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.

Predictors of long-term survival in Japanese patients with heart failure with reduced ejection fraction (HFrEF) treated with cardiac resynchronization therapy-defibrillators (CRT-D).

BACKGROUND: Reports on the factors predicting long-term survival of CRT-D cases from Western countries are increasing, however, those from Asia including Japan are still sparse. We aimed to clarify the factors predicting long-term survival of Japanese CRT-D cases. METHODS: We retrospectively analyzed consecutive 133 patients who underwent CRT-D implantation between 2006 and 2021. We compared clinical factors between patients who died within 5 years after implantation (short-survival group: n = 31) and who had survived for more than 5 years (long-survival group: n = 36) after implantation. RESULTS: Major underlying heart diseases were dilated cardiomyopathy (45%) and ischemic heart disease (12%). There was no difference between the short-survival group and the long-survival group in incidence of CLBBB (32% vs. 30%), whereas CRBBB was more common in the short-survival group (26% vs. 0%, p = .004). Mechanical dyssynchrony at implantation was more frequent in the long-survival group (48% vs. 78%, p = .02). The incidence of response to CRT at 1 year after implantation was higher in long-survival group (19% vs. 50%, p = .02). Multiple logistic regression analysis identified NYHA class, mechanical dyssynchrony at implantation, and response at one year as predictors of long-term survival. CONCLUSIONS: In Japanese CRT-D cases, lower NHYA class, preexisting mechanical dyssynchrony, and 1-year response to CRT predict long-term survival.

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.

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.

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.

J point elevation in high precordial leads associated with risk of ventricular fibrillation.

INTRODUCTION: The significance of high precordial electrocardiograms in idiopathic ventricular fibrillation (IVF) is unknown. METHOD: This study included 50 consecutive patients (48 men; age, 42 ± 18 years) who had spontaneous ventricular fibrillation not linked to structural heart disease and received implantable cardiac defibrillator therapy. IVF was diagnosed in 35 patients and Brugada syndrome was diagnosed in other 15 patients. Electrocardiograms in high intercostal space were compared between 35 patients with IVF and 105 age- and sex-matched healthy controls (patient: control ratio, 1:3). RESULTS: The frequency of J point elevation ≥ 0.1 mV in the 4th intercostal spaces was similar between patients with IVF (14%) and healthy controls (7%). However, the frequency of J point elevation ≥ 0.1 mV in the 3rd intercostal space was higher in patients with IVF (40%) than controls (11%) (p < .01). J point elevation was present only in the 3rd intercostal space but not in the 4th intercostal space in 30% of patients with IVF but only in 6% of controls (p < .01). During follow-up, the recurrence of ventricular fibrillation was higher in patients with IVF who had J point elevation in the 3rd intercostal space (36%) and Brugada syndrome(40%) than those with IVF who did not have J point elevation in the 3rd intercostal space(11%) (p < .05 for both). CONCLUSION: J point elevation in the 3rd intercostal space was associated with IVF and recurrences of ventricular fibrillation. Electrocardiogram recordings in the high intercostal space may be useful to identify risk of sudden death.

Intra-day change in occurrence of out-of-hospital ventricular fibrillation in Japan: The JCS-ReSS study.

BACKGROUND: Real-world evidence of out-of-hospital ventricular fibrillation (VF), especially regarding intra-day change, remains unclear. We aimed to investigate that age- and gender-dependent difference of intra-day change of VF occurrence. METHOD: We enrolled 71,692 patients (males: 56,419 [78.7%], females: 15,273 [21.3%]) in whom cardiac VF had been documented from the 2005-2015 All-Japan Utstein Registry data. Subjects were divided into four groups: group-I (<18 years old), group-II (18-39), group-III (40-69), and group-IV (≥70). Among four groups in each of male and female, we compared the intra-day change of VF occurrence, and evaluated the risk factors of the unfavorable neurologic outcomes at 1 month after VF. RESULTS: Regardless of age, the incidence of VF was significantly greater in male than in female subjects. In male subjects, VF in group-I, III and IV occurred higher at daytime, however, group-II had no intra-day difference because group-II had a higher VF events at midnight~ early morning compared with other aged groups (Poisson regression analysis, p = .03). While in female, each group showed similar intra-day pattern of VF occurrence. Logistic regression analysis revealed that some of the clinical parameters such as time periods from call receipt to first shock and the presence of bystander cardiopulmonary resuscitation were important for risk of 30-day neurologically unfavorable outcomes. CONCLUSIONS: The intra-day change of VF occurrence was age-dependently different in males but not in females, suggesting age- and gender-dependent differences in underlying cardiac diseases. These might affect the significant difference in unfavorable neurologic outcome.

Early repolarization and risk of lone atrial fibrillation.

INTRODUCTION: Early repolarization syndrome is a recently proposed condition characterized by an early repolarization pattern in the electrocardiogram (ECG) and ventricular fibrillation in the absence of structural heart abnormalities. Although some studies have suggested that early repolarization is associated with frequency of atrial fibrillation, the association of early repolarization with atrial fibrillation is not well known. HYPOTHESIS: Early repolarization indicates the substrate for atrial fibrillation in addition to that for ventricular fibrillation. METHOD: This study included 79 patients (57 men [72%]; age, 45 ± 12 years) aged less than 60 years who had paroxysmal lone atrial fibrillation and 395 age- and sex-matched healthy controls (patient:control ratio, 1:5). Patients who had structural heart disease, hypertension, diabetes, hyperthyroidism, history of successful resuscitation, or the Brugada type ECG were excluded. ECGs recorded during sinus rhythm were compared between patients with atrial fibrillation and healthy controls. RESULTS: Early repolarization in the inferior and/or lateral leads was more common in patients with atrial fibrillation (25%) than controls (10%; P = 0.001). The location and magnitude of early repolarization were similar between the two groups. Other electrocardiographic measurements were not different between the two groups. Among patients with atrial fibrillation, there was no difference in clinical characteristics including age at atrial fibrillation development, sex, and body mass index between patients with early repolarization and those without early repolarization. Electrocardiographic measurements were not different between patients with early repolarization and those without early repolarization. CONCLUSION: Early repolarization was associated with lone atrial fibrillation. Early repolarization may indicate increased susceptibility to atrial fibrillation.