Chinese consensus on the use of antiarrhythmic drugs for rhythm control in atrial fibrillation / 中华内科杂志

Rhythm control is crucial part of comprehensive management of atrial fibrillation (AF). Rhythm control can reduce the burden of AF effectively, reduce symptoms, and improve the prognosis in early AF. Antiarrhythmic drugs (AADs) are the first-line treatment for rhythm-control strategies. This consensus focuses on the principle of rhythm control in AF, the characteristics of AADs, and the medication recommendations for patients in different populations suffering from AF. Hence, this consensus aims to support clinical decision-making for AF therapy.

Antiarrhythmic active components in traditional Chinese medicine acting on potassium channels / 中国中药杂志

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.

Ablation therapies for paroxysmal atrial fibrillation: A systematic review and patient-level network meta-analysis

INTRODUCTION@#Despite promising trials, catheter ablation is still regarded as an adjunct to antiarrhythmic drugs (AADs) in the treatment of paroxysmal atrial fibrillation (PAF). This study aimed to compare the effectiveness of various ablation therapies and AADs.@*METHOD@#Randomised controlled trials or propensity score-matched studies comparing atrial tachyarrhythmia recurrence among any combination of ablation modalities or AAD were retrieved. Kaplan-Meier curves and risk tables for this outcome were graphically reconstructed to extract patient-level data. Frequentist network meta-analysis (NMA) using derived hazard ratios (HRs), as well as 2 restricted mean survival time (RMST) NMAs, were conducted. Treatment strategies were ranked using P-scores.@*RESULTS@#Across 24 studies comparing 6 ablation therapies (5,132 patients), Frequentist NMA-derived HRs of atrial fibrillation recurrence compared to AAD were 0.35 (95% confidence interval [CI]=0.25-0.48) for cryoballoon ablation (CBA), 0.34 (95% CI=0.25-0.47) for radiofrequency ablation (RFA), 0.14 (95% CI=0.07-0.30) for combined CBA and RFA, 0.20 (95% CI=0.10-0.41) for hot-balloon ablation, 0.43 (95% CI=0.15-1.26) for laser-balloon ablation (LBA), and 0.33 (95% CI=0.18-0.62) for pulmonary vein ablation catheter. RMST-based NMAs similarly showed significant benefit of all ablation therapies over AAD. The combination of CBA + RFA showed promising long-term superiority over CBA and RFA, while LBA showed favourable short-term efficacy.@*CONCLUSION@#The advantage of ablation therapies over AAD in preventing atrial tachyarrhythmia recurrence suggests that ablation should be considered as the first-line treatment for PAF in patients fit for the procedure. The promising nature of several specific therapies warrants further trials to elicit their long-term efficacy and perform a cost-benefit analysis.

ablación de fibrilación auricular como tratamiento de primera línea: revisión de la literatura / Ablation as a first line treatment for atrial fibrillation: a review

RESUMEN La ablación con radiofrecuencia (RF) o con Criobalón (CRIO) en pacientes con fibrilación auricular (FA) paroxística y persistente es un tratamiento seguro y eficaz en pacientes seleccionados. Datos recientes demuestran que la ablación proporciona mejores resultados en comparación con fármacos antiarrítmicos (FAA) en el tratamiento de la FA temprana. Los estudios que comparan RF y CRIO mostraron una eficacia y seguridad comparables en el aislamiento de venas pulmonares (PVI) para pacientes con FA paroxística sintomática. OBJETIVOS: Revisar estudios clínicos que comparan el tratamiento de la FA con ablación versus FAA como terapia de primera línea en pacientes con FA sin tratamiento previo. La eficacia y la seguridad se compararán entre las dos cohortes y entre los subgrupos. MÉTODO: Se incluye un total de 6 estudios en los que participaron 1212 pacientes con FA: 609 pacientes fueron aleatorizados a ablación de FA y 603 a tratamiento farmacológico En comparación con el tratamiento con FAA, la ablación se asoció con una reducción en la recurrencia de arritmias auriculares (32,3 % frente a 53 %; riesgo relativo [RR], 0,62; IC del 95 %, 0,51-0,74; P < 0,001; I 2 = 40 %, NNT: 5). El uso de ablación también se asoció con una reducción de las arritmias auriculares sintomáticas (11,8 % frente a 26,4 %; RR, 0,44; IC del 95 %, 0,27-0,72; P = 0,001; I 2 = 54%) y hospitalización (5,6% vs 18,7%; RR, 0,32; IC 95%, 0,19-0,53; P< 0,001) sin diferencias significativas en los eventos adversos graves entre los grupos (4,2 % frente a 2,8 %; RR, 1,52; IC del 95 %, 0,81-2,85; P = 0,19). CONCLUSIÓN: En pacientes con FA paroxística, una estrategia de control precoz del ritmo cardíaco, se asocia con una mayor probabilidad de supervivencia, menos procedimientos repetidos, menos hospitalizaciones y, probablemente, una disminución en la progresión a FA persistente.

INTRODUCTION: Radiofrequency (RF) or cryoballoon (CRYO) ablation in patients with paroxysmal and persistent atrial fibrillation (AF) are safe and effective treatments in selected patients. Recent data show that ablation provides better results compared to antiarrhythmic drugs (AAD) in the treatment of early AF. Studies comparing RF and CRYO showed comparable efficacy and safety in pulmonary vein isolation (PVI) for patients with symptomatic paroxysmal AF. OBJETIVES: Review of clinical trials comparing treatment of AF with ablation versus AAD as first-line therapy in patients with AF with no previous treatment. Efficacy and safety are compared between the two cohorts and between subgroups. METHODS: A total of 6 studies involving -212 AF patients were included: 609 were randomized to AF ablation and 603 to pharmacological treatment. Ablation, compared with AAD, was associated with a reduction in recurrence of atrial arrhythmias (32.3% vs. 53%; relative risk [RR], 0.62; 95% CI, 0.51-0.74, P< 0.001, I2 = 40%, NNT: 5). The use of ablation was also associated with a reduction in symptomatic atrial arrhythmias (11.8% vs. 26.4%; RR, 0.44; 95% CI, 0.27-0.72; P= 0.001; I2 = 54%) and hospitalization (5.6% vs 18.7%; RR, 0.32; 95% CI, 0.19-0.53; P <0.001) with no significant differences in major adverse events (4.2% vs. 2.8%; RR, 1.52; 95% CI, 0.81-2.85; P=0.19). CONCLUSION: In patients with paroxysmal AF, an early cardiac rhythm control with ablation is associated with a higher probability of survival, fewer repeat procedures, fewer hospitalizations, and probably a decrease in progression to persistent AF.

Uso de la ivrabadina para el tratamiento de la taquicardia ectópica de la unión congénita / Use of ivabradine for the treatment of congenital junctional ectopic tachycardia

Resumen La taquicardia ectópica de la unión en su variante congénita es una taquiarritmia pediátrica poco frecuente, que por su naturaleza incesante y su refractariedad a los agentes farmacológicos tradicio nales lleva asociada una alta morbimortalidad. Se presentan los casos clínicos de dos pacientes pediátricos con diagnóstico de taquicardia ectópica de la unión congénita, que mostraron respuesta inadecuada a las alternativas de tratamiento habituales y que, en consecuencia, desarrollaron miocardiopatía dilatada y disfunción ventricular secundaria a la taquicardia sostenida. En ambos se utilizó ivabradina como alternativa farmacológica innovadora pare el control de ésta con excelente respuesta clínica.

Abstract The congenial form of junctional ectopic tachycardia is a rare variant of pediatric tachyarrhythmia that due to its incessant nature and its refractoriness to the traditionally used antiarrhythmic agents has a high morbimortality The clinical cases of two patients with a diagnosis of congenital junctional ectopic tachycardia with inadequate response to the regular pharmacological options, who developed dilated cardiomyopathy and ventricular dysfunc tion secondary to sustained tachycardia, are presented. In both ivrabadine, a new innovative option was used with excellent clinical response.

Fibrilação Atrial (Parte 1): Fisiopatologia, Fatores de Risco e Bases Terapêuticas / Atrial Fibrillation (Part 1): Pathophysiology, Risk Factors, and Therapeutic Basis

Resumo A fibrilação atrial é a arritmia sustentada mais comum na prática clínica com predileção pelas faixas etárias mais avançadas. Com o envelhecimento populacional, as projeções para as próximas décadas são alarmantes. Além de sua importância epidemiológica, a fibrilação atrial é destacada por suas repercussões clínicas, incluindo fenômenos tromboembólicos, hospitalizações e maior taxa de mortalidade. Seu mecanismo fisiopatológico é complexo, envolvendo uma associação de fatores hemodinâmicos, estruturais, eletrofisiológicos e autonômicos. Desde os anos 1990, o estudo Framingham em análises multivariadas já demonstrou que, além da idade, a presença de hipertensão, diabetes, insuficiência cardíaca e doença valvar é preditor independente dessa normalidade do ritmo. Entretanto, recentemente, vários outros fatores de risco estão sendo implicados no aumento do número de casos de fibrilação atrial, tais como sedentarismo, obesidade, anormalidades do sono, tabagismo e uso excessivo de álcool. Além disso, as mudanças na qualidade de vida apontam para uma redução na recorrência de fibrilação atrial, tornando-se uma nova estratégia para o tratamento de excelência dessa arritmia cardíaca. A abordagem terapêutica envolve um amplo conhecimento do estado de saúde e hábitos do paciente, e compreende quatro pilares principais: mudança de hábitos de vida e tratamento rigoroso de fatores de risco; prevenção de eventos tromboembólicos; controle da frequência; e controle do ritmo. Pela dimensão de fatores envolvidos no cuidado ao paciente portador de fibrilação atrial, ações integradas com equipes multiprofissionais estão associadas aos melhores resultados clínicos.

Abstract Atrial fibrillation is the most common sustained arrhythmia in clinical practice, with a preference for older age groups. Considering population ageing, the projections for the next decades are alarming. In addition to its epidemiological importance, atrial fibrillation is evidenced by its clinical repercussions, including thromboembolic phenomena, hospitalizations, and a higher mortality rate. Its pathophysiological mechanism is complex and involves an association of hemodynamic, structural, electrophysiological, and autonomic factors. Since the 1990s, the Framingham study of multivariate analyses has demonstrated that hypertension, diabetes, heart failure, and valvular disease are independent predictors of this rhythm abnormality along with age. However, various other risk factors have been recently implicated in an increase of atrial fibrillation cases, such as sedentary behavior, obesity, sleep disorders, tobacco use, and excessive alcohol use. Moreover, changes in quality of life indicate a reduction in atrial fibrillation recurrence, thus representing a new strategy for excellence in the treatment of this cardiac arrhythmia. Therapeutic management involves a broad knowledge of the patient's health state and habits, comprehending 4 main pillars: lifestyle changes and rigorous treatment of risk factors; prevention of thromboembolic events; rate control; and rhythm control. Due to the dimension of factors involved in the care of patients with atrial fibrillation, integrated actions performed by interprofessional teams are associated with the best clinical results.

Cardiomiopatia arritmogênica do ventrículo direito em maratonista: relato de caso / Arrhythmogenic right ventricular cardiomyopathy in marathon runners: case report

A cardiomiopatia arritmogênica do ventrículo direito é uma desordem hereditária caracterizada pela substituição fibrogordurosa do músculo cardíaco. O manejo clínico busca reduzir os riscos de morte súbita e melhorar a qualidade de vida, aliviando os sintomas arrítmicos e de insuficiência cardíaca. O ecocardiograma é o exame inicial para a investigação da cardiomiopatia arritmogênica do ventrículo direito, podendo apresentar dilatação das câmaras direitas e disfunção sistólica do ventrículo direito. Este relato chama atenção por envolver o diagnóstico de cardiomiopatia arritmogênica do ventrículo direito em paciente atleta. Mulher, 47 anos, maratonista, sem história familiar de morte súbita cardíaca, deu entrada na emergência com palpitação associada à pré-síncope. O eletrocardiograma da admissão mostrava taquicardia ventricular. O ecocardiograma revelou aumento de câmaras cardíacas direitas e disfunção sistólica do ventrículo direito. O cateterismo cardíaco não evidenciou doença coronária obstrutiva. A paciente foi orientada acerca da necessidade de suspensão de atividades físicas, porém, 3 meses depois, foi readmitida com instabilidade hemodinâmica por nova taquicardia ventricular, tendo sido cardiovertida. Realizou ressonância cardíaca, que evidenciou áreas de discinesia e formação de microaneurismas em ventrículo direito. Foi diagnosticada com cardiomiopatia arritmogênica do ventrículo direito, tendo sido com cardioversor desfibrilador implantável, amiodarona e betabloqueador. A diferenciação entre a cardiomiopatia arritmogênica do ventrículo direito e o coração do atleta representa um desafio, devido à sobreposição de alterações estruturais que coexistem nessas entidades, daí a importância da análise integrada de fatores clínicos, eletrocardiográficos e morfofuncionais.(AU)

Ações Transmurais Inotrópicas e Antiarrítmicas da Ranolazina em um Modelo Celular da Síndrome do QT Longo Tipo 3 / Inotropic and Antiarrhythmic Transmural Actions of Ranolazine in a Cellular Model of Type 3 Long QT Syndrome

Resumo A Ranolazina (RANO), conhecida na clínica como Ranexa, é um fármaco que previne a arritmia cardíaca através da inibição da corrente de sódio tardia (INaT). Um gradiente de voltagem transmural do canal Nav1.5 encontra-se na parede ventricular esquerda do coração. Assim, investigamos os efeitos da RANO em cardiomiócitos saudáveis e em modelo celular da Síndrome do QT longo tipo 3 (SQTL tipo 3). Usamos células isoladas do endocárdio (ENDO) e do epicárdio (EPI) e um software de medição com detecção de bordas por vídeo e microscopia de fluorescência para monitorar os transientes de cálcio. A RANO (0,1, 1, 10 e 30 uM, a 25OC) em uma série de frequências de estimulação teve impacto pouco significativo sobre ambos os tipos de células, mas a RANO (30uM) a 35OC minimizou o encurtamento dos sarcômeros em ~21% para células do endocárdio. Em seguida, para simular a SQTL tipo 3, as células do ENDO e EPI foram expostas à toxina ATX-II da anêmona do mar, que aumenta a INaT. As arritmias celulares induzidas por ATX-II foram suprimidas com o uso da RANO (30 µM) a 35OC. Com base nesses resultados, podemos concluir que a RANO tem um impacto pouco significativo sobre o encurtamento dos sarcômeros de células saudáveis do ENDO e EPI. Além disso, ela suprime as arritmias induzidas por INaT para níveis semelhantes nas células do ENDO e EPI.

Abstract Ranolazine (RANO) prevents cardiac arrhythmia by blocking the late sodium current (INaL). A transmural gradient of Nav1.5 is found in the left ventricular wall of the heart. Thus, we investigated the effects of RANO in healthy cardiomyocytes and in a cellular model of type 3 long QT syndrome (LQT3). We used isolated endocardium (ENDO) and epicardium (EPI) cells and a video edge detection system and fluorescence microscopy to monitor calcium transients. RANO (0.1, 1, 10 and 30 uM, at 25oC) at a range of pacing frequencies showed a minor impact on both cell types, but RANO at 30uM and 35oC for ENDO cells attenuated sarcomere shortening by~21%. Next, to mimic LQT3, we exposed ENDO and EPI cells to anemone toxin II (ATX-II), which augments INaL. Cellular arrhythmias induced by ATX-II were abrogated by RANO (30 µM) at 35oC. Based on our results we can conclude that RANO has a minor impact on sarcomere shortening of healthy ENDO and EPI cells and it abrogates arrhythmias induced by INaLto a similar level in ENDO and EPI cells.

Reconhecimento da paralisia periódica hipocalêmica tireotóxica na emergência: relato de caso e revisão da literatura / Recognizing thyrotoxic hypokalemic periodic paralysis on emergency settings: a case report and literature revie

A paralisia periódica hipocalêmica tireotóxica é uma complicação inusitada do hipertireoidismo, porém é considerada urgência endocrinológica e ainda frequentemente subdiagnosticada. Sua apresentação clínica consiste na tríade de défice de potássio, tireotoxicose e fraqueza muscular ­ sendo esse último sintoma comum em diversas patologias. Realizamos uma revisão bibliográfica e destacamos, por meio do relato de caso, a importância do diagnóstico precoce dessa doença, possibilitando uma evolução favorável ao paciente, independente de sua etnia, sexo ou região geográfica. Atentamos ainda ao tratamento da doença, que, apesar de sua simplicidade, acarreta muitos equívocos.

The thyrotoxic hypokalemic periodic paralysis is a rare complication of hyperthyroidism, but is considered an endocrinological urgency, and yet frequently underdiagnosed. Its clinical presentation consists of potassium deficit, thyrotoxicosis, and muscular weakness, with the latter symptom being very common in several pathologies. We performed a bibliographic review and highlight, through a case report, the importance of the early diagnosis of this disease to allow favorable progression to the patient, regardless of ethnicity, sex, or geographical region. We also reinforce the importance of the disease treatment which, despite its simplicity, leads to many mistakes.

Association between use of amiodarone for non-valvular atrial fibrillation and patient survival: from the prospective China Atrial Fibrillation Registry / 中华医学杂志(英文版)

BACKGROUND@#Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.@*METHODS@#Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.@*RESULTS@#Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.@*CONCLUSIONS@#Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Current status of the clinical practice and analysis on the ratioanl prescription of antiarrhythmic drugs in Chinese patients with atrial fibrillation: Results from the Chinese Atrial Fibrillation Registry (CAFR) trial / 中华心血管病杂志

Objective: To explore the practice patterns and the related factors of oral antiarrhythmic drug (AAD) treatment in Chinese patients with atrial fibrillation (AF), and to evaluate the compliance of AAD application to atrial fibrillation management guidelines. Methods: From August 2011 to August 2016, medical records from 18 014 patients with AF were analyzed based on data from the Chinese Atrial Fibrillation Registry trial. Patients were divided into AAD group (7 788 cases, 43.23%) and non-AAD group (10 226 cases, 56.77%) according to whether AAD was used at baseline or at the time of first use during follow-up. Amiodarone (4 129 cases, 53.02%) and propafenone (3 211 cases, 41.23%) were the mostly prescribed AAD and subgroup analysis was performed accordingly. Medical records were analyzed by random forest regression to evaluate the use of AAD and related factors in patients with AF, and the rationality of AAD was analyzed according to the guidelines for the management of atrial fibrillation. Result: A total of 18 014 patients were included in this study, of which 60.48% (10 895/18 014) were male patients, 22.65% (4 081/18 014) were elderly patients(≥75 years old), there were 7 788 patients (43.23%) in AAD group, and 10 226 patients(56.77%) in non-AAD group. Compared with the non-AAD group, the elderly patients (≥75 years old, 13.74%(1 070/7 788) vs. 29.44%(3 011/10 226)), persistent AF (28.95% (2 250/7 788) 45.80% (4 683/10 226)), heart failure(8.29% (646/7 788) vs. 21.95% (2 245/10 226)), stroke and (or) TIA(12.15% (946/7 788) vs. 19.95% (2 040/10 226)), renal dysfunction(16.36%(1 274/7 788) vs. 29.37% (3 003/10 226)), and high thromboembolism risk(60.17% (4 748/7 788) vs. 76.40% (7 813/10 226)) were less prevalent in the AAD subgroup (P<0.001). Multivariate analysis showed that patients in tertiary hospitals (OR=3.72, 95%CI 3.17-4.37) were more likely to use AAD, elderly patients (≥75 years old, OR=0.47, 95%CI 0.39-0.55), persistent atrial fibrillation (OR=0.66, 95%CI 0.60-0.72), and patients with heart failure (OR=0.54, 95%CI 0.47-0.63), stroke and (or) TIA (OR=0.77, 95%CI 0.68-0.87), renal dysfunction (OR=0.75, 95%CI 0.59-0.95) and high thromboembolism risk(OR=0.7, 95%CI 0.58-0.84) were more likely not to use AAD(P<0.05). In the AAD group, amiodarone and propafenone were the most commonly used AAD, accounting for 53.02% (4 129/7 788) and 41.23% (3 211/7 788), respectively. Multivariate analysis showed that patients with persistent atrial fibrillation (OR=4.57, 95%CI 3.94-5.29) and coronary heart disease (OR=4.14, 95%CI 3.03-5.64), heart failure (OR=2.07, 95%CI 1.48-2.89), non-ischemic cardiomyopathy (OR=4.84, 95%CI 2.41-9.73) were more likely to use amiodarone, and those with normal left ventricular ejection fraction (OR=0.31, 95%CI 0.15-0.65) and low thromboembolism risk (OR=0.78, 95%CI 0.63-0.97) were more likely to use propafenone (P<0.001). The overall incidence of AAD treatment, which was not indicated by the guidelines was 6.5% (480/7 340); 5.1% (212/4 129) in the amiodarone group and 8.3% (268/3 211) in the propafenone group, respectively. Compared with the rational AAD use group, the proportion of irrational drug use was higher in the elderly (≥75 years old) (20.4% (98/480) vs. 12.9% (887/6 860)), patients of high thromboembolism risk (77.1% (379/480) vs. 59.0% (4 047/6 860)), and in non-tertiary hospitals (7.1% (34/480) vs. 3.3% (299/6 860)), but lower in men(50.8% (244/480) vs. 64.5% (4 427/6 860)), P<0.001. Conclusions: The patients with paroxysmal atrial fibrillation, who were treated with AAD, were mostly patients with fewer complications, and the patients who were treated with amiodarone were mostly patients with persistent atrial fibrillation, patients were more likely to complicate with organic heart disease. The incidence of AAD that do not comply with the guidelines was low, and it was more common in non-tertiary hospitals and the elder patients with high thromboembolism risk.

Association between duration of digoxin use and adverse outcomes among Chinese patients with atrial fibrillation / 中华心血管病杂志

Objective: We aimed to explore the impact of digoxin use on outcomes in Chinese patients with atrial fibrillation (AF). Methods: We used the dataset from the Chinese Atrial Fibrillation Registry, a prospective, multicenter, hospital-based registry study. According to the inclusion and exclusion criteria, 10 472 eligible patients enrolled from August 2011 to December 2016 were included in this ancillary study. The patients were classified into three groups according to the status of digoxin use at study enrollment, patients already receiving digoxin before registry were represented as continuous group, patients initiated on digoxin for the first time were represented as newly group, and patients without digoxin prescription at enrollment were represented as control group. Patients were followed by telephone or outpatient service every 6 months. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to investigate the association of digoxin use with adverse outcomes (all-cause death, cardiovascular death and cardiovascular hospitalization). Results: In the overall study population, men accounted for 42.8%, and the average age was (66.9±11.8) years. There were 777（7.42%）patients in continuous group, 375 (3.58%) patients in newly group, and 9 320 (89.00%) patients in control group. Compared with the control group, the patients in the newly group and the continuous group were older, had faster heart rate, lower estimated glomerular filtration rate, higher proportion of persistent atrial fibrillation, heart failure, renal insufficiency, diabetes mellitus, ischemic stroke, coronary heart disease, vascular disease and bleeding history. At the same time, the patients in the newly group and the continuous group were treated more often with anticoagulants, antiplatelet drugs, ACE inhibitors or angiotensin receptor blockers, beta-receptor blockers while the proportion of antiarrhythmic drugs was lower as compared to control group (P<0.05). During a median follow-up of 36 months (interquartile range: 18-48 month), risk of all-cause mortality was significantly higher in newly group compared to control group (7.3% vs. 4.7%, P<0.05), the rates of all-cause mortality, cardiovascular death and cardiovascular hospitalization were all higher in continuous group than in control group (8.0% vs. 4.7%; 4.7% vs. 3.0%; 16.7% vs. 11.8%; P all<0.05). After adjustment for age, male, body mass index, blood pressure, heart rate, renal function, AF type, history of stroke, heart failure, diabetes, coronary artery disease and other drugs treatment, the association between newly group and adverse outcomes was not significant, however, digoxin use was associated with increased all-cause mortality (HR 1.26; 95%CI 1.04-1.56; P=0.019), cardiovascular death (HR 1.38; 95%CI 1.08-1.77, P =0.01), and cardiovascular hospitalization (HR 1.10; 95%CI 1.06-1.52, P=0.02) in continuous group. Conclusion: Continuous digoxin use is associated with a significant increase in adverse outcomes among Chinese patients with atrial fibrillation.

Bradycardic and Antiarrhythmic Effects of the D-Limonene in Rats / Efeitos Bradicárdicos e Antiarrítmicos do D-Limoneno em Ratos

Abstract Background: D-limonene (DL) is a monoterpene and is the major component in the essential oil of citrus fruit. It presents antihyperglycemic and vasodilatation activities. Objectives: This study evaluated the cardiovascular effects and potential antiarrhythmic of DL in rats. Methods: Hemodynamic and electrocardiographic (ECG) parameters were measured in male Wistar rats, which under anesthesia had been cannulated in the abdominal aorta and lower vena cava and had electrodes subcutaneously implanted. In the in vitro approach, the heart was removed and perfused using the Langendorff technique. The significance level adopted was 5% (p < 0.05). Results: DL, in doses of 10, 20, and 40 mg/kg (i.v), produced intense and persistent bradycardia associated with hypotension. Bradycardia with prolonged QTc was observed in the ECG in vivo recording. In the in vivo model of arrhythmia induced by Bay K8644, DL (10 mg/kg) decreased the arrhythmia score from 15.33 ± 3.52 to 4.0 ± 2.64 u.a (p < 0.05, n = 4). In isolated perfused hearts, DL (10-3 M) promoted significant reductions in heart rate (from 228.6 ± 8.5 ms to 196.0 ± 9.3 bpm; p < 0.05) and left ventricular development pressure (from 25.2 ± 3.4 to 5.9 ± 1.8 mmHg; n = 5, p < 0.05). Conclusions: DL produces bradycardia and antiarrhythmic activity in rat heart.

Resumo Fundamento: O D-limoneno (DL) é um monoterpeno e o principal componente do óleo essencial de frutas cítricas. Ele apresenta atividades anti-hiperglicêmicas e vasodilatadoras. Objetivos: Este estudo avaliou os efeitos cardiovasculares e antiarrítmicos potenciais do DL em ratos. Métodos: Os parâmetros hemodinâmicos e eletrocardiográficos (ECG) foram mensurados em ratos Wistar machos que, sob anestesia, tiveram a aorta abdominal e a veia cava inferior canuladas e receberam eletrodos implantados subcutaneamente. Na abordagem in vitro, o coração foi removido e perfundido utilizando a técnica de Langendorff. O nível de significância adotado foi de 5% (p < 0,05). Resultados: DL, nas doses de 10, 20 e 40 mg/kg (i.v), produziu bradicardia intensa e persistente associada à hipotensão. A bradicardia com QTc prolongado foi observada no registro in vivo do ECG. No modelo in vivo de arritmia induzida por Bay K8644, DL (10 mg / kg) houve diminuição do escore da arritmia de 15,33 ± 3,52 para 4,0 ± 2,64 u.a (p < 0,05, n = 4). Em corações perfundidos isolados, o DL (10-3 M) promoveu reduções significativas na frequência cardíaca (de 228,6 ± 8,5 ms para 196,0 ± 9,3 bpm; p < 0,05) e na pressão desenvolvida do ventrículo esquerdo (de 25,2 ± 3,4 para 5,9 ± 1,8 mmHg; n = 5, p < 0,05). Conclusões: O DL produz bradicardia e atividade antiarrítmica no coração de ratos.

Evaluación diagnóstica y manejo terapéutico farmacológico en pacientes con fibrilación auricular / Diagnostic evaluation and pharmacological therapeutic management in patients with atrial fibrillation

La fibrilación auricular (FA) es la arritmia sostenida más frecuente que puede presentarse en una amplia variedad de condiciones clínicas. A pesar de los progresos en el tratamiento de los pacientes con FA, esta arritmia sigue siendo una de las más importantes causas de accidente cerebrovascular, insuficiencia cardiaca, muerte súbita y morbilidad cardiovascular en todo el mundo. El objetivo del tratamiento con fármacos antiarrítmicos es mejorar los síntomas relacionados con la FA, y buscar un equilibrio entre la carga sintomática, la posibilidad de reacciones farmacológicas adversas y las preferencias del paciente. El control de la frecuencia cardiaca a corto y largo plazo se puede lograr con bloqueadores beta, digoxina, bloqueadores de los canales del calcio o tratamiento combinado. Si bien otros fármacos antiarrítmicos de clase III también tienen un efecto limitador de la frecuencia, solo deben emplearse para el control del ritmo cardiaco. Restaurar y mantener el ritmo sinusal también es una parte integral del tratamiento de la FA. Los fármacos antiarrítmicos de clase III duplican la tasa de pacientes en ritmo sinusal. El tratamiento para el control del ritmo está indicado para mejorar los síntomas de los pacientes con FA que siguen sintomáticos a pesar del tratamiento adecuado para el control de la frecuencia cardiaca. La combinación de antiarrítmicos que prolongan el intervalo QT no se debe emplear para el control del ritmo cardiaco en la FA(AU)

Atrial fibrillation (AF) is the most frequent sustained arrhythmia that can occur in a wide variety of clinical conditions. Despite progress in the treatment of patients with AF, this arrhythmia remains one of the most important causes of stroke, heart failure, sudden death and cardiovascular morbidity worldwide. The aim of treatment with antiarrhythmic drugs is to improve the symptoms related to AF, and to look for a balance between the symptomatic load, the possibility of adverse pharmacological reactions and the patient preferences. The short and long term heart rate control can be achieved with beta blockers, digoxin, calcium channel blockers or combination therapy. Although other class III antiarrhythmic drugs also have a frequency-limiting effect, they should only be used for the control of heart rhythm. Restoring and maintaining sinus rhythm is also an integral part of the treatment of AF. Class III antiarrhythmic drugs double the rate of patients who maintain their sinus rhythm. Treatment for rhythm control is indicated to improve the symptoms of patients with AF who remain symptomatic despite adequate treatment for heart rate control. The combination of antiarrhythmics that prolong the QT interval should not be used to control heart rhythm in AF(AU)

Prevenção da fibrilação atrial além do antiarrítmico - abordagem multifatorial / Atrial fibrillation prevention beyond antiarrhythmic drug therapy - multifactorial approach

A prevenção da fibrilação atrial (FA) envolve uma abordagem individualizada, multidisciplinar e integrada do paciente, que vai além da arritmia per se. Por se tratar de uma arritmia multifatorial e com fisiopatologia complexa, os pacientes com FA devem ser avaliados em sua integralidade, que inclui aspectos eletrocardiográficos, eletrofisiológicos, medidas comportamentais e otimização de tratamento de doenças crônicas, como hipertensão arterial e insuficiência cardíaca. Neste artigo descrevere-mos as principais intervenções estudadas na literatura com benefício na prevenção da fibrilação atrial

AF (atrial fibrillation) prevention involves an ndividualized, multidisciplinary and integrated approach taken by the patient, which emcompasses more than just arrhy- thmima per se. Because it is a multifactorial arrhythmia with complex physiopathology, patients with AF should undergo a complete assessment, including electrocardiographic and electrophysiological aspects, behavioral measures and optimization of the treatment of chronic diseases, such as hypertension and heart failure. In this article we describe the main interventions studied in literature that are beneficial in the prevention of atrial fibrillation

Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil / Dabigatrana e varfarina em pacientes com fibrilação atrial não valvar ou flutter em ambulatório especializado no Brasil

ABSTRACT Objectives: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. Methods: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. Results: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. Conclusion: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

RESUMO Objetivos: Comparar varfarina e dabigatrana para prevenção de eventos tromboembólicos em pacientes com fibrilação atrial não valvar ou flutter (FA). Métodos: Coorte retrospectiva de pacientes com FA em uso de varfarina ou dabigatrana em serviço especializado no Brasil. Resultados: Foram avaliados 112 pacientes (média idade 65,5), com 55,3% no grupo varfarina. A mediana do tempo de seguimento foi de 1,9 anos para o grupo varfarina e 1,6 para dabigatrana (p = 0,167). No grupo varfarina houve maior mediana de consultas médicas (CM) por ano (8,3[6,8-10,4] vs. 3,1[2,3-4,2], p < 0,001), com frequência de sangramento menor quatro vezes maior (17,7% vs. 4,0%, p = 0,035). Nos pacientes com acidente vascular cerebral isquêmico prévio, o grupo varfarina teve 2,6 vezes mais CM por pessoas-ano de seguimento (8,5 vs. 3,3). Não houve sangramento maior ou eventos embólicos no período de seguimento. Conclusão: Pacientes em uso de dabigatrana tiveram menor número de sangramento menor e CM que aqueles em uso de varfarina, sem aumentar eventos embólicos ou sangramentos maiores.

Prevenção secundária de morte súbita cardíaca na cardiopatia chagásica crônica e função ventricular quase-normal / Secondary prevention of sudden cardiac death in chronic chagasic cardiopathy and near-normal ventricular function

Introdução: A cardiopatia chagásica crônica (CCC) engloba complexo espectro de apresentações, não sendo incomuns episódios de morte arrítmica em portadores de função ventricular esquerda preservada (FVEP) ou quase normal (FVEQN). Métodos: Avaliação retrospectiva de 7 portadores de CCC por 4 anos, com FVEP, submetidos a implante de cardiodesfibrilador implantável (CDI) devido taquicardia ou fibrilação ventricular (TV/FV). Foram realizadas avaliações clínica, estrutural e eletrocardiográfica. Resultados: Idade média: 57,5±4,45 anos e 71,4% do sexo masculino. Função ventricular esquerda (FVE) inicial foi de 56,14%±4,45, com alterações contrácteis em 100% e hipocinesia inferior em 85,7%. Classe funcional I: 100% sem modificações ao seguimento. Escore de Rassi avaliado previamente ao evento foi de 4,85±0,89. Síncope constituiu a apresentação inicial em 100%, média de 2 episódios por paciente e intervalo de 4 semanas entre os mesmos. Houve alterações em 85,71% dos eletrocardiogramas, sendo bloqueio de ramo direito a principal. TV sustentada foi encontrada em 100%; sítio epicárdico em 71,42% e saída anterolateral do ventrículo esquerdo em 57,14%. A FVE sequencial foi de 54%±3,31; sem alterações contráteis novas. Amiodarona e betabloqueadores foram os fármacos utilizados. Terapias apropriadas aconteceram em 100%; média de 2,1 choques por paciente, com 52,63% dos registros nos primeiros 14 meses. Não foram evidenciados óbitos, terapias inapropriadas ou tempestade elétrica. Conclusão: O elevado número de terapias corrobora o risco arrítmico desta população, ratifica a importância do dispositivo e alerta para a eficácia da terapia clínica. Síncope pode estar associada a maior risco de eventos arrítmicos na CCC

Introduction: Chronic chagasic cardiopathy (CCC) encompasses a complex spectrum of presentations, and episodes of arrhythmic death in patients with preserved left ventricular (PLVF) or near normal (VFNN) are not uncommon. Methods: Retrospective evaluation of 7 patients with PLVF, submitted for implantation of implantable cardioverter defibrillator (ICD) due to tachycardia or ventricular fibrillation (VT / VF). Clinical, structural and electrocardiographic evaluations were performed. Results: Mean age was 57.5±4.45 years. Male sex comprised 71.4%. Left ventricular function (LVF) was 56.14%±4.45 with contractile changes in 100% and lower hypokinesia in 85.7%. Functional class I was evidenced in 100% without changes in follow-up. The Rassi score evaluated before the event was 4.85±0.89. Syncope was the initial presentation in 100%, average of 2 episodes per patient and interval of 4 weeks between them. Electrocardiogram showed alterations in 85.71% being right bundle branch block. Sustained VT was evidenced in 100%; epicardial site in 71.42% and left ventricular anterolateral outlet in 57.14%. The sequential LVF was 54%±3.31; without new contractile changes. Amiodarone and beta-blockers were the drugs used. Appropriate therapies occurred in 100%; average of 2.1 shocks per patient with 52.63% of the records in the first 14 months. There were no deaths, inappropriate therapies or electrical storm. Conclusion: The high number of therapies corroborates the arrhythmic risk of this population, ratifies the importance of the device and disputes the effectiveness of clinical therapy. Syncope may be associated with an increased risk of arrhythmic events in CCC