RESUMEN
Antioxidants play an important role in protecting cardiac arrhythmias. Silymarin, strong antioxidant, is effective in reducing the complications caused by arrhythmias. This study was conducted to determine the effect of silymarin on the prevention and treatment of calcium chloride-induced arrhythmia. In total, 48 male rats were randomly divided into six groups: the first control group for acute administration received intravenous injection of 0.2 mL of dimethylsulfoxide, a cosolvent, immediately after induction of arrhythmia; the second control group for chronic administration, daily gavage of dimethylsulfoxide for 2 weeks before induction of arrhythmia; acute silymarin group, 100 mg/kg intravenous, immediately after the occurrence of arrhythmia; chronic silymarin group, daily gavage of 50 mg/kg for 2 weeks before induction of arrhythmia; amiodarone standard treatment, 5 mg/kg intravenous, immediately after induction of arrhythmia; and quinidine standard treatment, 10 mg/kg intravenous, immediately after induction of arrhythmia. Calcium chloride (140 mg/kg, i.v.) was used to induce arrhythmia. Electrocardiogram was recorded and monitored by PowerLab™ system. The incidence rates of premature ventricular beat (PVB), ventricular tachycardia (VT), and ventricular fibrillation (VF) were calculated. The antiarrhythmic effect of silymarin was observed with a significant decrease in the incidence of premature ventricular beat (22.56 ± 1.04%, P < 0.001), ventricular tachycardia (34.150 ± 1.59%, P < 0.001), and ventricular fibrillation (24.31 ± 1.02%, P < 0.001) compared with the control group (100%). These effects were comparable to antiarrhythmic drugs such as quinidine (29.23% ± 1.24%, 52.23% ± 1.13%, 66.31% ± 1.81%) and amiodarone (22.91% ± .72%, 41.09% ± 1.66%, 61.59% ± 1.11%). Silymarin exerts a potent antioxidant effect, thereby mitigating the risk of VT, VF, and PVC.
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Arritmias Cardíacas , Cloruro de Calcio , Silimarina , Animales , Masculino , Silimarina/farmacología , Silimarina/uso terapéutico , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/inducido químicamente , Ratas , Cloruro de Calcio/farmacología , Ratas Sprague-Dawley , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Electrocardiografía , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
BACKGROUND: Hailey-Hailey disease (HHD) is a rare autosomal dominant skin disease caused by mutations in the ATP2C1 gene, which encodes the secretory Ca2+/Mn2+-ATPase (SPCA1) pump in the Golgi apparatus. Although ATP2C1 is ubiquitously expressed in the body, possible extracutaneous manifestations of HHD are unknown. However, dysfunction of the Golgi apparatus not specifically coupled to ATP2C1 has been associated with heart disease. OBJECTIVE: To investigate the association between HHD and common heart disease in a Swedish, population-based cohort. METHODS: We conducted a population-based cohort study based on a linkage of Swedish nationwide registers to investigate the relationship between HHD and heart disease. We have been granted ethical approval from the Swedish Ethical Review Authority to conduct this study. The patients in this manuscript have given written informed consent to the publication of their case details. A total of 342 individuals with an ICD-10 diagnosis of HHD (Q82.8E) were identified and matched with randomly selected comparison individuals without HHD on a 1:100 ratio. Furthermore, in a separate clinical cohort we matched 23 HHD patients for age, sex, and BMI with control subjects to examine electrocardiogram parameters, electrolytes, and cardiovascular biomarkers. RESULTS: Compared with individuals without HHD, individuals with HHD had an excess risk of arrhythmia (RR 1.4, CI 1.0-2.0), whereas no increased risks of myocardial infarction (RR 1.1, CI 0.6-1.7) or heart failure (RR 1.0, CI 0.6-1.6; Table 1) were found. We found no difference in ECG parameters, cardiovascular biomarkers, and electrolytes in the clinical subset. CONCLUSION: This study reveals that HHD is associated with an increased risk of arrhythmia and represents the first data of any extracutaneous comorbidity in HHD. Thus, HHD may be a systemic disease. Our findings also shed light on the importance of the Golgi apparatus' Ca2+/Mn2+ homeostasis in common heart disease.
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Arritmias Cardíacas , Pénfigo Familiar Benigno , Humanos , Arritmias Cardíacas/genética , Femenino , Masculino , Pénfigo Familiar Benigno/genética , Pénfigo Familiar Benigno/complicaciones , Persona de Mediana Edad , Adulto , Suecia/epidemiología , Anciano , Estudios de Cohortes , ATPasas Transportadoras de Calcio/genética , ATPasas Transportadoras de Calcio/metabolismo , Factores de Riesgo , Estudios de Casos y ControlesRESUMEN
The multi-lead electrocardiogram (ECG) is widely utilized in clinical diagnosis and monitoring of cardiac conditions. The advancement of deep learning has led to the emergence of automated multi-lead ECG diagnostic networks, which have become essential in the fields of biomedical engineering and clinical cardiac disease diagnosis. Intelligent ECG diagnosis techniques encompass Recurrent Neural Networks (RNN), Transformers, and Convolutional Neural Networks (CNN). While CNN is capable of extracting local spatial information from images, it lacks the ability to learn global spatial features and temporal memory features. Conversely, RNN relies on time and can retain significant sequential features. However, they are not proficient in extracting lengthy dependencies of sequence data in practical scenarios. The self-attention mechanism in the Transformer model has the capability of global feature extraction, but it does not adequately prioritize local features and cannot extract spatial and channel features. This paper proposes STFAC-ECGNet, a model that incorporates CAMV-RNN block, CBMV-CNN block, and TSEF block to enhance the performance of the model by integrating the strengths of CNN, RNN, and Transformer. The CAMV-RNN block incorporates a coordinated adaptive simplified self-attention module that adaptively carries out global sequence feature retention and enhances spatial-temporal information. The CBMV-CNN block integrates spatial and channel attentional mechanism modules in a skip connection, enabling the fusion of spatial and channel information. The TSEF block implements enhanced multi-scale fusion of image spatial and sequence temporal features. In this study, comprehensive experiments were conducted using the PTB-XL large publicly available ECG dataset and the China Physiological Signal Challenge 2018 (CPSC2018) database. The results indicate that STFAC-ECGNet surpasses other cutting-edge techniques in multiple tasks, showcasing robustness and generalization.
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Arritmias Cardíacas , Electrocardiografía , Redes Neurales de la Computación , Electrocardiografía/métodos , Humanos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Aprendizaje Profundo , Algoritmos , Procesamiento de Señales Asistido por ComputadorRESUMEN
The electrocardiogram (ECG) is a fundamental and widely used tool for diagnosing cardiovascular diseases. It involves recording cardiac electrical signals using electrodes, which illustrate the functioning of cardiac muscles during contraction and relaxation phases. ECG is instrumental in identifying abnormal cardiac activity, heart attacks, and various cardiac conditions. Arrhythmia detection, a critical aspect of ECG analysis, entails accurately classifying heartbeats. However, ECG signal analysis demands a high level of expertise, introducing the possibility of human errors in interpretation. Hence, there is a clear need for robust automated detection techniques. Recently, numerous methods have emerged for arrhythmia detection from ECG signals. In our research, we developed a novel one-dimensional deep neural network technique called linear deep convolutional neural network (LDCNN) to identify arrhythmias from ECG signals. We compare our suggested method with several state-of-the-art algorithms for arrhythmia detection. We evaluate our methodology using benchmark datasets, including the PTB Diagnostic ECG and MIT-BIH Arrhythmia databases. Our proposed method achieves high accuracy rates of 99.24% on the PTB Diagnostic ECG dataset and 99.38% on the MIT-BIH Arrhythmia dataset.
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Arritmias Cardíacas , Electrocardiografía , Redes Neurales de la Computación , Humanos , Electrocardiografía/métodos , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Aprendizaje Profundo , Procesamiento de Señales Asistido por Computador , AlgoritmosRESUMEN
Sudden cardiac arrest (SCA) is a lethal cardiac arrhythmia that poses a serious threat to human life and health. However, clinical records of sudden cardiac death (SCD) electrocardiogram (ECG) data are extremely limited. This paper proposes an early prediction and classification algorithm for SCA based on deep transfer learning. With limited ECG data, it extracts heart rate variability features before the onset of SCA and utilizes a lightweight convolutional neural network model for pre-training and fine-tuning in two stages of deep transfer learning. This achieves early classification, recognition and prediction of high-risk ECG signals for SCA by neural network models. Based on 16 788 30-second heart rate feature segments from 20 SCA patients and 18 sinus rhythm patients in the international publicly available ECG database, the algorithm performance evaluation through ten-fold cross-validation shows that the average accuracy (Acc), sensitivity (Sen), and specificity (Spe) for predicting the onset of SCA in the 30 minutes prior to the event are 91.79%, 87.00%, and 96.63%, respectively. The average estimation accuracy for different patients reaches 96.58%. Compared to traditional machine learning algorithms reported in existing literatures, the method proposed in this paper helps address the requirement of large training datasets for deep learning models and enables early and accurate detection and identification of high-risk ECG signs before the onset of SCA.
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Algoritmos , Muerte Súbita Cardíaca , Electrocardiografía , Redes Neurales de la Computación , Humanos , Electrocardiografía/métodos , Muerte Súbita Cardíaca/prevención & control , Frecuencia Cardíaca , Sensibilidad y Especificidad , Aprendizaje Profundo , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatología , Procesamiento de Señales Asistido por ComputadorRESUMEN
S-Limonene (s-Lim) is a monocyclic monoterpene found in a variety of plants and has been shown to present antioxidant and cardioprotective activity in experimental models of myocardial infarction. The aim of this study was to evaluate the potential mechanism by which s-Lim exerts its antiarrhythmic effect, focusing on the blockade of ß-adrenoceptor (ß-AR) and its effects on various in vivo and in vitro parameters, including electrocardiogram (ECG) measurements, left ventricular developed pressure (LVDP), the ß-adrenergic pathway, sarcomeric shortening and L-type calcium current (ICa,L). In isolated hearts, 10 µM of s-Lim did not alter the ECG profile or LVPD. s-Lim increased the heart rate corrected QT interval (QTc) (10.8%) at 50 µM and reduced heart rate at the concentrations of 30 (12.4%) and 50 µM (16.6%). s-Lim (10 µM) also inhibited the adrenergic response evoked by isoproterenol (ISO) (1 µM) reducing the increased of heart rate, LVDP and ECG changes. In ventricular cardiomyocyte, s-Lim antagonized the effect of dobutamine by preventing the increase of sarcomeric shortening, demonstrating a similar effect to atenolol (blocker ß1-AR). In vivo, s-Lim antagonized the effect of ISO (agonists ß1-AR), presenting a similar effect to propranolol (a non-selective blocker ß-AR). In ventricular cardiomyocyte, s-Lim did not alter the voltage dependence for ICa,L activation or the ICa,L density. In addition, s-Lim did not affect changes in the ECG effect mediated by 5 µM forskolin (an activator of adenylate cyclase). In an in vivo caffeine/ISO-induced arrhythmia model, s-Lim (1 mg/kg) presented antiarrhythmic action verified by a reduced arrhythmia score, heart rate, and occurrence of ventricular premature beats and inappropriate sinus tachycardia. These findings indicate that the antiarrhythmic activity of s-Lim is related to blockade of ß-AR in the heart.
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Antiarrítmicos , Limoneno , Ratas Wistar , Receptores Adrenérgicos beta , Transducción de Señal , Animales , Ratas , Antiarrítmicos/farmacología , Masculino , Receptores Adrenérgicos beta/metabolismo , Limoneno/farmacología , Transducción de Señal/efectos de los fármacos , Terpenos/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Ciclohexenos/farmacología , Arritmias Cardíacas/tratamiento farmacológico , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/fisiopatología , Isoproterenol/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismoRESUMEN
Clinical conditions, including chronic obstructive pulmonary disease or pulmonary arterial hypertension (PAH), can lead to chronic right ventricle pressure overload and progressive right heart failure (RHF). RHF can be identified by right-sided cardiac hypertrophy and dilation associated with abnormal myocardial function affecting the RV and the right atrium (RA). We recently demonstrated that severe RHF is accompanied by an increased risk of atrial inflammation, atrial fibrosis, and atrial fibrillation (AF), the most common type of cardiac arrhythmia (CA). Recent studies have shown that RV and RA inflammation plays an important role in the arrhythmogenesis of CA, including AF. However, the impact of inflammation in the development of CA and AF in RHF is poorly described. Experimental models of RHF are required to better understand the association between right-sided myocardial inflammation and CA. The rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH) is well-established to provoke RHF. However, MCT triggers severe pneumo-toxicity and pulmonary inflammation. Hence, MCT-induced RHF does not help to distinguish whether the subsequent myocardial inflammation originates from the RHF per se or circulating inflammatory signals secreted by the injured lung. In this article, a mechanical method involving pulmonary artery trunk banding (PAB) was used to provoke right-sided cardiac arrhythmogenesis. The PAB consists of performing a permanent suture of the pulmonary artery trunk for 3 weeks. Such an approach generates increased right-sided pressure overload. At D21 post-PAB, the suture results in hypertrophied, dilated, and inflamed RV and RA. The PAB-induced RHF is also accompanied by vulnerability to ventricular and atrial arrhythmias, including AF.
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Arritmias Cardíacas , Modelos Animales de Enfermedad , Arteria Pulmonar , Animales , Ratas , Arteria Pulmonar/patología , Arteria Pulmonar/fisiopatología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/fisiopatología , Remodelación Ventricular/fisiología , Masculino , Hipertensión Pulmonar/fisiopatologíaRESUMEN
Palpitations are a common symptom described by patients as a feeling of a racing or fluttering heart, a pounding chest, irregular or skipped heartbeats, or a pounding sensation in the neck. They are associated with a low mortality rate; however, recurrent palpitations have been shown to impair quality of life and increase health care use. Common triggers are cardiac disorders, endocrine and metabolic disorders, medication or illicit drug use, or psychosomatic disorders. A detailed history, physical examination, directed laboratory studies, and 12-lead electrocardiography are often sufficient to identify the etiology of palpitations. Additional testing may be indicated to include echocardiography, cardiac stress testing, electrocardiogram monitoring, or electrophysiologic studies to distinguish whether symptoms correlate with cardiac arrhythmia or structural or ischemic heart disease. Management of palpitations is based on the suspected etiology. In most cases of cardiac-induced palpitations, the treatment can include reassurance, education, trigger avoidance, or use of atrioventricular nodal blockers. Tachyarrhythmias may require cardiac ablation. Patients who have palpitations with no arrhythmia causality and no cardiac disease should be reassured; however, screening for psychosomatic disorders should be considered. Wearable smart devices with ambulatory electrocardiogram monitoring technologies are currently available to consumers; these tools have shown diagnostic accuracy for detection of arrhythmias, allowing patients to have greater participation in their health care. Am Fam Physician. 2024; 110(3):259-269.
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Arritmias Cardíacas , Dispositivos Electrónicos Vestibles , Humanos , Arritmias Cardíacas/terapia , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiología , Electrocardiografía Ambulatoria/instrumentación , Electrocardiografía Ambulatoria/métodos , Electrocardiografía/métodos , Electrocardiografía/instrumentaciónRESUMEN
Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.
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Tratamiento Basado en Trasplante de Células y Tejidos , Simulación por Computador , Infarto del Miocardio , Humanos , Infarto del Miocardio/terapia , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Arritmias Cardíacas/terapia , Arritmias Cardíacas/fisiopatología , Modelos Cardiovasculares , Enfermedad Crónica , Masculino , Ramos Subendocárdicos/fisiopatología , Electrocardiografía , Enfermedad Aguda , Femenino , Persona de Mediana EdadRESUMEN
Heart failure, the leading cause of mortality and morbidity in the developed world, is characterized by cardiac ryanodine receptor 2 channels that are hyperphosphorylated, oxidized, and depleted of the stabilizing subunit calstabin-2. This results in a diastolic sarcoplasmic reticulum Ca2+ leak that impairs cardiac contractility and triggers arrhythmias. Genetic mutations in ryanodine receptor 2 can also cause Ca2+ leak, leading to arrhythmias and sudden cardiac death. Here, we solved the cryogenic electron microscopy structures of ryanodine receptor 2 variants linked either to heart failure or inherited sudden cardiac death. All are in the primed state, part way between closed and open. Binding of Rycal drugs to ryanodine receptor 2 channels reverts the primed state back towards the closed state, decreasing Ca2+ leak, improving cardiac function, and preventing arrhythmias. We propose a structural-physiological mechanism whereby the ryanodine receptor 2 channel primed state underlies the arrhythmias in heart failure and arrhythmogenic disorders.
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Arritmias Cardíacas , Calcio , Microscopía por Crioelectrón , Insuficiencia Cardíaca , Canal Liberador de Calcio Receptor de Rianodina , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/química , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/genética , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/genética , Humanos , Animales , Calcio/metabolismo , Mutación , Retículo Sarcoplasmático/metabolismo , Muerte Súbita Cardíaca/etiologíaAsunto(s)
Muerte Súbita Cardíaca , Países en Desarrollo , Domperidona , Humanos , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Domperidona/uso terapéutico , Domperidona/efectos adversos , Anciano , Arritmias Cardíacas/epidemiología , Taquicardia Ventricular , Antieméticos/uso terapéutico , Masculino , Pakistán/epidemiología , FemeninoRESUMEN
The KCNE2 protein is encoded by the kcne2 gene and is a member of the KCNE protein family, also known as the MinK-related protein 1 (MiRP1). It is mostly present in the epicardium of the heart and gastric mucosa, and it is also found in the thyroid, pancreatic islets, liver and lung, among other locations, to a lesser extent. It is involved in numerous physiological processes because of its ubiquitous expression and partnering promiscuity, including the modulation of voltage-dependent potassium and calcium channels involved in cardiac action potential repolarization, and regulation of secretory processes in multiple epithelia, such as gastric acid secretion, thyroid hormone synthesis, generation and secretion of cerebrospinal fluid. Mutations in the KCNE2 gene or aberrant expression of the protein may play a critical role in cardiovascular, neurological, metabolic and multisystem disorders. This article provides an overview of the advancements made in understanding the physiological functions in organismal homeostasis and the pathophysiological consequences of KCNE2 in multisystem diseases.
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Arritmias Cardíacas , Canales de Potasio con Entrada de Voltaje , Humanos , Canales de Potasio con Entrada de Voltaje/metabolismo , Canales de Potasio con Entrada de Voltaje/genética , Arritmias Cardíacas/genética , Arritmias Cardíacas/metabolismo , AnimalesRESUMEN
While 3-N-butylphthalide (NBP) has demonstrated notable cardioprotective effects, its precise role in mitigating myocardial arrhythmia following ischemia/reperfusion (IR) injury in diabetes remains unclear. This study aimed to explore the potential mechanisms through which NBP mitigates reperfusion-induced myocardial arrhythmia in diabetic rats, with a particular focus on mitochondrial function and biogenesis, endoplasmic reticulum (ER) stress, and oxidative/inflammatory responses. Sixty Sprague-Dawley rats were divided into non-diabetic and diabetic groups, subjected to in-vivo myocardial IR injury, and treated with NBP (100 mg/kg, intraperitoneally) through different modalities: preconditioning, postconditioning, or a combination of both. Electrocardiography (ECG) was employed to assess the incidence and severity of arrhythmia. Fluorometric, Western blotting and ELISA analyses were utilized to measure the mitochondrial, ER stress, and cellular outcomes. Treatment of non-diabetic rats with NBP in preconditioned, postconditioned, and combined approaches significantly reduced cardiotroponin-I and the frequency and severity of arrhythmias induced by IR injury. However, only the combined preconditioning plus postconditioning approach of NBP had protective and antiarrhythmic effects in diabetic rats, in an additive manner. Moreover, the NBP combined approach improved mitochondrial function and upregulated the expression of PGC-1?, Sirt1, and glutathione while concurrently downregulating ER stress and oxidative and pro-inflammatory-related proteins in diabetic rats. In conclusion, the combined approach of NBP treatment was effective in mitigating myocardial arrhythmia in diabetic rats. This approach coordinates interactions within the mitochondria-endoplasmic reticulum network and inhibits oxidative and inflammatory mediators, offering a promising strategy for managing myocardial arrhythmia in diabetic patients. Key words: Myocardial Infarction, Mitochondria, Arrhythmia, Reperfusion, Diabetes, Ischemia.
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Arritmias Cardíacas , Benzofuranos , Diabetes Mellitus Experimental , Estrés del Retículo Endoplásmico , Daño por Reperfusión Miocárdica , Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/prevención & control , Benzofuranos/farmacología , Benzofuranos/uso terapéutico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/complicaciones , Masculino , Arritmias Cardíacas/etiología , Arritmias Cardíacas/prevención & control , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/tratamiento farmacológico , Ratas , Estrés del Retículo Endoplásmico/efectos de los fármacos , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Inflamación/metabolismo , Inflamación/tratamiento farmacológicoRESUMEN
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are widely used for disease modeling and pharmacological screening. However, their application has mainly focused on inherited cardiopathies affecting ventricular cardiomyocytes, leading to extensive knowledge on generating ventricular-like hiPSC-CMs. Electronic pacemakers, despite their utility, have significant disadvantages, including lack of hormonal responsiveness, infection risk, limited battery life, and inability to adapt to changes in heart size. Therefore, developing an in vitro multiscale model of the human sinoatrial node (SAN) pacemaker using hiPSC-CM and SAN-like cardiomyocyte differentiation protocols is essential. This would enhance the understanding of SAN-related pathologies and support targeted therapies. Generating SAN-like cardiomyocytes offers the potential for biological pacemakers and specialized conduction tissues, promising significant benefits for patients with conduction system defects. This review focuses on arrythmias related to pacemaker dysfunction, examining protocols' advantages and drawbacks for generating SAN-like cardiomyocytes from hESCs/hiPSCs, and discussing therapeutic approaches involving their engraftment in animal models.
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Relojes Biológicos , Diferenciación Celular , Células Madre Pluripotentes Inducidas , Miocitos Cardíacos , Nodo Sinoatrial , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Humanos , Nodo Sinoatrial/citología , Células Madre Pluripotentes Inducidas/citología , Células Madre Pluripotentes Inducidas/metabolismo , Animales , Arritmias Cardíacas/terapia , Arritmias Cardíacas/patologíaRESUMEN
INTRODUÇÃO A mutação do fator V de Leiden é uma condição genética que acomete um ponto único no sítio de inativação do fator V impedindo a ligação com a proteína C ativada, resultando em um estado pró-trombótico. A fibrilação atrial (FA) é a arritmia mais comum do mundo com predomínio na população idosa, e está relacionada com elevado risco de eventos tromboembólicos. A oclusão do apêndice atrial esquerdo (OAA) é um procedimento minimamente invasivo, visando a tromboprofilaxia em pacientes com FA e contraindicação de anticoagulação oral (ACO). DESCRIÇÃO DO CASO Paciente M.S.F.R.S., octogenária com fragilidade severa, dependente para atividades básicas e instrumentais da vida diária, portadora da mutação heterozigótica do fator V de Leiden, dislipidêmica, ex-tagabista, obesidade sarcopênica e apresenta FA permanente em uso inicial de varfarina. Antecedentes de trombose venosa profunda em membro inferior direito, comunicação interatrial corrigida por atriosseptoplastia, quatro eventos prévios de acidente vascular encefálico (AVE) com sequela motora à direita, e osteoporose associado a múltiplas fraturas de vértebras com correção cirúrgica. Além disso, apresentava má adesão ao uso de varfarina com acompanhamento irregular do controle de INR, associado com episódios de sangramentos gastrointestinais. Por isso, optou-se pela realização da oclusão do apêndice atrial esquerdo para prevenção secundária de eventos tromboembólicos. A paciente fez uso de ácido acetilsalicílico (AAS) 100mg e clopidogrel 75mg durante 6 meses pós-procedimento, seguido da suspensão dessas medicações e introdução da rivaroxabana 15mg, devido ao risco elevado de eventos tromboembólicos propiciados pela trombofilia. Atualmente em uso de metoprolol 200mg/dia; digoxina 0,125mg/dia; omeprazol 20mg/dia; clonazepam 2mg/dia e rivaroxabana 15mg/dia. CONCLUSÃO Segundo ensaios clínicos randomizados, a OAA não mostrou-se inferior ao uso de ACO quanto a ocorrência de AVE e embolismo sistêmico, como também demonstrou superioridade quanto a menores taxas de mortalidade cardiovascular. O estudo PROTECT-AF recomenda o uso de ACO associado ao AAS por 45 dias, seguido da dupla antiagregação plaquetária durante 6 meses e após isso, uso indeterminado de AAS isolado. Porém a anticoagulação ideal pós-intervenção permanece um desafio. O futuro da OAA está relacionado com a experiência do operador, evolução da tecnologia dos dispositivos, consenso da terapia antitrombótica e manejo das principais complicações.
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Humanos , Femenino , Anciano de 80 o más Años , Fibrilación Atrial , Factor V , Apéndice Atrial , Arritmias Cardíacas , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular , Defectos del Tabique InteratrialRESUMEN
We propose a state-of-the-art deep learning approach for accurate electrocardiogram (ECG) signal analysis, addressing both waveform delineation and beat type classification tasks. For beat type classification, we integrated two novel schemes into the deep learning model, significantly enhancing its performance. The first scheme is an adaptive beat segmentation method that determines the optimal duration for each heartbeat based on RR-intervals, mitigating segmenting errors from conventional fixed-period segmentation. The second scheme incorporates relative heart rate information of the target beat compared to neighboring beats, improving the model's ability to accurately detect premature atrial contractions (PACs) that are easily confused with normal beats due to similar morphology. Extensive evaluations on the PhysioNet QT Database, MIT-BIH Arrhythmia Database, and real-world wearable device data demonstrated the proposed approach's superior capabilities over existing methods in both tasks. The proposed approach achieved sensitivities of 99.81% for normal beats, 99.08% for premature ventricular contractions, and 97.83% for PACs in beat type classification. For waveform delineation, we achieved F1-scores of 0.9842 for non-waveform, 0.9798 for P-waves, 0.9749 for QRS complexes, and 0.9848 for T-waves. It significantly outperforms existing methods in PAC detection while maintaining high performance across both tasks. The integration of aforementioned two schemes into the deep learning model improved the accuracy of normal sinus rhythms and arrhythmia detection.
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Aprendizaje Profundo , Electrocardiografía , Frecuencia Cardíaca , Procesamiento de Señales Asistido por Computador , Humanos , Electrocardiografía/métodos , Frecuencia Cardíaca/fisiología , Bases de Datos Factuales , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/diagnósticoRESUMEN
BACKGROUND: Ventricular repolarization time (ECG QT and JT intervals) is associated with malignant arrhythmia. Genome-wide association studies have identified 230 independent loci for QT and JT; however, 50% of their heritability remains unexplained. Previous work supports a causal effect of lower serum calcium concentrations on longer ventricular repolarization time. We hypothesized calcium interactions with QT and JT variant associations could explain a proportion of the missing heritability. METHODS AND RESULTS: We performed genome-wide calcium interaction analyses for QT and JT intervals. Participants were stratified by their calcium level relative to the study distribution (top or bottom 20%). We performed a 2-stage analysis (genome-wide discovery [N=62 532] and replication [N=59 861] of lead variants) and a single-stage genome-wide meta-analysis (N=122 393, [European ancestry N=117 581, African ancestry N=4812]). We also calculated 2-degrees of freedom joint main and interaction and 1-degree of freedom interaction P values. In 2-stage and single-stage analyses, 50 and 98 independent loci, respectively, were associated with either QT or JT intervals (2-degrees of freedom joint main and interaction P value <5×10-8). No lead variant had a significant interaction result after correcting for multiple testing and sensitivity analyses provided similar findings. Two loci in the single-stage meta-analysis were not reported previously (SPPL2B and RFX6). CONCLUSIONS: We have found limited support for an interaction effect of serum calcium on QT and JT variant associations despite sample sizes with suitable power to detect relevant effects. Therefore, such effects are unlikely to explain a meaningful proportion of the heritability of QT and JT, and factors including rare variation and other environmental interactions need to be considered.
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Calcio , Estudio de Asociación del Genoma Completo , Humanos , Calcio/sangre , Masculino , Femenino , Persona de Mediana Edad , Electrocardiografía , Adulto , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/sangre , Arritmias Cardíacas/diagnóstico , Anciano , Potenciales de Acción , Polimorfismo de Nucleótido Simple , Factores de Tiempo , Frecuencia Cardíaca/genética , Frecuencia Cardíaca/fisiología , Predisposición Genética a la Enfermedad , Factores de RiesgoAsunto(s)
Trastorno Autístico , Modelos Animales de Enfermedad , Síndrome de QT Prolongado , Sindactilia , Animales , Humanos , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatología , Trastorno Autístico/genética , Trastorno Autístico/fisiopatología , Discapacidades del Desarrollo/genética , Técnicas de Sustitución del Gen , Síndrome de QT Prolongado/genética , Síndrome de QT Prolongado/fisiopatología , Síndrome de QT Prolongado/diagnóstico , Porcinos , Sindactilia/genéticaRESUMEN
Arrhythmias range from mild nuisances to potentially fatal conditions, detectable through electrocardiograms (ECGs). With advancements in wearable technology, ECGs can now be monitored on-the-go, although these devices often capture noisy data, complicating accurate arrhythmia detection. This study aims to create a new deep learning model that utilizes generative adversarial networks (GANs) for effective noise removal and ResNet for precise arrhythmia classification from wearable ECG data. We developed a deep learning model that cleans ECG measurements from wearable devices and detects arrhythmias using refined data. We pretrained our model using the MIT-BIH Arrhythmia and Noise databases. Least squares GANs were used for noise reduction, maintaining the integrity of the original ECG signal, while a residual network classified the type of arrhythmia. After initial training, we applied transfer learning with actual ECG data. Our noise removal model significantly enhanced data clarity, achieving over 30 dB in a signal-to-noise ratio. The arrhythmia detection model was highly accurate, with an F1-score of 99.10% for noise-free data. The developed model is capable of real-time, accurate arrhythmia detection using wearable ECG devices, allowing for immediate patient notification and facilitating timely medical response.
Asunto(s)
Arritmias Cardíacas , Electrocardiografía , Procesamiento de Señales Asistido por Computador , Relación Señal-Ruido , Dispositivos Electrónicos Vestibles , Arritmias Cardíacas/diagnóstico , Humanos , Electrocardiografía/métodos , Algoritmos , Aprendizaje Profundo , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. Heart rate variability (HRV) may be associated with AF risk. The aim of this study was to test HRV indices and arrhythmias as predictors of paroxysmal AF based on 24-hour dynamic electrocardiogram recordings of patients. METHODS: A total of 199 patients with paroxysmal AF (AF group) and 204 elderly volunteers over 60 years old (Control group) who underwent a 24-hour dynamic electrocardiogram from August 2022 to March 2023 were included. Time-domain indices, frequency-domain indices, and arrhythmia data of the two groups were classified and measured. Binary logistic regression analysis was performed on variables with significant differences to identify independent risk factors. A nomogram prediction model was established, and the sum of individual scores of each variable was calculated. RESULTS: Gender, age, body mass index and low-density lipoprotein (LDL) did not differ significantly between AF and Control groups (p > 0.05), whereas significant group differences were found for smoking, hypertension, diabetes, and high-density lipoprotein (HDL) (p < 0.05). The standard deviation of all normal to normal (NN) R-R intervals (SDNN), standard deviation of 5-minute average NN intervals (SDANN), root mean square of successive NN interval differences (rMSSD), 50 ms from the preceding interval (pNN50), low-frequency/high-frequency (LF/HF), LF, premature atrial contractions (PACs), atrial tachycardia (AT), T-wave index, and ST-segment index differed significantly between the two groups. Logistic regression analysis identified rMSSD, PACs, and AT as independent predictors of AF. For each unit increase in rMSSD and PACs, the odds of developing AF increased by 1.0357 and 1.0005 times, respectively. For each unit increase in AT, the odds of developing AF decreased by 0.9976 times. The total score of the nomogram prediction model ranged from 0 to 110. CONCLUSION: The autonomic nervous system (ANS) plays a pivotal role in the occurrence and development of AF. The individualized nomogram prediction model of AF occurrence contributes to the early identification of high-risk patients with AF.