Intravenous Cavutilide for Pharmacological Conversion of Paroxysmal and Persistent Atrial Fibrillation in Patients with Heart Failure.

This work aimed to study the efficacy and safety of the class III antiarrhythmic agent cavutilide (Niferidil, Refralon) for pharmacological cardioversion in patients with paroxysmal and persistent atrial fibrillation (AF) and heart failure (HF). METHODS AND RESULTS: In this retrospective cohort study, 58 patients with stable HF (aged 69 [61;73] years, 30 males, 78% with persistent AF) and 274 patients without HF (aged 63 [57;70] years, 196 males, 56% with persistent AF) were included. The median AF duration in the group with HF was 35.5 [10.6;124] days, and that in the group without HF was 14.5 [3.6;90] days. All patients received 5-30 µg/kg cavutilide intravenously in one to four (if needed) boluses of 5-5-10-10 µg/kg at 15 min intervals. Subsequent boluses were not administered if the patient's sinus rhythm (SR) was restored or if bradycardia, QT prolongation > 500 ms or evidence of proarrhythmia was observed. Holter electrocardiogram monitoring was started before infusion and was continued for 24 h. The main criterion for an antiarrhythmic effect was sinus rhythm restoration within 24 h of the initial bolus. RESULTS: Cavutilide converted AF to SR in 37.9% of patients with HF after bolus 1 (5 µg/kg), in 58.6% after bolus 2 (cumulative dose = 10 µg/kg), in 74% of cases after bolus 3 (cumulative dose = 20 µg/kg) and in 92.8% of cases after bolus 4 (cumulative dose = 30 µg/kg). Cavutilide was effective in 89% of cases with persistent AF with a median duration of 70.5 [30;159] days and in 92% of cases with paroxysmal AF with a median duration of 36 [24;102] h. In the group of patients without HF, the effectiveness of bolus 1 was 36.9%, that of the bolus 2 was 58%, that of the bolus 3 was 77% and that of the bolus 4 was 90.1%. Cavutilide restored SR in 90% of patients with persistent AF with a median duration of 82.5 [28;180] days and in 90% of cases with paroxysmal AF with a median duration of 50 [24;120] h. No statistically significant difference in the probability of SR restoration or the effectiveness of each bolus of cavutilide was found between patients with and without HF. The median time to restoration of SR in patients with HF was 23 [11;55] min, and that in patients without HF was 22 [10;45] min (p = 0.424). No cases of symptomatic/severe bradycardia were observed in either group. QT prolongation over 500 ms after cavutilide injection was registered in 19% of patients without HF and in 15.5% of those with HF (p = 0.58). Short runs of Torsade de pointes tachycardia occurred in one patient (0.4%) without HF after 10 µg cavutilide administration and were successfully treated with MgSO4. CONCLUSIONS: Cavutilide demonstrated a high likelihood of AF conversion to SR in paroxysmal (92%) and persistent (89%) arrhythmia and HF. Concomitant HF and its severity do not affect the efficacy and safety of cavutilide.

Implication of inflammation on Coxsackie virus and Adenovirus receptor expression on cardiomyocytes and the role of platelets in patients with dilated cardiomyopathy.

BACKGROUND: Coxsackie Virus and Adenovirus Receptor (CXADR or CAR) is involved in the pathogenesis of inflammatory dilated cardiomyopathy (DCM). We aimed to examine the relationship of CAR expression on platelets and cardiomyocytes with virus persistence, local and systemic inflammation and platelet activity in patients with DCM. METHODS: Endomyocardial biopsy (EMB) samples of 38 patients (mean age 39.5±11.3 years, 20 male) with DCM were analyzed for CAR expression, local inflammation grade by immunohistochemistry and virus persistence by real-time PCR. Platelet morphology was analyzed in all patients and 30 healthy subjects (HS) using scanning electron microscopy, platelet activity by light transmission aggregation, and CAR persistence by immunofluorescence. Platelets of 20 patients were analyzed for cytomegalovirus and herpes simplex virus 1-2 by immunofluorescence. Serum levels of tumor necrosis factor alpha (TNF α) and Interleukin-6 were assessed using ELISA in all studied subjects. RESULTS: CAR expression in EMB samples was related to the heart failure functional class and the level of IL-6. Platelets from DCM patients showed enhanced spontaneous and ADP induced aggregation. Platelets' CAR expression was >4 fold higher in DCM than HS and was observed predominantly at sites of intercellular communications in microaggregates and leukocyte-platelet aggregates. CAR-positive patients showed significantly higher TNF-α and IL-6 serum levels in CAR-negative patients. Platelets of 6 (30%) DCM patients revealed the mature cytomegalovirus and herpes simplex viruses particles. CONCLUSION: Tight junction protein CAR may serve as a docking pin creating a new type of contact structure that could be responsible for signaling between neighboring cells in pathological conditions.

Intensity and Distribution of Patchy Late Gadolinium Enhancement in Left Atrium in Patients With Atrial Fibrillation.

PURPOSE: Late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (MRI) studies were performed on healthy individuals to establish signal intensity thresholds for reproducible left atrial (LA) patchy LGE detection. Using established criteria, differences in LA patchy LGE between healthy volunteers (HV) and patients with atrial fibrillation (AF) or hypertension were analyzed. METHODS: Fifty-three patents with AF (mean age 56 years, 60% men), 25 patients with hypertension and no history of AF (mean age 54 years, 40% men), and 28 HV (mean age 50 years, 52% men) were enrolled in an observational, non-interventional, case-control prospective study. LA patchy LGE quantification was performed using LGE MRI (1.5 T scanner, voxel size 1.25x1.25x2.5 mm) and the custom-built software based on estimation of LA voxel image intensity ratio and comparison with threshold value obtained from HV data. RESULTS: Based on analysis of healthy individuals' data, the optimal threshold value for the left atrial patchy LGE quantification was determined at 1.38. Patients with AF had a higher extent of LA patchy LGE (9.1 [1.72; 18.58] %) than patients with hypertension (3.81 [0.57; 9.51] %) and HV (0.78 [0.05; 3.5] %). The predominant location of LA patchy LGE in AF was in the pulmonary vein ostia region, in hypertension - LA posterior wall, and in HV - lower part of LA posterior wall. In AF patients, the extent of LA patchy LGE correlated with LA end-diastolic volume (r=0.37) and LA ejection fraction (r=-0.4), in HV - with age (r=0.66) and LA end-diastolic volume (r=0.4). CONCLUSION: AF and hypertension are associated with higher extent and different location of LA patchy LGE compared to changes caused by natural aging. The extent of LA patchy enhancement correlates with LA dilatation.

Rare Cause of Wide QRS Tachycardia.

Cardiac involvement is a well-known feature of neuromuscular diseases. Most commonly cardiac manifestations occur later in the course of the disease. Occasionally severe cardiac disease, including conduction disturbances, life-threatening arrhythmias, and cardiomyopathy, with its impact on prognosis, may be dissociated from peripheral myopathy. We report a case of bundle branch reentrant ventricular tachycardia as primary manifestation of myotonic dystrophy and discuss associated diagnostic and treatment challenges.

Efficacy of a new class III drug niferidil in cardioversion of persistent atrial fibrillation and flutter.

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.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Atrial appendage transcriptional profile in patients with atrial fibrillation with structural heart diseases.

During the last few years DNA microarray studies of gene expression changes in human atrial tissues from patients with and without atrial fibrillation (AF) have been performed. For this purpose, tissue samples are usually collected from AF patients undergoing open heart surgery. These investigations have limitations associated with the unavoidable heterogeneity of compared groups which is due to the presence of various structural changes accompanying different sets of underlying heart diseases in both groups. It is thus reasonable to compare the atrial tissue samples from AF patients with those from individuals without signs of cardiovascular disease. To address this, we selected the atrial tissue samples from 12 AF patients (who underwent open heart surgery) and compared them with control atrial tissue samples from 10 individuals with no signs of cardiovascular diseases (those who died due to street accident). cDNA microarray method and reverse transcription-polymerase chain reaction (RT-PCR) analysis were used to identify genes which can discriminate between control and pathologically altered atrial tissues. Thirty-nine genes were found to be differentially expressed in pathologically altered tissues samples independently of the type of the underlying structural heart disease. These genes are involved in signal transduction, gene transcription regulation, cell proliferation, and apoptosis. The greatest alterations were observed for NOR1, DEC1, MSF, and Bcl2A1 genes (5 to 28-fold decrease, P < 0.05). Additional studies are needed to determine the specific role of each selected gene in pathophysiological changes leading to AF.