XaMINA: A Real-World, Prospective, Observational Study of Treatment-Naïve Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Asia.

INTRODUCTION: The efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism have been demonstrated in Asian and non-Asian patients with non-valvular atrial fibrillation (NVAF) in multiple studies. However, limited published data exist on its use specifically in treatment-naïve patients from the Asia region. Patients in South Korea and Taiwan can now receive rivaroxaban as first-line therapy, allowing for data generation in this patient group. METHODS: XaMINA was a prospective, real-world, multicenter, single-arm, observational cohort study of patients with NVAF in South Korea and Taiwan naïve to anticoagulation and initiating rivaroxaban. The primary outcome was major bleeding; secondary outcomes included all-cause mortality, symptomatic thromboembolic events, and treatment persistence. RESULTS: In total, 1094 patients were included and the follow-up was 1 year. The baseline mean CHADS2 score was 1.63 ± 0.98, mean CHA2DS2-VASc score was 2.92 ± 1.42, and mean HAS-BLED score was 1.00 ± 0.75. The primary outcome occurred in 20 (1.8%) patients [incidence rate 2.1 events per 100 patient-years (95% CI 1.35-3.25)]. Thromboembolic events occurred in 9 (0.8%) patients, of whom 5 (0.5%) had stroke, 3 (0.3%) myocardial infarction, and 1 (0.1%) a transient ischemic attack. There were no cases of non-central nervous system systemic embolism, and 735 (67.2%) patients persisted with rivaroxaban treatment for 1 year. CONCLUSION: XaMINA demonstrated low incidence rates of major bleeding events and thromboembolic events in patients with NVAF newly initiating rivaroxaban in South Korea and Taiwan, consistent with previous real-world studies reconfirming the results of the ROCKET AF study. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (identifier NCT03284762) on 15 September 2017.

Exploratory Evaluation of Rhythm Control by Dronedarone in Combination With Low-Dose Rivaroxaban, Warfarin, Antiplatelet, or None of the Antithrombotic Therapy in High-Risk Patients With Non-Permanent Atrial Fibrillation: A Retrospective Cohort Study.

The emerging data supports rhythm control to prevent major adverse cardiac events (MACE) in high-risk patients with atrial fibrillation (AF). Limited data demonstrated rivaroxaban 10 mg combining dronedarone seemed feasible. This study aimed at investigating clinical events in a dronedarone-treated cohort. This exploratory, retrospective chart review was conducted in nonpermanent AF patients receiving dronedarone for ≥ 3 months between 2009/1 and 2016/2. In Taiwan, dronedarone's labeled indication was strict to age ≥ 70 or 65 to 70 years with either hypertension, diabetes, prior stroke, or left atrium >50 mm. We divided all into 4 groups using antithrombotic strategies to evaluate the safety, effectiveness, and MACE endpoints. A total of 689 patients (mean CHA2DS2-VASc score 3.8 ± 1.4) were analyzed: rivaroxaban 10 mg (n = 93, 13.5%), warfarin (n = 89, 12.9%), antiplatelet (n = 331, 48.0%), and none (n = 176, 25.5%). During the follow-up period (mean 946 ± 493.8 days), the rivaroxaban group did not report any stroke or thromboembolism (ishcmeic stroke rate: antiplatelet [0.6%], none [1.1%]; hemorrahgic stroke rate: warfarin [2.2%]; thromboembolism rate: warfarin [2.2%]). There was no significant difference in safety, effectiveness, and MACE endpoints between groups. Also, >104 weeks of dronedarone use was the independent predictor for MACE after adjusting the strategy and other covariates (hazard ratio 0.14 [95% confidence interval 0.04-0.44], P = .001). Our findings warrant concomitant rivaroxaban 10 mg and dronedarone for further investigation. Regardless of antithrombotic strategies, a more extended persistence of dronedarone was associated with fewer MACE.

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.

C-type natriuretic peptide in individuals with normal left ventricular systolic function.

OBJECTIVE: The objective of this study was to evaluate production or release of CNP in individuals without CHF. METHODS: Nineteen patients with symptomatic paroxysmal supraventricular tachycardia (PSVT) and normal left ventricular systolic function were enrolled into the study. Blood samples were collected from the coronary sinus (CS), the femoral artery (FA), and the peripheral vein (PV) before pacing, after rapid RA pacing, and post electrophysiological study (EPS) and/or radiofrequency (RF) ablation. RESULTS: The CNP level in the CS, compared to FA and PV, was significantly higher before pacing (CS, 3.2+/-0.8; FA, 2.6+/-0.7; PV, 2.5+/-0.5 pg/ml; CS vs. either FA or PV, both p<0.001), after the pacing (CS, 3.2+/-1.3; FA, 2.4+/-0.6 pg/ml; p=0.004), and post the EPS and/or RF ablation (CS, 3.1+/-0.7; FA, 2.6+/-0.9; PV, 2.5+/-0.8 pg/ml; CS vs. either FA or PV, both p<0.01). CONCLUSION: The myocardium regularly produces or releases CNP in patients with normal LV systolic function. Brief periods of rapid RA pacing, PSVT, or EPS does not change the production and/or release.

The electrophysiologic characteristics of atrioventricular nodal reentry tachycardia with eccentric retrograde activation.

BACKGROUND: The occurrence of eccentric retrograde atrial activation has been demonstrated to be from 6 to 8% in patients with atrioventricular nodal reentrant tachycardia (AVNRT) by several previous reports. However, most of those reports were limited by the absence of coronary sinus venography to confirm if the retrograde activation was truly left sided. The purposes of this study were to 1) determine the incidence of left sided retrograde atrial activation in our center, 2) determine the specific electrophysiologic characteristics of eccentric and concentric atrial activation and 3) determine the outcome of radiofrequency catheter ablation for AVNRT with eccentric retrograde atrial activation. METHODS: From November 2001 to July 2004, 290 consecutive patients with AVNRT who underwent an electrophysiologic study and radiofrequency ablation were included. Group 1 consisted of AVNRT patients with eccentric retrograde atrial activation; group 2 consisted of AVNRT patients with concentric retrograde atrial activation. The electrophysiologic characteristics of the group 1 and group 2 patients were then compared. RESULTS: The incidence of AVNRT with eccentric retrograde activation confirmed by CS venography was 6.5%. There were more females and atypical AVNRT in patients with retrograde eccentric conduction. There was more VA block after ablation and tachycardia induction by right ventricular pacing/extrastimuli in eccentric rather than concentric retrograde atrial activation. A shorter antegrade fast functional refractory period of the AV node was demonstrated in the atypical eccentric group as compared to the atypical concentric group. CONCLUSION: This study demonstrated the different electrophysiologic characteristics between the AVNRT patients with eccentric and concentric retrograde atrial activation. Successful ablation sites were similar to the standard RA ablation sites in patients with retrograde eccentric conduction.

Coronary sinus morphology in different types of supraventricular tachycardias.

BACKGROUND: Atrioventricular nodal reentry tachycardia (AVNRT) is based on the concept of dual AV node pathways that are functionally and anatomically distinct. The bigger coronary sinus ostium (CSO) in patients with AVNRT compared to other supraventricular tachycardias (SVTs) may produce separation of atrial inputs into the AV node or create anisotropic conduction, thus giving rise to a different AV nodal physiology. Previous studies measuring the size of the CSO using CS angiography between patients with AVNRT and other SVTs showed conflicting results. Besides, no previous studies have compared the CS morphology of the different forms of AVNRT. OBJECTIVES: This study compares the size and morphology of the CS among patients with typical AVNRT, atypical AVNRT and accessory pathways mediated reentrant tachycardia (AVRT). METHODS: Ninety-six patients with clinically documented SVTs were divided into three groups. The diameter of the CS was measured in LAO projection during end ventricular systole (by choosing the last ventricular inward motion). The CSO as well as 5, 10 and 15 mm inside the CS were measured. CS morphology is defined as either wind-sock shape or tubular shape. RESULTS: The size of the CS ostium was 13.58 +/- 3.98, 15.93 +/- 4.86 and 12.50 +/- 2.83 mm for the atypical AVNRT, typical AVNRT and AVRT, respectively (p = 0.03). There was significant difference in the size of the CS from the ostium until 15 mm into the CS between 1) typical AVNRT and AVRT, 2) typical AVNRT and atypical AVNRT. Typical and atypical AVNRT patients had more windsock morphology CS (13/32, 40.6% and 10/32, 31.2%) compared to AVRT which had only one (1/32, 3.1%) windsock morphology (p = 0.002). CONCLUSION: The easier CS cannulation in patients with typical AVNRT could be due to a bigger CS size and to a more windsock morphology. The CS size and morphology may be a very important substrate of tachycardia in patients with AVNRT.

Electrocardiographic and electrophysiologic characteristics of midseptal accessory pathways.

BACKGROUND: The purpose of the present study was to investigate the electrocardiographic and electrophysiologic characteristics of right midseptal (RMS) and left midseptal (LMS) accessory pathways (APs), and to develop a stepwise algorithm to differentiate RMS from LMS APs. METHODS AND RESULTS: From May 1989 to February 2004, 1591 patients with AP-mediated tachyarrhythmia underwent RF catheter ablation in this institution, and 38 (2.4%) patients had MS APs. The delta wave and precordial QRS transition during sinus rhythm, retrograde P wave during orthodromic tachycardia, and electrophysiologic characteristic and catheter ablation in 30 patients with RMS APs and 8 patients with LMS APs were analyzed. There was no significant difference in electrophysiologic characteristics and catheter ablation between RMS and LMS APs. The polarity of retrograde P wave during orthodromic tachycardia also showed no statistical difference between patients with RMS and LMS APs. The delta wave polarity was positive in leads I, aVL, and V3 to V6 in patients with RMS and LMS APs. Patients with LMS APs had a higher incidence of biphasic delta wave in lead V1 than patients with RMS APs (80% vs. 15%, P=0.012). The distributions of precordial QRS transition were different between RMS APs (leads V2; n = 10, V3; n = 7 and V4; n = 3) and LMS APs (leads V1; n = 1 and V2; n = 4) (P = 0.03). The combination of a delta negative wave in lead V1 or precordial QRS transition in lead V3 or V4 had a sensitivity of 90%, specificity of 80%, positive predictive value of 95%, and negative predictive value of 66% in predicting an RMS AP. CONCLUSIONS: Delta wave polarity in lead V1 and precordial QRS transition may differentiate RMS and LMS APs.