Identification of an elusive spliceogenic MYBPC3 variant in an otherwise genotype-negative hypertrophic cardiomyopathy pedigree.

The finding of a genotype-negative hypertrophic cardiomyopathy (HCM) pedigree with several affected members indicating a familial origin of the disease has driven this study to discover causative gene variants. Genetic testing of the proband and subsequent family screening revealed the presence of a rare variant in the MYBPC3 gene, c.3331-26T>G in intron 30, with evidence supporting cosegregation with the disease in the family. An analysis of potential splice-altering activity using several splicing algorithms consistently yielded low scores. Minigene expression analysis at the mRNA and protein levels revealed that c.3331-26T>G is a spliceogenic variant with major splice-altering activity leading to undetectable levels of properly spliced transcripts or the corresponding protein. Minigene and patient mRNA analyses indicated that this variant induces complete and partial retention of intron 30, which was expected to lead to haploinsufficiency in carrier patients. As most spliceogenic MYBPC3 variants, c.3331-26T>G appears to be non-recurrent, since it was identified in only two additional unrelated probands in our large HCM cohort. In fact, the frequency analysis of 46 known splice-altering MYBPC3 intronic nucleotide substitutions in our HCM cohort revealed 9 recurrent and 16 non-recurrent variants present in a few probands (≤ 4), while 21 were not detected. The identification of non-recurrent elusive MYBPC3 spliceogenic variants that escape detection by in silico algorithms represents a challenge for genetic diagnosis of HCM and contributes to solving a fraction of genotype-negative HCM cases.

Immediate and one-year results in 35 consecutive patients after closure of left atrial appendage with the Amplatzer cardiac plug.

INTRODUCTION AND OBJECTIVES: Left atrial appendage closure can be an attractive option for patients with nonvalvular atrial fibrillation and a contraindication to oral anticoagulants, provided that satisfactory results can be achieved during implantation and follow-up. METHODS: Thirty-five consecutive patients, not eligible for randomized trials with oral anticoagulants, had an Amplatzer occlusion device implanted under general anesthesia. After the first 5 patients, 3-dimensional imaging was incorporated. The results of the implantation and the follow-up were analyzed over a 1-year period. RESULTS: The mean age was 74.65 (7.61) years, with a CHADS2 score of 2.41 (1.53) and a CHA2DS2-VASc score of 3.17 (1.60). Implantation failed in 1 patient and 5 needed a change in the selected plug size. There were no cardiac complications during the implantation or hospital stay. There was 1 vascular complication (arteriovenous fistula). Transesophageal echocardiography monitoring was performed at 24h, 1, 3, 6, and 12 months and we found 5 thrombi which were resolved with heparin. In the follow-up period of 21.14 (10.09) months, 3 patients aged>80 years died, none of them due to heart problems, and one transient ischemic stroke without further consequences. CONCLUSIONS: Left atrial appendage closure by an experienced operator can be a treatment option with few complications and with efficient results at>1 year in reducing thromboembolic and hemorrhagic complications, even in very high-risk groups.

[Acute miopericarditis as the presenting feature of adult-onset Still's disease]. / Miopericarditis aguda como presentación de enfermedad de Still del adulto.

Adult Still's disease (ASD) was described by George Still in 1896. ASD is a rare inflammatory disorder, of unknown etiology, whose clinical manifestations are manifold. Diagnosis requires high clinical suspicion and exclusion of different etiologies. We report the case of a 20 year old male with fever, arthritis, dyspnea and chest pain. Laboratory findings showed increased levels of cardiac enzymes, and a pleuropericardic effusion was detected in imaging tests, both of them showing myopericarditis. Corticosteroid treatment was started with initial improvement, although the addition of methotrexate was necessary in the following months.

Resultados inmediatos y a más de un año en 35 pacientes consecutivos a los que se realiza cierre de orejuela izquierda con el dispositivo Amplatzer Cardiac Plug / Immediate and one-year results in 35 consecutive patients after closure of left atrial appendage with the amplatzer cardiac plug

Introducción y objetivos. El cierre del apéndice auricular izquierdo puede ser una opción terapéutica atractiva para pacientes con fibrilación auricular no valvular y contraindicación para tomar anticoagulantes orales, siempre que se obtengan buenos resultados durante la implantación y en el seguimiento. Métodos. Se analizó a 35 pacientes consecutivos y no elegibles para los estudios aleatorizados con anticoagulantes orales a los que se implantó el dispositivo oclusor Amplatzer. Tras los primeros 5 casos, se incorporó una técnica de imagen 3D. Se analizaron los resultados de la implantación y de seguimiento durante 1 año. Resultados. La media de edad era 74,65 ± 7,61 años, con un CHADS2 de 2,41 ± 1,53 y un CHA2DS2-VASc de 3,17 ± 1,60. No se pudo implantar el dispositivo en 1 caso y en 5 fue necesario cambiar la medida seleccionada. No hubo ninguna complicación cardiaca durante la implantación ni durante la estancia hospitalaria. Hubo una complicación vascular (fístula arteriovenosa). Se realizó seguimiento con ecocardiografía transesofágica a las 24 h y tras 1, 3, 6 y 12 meses; se documentaron 5 trombos, que se resolvieron con heparina. En el seguimiento de 21,14 ± 10,09 meses, hubo 3 muertes de pacientes mayores de 80 años, ninguna de ellas cardiológica, y un accidente isquémico transitorio sin secuelas. Conclusiones. El cierre del apéndice auricular izquierdo por un operador con cierta experiencia puede ser una opción terapéutica con pocas complicaciones y con resultados a más de 1 año eficaces en la reducción de complicaciones tromboembólicas y hemorrágicas, incluso en poblaciones de muy alto riesgo (AU)

Introduction and objectives. Left atrial appendage closure can be an attractive option for patients with nonvalvular atrial fibrillation and a contraindication to oral anticoagulants, provided that satisfactory results can be achieved during implantation and follow-up. Methods. Thirty-five consecutive patients, not eligible for randomized trials with oral anticoagulants, had an Amplatzer occlusion device implanted under general anesthesia. After the first 5 patients, 3-dimensional imaging was incorporated. The results of the implantation and the follow-up were analyzed over a 1-year period. Results. The mean age was 74.65 (7.61) years, with a CHADS2 score of 2.41 (1.53) and a CHA2DS2-VASc score of 3.17 (1.60). Implantation failed in 1 patient and 5 needed a change in the selected plug size. There were no cardiac complications during the implantation or hospital stay. There was 1 vascular complication (arteriovenous fistula). Transesophageal echocardiography monitoring was performed at 24h, 1, 3, 6, and 12 months and we found 5 thrombi which were resolved with heparin. In the follow-up period of 21.14 (10.09) months, 3 patients aged>80 years died, none of them due to heart problems, and one transient ischemic stroke without further consequences. Conclusions. Left atrial appendage closure by an experienced operator can be a treatment option with few complications and with efficient results at>1 year in reducing thromboembolic and hemorrhagic complications, even in very high-risk groups (AU)

Miopericarditis aguda como presentación de enfermedad de Still del adulto / Acute miopericarditis as the presenting feature of adult-onset Still's disease

La enfermedad del Still del adulto (ESA) fue descrita en niños por George Still en 1896. La ESA es una entidad inflamatoria, infrecuente, de etiología desconocida cuyas manifestaciones clínicas son múltiples. El diagnóstico requiere una alta sospecha clínica y la exclusión de diferentes etiologías. Presentamos el caso de un varón de 20 años que consultó por fiebre, artritis, disnea y dolor costal. Se objetivaron elevación de enzimas cardiacas, y en las pruebas de imagen, derrame pleuropericárdico compatibles con miopericarditis. Se inició tratamiento con corticoides con mejoría inicial, precisando en los meses posteriores la adición de metotrexato (AU)

Adult Still's disease (ASD) was described by George Still in 1896. ASD is a rare inflammatory disorder, of unknown etiology, whose clinical manifestations are manifold. Diagnosis requires high clinical suspicion and exclusion of different etiologies. We report the case of a 20 year old male with fever, arthritis, dyspnea and chest pain. Laboratory findings showed increased levels of cardiac enzymes, and a pleuropericardic effusion was detected in imaging tests, both of them showing myopericarditis. Corticosteroid treatment was started with initial improvement, although the addition of methotrexate was necessary in the following months (AU)