22q11.2 deletion detected by in situ hybridization in Mexican patients with velocardiofacial syndrome-like features / Deleción 22q11.2 detectada por hibridación in situ en pacientes mexicanos con características clínicas similares al síndrome velocardiofacial

Abstract Introduction: Deletion 22q11.2 occurs in 1:4,000-1:6,000 live births while 10p13p14 deletion is found in 1:200,000 newborns. Both deletions have similar clinical features such as congenital heart disease and immunological anomalies. Objective: We looked for a 22q11.2 deletion in Mexican patients with craniofacial dysmorphisms suggestive of DiGeorge or velocardiofacial syndromes and at least one major phenotypic feature (cardiac anomaly, immune deficiency, palatal defects or development delay). Methods: A prospective study of 39 patients recruited in 2012-2015 at the Instituto Mexicano del Seguro Social at Guadalajara, Mexico. The patients with velocardiofacial syndrome-like features or a confirmed tetralogy of Fallot (TOF) or complex cardiopathy were studied by G-banding and fluorescence in situ hybridization (FISH) with a dual TUPLE1(HIRA)/ARSA or TUPLE1(22q11)/22q13(SHANK3) probe, six patients without the 22q11.2 deletion (arbitrarily selected) were tested with the dual DiGeorge II (10p14)/D10Z1 probe. Results: Twenty-two patients (7 males and 15 females) had the 22q11.2 deletion and 17/39 did not have it; no patient had a 10p loss. Among the 22 deleted patients, 19 had congenital heart disease (mostly TOF). Twelve patients without deletion had heart defects such as TOF (4/12), isolate ventricular septal defect (2/12) or other disorders (6/12). Conclusion: In our small sample about ~56% of the patients, regardless of the clinical diagnosis, had the expected 22q11.2 deletion. We remark the importance of early cytogenetic diagnosis in order to achieve a proper integral management of the patients and their families.

Resumen Introducción: La deleción 22q11.2 ocurre con una frecuencia de 1:4,000-1:6,000 nacidos vivos, mientras que la deleción 10p13p14 es detectada en 1:200,000 recién nacidos. Ambas deleciones comparten características clínicas similares tales como defectos cardiacos congénitos y anomalías inmunológicas. Objetivo: Identificar la deleción 22q11.2 en pacientes mexicanos con dismorfismo craneofacial sugestivo de síndrome DiGeorge o velocardiofacial y por lo menos con una característica clínica mayor (anomalía cardiaca, deficiencia inmunológica, defectos en paladar o retardo en el desarrollo) Métodos: Estudio prospectivo de 39 pacientes captados entre 2012-2015 en el Instituto Mexicano del Seguro Social en Guadalajara, México. Los pacientes con características clínicas sugerentes de síndrome velocardiofacial o diagnostico confirmado de tetralogía de Fallot (TOF) o cardiopatía compleja fueron estudiados por bandas G y por hibridación in situ fluorescente (FISH) con una sonda dual TUPLE1(HIRA)/ARSA o TUPLE1(22q11)/22q13(SHANK3), seis pacientes sin la deleción 22q11.2 (seleccionados arbitrariamente) fueron estudiados con la sonda dual DiGeorge II (10p14)/D10Z1. Resultados: Veintidós pacientes (7 hombres y 15 mujeres) tuvieron la deleción 22q11.2 y 17/39 no la tuvieron, ningún paciente tuvo la pérdida de 10p. Entre los 22 pacientes delecionados, 19 tuvieron defecto cardiaco congénito (principalmente TOF). Doce pacientes sin la deleción tuvieron defectos cardiacos congénitos como TOF (4/12), defecto del septo ventricular aislado (2/12) y otros trastornos cardiacos (6/12). Conclusión: En nuestra pequeña muestra, alrededor de ~56% de los pacientes, independientemente de su diagnostico clínico, tuvieron la deleción 22q11.2 esperada. Resaltamos la importancia del diagnóstico citogenético temprano para determinar un apropiado manejo integral para el paciente y sus familiares.

Anestesia para cirugía convencional en paciente con tetralogía de Fallot. Presentación de un caso / Anesthesia for conventional surgery in a patient with Tetralogy of Fallot. Case presentation

La tetralogía de Fallot es la forma más frecuente de cardiopatía congénita cianótica que se presenta en los neonatos. Los cuatro componentes de la enfermedad son: la alineación anormal de la comunicación interventricular, la obstrucción infundibular del ventrículo derecho, el cabalgamiento aórtico de la comunicación interventricular y la hipertrofia del ventrículo derecho. En este trabajo se trata un caso que se presentó para una cirugía convencional frecuente, la Histerectomía Abdominal Total debido a un mioma uterino, en una paciente que padecía de tetralogía de Fallot, con 43 años de edad, situación poco frecuente en la práctica diaria. El objetivo de este trabajo es exponer la experiencia del caso, que necesitó un manejo cuidadoso y que no aparece en la literatura básica. Habitualmente se aplica anestesia para niños con esta malformación para mejorar la calidad de vida o corregirla definitivamente, y porque precisamente solo el 2 % de los pacientes con esta enfermedad, que no han sido tratados quirúrgicamente, pueden arribar a la cuarta década de vida (AU).

The tetralogy of Fallot is the most frequent form of cyanotic congenital heart diseases presented in newborns. The disease’s four components are: abnormal alignment of intraventricular communication, right ventricle infundibular obstruction, aortic straddling of intraventricular communication, and right ventricle hypertrophy. The case presented is a case of a frequent conventional surgery, the total abdominal hysterectomy due to a uterine myoma, in a patient, aged 43 years, suffering for tetralogy of Fallot, a little frequent situation in the daily practice. The objective is exposing the experience of the case, demanding a careful management, which was not found in the main literature sources. Anesthesia is usually used in children with this malformation to improve their life quality or it is definitively corrected; only 2 % of the patients suffering this disease that have not been surgically treated are still alive in the fourth decade of life (AU).

Tetralogy of Fallot in a Case of Dextrocardia with Situs Solitus.

Dextrocardia associated with situs solitus (so called ‘dextroversion’) is a cardiac positional anomaly in which the heart is located in the right hemithorax with its base-toapex axis directed to the right and caudad along with normal anatomical position of other intrathoracic and abdominal viscera. The malposition is intrinsic to the heart and not caused by extracardiac abnormalities. Dextroversion is the second most common type of dextrocardia. In dextroversion, there is a 90% incidence of additional cardiac malformations, including anomalous pulmonary venous return, Tetralogy of Fallot, septal defects, pulmonic stenosis, coarctation of the aorta, and corrected TGA.Here we report a rare case of Tetralogy of Fallot in a 17 year old male with dextroversion.

thirteen-year-old boy with undiagnosed congenital heart disease presented with brain abscess

Tetralogy of Fallot is the most common form of cyanotic heart disease and it is associated with intracerebral abscess in childhood. We report a thirteen-year-old boy with undiagnosed cyanotic heart disease who presented to the emergency department with history of fever, vomiting, headache and left sided body weakness. The neuroradiological images were suggestive of brain abscess and echocardiogram confirmed the diagnosis of Tetralogy of Fallot. An emergency craniotomy and brain abscess drainage was done and the patient showed a complete recovery of his clinical symptoms

Estudio preliminar de índices ecocardiográficos que permitanoptimizar la indicación de resonancia cardíaca en pacientes conTetralogía de Fallot reparada / Echocardiographic indexes help predict the need for nuclear magnetic resonance evaluation of patients with repaired tetralogy of fallot

Introducción: La Tetralogía de Fallot reparada (TOFr) a largo plazo evoluciona frecuentemente con insuficiencia pulmonar (IP). La resonancia magnética cardíaca (RMC) juega un rol fundamental en la indicación de recambio valvular pulmonar destinada a evitar las complicaciones de la IP. Objetivo: El objetivo de este trabajo es buscar qué índice(s) ecocardiográfico(s) permite(n) identificar a los pacientes con TOFr que tienen VD dilatado y fracción de eyección (FE) disminuida en la RMC. Método: En 20 pacientes (9 mujeres, 8-25 años, promedio 15,8 años) con TOFr se realizó ecocardiograma (ECO) y RMC en el Hospital Sótero del Río. Por ECO se obtuvieron mediciones de excursión sistólica máxima anular tricuspídea (TAPSE), onda s tisular, aceleración miocárdica isovolumétrica (IVA), y grado de IP (leve, moderado o severo). Por RMC se midieron la FE, volumen fin de diástole (VFD) del VD y fracción de regurgitación de la arteria pulmonar (FR). Se realizó un análisis estadístico multivariado. Resultados: No se obtuvo ninguna correlación entre algún parámetro de ECO versus VFD o FE del VD. Sin embargo, se encontró un modelo basado en el TAP-SE e IP que en nuestros pacientes pudo predecir el VDF del VD con un r2 = 0.6. (VDF-VD = 8.60*TAPSE + 36.19*IP - 77.213). Al comparar la IP con la FR se encontró que la ecografía puede distinguir correctamente aquellos casos que tienen IP leve de severa (p<0.001), o moderada de severa (p=0.004), pero no puede diferenciar con significancia estadística aquellos casos de IP leve de moderada (p=0.272). Conclusión: En este estudio preliminar se encontró un modelo estadístico basado en el TAPSE e IP que podría ser útil en la selección de pacientes que son derivados para estudio con RMC. La estimación del grado de IP medida por ECO es un parámetro fácil de obtener, sin embargo no siempre es informado en forma categórica (leve, moderado o severo). Si bien este estudio se debe validar en un mayor número de pacientes, éste nos indica la...

Background: Pulmonary insufficiency (PI) frequently appears long-term after repair of Tetralogy of Fallot (TOFr). Cardiac magnetic resonance (CMR) plays a fundamental role in the indication of pulmonary valve replacement, in order to avoid complications of PI. However, CMR is a scarce and expensive resource in our reality, which is why its indication must be optimized. Aim: The objective of this work is to find echocar-diographic indices to identify patients with TOFr with dilated RV and reduced ejection fraction (EF). Method: Images from echocardiograms (ECHO) and CMR in 20 patients (9 women, 8-25 years of age, average 15,8 years old) with TOFr were retrospectively reviewed. From ECHO images we obtained measurements for tricuspid annular plane systolic excursion (TAPSE), tissular s wave, isovolumetric acceleration (IVA), and severity of PI (mild, moderate, or severe). From CMR images, we measured EF, end diastolic volume (EDV) of the RV, and regurgitant fraction (RF) of the pulmonary artery. We performed a multivariate statistical analysis to explore the relation between ECHO parameters and CMR findings. Results: No correlation was found between individual ECHO parameters and EDV or RV EF. However, we did find a model based on the TAPSE and PI that was able to predict the EDV of the RV with an r2 = 0.6. (FDV-RV = 8.60*TAPSE + 36.19*PI - 77.213). After comparing the PI with RF, we found that that echocar-diography could correctly distinguish cases with mild PI from those with severe PI (p<0.001), or moderate from severe (p=0.004), but not mild from moderate PI. Conclusion: In this preliminary study, we found a statistical model based on the TAPSE and PI which could be useful in the selection of patients with TOFr that are referred to CMR. While this study needs to be validated on a greater number of patients, it indicates the relevance of some echocardiographic parameters, which should always be included in the evaluation of patients with TOFr.

Postoperative tetralogy of fallot with concomitant atrial fibrillation and ventricular tachycardia / Tetralogía de fallot postoperatoria con fibrilación atrial concomitante y taquicardia ventricular

Postoperative tetralogy of Fallot patients, since the first corrective surgical correction in the 1960s, have borne a burden of postoperation arrhythmias and sudden death. This is confirmed to be secondary to supraventricular arrhythmias and predominantly ventricular arrhythmias. It is rare to have both types of arrhythmias in the same patient, which the index case developed. Attempts to stratify patients in groups to predict which patients are susceptible to sudden death and arrhythmias have not been unanimous, despite multiple retrospective and prospective analysis of this group of patients.

Los pacientes de tetralogía de Fallot postoperatoria, desde la primera corrección quirúrgica en los años sesenta, ha soportado una pesada carga de arritmias postoperatorias y muerte súbita. Esto se confirma como secundario a las arritmias supraventriculares y las arritmias predominantemente ventriculares. Es raro encontrar ambos tipos de arritmias en el mismo paciente, como ocurrió en el caso del paciente índice. Los esfuerzos por estratificar a los pacientes en grupos para predecir qué pacientes son susceptibles a la muerte súbita y las arritmias no han sido unánimes, a pesar de los múltiples análisis prospectivos y retrospectivos de este grupo de pacientes.

Resultados quirúrgicos y factores de riesgo relacionados a mortalidad operatoria en la corrección quirúrgica de 276 pacientes consecutivos con tetralogía de Fallot / Surgical outcomes and risk factors of operative mortality in 276 consecutives patients with tetralogy of Fallot

La tetralogía de Fallot es una de las cardiopatías congénitas cianógenas más frecuentes. A pesar de ello no existen en Venezuela reportes actualizados de los resultados de su corrección quirúrgica. Describir los resultados obtenidos en la reparación quirúrgica de pacientes con tetralogía de Fallot y evaluar los factores de riesgo de mortalidad operatoria relacionados así como describir la sobrevida actuarial y la libertad de reoperación del tracto de salida del ventrículo derecho. Se incluyeron en forma restrospectiva a todos aquellos pacientes intervenidos de corrección total de tetralogía de Fallot entre octubre 2006 a mayo 2010. Se evaluó el tiempo de by-pass cardiopulmonar, tiempo de pinzamiento aórtico, edad, peso, talla, relación de presiones entre el ventrículo derecho e izquierdo después de la corrección. Adicionalmente se trazaron las curvas actuariales para sobrevida y libertad de reoperación para el tracto de salida derecho. Solo el tiempo de circulación extracorporea mayor a 100 minutos estuvo relacionado a mortalidad operatoria. La mortalidad operatoria global fue de 5,8%. La sobrevida actuarial a los 4 años fue de 92,5%, y la libertad de reoperación por obstrucción del tracto de salida derecho fue de 98,4%. Los resultados obtenidos son similares a los observados en la literatura mundial en relación con la mortalidad operatoria y libertad de reoperación del tracto de salida derecho. Los tiempos de circulación extracorporea mayores a 100 minutos podrían estar relacionados a una mayor dificultad técnica de la corrección y esto a su vez estar relacionado a mortalidad.

Tetralogy of Fallot is one of the most common cyanotic congenital heart defects. However, in Venezuela there are no current reports of results of its surgical correction. To describe the results of surgical repair of Tetralogy of Fallot patients and evaluate the risk factors related to operative mortality and to describe the actuarial survival curves and freedom from reoperation for the right ventricule outflow tract obstruction. We included retrospectively all patients undergoing total correction of tetralogy of Fallot from October 2006 to May 2010. We evaluated time of cardiopulmonary bypass, aortic cross-clamp time, age, weight, height, and pressure ratio between right and left ventricle after correction. Additionally actuarial curves were plotted for survival and freedom from reoperation for right outflow tract obstruction. Cardiopulmonary by-pass times longer than 100 minutes was related to operative mortality. The overall operative mortality was 5.8%. The actuarial survival at 4 years was 92.5%, and freedom from reoperation for right outflow tract obstruction was 98.4%. These results are similar to those observed in the literature regarding the operative mortality and freedom from reoperation for right outflow tract obstruction. Cardiopulmonary by-pass times longer than 100 minutes could be related to increased technical difficulties during correction and this in turn be related to mortality.

Diagnosis and management of cyanotic congenital heart disease: part I.

Most commonly encountered cyanotic cardiac lesions in children, namely, tetralogy of Fallot, transposition of the great arteries and tricuspid atresia are reviewed. Pathology, pathophysiology, clinical features, non-invasive and invasive laboratory studies and management are discussed. The clinical and non-invasive laboratory features are sufficiently characteristic for making the diagnosis and invasive cardiac catheterization and angiographic studies are not routinely required and are needed either to define features, not clearly defined by non-invasive studies or as a part of catheter-based intervention. Surgical correction or effective palliation can be undertaken with relatively low risk. However, residual defects, some requiring repeat catheter or surgical intervention, are present in a significant percentage of patients and therefore, continued follow-up after surgery is mandatory.

Anatomical variations of pulmonary artery and associated cardiac defects in tetralogy of Fallot

To determine pulmonary artery variations and other associated cardiac defects in patients with Tetralogy of Fallot [TOF]. Cross-sectional, descriptive study. The Children's Hospital and the Institute of Child Health, Lahore, from April 2006 to October 2007. All patients with TOF, who underwent cardiac catheterization during this period, were included. Standard cine-angiograms were recorded and pulmonary artery sizing was done using z-scoring. A total of 216 patients with TOF were catheterized. Pulmonary Artery [PA] abnormalities were present in 84 [38.9%] patients. The commonest abnormality was isolated Left Pulmonary Artery [LPA] stenosis [n=27, 32.14%] followed by isolated hypoplasia of Main Pulmonary Artery [MPA] [n=18, 21.43%] and supra-valvular stenosis in [n=11, 13.1%] patients. LPA was absent in one patient, while 2 patients had both absent right and left PA with segmental branch pulmonary arteries originating directly from MPA. Associated cardiac lesions included right aortic arch in 34 [15%], additional muscular VSD vary in 13 [5.5%], Patent Ductus Arteriosus [PDA] in 11 [6%] and Major Aortopulmonary Collateral Arteries [MAPCA] in 2 [1.9%] patients. Significant coronary artery abnormality was present in 10 [4.6%] children. Pulmonary artery abnormalities were present in 38.9% of patients with TOF. Isolated LPA origin stenosis and MPA hypoplasia were the most common abnormalities. Significant associated cardiac lesions were present in one-third of the patients and included PDA, additional muscular VSD, coronary artery abnormalities and MAPCA

Correção intracardíaca da tetralogia de Fallot no primeiro ano de vida: resultados a curto e médio prazos / Intracardiac correction of tetralogy of Fallot in the first year of life: short-term and midium-term results

OBJETIVO: Avaliar os resultados a curto e médio prazos da correção intracardíaca da tetralogia de Fallot no primeiro ano de vida. MÉTODOS: De janeiro de 1996 a outubro de 2004, 67 crianças com idade variando de 1 a 11 meses (média: 7,2 meses) e pesando entre 4 a 10 quilos (média: 7,1 kg) foram eletivamente submetidas a correção intracardíaca da tetralogia de Fallot. A cirurgia foi realizada com circulação extracorpórea convencional e hipotermia moderada. Ventriculotomia direita foi realizada em 60 (89,5 por cento) casos e em sete (10,5 por cento) utilizou-se a abordagem do defeito pela via atriopulmonar. RESULTADOS: O tempo de circulação extracorpórea variou de 35 a 147 minutos (média:78,8 ± 21 minutos), e o tempo de pinçamento da aorta variou de 25 a 86 minutos (média: 51,8 ± 15,6 minutos). Ampliação transanular da via de saída do ventrículo direito foi necessária em 50 (64,1 por cento) casos. O gradiente entre o ventrículo direito e a artéria pulmonar, após a correção, variou de 0 a 54 mmHg (média: 15,5 ± 10,8 mmHg). Ocorreram dois (2,98 por cento) óbitos no pós-operatório imediato. O seguimento tardio variou de 7 a 115 meses (média: 44,0 ± 35 meses). Houve uma morte tardia não-cardíaca. Todos os outros pacientes estão assintomáticos. A curva de sobrevida actuarial, incluindo a mortalidade operatória, revelou que a probabilidade de sobrevida, 12 anos após a operação, é de 97 por cento. Dez pacientes foram avaliados por angiorresonânia magnética nuclear. CONCLUSÕES: A correção intracardíaca da tetralogia de Fallot no primeiro ano de vida pode ser feita com baixas morbidade e mortalidade e bons resultados tardios.

OBJECTIVE: To evaluate short-term and medium-term results of intracardiac correction of Tetralogy of Fallot in the first year of life. METHODS: From January 1996 to October 2004, 67 consecutive infants ranging in age from 1 to 11 months (mean: 7.2 months) and weighing from 4 to 10 kilograms (mean: 7.1 kilograms) underwent elective total correction of Tetralogy of Fallot. The surgery was accomplished with conventional cardiopulmonary bypass and moderate hypothermia. Right ventriculotomy was performed in 60 (89.5 percent) cases and an atriopulmonary approach was used in the other seven (10.5 percent) cases. RESULTS: Cardiopulmonary bypass time ranged from 35 to 147 minutes (mean: 78.8 ± 21 minutes), and aortic clamping time ranged from 25 to 86 minutes (mean: 51.8 ± 15.6 minutes). Transannular enlargement of the right ventricular outflow tract was needed in 50 (64.1 percent) patients. Gradient between the right ventricle and pulmonary artery after correction varied from 0 to 54 mmHg (mean: 15.5 ± 10.8 mmHg). There were two (2.98 percent) early deaths. Follow-up of the 65 survivors ranged from 7 to 115 months (mean:44.0 ± 35 months). There was one late noncardiac death. All other patients are asymptomatic. The actuarial survival curve at 12 years, including operative mortality, was 97 percent. Ten patients were evaluated by magnetic nuclear angioresonance. CONCLUSIONS: Intracardiac correction of Tetralogy of Fallot in the first year of life may be performed with low morbidity and mortality and good late results.