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BACKGROUND: The incidence of myocardial infarction (MI) and sudden cardiac death (SCD) is significantly higher in individuals with Type 2 Diabetes Mellitus (T2DM) than in the general population. Strategies for the prevention of fatal arrhythmias are often insufficient, highlighting the need for additional non-invasive diagnostic tools. The T-wave heterogeneity (TWH) index measures variations in ventricular repolarization and has emerged as a promising predictor for severe ventricular arrhythmias. Although the EMPA-REG trial reported reduced cardiovascular mortality with empagliflozin, the underlying mechanisms remain unclear. This study investigates the potential of empagliflozin in mitigating cardiac electrical instability in patients with T2DM and coronary heart disease (CHD) by examining changes in TWH. METHODS: Participants were adult outpatients with T2DM and CHD who exhibited TWH > 80 µV at baseline. They received a 25 mg daily dose of empagliflozin and were evaluated clinically including electrocardiogram (ECG) measurements at baseline and after 4 weeks. TWH was computed from leads V4, V5, and V6 using a validated technique. The primary study outcome was a significant (p < 0.05) change in TWH following empagliflozin administration. RESULTS: An initial review of 6,000 medical records pinpointed 800 patients for TWH evaluation. Of these, 412 exhibited TWH above 80 µV, with 97 completing clinical assessments and 90 meeting the criteria for high cardiovascular risk enrollment. Empagliflozin adherence exceeded 80%, resulting in notable reductions in blood pressure without affecting heart rate. Side effects were generally mild, with 13.3% experiencing Level 1 hypoglycemia, alongside infrequent urinary and genital infections. The treatment consistently reduced mean TWH from 116 to 103 µV (p = 0.01). CONCLUSIONS: The EMPATHY-HEART trial preliminarily suggests that empagliflozin decreases heterogeneity in ventricular repolarization among patients with T2DM and CHD. This reduction in TWH may provide insight into the mechanism behind the decreased cardiovascular mortality observed in previous trials, potentially offering a therapeutic pathway to mitigate the risk of severe arrhythmias in this population. TRIAL REGISTRATION: NCT: 04117763.
Assuntos
Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Glucosídeos , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Compostos Benzidrílicos/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Glucosídeos/uso terapêutico , Glucosídeos/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Idoso , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Resultado do Tratamento , Fatores de Tempo , Potenciais de Ação/efeitos dos fármacos , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/diagnóstico , Eletrocardiografia , Fatores de RiscoRESUMO
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.
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INTRODUCTION: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. METHODS AND RESULTS: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. CONCLUSIONS: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.
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Canais de Potássio Éter-A-Go-Go , Síndrome do QT Longo , Humanos , Masculino , Feminino , Canais de Potássio Éter-A-Go-Go/genética , Canal de Potássio ERG1/genética , Fatores Sexuais , Mutação/genética , Síndrome do QT Longo/genética , Síndrome do QT Longo/diagnóstico , Síncope , LidocaínaRESUMO
Introducción: Las evidencias científicas han demostrado que durante el período pandémico por la COVID-19 ha existido un incremento de la incidencia de muerte súbita cardiovascular, proporcional al incremento de los casos y a la letalidad por la enfermedad. Objetivos: Compilar información sobre los fármacos empleados en el tratamiento de la COVID-19 y sus posibles efectos en la prolongación del intervalo QT y la aparición de muerte súbita. Métodos: Se realizó una búsqueda de información a partir de las bases de datos PubMed, Medline y SciELO, en los idiomas español e inglés en el período de enero de 2020 a enero de 2023. Resultados: Los hallazgos más recientes sugieren que los factores relacionados con el tratamiento médico del paciente para sus enfermedades cardiovasculares previas, el empleo concomitante de drogas para otras comorbilidades, el ensayo de nuevas drogas que se investigan en la actualidad para el tratamiento de la enfermedad y el uso inadecuado de fármacos en complicaciones graves por la COVID-19, pueden ocasionar prolongación del intervalo QT y arritmias ventriculares tipo torsades de pointes, lo que puede conllevar a la aparición de muerte súbita. Conclusiones: Ha sido demostrado el efecto deletéreo de los fármacos en el tratamiento de la COVID-19 y sus posibles asociaciones a la terapéutica del paciente, en la prolongación del tiempo de repolarización ventricular cardíaca, cuya traducción eléctrica es un intervalo QT prolongado y su contribución a la génesis de arritmias malignas potencialmente fatales capaces de desencadenar un paro cardíaco y evolucionar a la muerte súbita(AU)
Scientific evidence has shown an increase in the incidence of sudden cardiovascular death during the COVID-19 pandemic period. This has been proportional to the increase in cases and mortality from the disease. Direct and indirect injury to the myocardium and vascular system allow to partially explain the statistics. Among the factors related to the medical treatment of the patient for previous cardiovascular diseases, it is the concomitant use of drugs for other comorbidities. The trial of new drugs for the treatment of this condition and the inappropriate use of drugs in serious complications from COVID-19 are currently being investigated. These can cause QT prolongation and torsades de pointes ventricular arrhythmias, which can lead to sudden death. Monitoring the QT interval is recommended, before and during treatment, in patients who come to the emergency room with a clinical condition suggestive of COVID-19. Additionally, modifiable factors favoring its prolongation should be evaluated. Decision-making in the application of therapeutic protocols in patients with COVID-19 with prolonged QTc at baseline, or with increased QTc after starting treatment, must go through the analysis of the risk/benefit ratio defined by a multi- and interdisciplinary team(AU)
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Humanos , Masculino , Feminino , Arritmias Cardíacas , Síndrome do QT Longo , Morte Súbita Cardíaca/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , COVID-19/epidemiologiaRESUMO
BACKGROUND/PURPOSE: Andersen-Tawil syndrome type 1 is a rare autosomal dominant disease caused by a KCNJ2 gene mutation and clinically characterized by dysmorphic features, periodic muscular paralysis, and frequent ventricular arrhythmias (VAs). Although polymorphic and bidirectional ventricular tachycardias are prevalent, PVCs are the most frequent VAs. In addition, a "dominant" morphology with RBBB pattern associated with either superior or inferior axis is seen in most of the patients. Due to the limited efficacy of most antiarrhythmic drugs, catheter ablation (CA) is an alternative in patients with monomorphic VAs. Based on our experience, we aimed to review the arrhythmogenic mechanisms and substrates for VAs, and we analyzed the potential reasons for CA failure in this group of patients. METHODS: Case report and focused literature review. RESULTS: Catheter ablation has been reported to be unsuccessful in all of the few cases published so far. Most of the information suggests that VAs are mainly originated from the left ventricle and probably in the Purkinje network. Although identifying well-established and accepted mapping criteria for successful ablation of a monomorphic ventricular arrhythmia, papillary muscles seem not to be the right target. CONCLUSIONS: More research is needed to understand better the precise mechanism and site of origin of VAs in Andersen-Tawil syndrome patients with this particular "dominant" monomorphic ventricular pattern to establish the potential role of CA.
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Síndrome de Andersen , Ablação por Cateter , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Humanos , Síndrome de Andersen/genética , Síndrome de Andersen/cirurgia , Síndrome de Andersen/complicações , Ventrículos do Coração/cirurgia , Complexos Ventriculares Prematuros/cirurgia , Ablação por Cateter/efeitos adversosRESUMO
Abstract Introduction: Long QT Syndrome (LQTS) is an inherited disease with an abnormal electrical conduction system in the heart that can cause sudden death as a result of QT prolongation. LQT2 is the second most common subtype of LQTS caused by loss of function mutations in the potassium voltage-gated channel subfamily H member 2 (KCNH2) gene. Although more than 900 mutations are associated with the LQTS, many of these mutations are not validated or characterized. Methods and results: Sequencing analyses of genomic DNA of a family with LQT2 identified a putative mutation. i.e., KCNH2(NM_000238.3): c.3099_3112del, in KCNH2 gene which appeared to be a definite pathogenic mutation. The family pedigree information showed a gender difference in clinical features and T-wave morphology between male and female patients. The female with mutation exhibited recurring ventricular arrhythmia and syncope, while two male carriers did not show any symptoms. In addition, T-wave in females was much flatter than in males. The female proband showed a positive reaction to the lidocaine test. Lidocaine injection almost completely blocked ventricular arrhythmia and shortened the QT interval by ≥30 ms. Treatment with propranolol, mexiletine, and implantation of cardioverter-defibrillators prevented the sustained ventricular tachycardia, ventricular fibrillation, and syncope, as assessed by a 3-year follow-up evaluation. Conclusions: A putative mutation c.3099_3112del in the KCNH2 gene causes LQT2 syndrome, and the pathogenic mutation mainly causes symptoms in female progeny.
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Electrophysiological alterations of the myocardium caused by acute ischemia constitute a pro-arrhythmic substrate for the generation of potentially lethal arrhythmias. Experimental evidence has shown that the main components of acute ischemia that induce these electrophysiological alterations are hyperkalemia, hypoxia (or anoxia in complete artery occlusion), and acidosis. However, the influence of each ischemic component on the likelihood of reentry is not completely established. Moreover, the role of the His-Purkinje system (HPS) in the initiation and maintenance of arrhythmias is not completely understood. In the present work, we investigate how the three components of ischemia affect the vulnerable window (VW) for reentry using computational simulations. In addition, we analyze the role of the HPS on arrhythmogenesis. A 3D biventricular/torso human model that includes a realistic geometry of the central and border ischemic zones with one of the most electrophysiologically detailed model of ischemia to date, as well as a realistic cardiac conduction system, were used to assess the VW for reentry. Four scenarios of ischemic severity corresponding to different minutes after coronary artery occlusion were simulated. Our results suggest that ischemic severity plays an important role in the generation of reentries. Indeed, this is the first 3D simulation study to show that ventricular arrhythmias could be generated under moderate ischemic conditions, but not in mild and severe ischemia. Moreover, our results show that anoxia is the ischemic component with the most significant effect on the width of the VW. Thus, a change in the level of anoxia from moderate to severe leads to a greater increment in the VW (40 ms), in comparison with the increment of 20 ms and 35 ms produced by the individual change in the level of hyperkalemia and acidosis, respectively. Finally, the HPS was a necessary element for the generation of approximately 17% of reentries obtained. The retrograde conduction from the myocardium to HPS in the ischemic region, conduction blocks in discrete sections of the HPS, and the degree of ischemia affecting Purkinje cells, are suggested as mechanisms that favor the generation of ventricular arrhythmias.
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Isquemia Miocárdica , Arritmias Cardíacas , Coração , Sistema de Condução Cardíaco , Humanos , MiocárdioRESUMO
INTRODUCTION: Considering the importance of ventricular arrhythmias in the prediction of sudden cardiac death in chronic Chagas heart disease, the aim of the present study was to associate late potentials observed in the signal-averaged electrocardiogram (SAECG) with either non-sustained ventricular tachycardia in the 24-hour Holter monitoring or reduced left ventricular ejection fraction in the 2-dimension echocardiogram. METHODS: This was a retrospective transversal study. The medical charts of 49 patients with chronic Chagas heart disease that underwent 24-hour Holter monitoring at our institution from September 2012 to December 2015 were reviewed. In the univariate analysis, variables associated with SAECG at a p value <0.05 were entered a multivariate stepwise logistic regression analysis through the model forward. A p value <0.05 was considered to have statistical significance. RESULTS: In the univariate analysis, right bundle branch block, left atrial diameter, left ventricular systolic diameter, and left ventricular ejection fraction were associated with late potential in the SAECG. In the multivariate analysis, however, right bundle branch block and left atrial diameter were retained as independent predictors of late potentials in the SAECG. CONCLUSIONS: Neither ventricular arrhythmias in the 24-Holter monitoring nor reduced left ventricular ejection fraction in the 2-D echocardiogram were associated with late potentials in the SAECG of patients with chronic Chagas heart disease.
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Doença de Chagas , Eletrocardiografia , Doença de Chagas/complicações , Doença de Chagas/diagnóstico , Seguimentos , Humanos , Prognóstico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: Many commonly used drugs can prolong the QTc interval (QTc), which can lead to potentially life-threatening arrhythmias. In the current era of the COVID-19 pandemic, it is worth mentioning that the disease itself and several drugs used for its treatment have been associated with QTc prolongation. OBJECTIVE: To evaluate the agreement and clinical precision of a portable single-lead electrocardiogram (ECG) device to measure the QTc interval compared to the standard 12-lead ECG. METHODS: In sequential tests, QTc of ECG recordings obtained with the KardiaMobile (KM-1L) device (AliveCor, San Francisco, CA) were compared to QTc obtained with conventional 12-lead ECG. Agreement was evaluated using Bland-Altman plots and Lin's concordance coefficient. Consistency between the 2 devices in determining QTc prolongation (QTc ≥470 ms in males or ≥480 ms in females) was evaluated with kappa statistics. RESULTS: A total of 128 patients with a presumed or confirmed diagnosis of COVID-19 admitted to a university hospital were included. QTc intervals measured with KM-1L were similar to QTc measured with conventional ECG (442.45 ± 40.5 vs 441.65 ± 40.3 ms, P = .15). Bland-Altman analysis showed no significant difference in QTc values (average difference of -0.797, 95% limits of agreement:-13.179; 11.585). Lin's concordance coefficient showed an excellent agreement (0.988, P < .001). Concordance between the 2 devices for determining QTc prolongation was excellent (kappa >0.90). CONCLUSION: ECG recordings obtained with KM-1L allow an accurate QTc interval assessment. Considering its simplicity of use, this approach has advantages over conventional ECG and can provide an alternative for the evaluation of QTc in hospitalized patients, during the current time of the COVID-19 pandemic and beyond.