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Irritable bowel syndrome (IBS) is one of the most widely recognized functional bowel disorders (FBDs) with a genetic component. SCN5A gene and SCN1B loci have been identified in population-based IBS cohorts and proposed to have a mechanistic role in the pathophysiology of IBS. These same genes have been associated with Brugada syndrome (BrS). The present study examines the hypothesis that these two inherited syndromes are linked. Prevalence of FBDs over a 12 months period were compared between probands with BrS/drug-induced type 1 Brugada pattern (DI-Type 1 BrP) (n = 148) and a control group (n = 124) matched for age, female sex, presence of arrhythmia and co-morbid conditions. SCN5A/SCN1B genes were screened in 88 patients. Prevalence of IBS was 25% in patients with BrS/DI-Type 1 BrP and 8.1% in the control group (p = 2.34 × 10 -4 ). On stepwise logistic regression analysis, presence of current and/or history of migraine (OR of 2.75; 95% CI: 1.08 to 6.98; p = 0.033) was a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. We identified 8 putative SCN5A/SCN1B variants in 7 (12.3%) patients with BrS/DI-Type 1 BrP and 1 (3.2%) patient in control group. Five out of 8 (62.5%) patients with SCN5A/SCN1B variants had FBDs. In conclusion, IBS is a common co-morbidity in patients with BrS/DI-Type 1 BrP. Presence of current and/or history of migraine are a predictor of underlying BrS/DI-Type 1 BrP among patients with FBDs. Frequent co-existence of IBS and BrS/DI-Type 1 BrP necessitates cautious use of certain drugs among the therapeutic options for IBS that are known to exacerbate the Brugada phenotype., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons. All consecutive patients from 2008 to 2019 who underwent ajmaline testing were prospectively included. A total of 2,456 patients underwent ajmaline testing, 742 (30.2%) in the context of familial screening for BrS. In non-familial screening group (1,714) ajmaline testing resulted positive in 186 (10.9%). Indications for ajmaline testing were: suspicious BrS ECG in 23 cases (12.4%), palpitations in 27 (14.5%), syncope in 71 (38.2%), presyncope in 7 (3.8%), family history of sudden cardiac death in 18 (9.7%), documented ventricular arrhythmias in 12 (6.5%), unexplained cardiac arrest in 4 (2.2%), atrial fibrillation in 16 (8.5%), brady-arrhythmias in 1 (0.5%), and cerebrovascular accidents in 7 (3.7%). Compared with the overall population, ajmaline testing positive patients were younger (42.8 ± 15.5 vs 48.9 ± 20.4; p <0.001) and more frequently male (65.1% vs 56.3%; p = 0.023). Implantable cardioverter defibrillator was implanted in 84 patients (45.2%). During a median follow-up of 42.4 months, 12 appropriate shocks and 13 implantable cardioverter defibrillator related complications were reported. In conclusion, the BrS was diagnosed in an unexpected high proportion of patients that underwent ajmaline testing for a variety of cardiovascular symptoms. This can lead to an adequate counseling and clinical management in BrS patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Reports on development of frequent ventricular premature complexes (fVPC), (non)sustained ventricular tachycardias ([n]sVT), or ventricular fibrillation (VF) and their interrelationship in patients with different inherited cardiac arrhythmia (ICA) have sofar not been reported. The aim of this study is therefore to examine incidences and recurrences rates of sVT and VF ("malignant ventricular tachyarrhythmias, VTA") in addition to the incidence of fVPC and nsVT ("ventricular dysrhythmias, VDR") in patients with various ICA during long-term follow up. Patients (N = 167, 88 male, age 45 ± 15 years) with ICA including definite/borderline arrhythmogenic right ventricular cardiomyopathy (ARVC, N = 47), Brugada syndrome (BrS, N = 71), catecholaminergic polymorphic ventricular tachycardia (CPVT, N = 7), long QT syndrome (LQTS, N = 41) or short QT syndrome (SQTS, N = 1) who had frequent 24-hour Holter monitoring during a follow-up period of 4.6 ± 4.4 years. During the initial screening visit, 15 patients had a history of malignant VTA. fVPC and nsVT was observed in respectively 19% (OHCA/VF/sVT: N = 9) and 13% (OHCA/VF/sVT: N = 4) of all patients. Compared with the ARVC group, patients with BrS and LQTS had less frequent fVPC and nsVT (fVPC: odds ratio [OR] 0.20, 95% confidence interval [CI] 0.08 to 0.49, p <0.000 and OR 0.09, 95% CI 0.02 to 0.33, p <0.000; nsVT:OR 0.17, 95% CI 0.06 to 0.50, p = 0.001 and OR 0.09, 95% CI 0.02 to 0.46, p = 0.003). The recurrence rate of malignant VTA was 33%. In conclusion, variety of VDR and malignant VTA were found during long-term follow-up in patients with ICA. During nearly a 5 years follow-up period, the recurrence rate of malignant VTA was considerable. fVPC, nsVT, and malignant VTA were most often found in patients with an ARVC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study analyzes the natural history of a large cohort of probands with Brugada syndrome (BrS) to assess the predictive value of different clinical and electrocardiographic parameters for the development of ventricular fibrillation (VF) or sudden cardiac death (SCD) during a long-term follow-up. Baseline characteristics of 289 consecutive probands (203 men; mean age 45 ± 16 years) with a Brugada type 1 electrocardiogram were analyzed. After a mean follow-up of 10.1 ± 4.6 years, 29 malignant arrhythmias occurred. On multivariate analysis, a history of VF and syncopal episodes, fragmented QRS (f-QRS), spontaneous type 1 electrocardiogram, and early repolarization pattern were significantly associated with later occurrence of VF/SCD. In patients with drug-induced BrS, the accentuation or de novo appearance of f-QRS in other leads was always associated with VF/SCD. Cerebrovascular events occurred in 8 patients with atrial fibrillation (15.1%), most of them (75%) presenting as the first clinical manifestation. The time-to-diagnosis was found to be significantly shorter in those patients who directly came to our center than in those who referred to our center for a second opinion. In conclusion, systematic use of the pharmacologic challenge in patients with unexplained cardiovascular symptoms and/or atrial fibrillation might significantly improve the identification of BrS with a shortening of the time-to-diagnosis. The CHA 2 DS 2 VASc score might be inappropriate for predicting transient ischemic attack or stroke in BrS. This study confirms the independent predictive value of previous VF and syncopal episodes, f-QRS, type 1 electrocardiogram, and early repolarization pattern. In BrS a sufficiently long follow-up is necessary before conclusions on prognosis are apparent., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Prolonged P-wave duration, a marker of left atrial abnormality, is associated with myocardial fibrosis, atrial fibrillation, and all-cause death. It is not known if prolonged P-wave duration is associated with sudden cardiac death (SCD) in the general population. We aimed to evaluate whether prolonged P-wave duration is independently associated with SCD risk in the Atherosclerosis Risk in Communities Study, a community-based prospective cohort study. We included 15,321 participants in our analysis (age 54.2 ± 5.7 years, 55.2% women, 26.4% black). Prolonged P-wave duration was defined as maximum P-wave duration >120 ms and was determined from 12-lead electrocardiograms obtained during 4 exams (1987 to 1999). SCD was physician adjudicated and defined as a sudden, pulseless condition in a previously stable patient without evidence for noncardiac cause of death. We used Cox proportional hazard models to assess the association between prolonged P-wave duration and SCD, adjusting for cardiovascular risk factors and conditions including atrial fibrillation. During a mean follow-up of 12.5 years (1987 to 2001), 268 SCDs were identified. The multivariable hazard ratio (95% confidence interval) of prolonged P-wave duration for SCD was 1.70 (1.31 to 2.20). This association was attenuated but remained significant after updating covariates to the end of follow-up with a hazard ratio of 1.35 (1.04 to 1.76). In conclusion, prolonged P-wave duration is independently associated with an increased risk of SCD in the general population. This association is independent of atrial fibrillation and is only partially mediated by shared cardiovascular risk factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)

We investigated the prognostic value of newly developed T-wave inversion after primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction. New T-wave inversion was defined as new onset of T-wave inversion after the primary PCI, without negative T waves on the presenting electrocardiogram. The primary end point was the occurrence of major adverse cardiac events (MACE), which consisted of cardiovascular mortality, nonfatal myocardial infarction, and rehospitalization for heart failure. A total of 271 patients were analyzed and followed up for 24 months in this study. New T-wave inversion was observed in 194 patients (72%), whereas the remaining 77 patients (28%) did not show T-wave inversion after the index PCI. Post-PCI Thrombolysis In Myocardial Infarction flow grade 2 or 3 was observed more frequently in patients with new T-wave inversion (97% vs 90%; p = 0.011). The cumulative MACE rate was significantly lower in patients with new T-wave inversion than in those without new T-wave inversion (8% vs 30%; odds ratio 0.197, 95% confidential interval 0.096 to 0.403; p <0.001). In multivariate Cox regression analysis, new T-wave inversion was an independent prognostic factor for MACE (hazard ratio 0.297, 95% confidential interval 0.144 to 0.611; p = 0.001). In conclusion, newly developed T-wave inversion after primary PCI was associated with favorable long-term outcome., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Reports on the association between the PR-interval and atrial fibrillation (AF) are conflicting. We hypothesized that inconsistencies stem from that fact that the PR-interval represents a composite of several distinct components. We examined the associations of the PR-interval and its components (P-wave onset to P-wave peak duration, P-wave peak to P-wave end duration, and PR-segment) with incident AF in 14,924 participants (mean age 54 ± 5.8 years; 26% black; 55% women) from the Atherosclerosis Risk In Communities study. The PR-interval and its components were automatically measured at baseline (1987 to 1989) from standard 12-lead electrocardiograms. PR-interval >200 ms was considered prolonged and values above the ninety-fifth percentile defined abnormal PR-interval components. AF was ascertained during follow-up through December 31, 2010. Over a median follow-up of 21.2 years, 1,985 participants (13%) developed AF. Prolonged PR-interval was associated with an increased risk of AF (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.02 to 1.40). However, PR-interval components showed varying levels of association with AF (P-wave onset to P-wave peak duration: HR 1.57, 95% CI 1.31 to 1.88; P-wave peak to P-wave end duration: HR 1.20, 95% CI 0.99 to 1.46; and PR-segment: HR 1.05, 95% CI 0.85 to 1.29). In addition, the components of the PR-interval had weak-to-moderate correlation with each other (correlation r ranged from -0.44 to 0.06). In conclusion, our findings suggest the PR-interval represents a composite of distinct components that are not uniformly associated with AF. Without considering the contribution of each component, inconsistent associations between the PR-interval and AF are inevitable., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The association between the J wave, a key component of the early repolarization pattern, and adverse cardiovascular outcomes remains unclear. Inconsistencies have stemmed from the different methods used to measure the J wave. We examined the association between the J wave, detected by an automated method, and adverse cardiovascular outcomes in 14,592 (mean age = 54 ± 5.8 years; 56% women; 26% black) participants from the Atherosclerosis Risk In Communities (ARIC) study. The J wave was detected at baseline (1987 to 1989) and during follow-up study visits (1990 to 1992, 1993 to 1995, and 1996 to 1998) using a fully automated method. Sudden cardiac death, coronary heart disease death, and cardiovascular mortality were ascertained from hospital discharge records, death certificates, and autopsy data through December 31, 2010. A total of 278 participants (1.9%) had evidence of a J wave. Over a median follow-up of 22 years, 4,376 of the participants (30%) died. In a multivariable Cox regression analysis adjusted for demographics, cardiovascular risk factors, and potential confounders, the J wave was not associated with an increased risk of sudden cardiac death (hazard ratio [HR] 0.74, 95% CI 0.36 to 1.50), coronary heart disease death (HR 0.72, 95% CI 0.40 to 1.32), or cardiovascular mortality (HR 1.16, 95% CI 0.87 to 1.56). An interaction was detected for cardiovascular mortality by gender with men (HR 1.54, 95% CI 1.09 to 2.19) having a stronger association than women (HR 0.74, 95% CI 0.43 to 1.25; P-interaction = 0.030). In conclusion, our findings suggest that the J wave is a benign entity that is not associated with an increased risk for sudden cardiac arrest in middle-aged adults in the United States., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Patients with drug-induced type 1 Brugada electrocardiograms (BrECGs) are considered to have good prognosis. Spontaneous type 1 is, instead, considered a risk factor; however, it is probably underestimated because of the BrECG fluctuations. The aim of this study was to analyze, in a large population of patients with Br, the real prevalence of type 1 BrECG using 12-lead 24-hour Holter monitoring (12L-Holter) and its correlation with the time of the day. We recorded 303 12L-Holter in 251 patients. Seventy-five (30%) patients exhibited spontaneous type 1 BrECG at 12-lead ECG (group 1) and 176 (70%) had only drug-induced type 1 (group 2). Type 1 BrECG was defined as "persistent" (>85% of the recording), "intermittent" (<85%), or "absent." In group 1, 12% showed persistent type 1 at 12L-Holter, 57% intermittent type 1%, and 31% never had type 1; in group 2, none had persistent type 1, 20% had intermittent type 1%, and 80% never showed type 1. To evaluate the circadian fluctuations of BrECG, 4 periods in the day were considered. Type 1 BrECG was more frequent between 12-noon and 6 p.m. (52%, p <0.001). In conclusion, in patients with drug-induced type 1, spontaneous type 1 BrECG can be detected more frequently with 12L-Holter than with conventional follow-up with periodic ECGs and this has important implications in the risk stratification. 12L-Holter recording might avoid 20% of the pharmacological challenges with sodium channel blockers, which are not without risks, and should thus be considered as the first screening test, particularly in children or in presence of borderline diagnostic basal ECG., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Prevalence and prognostic value of conduction disturbances in patients with the Brugada syndrome (BrS) remains poorly known. Electrocardiograms (ECGs) from 325 patients with BrS (47 ± 13 years, 258 men) with spontaneous (n = 143) or drug-induced (n = 182) type 1 ECG were retrospectively reviewed. Two hundred twenty-six patients (70%) were asymptomatic, 73 patients (22%) presented with unexplained syncope, and 26 patients (8%) presented with sudden death or implantable cardioverter-defibrillator appropriated therapies at diagnosis or during a mean follow-up of 48 ± 34 months. P-wave duration of ≥120 ms was present in 129 patients (40%), first degree atrioventricular block (AVB) in 113 (35%), right bundle branch block (BBB) in 90 (28%), and fascicular block in 52 (16%). Increased P-wave duration, first degree AVB, and right BBB were more often present in patients after drug challenge than in patients with spontaneous type 1 ST elevation. Left BBB was present in 3 patients. SCN5A mutation carriers had longer P-wave duration and longer PR and HV intervals. In multivariate analysis, first degree AVB was independently associated with sudden death or implantable cardioverter-defibrillator appropriated therapies (odds ratio 2.41, 95% confidence interval 1.01 to 5.73, p = 0.046) together with the presence of syncope and spontaneous type 1 ST elevation. In conclusion, conduction disturbances are frequent and sometimes diffuse in patients with BrS. First degree AVB is independently linked to outcome and may be proposed to be used for individual risk stratification., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The familial prevalence of Brugada syndrome (BrS) in a consecutive series of patients was prospectively determined. BrS is genetically determined with autosomal dominant transmission. The familial prevalence of the BrS is unknown. A detailed pedigree of each family of patients with BrS was assembled and permission was obtained to invite relatives for electrocardiography and an ajmaline challenge. Sixty-two of 98 patients participated in the study and were included over a 6-year period. SCN5A genotyping was performed in 56 of these 62 patients (90%). Electrocardiograms (ECGs) of 488 relatives (mean age 38 ± 20 years, 45% men) were recorded and 270 of these relatives agreed to undergo an ajmaline challenge. Spontaneous type 1 BrS ECG was found in 4 of 488 relatives (0.8%). In the group of relatives in whom ajmaline challenge was performed (n = 270), the finding was positive in 79 subjects (29%). SCN5A genotyping identified 5 other affected relatives. As a result, the total number of affected relatives was 88. Standard 12-lead ECG was normal in 64 of the 88 affected relatives (73%). Mean percentage of affected relatives per family was 27 ± 32% (95% confidence interval 19 to 35). Familial forms of BrS were observed in 41 of the 62 families (66%) and no SCN5A mutations were found in sporadic forms. In conclusion, after active family screening affected relatives were found in almost 1/3 of subjects. BrS appeared to be a familial disease in 2/3 of subjects., (Copyright © 2010 Elsevier Inc. All rights reserved.)

There is controversy about the clinical significance of an incidental finding of a Brugada-type electrocardiogram (ECG) pattern. To assess the prognosis of subjects with a diagnosis of a Brugada-type ECG pattern during a health examination, 13,904 subjects (mean age 58 +/- 10 years) who had the annual health examination including an ECG offered to adult citizens of Moriguchi City, Osaka, Japan, in 1997 were studied. A Brugada-type ECG pattern was found in 98 subjects, and 37 subjects had type 1. During a mean follow-up of 7.8 +/- 1.6 years, there were 4 deaths (4.1%) and 1 cardiovascular death (1.0%) in subjects with a Brugada-type ECG pattern, whereas there were 612 deaths (4.4%) and 142 cardiovascular deaths (1.0%) in those without. One cardiovascular death in a subject with a Brugada-type ECG pattern was sudden death. Unadjusted proportional hazards regression analyses showed that Brugada-type ECG pattern was not associated with either all-cause (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.34 to 2.41) or cardiovascular mortality (HR 0.97, 95% CI 0.14 to 6.93). After adjustment for cardiovascular risk factors, Brugada-type ECG pattern had no association with either all-cause (HR 0.77, 95% CI 0.29 to 2.07) or cardiovascular mortality (HR 1.01, 95% CI 0.14 to 7.31). In conclusion, Brugada-type ECG patterns diagnosed during a health examination in a middle-aged population had a low risk of sudden death and were not associated with increased risk of either cardiovascular or all-cause mortality.

To investigate changes of electrocardiographic parameters with aging and their relation to the presence of SCN5A mutation in probands with Brugada syndrome (BS), we measured several electrocardiographic parameters prospectively during long-term follow-up (10 +/- 5 years) in 8 BS probands with SCN5A mutation (SCN5A-positive group, all men; age 46 +/- 10 years) and 36 BS probands without SCN5A mutation (SCN5A-negative group, all men; age 46 +/- 13 years). Throughout the follow-up period, depolarization parameters, such as P-wave (lead II), QRS (leads II, V(2), V(5)), S-wave durations (leads II, V(5)), and PQ interval (leads II) were all significantly longer and S-wave amplitude (II, V(5)) was significantly deeper in the SCN5A-positive group than in the SCN5A-negative group. The SCN5A-positive group showed a significantly longer corrected QT interval (lead V(2)) and higher ST amplitude (lead V(2)) than those in the SCN5A-negative group. The depolarization parameters increased with aging during the follow-up period in both groups; however, the PQ interval (lead II) and QRS duration (lead V(2)) were prolonged more prominently and the QRS axis deviated more to the left with aging in the SCN5A-positive group than in the SCN5A-negative group. In conclusion, conduction slowing was more marked and more progressively accentuated in Brugada probands with SCN5A mutation than in those without SCN5A mutation.

Brugada syndrome is a genetic dysfunction of the myocardial sodium channel that leads to ventricular dysrhythmias. The electrocardiographic (ECG) pattern of Brugada syndrome is occasionally seen after tricyclic antidepressant (TCA) ingestion; however, the outcome and complication risk for these patients is not clear. The objective of our study was to describe the incidence of Brugada ECG pattern (BEP) and serious complications of these patients in a large case series of intentional TCA ingestions. We also compared the proportion of complications of patients with BEP versus those without BEP. We evaluated 402 TCA ingestions, of which 9 (2.3%) were associated with the development of BEP. We compared the adverse outcomes of all TCA ingestions versus TCA ingestions with BEP. A increase in the adverse outcomes in the BEP group was found: seizures (relative risk [RR] 4; 95% confidence interval [CI] 1.5 to 10.8), widened QRS (RR 4.8; 95% CI 1.8 to 12.9), and hypotension (RR 3.9; 95% CI 2.1 to 7.4). To reduce confounding ingestants, we also compared all patients with an isolated TCA ingestion versus those with BEP. A significant increase in adverse outcomes was again found with the BEP group: seizures (RR 3; 95% CI 1.1 to 8.6), widened QRS (RR 4.8; 95% CI 1.5 to 15.1), and hypotension (RR 3.4; 95% CI 1.9 to 22.3). No deaths or dysrhythmias were found in the BEP group. In conclusion, BEP after TCA ingestion is rare, and death or dysrhythmias did not occur. However, patients with BEP are likely at increased risk for TCA-induced complications.