Safety and Effectiveness of Rivaroxaban in Combination with Various Antiarrhythmic Drugs in Patients with Non-Permanent Atrial Fibrillation.

INTRODUCTION: Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort. METHODS: This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes. RESULTS: Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p < 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs. CONCLUSION: Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

Electrophysiological predictors of propafenone efficacy in prevention of atrioventricular nodal re-entrant and atrioventricular re-entrant tachycardia.

AIM: To assess the efficacy of propafenone in prevention of atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic atrioventricular tachycardia (AVRT) based on the clinical results of arrhythmia recurrence and find the electrophysiological predictor of propafenone effectiveness. METHODS: This retrospective study included 44 participants in a 12-month period, who were divided in two groups: group A - in which propafenone caused complete ventriculo-atrial block and group B - in which propafenone did not cause complete ventriculo-atrial block. RESULTS: Group A had significantly lower incidence of tachycardia than group B (95% vs 70.8%, P=0.038), and complete ventriculo-atrial block predicted the efficacy of propafenone oral therapy in the prevention of tachycardia (sensitivity 87.5%, specificity 52.8%, positive predictive value 95%, negative predictive value 29.2%). Patients with AVNRT in group B who did not experience the recurrences of tachycardia had significantly shorter echo zone before intravenous administration of propafenone than the patients who experienced episodes of sustained tachycardia (median 40 ms [range 15-60 ms] vs 79 ms [range 50-180 ms], P=0.008). CONCLUSION: In patients with non-inducible tachycardia, complete ventriculo-atrial block can be used as an electrophysiological predictor of the efficacy of propafenone oral therapy in the prevention of tachycardia. In patients with non-inducible AVNRT, but without complete ventriculo-atrial block, propafenone was more effective in patients with shorter echo zone of tachycardia.

[Evaluation of shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation: a randomized, double-blind and controlled multicenter trial].

OBJECTIVE: To evaluate the efficacy and safety of Chinese medicinal shensongyangxin capsules in the treatment of paroxysmal atrial fibrillation. METHODS: From August 2007 to July 2008, Beijing Chaoyang Hospital conducted a multicenter study, select the eleven hospital's outpatient subjects, aged 18 to 75 years old, male or female, paroxysmal atrial fibrillation (at least one electrocardiogram diagnosis) seizure frequency ≥ 2 times/month, according to the ratio 1:1:1, subjects were randomly divided into three groups: a. shensongyangxin group, taking shensongyangxin capsule 4 + propafenone analogues 150 mg, 3 times a day; b. propafenone group, taking propafenone tablets 150 mg + 4 shensongyangxin analogues, 3 times a day; shensongyangxin capsule + propafenone group, taking shensongyangxin capsule 4 + propafenone 150 mg, 3 times a day. The treatment course is 8 weeks, with 3 times of follow-up. RESULTS: Total of 349 cases of paroxysmal atrial fibrillation, which 117 cases in shensongyangxin group, 115 cases in propafenone group; 117 cases in shensongyangxin + propafenone group. The baseline data analysis showed that there were no significantly difference (P > 0.05) among the three groups of atrial fibrillation seizure frequency, vital signs, general condition, medical history, 24-hour ambulatory ECG, 12-lead normal electrocardiogram, cardiac ultrasound and symptoms. The comparison before and after (8 weeks) treatment showed that the frequency (from 6 times/m to 2 times/m in each group, P < 0.01), number of cases [from 46 (43.3%) to 22 (20.8%), 43 (43.4%) to 25 (25.3%), and 40 (40.6%) to 31 (29.2%), respectively P < 0.01] and duration time of attack of atrial fibrillation (from 4 h to 0.5 h, 4 h to 0.5 h, and 4.25 h to 0.5 h, respectively P < 0.01) all decreased in three groups. No significant difference among the three groups comparing the overall effect (62.3%, 58.6%, and 58.5%, respectively, P > 0.05), while the efficacy of TCM symptoms in shensongyangxin group (80.2%) was better than that of propafenone group (67.7%) (P < 0.05). Safety evaluation showed that adverse reaction rate was 1.8% in shensongyangxin group, and 8.2% and 5.4% in propafenone group and shensongyangxin + propafenone group. CONCLUSION: Shensongyangxin capsules and propafenone have comparable efficacies in the treatment of PAF. The efficacy of TCM symptoms is better than propafenone. Shensongyangxin capsules have an excellent profile of safety.

[Efficacy of intravenous Acehytisine Hydrochloride versus propafenone on terminating paroxysmal supraventricular tachycardia: a double-blinded, randomized multi-center study].

OBJECTIVE: In this double-blinded, randomized, parallel study, we investigated the clinical efficacy of intravenous Acehytisine Hydrochloride (AHH) and propafenone on terminating paroxysmal supraventricular tachycardia (PSVT). METHODS: Patients (18 - 70 years old) with either spontaneous or induced sustained supraventricular tachycardia lasted at least 15 min were recruited in this study. Exclusion criteria included sick sinus syndrome, atrial ventricular block or intraventricular block, etc. Eligible patients were randomly assigned to receive intravenously AHH (n=101) or propafenone (n=100) according to a proportion of 1:1 in a double-blinded manner. AHH (4 mg/kg, iv.) or propafenone (PRO, 1 mg/kg, iv.) was administered in 5 min followed by the same dose if no response was observed. Conversion times, vital signs, electrocardiograms were documented before and after drug administration. RESULTS: Except for age, the demographic characteristics and clinical features were comparable between the two groups. Efficacy on PSVT termination was comparable between AHH (72/101, 71.3%) and PRO group (73/100, 73.0%, P=0.6368). The average time from drug administration to conversion was also similar [AHH: (9.62 +/- 8.39) min vs. PRO: (10.61 +/- 9.47) min, P=0.5035]. In the AHH group, 59/72 episodes of PSVT were terminated by the first dose, and 66/72 were terminated prematurely. The average AHH dose in the 72 converted patients was (273.7 +/- 111.2) mg. In the PRO group, 54/73 episodes of PSVT were terminated by the first dose. The electrocardiographic parameters, such as sinus recovery time, longest PP and RR interval, PR interval, QRS interval, QT interval after conversion were similar between the two groups. Transient adverse events were reported in 11/101 (10.9%) patients in the AHH group and in 18/100 (18.0%,) in the PRO group (P=0.1653). CONCLUSION: With the dosage used in the present study, the efficacy on terminating PSVT was comparable between AHH and PRO.

Typical counterclockwise atrial flutter occurring despite absence of the inferior vena cava.

A 74-year-old man with a structurally normal heart presented with typical atrial flutter, after treatment of atrial fibrillation with propafenone. Catheterization and computed tomographic imaging revealed absence of the inferior vena caval segment that normally traverses the liver to enter the right atrium. Abdominal venous return occurred via the hemi-azygous vein, draining into the superior vena cava. Hepatic veins inserted postero-inferiorly into the right atrium. Pacing atrial myocardium between the hepatic veins and the tricuspid valve resulted in concealed entrainment. Radiofrequency catheter ablation directed (via a superior approach from the right internal jugular vein) to this extraordinary "isthmus" abolished atrial flutter. The implications of this congenital abnormality on posterior barriers maintaining the atrial flutter circuit are discussed.

Long-term follow-up of sudden cardiac arrest survivors and electrophysiologically guided antiarrhythmic therapy.

Sudden cardiac arrest survivors have a high risk of suffering from recurrent arrhythmic events. Recent studies have shown that these patients have a significantly decreased mortality rate, if they are supplied with an implantable cardioverter/defibrillator (ICD). The aim of this study was to evaluate the long-term prognosis of patients with electrophysiologically guided antiarrhythmic drug therapy in comparison to patients with ICD. 204 consecutive survivors of sudden cardiac arrest were enrolled in this study. All patients were examined with an initial electrophysiologic study (EPS) with programmed ventricular stimulation. Patients were treated with antiarrhythmic drugs (if the inducible tachycardia was suppressed) or with the implantation of an ICD. The maximal follow-up period was 120 months, the mean period was 53.3 +/- 31.4 months (ICD) versus 60.3 +/- 35.5 months (EPS, nonsignificant). Patients with ICD showed an overall mortality rate of 14.6%, whereas EPS-guided patients had a mortality rate of 43.2% (p < 0.001). The cardiac and arrhythmogenic mortality rates were significantly lower in the ICD group (12 vs. 43%, p < 0.01, and 1 vs. 16%, p < 0.001, respectively). A reduction of the mortality risk was observed in the ICD group by up to 61% (all-cause mortality), 52% (cardiac mortality) and 97.2% (arrhythmogenic mortality). In arrhythmic event survivors with ICD, arrhythmic and overall mortality rates are significantly lower compared to patients with an EPS-guided drug therapy. In the secondary prevention of sudden cardiac death, ICD should be the first choice of antiarrhythmic therapy.

Electrophysiological mapping and histological examinations of the swine atrium with sustained (> or =24 h) atrial fibrillation: a suitable animal model for studying human atrial fibrillation.

OBJECTIVES: Interventional elimination of chronic persistent atrial fibrillation (AFib) remains difficult. An animal model mimicking the clinical situation is important. METHODS AND RESULTS: Twenty-five adult pigs were implanted with a high-speed atrial pacemaker. After continuous pacing at 600 bpm for 6 weeks, 20 (91%) of the 22 survivals developed sustained AFib lasting for at least 24 h. Epicardial dense mapping revealed multiple coexisting reentrant wavelets in the left and the right atrium (LA and RA, respectively; 10.6 +/- 2.9 vs. 7.6 +/- 2.4 wavelets/cm(2)/s; p < 0.002). The mean local A-A intervals were 87.2 +/- 14.6 ms in the LA and 103.3 +/- 19.0 ms in the RA (p < 0.0002). Acute termination of sustained AFib was successful in 3 of the 5 pigs by propafenone, but in none of the 6 by dl-sotalol. Epicardial cryothermal ablation failed to terminate any AFib by compartmentalization of the RA free wall alone (4 pigs) or together with the LA appendage (4 pigs). Electron microscopic examination demonstrated diffuse perinuclear myolysis, myofibrillar fragmentation and mitochondrial crystal disruption in the atrium. CONCLUSIONS: Pacing-induced sustained AFib (> or =24 h) in adult pigs is a feasible and efficient animal model with electrophysiological and histological characteristics closely similar to those seen in humans.

Long-term clinical significance of frequent and complex ventricular tachyarrhythmias in trained athletes.

OBJECTIVES: The aim of this study was to clarify the clinical relevance of ventricular tachyarrhythmias assessed by 24-h ambulatory electrocardiograms (ECG) in a large, unique, and prospectively evaluated athletic population. BACKGROUND: For athletes with ventricular tachyarrhythmias, the risk of sudden cardiac death associated with participation in competitive sports is unresolved. METHODS; We assessed 355 competitive athletes with ventricular arrhythmias (VAs) on a 24-h ambulatory (Holter) ECG that was obtained because of either palpitations, the presence of > or = 3 premature ventricular depolarizations (PVDs) on resting 12-lead ECG, or both. RESULTS: Athletes were segregated into three groups: Group A with > or = 2,000 PVDs/24 h (n = 71); Group B with > or = 100 <2,000 PVDs/24 h (n = 153); and Group C with only <100 PVDs/24 h (n = 131). Cardiac abnormalities were detected in 26 of the 355 study subjects (7%) and were significantly more common in Group A (21/71, 30%) than in Group B (5/153, 3%) or Group C athletes (0/131, 0% p < 0.001). Only the 71 athletes in Group A were excluded from competition. During follow-up (mean, 8 years), 70 of 71 athletes in Group A and each of the 284 athletes in Groups B and C have survived without cardiovascular events. The remaining Group A athlete died suddenly of arrhythmogenic right ventricular cardiomyopathy while participating in a field hockey game against medical advice. Frequent and complex ventricular tachyarrhythmias are common in trained athletes and are usually unassociated with underlying cardiovascular abnormalities. Such VAs (when unassociated with cardiovascular abnormalities) do not convey adverse clinical significance, appear to be an expression of "athlete's heart syndrome," and probably do not per se justify a disqualification from competitive sports.

Global distribution of atrial ectopic foci triggering recurrence of atrial tachyarrhythmia after electrical cardioversion of long-standing atrial fibrillation: a bi-atrial basket mapping study.

OBJECTIVES: The objective of this study was to assess the spatial distribution of atrial ectopic foci potentially triggering recurrent atrial tachyarrhythmias after electrical cardioversion of long-standing atrial fibrillation (AF). BACKGROUND: It remains unknown whether targeted ablation of atrial ectopic foci concentrated in the pulmonary veins is feasible in patients with long-standin

Clinical observation on 84 cases of ventricular premature beat with deficiency syndrome treated by qi lu tang.

From August 1989 to May 1994, 84 cases of ventricular premature beat (VPB) with deficiency syndrome were treated with our empirical prescription called Qi Lü Tang Decoction for Improving Abnormal Heart Beat). The total effective rate was 88.10%, being significantly different from that of the control group treated with the Western drug propafenone (P < 0.01). Qi Lü Tang exhibited a better therapeutic effect in cases of VPB with deficiency of qi, deficiency of both qi and blood, and deficiency of both qi and yin.

[Adenosine triphosphate for supraventricular tachycardia in newborns and suckling infants]. / Adenosintriphosphate bei supraventrikulären Tachykardien im Neugeborenen- und Säuglingsalter.

A previously healthy and normally developing 12-day-old female suddenly became restless and developed cold sweats, tachypnoea and tachycardia (300 beats/min). Neither electrocardiogram nor echocardiogram showed evidence of any cardiac defect. Carotid sinus massage and other vagus-stimulating manoeuvres, undertaken because paroxysmal supraventricular tachycardia (PSVT) was suspected, were unsuccessful. Before rapid digitalization, adenosine triphosphate was administered (0.1 mg/kg intravenously). Sinus rhythm was restored within about 60 s. Despite further treatment with digoxin and verapamil (4 mg/kg.d), further episodes of PSVT occurred, each again responding to ATP (0.1 to 0.3 mg/kg). There were no side effects. After 24-hour Holter ECG monitoring had revealed Wolff-Parkinson-White syndrome as cause of the PSVT, propafenone was administered (15 mg/kg daily) and has prevented further recurrence of the tachycardia.

Supraventricular tachycardia and pre-excitation syndromes: pharmacological therapy.

Tachyarrhythmias which originate above the bifurcation of the bundle of His or incorporate tissue proximal to it are classified as supraventricular tachyarrhythmias (SVT). Primary treatment of SVT attempts to influence the underlying disease. Therapy is subdivided into drug therapy, electrotherapeutic tools (e.g. antitachycardia pacemakers, catheter ablation) and antiarrhythmic surgery. Antiarrhythmic agents which slow conduction and suppress premature beats are efficient for emergency and long-term treatment of supraventricular tachycardias. We evaluated some of the most relevant antiarrhythmic drugs for SVT including propafenone, diprafenone, cibenzoline, lorcainide and sotalol; in addition, usage and efficacy of quinidine/verapamil, disopyramide, amiodarone, ajmaline, adenosine and flecainide are summarized. The principles for acute management of tachycardia episodes with narrow and broad complexes are outlined. The reason for the selection as well as the efficacy in the termination of the tachycardias is described for different antiarrhythmic agents including verapamil, adenosine, ajmaline, propafenone and flecainide.

The efficacy of cibenzoline and propafenone against inducible sustained and nonsustained ventricular tachycardias in conscious dogs with isolated chronic right ventricular infarction: a comparative study with procainamide.

The efficacy of intravenous cibenzoline (3 mg/kg), propafenone (4 mg/kg), and procainamide (20 mg/kg) against inducible sustained and nonsustained ventricular tachycardias (VT) was evaluated in 12 conscious dogs with chronic isolated right ventricular (RV) infarction. RV infarct was caused by permanent occlusion of the right coronary artery in the closed-chest dog by intracoronary balloon inflation. Three to 10 days following the occlusion period, programmed electrical stimulation reproducibly induced sustained and/or nonsustained VT, allowing evaluation of antiarrhythmic drug efficacy. Propafenone was effective in preventing the induction of sustained VT in only one out of six dogs tested, but caused a significant (p less than 0.05) slowing of VT rate (269 +/- 13 to 230 +/- 10 bpm). Procainamide had effects similar to those seen with propafenone. Propafenone and procainamide were ineffective against nonsustained VT, and on established sustained VT once induced. Cibenzoline was effective in preventing the induction of sustained VT in two out of seven dogs, an effect which was not significantly different from either propafenone or procainamide. However, cibenzoline was significantly (p less than 0.05) more effective than either procainamide or propafenone in terminating an established induced sustained VT (four out of six dogs). Furthermore, cibenzoline converted nonsustained to sustained VT in four out of seven dogs tested. Histopathologic studies have shown infarction of the basal two thirds of the RV (38.5 +/- 7.8% of the RV) with no left ventricular involvement. It is concluded that the isolated RV infarction model is highly suitable for serial drug testing against inducible VT in conscious dogs, and this model of VT appears to be fairly resistant to standard and newer antiarrhythmic drug therapy.