Clinical and genetic spectrum of sudden cardiac death in sport

Introducción: La muerte súbita cardíaca (MSC) en deportistas sucede generalmente tras una arritmia ventricular grave provocada por una enfermedad cardíaca hereditaria de base. Nuestro objetivo es describir el contexto clínico, el trasfondo genético y la penetrancia familiar de una serie de casos con MSC relacionados con el deporte. Material y métodos: se incluyeron probandos afectados por MSC, reanimada o no, y atendidos en una Unidad especializada desde 2012 a 2016. Se les aplicó un protocolo diagnóstico amplio con pruebas clínicas complejas en los supervivientes y autopsia clínica en los fallecidos. En todos los casos se realizó estudio familiar y en la mayoría de ellos, genético con next generation sequencing. Resultados: diez casos fueron estudiados y analizados de forma retrospectiva, todos varones y el 60 % fallecidos, con una edad media de 26,2 ±16,1 años. En el 50 % de los casos se había realizado un estudio clínico previo por la presencia de síntomas. Los deportes más prevalentes fueron el fútbol y la natación. En todos los casos excepto en uno se llegó finalmente al diagnóstico, siendo la miocardiopatía hipertrófica (3 casos) y la TVCP (3 casos) los diagnósticos más frecuentes, y el gen de la ryanodina el más frecuentemente mutado. De 31 familiares estudiados, 17 fueron diagnosticados de la patología del caso en concreto (54,8%). La probabilidad de identificar familiares afectos tendía a ser ligeramente mayor en caso de haber identificado una mutación causal en el probando. Conclusiones: La MSC asociada al deporte en nuestro medio muestra una baja incidencia y está causada por enfermedades cardíacas hereditarias, siendo las más frecuentes la MH y la TVCP. La presencia de síntomas previos fue frecuente y los deportes más relacionados fueron el fútbol y la natación. El test genético fue de utilidad para la identificación de casos entre los familiares, en los que se observó una alta penetrancia.Objective: Sudden cardiac death (SCD) in athletes usually occurs due to a ventricular arrhythmia caused by an hereditary heart disease. Our goal is to describe the clinical context, the genetic background and the familial penetrance of a case serie with SCD related to sport. Material and methods: Probands affected by SCD, reanimated or not, and studied in a specialized clinic from 2012-2016 were included. A comprehensive diagnostic protocol was applied with clinical tests in survivors and clinical autopsy on the deceased. In all the cases a familial study was performed, and in most of them, including genetic testing. Results: Ten cases were retrospectively studied, all were male and 60% dead, with an average age of 26,2 ± 16,1 years. In 50% of cases it had been made a previous clinical study due to the presence of symptoms. The most prevalent sports were football and swimming. Final diagnosis was reached in 9 cases, with hypertrophic cardiomyopathy (3 cases) and Cathecolaminergic Polymorphic Ventricular Tachycardia (3 cases) being the most commom underlying diseases. Ryanodine 2 was the the most frequently mutated gene.Thirty one family members were studied, of which 17 were diagnosed with the pathology (54,8%). The probability of identifying affected family members tended to be slightly higher if there was a causal mutation identified in the proband. Conclusion: SCD related to sports in our population is mainly caused by hereditary heart diseases, being the most frequent hypertrophic cardiomyopathy and Cathecolaminergic Polymorphic Ventricular Tachycardia. The presence of previous symptoms was common, and football and swimming were the most prevalent sports practiced by SCD probands. Genetic testing was useful for identifying cases among family members, in whom a high clinical penetrance was observed

Regression of Left Ventricular Hypertrophy in a Case of Sarcomeric Hypertrophic Cardiomyopathy: An Unexpected Outcome.

We present a case of sarcomeric hypertrophy cardiomyopathy diagnosed in a child who had hypertrophy degree regression during adolescence, with no left ventricular dysfunction and no increase of the ventricular diameters. (Level of Difficulty: Intermediate.).S

Cinco años de investigaciones en El Charcón (Alozaina, Málaga): (1999-2004)

In this article we present a revision of the archaeological research and works carried out at the open-air neolithic site called El Charcón at Cerro Ardite (Alozaina, Málaga), from 1999, when the site was discovered, to 2004, when a survey of the Neolithic pottery present at the site was finished. This article stresses the importance of an intensive and systematic prospection executed in 2001, which provided us a lot of data about prehistoric material culture at the site; because of the current state of the research, we will focus particularly in studying shards with decoration. Moreover, the prospection allowed us to make a proposal regarding the chronology of the site, consisting of two phases: Early-Medium Neolithic and Late Neolithic-Early Copper Age. Finally, we will present our medium-term objectives for the future of the site, taking into account its estimated archaeological potential.En este artículo realizamos una revisión de los trabajos e investigaciones arqueológicas llevadas a cabo en el yacimiento neolítico al aire libre de El Charcón de Cerro Ardite (Alozaina, Málaga), desde que en 1999 se diese a conocer dicho yacimiento hasta el estudio del material cerámico, finalizado en 2004. Estos últimos trabajos son fruto de una prospección intensiva y sistemática a la cual dedicaremos la mayor parte de nuestro estudio y gracias a la cual hemos podido documentar una gran diversidad de materiales arqueológicos; dado el estado actual de la investigación del yacimiento, nos centraremos en el estudio de la cerámica decorada. Del mismo modo, dicha prospección nos ha facilitado proponer un encuadre crono-cultural del yacimiento constituido por dos fases: Neolítico Antiguo-Medio y Neolítico Final-Cobre Antiguo. Para finalizar, expondremos los trabajos que a medio plazo se pretenden llevar a cabo en este yacimiento teniendo en cuenta el potencial arqueológico estimado para el mismo

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection

Supplementary data associated with this article can befound, in the online version, at https://doi.org/10.1016/j.medcli.2021.06.015Introduction and purpose: Atrial fibrillation (AF) is common in patients admitted with severe COVID- 19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. Methods: We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleed- ing, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. Results: 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p = 0.003; 52 (34.4%) vs 35 (23.2%), p = 0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. Conclusions: AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.Antecedentes y objetivos: La fibrilación auricular (FA) es frecuente en pacientes ingresados por COVID-19 grave. Sin embargo, los datos sobre el manejo de la anticoagulación crónica en estos pacientes son escasos. Analizamos la anticoagulación y la incidencia de episodios cardiovasculares mayores en pacientes con FA ingresados por la COVID-19. Métodos: Retrospectivamente, se identificaron todos los pacientes con FA ingresados por la COVID-19 entre marzo y mayo de 2020, en 9 hospitales espa ̃noles. Se seleccionó un grupo control de pacientes ingresados consecutivamente por la COVID-19 sin FA. Se compararon las características basales, inci- dencia de hemorragias mayores, episodios trombóticos y mortalidad. Para reducir potenciales factores de confusión se realizó un emparejamiento por puntuación de propensión, así como un análisis multivariante para predecir hemorragia mayor y mortalidad. Resultados: Se incluyeron 305 pacientes con FA ingresados por la COVID-19. Tras el emparejamiento por puntuación de propensión, 151 pacientes con FA fueron emparejados con 151 controles. Durante el ingreso, la heparina de bajo peso molecular fue el principal anticoagulante y la incidencia de hemorragia mayor y mortalidad fue mayor en el grupo de FA (16[10,6%] vs. 3[2%], p = 0,003; 52[34,4%] vs. 35[23,2%], p = 0,03, respectivamente). El análisis multivariante demostró la presencia de FA como predictor indepen- diente de sangrados y mortalidad intrahospitalaria en los pacientes con la COVID-19. En el grupo de FA, un segundo análisis multivariante identificó valores elevados de dímero-D como predictor independiente de hemorragia mayor intrahospitalaria. Conclusiones: Los pacientes con FA ingresados por la COVID-19 representan una población de alto riesgo de sangrado y mortalidad durante el ingreso. Parece recomendable individualizar la anticoagulación durante el ingreso, considerando el riesgo específico de sangrado y trombosis

Heterozygous Arrhythmogenic Cardiomyopathy-desmoplakin Mutation Carriers Exhibit a Subclinical Cutaneous Phenotype with Cell Membrane Disruption and Lack of Intercellular Adhesion

Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 ◦C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.Andalusian Society of Cardiology with a “beca de Investigación general

Novel SCN5A mutation associated with idiopathic ventricular fibrillation due to subclinical Brugada syndrome

Idiopathic ventricular fibrillation can be caused by subclinical channelopathies such as Brugada syndrome. Our objective is to study the clinical behaviour of a new SCN5A mutation found in a woman with idiopathic ventricular fibrillation. A 53-year-old woman presented with multiple episodes of ventricular fibrillation, a structurally normal heart and normal baseline electrocardiogram. Genetic testing included KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2 and KCNJ2 and identified a mutation in SCN5A (D1816fs/g98747-98748insT). We studied 15 immediate family members by means of electrocardiogram, echocardiogram, flecainide challenge test and genetic study. Eight subjects had the mutation. The flecainide challenge test was positive for Brugada syndrome in two subjects in the case group and none in the control group. The PR and QRS intervals on the baseline electrocardiogram were longer in the case group. The left atrial volume indexed to body surface was higher in the case group, likely due to the fact that two patients with the mutation had atrial fibrillation and none had it in the control group. The D1816fs/g98747-98748insT mutation in SCN5A may be associated with idiopathic ventricular fibrillation and Brugada syndrome with a broad phenotypic spectrum and incomplete penetrance. Genetic testing may be useful to identify the etiology of idiopathic ventricular fibrillation in patients with a negative thorough clinical evaluation

Prevalence of bleeding secondary to anticoagulation and mortality in patients with atrial fibrillation admitted with SARS-CoV-2 infection.

Atrial fibrillation (AF) is common in patients admitted with severe COVID-19. However, there is limited data about the management of chronic anticoagulation therapy in these patients. We assessed the anticoagulation and incidence of major cardiovascular events in hospitalized patients with AF and COVID-19. We retrospectively investigated all consecutive patients with AF admitted with COVID-19 between March and May 2020 in 9 Spanish hospitals. We selected a control group of non-AF patients consecutively admitted with COVID-19. We compared baseline characteristics, incidence of major bleeding, thrombotic events and mortality. We used propensity score matching (PSM) to minimize potential confounding variables, as well as a multivariate analysis to predict major bleeding and death. 305 patients admitted with AF and COVID-19 were included. After PSM, 151 AF patients were matched with 151 control group patients. During admission, low-molecular-weight heparin was the principal anticoagulant and the incidence of major bleeding and mortality were higher in the AF group [16 (10.6%) vs 3 (2%), p=0.003; 52 (34.4%) vs 35 (23.2%), p=0.03, respectively]. The multivariate analysis showed the presence of AF as independent predictor of in-hospital major bleeding and mortality in COVID-19 patients. In AF group, a secondary multivariate analysis identified high levels of D-dimer as independent predictor of in-hospital major bleeding. AF patients admitted with COVID-19 represent a population at high risk for bleeding and mortality during admission. It seems advisable to individualize anticoagulation therapy during admission, considering patient specific bleeding and thrombotic risk.S

Differential diagnosis of systemic lupus erythematosus: Key aspects of day-to-day

Este artículo aborda el diagnóstico diferencial del Lupus eritematoso sistémic

Truncating FLNC Mutations Are Associated With High-Risk Dilated and Arrhythmogenic Cardiomyopathies

BACKGROUND: Filamin C (encoded by the FLNC gene) is essential for sarcomere attachment to the plasmatic membrane. FLNC mutations have been associated with myofibrillar myopathies, and cardiac involvement has been reported in some carriers. Accordingly, since 2012, the authors have included FLNC in the genetic screening of patients with inherited cardiomyopathies and sudden death. OBJECTIVES: The aim of this study was to demonstrate the association between truncating mutations in FLNC and the development of high-risk dilated and arrhythmogenic cardiomyopathies. METHODS: FLNC was studied using next-generation sequencing in 2,877 patients with inherited cardiovascular diseases. A characteristic phenotype was identified in probands with truncating mutations in FLNC. Clinical and genetic evaluation of 28 affected families was performed. Localization of filamin C in cardiac tissue was analyzed in patients with truncating FLNC mutations using immunohistochemistry. RESULTS: Twenty-three truncating mutations were identified in 28 probands previously diagnosed with dilated, arrhythmogenic, or restrictive cardiomyopathies. Truncating FLNC mutations were absent in patients with other phenotypes, including 1,078 patients with hypertrophic cardiomyopathy. Fifty-four mutation carriers were identified among 121 screened relatives. The phenotype consisted of left ventricular dilation (68%), systolic dysfunction (46%), and myocardial fibrosis (67%); inferolateral negative T waves and low QRS voltages on electrocardiography (33%); ventricular arrhythmias (82%); and frequent sudden cardiac death (40 cases in 21 of 28 families). Clinical skeletal myopathy was not observed. Penetrance was >97% in carriers older than 40 years. Truncating mutations in FLNC cosegregated with this phenotype with a dominant inheritance pattern (combined logarithm of the odds score: 9.5). Immunohistochemical staining of myocardial tissue showed no abnormal filamin C aggregates in patients with truncating FLNC mutations. CONCLUSIONS: Truncating mutations in FLNC caused an overlapping phenotype of dilated and left-dominant arrhythmogenic cardiomyopathies complicated by frequent premature sudden death. Prompt implantation of a cardiac defibrillator should be considered in affected patients harboring truncating mutations in FLNC.Instituto de Salud Carlos III [PI11/0699, PI14/0967, PI14/01477, RD012/0042/0029, RD012/0042/0049, RD012/0042/0066, RD12/0042/0069]; Spanish Ministry of Economy and Competitiveness [SAF2015-71863-REDT]; Plan Nacional de I+D+I; Plan Estatalde I+D+I, European Regional Development Fund; Health in Code SLS

Emery-Dreifuss Muscular Dystrophy 1 is associated with high risk of malignant ventricular arrhythmias and end-stage heart failure.

BACKGROUND AND AIMS Emery-Dreifuss muscular dystrophy (EDMD) is caused by variants in EMD (EDMD1) and LMNA (EDMD2). Cardiac conduction defects and atrial arrhythmia are common to both, but LMNA variants also cause end-stage heart failure (ESHF) and malignant ventricular arrhythmia (MVA). This study aimed to better characterise the cardiac complications of EMD variants. METHODS Consecutively referred EMD variant-carriers were retrospectively recruited from 12 international cardiomyopathy units. MVA and ESHF incidence in male and female variant-carriers was determined. Male EMD variant-carriers with a cardiac phenotype at baseline (EMDCARDIAC) were compared to consecutively recruited male LMNA variant-carriers with a cardiac phenotype at baseline (LMNACARDIAC). RESULTS Longitudinal follow-up data were available for 38 male and 21 female EMD variant-carriers (mean [SD] ages 33.4 [13.3] and 43.3 [16.8] years, respectively). Nine (23.6%) males developed MVA and five (13.2%) developed ESHF during a median [IQR] follow-up of 65.0 [24.3, 109.5] months. No female EMD variant-carrier had MVA or ESHF, but nine (42.8%) developed a cardiac phenotype at a median [IQR] age of 58.6 [53.2, 60.4] years. Incidence rates for MVA were similar for EMDCARDIAC and LMNACARDIAC (4.8 and 6.6 per 100 person-years, respectively; log-rank p = 0.49). Incidence rates for ESHF were 2.4 and 5.9 per 100 person-years for EMDCARDIAC and LMNACARDIAC, respectively (log-rank p = 0.09). CONCLUSIONS Male EMD variant-carriers have a risk of progressive heart failure and ventricular arrhythmias similar to that of male LMNA variant-carriers. Early implantable cardioverter defibrillator implantation and heart failure drug therapy should be considered in male EMD variant-carriers with cardiac disease.The work reported in this publication was funded by: a British Heart Foundation Clinical Research Training Fellowship to D.E.C. (FS/CRTF/ 20/24022); a British Heart Foundation Clinical Research Training fellowship to A.P. (FS/18/82/34024); The Ministry of Health, Italy, project RC-2022-2773270 to E.B.; the National Institutes of Health (NIH) (R01HL69071, R01HL116906, R01HL147064, NIH/NCATS UL1 TR002535, and UL1 TR001082) to L.M.; and support from the Rose Foundation for K.M.S