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.

Interpretation of 2018 American Heart Association Focused Update on Pediatric Advanced Life Support:An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care / 中国实用儿科杂志

In November 2018,the American Heart Association(AHA) updated Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. The new guideline provided the evidence review and treatment recommendation for antiarrhythmic drug therapy in pediatric shock-refractory ventricular fibrillation/pulseless ventricular tachycardia cardiac arrest. The update was carried out by the Pediatrics Working Group of the International Liaison Committee on Resuscitation(ILCOR)for ongoing clinical evidence review. The update continues with the view of 2015's edition that either lidocaine or amiodarone may be used to treat pediatric patients with shock-refractory ventricular fibrillation or pulseless ventricular tachycardia. The flow chart of cardiac arrest for pediatric advanced life support was slightly adjusted.

Introduction of ICH E14 Clinical Evaluation of QT Prolongation Caused by Non-Antiarrhythmic Drug: Q&As (R3) / 药物评价研究

To detect and determine the QT interval prolongation caused by non antiarrhythmic drugs,ICH released the E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs and released E14's questions and answers (ICH E14 Q&As) in 2008 which explained some specific questions.Subsequently,This Q&As were revised third times and in June 2017 forwarded by FDA.The number of questions and answers in the revised edition doubled compared with the original.This article introduces the details of this revised edition,and hopes to be helpful to the research and supervision in China.

The Effects of a Bidirectional Cavo-Tricuspid Isthmus Block in Persistent Atrial Fibrillation

PURPOSE: Hybrid therapy with catheter ablation of the cavo-tricuspid isthmus (CTI) and continuation of anti-arrhythmic drugs (AAD), or electrical cardioversion with AADs might be alternative treatments for patients with persistent atrial fibrillation (AF). The goal of study was to assess the long term success rate of hybrid therapy for persistent AF compared to antiarrhythmic medication therapy after electrical cardioversion and identify the independent risk factors associated with recurrence after hybrid therapy. MATERIALS AND METHODS: A total of 32 patients with persistent AF who developed atrial flutter after the administration of a class Ic or III anti-arrhythmic drug were enrolled. This group was compared with a group (33 patients) who underwent cardioversion and received direct current cardioversion with AADs. Baseline data were collected, and electrocardiogram and symptom driven Holter monitoring were performed every 2-4 months. RESULTS: There was no significant difference in the baseline characteristics between the groups. The 12 month atrial arrhythmia free survival was better in the hybrid group, 49.0% vs. 33.1%, p=0.048. However, during a mean 55.7+/-43.0 months of follow up, the improved survival rate regressed (p=0.25). A larger left atrium size was an independent risk factor for the recurrence of AF after adjusting for confounding factors. CONCLUSION: Despite favorable outcome during 12 month, the CTI block with AADs showed outcomes similar to AAD therapy after electrical cardioversion over a 12 month follow up period. Minimal substrate modification with AADs might be an alternative treatment for persistent AF with minimal atrial remodeling.

How frequently should a patient taking amiodarone be screened for thyroid dysfunction?

Amiodarone-induced thyroid dysfunction (AITD) is a common complication of amiodarone therapy and its prevalence varies according to iodine intake, subclinical thyroid disorders and the definition of AITD. There is no consensus about the frequency of screening for this condition. We evaluated 121 patients on chronic regular intake of amiodarone (mean intake = 248.5 ± 89 mg; duration of treatment = 5.3 ± 3.9 years, range = 0.57-17 years) and with stable baseline cardiac condition. Those with noAITD were followed up for a median period of 3.2 years (range: 0.6-6.7) and the incidence rate of AITD, defined by clinical and laboratorial findings as proposed by international guidelines, was obtained (62.8 per 1000 patients/year). We applied the Coxproportional hazard model to adjust for potential confounding factors and used sensitivity analysis to identify the best screening time for follow-up. We detected thyroid dysfunction in 59 (48.7%) of the 121 patients, amiodarone-induced hypothyroidism in50 (41.3%) and hyperthyroidism in 9 (7.5%). Compared with patients without AITD, there was no difference regarding dosage or duration of therapy, heart rhythm disorder or baseline cardiac condition. During the follow-up of the 62 patients without AITD at baseline evaluation, 11 developed AITD (interquartile range, IR: 62.8 (95%CI: 31.3-112.3) cases per 1000 patients/year), 9 of them with hypothyroidism - IR: 11.4 (95%CI: 1.38-41.2), and 2 hyperthyroidism - IR: 51.3 (95%CI: 23.4-97.5). Age, gender,dose, and duration of treatment were not significant after adjustment. During the first 6 months of follow-up the incidence rate for AITD was 39.3 (9.2-61.9) cases per 1000 patients/year. These data show that AITD is quite common, and support the need for screening at 6-month intervals, unless clinical follow-up dictates otherwise or further information regarding the prognosis of untreated subclinical AITD is available.

Antiarrhythmic Drug

The pharmacological therapy of cardiac arrhythmias is still challenging. As is well known, antiarrhythmic drugs have a narrow therapeutic-toxic window and can induce lethal proarrhythmia (antiarrhythmic drug-induced arrhythmia). The harmful effect of antiarrhythmic drug was proven by CAST and so many clinical trials. Thus we need strict indications for prescription and objective parameters for monitoring of the drug action and side effects. The cardiac arrhythmias are classified as ectopic beats, bradyarrhythmia, and tachyarrhythmia. The main target of antiarrhythmic drugs is tachyarrhythmia. The clinical role of antiarrhythmic drugs is the acute conversion of arrhythmia to sinus rhythm and the chronic suppression/prevention of tachycardia. The cardiac arrhythmia (arrhythmogenesis) occurs in harmony of 3 components, namely, substrate, precipitating (modulating) factors, and trigger. The acute modification of arrhythmogenic environment by drug may be efficient, but the chronic suppression of arrhythmia only by the drug may not be complete. Recently, the clinical role of chronic drug therapy is replaced by RFCA (in patients with SVT except atrial fibrillation) and ICD (VT/SCD). The antiarrhythmic drugs are usually classified into Class I (sodium channel blocker), Class II (beta-blocker), Class III (potassium channel blocker), Class IV (calcium channel blocker), and others (digoxin and adenosine), according to Vaughn-Williams suggestion. Nowadays, the clinical electrophysiologist reclassified the agents into calcium channel-dependent drug (Class II, IV, digoxin, and adenosine) and sodium/potassium channel-dependent drug (Class I and III). The drug is effective only when the concentration in blood or tissue is sufficient to modify the arrhythmogenic substrate. We need to know the pharmacokinetic and pharmacodynamic properties of antiarrhythmic drugs exactly. We can expect the blood concentration of a drug if we know the elimination half-life and the dosing schedule of the drug because most drugs (including antiarrhythmic agents) have the first-order (elimination) kinetic. For a new steady-state of drug concentration, we should wait for 3 to 4 times of the half-life after changing the dosage (prescription). Finally, the consideration and management of the underlying heart disease and precipitating/modulating factors are needed for the effective antiarrhythmic drug therapy.