The effect of off-label use of reduced-dose direct oral anticoagulants therapy in the treatment of pulmonary embolism comparable to standard-dose therapy.

Direct oral anticoagulants (DOACs) have been shown to be effective and safe in preventing pulmonary embolism recurrence. In this single-center retrospective observational study, we aimed to evaluate the efficacy and safety of reduced-dose DOACs in 86 consecutive patients with acute pulmonary embolism. Patients were divided into standard-dose and reduced-dose DOACs groups. Initial clot volume did not significantly differ between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 18.8 [Q1-Q3 7.3-30.8] mL vs. 10.0 [Q1-Q3 3.2-27.9] mL, p = 0.1). Follow-up computed tomography (CT) within 30 days showed a higher rate of clot volume reduction or disappearance in the standard-dose group compared to the reduced-dose group (standard-dose DOACs vs. reduced-dose DOACs, 81.6% vs. 53.9%, p = 0.02). However, at the final follow-up CT, there was no significant difference in clot volume change between the two groups (standard-dose DOACs vs. reduced-dose DOACs, 91.5% vs. 82.0%, p = 0.19). Major bleeding occurred in two patients in the standard-dose group (4.3%) and three patients in the reduced-dose DOACs group (7.7%) (p = 0.5). In conclusion, while standard-dose DOACs demonstrated superior efficacy in early clot reduction, reduced doses of apixaban and edoxaban showed comparable efficacy and safety profiles in long-term treatment of acute pulmonary embolism in certain patients.

Radiofrequency Ablation of Re-entrant Atrial Tachycardia Originating from the Superior Vena Cava with a High-resolution, 3-dimensional Mapping System.

An 80-year-old man with no previous history of catheter ablation or cardiac surgery underwent catheter ablation for atrial tachycardia (AT). We suspected that the mechanism causing AT was re-entry indicated by the entrainment phenomenon during AT and through activation mapping with a 3-dimensional mapping system (EnSite™ X EP system; Abbott, Chicago, IL, USA). We used a multipolar catheter (Advisor™ HD Grid Mapping Catheter; Abbott) inserted into the superior vena cava (SVC) to accomplish activation mapping. The AT circuit was localized inside the SVC with a fractionated potential recorded on its right lateral wall. A similar fractionated potential was observed in the surrounding area. These areas functioned as the critical isthmus of the AT. Radiofrequency (RF) catheter ablation at these sites eliminated the tachycardia. After RF delivery, no tachycardia was induced by programmed stimulation, even during isoproterenol infusion. Consequently, there was no recurrence of tachycardia even after catheter ablation.

Histopathological characteristics of the arrhythmogenic right ventricular cardiomyopathy presenting the electrocardiographic characteristics with Brugada syndrome.

INTRODUCTION: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. METHODS: A 71-year-old man showed coved-type ST-segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. RESULTS: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. CONCLUSION: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC.

Usefulness of P-wave duration in patients with sick sinus syndrome as a predictor of atrial fibrillation.

BACKGROUND: This study aimed to clarify P-wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure. METHODS: We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day. RESULTS: In the study population, 17 patients (23%) had worsening AF burden during the follow-up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352-21.523; P = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event-free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P = .005). CONCLUSIONS: Prolonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation.

Dynamic Changes in Electrocardiogram Parameters After Epicardial Substrate Catheter Ablation of Brugada Syndrome.

BACKGROUND: Catheter ablation (CA) is effective for recurrent episodes of ventricular fibrillation (VF) in Brugada syndrome (BrS). VF development in BrS is associated with several electrocardiogram (ECG) abnormalities. This study investigated changes in ECG parameters in high-risk BrS patients who underwent epicardial CA.Methods and Results:In all, 27 BrS patients were implanted with an implantable cardioverter-defibrillator (ICD). Patients were divided into 2 groups: (1) an ablation group (n=11) that underwent epicardial CA because of VF recurrence; and (2) a primary prevention (PP) group (n=16) with ICD implantation only. ECG parameters were evaluated before and 12 months after CA and compared with ECG parameters in the PP group. The T wave peak-to-end interval was significantly longer and the number of abnormal spikes in leads V1-V3 at the second, third, and fourth intercostal spaces was greater in the ablation than PP group. After ablation, ST levels and the sum of abnormal spikes in leads V1-V3 were significantly decreased. The mean (±SD) number of ICD shocks decreased markedly during a mean follow-up period of 42.0 months (from 3.8±3.7 to 0.2±0.4/year). Four patients had an ICD shock following the ablation procedure. Greater reductions in ST-segment elevation and abnormal spikes were observed in the group without than with VF recurrence. CONCLUSIONS: Improvements in surface ECG parameters appear to be associated with successful ablation in high-risk BrS patients.

The mechanism and prognosis of acute and late improvement in mitral regurgitation after cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) improves functional mitral regurgitation (MR); however, the mechanism and differences in acute and late improvement in MR are unclear. We aimed to evaluate the factors associated with the acute and late MR improvements and the prognosis of MR improvement after CRT. This retrospective study included 121 patients who underwent CRT implantation with full echocardiography assessment at baseline, 1 week, and 6 months after implantation. MR severity was classified into five grades (0: none to 4: severe). Two-dimensional speckle-tracking echocardiography with radial strain was used to assess dyssynchrony, and the time difference between the lateral and inferior segments at papillary muscle levels (TDlate-inf) was calculated. The MR improved 1 week and 6 months after CRT in 40 (33%) and 45 (37%) patients, respectively. On multivariate analyses, TDlate-inf (baseline-1 week) and SPWMD were independently associated with acute MR improvement. The %reduction in left ventricular end-systolic volume (LVESV) (baseline-6 months) and TDlate-inf (baseline-1 week) were independently correlated with late MR improvement. The patients with pre-MR grades 2-4 and improved MR after CRT showed significantly better prognosis in heart failure hospitalization. Cutoff values of ≥ 19.5 ms of the reduction of TDlate-inf and ≥ 30.8% of the %reduction of LVESV were significantly associated with the decrease in heart failure hospitalization. The improved interpapillary muscle activation time delay and volume reduction after CRT were associated with acute and late MR improvements. There may be different time course of recovery and distinct causes for late MR improvement.

Early improvement of daily physical activity after catheter ablation for atrial fibrillation in an accelerometer assessment: A prospective pilot study.

BACKGROUND: Catheter ablation improves physical activity in patients with atrial fibrillation (AF). However, continuous daily evaluation and time course of improvement in physical activity after ablation have not been fully assessed. This prospective study was conducted to evaluate the daily physical activities and changes in the physical performance in patients undergoing catheter ablation for AF by continuous monitoring of a portable accelerometer. METHODS: Ten patients scheduled for catheter ablation for AF were fitted with a uniaxial accelerometer prior to and 6 months after the procedure. This study evaluated changes in daily steps, activity intensity, and activity duration. We also evaluated changes in activity intensity using a short version of the International Physical Activity Questionnaire (IPAQ). RESULTS: The maximum daily steps significantly increased from baseline to postablation (baseline, 9,232 [6,716-11,485]; after 1-3 months, 11,605 [8,285-14,802]; and after 4-6 months, 11,412 [8,939-13,808], p = .020). Similarly, Δ maximum-mean daily steps increased significantly (baseline, 2,431 [1,199-6,181]; after 1-3 months, 4,674 [4,164-6,474]; and after 4-6 months, 4,871 [3,657-6,117], p = .014). These improvements were more pronounced in patients with paroxysmal and symptomatic AF. The total IPAQ score significantly improved from baseline to after 6 months ablation (from 1,170 [693-3,930] to 4,312 [1,865-6,569], p = .037). All patients were recurrence-free from AF after ablation. CONCLUSIONS: The physical activity improved significantly even in the early phase following catheter ablation. The effect of suppressing AF on activity levels was apparent soon after the procedure.

Periprocedural Management of Cardiac Tamponade During Catheter Ablation for AF Under Uninterrupted DOAC and Warfarin.

OBJECTIVES: This was a retrospective analysis of a registry of patients who underwent catheter ablation for atrial fibrillation (AF) under uninterrupted direct oral anticoagulant (DOAC) and warfarin administration. BACKGROUND: Uninterrupted DOAC used during catheter ablation for AF causes a life-threatening bleeding risk of cardiac tamponade. METHODS: Of 3,149 catheter ablation procedures for AF with uninterrupted oral anticoagulants used in 2,406 patients in 3 institutions, DOAC and warfarin were administered in 1,896 and 1,253 procedures, respectively. Among them, cardiac tamponade requiring pericardiocentesis and surgical intervention occurred in 13 (0.7%) and 11 (0.9%) procedures in the DOAC and warfarin groups, respectively. In this study, the outcomes between these 2 groups were compared. RESULTS: The total blood volumes drained after pericardiocentesis was 300 (190 to 715) ml and 300 (200 to 380) ml in the DOAC and warfarin groups, respectively (p = 0.697). Approximately two-thirds of patients (9 in the DOAC group and 7 in the warfarin group) recovered with only pericardiocentesis and protamine infusion (including vitamin K in the warfarin group) in both groups. Two patients in the DOAC group underwent surgical intervention but recovered uneventfully, whereas none of the patients taking warfarin required surgical intervention. DOAC and warfarin were successfully resumed 2.0 (2.0 to 5.0) days and 4.0 (2.0 to 5.5) days after tamponade in all patients without an increase in effusion (p = 0.102). CONCLUSIONS: Managing cardiac tamponade under uninterrupted DOAC administration was feasible. Early intensive treatment resulted in hemostasis in most patients. However, surgical intervention was required in some cases refractory to the initial treatment.

Electrocardiogram characteristics of P wave associated with successful pulmonary vein isolation in patients with paroxysmal atrial fibrillation: Significance of changes in P-wave duration and notched P wave.

BACKGROUND: The mechanisms involved in changes in P wave following catheter ablation for atrial fibrillation (AF) are uncertain. This study aimed to assess the relationship between changes in P-wave morphology and pulmonary vein (PV) reconnection following ablation by the assessment of 12-lead surface electrocardiogram and signal-averaged electrocardiogram. METHODS: This retrospective study included 115 consecutive patients with paroxysmal AF that underwent repeat ablation for recurrence following initial ablation. We investigated changes in P-wave morphology between baseline and repeat procedure in patients with and without PV reconnection. The study also included as validation group without recurrence (n = 67) following initial ablation. RESULTS: The maximum P-wave duration (PWD) was significantly decreased from baseline to just after the procedure in all groups. However, for the PV reconnection group (n = 100), the maximum PWD was significantly increased again at the repeat procedure. In contrast, the maximum PWD was significantly reduced between baseline and repeat procedure in the non-PV reconnection group (n = 15). The signal-averaged PWD was significantly decreased from baseline to repeat procedure in the non-PV reconnection group, but, conversely, was increased in the PV reconnection group. In the non-PV reconnection group, the disappearance of notched P wave was detected in 8 of 15 patients (53%), which was significantly higher than in other groups (p = .001). A new or delayed notched P wave was identified in the PV reconnection group only. These results were confirmed in the validation group. CONCLUSIONS: The reverse dynamics of PWD after initial shortening directly following ablation were significantly associated with PV reconnection.

Prothrombotic Responses After Catheter Ablation for Atrial Fibrillation During Uninterrupted Oral Anticoagulant Agent Administration.

OBJECTIVES: The aim of this study was to evaluate the extent of changes in prothrombotic responses after catheter ablation for atrial fibrillation (AF) under uninterrupted oral anticoagulant agent (OAC) administration. BACKGROUND: Catheter ablation for AF has a potential risk for prothrombotic activation and silent thromboembolic events. METHODS: A total of 814 patients (n = 172 [warfarin], n = 153 [dabigatran], n = 134 [rivaroxaban], and n = 301 [apixaban] patients undergoing AF ablation and a control group of 54 patients undergoing non-AF ablation) were included. Uninterrupted OACs were administered during the procedure in patients with AF. Blood samples were collected the day before and 3 days after the procedure. RESULTS: At baseline, D-dimer levels were within normal limits (≤1.0 µg/ml) in more than 90% of the patients in all groups. However, after 3 days, this proportion decreased to 67%, 73%, 59%, 68%, and 65% in the warfarin, dabigatran, rivaroxaban, apixaban, and control groups, respectively (p = 0.180). Changes in prothrombin fragment 1+2 levels differed (p < 0.001), whereas fibrin monomer complex levels 3 days after ablation at a trough were equivalent within normal ranges among the groups (p = 0.146). Multivariate analysis revealed that age, CHA2DS2-VASc score, first session, and radiofrequency ablation were independent predictors of increased D-dimer levels after the procedure. Various changes in prothrombotic markers were observed between the warfarin and direct OAC groups after propensity score matching analyses. CONCLUSIONS: The coagulation cascade was activated after catheter ablation for AF under uninterrupted OAC administration. The changes in various prothrombotic markers differed among the OAC groups.

Discontinuous contraction in the left ventricle assessed by 2-D speckle tracking echocardiography benefits from CRT.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves the morbidity and mortality rate in patients with left bundle-branch block (LBBB); however, some LBBB patients are non-responders for CRT. Previous studies have shown that a transmural functional line block alters the left ventricular (LV) activation sequence, and that the presence of a line block is predictive for responders. We investigated whether responders could be predicted in patients with LBBB by 2-dimensional (2-D) speckle tracking strain imaging. METHODS: We enrolled 54 patients with LBBB, who underwent echocardiography before and 6 months after CRT implantation. A responder was defined by a decrease in the LV end-systolic volume >15% at the 6-month follow-up. We calculated a difference in the time from QRS onset to maximum strain between adjacent segments and defined the Tmax-diff as the maximum difference among six intersegments. We compared the Tmax-diff between responders and non-responders. RESULTS: Among 54 patients, 37 patients were identified as responders. The Tmax-diff of the responders was significantly longer than that of the non-responders (309.6 ± 168.6 ms vs 181.5 ± 138.4 ms, P = .009). Furthermore, Tmax-diff ≥ 195 ms was higher in the septal and the anterior area. And patients with a Tmax-diff ≥ 195 ms tended to be responders (P = .02). CONCLUSION: The present study showed that discontinuous contraction of the LV could be detected in CRT responders by 2-D speckle tracking strain imaging, which may be a useful tool to identify the contraction pattern of patients with LBBB and predict CRT responders.

T-wave changes of cardiac memory caused by frequent premature ventricular contractions originating from the right ventricular outflow tract.

INTRODUCTION: Cardiac memory is recognized as altered T-waves when the sinus rhythm resumes after an abnormal myocardial activation period that recovers slowly over several weeks. The T-wave changes after ablation of frequent premature ventricular contractions (PVCs) as cardiac memory was not known. OBJECTIVE: This study identified whether cardiac memory exists after successful ablation of PVCs from the right ventricular outflow tract (RVOT). METHODS: We investigated 45 patients who underwent successful ablation of PVCs from RVOT and 10 patients who underwent unsuccessful ablation. We analyzed the amplitude of the T-wave, QT intervals, and QRST time-integral values of a 12-lead electrocardiogram before ablation and 1 day, 3 days, and 1 month after ablation. RESULTS: In the successful ablation group, the amplitude of the T-wave and QRST time-integral values of lead II, III, aVR, aVL, and aVF significantly changed after ablation and gradually normalized within 1 month. In addition, if the number of pre-ablation PVCs was small, then the corresponding impact was also small. However, the greater the number of pre-ablation PVCs, the more prominent the changes. Significant changes were not observed in the unsuccessful ablation group. CONCLUSION: When ablation of PVCs from RVOT was successful, primary T-wave changes because of cardiac memory and the gradual normalization of the amplitude of the T-wave were observed. No significant T-wave changes were detected after unsuccessful ablation.