Early initiation of anti-relapse antiarrhythmic therapy in patients with atrial fibrillation and flutter after pharmacological cardioversion with refralon.

Aim      Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Aim      Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Material and methods  The study included 247 patients with atrial fibrillation/atrial flutter (AF/AFL) (142 men) who underwent pharmacological cardioversion (PCV) with refralon. A 4-step schedule of drug administration was used (successive intravenous infusions at doses of 5, 5, 10, and 10 µg/kg; maximum total dose was 30 µg/kg). Patients who recovered SR and had no contraindications were prescribed antirecurrence AAT in the early (≤24 h; n=101) or delayed (≥24 h; n=95) period. Lappaconitine hydrobromide, propafenone, and sotalol were administered orally as the antirecurrence therapy. The decision on the time of initiating ATT and the choice of the drug and its dose was taken by the attending physician individually. The safety criteria included a prolonged PQ interval >200 ms; second- or third-degree atrioventricular block; QRS complex duration >120 ms; QT prolongation >500 ms; and heartbeat pauses >3 s. The efficacy criteria included the absence of sustained recurrence of AF/AFL after initiation of AAT and the duration of hospitalization after PCV. Patients were followed up during the study until they were discharged from the hospital.Results SR was recovered in 229 (92.7 %) patients. In the group of early AAT initiation, a PQ duration >200 ms was observed in 8 (7.9 %) patients, whereas in the group of delayed AAT initiation, in 7 patients (7.4 %; p=1.000). A wide QRS complex >120 ms was recorded in 1 (1.1 %) patient of the delayed AAT initiation group and in none of the patients of the early AAT initiation group (p=0.485). Ventricular arrhythmogenic effects and QT prolongation >500 ms were not detected in any patient. Numbers of early AF recurrence did not differ in the groups of early and delayed AAT initiation: 6 (5.9 %) vs. 5 (5.3 %), respectively (p=1.000). Median duration of hospitalization after PCV was 4 days in the group of early AAT initiation and 5 days in the group of delayed AAT initiation (р=0.009).Conclusion      Early initiation of the refralon AAT does not increase the risk of drug adverse effects and reduces the duration of stay in the hospital.

[Left bundle branch block - dilated cardiomyopathy - heart failure: common links in the closed pathogenetic chain].

This review summarizes the available information on the epidemiology and prognosis of patients with left bundle branch block (LBBB), morphological alterations of the myocardium both resulting in and ensuing LBBB, cardiac biomechanics in LBBB, and possibilities of its correction.

[Potential risk factors of atrial fibrillation recurrence after cryoballoon ablation].

Aim      To identify risk factors for recurrence of atrial fibrillation (AF) following cryoballoon ablation (CBA).Material and methods  This prospective study included patients with paroxysmal AF who had undergone CBA (141 patients, median age 60 years, 3% men). The evaluation prior to CBA included clinical instrumental parameters (electrocardiography (ECG), 24-h ECG monitoring, echocardiography, contrast-enhanced cardiac multispiral computed tomography). Also, possible intraoperative indexes that could affect the CBA effectivity, were evaluated. The postoperative follow-up duration was 12 months. Effectivity was assessed during in-person visits at 3, 6, and 12 months, when questioning of patients and 24-h ECG monitoring were performed. CBA was considered ineffective if the patient had recurrences of any atrial tachyarrhythmia longer than 30 sec after the end of the 3-month "blind" period.Results During the 12-month follow-up, recurrences of atrial tachyarrhythmia were observed in 46 (32.6 %) patients. Patients with ineffective CBA more frequently had AF during the first 3 months (71.7 % vs. 11.6 %; р<0.001). Such patients had a history of multiple ineffective treatments with antiarrhythmic drugs (AAD), common pulmonary venous (PV) collector (41.3 % vs. 20.0 %; р=0.008), and stroke/recurrent ischemic attacks (15.2 % vs. 5.2 %; р=0.047). Multifactorial regression analysis showed that the factors of AF recurrence included common PV collector (relative risk (RR) 2.35; 95 % confidence interval (CI) 1.29-4.25; р=0.005), multiple ineffective AADs (RR 1.42; 95 % CI 1.08-1.86; р=0.011), and early AF recurrence (RR 7.57; 95 % CI 3.84-14.90; р<0.001).Conclusion      Common PV collector and multiple ineffective AADs are risk factors of ineffective CBA. Early recurrences during the first 3 postoperative months are a significant risk factor of long-term AF recurrences.

[Efficiency and safety of using the modified protocol for the administration of the domestic class III antiarrhythmic drug for the relief of paroxysmal atrial fibrillation].

AIM: Evaluation of the efficacy and safety of the modified refralon administration protocol for the relief of paroxysmal atrial fibrillation (AF). MATERIALS AND METHODS: The study included 39 patients (19 men, mean age 6312.8 years). All patients, after excluding contraindications in the intensive care unit, were injected intravenously with refralon at an initial dose of 5 mg/kg. If AF was preserved and there were no contraindications, after 15 min, repeated administration was performed at a dose of 5 mg/kg (total dose of 10 mg/kg). After another 15 min, while maintaining AF and the absence of contraindications, the third injection of the drug was performed at a dose of 10 mg/kg (total dose of 20 mg/kg). In the absence of relief and the absence of contraindications, another injection of refralon at a dose of 10 mg/kg was performed after another 15 min (in this case, the maximum total dose of 30 mg/kg was reached). After each injected bolus and before the introduction of the next one, the ECG parameters and the general condition of the patient were assessed. The patient was monitored for 24 hours to exclude the arrhythmogenic effect and other possible adverse events. RESULTS: Restoration of sinus rhythm (SR) was noted in 37 patients out of 39 (95%). Of these, 19 people (48.7%) had SR recovery after the administration of a minimum dose of refralone of 5 mg/kg. The effectiveness of the total dose of 10 mg/kg was 76.9%, the dose of 20 mg/kg was 89.7%, and the dose of 30 mg/kg was 95%. Only two patients did not recover HR after administration of the maximum dose of refralon 30 mg/kg. Pathological prolongation of the QTc interval (500 ms) was recorded in 5% of patients. Not a single case of ventricular arrhythmogenic action (induction of Torsade de pointes) has been reported. Bradyarrhythmias (pauses, bradycardia) were registered in 13% of cases, were of a transient nature. CONCLUSION: Refralon has a high efficiency of relief (95%) of paroxysmal AF, while in almost half of cases (48.7%), SR recovery is achieved using the minimum dose of refralon 5 mg/kg. Despite the prolongation of the QTc500 ms recorded in 5% of cases, none of the patients developed Torsade de pointes after administration of the drug.

New ECG criteria for differential diagnosis of wide QRS complex tachycardias with right bundle branch block pattern.

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: 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.

[Recent advances in diagnosis and management of atrial fibrillation].

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.

[Restoration of Sinus Rhythm in Patients With Persistent Atrial Fibrillation and Obesity: New Possibilities of Pharmacological Cardioversion].

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.

[Refralon (niferidil) is a new class III antiarrhythmic agent for pharmacological cardioversion for persistent atrial fibrillation and atrial flutter].

AIM: 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). SUBJECTS AND METHODS: 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. RESULTS: 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. CONCLUSION> Pharmacological cardioversion with niferidil for persistent AF and VT may be regarded as a possible alternative to electrical cardioversion.

[Ventricular Tachycardia as a First Manifestation of Myotonic Dystrophy].

We report a case of bundle-branch reentrant ventricular tachycardia as a first and severe manifestation of myotonic dystrophy. Progressive cardiac conduction disturbances and cardiac arrhythmias are well-known features of myotonic dystrophy, although they are commonly found in late stage of disease in patients with established diagnosis. We review clinical manifestations, diagnostics, management, and prognostic value of cardiac involvement in myotonic dystrophy.

[Novel class III antiarrhythmic agent niferidile: review of experimental and clinical studies].

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.

[Efficiency and safety of allapinin in short- and long-term treatment of patients with normal heart and ventricular premature beats].

UNLABELLED: Allapinin, class 1C antiarrhythmic drug, is highly effective in treatment of patients with ventricular premature beats (VPB). The purpose of work was retrospective assessment of efficacy and safety of allapinin in patients with benign ventricular arrhythmias. 73 patients with VPB and no structural heart disease were selected from a database. In short course allapininin in dose of 75-150 mg per os daily decreased the number of VPB for more than 90% in 46,6% of patients. In 34,4% cases tolerable drug side effects were observed. Among patients with VPB burden of 10% and higher allapinin reduced this quantity below the indicated value in 76% of cases with tolerable drug side effects in 38,6% of cases. In long treatment study antiarrhythmic effect of allapinin persisted and no other side effects of the drug were documented. CONCLUSION: Allapinin is highly effective in treatment of patients with VPB without structural heart disease.

[Efficacy and safety of allapinine and quinidine bisulphate in the treatment of patients with persistent atrial fibrillation after cardioversion].

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.

[Cardiac resynchronization therapy in patients with permanent atrial fibrillation].

UNLABELLED: In our study we compared effect of cardiac resynchronization therapy (CRT) in chronic heart failure (CHF) patients with permanent atrial fibrillation (AF) and patients with sinus rhythm. Special feature of our work was that patients with permanent atrial fibrillation didnt have obligatory ablation of atrio-ventricular node but underwent aggressive rate control to achieve more than 90% of biventricular (BV) complexes. We used 24 hours Holter monitoring because there are data that this method is more accurate than CRT counters. METHODS: We included 30 patients: 21 patients with sinus rhythm and 9 patients with permanent AF with ejection fraction <35%, II-IV NYHA class and wide QRS (>120 ms). We examined patients before implantation of CRT and after 6 months. RESULTS: mean NYHA class decreased from III to II. Distance at 6-min walk test increased by 107 m in AF group and by 105 in sinus rhythm group. EF increased by 7% in AF group and by 6% in sinus rhythm group. Mean time of further observation was 2 years (from 10 months to 5 years). There was 1 death (11.1%) in AF group and 3 deaths (15%) in sinus rhythm group (p>0,05). CONCLUSION: CRT is effective in CHF patients with permanent AF and pharmacological rate control if percent of BV pacing is more than 90% on Holter monitoring.

[Electrophysiological effects and antiarrhythmic activity of novel domestic class III antiarrhythmogenic drug niferidil administered in patients with paroxismal supraventricular tachycardia].

Intracardiac electrophysiological effects and antiarrhythmic activity of novel domestic class III antiarrhythmogenic drug niferidil has been studied in a group of 25 patients with paroxismal supraventricular tachycardia (PSVT) diagnosis. The drug was administered in a dose of 20 mg/kg (i.v.). Niferidil injections increased the refractory periods in both right and left atrium (by 22 and 20%, respectively, p < 0.001), right ventricle (12%, p < 0.01), and the His-Purkinje system (34%, p < 0.001) and improved additional anterograde and retrograde conduction (by 22 and 31%, respectively, p < 0.001), while not influencing the conduction via excitable cardiac tissues. Elongation of the QTc interval (22%, p <0.05) in one case was accompanied by an arrythmogenic effect (induction of short-term polymorphous ventricular tachycardia of the "torsade de pointes" type. Niferidil arrested PSVT in 78% cases and prevented PSVT development in response to endocardial stimulation in 86% of patients.

[First experience of clinical use of new class III antiarrhythmic agent niferidil in patients with persistent atrial fibrillation and flutter].

The aim of the study was to evaluate the efficacy and safety of administered intravenously niferidil in doses 10, 20 and 30 mkg per kg in patients with persistent atrial fibrillation (AF) and flutter (AFL) for pharmacological cardioversion. The study included 30 patients (22 male) with persistent AF (n = 28) and AFL (n = 2) without structural heart diseases with median arrhythmia duration 6.1 +/- 4.8 months (2 weeks to 24 months). Niferidil was administered as 3 bolus injections (10 mkg per kg each) performed with the interval of 15 minutes. Antiarrhythmic efficacy of niferidil in dose of 10 mkg per kg was 60%, in dose of 20 mkg per kg it was 70%, and in dose of 30 mkg per kg reached 90% prespectively. The part of the patients, in whom QTc prolongation exceeded potentionally dangerous value of 500 mc, was 22.2% (6 of 27). None of the patients developed proarrhythmic side effect as torsade de pointes.

[Treatment of patients with long nocturnal asystoles and obstructive sleep apnea syndrome by creating continuous positive air pressure in the upper respiratory tract].

AIM: To study prevalence of obstructive sleep apnea syndrome (OSAS) in patients with nocturnal asystoles, and assess therapeutic efficiency of constant positive air pressure (CPAP) applied to upper respiratory tract in this category of patients. METHODS: The study incorporated 37 patients (33 men and 4 women, average age 50+/-11 years) with nocturnal heart beat interruptions of over 3 seconds. Baseline examination revealed grade II-III arterial hypertension in 67.5%, coronary heart disease - in 19%, diabetes mellitus in 8% and no cardiovascular disease - in 5.5% of patients. Sinus rhythm was registered in 30 (81%) of patients, 7 (19%) patients had permanent atrial fibrillation. Causes of deteriorated cardiac conduction were as follows: sinoatrial blocks and sinoatrial arrests (n=18), grade II-III atrio ventricular block (n=10), combination of these forms of bradyarrhythmias (n=2) and block of conduction to ventricles in permanent atrial fibrillation (n=7). According to intra esophageal cardiac pacing, the function of sinus node and atrio ventricular conduction appeared to be undisturbed in all patients with sinus rhythm. All patients have undergone polysomnographic (PSG) examination. For patients with OSAS, an individual selection of therapeutic pressure was carried out using the CPAP apparatuses. CPAP therapy was considered effective against OSAS if normalization of apnea/hypopnea index (AHI) was observed. RESULTS: OSAS was registered in 25 cases (68%) (mean AHI 54.9+/-28.7), 20 patients (80%) had severe grade of the syndrome. CPAP therapy appeared to be effective in all patients. At the background of treatment AHI decreased from 60.7 to 5.5 episodes per hour of sleep, mean oxygen saturation of arterial blood rose from 74 to 90%. Effect of CPAP therapy relative to cardiac conduction abnormalities was attained in all 19 patients with sinus rhythm and only in one patient with permanent atrial fibrillation. CONCLUSION: OSAS was revealed in 68% of patients with nocturnal bradyarrhythmias. Individually selected therapy with constant positive pressure in patients with nocturnal asystoles and OSAS efficiently eliminated in sleep asystoles and made it possible to avoid pacemaker implantation in some patients.

[The efficacy and safety of nibentan for pharmacological cardioversion in patients with persistent atrial fibrillation and flutter: the role of dose limitation and magnesium sulfate administration].

The aim of the study was to evaluate the influence of magnesium sulfate on the efficacy and safety of pharmacological cardioversion with nibentan (NB) in doses up to 0,125 mg/kg in patients with persistent atrial fibrillation (AF) and flutter (AFL). Calculated dose of NB was 0.125 mg/kg. It was administered as 2 bolus injections (0.0625 mg/kg each) performed with the interval of 15 minutes. The study included 64 patients (pts) (45 male, age 54+/-9,9 years) with persistent AF (n=56) and AFL (n=8) with median arrhythmia duration 6,7+/-6,8 months (8 days to 36 months). Pts were divided into two groups. In the first (I) group NB was used without preliminary magnesium sulfate administration, in the second group (II) magnesium sulfate was injected in a dose of 50 mg/kg, followed by 0.83 mg/kg/min infusion before NB administration. There was no difference between groups in conversion rates of atrial arrhythmias: 74% and 69%, in groups I and II, respectively (p>0.4). Mean effective dose of NB was the same in investigated groups - 0.09 mg/kg. Administration of initial dose of NB (0.0625 mg/kg) converted AF/AFL to sinus rhythm within 15-min interval in 29.7% of patients. Efficacy of full dose of NB (0.125 mg/kg) was 100% in AFL, 68% in AF. No side effects were registered after initial injection of 0.0625 mg/kg. After administration of 2 boluses (0.125 mg/kg) "torsade de pointes" developed in 2 pts (3%). Magnesium sulfate administration had no influence on NB efficacy and rate of its proarrhythmic events. Limitation of NB total dose to

[Efficasy of compression therapy of the lower limbs in the treatment of patients with vasovagal syncopes].

AIM: To study efficacy and tolerance of compressive textile in the treatment of vasovagal syncopes. MATERIAL AND METHODS: The trial included 9 patients with recurrent vasovagal syncopes confirmed at bicycle exercise tests. The patients wore long medical stockings (Sigvaris, Ganzoni & Cie AG, compression of class II). The textile was tailored individually in all the patients. The effect of wearing stockings was tested at bicycle exercise (two tests before wearing to the syncope, one test 1-3 days after the second test upon 1 hour of wearing the stockings). RESULTS: None of the bicycle exercise tests done in the stockings was accompanied with syncopes. None of the patients experienced discomfort while putting on, wearing the stockings or performing the exercise. CONCLUSION: Good therapeutic effects and tolerance were registered when wearing therapeutic textile.

[Interrelationship between changes of rate and variability of cardiac rhythm under influence of beta-adrenoblockers].

BACKGROUND: Beta-blocking agents (BB) decrease mortality particularly sudden in post-myocardial infarction patients and in patients with chronic heart failure that is closely related to heart rate (HR) lowering at rest. The hypothesis exists that BB decrease mortality due to increase of cardiac vagal activity. AIM: To evaluate the relation between HR changes on therapy with BB and changes in heart rate variability (HRV). MATERIAL AND METHODS: Sixty patients with arterial hypertension randomized in three groups were studied before and after treatment with atenolol (AT), acebutolol (AC) or talinolol (TL) until doses of 100, 600 and 300 mg/d correspondingly were reached or resting HR was decreased by 10 bpm. 24-hour Holter monitoring was used to measure HR and HRV indexes. RESULTS: Arterial blood pressure decreased significantly in every group. HR max, min and average decreased significantly on AT. AC and TL lowered HR max and AT average but did not change HR min. AT did not change SDNN, SDANN, TotP and ULFP, but AC and NL decreased them significantly (p < 0.001). AT increased SDNNind, VLFP (p < 0.002), rMSSD, pNNSO and HFP (p < 0.003), but did not change LFP. AC and TL did not change these indexes. Changes of HRV indexes were closely related to changes of HR particularly HR min (r=0.53 - 0.84). Linear regressions of these relations did not differ between three drugs except for low frequency indexes of HRV between AC and TL. According to the equations the differences in HRV indexes between the drugs were well explained by the differences in HR changes. When all patients were evaluated together statistical significance of increase in rMSSD, pNN50 and HFP was not reached until HR average decreased by 10 bpm or more. The effect of TL on HR and HRV is very similar to AC what suggests its intrinsic sympathomimetic activity or anticholinergic properties.