to -3.1 mL/m2, P = .022); and greater right ventricular ejection fraction (mean difference, 5.4%; 95% CI 2.4%-8.3%, P = .002) at median 36 months follow-up, without deaths in either group. CONCLUSIONS: Percutaneous PVR using Venus P-valve appeared to be a safe, efficacious and minimally invasive alternative to surgical PVR in selected patients with large right ventricular outflow tract yielding better right ventricular and pulmonary valve function at midterm follow-up.
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Cateterismo Cardíaco/métodos , Implantación de Prótesis de Válvulas Cardíacas/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/cirugía , Válvula Pulmonar/cirugía , Volumen Sistólico/fisiología , Función Ventricular Derecha/fisiología , Adulto , Femenino , Estudios de Seguimiento , Ventrículos Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Cinemagnética , Masculino , Válvula Pulmonar/diagnóstico por imagen , Insuficiencia de la Válvula Pulmonar/diagnóstico , Insuficiencia de la Válvula Pulmonar/fisiopatología , Estudios RetrospectivosRESUMEN
BACKGROUND: Surgical or percutaneous interventional treatment of severe congenital aortic valve stenosis (CAS) in early infancy remains challenging. This single-center, retrospective study analyzed midterm outcomes of a hybrid balloon valvuloplasty procedure through the ascending aorta by way of median sternotomy, including cases with improved technique. METHODS: Included were 45 consecutive infants (aged <90 days) with CAS and selected for biventricular repair who underwent hybrid balloon valvuloplasty in a hybrid or ordinary operating room from October 2010 to March 2016. Patients were assessed at 1, 3, 6, and 12 months and yearly thereafter. RESULTS: Hybrid balloon valvuloplasty was successful in all patients, with the last 8 treated in an ordinary operating room under only echocardiography guidance with a new sheath. Thirty-two patients were successfully rescued from low heart rate or left ventricular systolic dysfunction, or both, by cardiac massage under direct visualization; none required cardiopulmonary bypass. The degree of new aortic insufficiency was mild in 7 patients and changed from mild to moderate in 1 patient. Aortic valve pressure gradient decreased from 70.6 ± 17.5 mm Hg preoperatively to 15.2 ± 4.2 mm Hg immediately postoperatively (p < 0.001). Fluoroscopy time was 4.8 ± 2.3 minutes. At a median of 32.1 months (range, 1 to 68 months) follow-up, all patients were alive and healthy. Aortic valve pressure gradient remained low (19.1 ± 5.2 mm Hg). Left ventricular ejection fraction increased from 0.515 ± 0.134 (range, 0.21 to 0.70) preoperatively to 0.633 ± 0.035 (range, 0.58 to 0.75; p < 0.001). No aortic insufficiency developed, and no patient required reintervention. CONCLUSIONS: For infants with severe CAS, hybrid balloon valvuloplasty through the ascending aorta by way of a median sternotomy appears efficacious and safe up to midterm follow-up.
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Estenosis de la Válvula Aórtica/congénito , Estenosis de la Válvula Aórtica/cirugía , Valvuloplastia con Balón/métodos , Aorta , Valvuloplastia con Balón/instrumentación , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Esternotomía , Resultado del TratamientoRESUMEN
Objectives: To assess safety and effectiveness of symmetric and asymmetric occluders in perventricular device closure without cardiopulmonary bypass of perimembranous ventricular septal defects (pmVSDs). Methods: The present retrospective study enrolled 581 patients who underwent perventricular device closure of pmVSDs under transoesophageal echocardiography guidance from May 2011 to April 2016, and outpatient electrocardiography and transthoracic echocardiography assessments at 1, 3, 6 and 12 months, and yearly thereafter. Results: The overall success rate of device implantation was 92.6% (43 surgical conversions immediately). Between patients receiving symmetric ( n = 353) and asymmetric ( n = 185) occluders, there were no significant differences in age, weight and defect diameter distributions; however, both before discharge and at mean 28.6 ± 21.2 (range, 1-60)-month follow-up, the symmetric group had lower rates of trivial residual shunt (5.7% vs 11.4%, P = 0.018; and 0.8% vs 5.9%, P = 0.001) and bundle branch block (0.8% vs 5.4%, P = 0.002; and 0.6% vs 3.8%, P = 0.009); and at follow-up, the asymmetric group had lower residual shunt (47.6% vs 85.0%, P = 0.020) and similar branch block (30.0% vs 33.3%, P = 1.000) disappearance rates. There were no severe complications, i.e. aortic regurgitation, malignant arrhythmias, haemolysis or device dislocation. Conclusions: Perventricular device closure of pmVSDs appears safe and effective with symmetric and asymmetric occluders. However, the lower residual shunt disappearance and higher branch block incidence rates for asymmetric occluders would favour more proactive conversion to surgical repair immediately when residual shunt is present intraoperatively.
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Defectos del Tabique Interventricular/cirugía , Dispositivo Oclusor Septal , Adolescente , Adulto , Niño , Preescolar , Ecocardiografía/métodos , Ecocardiografía Transesofágica/métodos , Electrocardiografía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Diseño de Prótesis , Implantación de Prótesis/efectos adversos , Implantación de Prótesis/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: The objective of this study was to assess the feasibility of percutaneous balloon pulmonary valvuloplasty (PBPV) under echocardiographic guidance only. SETTING: PBPV has become the preferred choice for pulmonary valve stenosis (PS). We report the first-in-human successful PBPV under only echocardiography guidance for isolated PS. METHODS: From March 2013 to December 2014, 34 patients with congenital PS underwent PBPV with echocardiography as the only imaging modality in the ordinary operation room or catheter lab. Outpatient follow-up including chest radiography, electrocardiography, and transthoracic echocardiography (TTE) was conducted at 1, 3, 6, and 12 months. RESULTS: All 34 patients successfully underwent PBPV under echocardiography guidance without radiation and contrast agent. The pulmonic transvalvular pressure gradient dropped from 62.8 ± 10.1 mm Hg to 14.7 ± 4.2 mm Hg measured on catheterization (P < .05). The balloon diameter/pulmonary annulus diameter ratio was 1.34 ± 0.07. Slight regurgitation of the pulmonary valve occurred in five patients and mild pulmonary regurgitation occurred in one patients. The pulmonic transvalvular pressure gradient measured on TTE 12 months after the procedure was 14.1 ± 4.6 mm Hg. No pericardial effusion and peripheral vascular complications occurred. CONCLUSION: This study demonstrated that PBPV can be successfully performed under only echocardiography guidance and appears safe and effective while avoiding radiation and contrast agent use.
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Valvuloplastia con Balón/métodos , Ecocardiografía , Estenosis de la Válvula Pulmonar/terapia , Válvula Pulmonar/diagnóstico por imagen , Ultrasonografía Intervencional/métodos , Adolescente , Valvuloplastia con Balón/efectos adversos , Niño , Preescolar , China , Ecocardiografía/efectos adversos , Estudios de Factibilidad , Femenino , Hemodinámica , Humanos , Masculino , Seguridad del Paciente , Valor Predictivo de las Pruebas , Válvula Pulmonar/fisiopatología , Insuficiencia de la Válvula Pulmonar/etiología , Estenosis de la Válvula Pulmonar/congénito , Estenosis de la Válvula Pulmonar/diagnóstico por imagen , Estenosis de la Válvula Pulmonar/fisiopatología , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Intervencional/efectos adversosRESUMEN
INTRODUCTION: Percutaneous patent ductus arteriosus (PDA) occlusion has become the preferred therapeutic option, which uses fluoroscopy as the guidance. To reduce the x-ray exposure, PDA occlusion using the Amplatzer Duct Occluder II (ADO II) under guidance of transthoracic echocardiography only was conducted. This single center study aims to access the safety and efficiency of this new strategy. METHODS AND RESULTS: From June 2013 to May 2015, 63 consecutive PDA patients underwent transthoracic echocardiography-guided PDA occlusion through the femoral artery. Outpatient follow-up was conducted at 1, 3, and 6 months, and yearly. Sixty-two patients successfully underwent echocardiography-guided percutaneous PDA occlusion. One patient was converted to minimally invasive transthoracic occlusion due to failure of delivery sheath passage through tortuous PDA. Mean procedure duration was 24.3 ± 7.0 minutes; ADO II diameter averaged 4.6 ± 0.9 mm; 8 cases showed traces of residual shunt immediately after operation which resolved after 24 hours; and mean hospital stay was 3.4 ± 0.5 days. There was no occluder migration, hemolysis, pericardial effusion, pulmonary branch or aortic stenosis at mean 13.5 ± 4.8 months follow-up. CONCLUSIONS: This study demonstrated that percutaneous PDA occlusion can be successfully performed under guidance of transthoracic echocardiography only and appears safe and effective while avoiding radiation and contrast agent use.
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Conducto Arterioso Permeable/diagnóstico por imagen , Conducto Arterioso Permeable/cirugía , Ecocardiografía/métodos , Dispositivo Oclusor Septal , Cirugía Asistida por Computador/instrumentación , Cirugía Asistida por Computador/métodos , Procedimientos Quirúrgicos Cardíacos/instrumentación , Procedimientos Quirúrgicos Cardíacos/métodos , Preescolar , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Diseño de Prótesis , Procedimientos de Cirugía Plástica/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Transesophageal echocardiogram-guided minimally invasive periventricular device closure of perimembranous ventricular septal defects (pmVSDs) without cardiopulmonary bypass is a treatment option for pmVSDs. We introduce our improvements to this technique and mid-term follow-up results. METHODS: From May 2011 to May 2014, 187 patients with pmVSDs aged 6 months to 31 years (8.2 ± 10.2 years) were enrolled in this study. The procedure was performed through a new transthoracic approach of 1 to 2 cm without sternotomy. Device selection and the operative procedure were monitored by transesophageal echocardiogram. The patients underwent follow-up examinations of echocardiography and electrocardiogram at 1 month, 3 months, 6 months, and 1 year after the operation and annually thereafter. RESULTS: The defects were closed successfully in 179 patients (95.7%), and in 8 patients the operation was converted to conventional surgical repair. Six patients (3.4%) had an incomplete right bundle branch block. One patient experienced an intermittent complete atrioventricular block on the fourth day after the operation, and sinus rhythm was restored by corticosteroid therapy after 5 days. A trivial residual shunt was observed in 8 patients (4.5%) during the procedure. The average hospital stay was 3.1 ± 0.9 days. Follow-up in all patients ranged from 1 month to 36 months (median, 12.6 months), and aortic regurgitation, malignant arrhythmia, and device dislocation were not observed in any patients. However, 3 patients (1.7%) still had a trivial residual shunt at their last follow-up. CONCLUSIONS: Periventricular device closure through a modified transthoracic approach without sternotomy is a potentially safe and effective treatment option for pmVSDs. Controlled studies with long-term follow-up are necessary.
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Ecocardiografía Transesofágica/métodos , Defectos del Tabique Interventricular/diagnóstico por imagen , Defectos del Tabique Interventricular/cirugía , Cirugía Asistida por Computador , Adolescente , Adulto , Niño , Preescolar , Ecocardiografía Transesofágica/instrumentación , Estudios de Seguimiento , Humanos , Lactante , Estudios Retrospectivos , Cirugía Asistida por Computador/métodos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: Demonstrate the benefits of percutaneous atrial septal defect (ASD) closure under guidance of transthoracic echocardiography (TTE) without fluoroscopy. METHODS: From February 2013 to April 2014, 127 consecutive patients with an isolated type II ASD were recruited to undergo percutaneous closure under either TTE (n = 60, TTE group) or TEE (n = 67, TEE group) guidance. The TTE group received local anesthesia or sedation with propofol, and the TEE group received general anesthesia with endotracheal intubation. Follow-up examinations were performed for both groups at 1 month, 3 months, 6 months, and 1 year after discharge and annually thereafter. RESULTS: The TTE group had a significantly shorter procedure time and respirator ventilation duration than the TEE group. The dose of propofol required, the cost, and the pharyngeal complication rate were significantly lower in the TTE group than in the TEE group. The median follow-up of 11.6 months was uneventful in all patients. CONCLUSIONS: Percutaneous ASD closure with TTE guidance as the only imaging tool avoids fluoroscopy, endotracheal intubation, and probe insertion and is associated with a satisfactory procedural success rate and lower costs. This procedure is a safe and reliable treatment for ASD.
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Cateterismo Cardíaco , Ecocardiografía , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/terapia , Dispositivo Oclusor Septal , Anestesia General , Anestesia Local , Niño , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Humanos , Hipnóticos y Sedantes/administración & dosificación , Intubación Intratraqueal , Masculino , Propofol/administración & dosificación , Estudios RetrospectivosRESUMEN
BACKGROUND: Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). METHODS AND RESULTS: Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. CONCLUSIONS: Rare CNVs contribute to the pathogenesis of PA (9.8%), suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism (FOCM). With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical gene(s) in CHD and may provide novel insights about CHD pathogenesis.
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Aberraciones Cromosómicas , Cromosomas Humanos Par 16 , Cromosomas Humanos Par 17 , Cromosomas Humanos Par 22 , Variaciones en el Número de Copia de ADN , Cardiopatías Congénitas/genética , Atresia Pulmonar/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Ácido Fólico/metabolismo , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/cirugía , Humanos , Lactante , Recién Nacido , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Atresia Pulmonar/diagnóstico por imagen , Atresia Pulmonar/patología , Atresia Pulmonar/cirugía , Ultrasonografía , Vitamina B 12/metabolismoRESUMEN
Interstitial duplications of 8q12 encompassing CHD7 have recently been described as a new microduplication syndrome. Three 8q12 duplications have been reported with shared recognizable phenotype: Duane anomaly, developmental delay and dysmorphic facial features. We identified a 2.7 Mb duplication on chromosome 8q12 with SNP-array in a patient with growth delay, congenital heart defects, ear anomalies and torticollis. To our knowledge, this is the smallest duplication reported to date. Our findings support the notion that increased copy number of CHD7 may underlie the phenotype of the 8q12 duplication. Our study together with previous studies suggest that the 8q12 duplication could be defined as a novel syndrome.