Uric acid and incident atrial fibrillation of 14 years population-based cohort study: The Suita Study.

BACKGROUND: Higher baseline uric acid (UA) was significantly associated with higher atrial fibrillation (AF) incidence in Japanese women. However, no prospective study is evident in the association between UA and incident AF in Japanese urban residents. METHODS: A total of 6863 participants (aged 30-79 years; 47% men) without prior AF were followed for 13.9 years on average in the Suita Study. According to the UA categories, cox proportional hazards regression models were used to estimating the Hazard Ratios (HRs) and 95% confidence intervals (CIs) for incident AF. RESULTS: During 95178 person-years of follow-up, we observed 311 cases of incident AF (204 cases in men and 107 cases in women). Compared to the subjects with UA of 4.0-4.9 mg/dL, multivariable-adjusted HR (95% CIs) of incident AF was 1.50 (1.01-2.25) (P = .047) for the subjects with UA ≥7.0 mg/dL. CONCLUSION: High UA was associated with an increased risk for incident AF in the Japanese population.

The association between late-phase early recurrence within the blanking period after atrial fibrillation catheter ablation and long-term recurrence: Insights from a large-scale multicenter study.

BACKGROUND: The relationship between the timing of the first early recurrence and late recurrence after a single catheter ablation procedure for atrial fibrillation is controversial. METHODS: The Efficacy of Short-Term Use of Antiarrhythmic Drugs After Catheter Ablation for Atrial Fibrillation trial followed 2038 patients who underwent radiofrequency catheter ablation for atrial fibrillation. RESULTS: Of the patients, 907 (45%) had early recurrences within 90 days after the initial ablation. We divided these patients into two groups according to the timing of the first early recurrence episode, namely the ER1 group (early recurrence during the early phase; 0-30 days, n = 814) and ER2 group (early recurrence during the late phase; 31-90 days, n = 93). Three years after ablation, patients with early recurrences had a significantly lower event-free rate from late recurrences after a 90-day blanking period than patients without early recurrences (36.2% and 74.2%, respectively; log-rank, P < 0.0001). Three years after ablation, the event-free rate was significantly higher in the ER1 than the ER2 group (38.3% and 17.1%, respectively; log-rank, P < 0.0001). Moreover, the event-free rate at 3 years in the ER2 group was extremely low (5.6%) in patient with non-paroxysmal atrial fibrillation. CONCLUSION: Early recurrences were strongly associated with late recurrences, especially in patients with the first recurrence episode at >1 month within the blanking period after a single ablation procedure. Therefore, these patients should undergo close observation during follow-up, when they had especially with non-paroxysmal atrial fibrillation.

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.

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.

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.

Prognosis and Outcomes of Clinically Diagnosed Cardiac Sarcoidosis Without Positive Endomyocardial Biopsy Findings.

Background: Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS. Objectives: Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey. Methods: Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined. Results: Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or 18F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis (P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome (P < 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period (P < 0.001). Conclusions: In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS.

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 Differences in Japanese Patients Between Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy With Long-Term Follow-Up.

Some Brugada syndrome (BrS) patients have been suspected of being in the initial state of arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aimed to clarify the electrocardiographic (ECG) and clinical differences between BrS and ARVC in long-term follow-up (mean 11.9 ± 6.3 years). A total of 50 BrS and 65 ARVC patients with fatal ventricular tachyarrhythmia (VTA) were evaluated according to the revised Task Force Criteria for ARVC. Based on the current diagnostic criteria concerning electrocardiographic, repolarization abnormality was positive in 2.0% and 2.6% of BrS patients at baseline and follow-up, and depolarization abnormality was positive in 6.0% and 12.8% of BrS patients at baseline and follow-up, respectively. At baseline, none of the BrS patients were definitively diagnosed with ARVC. Considering patients' lives since birth, Kaplan-Meier analysis revealed that age at first VTA attack showed the same tendency between the groups (BrS: mean 42.2 ± 12.5 years old vs ARVC: mean 44.8 ± 13.7 years old, log-rank p = 0.123). Moreover, the incidence of VTA recurrence was similar between the groups during follow-up (log-rank p = 0.906). Incidence of sustained monomorphic ventricular tachycardia was significantly higher in ARVC than in BrS whereas the opposite was true for ventricular fibrillation (log-rank p <0.001 and p <0.001, respectively). None of the diagnoses of BrS patients were changed to ARVC during follow-up. During long-term follow-up, although age at first VTA attack and VTA recurrence were similar, BrS consistently exhibited features that differed from those of ARVC.

Association of Genetic and Clinical Aspects of Congenital Long QT Syndrome With Life-Threatening Arrhythmias in Japanese Patients.

Importance: Long QT syndrome (LQTS) is caused by several ion channel genes, yet risk of arrhythmic events is not determined solely by the responsible gene pathogenic variants. Female sex after adolescence is associated with a higher risk of arrhythmic events in individuals with congenital LQTS, but the association between sex and genotype-based risk of LQTS is still unclear. Objective: To examine the association between sex and location of the LQTS-related pathogenic variant as it pertains to the risk of life-threatening arrhythmias. Design, Setting, and Participants: This retrospective observational study enrolled 1124 genotype-positive patients from 11 Japanese institutions from March 1, 2006, to February 28, 2013. Patients had LQTS type 1 (LQT1), type 2 (LQT2), and type 3 (LQT3) (616 probands and 508 family members), with KCNQ1 (n = 521), KCNH2 (n = 487) and SCN5A (n = 116) genes. Clinical characteristics such as age at the time of diagnosis, sex, family history, cardiac events, and several electrocardiographic measures were collected. Statistical analysis was conducted from January 18 to October 10, 2018. Main Outcomes and Measures: Sex difference in the genotype-specific risk of congenital LQTS. Results: Among the 1124 patients (663 females and 461 males; mean [SD] age, 20 [15] years) no sex difference was observed in risk for arrhythmic events among those younger than 15 years; in contrast, female sex was associated with a higher risk for LQT1 and LQT2 among those older than 15 years. In patients with LQT1, the pathogenic variant of the membrane-spanning site was associated with higher risk of arrhythmic events than was the pathogenic variant of the C-terminus of KCNQ1 (HR, 1.60; 95% CI, 1.19-2.17; P = .002), although this site-specific difference in the incidence of arrhythmic events was observed in female patients only. In patients with LQT2, those with S5-pore-S6 pathogenic variants in KCNH2 had a higher risk of arrhythmic events than did those with others (HR, 1.88; 95% CI, 1.44-2.44; P < .001). This site-specific difference in incidence, however, was observed in both sexes. Regardless of the QTc interval, however, female sex itself was associated with a significantly higher risk of arrhythmic events in patients with LQT2 after puberty (106 of 192 [55.2%] vs 19 of 94 [20.2%]; P < .001). In patients with LQT3, pathogenic variants in the S5-pore-S6 segment of the Nav1.5 channel were associated with lethal arrhythmic events compared with others (HR, 4.2; 95% CI, 2.09-8.36; P < .001), but no sex difference was seen. Conclusions and Relevance: In this retrospective analysis, pathogenic variants in the pore areas of the channels were associated with higher risk of arrhythmic events than were other variants in each genotype, while sex-associated differences were observed in patients with LQT1 and LQT2 but not in those with LQT3. The findings of this study suggest that risk for cardiac events in LQTS varies according to genotype, variant site, age, and sex.

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.

Low-Voltage Type 1 ECG Is Associated With Fatal Ventricular Tachyarrhythmia in Brugada Syndrome.

Background Epicardial mapping can reveal low-voltage areas on the right ventricular outflow tract in patients with Brugada syndrome with several ventricular fibrillation ( VF ) episodes. A type 1 ECG is associated with an abnormal electrogram on right ventricular outflow tract epicardium. This study investigated the clinical significance of the amplitude of type 1 ECGs in patients with Brugada syndrome. Methods and Results In 209 patients with Brugada syndrome with a spontaneous type 1 ECG (26 resuscitated from VF , 54 with syncope, and 129 asymptomatic), the amplitude of the ECG in leads exhibiting type 1 was measured among V1 to V3 leads positioned in the standard and upper 1 and 2 intercostal spaces. The number of ECG leads exhibiting type 1 did not differ among groups. The averaged amplitude of type 1 ECG was, however, significantly smaller in the group resuscitated from VF than in the asymptomatic group ( P<0.05). Moreover, the minimum amplitude of type 1 ECG was significantly smaller in the group resuscitated from VF than in the group with syncope and the asymptomatic group ( P<0.05 and P<0.01, respectively). During follow-up (56±48 months), VF occurred in 29 patients. Kaplan-Meier analysis revealed that patients with the minimum amplitude of type 1 ECG lower than or at the median value had a higher incidence of VF (log-rank test, P<0.01). In multivariate analysis, syncope, past VF episode, and minimum amplitude of type 1 ECG ≤0.8 mV were independent predictors of VF events during follow-up. Conclusions Low-voltage type 1 ECG is highly and independently related to fatal ventricular tachyarrhythmia in patients with Brugada syndrome.

Development of Heart Failure From Transient Atrial Fibrillation Attacks in Responders to Cardiac Resynchronization Therapy.

OBJECTIVES: This study aimed to clarify the clinical impact of transient atrial fibrillation (AF) attacks themselves and the efficacy of cardiac resynchronization therapy (CRT) in patients with intermittent AF. BACKGROUND: The benefit of CRT in patients with intermittent AF, especially the effect of the AF attacks themselves, remains unclear. METHODS: Among our cohort of 269 consecutive CRT patients, we compared the percent of biventricular pacing (BIVP%) and other clinical characteristics between patients with intermittent AF and those with sinus rhythm (SR). RESULTS: During a median follow-up of 942 days (interquartile range: 379 to 1,464 days) a total of 22 patients, including 59% of CRT responders, developed heart failure (HF) due to a transient AF attack itself, and that accounted for 21% of all HF events. The BIVP% during the AF attacks was significantly lower than that during SR (p < 0.05). When compared to the SR groups, patients with intermittent AF had a significantly higher risk of developing HF or death (hazard ratio: 2.2; 95% confidence interval: 1.3 to 3.8). However, the patients who received a BIVP% of ≥90% during AF attacks were comparable to those with SR (hazard ratio: 1.2; 95% confidence interval: 0.4 to 3.0). CONCLUSIONS: A substantial number of patients developed HF due to transient AF attacks themselves even in the CRT responders, and the reason was mainly due to the loss of the BIVP%.

Significance of Coronary Artery Spasm Diagnosis in Patients With Early Repolarization Syndrome.

BACKGROUND: Previously described patients with early repolarization syndrome (ERS) may have experienced silent coronary artery spasm (CAS) because the diagnosis of CAS was mainly based on symptoms or coronary angiography findings, without performing a spasm provocation test. This study investigated the significance of CAS diagnosis and evaluated the incidence of silent CAS in patients with possible ERS (ie, idiopathic ventricular fibrillation [VF] and inferolateral J wave). METHODS AND RESULTS: The study included 34 patients with idiopathic VF and inferolateral J wave. Thirteen patients (38%) were diagnosed as having CAS on the basis of coronary angiography with spasm provocation test (n=8) and documentation of spontaneous ST elevation (n=5). Of the 13 patients with CAS, 5 (38%) did not experience chest symptoms before and during VF, and were diagnosed as having silent CAS. The remaining 21 patients (62%), with a negative provocation test result and absence of chest symptoms, were considered to have ERS. During the 92 months of follow-up, patients with CAS receiving appropriate medical treatment with antianginal drugs showed a favorable outcome. In contrast, 4 of 21 patients with ERS (19%) had VF recurrences. The use of monotherapy or combination therapy, consisting of quinidine, cilostazol, and bepridil, in the 4 patients with ERS, was effective in suppressing VF. CONCLUSIONS: Approximately 40% of patients with CAS with documented VF and inferolateral J wave did not experience chest symptoms at the first VF, and could have been misdiagnosed as having ERS. The use of the spasm provocation test is considered essential to differentiate patients for optimal medical treatment.

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.

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.

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.