Exploring Atrial Fibrillation: Understanding the Complex Relation Between Lifestyle and Genetic Factors.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide across diverse ethnic groups. Among these, atrial fibrillation (AF) stands as one of the most prevalent types of arrhythmias and the primary cause of stroke. Risk factors associated with AF include alcohol consumption, aging, high blood pressure, hypertension, inflammation, and genetic factors. A family history of CVD could indicate an increased risk. Consequently, genetic, and genomic testing should be performed to identify the molecular etiology of CVDs and assess at-risk patients. It is important to note that CVDs are the results of the complex interplay of genes and environmental factors, including ethnicity. In this case, the proband's clinic story includes a history of smoking abuse for 10 years (10 cigarettes per day), obesity, hypertension, and an associated familial history. These risk factors, along with genetic variants, could trigger the early onset of AF. In recent years, genetic and genomic studies have significantly advanced our understanding of CVD etiology, given that next-generation sequencing (NGS) allows for the identification of genetic variants that could contribute to these pathologies. Furthermore, NGS facilitates early diagnosis, personalized pharmacological approaches, and identification of novel biomarkers. Thus, NGS is a valuable tool in CVD management. However, such studies are limited in Ecuador, a low- and middle-income country. Several challenges contribute to this gap, encompassing economic, infrastructural, and educational obstacles. Notably, the cost of genetic and genomic studies may also pose a barrier, restricting access to a portion of the population. In this case report, we present a 56-year-old Ecuadorian woman, who has been diagnosed with AF; however, after performing NGS no disease-associated variants were found, despite having strong clinical signs and symptoms. In summary, this case report contributes valuable insights into the complex interplay between genetic and lifestyle factors in the development and management of AF. The case report aims to underscore the potential impact of genetic variants on disease risk, even when classified as variants of uncertain significance, and the importance of an integral approach to patient care that includes genetic screening, lifestyle interventions, and tailored pharmacological treatment.

Genomic analysis of an Ecuadorian individual carrying an SCN5A rare variant.

BACKGROUND: Ion channels, vital transmembrane protein complexes, regulate ion movement within cells. Germline variants in channel-encoding genes lead to channelopathies. The sodium channels in cardiac cells exhibit a structure of an alpha subunit and one to two beta subunits. The alpha subunit, encoded by the SCN5A gene, comprises four domains. CASE PRESENTATION: A fifteen-year-old Ecuadorian female with atrial flutter and abnormal sinus rhythm with no familial history of cardiovascular disease underwent NGS with the TruSight Cardio kit (Illumina). A likely pathogenic SCN5A gene variant (NM_188056.2:c.2677 C > Tp. Arg893Cys) was identified, associated with arrhythmias, long QT, atrial fibrillation, and Brugada syndrome. Ancestral analysis revealed a predominant European component (43.9%), followed by Native American (35.7%) and African (20.4%) components. CONCLUSIONS: The participant presents atrial flutter and conduction disorders, despite lacking typical cardiovascular risk factors. The proband carries a SCN5A variant that has not been previously reported in Latin America and may be associated to her phenotype. The documented arginine-to-cysteine substitution at position 893 in the protein is crucial for various cellular functions. The subject's mixed genetic composition highlights potential genetic contributors to atrial flutter, emphasizing the need for comprehensive genetic studies, particularly in mixed populations like Ecuadorians. This case underscores the importance of genetic analysis for personalized treatment and the significance of studying diverse genetic backgrounds in understanding cardiovascular diseases.

Identifying genomic variant associated with long QT syndrome type 2 in an ecuadorian mestizo individual: a case report.

Introduction: Long QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the KCNH2 gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds. Case presentation: A 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the KCNH2 gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the AKAP9 p.(Arg1654GlyfsTer23) (rs779447911), and TTN p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion. Conclusion: Based on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.

Associations of MYPN, TTN, SCN5A, MYO6 and ELN Mutations With Arrhythmias and Subsequent Sudden Cardiac Death: A Case Report of an Ecuadorian Individual.

Cardiac pathologies are among the most frequent causes of death worldwide. Regarding cardiovascular deaths, it is estimated that 5 million cases are caused by sudden cardiac death (SCD) annually. The primary cause of SCD is ventricular arrhythmias. Genomic studies have provided pathogenic, likely pathogenic, and variants of uncertain significance that may predispose individuals to cardiac causes of sudden death. In this study, we describe the case of a 43-year-old individual who experienced an episode of aborted SCD. An implantable cardioverter defibrillator was placed to prevent further SCD episodes. The diagnosis was ventricular fibrillation. Genomic analysis revealed some variants in the MYPN (pathogenic), GCKR (likely pathogenic), TTN (variant of uncertain significance), SCN5A (variant of uncertain significance), MYO6 (variant of uncertain significance), and ELN (variant of uncertain significance) genes, which could be associated with SCD episodes. In addition, a protein-protein interaction network was obtained, with proteins related to ventricular arrhythmia and the biological processes involved. Therefore, this study identified genetic variants that may be associated with and trigger SCD in the individual. Moreover, genetic variants of uncertain significance, which have not been reported, could contribute to the genetic basis of the disease.

Identification of mutations on the EMD and EYA4 genes associated with Emery-Dreifuss muscular dystrophy and deafness: a case report.

Introduction: Hearing loss is the most common sensory disability, and it is estimated that 50% of cases are caused by genetic factors. One of the genes associated with deafness is the eyes absent homolog 4 (EYA4) gene, a transcription factor related to the development and function of the inner ear. Emery-Dreifuss muscular dystrophy is a rare inherited disease characterized by atrophy and weakness of the humeroperoneal muscles, multi-joint contractures, and cardiac manifestations. It is inherited in an autosomal-dominant, X-linked, or less frequently autosomal recessive manner; one of the genes associated with EDMD is the emerin (EMD) gene. Case description: A total of two Ecuadorian siblings aged 57 (Subject A) and 55 (Subject B) were diagnosed with deafness and an unspecified type of muscular dystrophy based on family history and clinical findings. Next-generation sequencing (NGS) using the TruSight Cardio and Inherited Disease kits at the Centro de Investigación Genética y Genómica CIGG, Universidad UTE, was performed. The genetic analyses showed two mutations: a stop mutation in exon 11/20 (NM_004100.4:c.940G>T) of the EYA4 gene and a missense mutation in exon 6 (NM_000117.2:c.548C>G) of the EMD gene. Discussion and conclusion: The in silico predictions described the EYA4 variant as likely pathogenic and the EMD variant as a variant of uncertain significance (VUS). Moreover, an ancestry analysis was performed using 46 Ancestry Informative Insertion/Deletion Markers (AIM-InDels), and the ancestral composition of subject A was 46% African, 26.1% European, and 27.9% American Indian ancestry, whereas the ancestral composition of subject B was 41.3% African, 38.2% European, and 20.5% American Indian ancestry. The present case report describes two Ecuadorian siblings with a mainly African ancestral component, muscular dystrophy, and deafness phenotypes. Moreover, using next-generation sequencing (NGS), a mutation in the EMD and a novel mutation in EYA4 genes possibly associated with the subjects' phenotype were identified and discussed.

Genomic analysis of a novel pathogenic variant in the gene LMNA associated with cardiac laminopathies found in Ecuadorian siblings: A case report.

Introduction: Cardiac laminopathies are caused by mutations in the LMNA gene and include a wide range of clinical manifestations involving electrical and mechanical changes in cardiomyocytes. In Ecuador, cardiovascular diseases were the primary cause of death in 2019, accounting for 26.5% of total deaths. Cardiac laminopathy-associated mutations involve genes coding for structural proteins with functions related to heart development and physiology. Family description: Two Ecuadorian siblings, self-identified as mestizos, were diagnosed with cardiac laminopathies and suffered embolic strokes. Moreover, by performing Next-Generation Sequencing, a pathogenic variant (NM_170707.3:c.1526del) was found in the gene LMNA. Discussion and conclusion: Currently, genetic tests are an essential step for disease genetic counseling, including cardiovascular disease diagnosis. Identification of a genetic cause that may explain the risk of cardiac laminopathies in a family can help the post-test counseling and recommendations from the cardiologist. In the present report, a pathogenic variant ((NM_170707.3:c.1526del) has been identified in two Ecuadorian siblings with cardiac laminopathies. The LMNA gene codes for A-type laminar proteins that are associated with gene transcription regulation. Mutations in the LMNA gene cause laminopathies, disorders with diverse phenotypic manifestations. Moreover, understanding the molecular biology of the disease-causing mutations is essential in deciding the correct type of treatment.

Estimulación cardíaca temporal de larga duración con cable activo y marcapaso permanente externo / Long-term temporary cardiac pacing with active lead and external permanent pacemaker

INTRODUCCIÓN. La estimulación cardíaca temporal de larga duración con cable activo y marcapaso permanente externo es una técnica recientemente incluida en las guías de manejo de bradicardias sintomáticas. CASOS CLÍNICOS. Se describen 4 casos de pacientes sometidos a estimulación cardíaca temporal de larga duración con cable activo y marcapaso permanente externo de la unidad de Hemodinámica del Hospital de Especialidades Carlos Andrade Marín, con indicaciones diversas. DISCUSIÓN. El tiempo medio de permanencia con el cable activo y el marcapaso externalizado fue 23 días. No hubo complicaciones del procedimiento. Un paciente falleció por causas no relacionadas con la estimulación y 2 se recuperaron en sus domicilios. CONCLUSIÓN. La técnica de estimulación temporal utilizando marcapasos permanentes recuperados se muestra extremadamente útil para mantener un marcapaso cardíaco seguro, incluso ambulatorio y por largo tiempo, hasta el implante de dispositivos definitivos. Su limitación es la factibilidad de hacerlo solo en centros de tercer nivel.

INTRODUCTION. Long-duration temporary cardiac pacing with active lead and permanent external pacemaker is a technique recently included in the guidelines for the management of symptomatic bradycardias. CLINICAL CASES. We describe 4 cases of patients who underwent long-duration temporary cardiac pacing with active lead and external permanent pacemaker at the Hemodynamics Unit of the Hospital de Especialidades Carlos Andrade Marín, with different indications. DISCUSSION. The mean length of stay with the active lead and externalized pacemaker was 23 days. There were no procedural complications. One patient died of causes unrelated to pacing and 2 recovered at home. CONCLUSIONS. The technique of temporary pacing using retrieved permanent pacemakers is extremely useful for maintaining safe cardiac pacing, even on an outpatient basis and for a long period of time, until implantation of definitive devices. Its limitation is the feasibility of doing it only in third level centers.

Utilidad del Monitoreo Holter de 96 horas para la Detección de Fibrilación Auricular en eventos Cerebrovasculares Agudos / Usefulness of 96-hour Holter Monitoring for auricular fibrillation detection in acute cerebrovascular events

Introducción: Cerca del 25% de eventos isquémicos cerebrales son secundarios a fibrilación auricular (FA) paroxística y los pacientes requieren anticoagulación oral permanente. Es necesario identificarlos para prevenir su aparición. El método de rutina utilizado es el Holter de 24 horas. Materiales y Métodos: En un período de 21 meses, 100 pacientes con diagnóstico presuntivo de un evento cerebrovascular isquémico agudo (ECV) o ataque isquémico transitorio (AIT), de origen embólico, fueron sometidos a monitoreo Holter de 96 horas, para detectar fibrilación auricular paroxística. Resultados: En 7% de ellos se encontró alguna forma de esta arritmia, así como en 7,8% de aquellos con diagnóstico de ECV o AIT confirmados y sin evidencia de fuente cardioembólica. Discusión: Concluimos que el método de Holter de 96 horas es mejor que el rutinario de 24 horas, pero para mejorar su sensibilidad, se requiere seleccionar a los pacientes con mayor probabilidad de presentar la arritmia.

Introduction: Close to 25% of cerebrovascular events are related to paroxistic atrial fibrillation (AF), that is why AF patients need to receive permanent oral anticoagulation. We need to identify them to prevent the events. The usual test employed has been the 24 hours Holter. Methods: In a period of 21.5 months, 100 patients with presumptive diagnosis of acute ischemic cerebrovascular event or transient ischemic attack of embolic origin, underwent 96 hours Holter monitoring to detect paroxysmal atrial fibrillation. Results: In nearly 7% of these patients this kind of arrhythmia was found, as well as, in 7.8% of those with confirmed stroke without evidence of cardioembolic source. Discusion: We conclude that the 96 hours Holter is better than the routinary 24-hour Holter, though, in order to incresae the sensitivity of this test, it is worthwhile to choose patientes with higher probability to present this arrhytmia.

Comparación de dos accesos venosos para el implante de dispositivos de estimulación cardíaca / Comparison of two poisonous gateways for implanting cardiac stimulation devices

Introducción: se pretende comparar las complicaciones del implante con abordaje venoso percutáneo versus uno por venodisección. Materiales y métodos: se incluyó implantes entre enero 2010 y diciembre 2012. Se excluyó los cambios de generador, implantes no exitosos, aquellos por vía yugular o femoral y los realizados fuera del laboratorio de electrofisiología. Evaluamos las complicaciones, tales como: hematoma, infección, neumotórax, desplazamiento de lead, reintervención y muerte. Resultados: se analizó 161 implantes. La infección de bolsillo se presentó en 3,7% del acceso percutáneo y 1,25% con el cefálico (p: 0,27). El hematoma de bolsillo se presentó en 2,49% con el acceso percutáneo y 1,25% con el cefálico (p: 0.57). Hubo desplazamiento de lead auricular en 2,5% del acceso cefálico vs 1,23% con el percutáneo (p: 0.56). El desplazamiento de lead ventricular se presentó en el 1,23% del grupo percutáneo vs 1,25% con el cefálico (p: 0.99). Hubo neumotórax en el 2,49% del grupo subclavio vs 0% con cefálico (p: 0.29). Se reportó una muerte en el grupo cefálico 1,25% (p: 0.49). La reintervención fue requerida en 6,1% del grupo percutáneo vs 3,75% con cefálico (p: 0.48). Conclusión: no existió diferencia en la presentación de complicaciones en el abordaje percutáneo en comparación con la venodisección cefálica.

Introduction: we intend to compare the complications related to the subclavian/axilar puncture versus cephalic vein cut down in pacemaker implantation. Materials and methods: all procedures between january 2010 and december 2013 were included. We excluded pulse generator substitution, unsuccessful implantations, jugular or femoral access and implantation performed outside the electrophysiology laboratory. We analyzed early complications such as pocket hematoma, pocket infection, pneumothorax, lead displacement, re intervention and death. Results: 161 procedures were analyzed. Pocket infection presented in 3,7% with subcalvian/axilar access and in 1,25% with cephalic access (p:0,27). Pocket hematoma presented in 2,49% with subclavian/axilar access vs 1,25% with cephalic access (0,57). There were atrial lead displacement in 2,5% with cephalic access vs 1,23% with subcalvian/axilar access (p:0,56). Ventricular lead displacement presented in1,23% with subclavian/axilar access vs 1,25% with cephalic access (p:0,99). Pneumothorax presented in 2,49% with subclavian/axilar access vs 0% with cephalic access (p:0,29). We reported one death with cephalic access (p: 0,49). Re intervention was needed in 6,1% with subclavian/axilar access vs 3,75% with cephalic access (p:0.48). Conclusion: complication rates presented no differences between subclavian/axilar access and cephalic access.

[Radiofrequency ablation of a left free-wall accessory pathway by transradial approach]. / Ablación por radiofrecuencia de una vía accesoria lateral izquierda por abordaje transradial.

Radiofrequency ablation of left free-wall accessory pathways in the Wolff-Parkinson-White syndrome is conventionally made by retrograde transaortic approach from one of the femoral arteries. We report the case of a patient with a left anterolateral pathway, with difficulties in the approach through the iliac arteries, which pathway was ablated from the right radial artery.

Ablación por radiofrecuencia de una vía accesoria lateral izquierda por abordaje transradial / Radiofrequency ablation of a left free-wall accessory pathway by transradial approach

La ablación por radiofrecuencia de las vías accesorias izquierdas en el síndrome de Wolff-Parkinson-White, convencionalmente se realiza por vía transaórtica retrógrada desde una de las arterias femorales. Nosotros informamos el caso de un paciente portador de una vía anterolateral izquierda, con dificultades para el acceso a través de las arterias ilíacas, cuya vía pudo ser ablacionada utilizando la arteria radial derecha.

Radiofrequency ablation of left free-wall accessory pathways in the Wolff-Parkinson-White syndrome is conventionally made by retrograde transaortic approach from one of the femoral arteries. We report the case of a patient with a left anterolateral pathway, with difficulties in the approach through the iliac arteries, which pathway was ablated from the right radial artery.

Estrategias de tratamiento no farmacológico de la fibrilación auricular / Strategy of nonfarmacológico processing of the auricular fibrilación

Expone que la fibrilación auricular es la arritmia sostenida más frecuente. Se ha desarrollado varias estrategias no farmacológicas para su manejo, entre ellas: la cirugía, la ablación transcatéter y los desfibriladores implantables. El desarrollo de las técnicas quirúrgicas se ha fundamentado sobre el principio de que el mecanismo electrofisiológico de la FA es la reentrada aleatoria. La cirugía del Laberinto, desarrollada por Cox et al. es al momento el procedimiento que cumple con los que son objetivos primordiales del tratamiento eficiente de la FA: evitar el tromboembolismo, preservar la función atrial y mantener la sincronía atrioventricular. Al momento, se ha indicado en los casos de una arritmia mal tolerada y refractaria al máximo tratamiento médico preoperatorio, y se han incluido pacientes con tromboembolismo cerebral documentado secundario a FA crónica o paroxística, en ausencia de otras etiologías demostrables. Como procedimiento accesorio a otras cirugías de reparación también se ha demostrado eficiente y seguro...