Functionally validated SCN5A variants allow interpretation of pathogenicity and prediction of lethal events in Brugada syndrome.

AIMS: The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability. METHODS AND RESULTS: Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves. CONCLUSION: In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.

High-risk atrioventricular block in Brugada syndrome patients with a history of syncope.

BACKGROUND: Determining the etiology of syncope is challenging in Brugada syndrome (BrS) patients. Implantable cardioverter defibrillator placement is recommended in BrS patients who are presumed to have arrhythmic syncope. However, arrhythmic syncope in BrS patients can occur in the setting of atrioventricular block (AVB), which should be managed by cardiac pacing. The clinical characteristics of BrS patients with high-risk AVB remain unknown. METHODS: This study included 223 BrS patients with a history of syncope from two centers. The clinical characteristics of patients with high-risk AVB (Mobitz type II second-degree AVB, high-degree AVB, or third-degree AVB) were investigated. RESULTS: During the 99 ± 78 months of follow-up, we identified six BrS patients (2.7%) with high-risk AVB. Three of the six patients (50%) with AVB presented with syncope associated with prodromes or specific triggers. Four patients (67%) were found to have paroxysmal third-degree AVB during the initial evaluation for BrS and syncope, while two patients developed third-degree AVB during the follow-up period. The incidence of first-degree AVB was significantly higher in AVB patients than in non-AVB patients (83% vs. 15%; p = .0005). There was no significant difference in the incidence of ventricular fibrillation between AVB and non-AVB patients (AVB [17%], non-AVB [12%]; p = .56). CONCLUSION: High-risk AVB can occur in BrS patients with various clinical presentations. Although rare, the incidence is worth considering, especially in BrS patients with first-degree AVB.

Electrocardiographic features of arrhythmogenic right ventricular cardiomyopathy in school-aged children.

It can be difficult to distinguish children with early-stage arrhythmogenic right ventricular cardiomyopathy (ARVC) from those with benign premature ventricular contraction (PVC). We retrospectively evaluated six school-aged children with ARVC and compared with those of 20 with benign PVC. The median age at initial presentation was 11.4 and 10.2 years in ARVC and benign PVC, respectively. None of the ARVC patients fulfilled the diagnostic criteria of ARVC at initial presentation. At ARVC diagnosis, the treadmill exercise test and Holter monitoring showed provoked PVC during exercise and pleomorphic PVC in all ARVC cases, respectively. During the observation period, terminal activation duration (TAD) was prolonged in all ARVC patients. In addition, ΔTAD (5.5 [3-10] ms) were significantly longer than those with benign PVC (p < 0.001). A new notched S-wave in V1 appeared in four (67%) ARVC patients, who had myocardial abnormalities in the right ventricle, and in zero benign PVC. Our electrocardiographic findings, such as provoked PVC during exercise, pleomorphic PVC, prolonged TAD, and a new notched S-wave in V1 could contribute to the early detection of ARVC in school-aged children.

Novel Non-Invasive Index for Prediction of Responders in Cardiac Resynchronization Therapy Using High-Resolution Magnetocardiography.

BACKGROUND: Approximately one-third of patients with advanced heart failure (HF) do not respond to cardiac resynchronization therapy (CRT). We investigated whether the left ventricular (LV) conduction pattern on magnetocardiography (MCG) can predict CRT responders.Methods and Results:This retrospective study enrolled 56 patients with advanced HF (mean [±SD] LV ejection fraction [LVEF] 23±8%; QRS duration 145±19 ms) and MCG recorded before CRT. MCG-QRS current arrow maps were classified as multidirectional (MDC; n=28) or unidirectional (UDC; n=28) conduction based on a change of either ≥35° or <35°, respectively, in the direction of the maximal current arrow after the QRS peak. Baseline New York Heart Association functional class and LVEF were comparable between the 2 groups, but QRS duration was longer and the presence of complete left bundle branch block and LV dyssynchrony was higher in the UDC than MDC group. Six months after CRT, 30 patients were defined as responders, with significantly more in the UDC than MDC group (89% vs. 14%, respectively; P<0.001). Over a 5-year follow-up, Kaplan-Meyer analysis showed that adverse cardiac events (death or implantation of an LV assist device) were less frequently observed in the UDC than MDC group (6/28 vs. 15/28, respectively; P=0.027). Multivariate analysis revealed that UDC on MCG was the most significant predictor of CRT response (odds ratio 69.8; 95% confidence interval 13.14-669.32; P<0.001). CONCLUSIONS: Preoperative non-invasive MCG may predict the CRT response and long-term outcome after CRT.

Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography.

BACKGROUND: The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64-channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs. METHODS: Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP-VF(+)) and 103 with no history of VF (ERP-VF(-)). We measured the following MCG parameters in a time-domain waveform of relative current magnitude: (a) QRS duration (MCG-QRSD), (b) root-mean-square of the last 40 ms (MCG-RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG-LAS). RESULTS: Compared to ERP-VF(-), ERP-VF(+) subjects presented a significantly longer MCG-QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG-RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG-LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG-QRSD and MCG-RMS40 showed significantly larger area under the ROC curve compared to J-peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG-QRSD ≥ 100 ms and MCG-RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80-22.3), and 92%, 48%, and 10.9 (95% CI, 1.37-86.8), respectively. CONCLUSION: Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.

Clinical and Electrocardiographic Differences in Brugada Syndrome With Spontaneous or Drug-Induced Type 1 Electrocardiogram.

BACKGROUND: Spontaneous type 1 electrocardiogram (ECG) in the right precordial lead is a dominant predictor of ventricular fibrillation (VF) in Brugada syndrome (BrS). In some BrS patients with VF, however, spontaneous type 1 ECG is undetectable, even in repeated ECG and immediately after VF. This study investigated differences between BrS patients with spontaneous or drug-induced type 1 ECG. Methods and Results: We evaluated 15 BrS patients with drug-induced (D-BrS) and 29 with spontaneous type 1 ECG (SP-BrS). All patients had had a previous VF episode. In each D-BrS patient, ECG was recorded more than 15 times (mean, 46±34) during 7.2±5.1 years of follow-up. Age and family history were comparable between groups. Inferolateral early repolarization (ER) was observed in 13 D-BrS (87%) at least once but in only 3 SP-BrS (10%, P<0.01). Immediately after VF, inferolateral ER was accentuated in 9 of 10 D-BrS, while type 1 ECG was accentuated in 12 of 16 SP-BrS. Fragmented QRS in the right precordial lead and aVR sign were absent in D-BrS but present in 20 (69%, P<0.01) and 11 (38%, P<0.01) SP-BrS, respectively. There was no prognostic difference between groups. CONCLUSIONS: Although having similar clinical profiles, there are obvious ECG differences between VF-positive BrS patients with spontaneous or drug-induced type 1 ECG. The inferolateral lead rather than the right precordial lead on ECG may be particularly crucial in some BrS patients.

Genotype-Phenotype Correlation of SCN5A Mutation for the Clinical and Electrocardiographic Characteristics of Probands With Brugada Syndrome: A Japanese Multicenter Registry.

BACKGROUND: The genotype-phenotype correlation of SCN5A mutations as a predictor of cardiac events in Brugada syndrome remains controversial. We aimed to establish a registry limited to probands, with a long follow-up period, so that the genotype-phenotype correlation of SCN5A mutations in Brugada syndrome can be examined without patient selection bias. METHODS: This multicenter registry enrolled 415 probands (n=403; men, 97%; age, 46±14 years) diagnosed with Brugada syndrome whose SCN5A gene was analyzed for mutations. RESULTS: During a mean follow-up period of 72 months, the overall cardiac event rate was 2.5%/y. In comparison with probands without mutations (SCN5A (-), n=355), probands with SCN5A mutations (SCN5A (+), n=60) experienced their first cardiac event at a younger age (34 versus 42 years, P=0.013), had a higher positive rate of late potentials (89% versus 73%, P=0.016), exhibited longer P-wave, PQ, and QRS durations, and had a higher rate of cardiac events (P=0.017 by log-rank). Multivariate analysis indicated that only SCN5A mutation and history of aborted cardiac arrest were significant predictors of cardiac events (SCN5A (+) versus SCN5A (-): hazard ratio, 2.0 and P=0.045; history of aborted cardiac arrest versus no such history: hazard ratio, 6.5 and P<0.001). CONCLUSIONS: Brugada syndrome patients with SCN5A mutations exhibit more conduction abnormalities on ECG and have higher risk for cardiac events.

Change in QRS morphology as a marker of spontaneous elimination in verapamil-sensitive idiopathic left ventricular tachycardia.

BACKGROUND: Verapamil-sensitive idiopathic left ventricular tachycardia (verapamil-ILVT) is thought to be due to a reentry within the LV fascicular system. Radiofrequency catheter ablation (RFCA) is effective for elimination of the VT; however, a long-term prognosis of patients with verapamil-ILVT is still unclear. METHODS AND RESULTS: Eighty consecutive verapamil-ILVT patients (62 men, 31 ± 12 years of age, LVEF: 65 ± 4%) were enrolled. Seventy-six (95%) cases of VT involved right bundle branch block and left axis deviation. We retrospectively analyzed changes in the QRS duration (ΔQRS-d) and QRS axis (ΔQRS-axis) during follow-up and compared them with recurrence of VT. During a mean follow-up period of 10 years (2-32 years), no sudden death or heart failure occurred. Fifty-one (64%) patients underwent RFCA, and 46 (90%) of them had no VT without any medication after RFCA. The ΔQRS-d (16 ± 2 vs. 8 ± 1 ms, P = 0.24) and ΔQRS-axis (20 ± 4 vs. 4 ± 3 degrees, P = 0.23) were not different in patients with no VT (VT[-]) and those with recurrence of VT (VT[+]). However, in the remaining 29 patients without RFCA, VT was spontaneously eliminated in 16 patients. The ΔQRS-d (30 ± 6 vs. 6 ± 1 ms, P = 0.002) and ΔQRS-axis (23 ± 4 vs. 5 ± 2 degrees, P = 0.001) were significantly larger in VT(-) patients compared to VT(+) patients during follow-up. CONCLUSIONS: Some verapamil-ILVT patients who show QRS morphology changes over the follow-up period may become free from VT without any invasive or pharmacological treatments, suggesting that further altered LV fascicular conduction might eliminate the reentry of verapamil-ILVT.

Clinical outcome of patients with the Brugada type 1 electrocardiogram without prophylactic implantable cardioverter defibrillator in primary prevention: a cumulative analysis of seven large prospective studies.

Aims: Patients with the Brugada type 1 ECG (Br type 1) without previous aborted sudden death (aSD) who do not have a prophylactic ICD constitute a very large population whose outcome is little known. The objective of this study was to evaluate the risk of SD or aborted SD (aSD) in these patients. Methods and results: We conducted a meta-analysis and cumulative analysis of seven large prospective studies involving 1568 patients who had not received a prophylactic ICD in primary prevention. Patients proved to be heterogeneous. Many were theoretically at low risk, in that they had a drug-induced Br type 1 (48%) and/or were asymptomatic (87%), Others, in contrast, had one or more risk factors. During a mean/median follow-up ranging from 30 to 48 months, 23 patients suffered SD and 1 had aSD. The annual incidence of SD/aSD was 0.5% in the total population, 0.9% in patients with spontaneous Br type 1 and 0.08% in those with drug-induced Br type 1 (P = 0.0001). The paper by Brugada et al. reported an incidence of SD more than six times higher than the other studies, probably as a result of selection bias. On excluding this paper, the annual incidence of SD/aSD in the remaining 1198 patients fell to 0.22% in the total population and to 0.38 and 0.06% in spontaneous and drug-induced Br type 1, respectively. Of the 24 patients with SD/aSD, 96% were males, the mean age was 39 ± 15 years, 92% had spontaneous Br type 1, 61% had familial SD (f-SD), and only 18.2% had a previous syncope; 43% had a positive electrophysiological study. Multiple meta-analysis of individual trials showed that spontaneous Br type 1, f-SD, and previous syncope increased the risk of SD/aSD (RR 2.83, 2.49, and 3.03, respectively). However, each of these three risk factors had a very low positive predictive value (PPV) (1.9-3.3%), while negative predictive values (NPV) were high (98.5-99.7%). The incidence of SD/aSD was only slightly higher in patients with syncope than in asymptomatic patients (2% vs. 1.5%, P = 0.6124). Patients with SD/aSD when compared with the others had a mean of 1.74 vs. 0.95 risk factors (P = 0.026). Conclusion: (i) In patients with Br type 1 ECG without an ICD in primary prevention, the risk of SD/aSD is low, particularly in those with drug-induced Br type 1; (ii) spontaneous Br type 1, f-SD, and syncope increase the risk. However, each of these risk factors individually has limited clinical usefulness, owing to their very low PPV; (iii) patients at highest risk are those with more than one risk factor.

Feasibility evaluation of long-term use of beta-blockers and calcium antagonists in patients with Brugada syndrome.

Aims: Beta-blockers (BBs) and calcium antagonists (CAs) are reported to aggravate ST-segment elevation in some patients with Brugada syndrome (BrS). The feasibility of their long-term use in BrS still remains unknown. We investigated the safety of long-term use of BB and CA in BrS patients. Methods and results: Of the 360 consecutive BrS patients, 29 [5: a history of ventricular fibrillation (VF), 17: syncope, 7: asymptomatic] took BB and/or CA (BB: 22, CA: 8) for more than 1 year for the treatment of co-morbidities such as atrial tachyarrhythmia, vasospastic angina, and neurally mediated syncope. The electrocardiographic changes and clinical outcome after the treatment were evaluated. Eleven patients showed type 1 electrocardiogram (ECG) at baseline. BBs and CAs were used within normal dosage range in all patients. After starting a BB and/or CA, type 1 ECG was still observed in 9 patients. There were no significant differences in the ECG parameters such as the amplitude of J-point, QRS duration, and corrected QT intervals before and after starting BB and/or CA. During follow-up of 89 ± 65 months after initiation of the drugs, 1 patient experienced a VF recurrence without significant changes of ECG parameters 2 years after BB therapy was started. Conclusion: Long-term intake of BB or CA within normal dosage range was not associated with the aggravation of ECG parameters and clinical outcome in patients with BrS. The use of BBs and CAs is acceptable under careful observation.

Different responses to exercise between Andersen-Tawil syndrome and catecholaminergic polymorphic ventricular tachycardia.

Aims: Andersen-Tawil Syndrome (ATS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are both inherited arrhythmic disorders characterized by bidirectional ventricular tachycardia (VT). The aim of this study was to evaluate the diagnostic value of exercise stress tests for differentiating between ATS and CPVT. Methods and results: We included 26 ATS patients with KCNJ2 mutations from 22 families and 25 CPVT patients with RyR2 mutations from 22 families. We compared the clinical and electrocardiographic (ECG) characteristics, responses of ventricular arrhythmias (VAs) to exercise testing, and the morphology of VAs between ATS and CPVT patients. Ventricular arrhythmias were more frequently observed at baseline in ATS patients compared with CPVT patients [the ratio of ventricular premature beats (VPBs)/sinus: 0.83 ± 1.87 vs. 0.06 ± 0.30, P = 0.01]. At peak exercise, VAs were suppressed in ATS patients, whereas they were increased in CPVT patients (0.14 ± 0.40 vs. 1.94 ± 2.71, P < 0.001). Twelve-lead ECG showed that all 25 VPBs and 15 (94%) of 16 bidirectional VTs were right bundle branch block (RBBB) morphology in ATS patients, whereas 19 (86%) of 22 VPBs had left bundle branch block (LBBB), and 12 (71%) of 17 bidirectional VT had LBBB and RBBB morphologies in CPVT patients. Conclusion: In patients with ATS, VAs with RBBB morphology were frequently observed at baseline and suppressed at peak exercise. In contrast, exercise provoked VAs with mainly LBBB morphology in patients with CPVT. In adjunct to clinical and baseline ECG assessments, exercise testing might be useful for making the diagnosis of ATS vs. CPVT, both characterized by bidirectional VT.

Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

BACKGROUND: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of ß-blocker therapy has not been studied previously in a large LQT3 population. METHODS: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries. Cox regression analysis was used to evaluate the independent contribution of clinical, genetic, and therapeutic factors to the first occurrence of time-dependent cardiac events (CEs) from age 1 to 41 years. RESULTS: Of the 391 patients, 118 (41 males, 77 females) patients (30%) experienced at least 1 CE (syncope, aborted cardiac arrest, or long-QT syndrome-related sudden death), and 24 (20%) suffered from LQT3-related aborted cardiac arrest/sudden death. The risk of a first CE was directly related to the degree of QTc prolongation. Cox regression analysis revealed that time-dependent ß-blocker therapy was associated with an 83% reduction in CEs in females (P=0.015) but not in males (who had many fewer events), with a significant sex × ß-blocker interaction (P=0.04). Each 10-ms increase in QTc duration up to 500 ms was associated with a 19% increase in CEs. Prior syncope doubled the risk for life-threatening events (P<0.02). CONCLUSIONS: Prolonged QTc and syncope predispose patients with LQT3 to life-threatening CEs. However, ß-blocker therapy reduces this risk in females; efficacy in males could not be determined conclusively because of the low number of events.

Isolated Late Activation Detected by Magnetocardiography Predicts Future Lethal Ventricular Arrhythmic Events in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Risk stratification of ventricular arrhythmias is vital to the optimal management in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect isolated late activation (ILA) by overcoming the limitations of conventional noninvasive predictors of ventricular tachyarrhythmias, including epsilon waves, late potential (LP), and right ventricular ejection fraction (RVEF), in ARVC patients.Methods and Results:We evaluated ILA on MCG, defined as discrete activations re-emerging after the decay of main RV activation (%magnitude >5%), and conventional noninvasive predictors of ventricular tachyarrhythmias (epsilon waves, LP, and RVEF) in 40 patients with ARVC. ILA was noted in 24 (60%) patients. Most ILAs were found in RV lateral or inferior areas (17/24, 71%). We defined "delayed ILA" as ILA in which the conduction delay exceeded its median (50 ms). During a median follow-up of 42.5 months, major arrhythmic events (MAEs: 1 sudden cardiac death, 3 sustained ventricular tachycardias, and 4 appropriate implantable cardioverter defibrillator discharges) occurred more frequently in patients with delayed ILA (6/12) than in those without (2/28; log-rank: P=0.004). Cox regression analysis identified delayed ILA as the only independent predictor of MAEs (hazard ratio 7.63, 95% confidence interval 1.72-52.6, P=0.007), and other noninvasive parameters were not significant predictors. CONCLUSIONS: MCG is useful to identify ARVC patients at high risk of future lethal ventricular arrhythmias.

Risk factors associated with bleeding after multi antithrombotic therapy during implantation of cardiac implantable electronic devices.

Previous studies showed that continuous anticoagulation or single antiplatelet therapy during implantations of cardiac implantable electronic devices (CIED) was relatively safe. However, the safety of continuous multi antithrombotic therapy (AT) in patients undergoing CIED interventions has not been clearly defined. We sought to evaluate the safety of this therapy during CIED implantations. A total of 300 consecutive patients (mean 69 years old, 171 males) with CIED implantations were enrolled in this study. The patients were divided into 6 groups [No-AT, oral anticoagulant therapy (OAT), single antiplatelet therapy (SAPT), OAT and SAPT, dual antiplatelet therapy (DAPT), triple AT (TAT)], and the perioperative complications were evaluated. Clinically significant pocket hematomas (PH) were defined as PH needing surgical intervention, prolonged hospitalizations, interruption of AT, or blood product transfusions. There were 129, 89, 49, 20, 10, and 3 patients in No-AT, OAT, SAPT, OAT + SAPT, DAPT, and TAT groups, respectively. The occurrence of clinically significant PH and thromboembolism did not differ among 6 groups (p = 0.145 and p = 0.795, respectively). However, high HAS-BLED score and valvular heart disease (VHD) were associated with clinically significant PH (p = 0.014 and p = 0.015, respectively). Continuous multi AT may be tolerated, but patients with high HAS-BLED score or VHD would require a careful attention during CIED implantations.

Persistent tachycardia within isolated pulmonary veins during atrial fibrillation ablation.

During circumferential pulmonary vein (PV) isolation for ongoing atrial fibrillation (AF), distinguishing passive conduction to the pulmonary vein (PV) from rapid PV arrhythmia in the isolated PV is difficult. Hence, the purpose of this study is to investigate both the feasibility of distinguishing the PV tachycardia after circumferential PV isolation and the electrophysiological characteristics of these tachycardia. Among 178 consecutive patients who underwent circumferential PV isolation during ongoing AF, fibrillatory PV converted to a regular cycle length PV tachycardia independent of the atrial rhythm (=independent PV tachycardia) in 13 PVs among 12 (7%) patients. We classified independent PV tachycardia according to 3 different atrial rhythms: sinus rhythm (type 1, n = 2), atrial tachycardia (type 2, n = 4), and AF (type 3, n = 6). independent PV tachycardia was observed in 3 right PV and 10 left PV (P = 0.0864). There were 10 mappable independent PV tachycardia, in which 8 were focal and 2 were macroreentrant tachycardia. i-PVT can be diagnosed in a small number of patients who underwent circumferential PV isolation during AF. The main mechanism or independent PV tachycardia was focal tachycardia mainly in the left PV.

"Window Sliding" analysis combined with high-density and rapid electroanatomical mapping: its efficacy and the outcome of catheter ablation of atrial tachycardia.

Atrial tachycardia (AT) is a clinically challenging arrhythmia that can occur based on atrial substrates. Nowadays, a rapid construction of three-dimensional electroanatomical maps, which has an analysis function for complex arrhythmias, named 'Window Sliding' (WS) is available. However, little data has revealed the efficacy of this mapping strategy. The aim of this study was to investigate the efficacy of the WS analysis for AT treatments. All patients underwent electrophysiological studies during ATs and the characteristics of the ATs were analyzed using rapid high-density mapping followed by the WS analysis. RFA was then performed. Fifty-five ATs were identified in 34 patients (63 ± 17 year-old) and in 51 activation maps (cycle length, 322 ± 120 milliseconds) were successfully constructed with 644 ± 433 points per map during 5.3 ± 2.5 min. The types of detected ATs were macro-reentries around the mitral (8) and, tricuspid (12) valves, roof-dependent reentry (5), others (13), and focal patterns (13). Of those that underwent RFA, 46 (98%) were treated successfully. Two ATs were abandoned since their critical sites were close to the His bundle and sinoatrial node. During a mean follow-up period of 179 ± 176 days, 7 patients had documented recurrences of AT. This high-density mapping using the WS analysis was useful for creating the entire picture of the ATs in a short time, resulting in favorable RFA outcomes.

Significance of electrocardiogram recording in high intercostal spaces in patients with early repolarization syndrome.

AIMS: Published reports regarding inferolateral early repolarization (ER) syndrome (ERS) before 2013 possibly included patients with Brugada-pattern electrocardiogram (BrP-ECG) recorded only in the high intercostal spaces (HICS). We investigated the significance of HICS ECG recording in ERS patients. METHODS AND RESULTS: Fifty-six patients showing inferolateral ER in the standard ECG and spontaneous ventricular fibrillation (VF) not linked to structural heart disease underwent drug provocation tests by sodium channel blockade with right precordial ECG (V1-V3) recording in the 2nd-4th intercostal spaces. The prevalence and long-term outcome of ERS patients with and without BrP-ECG in HICS were investigated. After 18 patients showing type 1 BrP-ECG in the standard ECG were excluded, 38 patients (34 males, mean age; 40.4 ± 13.6 years) were classified into four groups [group A (n = 6;16%):patients with ER and type 1 BrP-ECG only in HICS, group B (n = 5;13%):ERS with non-type 1 BrP-ECG only in HICS, group C (n = 8;21%):ERS with non-type 1 BrP-ECG in the standard ECG, and group D (n = 19;50%):ERS only, spontaneously or after drug provocation test]. During follow-up of 110.0 ± 55.4 months, the rate of VF recurrence including electrical storm was significantly higher in groups A (4/6:67%), B (4/5:80%), and C (4/8:50%) compared with D (2/19:11%) (A, B, and C vs. D, P < 0.05). CONCLUSIONS: Approximately 30% of the patients with ERS who had been diagnosed with the previous criteria showed BrP-ECG only in HICS. Ventricular fibrillation mostly recurred in patients showing BrP-ECG in any precordial lead including HICS; these comprised 50% of the ERS cohort.

Efficacy of Antiarrhythmic Drugs Short-Term Use After Catheter Ablation for Atrial Fibrillation (EAST-AF) trial.

AIMS: Substantial portion of early arrhythmia recurrence after catheter ablation for atrial fibrillation (AF) is considered to be due to irritability in left atrium (LA) from the ablation procedure. We sought to evaluate whether 90-day use of antiarrhythmic drug (AAD) following AF ablation could reduce the incidence of early arrhythmia recurrence and thereby promote reverse remodelling of LA, leading to improved long-term clinical outcomes. METHODS AND RESULTS: A total of 2038 patients who had undergone radiofrequency catheter ablation for paroxysmal, persistent, or long-lasting AF were randomly assigned to either 90-day use of Vaughan Williams class I or III AAD (1016 patients) or control (1022 patients) group. The primary endpoint was recurrent atrial tachyarrhythmias lasting for >30 s or those requiring repeat ablation, hospital admission, or usage of class I or III AAD at 1 year, following the treatment period of 90 days post ablation. Patients assigned to AAD were associated with significantly higher event-free rate from recurrent atrial tachyarrhythmias when compared with the control group during the treatment period of 90 days [59.0 and 52.1%, respectively; adjusted hazard ratio (HR) 0.84; 95% confidence interval (CI) 0.73-0.96; P = 0.01]. However, there was no significant difference in the 1-year event-free rates from the primary endpoint between the groups (69.5 and 67.8%, respectively; adjusted HR 0.93; 95% CI 0.79-1.09; P = 0.38). CONCLUSION: Short-term use of AAD for 90 days following AF ablation reduced the incidence of recurrent atrial tachyarrhythmias during the treatment period, but it did not lead to improved clinical outcomes at the later phase.

Single-Coil Defibrillator Leads Yield Satisfactory Defibrillation Safety Margin in Hypertrophic Cardiomyopathy.

BACKGROUND: Single-coil defibrillator leads have gained favor because of their potential ease of extraction. However, a high defibrillation threshold remains a concern in patients with hypertrophic cardiomyopathy (HCM), and in many cases, dual-coil leads have been used for this patient group. There is little data on using single-coil leads for HCM patients. METHODS AND RESULTS: We evaluated 20 patients with HCM who received an implantable cardioverter-defibrillator (ICD) on the left side in combination with a dual-coil lead. Two sets of defibrillation tests were performed in each patient, one with the superior vena cava (SVC) coil "on" and one with the SVC coil "off". ICDs were programmed to deliver 25 joules (J) for the first attempt followed by maximum energy (35 J or 40 J). Shock impedance and shock pulse width at 25 J in each setting as well as the results of the shock were analyzed. All 25-J shocks in both settings successfully terminated ventricular fibrillation. However, shock impedance and pulse width increased substantially with the SVC coil programmed "off" compared with "on" (66.4±6.1 ohm and 14.0±1.3 ms "off" vs. 41.9±5.0 ohm and 9.3±0.8 ms "on", P<0.0001 respectively). CONCLUSIONS: Biphasic 25-J shocks with the SVC coil 'off' successfully terminated ventricular fibrillation in HCM patients, indicating a satisfactory safety margin for 35-J devices. Single-coil leads appear appropriate for left-sided implantation in this patient group. (Circ J 2016; 80: 2199-2203).

Utility of High-Resolution Magnetocardiography to Predict Later Cardiac Events in Nonischemic Cardiomyopathy Patients With Normal QRS Duration.

BACKGROUND: Nonischemic dilated cardiomyopathy (NIDCM) patients, even those with a narrow QRS, are at increased risk for major adverse cardiac events (MACE). We hypothesized that 64-channel magnetocardiography (MCG) would be useful to detect prognostic left intraventricular disorganized conduction (LiDC) by overcoming the limitations of fragmented QRS (fQRS, qualitative definitions, low specificity) and late potential (abnormality undetectable in earlier QRS).Methods and Results:We evaluated LiDC on MCG, defined as significant deviation from a global clockwise left ventricular (LV) activation pattern, and conventional noninvasive predictors of MACE, including fQRS and late potential, in 51 NIDCM patients with narrow QRS (LV ejection fraction, 22±7%; QRS duration, 99±11 ms). MACE was defined as cardiac death, lethal ventricular arrhythmias, or LV assist device (LVAD) implantation. LiDC was present in 22 patients. Baseline characteristics were comparable between patients with and without LiDC, except for the ratio of positive late potential. During a mean follow-up of 2.9 years, MACE developed in 16 NIDCM patients (3 cardiac deaths, 9 lethal ventricular arrhythmias, and 4 LVAD). MACE was more incident in patients with LiDC (13/22) than in those without (3/29, P<0.001). Multivariate analysis revealed LiDC, but not fQRS or late potential, as the strongest independent predictor of MACE (hazard ratio 4.28, 95% confidence interval 1.30-19.39, P=0.015). CONCLUSIONS: MCG accurately depicts LiDC, a promising noninvasive predictor of MACE in patients with NIDCM and normal QRS.