Incidence of ventricular arrhythmias related to COVID infection and vaccination in patients with Brugada syndrome: Insights from a large Italian multicenter registry based on continuous rhythm monitoring.

INTRODUCTION: Brugada syndrome (BrS) has a dynamic ECG pattern that might be revealed by certain conditions such as fever. We evaluated the incidence and management of ventricular arrhythmias (VAs) related to COVID-19 infection and vaccination among BrS patients carriers of an implantable loop recorder (ILR) or implantable cardioverter-defibrillator (ICD) and followed by remote monitoring. METHODS: This was a multicenter retrospective study. Patients were carriers of devices with remote monitoring follow-up. We recorded VAs 6 months before COVID-19 infection or vaccination, during infection, at each vaccination, and up to 6-month post-COVID-19 or 1 month after the last vaccination. In ICD carriers, we documented any device intervention. RESULTS: We included 326 patients, 202 with an ICD and 124 with an ILR. One hundred and nine patients (33.4%) had COVID-19, 55% of whom developed fever. Hospitalization rate due to COVID-19 infection was 2.76%. After infection, we recorded only two ventricular tachycardias (VTs). After the first, second, and third vaccines, the incidence of non-sustained ventricular tachycardia (NSVT) was 1.5%, 2%, and 1%, respectively. The incidence of VT was 1% after the second dose. Six-month post-COVID-19 healing or 1 month after the last vaccine, we documented NSVT in 3.4%, VT in 0.5%, and ventricular fibrillation in 0.5% of patients. Overall, one patient received anti-tachycardia pacing and one a shock. ILR carriers had no VAs. No differences were found in VT before and after infection and before and after each vaccination. CONCLUSIONS: From this large multicenter study conducted in BrS patients, followed by remote monitoring, the overall incidence of sustained VAs after COVID-19 infection and vaccination is relatively low.

Severity of Brugada syndrome disease manifestation and risk of new-onset depression or anxiety: a Danish nationwide study.

AIMS: Reduced psychological health is associated with adverse patient outcomes and higher mortality. We aimed to examine if a Brugada syndrome (BrS) diagnosis and symptomatic disease presentation were associated with an increased risk of new-onset depression or anxiety and all-cause mortality. METHODS AND RESULTS: All Danish patients diagnosed with BrS (2006-2018) with no history of psychiatric disease and available for ≥6 months follow-up were identified using nationwide registries and followed for up to 5 years after diagnosis. The development of clinical depression or anxiety was evaluated using the prescription of medication and diagnosis codes. Factors associated with developing new-onset depression or anxiety were determined using a multivariate Cox proportional hazards regression model. Disease manifestation was categorized as symptomatic (aborted cardiac arrest, ventricular tachycardia, or syncope) or asymptomatic/unspecified at diagnosis. A total of 223 patients with BrS and no history of psychiatric disease were identified (72.6% male, median age at diagnosis 46 years, 45.3% symptomatic). Of these, 15.7% (35/223) developed new-onset depression or anxiety after BrS diagnosis (median follow-up 5.0 years). A greater proportion of symptomatic patients developed new-onset depression or anxiety compared with asymptomatic patients [21/101 (20.8%) and 14/122 (11.5%), respectively, P = 0.08]. Symptomatic disease presentation (HR 3.43, 1.46-8.05) and older age (lower vs. upper tertile: HR 4.41, 1.42-13.63) were significantly associated with new-onset depression or anxiety. All-cause mortality in this group of patients treated according to guidelines was low (n = 4, 1.8%); however, 3/4 developed depression or anxiety before death. CONCLUSION: Approximately, one-sixth of patients with BrS developed new-onset depression or anxiety following a diagnosis of BrS. Symptomatic BrS disease manifestation was significantly associated with new-onset depression or anxiety.

Risk stratification of sudden cardiac death in asymptomatic female Brugada syndrome patients: A literature review.

BACKGROUND AND OBJECTIVES: Risk stratification in Brugada syndrome remains a difficult problem. Given the male predominance of this disease and their elevated risks of arrhythmic events, affected females have received less attention. It is widely known that symptomatic patients are at increased risk of sudden cardiac death (SCD) than asymptomatic patients, while this might be true in the male population; recent studies have shown that this association might not be significant in females. Over the past few decades, numerous markers involving clinical symptoms, electrocardiographic (ECG) indices, and genetic tests have been explored, with several risk-scoring models developed so far. The objective of this study is to review the current evidence of clinical and ECG markers as well as risk scores on asymptomatic females with Brugada syndrome. FINDINGS: Gender differences in ECG markers, the yield of genetic findings, and the applicability of risk scores are highlighted. CONCLUSIONS: Various clinical, electrocardiographic, and genetic risk factors are available for assessing SCD risk amongst asymptomatic female BrS patients. However, due to the significant gender discrepancy in BrS, the SCD risk amongst females is often underestimated, and there is a lack of research on female-specific risk factors and multiparametric risk scores. Therefore, multinational studies pooling female BrS patients are needed for the development of a gender-specific risk stratification approach amongst asymptomatic BrS patients.

Defining electrocardiographic criteria to differentiate non-type 1 Brugada ECG variants from normal incomplete RBBB patterns in the young SCD-SOS cohort.

INTRODUCTION: We assessed the prevalence of non-type 1 Brugada pattern (T1BrP) in children and young adults from the Sudden Cardiac Death-Screening Of risk factorS cohort and the diagnostic yield of nonexpert manual and automatic algorithm electrocardiogram (ECG) measurements. METHODS: Cross-sectional study. We reviewed 14 662 ECGs and identified 2226 with a rSr'-pattern in V1-V2. Among these, 115 were classified by experts in hereditary arrhythmic-syndromes as having or not non-T1BrP, and were compared with measurements of 5 ECG-derived parameters based on a triangle formed by r' -wave (d(A), d(B), d(B)/h, ß-angle) and ST-ascent, assessed both automatically and manually by nonexperts. We estimated intra- and interobserver concordance for each criterion, calculated diagnostic accuracy and defined the most appropriate cut-off values. RESULTS: A rSr'-pattern in V1-V2 was associated with higher PQ interval and QRS duration, male gender, and lower body mass index (BMI). The manual measurements of non-T1BrP criteria were moderately reproducible with high intraobserver and moderate interobserver concordance coefficients (ICC: 0.72-0.98, and 0.63-0.76). Criteria with higher discriminatory capacity were: distance d(B) (0.72; 95% confidence interval [CI]: 0.65-0.80) and ST-ascent (0.87; 95% CI: 0.82-0.92), which was superior to the 4 r'-wave criteria together (area under curve [AUC: 0.74]). We suggest new cut-offs with improved combination of sensitivity and specificity: d(B) ≥ 1.4 mm and ST-ascent ≥ 0.7 mm (sensitivity: 1%-82%; specificity: 71%-84%), that can be automatically measured to allow classification in four morphologies with increasing non-T1BrP probability. CONCLUSION: rSr'-pattern in precordial leads V1-V2 is a frequent finding and the detection of non-T1BrP by using the aforementioned five measurements is reproducible and accurate. In this study, we describe new cut-off values that may help untrained clinicians to identify young individuals who may require further work-up for a potential Brugada Syndrome diagnosis.

Fever following Covid-19 vaccination in subjects with Brugada syndrome: Incidence and management.

BACKGROUND: Fever is a potential side effect of the Covid-19 vaccination. Patients with Brugada syndrome (BrS) have an increased risk of life-threatening arrhythmias when experiencing fever. Prompt treatment with antipyretic drugs is suggested in these patients. AIM OF THE STUDY: To evaluate the incidence and management of fever within 48 h from Covid-19 vaccination among BrS patients. METHODS: One hundred sixty-three consecutive patients were enrolled in a prospective registry involving five European hospitals with a dedicated inherited disease ambulatory. RESULTS: The mean age was 50 ± 14 years and 121 (75%) patients were male. Prevalence of Brugada electrocardiogram (ECG) pattern type-1, -2, and -3 was 32%, 44%, and 24%, respectively. Twenty-eight (17%) patients had an implantable cardioverter-defibrillator (ICD). Fever occurred in 32 (19%) BrS patients after 16 ± 10 h from vaccination, with a peak of body temperature of 37.9° ± 0.5°. Patients with fever were younger (39 ± 13 vs. 48 ± 13 years, p = .04). No additional differences in terms of sex and cardiovascular risk factors were found between patients with fever and not. Twenty-seven (84%) out of 32 patients experienced mild fever and five (16%) moderate fever. Pharmacological treatment with antipyretic drugs was required in 18 (56%) out of 32 patients and was associated with the resolution of symptoms. No patient required hospital admission and no arrhythmic episode was recorded in patients with ICD within 48 h after vaccination. No induced type 1 BrS ECG pattern and new ECG features were found among patients with moderate fever. CONCLUSION: Fever is a common side effect in BrS patients after the Covid-19 vaccination. Careful evaluation of body temperature and prompt treatment with antipyretic drugs may be needed.

Risk stratification in asymptomatic patients with Brugada syndrome: Utility of multiple risk factor combination rather than programmed electrical stimulation.

BACKGROUND: The prognostic value of programmed electrical stimulation (PES) in Brugada syndrome (BrS) remains controversial. Asymptomatic BrS patients generally have a better prognosis than those with symptoms. The purpose of this study was to evaluate the value of nonaggressive PES with up to two extra stimuli and predict clinical factors for risk stratification in asymptomatic BrS patients. METHODS: The study enrolled 193 consecutive asymptomatic BrS patients with type 1 ECG (mean age: 50 ± 13 years, 180 males) who underwent PES using a nonaggressive uniform protocol. Cardiac events (CEs: sudden cardiac death or ventricular tachyarrhythmia) during the follow-up period were examined. RESULTS: During a mean follow-up of 101 ± 48 months, seven asymptomatic patients (3.6%) had a CE. The incidence of CEs was not different between patients with and without inducible ventricular tachyarrhythmia by PES (p = .51). The clinical significance of risk factor combinations, including spontaneous type 1 ECG, family history of sudden cardiac death, QRS duration in lead V2 , and presence of J wave, was evaluated. Using the Kaplan-Meier method according to the number of risk factors, the prevalence of CE in patients with three or four risk factors was determined to be significantly higher than in those with one risk factor (p = .02 and p = .004, respectively). CONCLUSIONS: The present study suggests that inducibility of ventricular tachyarrhythmia does not predict future CEs in asymptomatic BrS patients. Combination analysis of the other four clinical risk parameters may be effective for risk assessment.

Long-term follow-up in patients with Brugada Syndrome in South China.

OBJECTIVE: To evaluate the presence of Brugada electrocardiogram (ECG) pattern, clinical characteristics, treatment, and long-term prognosis of Brugada syndrome in southern Chinese population. METHODS: This prospective study consisted of a consecutive series of patients with diagnostic coved type I Brugada ECG pattern at baseline between January 2007 and February 2020. Histories of symptoms including ventricular tachycardia (VT)/ventricular fibrillation (VF) episode, syncope, and family history of Brugada Syndrome (BrS) or unexplained sudden cardiac death were collected. Electrophysiological study and implantable cardioverter-defibrillator (ICD) were performed. All patients included in this study were followed up in the outpatient department every 6 months after baseline evaluation. Occurrences of syncope, VF, and sudden death were independently analyzed by two cardiologists. RESULTS: 45 (56.3%) patients were diagnosed with BrS. During a mean follow-up of 7.9 ± 3.6 years, six patients had experienced documented VF/sudden cardiac death (SCD) or recurrent syncope. Two patients experienced episodes of syncope more than once. Two patients experienced onset of electrical storm with a total of 11 episodes of VF. There were 50% of these events occurring in fever status. One of patient with BrS died of SCD. CONCLUSION: There was a very low prevalence of Brugada syndrome in southern Chinese population. The risk of arrhythmic events was low in asymptomatic patients. ICD was high effective in preventing SCD without adverse device outcome in long-term follow-up. Fever can lead to predispose to malignant arrhythmia, and aggressive treatment of febrile state in Brugada syndrome was recommended.

COVID-19 FAQs in paediatric and congenital cardiology: AEPC position paper.

The COVID-19 pandemic has had a huge influence in almost all areas of life, affecting societies, economics, and health care systems worldwide. The paediatric cardiology community is no exception. As the challenging battle with COVID-19 continues, professionals from the Association for the European Paediatric and Congenital Cardiology receive many questions regarding COVID-19 in a Paediatric and Congenital Cardiology setting. The aim of this paper is to present the AEPC position on frequently asked questions based on the most recent scientific data, as well as to frame a discussion on how to take care of our patients during this unprecedented crisis. As the times are changing quickly and information regarding COVID-19 is very dynamic, continuous collection of evidence will help guide constructive decision-making.

Low rate of life-threatening events and limitations in predicting invasive and noninvasive markers of symptoms in a cohort of type 1 Brugada syndrome patients: Data and insights from the GenBra registry.

BACKGROUND: Brugada syndrome (BrS) has diagnostic challenges and controversial risk assessment. We aimed to investigate invasive and noninvasive parameters in symptomatic and asymptomatic patients from a Brazilian cohort of type-1 BrS. METHODS: Patients with spontaneous and drug-induced type-1 BrS were classified into two groups, asymptomatic (n = 116, 84.1%) and symptomatic (n = 22, 15.9%; 13 with arrhythmogenic syncope, 9 with aborted sudden cardiac death). Genetic testing, EPS parameters, and electrocardiogram (ECG) parameters were analyzed. RESULTS: A total of 138 consecutive patients were eligible, 101 men (73.2%), mean 41.4 years, mostly probands (79%). Spontaneous pattern, observed in 77.5% of the patients, was associated with symptoms only if expressed in V1 and V2 standard position (not high precordial leads; p = .014). All symptomatic patients were probands. The presence of right ventricular outflow tract conduction delay (RVOTcd) signs, positive EPS, and SCN5A status was similar between symptomatic and asymptomatic subjects. During the mean 75-month follow-up, eight patients had appropriate therapies. All had spontaneous type-1 ECG pattern and 2/8 (25%) were asymptomatic, with positive EPS. The overall LAE incidence of 1.1% per year dropped to 0.27% in asymptomatic patients. RVOTcd occurred more frequently in SCN5A carriers (QRS-f 33.3% vs. 7.7%; p = .005, AVR sign 58.3% vs. 13.6%; p < .001; deep S in lead I 75% vs. 48.5%, p = .025%), as well as longer HV interval (66 vs. 49 ms; p < .001). CONCLUSIONS: Spontaneous type-1 Brugada pattern in standard leads and proband status were more frequent in symptomatic subjects. RVOTcd, more common in SCN5A carriers, did not predict symptoms in BrS patients. EPS exhibited limited prognostic value for this low-risk population.

The utility of drug challenge testing in Brugada syndrome: A systematic review and meta-analysis.

INTRODUCTION: Brugada syndrome (BrS) is associated with ventricular arrhythmia leading to sudden cardiac death. Risk stratification is challenging, as major arrhythmic events (MAEs) are rare. We assessed the utility of drug challenge testing in BrS by a systematic review and meta-analysis. METHODS AND RESULTS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies compared the incidence of MAE between spontaneous and drug challenge-induced Type 1. Mixed-effects Poisson regression was used to calculate the incidence rate ratio (IRR). Eighteen studies from 2006 to 2018 were included (4099 patients, mean follow-up: 4.5 years). Pooled annual incidences of MAE in spontaneous, drug challenge induced (regardless of symptoms), asymptomatic drug challenge induced, and symptomatic drug challenge-induced Type 1 were 23.8 (95% confidence interval [CI]: 19.8-27.8), 6.5 (95% CI: 3.9-9.1), 2.1 (95% CI: -0.3 to 4.4), and 19.6 (95% CI: 9.9-29.3) per 1000 person-years, respectively. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was not statistically different (IRR = 1.0; 95% CI: 0.6-1.7). CONCLUSIONS: The incidence of MAE in drug challenge-induced Type 1 in asymptomatic patients is low. The incidence of MAE between symptomatic drug challenge induced and asymptomatic spontaneous Type 1 was similar.

Recognition and clinical implications of high prevalence of migraine in patients with Brugada syndrome and drug-induced type 1 Brugada pattern.

INTRODUCTION: We have previously reported high 1-year prevalence of migraine in patients with atrial arrhythmias associated with DI-type 1 BrP. The present study was designed to determine the lifetime prevalence of migraine in patients with Brugada syndrome (BrS) or drug-induced type 1 Brugada pattern (DI-type 1 BrP) and control group, to investigate the demographic and clinical characteristics, and to identify clinical variables to predict underlying BrS/DI-type 1 BrP among migraineurs. METHODS AND RESULTS: Lifetime prevalence of migraine and migraine characteristics were compared between probands with BrS/DI-type 1 BrP (n = 257) and control group (n = 370). Lifetime prevalence of migraine was 60.7% in patients with BrS/DI-type 1 BrP and 30.3% in control group (p = 3.6 × 10-14 ). On stepwise regression analysis, familial migraine (odds ratio [OR] of 4.4; 95% confidence interval [CI]: 2.0-9.8; p = 1.3 × 10-4 ), vestibular migraine (OR of 5.4; 95% CI: 1.4-21.0); p = .013), migraine with visual aura (OR of 1.8; 95% CI: 1.0-3.4); p = .04) and younger age-at-onset of migraine (OR of 0.95; 95% CI: 0.93-0.98); p = .004) were predictors of underlying BrS/DI-type 1 BrP among migraineurs. Use of anti-migraine drugs classified as "to be avoided" or "preferably avoided" in patients with BrS and several other anti-migraine drugs with potential cardiac INa /ICa channel blocking properties was present in 25.6% and 26.9% of migraineurs with BrS/DI-type 1 BrP, respectively. CONCLUSION: Migraine comorbidity is common in patients with BrS/DI-type 1 BrP. We identify several clinical variables that point to an underlying type-1 BrP among migraineurs, necessitating cautious use of certain anti-migraine drugs.

Atrial fibrillation in Brugada syndrome: Current perspectives.

The incidence of atrial fibrillation (AF) in Brugada syndrome (BrS) has been reported at between 9% and 53% by different series, but the true prevalence is unknown. However, AF may be the presenting feature in some patients. The underlying mechanisms for AF may be a combination of multiple factors, genetic or acquired, that may impact upon autonomic function, atrial structure, and conduction velocities or other unknown factors. The presence of AF has been associated with a more malignant course, with a greater incidence of syncope and ventricular arrhythmias, thus acting as marker of more advanced disease. Regarding the management of patients with AF, antiarrhythmic drugs effective in preventing malignant arrhythmias in BrS such as quinidine or invasive treatment with pulmonary vein isolation (PVI) may be useful in AF treatment. In this review, we aim to present the current perspectives regarding the genetics, pathophysiology, management, and prognosis of AF in patients with BrS.

Chest pain in Brugada syndrome: Prevalence, correlations, and prognosis role.

BACKGROUND: Brugada syndrome (BrS) is sometimes diagnosed because of chest pain. Prevalence and characteristics of such BrS patients are unknown. METHODS: A total of 200 BrS probands were retrospectively included. BrS diagnosis made because of chest pain (n = 34, 17%) was compared to the other ones. RESULTS: BrS probands with diagnosis because of chest pain had significantly more often smoker habits, increased body mass index, and familial history of coronary artery disease but less frequently previous resuscitated sudden death/syncope or atrial fibrillation. Presence of coronary spasm and familial coronary artery disease were independently associated with BrS diagnosed because of chest pain. They presented more often with spontaneous type 1 ST elevation (59% vs 26%, P = .0004) and higher ST elevation during the episode of chest pain compared to other patients or compared to baseline electrocardiogram after chest pain resumption. ST elevation during chest pain was lower compared to ajmaline test. A total of 20% of them had significant coronary artery disease and four (11%) had coronary spasm, and they experienced more often recurrent chest pain episodes (24% vs 5%, P = .0002). Presence of chest pain at BrS diagnosis was not correlated to future arrhythmic events in univariate analysis. Only previous sudden cardiac death (SD)/syncope and familial SD were still significantly associated with outcome in multivariate analysis. CONCLUSION: Chest pain is a common cause for BrS diagnosis, although major part is not apparently explained by ischemic heart disease. Mechanisms leading to chest main remain unknown in the other ones. ST elevation is higher in this situation but does not seem to carry poor prognosis.

Clinical Profile and Long-Term Follow-Up of Children with Brugada Syndrome.

Brugada syndrome (BrS) is a rare channelopathy associated with sudden cardiac death (SCD). Although outcome data of adult cohorts are well known, information on children are lacking. The aim of the present study was to analyze the clinical profile, treatment approach and long-term outcome of children affected with BrS. After a systematic review of the literature compiled from a thorough database search (PubMed, Web of Science, Cochrane Libary, Cinahl), data from a total of 4 studies which included 262 BrS patients were identified. The mean age of patients was 12.1 ± 5.5, 53.8% males and 19.8% spontaneous BrS type I. 80.2% of patients presented BrS ECG I after receiving sodium channel blockers. 76% of these patients were asymptomatic while only 17.9% suffered from recurrent syncope. Around 1.5% of the patients were admitted due to aborted SCD, and 3% suffered from atrial arrhythmias. Electrophysiological work-up was performed in 132 patients. Induction of ventricular tachycardia/ventricular fibrillation using programmed ventricular stimulation was inducible in 16 patients. 56 children received an ICD. 11 patients received quinidine. An electrical storm was documented in 1 patient. Appropriate shocks occured in 16% of the patients over a median follow-up period of 62.2 (54-64). ICD-related complications were observed in 11 patients (19.6%) with a predominance of inappropriate shocks and lead failure and/or fracture. Although BrS in the childhood is rare, diagnosis and management continues to be challenging. ICD therapy is an effective therapy in high-risk children with BrS, however, with relevant ICD-related complications.

The 10-Year Prognosis and Prevalence of Brugada-Type Electrocardiograms in Elderly Women: A Longitudinal Nationwide Community-Based Prospective Study.

BACKGROUND: Brugada syndrome is a disorder associated with sudden cardiac death and characterized by an abnormal electrocardiogram (ECG). Previous studies were predominantly conducted in men, and the data on long-term prognosis are limited. Information about women, especially elderly women, is lacking. OBJECTIVE: The aim of this study was to investigate the long-term prognosis of the Brugada ECG pattern in elderly women. METHOD: We investigated the 10-year prognosis of the Brugada ECG pattern in elderly women in a nationwide community-based population in Taiwan. Community-dwelling women older than 55 years were prospectively recruited from December 2008 to March 2013 by a stratified random sampling method. All enrolled individuals were followed up annually until April 2019, and the cause of death was documented by citizen death records. RESULTS: Among 2597 women, 60 (2.31%) had a Brugada-type ECG, and this prevalence was higher than the mean global prevalence of 0.23%. One woman had a type 1 ECG (0.04%), whereas 15 (0.58%) and 44 (1.70%) women had type 2 and type 3 ECG patterns, respectively. Cox survival analysis revealed that all-cause mortality and cardiac mortality were similar in the individuals with and without a Brugada-type ECG during a mean follow-up of 96.1 ± 20.5 months. CONCLUSIONS: Our findings suggest that Brugada ECG patterns are not infrequent in elderly women but are not associated with increased risk of mortality in long-term follow-up; these findings may help reduce unnecessary anxiety for physicians, nurses, allied health caregivers, and 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.

Prediction of ventricular tachyarrhythmia in Brugada syndrome by right ventricular outflow tract conduction delay signs.

BACKGROUND: Brugada syndrome (BrS) is an autosomal dominant disease responsible for sudden cardiac death in young individuals without structural anomalies. The most critical part in the management of this channelopathy is identification of high-risk patients, especially asymptomatic subjects. Prior studies have shown that conduction delay in the right ventricular outflow tract (RVOT) is the main mechanism for developing ventricular tachyarrhythmia (VTA) in BrS patients. The aim of this study was to investigate the significance of electrocardiographic RVOT conduction delay parameters as predictors for development of VTA in patients with BrS. METHODS AND RESULTS: We retrospectively analyzed electrocardiograms obtained from 147 BrS patients (43 ± 15 years, 65% men) and assessed the following electrocardiographic parameters: (1) Tzou criteria (V1R > 0.15 mV, V6S > 0.15 mV, and V6S:R > 0.2), (2) prominent S wave in lead I, lead II, and lead III, (3) SII > SIII, and (4) prominent Q wave in lead III as possible predictors of VTA occurrences during follow-up. Prominent SI, SII, SIII, SII > SIII, QIII, and +ve Tzou criteria occurred more frequently in patients who either presented with VTA or developed VTA during the follow-up of 56 (IQR: 40-76) months. SII > SIII has the highest area under the curve for prediction of VTA (AUC: 0.84, sensitivity: 80%, specificity: 89%). Multivariable regression analysis showed that prominent S waves in lead I, SII > SIII and +ve Tzou criteria are independent predictors for VTA in BrS patients. CONCLUSION: Prominent S in lead I, SII > SIII and +ve Tzou criteria can be used as effective signs for predicting VTA in patients with BrS.

Genotype-phenotype relationship and risk stratification in loss-of-function SCN5A mutation carriers.

INTRODUCTION: Loss-of-function (LoF) mutations in the SCN5A gene cause multiple phenotypes including Brugada Syndrome (BrS) and a diffuse cardiac conduction defect. Markers of increased risk for sudden cardiac death (SCD) in LoF SCN5A mutation carriers are ill defined. We hypothesized that late potentials and fragmented QRS would be more prevalent in SCN5A mutation carriers compared to SCN5A-negative BrS patients and evaluated risk markers for SCD in SCN5A mutation carriers. METHODS: We included all SCN5A loss-of-function mutation carriers and SCN5A-negative BrS patients from our center. A combined arrhythmic endpoint was defined as appropriate ICD shock or SCD. RESULTS: Late potentials were more prevalent in 79 SCN5A mutation carriers compared to 39 SCN5A-negative BrS patients (66% versus 44%, p = .021), while there was no difference in the prevalence of fragmented QRS. PR interval prolongation was the only parameter that predicted the presence of a SCN5A mutation in BrS (OR 1.08; p < .001). Four SCN5A mutation carriers, of whom three did not have a diagnostic type 1 ECG either spontaneously or after provocation with a sodium channel blocker, reached the combined arrhythmic endpoint during a follow-up of 44 ± 52 months resulting in an annual incidence rate of 1.37%. CONCLUSION: LP were more frequently observed in SCN5A mutation carriers, while fQRS was not. In SCN5A mutation carriers, the annual incidence rate of SCD was non-negligible, even in the absence of a spontaneous or induced type 1 ECG. Therefore, proper follow-up of SCN5A mutation carriers without Brugada syndrome phenotype is warranted.

Arrhythmic Events in Brugada Syndrome: A Nationwide Israeli Survey of the Clinical Characteristics, Treatment; and Long-Term Follow-up (ISRABRU-VF).

BACKGROUND: Limited information exists about detailed clinical characteristics and management of the small subset of Brugada syndrome (BrS) patients who had an arrhythmic event (AE). OBJECTIVES: To conduct the first nationwide survey focused on BrS patients with documented AE. METHODS: Israeli electrophysiology units participated if they had treated BrS patients who had cardiac arrest (CA) (lethal/aborted; group 1) or experienced appropriate therapy for tachyarrhythmias after prophylactic implantable cardioverter defibrillator (ICD) implantation (group 2). RESULTS: The cohort comprised 31 patients: 25 in group 1, 6 in group 2. Group 1: 96% male, mean CA age 38 years (range 13-84). Nine patients (36%) presented with arrhythmic storm and three had a lethal outcome; 17 (68%) had spontaneous type 1 Brugada electrocardiography (ECG). An electrophysiology study (EPS) was performed on 11 patients with inducible ventricular fibrillation (VF) in 10, which was prevented by quinidine in 9/10 patients. During follow-up (143 ± 119 months) eight patients experienced appropriate shocks, none while on quinidine. Group 2: all male, age 30-53 years; 4/6 patients had familial history of sudden death age < 50 years. Five patients had spontaneous type 1 Brugada ECG and four were asymptomatic at ICD implantation. EPS was performed in four patients with inducible VF in three. During long-term follow-up, five patients received ≥ 1 appropriate shocks, one had ATP for sustained VT (none taking quinidine). No AE recurred in patients subsequently treated with quinidine. CONCLUSIONS: CA from BrS is apparently a rare occurrence on a national scale and no AE occurred in any patient treated with quinidine.