Differences in coagulation responses to vascular injury between uninterrupted dabigatran and apixaban - a clinical prospective randomized study.

BACKGROUND: The coagulation response during vascular injury with uninterrupted administration of direct oral anticoagulants (DOACs) has not been elucidated. OBJECTIVE: Our aim was to evaluate differences in coagulation responses after vascular injury between uninterrupted direct thrombin inhibitor and direct factor Xa inhibitor recipients. METHODS: Patients scheduled for catheter ablation for atrial fibrillation were randomly assigned to receive dabigatran or apixaban in this prospective, randomized, comparative, parallel-group study. Venous blood was collected three times: 180 minutes after taking the anticoagulant on the day before the procedure, before vascular punctures of the ablation procedure, and 10-15 minutes after the start of vascular punctures. RESULTS: Forty-two patients were enrolled. The prothrombin fragment 1+2 (F1+2) level, the primary endpoint, was much larger after vascular puncture in the uninterrupted dabigatran recipients (median: 83 pmol/L; interquartile range: 56-133 pmol/L) than in the uninterrupted apixaban recipients (median: 1 pmol/L; interquartile range: -3-19 pmol/L; P < 0.001). Antithrombin levels decreased after vascular puncture in dabigatran recipients, and both protein C and antithrombin levels decreased after vascular puncture in apixaban recipients. CONCLUSIONS: Unlike uninterrupted apixaban, uninterrupted dabigatran does not inhibit thrombin generation in response to vascular injury.

Symmetrical recovery time course between impedance and intramyocardial temperature after bipolar radiofrequency ablation; Role of impedance monitoring to estimate temperature rise.

INTRODUCTION: During radiofrequency (RF) ablation, impedance monitoring has been used to avoid steam-pop caused by excessive intramyocardial temperature (IMT) rise. However, it is uncertain why the impedance decline is related to steam-pop and whether the impedance decline is correlated to IMT. METHODS: Twenty-one bipolar ablations (40 W, 30-g contact, 120 s) were attempted for seven perfused porcine myocardium. Immediately after ablation, a temperature electrode was inserted into the mid-myocardial portion, and the recovery process of impedance and its correlation to IMT were assessed. RESULTS: Transmural lesion was created in all 21 applications but steam-pop occurred in 5/21 applications with large impedance decline. In the 16 applications without steam-pop, impedance and IMT soon after ablation were 97.2 ± 4.0 Ω and 66.1 ± 4.8 °C, respectively. Reasonably high linear correlation was demonstrated between the maximum IMT after ablation and impedance differences before and after ablation. Recovery processes of the decreased impedance and the elevated IMT fit well to each equation of the single exponential decay function and showed symmetric shapes with no statistical difference of time constant (100.1 ± 34.5 s in impedance vs. 108.7 ± 27.3 s in IMT) and half-time of recovery (144.5 ± 49.8 s in impedance vs. 156.9 ± 39.4 s in IMT). Recovered impedance after ablation (104.8 ± 3.9 Ω) was 5.1 ± 2.0 Ω smaller than that before ablation (109.9 ± 2.7 Ω), suggesting several factors other than IMT rise participate in impedance decline in RF ablation. CONCLUSIONS: Recovery of impedance and IMT after ablation well correlated, which supports the usefulness of impedance monitoring for safe RF ablation.

Distribution of excitation recoverable myocardium after radiofrequency ablation and its relation to energy application time and irrigation.

INTRODUCTION: Radiofrequency (RF) catheter ablation induces excitation recoverable myocardium around durable core lesions, and its distribution may be different depending on energy delivery methods. METHODS AND RESULTS: In coronary perfusing porcine hearts, pacing threshold through the ventricle was measured using eight-pole (1-mm distance) needle electrodes vertically inserted into myocardium before, within 3 min after and 40 min after 40 W ablation with 10-g catheter contact (Group 1: irrigation catheter for 15 s, Group 2: irrigation catheter for 40 s, Group 3: nonirrigation catheter for 15 s, Group 4: nonirrigation catheter for 40 s). Ablation was accomplished in all 12 ablations in Groups 1-3 whereas in 8/12 ablations in Group 4 because of high-temperature rise. Within 3 min after ablation, 10.0 V pacing uncaptured electrodes were distributed from the surface to inside the myocardium, and its depth was deeper in 40 s than in 15 s ablation. 40 min after ablation, excitation recovery at one or more electrodes below the durable lesion was observed in all Groups. Excitation recovery electrodes were also observed on the surface in Group 1 but not the other Groups. Accordingly, the number of excitation-recovered electrodes were larger in Group 1 than the other Groups. CONCLUSIONS: Regardless of the ablation methods, excitation recoverable myocardium was present around 1.0 mm below the durable lesions. Lesions created by short application time using an irrigation catheter may have included large excitation recoverable myocardium soon after ablation because of the presence of reversible myocardium on well-irrigated myocardial surfaces.

The Atrial Natriuretic Peptide-to-brain Natriuretic Peptide Ratio Predicts Left Atrial Reverse Remodeling after Rhythm Control Therapy in Patients with Persistent Atrial Fibrillation.

Objective The association between natriuretic peptide levels in atrial fibrillation (AF) patients with advanced left atrial (LA) remodeling and reverse remodeling after rhythm control therapy has not been clarified. The present study assessed the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) measurements to predict LA reverse remodeling after catheter ablation (CA) in persistent AF patients with LA enlargement. Methods This study included 88 persistent AF patients with LA enlargement (volume index >48 mL/m2) who underwent CA. Plasma ANP and BNP levels were analyzed before CA in all patients. The study population was divided into 2 groups according to the extent of decrease in the LA volume index (LAVI) at 6 months after CA responders were those with a ≥15% reduction in the LAVI, and all others were non-responders. Results At follow-up, 58 patients (66%) were classified as responders. The preprocedural ANP level was significantly higher in the responders than in the non-responders (p=0.03). Furthermore, the ANP-to-BNP ratio (ANP/BNP) was significantly higher in the responders than in the non-responders (p<0.01). The ANP/BNP was correlated with the percentage decrease in the LAVI (r=0.391, p<0.01). A multivariate linear regression analysis revealed that the ANP/BNP before CA was an independent predictor of LA reverse remodeling (p<0.01). Conclusion The preprocedural ANP/BNP was a robust predictor of reverse remodeling of the enlarged LA after sinus rhythm restoration by rhythm control therapy in persistent AF patients.

Efficacy of SubcutAneous implantable cardioVErter-defibrillators in ≤18 year-old CHILDREN: SAVE-CHILDREN registry.

BACKGROUND: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old. METHODS: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed. RESULTS: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase. CONCLUSIONS: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.

Clinical impact of nocturnal ventricular tachyarrythmias in electrical storm.

BACKGROUND: The incidence of electrical storm (ES) is significantly higher during the daytime. However, the association between nocturnal ventricular tachyarrythmias during ES and prognosis remains unclear. Therefore, this study aimed to investigate the clinical characteristics and outcomes of ES with midnight ventricular tachyarrythmias. METHODS: We included 48 consecutive patients who had an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator implanted between 2010 and 2020 and those who had experienced the onset of an out-of-hospital ES episode. According to the midnight (0:00 a.m.-6:00 a.m.) occurrence of ventricular arrythmia events consisting of ventricular tachycardia (VT) and ventricular fibrillation (VF), we divided them into two groups (with-midnight group: n = 27, without-midnight group: n = 21). The clinical characteristics and outcomes of the two groups were compared. RESULTS: The patients in the with-midnight group were mostly males, had longer QRS duration, and longer corrected QT-interval than those in the without-midnight group (p < .05). The incidence of all-cause death, especially heart failure death, was higher in the with-midnight group than in the without-midnight group (p < .01). Multivariate analysis showed that the presence of midnight VT/VF during ES was the only independent risk factors for heart failure death (HR = 18.9, 95%CI = 1.98-181, p = .011). CONCLUSIONS: The presence of midnight VT/VF during ES might be associated with the poor prognosis. The loss of a sympathetic circadian pattern of VT/VF distribution during ES might suggest advanced stages of the cardiac disease.

Impedance-decline-guide power control long application time bipolar radiofrequency catheter ablation.

INTRODUCTION: Bipolar (BIP) radiofrequency (RF) ablation creates deep myocardial lesions but ideal energy application modes to treat ventricular arrhythmias originating from deep inside the thick myocardium have not been well established. An experimental study was performed to clarify whether high power and long application time BIP ablation were performable by impedance-decline-guide power control (PC) and whether it could create transmural lesions in the thick ventricle with a minimum risk of steam-pop. METHODS AND RESULTS: Perfused porcine ventricle (18.4 ± 2.3 mm) was placed in an experimental bath and BIP ablation (50 W) for 120 s was attempted with catheter contact of 30-g using two protocols; fixed power (FP) and impedance-decline-guide PC. In the latter protocol, BIP ablation was started from 50 W, while the energy was decreased to 40-20 W according to the impedance decline during RF ablation. FP ablation was attempted in 30 applications and the transmural lesion was created in all 30, although steam-pop occurred in 16/30 applications (53%). Low minimum impedance, large total impedance decline (TID), and %-TID were associated with the steam-pop occurrence. PC ablation was attempted in another 21 applications, and the transmural lesion was created in all 21 without steam-pop. PC ablation was superior to FP ablation (21/21 vs. 14/30, p < .001) in the creation of a transmural lesion without resulting in steam-pop. CONCLUSIONS: High power and long application time BIP ablation seems to be feasible according to the impedance-decline-guide approach, which could create transmural lesions in thick porcine ventricles with minimal risk of steam-pop.

The Risk of Ventricular Tachyarrhythmias in Patients with Antimitochondrial Antibodies-Related Noncardiac Diseases.

Antimitochondrial antibodies (AMA) are serum autoantibodies specific to primary biliary cholangitis and are linked to myopathy and myocardial damage; however, the presence of AMA as a risk factor for ventricular tachyarrhythmias (VTs) has remained unknown. This study aimed to elucidate whether the presence of AMA-related noncardiac diseases indicates VTs risk.This cohort study enrolled 1,613 patients (883 females) who underwent AMA testing to assess noncardiac diseases. The incidence of VTs and supraventricular tachyarrhythmias (SVTs) from a year before the AMA testing to the last visit of the follow-up were retrospectively investigated as primary and secondary objectives. Using propensity score matching, we extracted AMA-negative patients whose covariates were matched to those of 152 AMA-positive patients. In this propensity score-matched cohort, the incidence of VTs and SVTs in the AMA-positive patients were compared with that in AMA-negative patients.The AMA-positive patients had higher estimated cumulative incidence (log-rank, P = 0.013) and prevalence (5.9% versus 0.7%, P = 0.020) of VTs than the AMA-negative patients. The presence of AMA was an independent risk factor for VTs (hazard ratio, 4.02; 95% CI, 1.44-20.01; P = 0.005). Meanwhile, AMA were associated with atrial flutter and atrial tachycardia development. In AMA-positive patients, VTs were associated with male sex, underlying myopathy, high creatine kinase levels, presence of chronic heart failure or ischemic heart disease, left ventricular dysfunction, presence of SVTs, and the electrocardiographic parameters indicating atrial disorders.The presence of AMA-related noncardiac diseases is an independent risk factor for VTs.

Clinical impact of ECG changes on oversensing of subcutaneous implantable cardioverter-defibrillators.

BACKGROUND: Inappropriate shocks delivered by subcutaneous implantable cardioverter-defibrillators (S-ICDs) are most frequently caused by cardiac oversensing. However, the predictors for oversensing of S-ICD remain unclear. OBJECTIVE: We aimed to investigate the predictors for oversensing of S-ICD, especially clinical impact of an electrocardiographic (ECG) change. METHODS: We retrospectively enrolled 99 consecutive patients who underwent S-ICD implantation between 2013 and 2021. Oversensing events were defined as inappropriate charge of the capacitors induced by cardiac or noncardiac signals other than tachycardia. RESULTS: During a median follow-up period of 34 months (interquartile range 20-50 months), 11 of 99 patients (11%) experienced 34 oversensing events and 4 patients (4%) received inappropriate shocks during their events. Six patients exhibited ECG changes (bundle branch block, 3; ventricular pacing, 1; inverted T wave, 1; poor R-wave progression, 1) during the follow-up period. Oversensing events were observed in 4 of 6 patients with ECG change (67%), and 3 patients underwent S-ICD removal because of inevitable shock. Contrastingly, of the remaining patients without ECG change, all 7 patients who experienced oversensing events could continue using S-ICD with the reprogramming sensing vector and/or restriction of excessive exercise. Logistic regression analysis showed that lower voltage of Sokolow-Lyon ECG (V1S + V5R) was the predictor of oversensing in patients without ECG change. When the cutoff value was 2.1 mV, the sensitivity, specificity, positive predictive value, and negative predictive value were 85.7%, 62.7%, 15.7%, and 98.1%, respectively. CONCLUSION: Unavoidable oversensing resulting in S-ICD removal is caused by ECG change. Oversensing in patients without ECG change can be managed.

Efficacy of antitachycardia pacing alert by remote monitoring of implantable cardioverter-defibrillators for out-of-hospital electrical storm.

BACKGROUND: Remote monitoring (RM) has been shown to reduce all-cause mortality in patients with implantable cardioverter-defibrillators or cardiac resynchronization therapy defibrillators (ICD/CRT-D). Not all devices transmit an alert for antitachycardia pacing (ATP) therapy, and it is unknown whether differences of RM alert affect the outcomes of electrical storm (ES). METHODS: We enrolled 42 patients with ICD/CRT-D whose out-of-hospital ES were detected by RM between 2013 and 2020. We divided their 54 episodes into two groups (ATP-alert-on; 22, ATP-alert-off; 32), and clinical outcomes were compared between the two groups. RESULTS: In 35 of 54 episodes of ES, ventricular tachycardia (VT) could be terminated within 24 h of ES onset just by ATP (ATP-alert-on: 14, ATP-alert-off: 21); however, many patients subsequently received shock delivery for VT. Among the 35 episodes, only in ATP-alert-on group, seven patients were prompted to visit our hospital without ICD shock through confirmation of ES by ATP-alert. Episodes that led to shock delivery 24 h or longer after the ES onset were significantly less common in the ATP-alert-on group (ATP-alert-on: 1/14, ATP-alert-off: 9/21, p = .03). Although there were no significant differences in the number of shock deliveries between episodes in the two groups, the number of ATP deliveries were significantly fewer in the ATP-alert-on group (12[7-26] vs. 29[16-53] in ATP-alert-off group, p = .03). Multivariate logistic regression analyses showed that the only ATP-alert significantly reduced ATP deliveries (HR = 0.14, 95%CI = 0.04-0.57, p = .003). CONCLUSION: Remote monitoring with an ATP-alert function during electrical storm may reduce appropriate ICD therapy through prompting early review.

Anti-tachycardia pacing for non-fast and fast ventricular tachycardias in individual Japanese patients: From Nippon-storm study.

BACKGROUND: Anti-tachycardia pacing (ATP) delivered from an implantable device is a useful tool to terminate ventricular tachycardia (VT). But its real-world efficacy for those patients having multiple VTs with varying VT rates has not been fully studied. METHODS: Using the Nippon-storm study database, efficacy of patient-by-patient basis ATP programing for Japanese patients having both non-fast (120-187 bpm) and fast VT (≥188 bpm) was assessed. According to the useful criteria of ≥50% success termination by ATP, patients were divided into three subgroups; success ≥50% for both non-fast and fast VT (both useful), ≥50% only for non-fast VT (non-fast VT useful), or ≥50% for neither non-fast nor fast VT (neither useful). RESULTS: During a median follow-up of 28 months, ATP terminated 184 of the 203 non-fast VT episodes (91%) and 86 of the 113 fast VT episodes (76%) in all 41 patients. In the patient-by-patient analysis, efficacy of ATP was not different between non-fast and fast VT in most of the patients (36/41 = 88%); 32 patients were in the both useful and four other patients in the neither useful. Neither ischemic nor non-ischemic structural heart disease was associated with the ATP efficacy, whereas LVEF more than 37.0% and non-prescribed amiodarone were characteristics of the patients classified into the both useful. CONCLUSIONS: ATP well terminated both non-fast and fast VT occurring in individual Japanese patients with various structural heart diseases in the real-world device treatment and this finding further supports ATP programing for all device tachycardia detection zones in most patients with multiple VTs.

Novel electrocardiographic criteria for short QT syndrome in children and adolescents.

AIMS: Although shortening of the corrected QT interval (QTc) is a key finding in the diagnosis of short QT syndrome (SQTS), there may be overlap of the QTc between SQTS patients and normal subjects in childhood and adolescence. We aimed to investigate electrocardiographic findings for differentiation of SQTS patients. METHODS AND RESULTS: The SQTS group comprised 34 SQTS patients <20 years old, including 9 from our institutions and 25 from previous reports. The control group comprised 61 apparently healthy subjects with an QTc of <360 ms who were selected from 13 314 participants in a school-based screening programme. We compared electrocardiographic findings, including QT and Jpoint-Tpeak intervals (QT and J-Tpeak, respectively), those corrected by using the Bazett's and Fridericia's formulae (cB and cF, respectively) and early repolarization (ER) between the groups. QT, QTc by using Bazett's formula (QTcB), QTc by using Fridericia's formula (QTcF), J-Tpeak, J-Tpeak cB, and J-Tpeak cF were significantly shorter in the SQTS group than in the control group. On receiver operating characteristic curve analysis, the area under the curve (AUC) was largest for QTcB (0.888) among QT, QTcB, and QTcF, with a cut-off value of 316 ms (sensitivity: 79.4% and specificity: 96.7%). The AUC was largest for J-Tpeak cB (0.848) among J-Tpeak, J-Tpeak cB, and J-Tpeak cF, with a cut-off value of 181 ms (sensitivity: 80.8% and specificity: 91.8%). Early repolarization was found more frequently in the SQTS group than in the control group (67% vs. 23%, P = 0.001). CONCLUSION: A QTcB <316 ms, J-Tpeak cB < 181 ms, and the presence of ER may indicate SQTS patients in childhood and adolescence.

Progressive increase in activation delay during premature stimulation is related to ventricular fibrillation in Brugada syndrome.

INTRODUCTION: The local conduction delay has been deemed to play an important role in the perpetuation of ventricular fibrillation (VF) in Brugada syndrome (BrS). We evaluated the relationship between the activation delay during programmed stimulation and cardiac events in BrS patients. METHODS: This study included 47 consecutive BrS patients who underwent an electrophysiological study and received implantable cardiac defibrillator therapy. We divided the patients into two groups based on whether they had developed VF (11 patients) or not (36 patients) during the follow-up period of 89 ± 53 months. The activation delay was assessed using the interval between the stimulus and the QRS onset during programmed stimulation. The mean increase in delay (MID) was used to characterize the conduction curves. RESULTS: The MID at the right ventricular outflow tract (RVOT) was significantly greater in patients with VF (4.5 ± 1.2 ms) than in those without VF (2.2 ± 0.9 ms) (p < .001). A receiver operating characteristics curve analysis indicated that the optimal cut-off point for discriminating VF occurrence was 3.3 with 88.9% sensitivity and 91.3% specificity. Furthermore, patients with an MID at the RVOT ≥ 3.3 ms showed significantly higher rates of VF recurrence than those with an MID at the RVOT < 3.3 ms (p < .001). The clinical characteristics, including the signal-averaged electrocardiogram measurement and VF inducibility were similar between the two groups. CONCLUSION: A prolonged MID at the RVOT was associated with VF and maybe an additional electrophysiological risk factor for VF in BrS patients.