Cardiac arrhythmias are a global health burden, contributing significantly to morbidity and mortality worldwide. Despite technological advances in catheter ablation therapy, antiarrhythmic drugs (AADs) remain a cornerstone for the management of cardiac arrhythmias. Experimental and translational studies have shown that commonly used AADs exert multiple effects in the heart, the manifestation of which strongly depends on the exact experimental or clinical conditions. This diversity makes the optimal clinical application of AADs challenging. Here, we present a novel computational tool designed to facilitate a better understanding of the complex mechanisms of action of AADs (the Maastricht Antiarrhythmic Drug Evaluator, MANTA). In this tool, we integrated published computational cardiomyocyte models from different species (mouse, guinea pig, rabbit, dog, and human), regions (atrial, ventricular, and Purkinje cells) and disease conditions (atrial fibrillation- and heart failure-related remodeling). Subsequently, we investigated the effects of clinically available AADs (Vaughan-Williams Classes I, III, IV and multi-channel blockers) on action potential (AP) properties and the occurrence of proarrhythmic effects such as early afterdepolarizations. Steady-state drug effects were simulated based on a newly compiled overview of published IC50 values for each cardiac ion channel and by integrating state-dependent block of the cardiac Na+-current by Class I AADs using a Markov-model approach. Using MANTA, we demonstrated and characterized important species-, rate-, cell-type-, and disease-state-specific AAD effects, including 1) a stronger effect of Class III AADs in large mammals than in rodents; 2) a rate-dependent decrease in upstroke velocity with Class I AADs and reverse rate-dependent effects of Class III AADs on action potential duration; 3) ventricular-predominant effects of pure IKr blockers; 4) preferential reduction in atrial AP upstroke velocity with vernakalant; and 5) excessive AP prolongation with Class III AADs other than amiodarone under heart failure conditions. In conclusion, the effects of AADs are highly complex and strongly dependent on the experimental or clinical conditions. MANTA is a powerful and freely available tool reproducing a wide range of AAD characteristics that enables analyses of the underlying ionic mechanisms. Use of MANTA is expected to improve our understanding of AAD effects on cellular electrophysiology under a wide range of conditions, which may provide clinically-relevant information on the safety and efficacy of AAD treatment.

Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy.

Re-arrest during post-cardiac arrest care after the return of spontaneous circulation is not uncommon. However, little is known about the risk factors associated with re-arrest. A previous study failed to show a benefit of prophylactic antiarrhythmic drug infusion in all kinds of out-of-hospital cardiac arrest (OHCA) survivors. This study evaluated high-risk OHCA survivors who may have re-arrest with shockable rhythm during targeted temperature management (TTM). Medical records of consecutive OHCA survivors treated with TTM at four tertiary referral university hospitals in the Republic of Korea between January 2010 and December 2016 were retrospectively reviewed. Patients who did not have any shockable rhythm during cardiopulmonary resuscitation (CPR) or unknown initial rhythm were excluded. The primary outcome of interest was the recurrence of shockable cardiac arrest during TTM. There were 289 cases of initial shockable arrest rhythm and 132 cases of shockable rhythm during CPR. Of the 421 included patients, 11.4% of patients had a shockable re-arrest during TTM. Survival to discharge and good neurologic outcomes did not differ between non-shockable and shockable re-arrest patients (78.3% vs. 72.9%, p = 0.401; 53.1% vs. 54.2% p = 0.887). Initial serum magnesium level, ST segment depression or ventricular premature complex (VPC) in initial electrocardiography (ECG), prophylactic amiodarone infusion, and dopamine and norepinephrine infusion during TTM were significantly higher and more frequent in the shockable re-arrest group (all p values < 0.05). Normal ST and T wave in initial ECG was common in the non-shockable re-arrest group (p = 0.038). However, in multivariate logistic regression analysis, only VPC was an independent prognostic factor for shockable re-arrest (OR 2.806 (95% CI 1.276-6.171), p = 0.010). Initial VPC may be a prognostic risk factor for shockable re-arrest in OHCA survivors with shockable rhythm.