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Aim.We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 micrograms/kg) intravenously.Results.Conversion of AFib and AFl into sinus rhythm was achieved in 53,6% after administration of 10 mcg/kg dose, in 73% after administration of 20 mcg/kg dose and in 91,6% after administration of Refralon in dose up to 30 mcg/kg. No mortality and no major adverse cardiac events registered in our study. Asystole >3.0 sec observed in 5% (35 of 727) of patients): in 5% (24 of 451) of patients enrolled in primary center and in 4% (11 of 276) of patients enrolled in other hospitals; 95% confidence interval (CI) [-0.09; 0.113]. Asystole> 5.0 s observed in 1.7% of patients who further required non-urgent implantation of a permanent pacemaker due to manifestations of sinus node dysfunction. Cardiac conduction disturbances (exclusively sinus bradycardia) were registered in 7% (53 of 727) patients: in 8% (37 of 451) of patients enrolled in primary center and in 6% (17 of 276) of patients enrolled in other hospitals; 95% CI: [-0.1; 0.15]. Only 0.14% of patients had symptomatic sinus bradycardia that resolved after atropine injection. Ventricular arrhythmias (exclusively Torsade de pointes tachycardia in excessive QT interval prolongation) were registered in 1.7% (12 of 727) patients: in 2% (9 of 451) of patients in primary center and in 1% (3 of 276) of patients of other hospitals; 95% CI: [-0.06; 0.08]. QTc interval prolongation to values >500 ms documented in 19% (138 of 727) of patients: in 21% (95 of 451) of patients in primary center and in 16% (43 of 276) of patients in other hospitals; 95% CI: [-0.13; 0.24].Conclusion:In post-registration multicenter trial Refralon demonstrated good safety profile in conversion of AFib and AFl. Potential risk of TdP tachycardia mandates precautions with the use of the drug. In other hospitals Refralon did not demonstrate lower safety than in primary medical center.

We present two cases of successful pharmacological cardioversion using antiarrhythmic drug refralon in patients with persistent atrial fibrillation after pulmonary vein cryoablation and ineffective electrical cardioversion. These clinical cases represent the first experience of successful use of refralon in patients who underwent cryoablation.

Aim.We aimed to assess safety and effectiveness of class III antiarrhythmic drug Refralon for conversion of atrial fibrillation (AFib) and flutter (AFl) in post-registration trial and to compare data of primary center (National medical research center in cardiology) with data of other hospitals.Material and Methods. We performed retrospective cohort study in 727 patients (451 enrolled in primary center and 276 enrolled in other hospitals) admitted between June 24, 2014 and June 24, 2019. Refralon was administered for conversion of AFib and AFl in intense care units in escalating doses (10-30 mcg/kg) intravenously. Primary endpoints: restoration of sinus rhythm (SR) within 24 hours after the start of infusion of the study drug in a total dose of up to 30 pg / kg; registration of SR on an electrocardiogram (ECG) 24 hours after the start of the study drug infusion. Secondary endpoints: restoration of SR after infusion of the study drug at a dose of 10 pg / kg; restoration of SR after infusion of the studied drug in a total dose of up to 20 pg / kg; no recurrence of AFib/AFl after restoration of AFl within 24 hours of observation after the start of the study drug infusion.Results.Conversion to SR was achieved in 53,6% (391 of 727) after administration of 10 mcg/kg dose, in 73% (531 of 727) after administration of 20 mcg/kg dose and in 91,6% (666 of 727) after administration in dose up to 30 mcg/kg. SR was restored in 89% (402 of 451) of patients in primary center, and in 96% (264 of 276) of patients in other hospitals; 95% confidence interval (CI): (-0,1;-0,03). SR preserved 24 hours after conversion in 98% (650 of 666) successfully converted patients. In primary center SR preserved in 97% (390 of 402) successfully converted patients. In other hospitals - in 98,5% (260 of 264) successfully converted patients. 95 CI: (-0,09;0,06).Conclusion:In post-registration multicenter trial Refralon demonstrated high effectiveness in conversion of AFib and AFl to SR. In other hospitals Refralon did not demonstrate lower effectiveness than in primary medical center.

The possibility to identify potentially life-threatening ventricular arrhythmias by analysis of standard electrocardiography (ECG) parameters without the use of sophisticated and expensive diagnostic techniques, such as electrophysiological heart studies, has been an important achievement of the last decades. Current differential diagnostic methods for wide QRS complex tachycardias can be categorized into 4 groups: 1) identification the ECG signs diagnostic of ventricular tachycardia, such as atrioventricular dissociation and/or sinus captures and/or fusion QRS complexes; 2) analysis of the distinct morphological features of QRS complexes during wide QRS complex tachycardias; 3) analysis of the ECG characteristics in between wide QRS complex tachycardia attacks; 4) comparison of the morphological QRS features during wide QRS complex tachycardia and during sinus rhythm periods. The list of ECG algorithms for differential diagnosis of wide QRS complex tachycardias has been growing and updated year after year; however, all of them have their limitations. Most frequently, the differential diagnosis between ventricular and aberrant supraventricular tachycardias is based on the morphological criteria of wide QRS complexes developed by H.J. Wellens et al., P. Brugada et al., M. Griffith et al., K.E. Kindwal et al., A. Vereckei et al. At the same time, there is a continuous search for new algorithms or criteria that could be easily used without decreased specificity and/or sensitivity of the diagnosis of ventricular tachycardia. The aim of this review is to comprehensively analyze the literature data and results of our own studies on the potential and limitation of standard ECG for the differential diagnosis of ventricular and various aberrant supraventricular tachycardias.

Aim. To evaluate standard 12-lead ECG indices for the differential diagnosis of wide QRS tachycardias with right bundle branch block (RBBB) pattern. Materials and methods. Study analyses the 244 ECG indices in 111 patients (79 males and 32 females, age 53±17 years) with RBBB tachycardias, who underwent electrophysiological studies. First step includes retrospective analysis of QRS characteristics in 20 patients with ventricular tachycardias (VT), 24 pts with aberrant supraventricular tachycardias (SVT+RBBB) and 14 pts with antidromic SVTs (WPW). ROC- and multifactorial analyses were performed to develop diagnostic ECG algorithms. The prognostic accuracy of the algorithms was subsequently evaluated on a prospective group of patients with RBBB tachycardias (n=53). Results and discussion. ECG criteria of RBBB VTs were: 1) the presence Q-wave in lead II, 2) the duration interval R(peak)-S(end) >100 ms in lead V5. ECG criteria for antidromic SVTs with RBBB were: 1) the duration of the R wave in lead I ≥80 ms, 2) the absence of split (M-sharp) R-waves in lead V2, 3) the absence notch in ascending S wave in lead aVL. The accuracy of the algorhythm for diagnostic of VTs with RBBB was 83% (sensitivity 100%, specificity 73%). The accuracy of the algorhythm for diagnostic of antidromic SVTs with RBBB was 91% (sensitivity 85%, specificity 96%). Conclusion. The proposed algorithms are based on new ECG criteria for the differential diagnosis of wide QRS complexes tachycardias with RBBB pattern, unlike the previous algorithms.

Aim. To compare safety of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF). Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no significant differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg). Results. There were no mortality, stroke, transient ischemic attack, ventricular arrhythmia, asystole longer than 3,0 sec (primary safety criteria) in both groups. Prolongation of QT interval longer than 500 ms observed in 1 of 30 patients (3,3%) in DCC group and in 7 of 30 patients (23,3%) in PCV group. 2 patients (one patient in each group; 3,3%) developed asymptomatic bradycardia after conversion to SR that resolved spontaneously within 30 minutes. 95% confidence interval (95%CI) for secondary safety criteria is [0,02-0,38] for QT prolongation and [-0,04-0,04] for bradycardia. Conclusion. Safety of PCV is noninferior to DCC in patients with persistent AF in terms of primary safety criteria and bradyarrhythmias. More frequent QT interval prolongation to values >500 ms observed in PCV group points to necessity of precautions with use of the drug.

Alterations of heart rhythm are a common clinical event. They can be caused by almost any kind of heart disorder. Atrial fibrillation (AF) is the most common type of abnormal heart rhythm. Prevalence of AF in the general population is 1-2%, and given that AF incidence rate continues to increase it can be predicted that the number of patients will be doubled within the next 50 years. This review provides the most recent diagnostic and treatment methods, including both unique domestic antiarrhythmic drugs and non - drug methods for AF treatment which were developed and implemented in clinical practice at NMRC of Cardiology of the Ministry of Health of the Russian Federation.Нарушения ритма сердца - широко распространенное клиническое явление. Их возникновение может быть обусловлено практически любым видом сердечной патологии. Фибрилляция предсердий (ФП) является наиболее распространенной формой нарушений ритма сердца. Распространенность ФП в общей популяции составляет 1-2%, и продолжающийся рост заболеваемости позволяет прогнозировать удвоение количества больных в течение ближайших 50 лет. В данном обзоре представлены новейшие диагностические методики и методы лечения, включающие как уникальные отечественные антиаритмические препараты, так и немедикаментозные методы лечения ФП, разработанные и внедренные в клиническую практику в НМИЦ кардиологии Минздрава России.

Aim . To study the changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth stimulation gene-2 (sST2) to predict isolated episodes of ventricular tachyarrhythmias (VTA) and electrical storm (ES) in patients with systolic heart failure and implanted cardioverter-defibrillators, cardiac resynchronization therapy (CRT) defibrillators, as well as cardiac contractility modulation (CCM) devices. Material and methods . The study included 69 patients (mean, 59; women, 10; mean age, 59±13 years) with class I-III systolic HF and ischemic (n=36) or nonischemic (n=33) cardiomyopathy. The survey was carried out at baseline, as well as 1, 3, 6 and 12 months after device implantation. This included data collection, physical examination, determination of NT-proBNP and sST2, 6-minute walk test, electrocardiography (ECG), 24-hour Holter monitoring, echocardiography, assessment of device performance. Predictors of isolated VTA and ES were identified using ROC and multivariate analyzes. Results . According to the follow-up (median, 28 months) results, 3 groups of patients were formed: group 1 — without VTA (n=45); group 2 — isolated VTA (n=15); group 3 — ES (n=9). According to multivariate analysis, predictors of isolated VTA were as follows: 1) baseline NT-proBNP >3200 pg/ml; 2) minimum NTproBNP >1100 pg/ml during 12-month follow-up; 3) sST2 >26 ng/ml 3 months after device implantation; 4) presence of old myocardial infarction; 5) no echocardiographic signs of response to CRT or CCM therapy. There were following predictors of ES: 1) left ventricular end-systolic dimension >7,0 cm; 2) presence of VTA runs according to 24-hour Holter monitoring; 3) no echocardiographic signs of response to CRT or CCM therapy. Conclusion . The results obtained indicate that NT-proBNP and sST2 assessment in patients with systolic heart failure is promising for predicting isolated VTA, but not ES. Cardiac reverse remodeling as a result of effective CRT or CCM therapy is associated with a significant risk reduction for isolated VTA and ES.

Aim. We aimed to compare effectiveness of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AF). Material and methods. 60 patients with persistent AF were randomized to groups of DCC (n=30) and pharmacologic conversion (PCV; n=30). There were no differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups compared. Initial assessment excluded contraindications to restore sinus rhythm (SR). In DCC group two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg). Results. SR was restored in 27 of 30 patients (90%) in DCC group and in 28 of 30 patients (93.3%) in PCV group. 95% confidence interval (CI) for primary effectiveness criterion was [-0.1 – 0.16]. AF recurred in 1 patient after successful DCC. There were no AF recurrences in PCV group. 26 of 30 patients (86.7%) in DCC group and 28 of 30 patients (93.3%) in PCV group remained in SR 24 hours after cardioversion. 95%CI for secondary effectiveness criterion was [-0.07 – 0.19]. Conclusion. Effectiveness of Refralon is noninferior to DCC in patients with persistent AF.

Aim. Evaluation of CPAP treatment (continuous positive upper airway pressure) in obstructive sleep apnea patients (OSA) and atrial fibrillation (AF) in comparison with antiarrhythmic medication therapy. Material and methods. Totally, 36 patients included (58% males, mean age 61±11 y.) with AF and definite OSA by the data from cardiorespiratory monitoring. In 6 (17%) patients there was moderate level of respiratory disorders and in 30 (83%) — severe. Twenty four (67%) patients had paroxysmal and 12 (33%) — persistent AF. All patients, to retain sinus rhythm and prevent AF relapses, were taking antiarrhythmic medications (AAM). Therapy by CPAP was recommended to all patients, but after familiarization nights (1-3), 18 agreed to continue this type of treatment at home (group 1), other 18 (group 2) were unable to apply CPAP due to low tolerance. During 12 month follow-up, comparative analysis was done, of AAM efficacy in both groups of patients. Groups did not differ significantly by the medications being taken. Results. With CPAP therapy, in group 1 most patients (12, 67%) during 12 months did not develop AF relapses, and in the group 2 — only 6 (33%) did not have AF. It is worthy to mention than group 1 patients had potentially less chance for antiarrhythmic therapy success, if to consider traditional risk factors of AF, as they had higher body mass (body mass index 39,5 kg/m2 versus 34, p=0,07), more severe sleep respiration disorders (apnea-hypopnea index 50,8 events per hour versus 37,4, p=0,09) and larger left atrium (82 mL versus 60,5, p=0,02) comparing to group 2 patients. During 3-month CPAP treatment, in group 1 patients a significant decrease of P-wave dispersion was noted, by 30,8% (р=0,05). Conclusion . Therapy with CPAP in moderate and severe OSA makes it to more than two times (from 33% to 67%) increase efficacy of antiarrhythmic drug treatment for AF. One of the mechanisms of antiarrhythmic action of CPAP againts AF might be a decrease of atrial conduction time dispersion.

Aim. Comparison study of the parameters of intracardiac electrophysiological study (EPS) in patients with the typical atrial flutter (TAF) and atrial fibrillation (AF), of the courses as isolated types of arrhythmia. Material and methods. Totally, 82 patients included (59 (72%) males, mean age 55±10 y.o.), directed for catheter ablation procedure for TAF or AF. Depending on the anamnesis of arrhythmia, patients were selected to 4 groups: 1 — isolated TAF (n=26, 32%), 2 — AF with “spontaneous” TAF (n=27, 33%), 3 — AF and TAF, when the latter had been registered only under treatment by antiarrhythmics of IC and III classes (n=14, 17%), 4 — isolated AF (n=15, 18%). All patients underwent EPS within sinus rhythm and no antiarrhythmic therapy. During EPS the following parameters were defined: P-wave duration, time of interand intra-atrial conduction, effective refractory periods (ERP) in various areas of the atria. By the results of EPS, comparative statistical study performed of the listed parameters in the groups. Results. Patients with TAF (groups 1, 2, 3), in difference with isolated AF (group 4) had significantly longer P-wave and inter-atrial conduction time. Analysis of ERP showed similar heterogeneity of the parameters in different areas of the atria in all studied groups: the lowest ERP is found in the lateral area of the right atrium, the highest — in the distal area of coronary sinus. Intergroup differences by these parameters were non-significant. Conclusion . For TAF patients, as an isolated disorder or with AF, the characteristical is significant prolongation of the inter-atrial conduction time, that might expain tendency to tachiarrhythmias of re-entry genesis.

We present in this article 2 cases of successful pharmacological restoration of sinus rhythm by a new class III antiarrhythmic drug refralon in patients with obesity and persistent atrial fibrillation. In both cases, the effective use of refralon was preceded by repeated ineffective attempts of electrical cardioversion. In the article we discuss the role of obesity as the factor leading to a substantial increase of transthoracic electrical resistance, and thus significantly reducing the probability of sinus rhythm restoration by means of electrical cardioversion. The clinical examples described in this article clearly show that the use of refralon may represent a unique clinical alternative to electrical cardioversion for sinus rhythm restoration in patients with persistent atrial fibrillation, and in some cases where the success of electrical cardioversion is obviously questionable, like in patients with severe obesity, the use of refralon seems preferable.

To evaluate the efficacy and safety of refralon (niferidil), a new class III antiarrhythmic agent whose activity is related to the block of delayed rectifying potassium current and to the prolongation of atrial and ventricular action potential and refractory periods, when it is used as an agent for pharmacological cardioversion for atrial fibrillation (AF) and atrial flutter (AFL).The efficacy of the drug as 3 intravenous boluses of 10 μg/kg was evaluated in 134 patients (90 men; 57.8 ± 11 years) with a mean AF duration of 3 (1.5; 6) months. Its effect was controlled by 24-hour Holter ECG monitoring. The criterion for its antiarrhythmic effect was 24-hour sinus rhythm (SR) recovery.Niferidil restored SR in 47.7% of the patients with AF after administration of bolus 1, in 62% after bolus 2, and in 84.6% after bolus 3. SR was restored in all 100% patients with AFL. With the AF duration of less than 3 months, the efficacy of niferidil was 91.8%. There was nonsustained polymorphic ventricular tachycardia (VT) (torsade de pointes) in 1 (0.7%) patient and nonsustained monomorphic VT was stated in 5 (3.7%) patients. CONCLUSIONPharmacological cardioversion with niferidil for persistent AF and VT may be regarded as a possible alternative to electrical cardioversion.Цель исследования. Оценка эффективности и безопасности рефралона (ниферидила) - нового антиаритмического препарата III класса, действие которого связано с блокадой калиевых токов задержанного выпрямления, удлинением потенциала действия и рефрактерных периодов в предсердиях и желудочках, при его применении в качестве средства для медикаментозной кардиоверсии при фибрилляции предсердий (ФП) и трепетании предсердий (ТП). Материалы и методы. Эффективность препарата в виде 3 болюсов по 10 мкг/кг внутривенно оценена у 134 больных (57,8±11 лет, 90 мужчин) при средней длительности ФП 3 (1,5; 6) мес. Действие препарата контролировалось при 24-часовом холтеровском мониторировании электрокардиограммы. Критерием антиаритмического эффекта было восстановление синусового ритма (СР) в течение 24 ч. Результаты. Ниферидил восстановил СР у 47,7% больных с ФП после введения 1-го болюса, у 62% - после введения 2-го и у 84,6% - после введения 3-го болюса. СР восстановлен у всех 100% больных с ТП. При длительности ФП менее 3 мес эффективность ниферидила составила 91,8%. Неустойчивая полиморфная желудочковая тахикардия (ЖТ) типа torsades de pointes отмечена в 1 (0,7%) случае. Неустойчивая мономорфная желудочковая тахикардия (ЖТ) констатирована у 5 (3,7%) больных. Заключение. Медикаментозная кардиоверсия персистирующей ФП и ТП с использованием ниферидила может рассматриваться как возможная альтернатива электрической кардиоверсии.

OBJECTIVE To assess and compare the safety and efficacy of allapinine and quinidine bisulphate in the treatment of patients with persistent atrial fibrillation after cardioversion. Design--Prospective, randomised, open study. Patients--73 consecutive patients (men only, mean age 44 ± 11 years) with persisnent atrial fibrillation and flutter. Interventions--37 patients were randomised to allapinine (ALP) (1.5 mg/kg/d), 36 to quinidine bisulphate (QUIN) (15 mg/kg/d) with subsequent successful pharmacological or electrical cardioversion. Main outcome measures--Recurrence of atrial fibrillation or side effects. RESULTS In the ALP group 15 of the 37 patients developed atrial fibrillation up to 12 month of follow-up, while in the QUIN group 20 patients developed atrial fibrillation and 5 experienced significant side effects. Relative risk (RR) (ALP vs QUIN) 0.58 (95% CI 0.37-0.91, p < 0.02). The number needed to treat (NNT) was (-3.48) (14.2-1.97 harm). When 5 patients with significant side effects were excluded from the analysis RR was 0.62 (95% CI 0.39-1.0, p = 0.052) and NNT--(-4.1) (122.7-2.1 harm) but power of the study was too low--67%. CONCLUSION Allapinine is as effective as quinidine bisulphate in the long term treatment of patients with persistent atrial fibrillation after successful cardioversion but causes significantly less side effects.

We aimed to compare safety and effectiveness of new class III antiarrhythmic drug Refralon with direct current cardioversion (DCC) in patients with persistent atrial fibrillation (AFib). 60 patients with persistent AFib were randomized to groups of DCC (n=30) and pharmacological conversion (PCV; n=

This article reviews experimental and clinical studies of a novel antiarrhythmic agent niferidile. Niferidile, a class III antiarrhythmic agent, blocks potassium outward currents, prolongs repolarization and refractory periods predominantly in atria than in ventricles. Intravenous Niferidile was efficient for interruption of AV-nodal and orthodromic re-entrant tachycardias with rates of 75% to 80%. Niferidile had a conversion rate of up to 87.3% in persistent atrial fibrillation and up to 100% in persistent atrial flutter. Proarrhythmic action of niferidil administration manifested as nonsustained torsade de pointes and monomorphic ventricular tachycardia in 1.2 and 3.7% of cases, respectively. Niferidile can be used for pharmacological cardioversion of persistent atrial fibrillation and flutter as an alternative to electrical cardioversion.

Aims To study the efficacy and safety of the new class III antiarrhythmic agent niferidil for pharmacological cardioversion in patients with persistent atrial fibrillation (AF) and atrial flutter (AFl). Methods and results One hundred thirty-four adults (aged 57.8 ± 11 years, 90 males) were included with median AF duration of 3 (1.5-6) months. All patients received a total of 10-30 μg/kg, niferidil, intravenously, in 1-3 (if needed) consecutive boluses at 15-minute intervals. Holter electrocardiogram monitoring was started before infusion and was continued for 24 hours. The criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 hours of the initial bolus. Niferidil converted AF to sinus rhythm in 47.7% of cases after bolus 1, in 62% of cases after bolus 2, and in 84.6% of cases bolus 3. Niferidil induced a 100% recovery rate in patients with AFl and a 91.8% recovery rate in patients with AF of duration from 8 days to 3 months. Nonsustained torsade de pointes occurred in 1 patient (0.7%), and nonsustained monomorphic ventricular tachycardia was observed in 5 patients (3.7%). Conclusions The new intravenous class III drug niferidil demonstrated high conversion rates of 84.6% in patients with persistent AF and 100% in patients with persistent AFl. Niferidil may be used as a possible alternative to electrical cardioversion for pharmacological cardioversion of persistent AF/AFl.

Ferrite recrystallization in cold-rolled sheets of automotive steels has been studied using a Geeble 3800 complex. Mathematical models for quantitative description of the process kinetics and prediction of the recrystallized ferrite grain size have been developed. These models enable performing calculations for any arbitrary heating regimes, including those that are used in industrial production practice, and allow taking into account the effects of a fairly wide range variation of the chemical composition of steels.