ajmaline and Brugada-Syndrome

Pharmacologic challenge with sodium channel blockers is part of the diagnostic workout in patients with suspected Brugada syndrome. The test is overall considered safe but both ajmaline and flecainide detain well known pro-arrhythmic properties. Moreover, the treatment of patients with life-threatening arrhythmias during these diagnostic procedures is not well defined. Current consensus guidelines suggest to adopt cautious protocols interrupting the sodium channel blockers as soon as any ECG alteration appears. Nevertheless, the risk of life-threatening arrhythmias persists, even adopting a safe and cautious protocol and in absence of major arrhythmic risk factors. The authors revise the main published case studies of sodium channel blockers challenge in adults and in children, and summarize three cases of untreatable ventricular arrhythmias discussing their management. In particular, the role of advanced cardiopulmonary resuscitation with extra-corporeal membrane oxygenation is stressed as it can reveal to be the only reliable lifesaving facility in prolonged cardiac arrest.

Topics: Action Potentials; Adolescent; Adult; Aged; Aged, 80 and over; Ajmaline; Brugada Syndrome; Cardiopulmonary Resuscitation; Child; Electrocardiography; Extracorporeal Membrane Oxygenation; Female; Flecainide; Heart Arrest; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Sodium Channel Blockers; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation; Young Adult

A 31-year-old male patient presented with complaints of palpitations, dizziness, and recurrent episodes of syncope. A 12-lead electrocardiogram (ECG) revealed manifest ventricular preexcitation, which suggested Wolff Parkinson White syndrome. In addition, an incomplete right bundle branch block and a 3-mm ST segment elevation ending with inverted T-waves in V2 were consistent with coved-type (type 1) Brugada pattern. An electrophysiological study was performed, and during the mapping, the earliest ventricular activation with the shortest A-V interval was found on the mitral annulus posterolateral site. After successful radiofrequency catheter ablation of the accessory pathway, the Brugada pattern on the ECG changed, which prompted an ajmaline provocation test. A type 1 Brugada ECG pattern occurred following the administration of ajmaline. Considering the probable symptom combinations of these 2 coexisting syndromes and the presence of recurrent episodes of syncope, programmed ventricular stimulation was performed and subsequently, ventricular fibrillation was induced. An implantable cardioverter-defibrillator was implanted soon after.

Topics: Adult; Ajmaline; Animals; Anti-Arrhythmia Agents; Brugada Syndrome; Bundle-Branch Block; Catheter Ablation; Defibrillators, Implantable; Dizziness; Electrocardiography; Electrophysiologic Techniques, Cardiac; Humans; Male; Recurrence; Syncope; Ventricular Fibrillation; Wolff-Parkinson-White Syndrome

The Brugada syndrome is a genetic disease characterized by an abnormal electrocardiogram (ECG) and an elevated risk of sudden cardiac death. Sodium channel blockers (SCBs), such as ajmaline, are used to unmask the characteristic type 1 Brugada electrocardiographic pattern. We review the literature on the incidence of ventricular arrhythmia (VA) during SCB challenge. We evaluate the clinical and electrocardiographic characteristics of these patients as well as their prognosis. All articles published from January 2000 until August 2015, in which the incidence and predictors of VAs during SCB challenge were reported, are reviewed. The occurrence of VA during SCB challenge ranges from 0 to 17.8%. The weighted average for induction of any VA during sodium blocking challenge is 2.4%; for non-sustained ventricular tachycardia (VT), it is 0.34% and for sustained VT 0.59%. No fatal cases were reported. Predictors may be young age, conduction disturbance at baseline ECG, and mutations in the SCN5A gene. All other clinical and electrocardiographic characteristics failed to be consistent predictors. Life-threatening arrhythmias during SCB challenge are not an exceptional event. Therefore, provocation testing must necessarily be performed in an appropriate environment in which advanced life support facilities are present. Patients who have a higher risk for induced arrhythmias might be those who display a conduction disturbance at baseline ECG or have certain SCN5A mutations or are of a younger age. However, survivors of these induced arrhythmias do not seem to suffer from a worse prognosis.

Topics: Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Humans; Incidence; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Risk Factors; Tachycardia, Ventricular; Voltage-Gated Sodium Channel Blockers

Ajmaline is a pharmaceutical agent now administered globally for a variety of indications, particularly investigation of suspected Brugada syndrome. There have been previous reports suggesting that repetitive use of this agent may cause severe liver injury, but little evidence exists demonstrating the same effect after only a single administration.. A 33-year-old man of Libyan origin with no significant past medical history underwent an ajmaline provocation test for investigation of suspected Brugada syndrome. Three weeks later, he presented with painless cholestatic jaundice which peaked in severity at eleven weeks after the test. Blood tests confirmed no evidence of autoimmune or viral liver disease, whilst imaging confirmed the absence of biliary tract obstruction. A liver biopsy demonstrated centrilobular cholestasis and focal rosetting of hepatocytes, consistent with a cholestatic drug reaction. Over the course of the next few months, he began to improve clinically and biochemically, with complete resolution by one year post-exposure.. Whilst ajmaline-related hepatotoxicity was well-recognised in the era in which the drug was administered as a regular medication, clinicians should be aware that ajmaline may induce severe cholestatic jaundice even after a single dose administration.

Topics: Adult; Ajmaline; Brugada Syndrome; Chemical and Drug Induced Liver Injury; Humans; Jaundice, Obstructive; Male; Severity of Illness Index; Voltage-Gated Sodium Channel Blockers

We report on a youngster followed by his paediatrician from birth until 14 years of age for premature beats, most likely of ventricular origin. The sudden death of his sister provoked a re-assessment of his electrocardiograms (ECG), resulting in the diagnosis of Brugada syndrome and the subsequent implantation of a cardioverter defibrillator. This syndrome is a well known entity in adult cardiology, first described by Brugada and Brugada in 1992. It is considered to be the second most common cause of death in young adults after road traffic accidents. In children, however, the Brugada syndrome is not well known and we believe to be certainly underdiagnosed.

Topics: Adolescent; Adult; Ajmaline; Brugada Syndrome; Death, Sudden; Defibrillators, Implantable; Electrocardiography; Female; Humans; Male; Siblings; Sodium Channel Blockers; Tachycardia, Ventricular

The diagnostic type I ECG in Brugada syndrome (BS) is often concealed and fluctuates between the diagnostic and non-diagnostic pattern. Challenge with intravenous ajmaline is used to unmask the diagnostic Brugada ECG. The aim of this study was to evaluate the safety of the test and to identify predictors for the response to an intravenous ajmaline challenge.. In four tertiary referral centres, 677 consecutive patients underwent an intravenous ajmaline challenge for diagnosis or exclusion of BS in accordance with the recommendations of the Brugada consensus conferences. Two hundred and sixty-two ajmaline challenges (39%) were positive. Male gender, familial BS, sudden cardiac arrest (SCA), first-degree AV-block, basal saddleback type ECG, and basal right bundle branch block were identified as predictors for a positive ajmaline challenge. A predictor for negative ajmaline test was the absence of ST-segment elevation at baseline. Six of 12 patients who had experienced SCA, and five of 25 patients with a familial sudden death exhibited a positive response to ajmaline. Only one patient (0.15%) developed sustained ventricular tachyarrhythmias (ventricular fibrillation) during ajmaline challenge, which was terminated by a single external defibrillator shock.. Ajmaline challenge is a safe procedure to unmask the electrocardiographic pattern of BS. Electrocardiographic and clinical parameters were identified to predict patients' response to ajmaline. The results of this study guide the clinician in which setting an ajmaline challenge is an appropriate diagnostic step.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Female; France; Germany; Humans; Injections, Intravenous; Male; Reproducibility of Results; Sensitivity and Specificity; Tachycardia, Ventricular

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Humans

Drug-induced type I Brugada syndrome (BrS) is associated with a ventricular arrhythmia (VA) rate of 1 case per 100 person-years. This study aims to evaluate changes in electrocardiographic (ECG) parameters such as microvolt T wave alternans (mTWA) and heart rate variability (HRV) at baseline and during ajmaline testing for BrS diagnosis.. Consecutive patients diagnosed with BrS during ajmaline testing with 5-year follow-up were included in this study. For comparison, a negative ajmaline control group and an isoproterenol control group were also included. ECG recordings during ajmaline or isoproterenol test were divided in two timeframes from which ECG parameters were calculated: a 5-min baseline timeframe and a 5-min drug timeframe.. A total of 308 patients with BrS were included, 22 (0.7%) of which suffered VAs during follow-up. One hundred patients were included in both isoproterenol and negative ajmaline control groups. At baseline, there was no difference in ECG parameters between control groups and patients with BrS, nor between BrS with and without VAs. During ajmaline testing, BrS with VAs presented longer QRS duration [159 ± 34 ms versus 138 (122-155) ms, p = 0.006], higher maximum mTWA [33.8 (14.0-114) µV versus 8.00 (3.67-28.2) µV, p = 0.001], and lower power in low frequency band [25.6 (5.8-53.8) ms. Ajmaline induced important HRV changes similar to those observed during isoproterenol. Increased mTWA was observed only in patients with BrS. BrS with VAs during follow-up presented worse changes during ajmaline test, including lower LF power and higher maximum mTWA which were independent predictors of events.

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Heart Rate; Humans; Isoproterenol; Prognosis

Brugada syndrome (BrS) is an inherited arrhythmogenic disorder predisposing patients to a high risk of sudden cardiac death. Specific guidelines on the health surveillance of BrS workers are lacking. We report here three cases requiring assessment of specific job capacity, investigated with an interdisciplinary protocol including 24-h Holter electrocardiography with modified precordial leads, pharmacological test with ajmaline, molecular genetic analysis, electrophysiological study with ventricular stimulation, risk stratification, and occupational medicine evaluation: (1) a female 42-yr-old company manager with positive ajmaline test and CACNA1C gene mutation (judged fit for the job with limitations regarding work-related stress); (2) a male 44-yr-old welder with positive ajmaline test, SCN5A gene mutation, and associated OSAS (obstructive sleep apnea syndrome), who was advised to refrain from night shifts and driving company vehicles; (3) a male 45-yr-old electrical technician with inducible ventricular tachyarrhythmia, who was implanted with a biventricular cardioverter defibrillator, and therefore recommended to avoid exposure to electromagnetic fields and working at heights. We conclude that the collaboration between the cardiologist and the occupational physician allows defining the functional capabilities and the arrhythmogenic risk of BrS workers, to optimize job fitness assessment.

Topics: Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Electrocardiography, Ambulatory; Female; Humans; Male

Patients with Brugada syndrome (BrS) have an increased risk of arrhythmias, including atrial tachyarrhythmias (ATas).. The purpose of this study was to assess underlying atrial cardiomyopathy in BrS and the effect of ajmaline (AJM) test on the atrium of BrS patients using electrocardiogram imaging (ECGI).. All consecutive patients diagnosed with BrS in a monocentric registry were screened and included if they met the following criteria: 1) BrS diagnosed following current recommendations; and 2) ECGI map performed before and after AJM with a standard protocol. Consecutive patients with no structural heart disease or BrS who had undergone ECGI were included as a control group. Genetic analysis for SCN5A was performed in all BrS patients. Total atrial conduction time (TACT) and local atrial conduction time (LACT) were calculated from atrial ECGI. The primary endpoint was ATas during follow-up.. Forty-three consecutive BrS patients and 40 control patients were included. Both TACT and LACT were significantly prolonged in BrS patients compared with control patients. Furthermore, TACT and LACT were significantly higher after AJM administration and in BrS patients who were carriers of a pathogenic/likely pathogenic SCN5A variant. After a mean follow-up of 40.9 months, 6 patients experienced a first ATa occurrence (all in the BrS group, 13.9%). TACT was the only independent predictor of ATas with a cutoff of >138.5 ms (sensitivity 0.92 [95% CI: 0.83-0.98], specificity 0.70 [95% CI: 0.59-0.81]).. ECGI-calculated TACT and LACT are significantly prolonged in BrS patients compared with control patients, and in BrS patients after AJM. This may be consistent with a concealed atrial cardiomyopathy in BrS.

Topics: Ajmaline; Atrial Fibrillation; Brugada Syndrome; Cardiomyopathies; Electrocardiography; Humans

Brugada syndrome (BrS) is an inherited disease associated with an increased risk of ventricular arrhythmias. Recent studies have reported the presence of an altered atrial phenotype characterized by abnormal P-wave parameters. The aim of this study was to identify BrS based exclusively on P-wave features through an artificial intelligence (AI)-based model.. Continuous 5 min 12-lead ECG recordings were obtained in sinus rhythm from (i) patients with spontaneous or ajmaline-induced BrS and no history of AF and (ii) subjects with suspected BrS and negative ajmaline challenge. The recorded ECG signals were processed and divided into epochs of 15 s each. Within these epochs, P-waves were first identified and then averaged. From the averaged P-waves, a total of 67 different features considered relevant to the classification task were extracted. These features were then used to train nine different AI-based supervised classifiers. A total of 2228 averaged P-wave observations, resulting from the analysis of 33 420 P-waves, were obtained from 123 patients (79 BrS+ and 44 BrS-). Averaged P-waves were divided using a patient-wise split, allocating 80% for training and 20% for testing, ensuring data integrity and reducing biases in AI-based model training. The BrS+ patients presented with longer P-wave duration (136 ms vs. 124 ms, P < 0.001) and higher terminal force in lead V1 (2.5 au vs. 1.7 au, P < 0.01) compared with BrS- subjects. Among classifiers, AdaBoost model had the highest values of performance for all the considered metrics, reaching an accuracy of over 81% (sensitivity 86%, specificity 73%).. An AI machine-learning model is able to identify patients with BrS based only on P-wave characteristics. These findings confirm the presence of an atrial hallmark and open new horizons for AI-guided BrS diagnosis.

Topics: Ajmaline; Artificial Intelligence; Atrial Fibrillation; Brugada Syndrome; Electrocardiography; Humans

Ajmaline challenge can unmask subcutaneous implantable cardioverter-defibrillator (S-ICD) screening failure in patients with Brugada syndrome (BrS) and non-diagnostic baseline electrocardiogram (ECG). The efficacy of the SMART Pass (SP) filter, a high-pass filter designed to reduce cardiac oversensing (while maintaining an appropriate sensing margin), has not yet been assessed in patients with BrS. The aim of this prospective multicentre study was to investigate the effect of the SP filter on dynamic Brugada ECG changes evoked by ajmaline and to assess its value in reducing S-ICD screening failure in patients with drug-induced Brugada ECGs.. The S-ICD screening with conventional automated screening tool (AST) was performed during ajmaline challenge in subjects with suspected BrS. The S-ICD recordings were obtained before, during and after ajmaline administration and evaluated by the means of a simulation model that emulates the AST behaviour with and without SP filter. A patient was considered suitable for S-ICD if at least one sensing vector was acceptable in all tested postures. A sensing vector was considered acceptable in the presence of QRS amplitude >0.5 mV, QRS/T-wave ratio >3.5, and sense vector score >100. Of the 126 subjects (mean age: 42 ± 14 years, males: 61%, sensing vectors: 6786), 46 (36%) presented with an ajmaline-induced Brugada type 1 ECG. Up to 30% of subjects and 40% of vectors failed the screening during the appearance of Brugada type 1 ECG evoked by ajmaline. The S-ICD screening failure rate was not significantly reduced in patients with Brugada ECGs when SP filter was enabled (30% vs. 24%). Similarly, there was only a trend in reduction of vector-failure rate attributable to the SP filter (from 40% to 36%). The most frequent reason for screening failure was low QRS amplitude or low QRS/T-wave ratio. None of these patients was implanted with an S-ICD.. Patients who pass the sensing screening during ajmaline can be considered good candidates for S-ICD implantation, while those who fail might be susceptible to sensing issues. Although there was a trend towards reduction of vector sensing failure rate when SP filter was enabled, the reduction in S-ICD screening failure in patients with Brugada ECGs did not reach statistical significance.. https://clinicaltrials.gov Unique Identifier NCT04504591.

Topics: Adult; Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Defibrillators, Implantable; Electrocardiography; Humans; Male; Middle Aged; Prospective Studies

The pathogenesis of Brugada syndrome (BrS) and consequently of abnormal electrograms (aEGMs) found in the epicardium of the right ventricular outflow tract (RVOT-EPI) is controversial.. The purpose of this study was to analyze aEGM from high-density RVOT-EPI electroanatomic mapping (EAM).. All patients undergoing RVOT-EPI EAM with the HD-Grid catheter for BrS were retrospectively included. Maps were acquired before and after ajmaline, and all patients had concomitant noninvasive electrocardiographic imaging with annotation of RVOT-EPI latest activation time (RVOTat). High-frequency potentials (HFPs) were defined as ventricular potentials occurring during or after the far-field ventricular EGM showing a local activation time (HFPat). Low-frequency potentials (LFPs) were defined as aEGMs occurring after near-field ventricular activation showing fractionation or delayed components. Their activation time from surface ECG was defined as LFPat.. Fifteen consecutive patients were included in the study. At EAM before ajmaline, 7 patients (46.7%) showed LFPs. All patients showed HFPs before and after ajmaline and LFPs after ajmaline. Mean HFPat (134.4 vs 65.3 ms, P <.001), mean LFPat (224.6 vs 113.6 ms, P <.001), and mean RVOTat (124.8 vs 55.9 ms, P <.001) increased after ajmaline. RVOTat correlated with HFPat before (ρ = 0.76) and after ajmaline (ρ = 0.82), while RVOTat was shorter than LFPat before (P <.001) and after ajmaline (P <.001). BrS patients with history of aborted sudden cardiac death had longer aEGMs after ajmaline.. Two different types of aEGMs are described from BrS high-density epicardial mapping. This might correlate with depolarization and repolarization abnormalities.

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Epicardial Mapping; Humans; Retrospective Studies

The Brugada pattern manifests as a spontaneous variability of the electrocardiographic marker, suggesting a variability of the underlying electrical substrate.. The purpose of this study was to investigate the response of the epicardial substrate of Brugada syndrome (BrS) to programmed ventricular stimulation and to Na blocker infusion.. We investigated 6 patients (all male; mean age 54 ± 14 years) with BrS and recurrent ventricular fibrillation. Five had no type 1 BrS electrocardiogram pattern at admission. They underwent combined epicardial-endocardial mapping using multielectrode catheters. Changes in epicardial electrograms were evaluated during single endocardial extrastimulation and after low-dose ajmaline infusion (0.5 mg/kg in 5 minutes).. All patients had a region in the anterior epicardial right ventricle with prolonged multicomponent electrograms. Single extrastimulation prolonged late epicardial components by 59 ± 31 ms and in 4 patients abolished epicardial components at some sites, without reactivation by surrounding activated sites. These localized blocks occurred at an initial coupling interval of 335 ± 58 ms and then expanded to other sites, being observed in up to 40% of epicardial sites. Ajmaline infusion prolonged electrogram duration in all and produced localized blocks in 62% of sites in the same patients as during extrastimulation. Epicardial conduction recovery after ajmaline occurred intermittently and at discontinuous sites and produced beat-to-beat changes in local repolarization, resulting in an area of marked electrical disparity. These changes were consistent with models based on microstructural alterations under critical propagation conditions.. In BrS, localized functional conduction blocks occur at multiple epicardial sites and with variable patterns, without being reactivated from the surrounding sites.

Topics: Action Potentials; Adult; Aged; Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Heart Block; Humans; Male; Middle Aged

The mechanisms by which sodium channel blockade and high-rate pacing modify electrogram (EGM) substrates of Brugada syndrome (BrS) have not been elucidated.. The purpose of this study was to determine the effect of ajmaline and high pacing rate on the BrS substrates.. Thirty-two patients with BrS (mean age 40 ± 12 years) and frequent ventricular fibrillation episodes underwent right ventricular outflow tract substrate electroanatomical and electrocardiographic imaging (ECGI) mapping before and after ajmaline administration and during high-rate atrial pacing. In 4 patients, epicardial mapping was performed using open thoracotomy with targeted biopsies.. Ajmaline increased the activation time delay in the substrate (33%; P = .002), ST-segment elevation in the right precordial leads (74%; P < .0001), and the area of delayed activation (170%; P < .0001), coinciding with the increased substrate size (75%; P < .0001). High atrial pacing rate increased the abnormal EGM duration at the right ventricular outflow tract areas from 112 ± 48 to 143 ± 66 ms (P = .003) and produced intermittent conduction block and/or excitation failure at the substrate sites, especially after ajmaline administration. Biopsies from the 4 patients with thoracotomy showed epicardial fibrosis where EGMs were normal at baseline but became fractionated after ajmaline administration. In some areas, local activation was absent and unipolar EGMs had a monophasic morphology resembling the shape of the action potential.. Sodium current reduction with ajmaline severely compromises impulse conduction at the BrS fibrotic substrates by producing fractionated EGMs, conduction block, or excitation failure, leading to the Brugada ECG pattern and favoring ventricular fibrillation genesis.

Topics: Adult; Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Humans; Middle Aged; Sodium Channel Blockers; Ventricular Fibrillation

Background The rate of sudden cardiac death (SCD) in Brugada syndrome (BrS) is ≈1%/y. Noninvasive electrocardiographic imaging is a noninvasive mapping system that has a role in assessing BrS depolarization and repolarization abnormalities. This study aimed to analyze electrocardiographic imaging parameters during ajmaline test (AJT). Methods and Results All consecutive epicardial maps of the right ventricle outflow tract (RVOT-EPI) in BrS with CardioInsight were retrospectively analyzed. (1) RVOT-EPI activation time (RVOT-AT); (2) RVOT-EPI recovery time, and (3) RVOT-EPI activation-recovery interval (RVOT-ARI) were calculated. ∆RVOT-AT, ∆RVOT-EPI recovery time, and ∆RVOT-ARI were defined as the difference in parameters before and after AJT. SCD-BrS patients were defined as individuals presenting a history of aborted SCD. Thirty-nine patients with BrS were retrospectively analyzed and 12 patients (30.8%) were SCD-BrS. After AJT, an increase in both RVOT-AT [105.9 milliseconds versus 65.8 milliseconds,

Topics: Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Heart Rate; Humans; Retrospective Studies

Brugada syndrome (BrS) is caused by mutations in SCN5A gene in 15%-20% of cases. Previous studies showed worse prognosis in SCN5A mutation carriers (SCN5A+). To date, there are no data on genotype-phenotype correlation with electrocardiographic (ECG) imaging (ECGI) and high-density epicardial electroanatomic map.. This study aimed to correlate SCN5A mutation with substrate severity in BrS assessed by ECGI and high-density electroanatomic map.. All consecutive BrS patients undergoing ECGI and high-density epicardial electroanatomic map with HD Grid Mapping Catheter were retrospectively analyzed. On ECGI, the following parameters were analyzed before and after ajmaline administration: right ventricular outflow tract (RVOT) activation time (RVOT-AT) and RVOT recovery time (RVOT-RT). On electroanatomic map, the parameters analyzed before and after ajmaline were high-frequency potential activation time (HFPat), high-frequency potential duration (HFPd), high-frequency potential amplitude (HFPa), low-frequency potential activation time (LFPat), low-frequency potential duration (LFPd), and low-frequency potential amplitude (LFPa).. Thirty-nine BrS patients with ECGI were included. Eight patients (20.5%) were SCN5A+. At baseline ECGI map, mean RVOT-RT was longer in SCN5A+ (P = .024). After ajmaline administration, SCN5A+ patients showed longer RVOT-AT (125.6 vs 100.8 ms; P = .045) and longer RVOT-RT (426.4 vs 397 ms; P = .033). After ajmaline administration, SCN5A+ showed longer HFPat (164.1 vs 119.5 ms; P = .041); longer LFPat (272.7 vs 200.5 ms; P = .018); and longer LFPd (211.9 vs 151.2 ms; P = .033).. In BrS, SCN5A+ patients compared with SCN5A- patients exhibit marked depolarization and repolarization abnormalities as assessed by ECGI and epicardial high-density electroanatomic map.

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Humans; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Retrospective Studies

We report a case of 40‑year-old healthy patient presented with aborted sudden cardiac death. Echocardiography and coronarography were normal. ECG showed minimal non-specific changes in right precordial leads. A concealed Brugada syndrome was considered. We performed a provocative ajmaline test with Brugada‑specific lead placement in 2nd, 3rd and 4th intercostal spaces at both parasternal sides. The test has confirmed the supposed diagnose. Detailed history taking revealed that the patient underwent a calf tattoo procedure on the same day. In this case report, we describe a new mechanism in Brugada patients, possibly leading to sudden cardiac death. The skin tattoo procedure is in more than 7 % of cases accompanied with a "tattoo flu syndrome", manifesting with fever, headache and fatigue. The fever is well described as a provoking factor for malignant arrhythmias in Brugada patients. Thus, a simple and safe procedure like skin tattoo can potentially lead to death in concealed Brugada syndrome population (Fig. 7, Ref. 9). Keywords: adical gastrectomy, D2 lymph node dissection, neoadjuvant therapy.

Topics: Adult; Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Humans; Tattooing

Brugada syndrome (BrS) is diagnosed in patients with ST-segment elevation with coved-type morphology in the right precordial leads, occurring spontaneously or after provocative drugs. Due to electrocardiographic (ECG) inconsistency, provocative drugs, such as sodium-channel blockers, are useful for unmasking BrS. Ajmaline is superior to flecainide and procainamide to provoke BrS. Prolonged T-peak to T-end (TpTe) is associated with an increased risk of ventricular arrhythmia and sudden cardiac death in Brugada syndrome patients.. This study aimed to investigate the predictive value of T-peak to T-end interval and corrected T-peak to T-end interval for predicting the positive response of the ajmaline challenge test in suspected Brugada syndrome patients.. Patients who underwent the ajmaline test in our center were enrolled. Clinical characteristics and electrocardiographic parameters were analyzed, including TpTe, corrected TpTe, QT, corrected QT(QTc) interval, and S-wave duration, compared with the result of the ajmaline challenge test.. The study found that TpTe and corrected TpTe interval in suspected BrS patients were not significantly associated with a positive response to the ajmaline challenge test.. The T-peak to T-end interval and corrected T-peak to T-end interval could not predict the positive response of the ajmaline challenge test in suspected Brugada syndrome patients.

Topics: Ajmaline; Brugada Syndrome; Flecainide; Humans; Procainamide; Sodium Channel Blockers

The aim of this study was to investigate the reliability of a novel electrocardiographic (ECG) marker in predicting ventricular arrhythmia (VA) inducibility in individuals with drug-induced Brugada syndrome (BrS) type I pattern. Consecutive patients with drug-induced type I BrS pattern underwent programmed ventricular stimulation (PVS) and, according to their response, were divided into 2 groups. Clinical characteristics and 12-lead ECG intervals before and after ajmaline infusion were compared between the 2 groups. A novel ECG marker named dST-Tiso interval consisting in the interval between the onset of the coved ST-segment elevation and its termination at the isoelectric line was also evaluated. Our cohort included 76 individuals (median age 44 years, 75% male). Twenty-five (32.9%) had VA inducibility requiring defibrillation. As compared with not inducible subjects, those with VA inducibility were more frequently male (92% vs 65%, p = 0.013), had longer PQ interval (basal: 172 vs 152 ms, p = 0.033; after ajmaline: 216 vs 200 ms, p = 0.040), higher J peak (0.6 vs 0.5 mV, p = 0.006) and longer dST-Tiso (360 vs 240 ms, p < 0.001). The dST-Tiso showed a C-statistics of 0.90 (95% confidence interval: 0.82 to 0.99) and an adjusted odds ratio for VA of 1.03 (1.01 to 1.04, p < 0.001). A dST-Tiso interval >300 ms yielded a sensitivity of 92.0%, a specificity of 90.2%, positive and negative predictive values of 82.1% and 95.8%. In conclusion, the dST-Tiso interval is a powerful predictor of VA inducibility in drug-induced BrS type I pattern. External validation is needed, but this marker might be useful in the clinical counseling process of these individuals before invasive PVS.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Female; Heart Ventricles; Humans; Male; Middle Aged; Predictive Value of Tests; Reproducibility of Results

Patients with Brugada syndrome (BrS) can show a leftward deviation of the frontal QRS-axis upon provocation with sodium channel blockers. The cause of this axis change is unclear. In this study, we aimed to determine (1) the prevalence of this left axis deviation and (2) to evaluate its cause, using the insights that could be derived from vectorcardiograms. Hence, from a large cohort of patients who underwent ajmaline provocation testing (

Topics: Adult; Ajmaline; Brugada Syndrome; Electrocardiography; Evoked Potentials; Female; Heart Ventricles; Humans; Male; Middle Aged; Sodium Channel Blockers; Ventricular Function

Genetic testing in Brugada syndrome (BrS) is still not considered to be useful for clinical management of patients in the majority of cases, due to the current lack of understanding about the effect of specific variants. Additionally, family history of sudden death is generally not considered useful for arrhythmic risk stratification. We sought to demonstrate the usefulness of genetic testing and family history in diagnosis and risk stratification. The family history was collected for a proband who presented with a personal history of aborted cardiac arrest and in whom a novel variant in the

Topics: Adolescent; Adult; Aged; Ajmaline; Amino Acid Substitution; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Female; Genetic Testing; HEK293 Cells; Heterozygote; Humans; Loss of Function Mutation; Male; Middle Aged; Mutant Proteins; Mutation, Missense; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Pedigree; Polymorphism, Single Nucleotide; Recombinant Proteins

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Body Surface Potential Mapping; Brugada Syndrome; Diagnosis, Differential; Electrocardiography; Humans; Male; Reproducibility of Results; Wearable Electronic Devices

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Humans; Prospective Studies

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.

Topics: Adult; Aged; Ajmaline; Brugada Syndrome; Electrocardiography; Female; Humans; Male; Middle Aged; Prevalence; Prospective Studies

J wave syndromes (JWS), including Brugada (BrS) and early repolarization syndromes (ERS), are associated with increased risk for life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently very limited. Here, we evaluate the effects of the natural flavone acacetin.. The effects of acacetin on action potential (AP) morphology and transient outward current (Ito) were first studied in isolated canine RV epicardial myocytes using whole-cell patch clamp techniques. Acacetin's effects on transmembrane APs, unipolar electrograms and transmural ECGs were then studied in isolated coronary-perfused canine RV and LV wedge preparations as well as in whole-heart, Langendorff-perfused preparations from which we recorded a 12 lead ECG and unipolar electrograms. Using floating glass microelectrodes we also recorded transmembrane APs from the RVOT of the whole-heart model. The Ito agonist NS5806, sodium channel blocker ajmaline, calcium channel blocker verapamil or hypothermia (32°C) were used to pharmacologically mimic the genetic defects and conditions associated with JWS, thus eliciting prominent J waves and provoking VT/VF.. Acacetin (5-10 μM) reduced Ito density, AP notch and J wave area and totally suppressed the electrocardiographic and arrhythmic manifestation of both BrS and ERS, regardless of the experimental model used. In wedge and whole-heart models of JWS, increasing Ito with NS5806, decreasing INa or ICa (with ajmaline or verapamil) or hypothermia all resulted in accentuation of epicardial AP notch and ECG J waves, resulting in characteristic BrS and ERS phenotypes. Phase 2-reentrant extrasystoles originating from the RVOT triggered VT/VF. The J waves in leads V1 and V2 were never associated with a delay of RVOT activation and always coincided with the appearance of the AP notch recorded from RVOT epicardium. All repolarization defects giving rise to VT/VF in the BrS and ERS models were reversed by acacetin, resulting in total suppression of VT/VF.. We present experimental models of BrS and ERS capable of recapitulating all of the ECG and arrhythmic manifestations of the JWS. Our findings provide definitive support for the repolarization but not the depolarization hypothesis proposed to underlie BrS and point to acacetin as a promising new pharmacologic treatment for JWS.

Topics: Ajmaline; Animals; Brugada Syndrome; Disease Models, Animal; Dogs; Drug Evaluation, Preclinical; Electrocardiography; Flavones; HEK293 Cells; Humans; Hypothermia; Myocytes, Cardiac; Pericardium; Phenylurea Compounds; Tetrazoles; Verapamil

Sodium-channel blockers (SCBs) are associated with arrhythmia, but variability of cardiac electrical response remains unexplained. We sought to identify predictors of ajmaline-induced PR and QRS changes and Type I Brugada syndrome (BrS) electrocardiogram (ECG).. In 1368 patients that underwent ajmaline infusion for suspected BrS, we performed measurements of 26 721 ECGs, dose-response mixed modelling and genotyping. We calculated polygenic risk scores (PRS) for PR interval (PRSPR), QRS duration (PRSQRS), and Brugada syndrome (PRSBrS) derived from published genome-wide association studies and used regression analysis to identify predictors of ajmaline dose related PR change (slope) and QRS slope. We derived and validated using bootstrapping a predictive model for ajmaline-induced Type I BrS ECG. Higher PRSPR, baseline PR, and female sex are associated with more pronounced PR slope, while PRSQRS and age are positively associated with QRS slope (P < 0.01 for all). PRSBrS, baseline QRS duration, presence of Type II or III BrS ECG at baseline, and family history of BrS are independently associated with the occurrence of a Type I BrS ECG, with good predictive accuracy (optimism-corrected C-statistic 0.74).. We show for the first time that genetic factors underlie the variability of cardiac electrical response to SCB. PRSBrS, family history, and a baseline ECG can predict the development of a diagnostic drug-induced Type I BrS ECG with clinically relevant accuracy. These findings could lead to the use of PRS in the diagnosis of BrS and, if confirmed in population studies, to identify patients at risk for toxicity when given SCB.

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Clinical Decision Rules; Dose-Response Relationship, Drug; Electrocardiography; Female; Genetic Markers; Genome-Wide Association Study; Genotyping Techniques; Heart Rate; Humans; Infusions, Intravenous; Male; Polymorphism, Single Nucleotide; Risk Assessment; Sodium Channel Blockers

Abnormal delayed electrograms (EGMs) from the anterior wall of the right ventricular outflow tract (RVOT) epicardium have become the ablation target in Brugada syndrome (BrS).. The aim of this study was to analyze the safety, feasibility, and efficacy of a novel hybrid thoracoscopic approach to perform epicardial RVOT radiofrequency ablation in BrS.. Thirty-six patients with BrS (26 men (72.2%); mean age 36.6±15.8 years; range 3-63 years) who underwent hybrid thoracoscopic epicardial ablation of RVOT from January 2016 to April 2018 were included in this study. Two expert electrophysiologists analyzed the EGMs during ajmaline challenge and guided the surgeon to perform ablation. Ajmaline challenge was repeated after 1 month to assess the absence of the BrS electrocardiographic pattern. Patients were followed by remote monitoring and outpatient visits every 6 months.. The elimination of all abnormal EGMs was achieved in 94.4% of patients. After a mean follow-up of 16 ± 8 months (range 6-30 months), freedom from ventricular arrhythmias was obtained in 7 (77.8%) patients in secondary prevention 9/36 (25%) and in 24 (100%) patients in primary prevention 24/36 (75%). Major complications were observed in 1 patient (2.8%), who experienced late cardiac tamponade.. Hybrid thoracoscopic epicardial RVOT ablation in BrS is a safe and feasible approach, allowing direct visualization of ablation during radiofrequency delivery. Because of ventricular arrhythmia recurrences, implantable cardioverter-defibrillator implantation is still mandatory in patients treated in secondary prevention and with high risk.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Cardiac Tamponade; Catheter Ablation; Electrophysiologic Techniques, Cardiac; Feasibility Studies; Female; Heart Ventricles; Humans; Male; Pericardium; Postoperative Complications; Recurrence; Risk Adjustment; Tachycardia, Ventricular; Thoracic Surgery, Video-Assisted

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Defibrillators, Implantable; Device Removal; Electrocardiography; Humans; Male; Middle Aged; Prosthesis Failure

The authors studied the response rates and relative sensitivity of the most common agents used in the sodium-channel blocker (SCB) challenge.. A type 1 Brugada electrocardiographic pattern precipitated by an SCB challenge confers a diagnosis of Brugada syndrome.. Patients undergoing an SCB challenge were prospectively enrolled across Canada and the United Kingdom. Patients with no prior cardiac arrest and family histories of sudden cardiac death or Brugada syndrome were included.. Four hundred twenty-five subjects underwent SCB challenge (ajmaline, n = 331 [78%]; procainamide, n = 94 [22%]), with a mean age of 39 ± 15 years (54% men). Baseline non-type 1 Brugada ST-segment elevation was present in 10%. A total of 154 patients (36%) underwent signal-averaged electrocardiography, with 41% having late potentials. Positive results were seen more often with ajmaline than procainamide infusion (26% vs. 4%, p < 0.001). On multivariate analysis, baseline non-type 1 Brugada ST-segment elevation (odds ratio [OR]: 6.92; 95% confidence interval [CI]: 3.15 to 15.2; p < 0.001) and ajmaline use (OR: 8.76; 95% CI: 2.62 to 29.2; p < 0.001) were independent predictors of positive results to SCB challenge. In the subgroup undergoing signal-averaged electrocardiography, non-type 1 Brugada ST-segment elevation (OR: 9.28; 95% CI: 2.22 to 38.8; p = 0.002), late potentials on signal-averaged electrocardiography (OR: 4.32; 95% CI: 1.50 to 12.5; p = 0.007), and ajmaline use (OR: 12.0; 95% CI: 2.45 to 59.1; p = 0.002) were strong predictors of SCB outcome.. The outcome of SCB challenge was significantly affected by the drug used, with ajmaline more likely to provoke a type 1 Brugada electrocardiographic pattern compared with procainamide. Patients undergoing SCB challenge may have contrasting results depending on the drug used, with potential clinical, psychosocial, and socioeconomic implications.

Topics: Adult; Ajmaline; Brugada Syndrome; Cohort Studies; Electrocardiography; Female; Humans; Male; Middle Aged; Procainamide; Voltage-Gated Sodium Channel Blockers; Young Adult

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Humans; NAV1.5 Voltage-Gated Sodium Channel; Procainamide

Brugada syndrome (BrS) is associated with a pronounced risk to develop sudden cardiac death (SCD). Up to 21% of patients are related to mutations in SCN5A. Studies identified SCN10A as a contributor of BrS. However, the investigation of the human cellular phenotype of BrS in the presence of SCN10A mutations remains lacking. The objective of this study was to establish a cellular model of BrS in presence of SCN10A mutations using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).. Dermal fibroblasts obtained from a BrS patient suffering from SCD harbouring the SCN10A double variants (c.3803G>A and c.3749G>A) and three independent healthy control subjects were reprogrammed to hiPSCs. Human-induced pluripotent stem cells were differentiated into cardiomyocytes (hiPSC-CMs).The hiPSC-CMs from the BrS patient showed a significantly reduced peak sodium channel current (INa) and a significantly reduced ATX II (sea anemone toxin, an enhancer of late INa) sensitive as well as A-887826 (a blocker of SCN10A channel) sensitive late sodium channel current (INa) when compared with the healthy control hiPSC-CMs, indicating loss-of-function of sodium channels. Consistent with reduced INa the action potential amplitude and upstroke velocity (Vmax) were significantly reduced, which may contribute to arrhythmogenesis of BrS. Moreover, Ajmaline effects on action potentials were stronger in BrS-hiPSC-CMs than in healthy control cells. This is in agreement with the higher susceptibility of patients to sodium channel blocking drugs in unmasking BrS.. Patient-specific hiPSC-CMs are able to recapitulate single-cell phenotype features of BrS with SCN10A mutations and may provide novel opportunities to further elucidate the cellular disease mechanism.

Topics: Action Potentials; Ajmaline; Brugada Syndrome; Cardiotonic Agents; Case-Control Studies; Cellular Reprogramming Techniques; Cnidarian Venoms; Death, Sudden, Cardiac; Humans; Induced Pluripotent Stem Cells; Loss of Function Mutation; Male; Middle Aged; Morpholines; Mutation; Myocytes, Cardiac; NAV1.8 Voltage-Gated Sodium Channel; Niacinamide; Patch-Clamp Techniques; Phenotype; Tachycardia, Ventricular; Voltage-Gated Sodium Channel Blockers

Topics: Adult; Ajmaline; Brugada Syndrome; Electrocardiography; Heart Rate; Humans; Male; Oxygenators, Membrane; Voltage-Gated Sodium Channel Blockers

Familial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias.. This study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families.. Three hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion.. An inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort.. Systematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.

Topics: Adult; Ajmaline; Arrhythmias, Cardiac; Autopsy; Brugada Syndrome; Death, Sudden, Cardiac; Electrocardiography; Family; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Reproducibility of Results; United Kingdom; Voltage-Gated Sodium Channel Blockers

Topics: Ajmaline; Brugada Syndrome; Humans

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Humans; NAV1.5 Voltage-Gated Sodium Channel; Risk; Sodium Channel Blockers

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Humans; Risk

Topics: Ajmaline; Brugada Syndrome; Flecainide; Humans; Sodium Channel Blockers; Syncope

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Humans; Mutation; NAV1.5 Voltage-Gated Sodium Channel

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Humans; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Sodium Channel Blockers

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Humans; Undifferentiated Connective Tissue Diseases

Patients with drug-induced Brugada syndrome (BS) are considered at a lower risk than those with a spontaneous type I pattern. Nevertheless, they can present arrhythmic events.. The purpose of this study was to investigate their clinical characteristics, long-term prognosis and risk factors.. A consecutive cohort of 343 patients with drug-induced BS was included and compared with 78 patients with a spontaneous type I pattern.. The mean age was 40.7 ± 18.3 years. Sudden cardiac death (SCD) was the clinical presentation in 13 (3.8%) and syncope in 86 (25.1%); 244 (71.1%) were asymptomatic. Patients with drug-induced BS were less frequently men (180 (52.5%) vs 63 (80.8%); P < .01), were more frequently asymptomatic (244 (71.1%) vs 44 (56.4%); P < .01), and had less ventricular arrhythmias (VAs) induced during electrophysiology study (41 (13.2%) vs 31 (42.4%); P < .01). An implantable cardioverter-defibrillator was implanted in 128 patients (37.3%). During a median follow-up of 62.5 months (interquartile range 28.9-115.6 months), 34 patients presented arrhythmic events. The event rate was 1.1% person-year (vs 2.3% person-year in patients with a spontaneous type I pattern; P < .01). Presentation as SCD and inducible VAs were independent risk factors significantly associated with arrhythmic events (adjusted hazard ratio 22.0 and 3.5). Drug-induced BS was related to a better prognosis only in asymptomatic individuals.. Drug-induced BS has a good prognosis if asymptomatic; however, SCD is possible. Clinical presentation as SCD and inducible VAs during electrophysiology study are independent risk factors for arrhythmic events. In asymptomatic patients, proband status and inducible VAs can help to identify patients at higher risk, but further evidence is needed.

Topics: Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Belgium; Brugada Syndrome; Child; Child, Preschool; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Forecasting; Humans; Incidence; Infant; Injections, Intravenous; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors; Survival Rate; Time Factors; Young Adult

There is emerging evidence that localization and elimination of abnormal electric activity in the epicardial right ventricular outflow tract may be beneficial in patients with Brugada syndrome.. In Brugada syndrome, AES is commonly located in the right ventricle epicardium and ajmaline exposes its extent and distribution, which is correlated with the degree of coved ST-elevation. AES elimination by radiofrequency ablation results in ECG normalization and VT/VF noninducibility. Substrate-based ablation is effective in potentially eliminating the arrhythmic consequences of this genetic disease.. URL: https://clinicaltrials.gov. Unique identifier: NCT02641431.

Topics: Action Potentials; Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Catheter Ablation; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Electrophysiologic Techniques, Cardiac; Female; Heart Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Tachycardia, Ventricular; Treatment Outcome; Ventricular Fibrillation; Young Adult

Sodium-channel blocker challenge (SCBC) is frequently performed to unmask Brugada syndrome.. We aim to identify predictors of positivity and complications of SCBC in the setting of familial screening of Brugada syndrome.. All consecutive patients from 2000 to 2014 who benefit from a sodium-channel blocker and belong to a family with at least 2 subjects affected by the syndrome were enrolled and followed prospectively. Data were reviewed by 2 physicians blinded to the clinical and genetic status.. Of the 672 SCBCs performed in 137 families, 337 (50%) were positive. Multivariate analysis identified ajmaline (odds ratio [OR] 2.98; 95% CI 1.65-4.91) and a significant S wave in lead DII (OR 3.11; 95% CI 2.12-4.58), DIII (OR 2.75; 95% CI 1.78-4.25), or V. SCBC in the screening of familial Brugada syndrome is safe. The risk of complication is considerably increased in the case of familial history of complicated SCBC, in young patients, and in the presence of decreased electrocardiographic conduction parameters. However, QRS enlargement during the test is not directly related to complications and should not be used to prematurely stop the test unless leading to false-negative results.

Topics: Adult; Ajmaline; Brugada Syndrome; Dose-Response Relationship, Drug; Electrocardiography; False Positive Reactions; Female; Flecainide; Follow-Up Studies; Heart Rate; Humans; Injections, Intravenous; Male; Prognosis; Retrospective Studies; Voltage-Gated Sodium Channel Blockers

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Catheter Ablation; Electrocardiography; Humans; Tachycardia, Ventricular; Ventricular Fibrillation

Intravenous drug challenge is frequently performed to unmask Brugada syndrome (BrS). However, its true sensitivity has never been assessed. We used the obligate BrS transmitters in families affected by BrS to evaluate the true accuracy of drug challenge.. All consecutive patients from 2000 to 2014 who underwent drug challenge during familial screening for BrS were included in the study. Obligate BrS transmitters were defined as the presence of a descendant and non-descendant first-degree relative affected by BrS. Two physicians blinded to the clinical and genetic status reviewed the data.. Among 705 drug challenges performed in 149 families, 50 were performed in obligate transmitters from 42 different families. SCN5A mutations were identified in 20 families. Two obligate transmitters were not carrier of the familial mutation. Based on obligate transmitters, sensitivity was 100% for Ajmaline vs 77% for Flecainide (P=0.002). Based on the presence of the familial SCN5A mutation in all family relatives, sensitivity and specificity of sodium channel blocker challenge were respectively 78% (95/122) and 46% (68/148). During a median follow-up of 91 (26-136) months, 2 ventricular fibrillations occurred in obligate transmitters.. We demonstrated that Ajmaline challenge presents an excellent sensitivity that may rule out the diagnosis of BrS when negative. Conversely, a negative Flecainide challenge may not prevent from Brs inheritance and risk of SCD. This may lead to suggest systematic use of Ajmaline during drug challenge.

Topics: Administration, Intravenous; Adult; Ajmaline; Brugada Syndrome; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; NAV1.5 Voltage-Gated Sodium Channel; Prospective Studies; Single-Blind Method; Sodium Channel Blockers

This study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS.. Brugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects.. Action potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of I. Fractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used.. Our results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.

Topics: Action Potentials; Ajmaline; Animals; Arrhythmias, Cardiac; Brugada Syndrome; Disease Models, Animal; Dogs; Electrocardiography; Humans; Pinacidil; Radiofrequency Ablation; Treatment Outcome

The substrate location and underlying electrophysiological mechanisms that contribute to the characteristic ECG pattern of Brugada syndrome (BrS) are still debated. Using noninvasive electrocardiographical imaging, we studied whole heart conduction and repolarization patterns during ajmaline challenge in BrS individuals.. A total of 13 participants (mean age, 44±12 years; 8 men), 11 concealed patients with type I BrS and 2 healthy controls, underwent an ajmaline infusion with electrocardiographical imaging and ECG recordings. Electrocardiographical imaging activation recovery intervals and activation timings across the right ventricle (RV) body, outflow tract (RVOT), and left ventricle were calculated and analyzed at baseline and when type I BrS pattern manifested after ajmaline infusion. Peak J-ST point elevation was calculated from the surface ECG and compared with the electrocardiographical imaging-derived parameters at the same time point. After ajmaline infusion, the RVOT had the greatest increase in conduction delay (5.4±2.8 versus 2.0±2.8 versus 1.1±1.6 ms;. Magnitude of ST (J point) elevation in the type I BrS pattern is attributed to degree of conduction delay in the RVOT and not prolongation in repolarization time.

Topics: Action Potentials; Adult; Ajmaline; Anti-Arrhythmia Agents; Body Surface Potential Mapping; Brugada Syndrome; Case-Control Studies; Electrocardiography; Female; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Predictive Value of Tests; Refractory Period, Electrophysiological; Signal Processing, Computer-Assisted; Time Factors

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Electrocardiography; Humans; ST Elevation Myocardial Infarction

The class Ia anti-arrhythmic drug ajmaline is used clinically to unmask latent type I ECG in Brugada syndrome (BrS) patients, although its mode of action is poorly characterised. Our aims were to identify ajmaline's mode of action in human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs), and establish a simple BrS hiPSC platform to test whether differences in ajmaline response could be determined between BrS patients and controls. Control hiPSCs were differentiated into spontaneously contracting cardiac clusters. It was found using multi electrode array (MEA) that ajmaline treatment significantly lengthened cluster activation-recovery interval. Patch clamping of single CMs isolated from clusters revealed that ajmaline can block both I

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Cell Differentiation; Heart; Humans; Male; Middle Aged; Myocytes, Cardiac; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Pluripotent Stem Cells

Brugada syndrome is a disease characterized by a specific electrocardiographic pattern and an increased risk of sudden cardiac death. We present this case with the updated literature to emphasise the need to consider the diagnosis of Brugada syndrome in patients admitted to the emergency ward with sudden cardiac arrest.. A 16-year-old female patient was admitted to the emergency ward with complaints of weakness and abdominal pain, and she had four cardiac arrests during her evaluation period. She was referred to our clinic for permanent pacemaker implantation. She was on a temporary pace maker after having had C-reactive protein. Her physical exam was normal except for bilaterally decreased lung sounds. Lung x-ray and computed tomography, which were performed by another institution, revealed minimal pleural effusion and nothing else of significance. Blood and peritoneal fluid samples were sterile. Echocardiographic exam and cardiac enzymes were also in the normal ranges. Electrocardiographic showed incomplete right branch block in leads V1 and V2. An ajmaline test revealed specific electrocardiographic findings of the type I Brugada pattern. We proposed implanting an implantable cardioverter defibrillator to the patient as there were positive findings on the ajmaline test as well as a history of sudden cardiac arrest. After this treatment proposal, the patient's family admitted that she had taken a high dose of verapamil and thus, the encountered bradycardia was associated with verapamil overuse. The ajmaline test was repeated as it was contemplated that the previous positive ajmaline test had been associated with verapamil overuse. Implantable cardioverter defibrillator implantation was proposed again as there was a history of sudden cardiac arrest; however, the family did not consent to implantable cardioverter defibrillator, and the patient was discharged and followed up.. Brugada syndrome should be considered for patients who are admitted to the emergency ward with sudden cardiac arrest though surface electrocardiographic is normal. If there is a suspicion of Brugada syndrome, repeated electrocardiographic should be performed on different occasions. Diagnosis can be clarified by upper costal electrocardiographic or by administering Na channel blockers during electrocardiographic performance.

Topics: Adolescent; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; Electrocardiography; Female; Genetic Testing; Heart Arrest; Humans; Precipitating Factors; Sodium Channel Blockers; Suicide, Attempted; Treatment Outcome; Verapamil

Topics: Ajmaline; Brugada Syndrome; Catheter Ablation; Humans; Models, Theoretical; Radiofrequency Ablation

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Catheter Ablation; Defibrillators, Implantable; Epicardial Mapping; Humans; Male; Middle Aged; Tachycardia, Ventricular

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Heart Arrest; Humans; Lip

This study evaluated the yield of ajmaline testing and assessed the occurrence of confounding responses in a large cohort of families with unexplained cardiac arrest (UCA) or sudden unexplained death (SUD).. Ajmaline testing to diagnose Brugada syndrome (BrS) is routinely used in the evaluation of SUD and UCA, but its yield, limitations, and appropriate dosing have not been studied in a large cohort.. We assessed ajmaline test response and genetic testing results in 637 individuals from 482 families who underwent ajmaline testing for SUD or UCA.. Overall, 89 individuals (14%) from 88 families (18%) had a positive ajmaline test result. SCN5A mutations were identified in 9 of 86 ajmaline-positive cases (10%). SCN5A mutation carriers had positive test results at significantly lower ajmaline doses than noncarriers (0.75 [range: 0.64 to 0.98] mg/kg vs. 1.03 [range: 0.95 to 1.14] mg/kg, respectively; p < 0.01). In 7 of 88 families (8%), it was concluded that the positive ajmaline response was a confounder, either in the presence of an alternative genetic diagnosis accounting for UCA/SUD (5 cases) or noncosegregation of positive ajmaline response and arrhythmia (2 cases). The rate of confounding responses was significantly higher in positive ajmaline responses obtained at >1 mg/kg than in those obtained at ≤1 mg/kg (7 of 48 vs. 0 of 41 individuals; Fisher's exact test: p = 0.014).. In line with previous, smaller studies, a positive ajmaline response was observed in a large proportion of UCA/SUD families. Importantly, our data emphasize the potential for confounding possibly false-positive ajmaline responses in this population, particularly at high doses, which could possibly lead to a misdiagnosis. Clinicians should consider all alternative causes in UCA/SUD and avoid ajmaline doses >1 mg/kg.

Topics: Administration, Intravenous; Adult; Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Diagnostic Errors; Female; Genetic Testing; Heart Arrest; Heterozygote; Humans; Male; Middle Aged; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Pedigree; Phenotype; Ventricular Fibrillation; Voltage-Gated Sodium Channel Blockers

Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K.. Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one.. Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.

Topics: Action Potentials; Adolescent; Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; DNA Mutational Analysis; Electrocardiography; Female; Genetic Predisposition to Disease; Germany; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Phenotype; Predictive Value of Tests; Tertiary Care Centers; Time Factors; Voltage-Gated Sodium Channel Blockers; Young Adult

Topics: Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Defibrillators, Implantable; Electrocardiography; Female; Heart Arrest; Humans; Patient Positioning; Ventricular Fibrillation

Brugada syndrome (BS) in women is considered an infrequent condition with a more favourable prognosis than in men. Nevertheless, arrhythmic events and sudden cardiac death (SCD) also occur in this population. Long-term follow-up data of this group are sparse. The purpose of the present study was to investigate the clinical characteristics and long-term prognosis of women with BS.. A consecutive cohort of 228 women presenting with spontaneous or drug-induced Brugada type I ECG at our institution were included and compared with 314 men with the same diagnosis.. Mean age was 41.5±17.3 years. Clinical presentation was SCD in 6 (2.6%), syncope in 51 (22.4%) and the remaining 171 (75.0%) were asymptomatic. As compared with men, spontaneous type I ECG was less common (7.9% vs 23.2%, p<0.01) and less ventricular arrhythmias were induced during programmed electrical stimulation (5.5% vs 22.3%, p<0.01). An implantable cardioverter defibrillator (ICD) was implanted in 64 women (28.1%). During a mean follow-up of 73.2±56.2 months, seven patients developed arrhythmic events, constituting an event rate of 0.7% per year (as compared with 1.9% per year in men, p=0.02). Presentation as SCD or sinus node dysfunction (SND) was risk factor significantly associated with arrhythmic events (hazard risk (HR) 25.4 and 9.1).. BS is common in women, representing 42% of patients in our database. Clinical presentation is less severe than men, with more asymptomatic status and less spontaneous type I ECG and prognosis is more favourable, with an event rate of 0.7% year. However, women with SCD or previous SND are at higher risk of arrhythmic events.

Topics: Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Belgium; Brugada Syndrome; Child; Child, Preschool; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Forecasting; Heart Rate; Humans; Incidence; Infant; Injections, Intravenous; Male; Middle Aged; Prognosis; Prospective Studies; Sex Factors; Survival Rate; Young Adult

We present a case of a symptomatic patient with Brugada syndrome, who had sustained right ventricular outflow tract tachycardia after pronounced exercise-induced ST segment elevation in V

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Catheter Ablation; Electrocardiography; Heart Conduction System; Humans; Male; Metaproterenol; Middle Aged; Stimulation, Chemical; Tachycardia, Ventricular; Treatment Outcome

The underlying mechanisms of Brugada syndrome (BrS) are not completely understood. Recent studies provided evidence that the electrophysiological substrate, leading to electrocardiogram abnormalities and/or ventricular arrhythmias, is located in the right ventricular outflow tract (RVOT). The purpose of this study was to examine abnormalities of epicardial and endocardial local unipolar electrograms by simultaneous noninvasive mapping in patients with BrS.. Local epicardial and endocardial unipolar electrograms were analyzed using a novel noninvasive epi- and endocardial electrophysiology system (NEEES) in 12 patients with BrS and 6 with right bundle branch block for comparison. Fifteen normal subjects composed the control group. Observed depolarization abnormalities included fragmented electrograms in the anatomical area of RVOT endocardially and epicardially, significantly prolonged activation time in the RVOT endocardium (65±20 vs 38±13 ms in controls; P=0.008), prolongation of the activation-recovery interval in the RVOT epicardium (281±34 vs 247±26 ms in controls; P=0.002). Repolarization abnormalities included a larger area of ST-segment elevation >2 mV and T-wave inversions. Negative voltage gradient (-2.5 to -6.0 mV) between epicardium and endocardium of the RVOT was observed in 8 of 12 BrS patients, not present in patients with right bundle branch block or in controls.. Abnormalities of epicardial and endocardial electrograms associated with depolarization and repolarization properties were found using NEEES exclusively in the RVOT of BrS patients. These findings support both, depolarization and repolarization abnormalities, being operative at the same time in patients with BrS.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Bundle-Branch Block; Case-Control Studies; Electrocardiography; Endocardium; Epicardial Mapping; Female; Heart; Heart Ventricles; Humans; Male; Middle Aged; Young Adult

Myotonic dystrophy type 1 (DM1) generates missplicing of the SCN5A gene, encoding the cardiac sodium channel (Nav 1.5). Brugada syndrome, which partly results from Nav 1.5 dysfunction and causes increased VF occurrence, can be unmasked by ajmaline. We aimed to investigate the response to ajmaline challenge in DM1 patients and its potential impact on their sudden cardiac death risk stratification.. Among 36 adult DM1 patients referred to our institution, electrophysiological study and ajmaline challenge were performed in 12 patients fulfilling the following criteria: (1) PR interval >200 ms or QRS duration >100 ms; (2) absence of complete left bundle branch block; (3) absence of permanent ventricular pacing; (4) absence of implantable cardioverter-defibrillator (ICD); (5) preserved left-ventricular ejection fraction >50%; and (6) absence of severe muscular impairment. Of note, DM1 patients with ajmaline-induced Brugada pattern (BrP) were screened for SCN5A.. In all the 12 patients studied, the HV interval was <70 ms. A BrP was unmasked in three patients but none carried an SCN5A mutation. Ajmaline-induced sustained ventricular tachycardia occurred in one patient with BrP, who finally received an ICD. The other patients did not present any cardiac event during the entire follow-up (15 ± 4 months).. Our study is the first to describe a high prevalence of ajmaline-induced BrP in DM1 patients. The indications, the safety, and the implications of ajmaline challenge in this particular setting need to be determined by larger prospective studies.

Topics: Adolescent; Adult; Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myotonic Dystrophy; Prospective Studies

Atrioventricular nodal reentrant tachycardia (AVNRT) may coexist with Brugada syndrome (BrS).. The present study was designed to determine the prevalence of drug-induced type 1 Brugada ECG pattern (concealed BrS) in patients presenting with clinical spontaneous AVNRT and to investigate their electrocardiographic, electrophysiological, and genetic characteristics.. Ninety-six consecutive patients without any sign of BrS on baseline electrocardiogram undergoing electrophysiological study and ablation for symptomatic, drug-resistant AVNRT and 66 control subjects underwent an ajmaline challenge to unmask BrS. Genetic screening was performed in 17 patients displaying both AVNRT and BrS.. A concealed BrS electrocardiogram was uncovered in 26 of 96 patients with AVNRT (27.1%) and in 3 of 66 control subjects (4.5%) (P ≤ .001). Patients with concealed BrS were predominantly female patients (n=23 [88.5%] vs n=44 [62.9%], P = .015), had higher prevalence of chest pain (n=10 [38.5%] vs n=13 [18.6%], p=0.042), migraine headaches (n=10 [38.5%] vs n=10 [14.2%], p=0.008), and drug-induced initiation and/or worsening of duration and/or frequency of AVNRT (n=4 [15.4%] vs n=1 [1.4%], p=0.006) as compared to patients with AVNRT without BrS. Genetic screening identified 19 mutations or rare variants in 13 genes in 13 of 17 patients with both AVNRT and BrS (yield = 76.5%). Ten of these 13 genotype-positive patients (76.9%) harbored genetic variants known or suspected to cause a loss of function of cardiac sodium channel current (SCN5A, SCN10A, SCN1B, GPD1L, PKP2, and HEY2).. Our results suggest that spontaneous AVNRT and concealed BrS co-occur, particularly in female patients, and that genetic variants that reduce sodium channel current may provide a mechanistic link between AVNRT and BrS and predispose to expression of both phenotypes.

Topics: Adult; Ajmaline; Brugada Syndrome; Catheter Ablation; Electrocardiography; Electrophysiologic Techniques, Cardiac; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Mutation; NAV1.5 Voltage-Gated Sodium Channel; NAV1.8 Voltage-Gated Sodium Channel; Prevalence; Tachycardia, Atrioventricular Nodal Reentry; United States; Voltage-Gated Sodium Channel beta-1 Subunit; Voltage-Gated Sodium Channel Blockers

Topics: Ajmaline; Brugada Syndrome; Catheter Ablation; Female; Humans; Male; Tachycardia, Atrioventricular Nodal Reentry

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Humans; Male; Pericardium; Young Adult

The objective of this study was to correlate the electrocardiogram (ECG) modification during an Ajmaline challenge in patients affected by the Brugada syndrome and implanted with an implantable cardioverter-defibrillator (ICD) with the morphological changes of their ICD's intracardiac electrogram (IEGM).. Sixteen type 1 Brugada syndrome patients implanted with a St Jude Medical AnalyST(®) ICD were enrolled and underwent ajmaline challenge. Intracardiac electrograms and 12 lead ECG signals were collected over the duration of the study and analysed off-line. The right precordial ECG leads were in both the third and fourth intercostal space by putting V5 and V6 in V1 and V2 at the third intercostal space. Two patients were excluded from the analysis due to signal noise issues. Of the remaining 14 patients, 12 and 2 patients were adjudicated to have positive and negative ajmaline challenges, respectively, based on standard ECG criteria. In the ajmaline positive patients, the IEGM T wave amplitude changes were more prominent than those of the IEGM ST segment (-898 ± 463 vs. -55 ± 381 µV, P < 0.05). Furthermore, all of these T wave amplitude changes were in the negative polarity, whereas the change in polarity of the ST segment was mixed. The changes in the IEGM T wave amplitude and ST segment were significantly smaller in the ajmaline negative patients compared with those in the ajmaline positive patients [211 ± 158 (P < 0.05) and 107 ± 54 (P < 0.05) µV, respectively). Over all 14 analysable patients, the change in the ECG ST segment over the timecourse of the ajmaline challenge correlated better with the IEGM T wave amplitude change (R = 0.72 ± 0.33) than the IEGM ST segment change (R = 0.63 ± 0.33). Applying an IEGM T wave amplitude change cut-off of 400 µV for predicting the outcome of the ajmaline challenge yielded 92% sensitivity (11/12) and 100% specificity (2/2).. In Brugada patients, ajmaline challenge elicits significant T wave amplitude changes within the ICD IEGM, greater than those of the IEGM ST segment. This study is the first step to provide new tools able to continuously monitor the type I Brugada aspect in patients affected by the Brugada syndrome.

Topics: Ajmaline; Anti-Arrhythmia Agents; Body Surface Potential Mapping; Brugada Syndrome; Electrocardiography; Female; France; Humans; Male; Middle Aged; Reproducibility of Results; Sensitivity and Specificity

Topics: Adult; Ajmaline; Brugada Syndrome; Calcium Channel Blockers; Electrocardiography; Humans; Male

Topics: Adolescent; Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Child; Contraindications; Electrocardiography; Family Health; Female; Humans; Male; Middle Aged; NAV1.5 Voltage-Gated Sodium Channel; Pedigree; Young Adult

The goal of this study was to investigate the clinical features, management, and long-term follow-up of children with drug-induced Brugada syndrome (BS).. Patients with BS <12 years of age with a spontaneous type I electrocardiogram have a higher risk of arrhythmic events. Data on drug-induced BS in patients <12 years of age are lacking.. Among 505 patients with ajmaline-induced BS, subjects ≤12 years of age at the time of diagnosis were considered as children and eligible for this study.. Forty children (60% male; age 8 ± 2.8 years) were included. Twenty-four children (60%) had a family history of sudden death. Two (5%) had a previous episode of aborted sudden death, and 8 (20%) had syncope. Children experienced more frequent episodes of sinus node dysfunction (SND) compared with older subjects (7.5% vs. 1.5%; p = 0.04) and had a comparable incidence of atrial tachyarrhythmias. Children more frequently experienced episodes of ajmaline-induced sustained ventricular arrhythmias (VAs) compared with older patients (10.0% vs. 1.3%; p = 0.005). Twelve children (30%) received an implantable cardioverter-defibrillator (ICD). After a mean follow-up time of 83 ± 51 months, none of the children died suddenly. Spontaneous sustained VAs were documented in 1 child (2%). Among children with ICD, 1 (8%) experienced an appropriate shock, 4 (33%) had inappropriate ICD shocks, and 4 (33%) experienced device-related complications.. Drug-induced BS is associated with atrial arrhythmias and SND. Children are at higher risk of ajmaline-induced VAs. The rate of device-related complications, leading to lead replacement or inappropriate shocks, is considerable and even higher than with appropriate interventions. Based on these findings, the optimal management of BS in childhood should remain individualized, taking into consideration the patient's clinical history and family's wishes.

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Child; Defibrillators, Implantable; Disease Management; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Registries; Time Factors; Treatment Outcome

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Seizures

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Seizures

Both type 1 myotonic dystrophy (MD1) and Brugada syndrome (BrS) may be complicated by conduction disturbances and sudden death. Spontaneous BrS has been observed in MD1 patients, but the prevalence of drug-induced BrS in MD1 is unknown.. The purpose of this study was to prospectively assess the prevalence of type 1 ST elevation as elicited during pharmacologic challenge with Class 1C drugs in a subgroup of MD1 patients and to further establish correlations with ECG and electrophysiologic variables and prognosis.. From a group of unselected 270 MD1 patients, ajmaline or flecainide drug challenge was performed in a subgroup of 44 patients (27 men, median age 43 years) with minor depolarization/repolarization abnormalities suggestive of possible BrS. The presence of type 1 ST elevation after drug challenge was correlated to clinical, ECG, and electrophysiologic variables.. Eight of 44 patients (18%) presented with BrS after drug challenge. BrS was seen more often in men (26% vs 6%, P = .09) and was related to younger age (35 vs 48 years, P = .07). BrS was not correlated to symptoms, baseline ECG, HV interval, results of signal-averaged ECG, or abnormalities on ambulatory recordings. MD1 patients with BrS had longer corrected QT intervals, greater increase in PR interval after drug challenge, and higher rate of inducible ventricular arrhythmias (62% vs 21%, P = .03). Twelve patients were implanted with a pacemaker and 5 with an implantable cardioverter-defibrillator. Significant bradycardia did not occur in any patients, and malignant ventricular arrhythmia never occurred during median 7-year follow-up (except 1 hypokalemia-related ventricular fibrillation).. BrS is elicited by a Class 1 drug in 18% of MD1 patients presenting with minor depolarization/repolarization abnormalities at baseline, but the finding seems to be devoid of a prognostic role.

Topics: Adult; Ajmaline; Brugada Syndrome; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Flecainide; Follow-Up Studies; France; Humans; Incidence; Male; Myotonic Dystrophy; Prevalence; Prognosis; Prospective Studies; Survival Rate; Voltage-Gated Sodium Channel Blockers

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Humans; Male; Middle Aged; Phenotype; Voltage-Gated Sodium Channel Blockers

Sudden arrhythmic death syndrome defines a sudden unexpected and unexplained death despite comprehensive pathological and toxicological investigation. Previous studies have focused on evaluation of adult relatives. There is, however, a lack of data in children, leading to highly variable management. We sought to determine the clinical utility of cardiac evaluation in pediatric relatives of sudden arrhythmic death syndrome probands.. Retrospective review was undertaken of pediatric patients with a family history of sudden arrhythmic death syndrome assessed from 2010 to 2013 in 2 centers. Clinical history, cardiac, and genetic investigations were assessed, including diagnoses made after evaluation of adult relatives. A total of 112 pediatric relatives from 61 families were evaluated (median age at presentation, 8 years; range, 0.5-16 years). A probable diagnosis was made in 18 (29.5%) families: Brugada syndrome, 13/18 (72%); long QT syndrome, 3/18 (17%); and catecholaminergic polymorphic ventricular tachycardia, 2/18 (11%). Genetic testing identified mutations in 20% of Brugada syndrome (2/10) and 50% of long QT syndrome (1/2) and catecholaminergic polymorphic ventricular tachycardia families (1/2) who were tested. Pediatric evaluation diagnosed 6/112 relatives (5.4%), increasing to 7% (6/85) if only first-degree relatives were assessed. The only useful diagnostic tests were the 12-lead and exercise electrocardiograms and ajmaline provocation test. The median duration of follow-up was 2.1 years (range, 0.2-8.2 years) with no cardiac events.. The yield of evaluating pediatric relatives is significant and higher when focused on first-degree relatives and on conditions usually expressed in childhood. We propose a management pathway for these children.

Topics: Adolescent; Adult; Age Factors; Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Brugada Syndrome; Child; Child, Preschool; Death, Sudden, Cardiac; Electrocardiography; Female; Genetic Predisposition to Disease; Genetic Testing; Humans; Infant; London; Long QT Syndrome; Male; Middle Aged; Pedigree; Phenotype; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Factors; Tachycardia, Ventricular; Time Factors; Young Adult

Topics: Ajmaline; Brugada Syndrome; Cardiovascular Diseases; Child; Feasibility Studies; Humans; Tachycardia, Ventricular

ST-segment elevation in the right precordial electrocardiography (ECG) leads in Brugada syndrome (BS) can be unmasked by class I anti-arrhythmic drugs (sodium channel blockers) administration. It is still debated whether this ECG pattern is better explained by abnormal repolarization or ventricular conduction and depolarization. Conduction diseases can conceal type 1 BS-like ECG in standard V1-V3 leads. ECG alterations were found also in alternative leads. The role of electrophysiology study (EPS) in sudden cardiac death risk stratification remains controversial, and could depend on the phenotypic expression of the cardiac sodium channels disease.. We describe unmasked diffuse J-point and ST-segment anomalies in peripheral and precordial ECG leads and ventricular fibrillation (VF) induction by EPS after ajmaline administration in a patient with pre-existing atypical right bundle branch block (RBBB) concealing subtle anomalies in standard V1-V3 leads. RBBB was influenced by the underlying BS-like ECG associating repolarization anomaly and pre-existing conduction disease. EPS induced VF when RBBB was associated with BS-like ECG, and failed to induce VF when RBBB was present alone.. BS phenotype heterogeneity requires further studies to improve the knowledge of its pathophysiological mechanisms associated with conduction diseases in order to better identify an individual therapy and prognostic stratification.

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Bundle-Branch Block; Electrocardiography; Humans; Male; Middle Aged; Preexisting Condition Coverage; Ventricular Fibrillation

Topics: Adolescent; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Child; Electrocardiography; False Negative Reactions; Female; Follow-Up Studies; Humans; Male; Puberty; Young Adult

Brugada syndrome is associated with sudden cardiac death in patients with a structurally normal heart. The electrocardiogram (ECG) pattern of Brugada syndrome is characterised by complete or incomplete right bundle branch block and ST-segment elevation in the right precordial leads. These ECG signs may not always be apparent but can be unmasked with certain anti-arrhythmia agents. We report here a case of a 26-year-old woman without detectable structural heart disease but with a history of syncope, cardiac arrest, intubation and defibrillation for ventricular fibrillation. We performed challenge tests with propafenone and ajmaline. After infusion of propafenone, there were minimal ECG changes which were not diagnostic for Brugada syndrome. One week later the provocation test was repeated with ajmaline. During infusion of ajmaline, prominent J waves and ST-segment elevation appeared in the right precordial leads (V1-3). Premature ventricular complexes were seen on a 12-lead ECG. The patient's ECG showed Brugada type 1 pattern. She received an internal cardioverter/defibrillator and was discharged with a beta-blocker.

Topics: Adrenergic beta-Antagonists; Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Female; Heart Conduction System; Humans; Predictive Value of Tests; Propafenone

Topics: Ajmaline; Arrhythmogenic Right Ventricular Dysplasia; Brugada Syndrome; Diagnostic Imaging; Electrocardiography; Female; Humans; Male

The role of hormonal changes during pregnancy in Brugada syndrome is unknown. Only rare case reports of Brugada syndrome during pregnancy have been published. In this article, we describe a patient with first clinical manifestation of Brugada syndrome during pregnancy. The definitive diagnosis could only be achieved by drug challenge with ajmaline after childbirth because the spontaneous typical Brugada-like pattern was absent. Elevated hormone levels during pregnancy may increase the risk for arrhythmias in particular cases.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Defibrillators, Implantable; Diagnosis, Differential; Electrocardiography; Female; Humans; Pregnancy; Pregnancy Complications, Cardiovascular; Seizures; Treatment Outcome

Sustained ventricular arrhythmias (sVAs), such as polymorphic ventricular tachycardia or ventricular fibrillation, can complicate ajmaline challenge in patients with Brugada syndrome (BS).. To assess the incidence of life-threatening sVAs during ajmaline administration in a large series of patients with BS. In addition, clinical characteristics as well as prognosis of these patients were evaluated.. All consecutive patients with ajmaline-induced diagnosis of BS were eligible for this study.. A total of 503 patients were included. Nine (1.8%) patients (44% men; mean age 26 ± 18 years) developed a life-threatening sVA during ajmaline challenge. Three patients (33%)were children, and 2 (22%) patients experienced sVAs refractory to the first external defibrillation. One patient underwent venoarterial extracorporeal membrane oxygenation to restore sinus rhythm. Age at the time of ajmaline challenge was significantly lower in patients with sVAs compared with patients without sVAs (26 ± 18 years vs 41 ± 18 years; P = .01). Moreover, patients with sVAs presented more frequently with sinus node dysfunction compared with patients with normal response to ajmaline (22.2% vs 1.4%; P = .01). After a mean follow-up time of 29 ± 8 months, none of the patients who had developed a sVA during ajmaline challenge died suddenly or developed further life-threatening ventricular arrhythmias.. sVA during ajmaline challenge is not a rare event in BS occurring in 9 (1.8%) patients. Despite its challenging acute treatment, the occurrence of ajmaline-induced sVAs in patients with BS might not identify a category at higher risk for further arrhythmic events.

Topics: Adolescent; Adult; Ajmaline; Anti-Arrhythmia Agents; Belgium; Brugada Syndrome; Child; Dose-Response Relationship, Drug; Electrocardiography; Female; Follow-Up Studies; Humans; Incidence; Injections, Intravenous; Male; Middle Aged; Prognosis; Prospective Studies; Risk Factors; Survival Rate; Tachycardia, Ventricular; Time Factors; Young Adult

Topics: Ajmaline; Brugada Syndrome; Electrocardiography; Female; Humans; Male

We report the case of a very prolonged spontaneous episode of self-terminating ventricular fibrillation in a patient with Brugada syndrome (BrS). The patient first underwent implantation of an internal loop recorder after an episode of prolonged loss of consciousness (several minutes) that was suggestive of a nonarrhythmic cause. After a second episode of prolonged syncope, subsequent interrogation of the loop recorder revealed a very prolonged episode of self-terminating ventricular arrhythmia, lasting 2 minutes and 41 seconds. This short report emphasizes the fact that an arrhythmic cause of syncope should not be ruled out in patients with BrS presenting with very prolonged loss of consciousness.

Topics: Administration, Oral; Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Defibrillators, Implantable; Electrocardiography; Follow-Up Studies; Humans; Male; Quinidine; Signal Processing, Computer-Assisted; Tachycardia, Ventricular; Unconsciousness; Ventricular Fibrillation

Topics: Ajmaline; Alanine Transaminase; Alkaline Phosphatase; Anti-Arrhythmia Agents; Bilirubin; Biomarkers; Brugada Syndrome; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Female; Humans; Middle Aged; Serum Albumin; Serum Albumin, Human; Time Factors

J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While ajmaline, a class 1a antiarrhythmic drug, accentuates the J wave in Brugada syndrome, its effect on ER is unreported.. To describe the effect of ajmaline on the electrocardiogram in ER.. We analyzed electrocardiograms before and after the administration of intravenous ajmaline (1 mg/kg) in 31 patients with ER, 21 patients with Brugada type 1 electrocardiogram (Br), and 22 controls. ER was defined as J-point elevation of ≥1 mm with QRS slurring or notching in ≥2 inferolateral leads (I, aVL, II, III, aVF, V4-V6).. Ajmaline decreased mean J-wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups, but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R-wave amplitude was similar in all the groups (ER group -0.14 mV; Br group -0.11 mV; controls -0.13 mV; P = ns), but mean inferolateral S-wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001).. Ajmaline significantly decreases the J-wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J-wave amplitude in ER, although a specific effect of ajmaline on J waves cannot be excluded.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Case-Control Studies; Electrocardiography; Female; Heart Conduction System; Humans; Male

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Female; Heart Conduction System; Humans; Male

The diagnostic Brugada-electrocardiogram (Br-ECG) is characterized by "coved-type" ST-segment elevation (type 1) in V(1) to V(2)/V(3). The sodium-channel blocker test is clinically used to unmask diagnostic Br-ECG in patients with nondiagnostic "saddle-back" Br-ECG (type 2 and type 3).. To assess the prognostic value of the sodium-channel blockers test in individuals with a nondiagnostic Br-ECG.. We studied 153 consecutive patients (128 men; age 41.7 ± 14.0 years) with a type 2/3 Br-ECG who underwent a sodium-channel blocker test with either flecainide (48%) or ajmaline (52%). Nondiagnostic Br-ECGs were identified during the evaluation of cardiac arrest in 5 patients (3%), syncope in 36 (24%), cascade family screening in 48 (31%), and incidental ECG in 64 (42%). A spontaneous type 1 Br-ECG was systematically excluded by serial ECGs (6.1 ± 0.4) and recording of right precordial leads both at standard and second and third intercostal spaces.. The sodium-channel blocker test result was positive in 76 (50%) patients. During a follow-up of 59 ± 33 months, 9 (5.9%) patients experienced events such as syncope (n = 4), appropriate interventions of defibrillator (n = 4), or sudden death (n = 1). A positive sodium-channel blocker test was associated with a significantly higher event rate in symptomatic patients (P = .01) but not in asymptomatic individuals (P = .18). No events occurred among asymptomatic individuals with an incidental nondiagnostic Br-ECG.. In asymptomatic individuals with a nondiagnostic Br-ECG, the incidence of events is low regardless of the sodium-channel blocker test result while in symptomatic patients a positive sodium-channel blocker test result is associated with an adverse arrhythmic outcome and may contribute to risk stratification.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; Diagnostic Errors; Dose-Response Relationship, Drug; Electrocardiography; Exercise Test; Female; Flecainide; Follow-Up Studies; Humans; Incidence; Infusions, Intravenous; Italy; Male; Prognosis; Prospective Studies; Risk Assessment; Sodium Channel Blockers; Time Factors

We describe the case of a 52-year-old male patient with a recently diagnosed hereditary haemochromatosis who was referred to our electrophysiology laboratory due to presyncopal spells during physical exertion. The electrophysiological study unexpectedly revealed a sinus node dysfunction as well as a Brugada syndrome--both diagnosed on the grounds of an ajmaline test.

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Heart Conduction System; Hemochromatosis; Humans; Male; Middle Aged; Sick Sinus Syndrome; Syncope

Recently, we demonstrated that ajmaline caused ST segment elevation in the heart of an SCN5A mutation carrier by excitation failure in structurally discontinuous myocardium. In patients with Brugada syndrome, ST segment elevation is modulated by cardiac sodium (I(Na)), transient outward (I(to)), and L-type calcium currents (I(CaL)).. To establish experimentally whether excitation failure by current-to-load mismatch causes ST segment elevation and is modulated by I(to) and I(CaL).. In porcine epicardial shavings, isthmuses of 0.9, 1.1, or 1.3 mm in width were created parallel to the fiber orientation. Local activation was recorded electrically or optically (di-4-ANEPPS) simultaneously with a pseudo-electrocardiogram (ECG) before and after ajmaline application. Intra- and extracellular potentials and ECGs were simulated in a computer model of the heart and thorax before and after introduction of right ventricular structural discontinuities and during varying levels of I(Na), I(to), and I(CaL).. In epicardial shavings, conduction blocked after ajmaline in a frequency-dependent manner in all preparations with isthmuses ≤ 1.1 mm width. Total conduction block occurred in three of four preparations with isthmuses of 0.9 mm versus one of seven with isthmuses ≥ 1.1 mm (P<.05). Excitation failure resulted in ST segment elevation on the pseudo-ECG. In computer simulations, subepicardial structural discontinuities caused local activation delay and made the success of conduction sensitive to I(Na), I(to), and I(CaL). Reduction of I(to) and increase of I(CaL) resulted in a higher excitatory current, overcame subepicardial excitation failure, and reduced the ST segment elevation.. Excitation failure by current-to-load mismatch causes ST segment elevation and, like ST segment elevation in Brugada patients, is modulated by I(to) and I(CaL).

Topics: Ajmaline; Animals; Anti-Arrhythmia Agents; Brugada Syndrome; Computer Simulation; Electrocardiography; Heart Conduction System; In Vitro Techniques; Male; Swine

Topics: Ajmaline; Animals; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Heart Conduction System; Swine

The clinical characteristics and the results of ajmaline challenge in young individuals with suspected Brugada syndrome (BS) have not been systematically investigated.. Among a larger series of patients included in the BS database of our Department, 179 patients undergoing ajmaline challenge were included in the study and categorized in two groups according to age: group 1 (<18 years old) and group 2 (≥18 years old). Clinical features and results of the ajmaline challenge of each group were compared.. Young individuals were more often asymptomatic compared to adult patients (P = 0.002). They showed a higher number of normal ECGs (P = 0.023), a lower percentage of Brugada type II electrocardiographic pattern compared to the adult population (P = 0.011), and a comparable amount of spontaneous Brugada type III electrocardiographic pattern (P = 0.695). Ajmaline provoked a higher degree of intraventricular conduction delay (P = 0.002) and higher degree of prolongation of the ventricular repolarization phase (P = 0.013) in young individuals but its pro-arrhythmic risk was comparable in the two groups (P = 0.684). Furthermore, inducibility of ventricular arrhythmias in young patients with a positive ajmaline test was comparable to that of the adults with a positive ajmaline test (P = 0.694).. The present study demonstrates the low-risk profile of the ajmaline test in young patients when performed by experienced physicians and nurses in an appropriate environment.

Topics: Adolescent; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Child; Child, Preschool; Electrocardiography; Female; Humans; Infant; Infant, Newborn; Male; Reproducibility of Results; Sensitivity and Specificity; Young Adult

Sporadic cases have reported the coexistence of coronary spasm and Brugada syndrome. However, the prevalence of the Brugada phenotype in coronary spasm is unknown, particularly in non-Japanese populations. In this study, we sought to examine the prevalence of the type 1 Brugada electrocardiogram (ECG) in a large European patient population undergoing intracoronary provocation testing for suspected coronary spasm.. We retrospectively evaluated ECG data for the presence of type 1, 2, and 3 Brugada ECGs from 955 consecutive German patients without obstructive coronary artery disease undergoing intracoronary acetylcholine (ACH) provocation (ACH-test). Eight hundred and twenty-seven patients (age 63 ± 12 years; 42% male) with complete ECG data were eligible for further analysis. The ACH-test revealed coronary spasm in 325 patients (39.3%). A Brugada ECG of any type was found in six patients (0.7%) at baseline and eight patients (0.9%) at any time. There was no difference in the prevalence of coronary spasm in patients with (37.5%) and without (39.3%) Brugada-type ECGs. The type 1 Brugada ECG was not seen at baseline, but two type 1 Brugada ECGs were observed during ACH-administration into the right coronary artery (RCA; 0.2%), one with simultaneous RCA spasm and one without. Ajmaline provocation testing reproduced the type-1 Brugada ECG in the patient without coronary spasm but she had no other features of the Brugada syndrome.. This study reports a low prevalence of the type 1 Brugada ECG in the largest known European collection of intracoronary ACH provocation. In these patients, we found no evidence for the coexistence of Brugada syndrome and coronary spasm. This is in contrast to available Japanese data.

Topics: Acetylcholine; Aged; Ajmaline; Anti-Arrhythmia Agents; Asian People; Brugada Syndrome; Comorbidity; Coronary Vasospasm; Coronary Vessels; Electrocardiography; Female; Germany; Humans; Male; Middle Aged; Prevalence; Retrospective Studies; Vasodilator Agents; White People

The aim of this study was to evaluate new electrocardiographic (ECG) criteria for discriminating between incomplete right bundle branch block (RBBB) and the Brugada types 2 and 3 ECG patterns.. Brugada syndrome can manifest as either type 2 or type 3 pattern. The latter should be distinguished from incomplete RBBB, present in 3% of the population.. Thirty-eight patients with either type 2 or type 3 Brugada pattern that were referred for an antiarrhythmic drug challenge (AAD) were included. Before AAD, 2 angles were measured from ECG leads V(1) and/or V(2) showing incomplete RBBB: 1) α, the angle between a vertical line and the downslope of the r'-wave, and 2) β, the angle between the upslope of the S-wave and the downslope of the r'-wave. Baseline angle values, alone or combined with QRS duration, were compared between patients with negative and positive results on AAD. Receiver-operating characteristic curves were constructed to identify optimal discriminative cutoff values.. The mean β angle was significantly smaller in the 14 patients with negative results on AAD compared to the 24 patients with positive results on AAD (36 ± 20° vs. 62 ± 20°, p < 0.01). Its optimal cutoff value was 58°, which yielded a positive predictive value of 73% and a negative predictive value of 87% for conversion to type 1 pattern on AAD; α was slightly less sensitive and specific compared with β. When the angles were combined with QRS duration, it tended to improve discrimination.. In patients with suspected Brugada syndrome, simple ECG criteria can enable discrimination between incomplete RBBB and types 2 and 3 Brugada patterns.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Bundle-Branch Block; Electrocardiography; Female; Humans; Male; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; ROC Curve

The present study investigated whether several ECG markers of ventricular repolarization are associated with ventricular tachycardia/fibrillation (VT/VF) inducibility in subjects with type 1 ECG pattern of Brugada syndrome (BS).. The clinical data of 23 individuals (19 males, age 42.69 +/- 14.63) with spontaneous (n = 10) or drug-induced (n = 13) type 1 ECG pattern of BS who underwent programmed ventricular stimulation were analysed. Sustained VT/VF was induced in 17 subjects (74%) and was significantly associated with the presence of spontaneous type 1 ECG of BS (P = 0.012). Among the studied ECG repolarization markers, subjects with inducible VT/VF displayed an increased T(peak)-T(end) interval in leads V(2) (88.82 +/- 15.70 vs. 78.33 +/- 4.08 ms, P = 0.02) and V(6) (76.33 +/- 10.08 vs. 66.66 +/- 5.16 ms, P = 0.04) and a greater T(peak)-T(end)/QT ratio in lead V(6) (0.214 +/- 0.028 vs. 0.180 +/- 0.014, P = 0.009) compared with those without arrhythmias. Ventricular tachycardia/fibrillation inducibility was not associated with arrhythmic events during a mean follow-up period of 4.61 +/- 2.14 years (P = 0.739).. The T(peak)-T(end) interval and T(peak)-T(end)/QT ratio were associated with VT/VF inducibility in BS. The utility of T(peak)-T(end)/QT ratio as a new marker of arrhythmogenesis in BS requires further studies, including a large number of patients.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Biomarkers; Brugada Syndrome; Electrocardiography; Female; Flecainide; Heart Conduction System; Humans; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Risk Factors; Tachycardia, Ventricular; Ventricular Fibrillation

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Electrodes; Humans

The Brugada sign has been associated with mutations in SCN5A and with right ventricular structural abnormalities. Their role in the Brugada sign and the associated ventricular arrhythmias is unknown.. The purpose of this study was to delineate the role of structural abnormalities and sodium channel dysfunction in the Brugada sign.. Activation and repolarization characteristics of the explanted heart of a patient with a loss-of-function mutation in SCN5A (G752R) and dilated cardiomyopathy were determined after induction of right-sided ST-segment elevation by ajmaline. In addition, right ventricular structural discontinuities and sodium channel dysfunction were simulated in a computer model encompassing the heart and thorax.. In the explanted heart, disappearance of local activation in unipolar electrograms at the basal right ventricular epicardium was followed by monophasic ST-segment elevation. The local origin of this phenomenon was confirmed by coaxial electrograms. Neither early repolarization nor late activation correlated with ST-segment elevation. At sites of local ST-segment elevation, the subepicardium was interspersed with adipose tissue and contained more fibrous tissue than either the left ventricle or control hearts. In computer simulations entailing right ventricular structural discontinuities, reduction of sodium channel conductance or size of the gaps between introduced barriers resulted in subepicardial excitation failure or delayed activation by current-to-load mismatch and in the Brugada sign on the ECG.. Right ventricular excitation failure and activation delay by current-to-load mismatch in the subepicardium can cause the Brugada sign. Therefore, current-to-load mismatch may underlie the ventricular arrhythmias in patients with the Brugada sign.

Topics: Adolescent; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Cardiomyopathy, Dilated; Chromatography, High Pressure Liquid; Computer Simulation; Electrocardiography; Electrophysiologic Techniques, Cardiac; Female; Genetic Predisposition to Disease; Heart Transplantation; Humans; In Vitro Techniques; Lamin Type A; Muscle Proteins; Mutation; NAV1.5 Voltage-Gated Sodium Channel; Sodium Channels; Ventricular Dysfunction, Right

Topics: Action Potentials; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Cardiomyopathy, Dilated; Computer Simulation; Electrocardiography; Electrophysiologic Techniques, Cardiac; Humans; Sodium Channels; Ventricular Dysfunction, Right

Leads V(1) and V(2) recorded from the standard position (fourth intercostal space) have insufficient sensitivity to detect the diagnostic type 1 Brugada ECG pattern.. The purpose of this study was to compare the sensitivity of bipolar leads with a positive pole at V(2) and a negative pole at V(4) or V(5) with that of the standard unipolar lead V(2) for detection of the type 1 Brugada pattern.. We analyzed digital 15-lead ECGs (12 standard leads plus leads V(1) to V(3) recorded from the third intercostal space [V(1h) to V(3h)]) acquired during diagnostic ajmaline testing in 128 patients (80 men, age 37 +/- 15 years) with suspected Brugada syndrome and standard 12-lead ECGs recorded in 229 healthy subjects (111 men, age 33 +/- 4 years). Bipolar leads between V(2) (positive pole) and V(4) or V(5) (leads V(2-4), V(2-5)) were derived by subtracting leads V(4) and V(5) from V(2). All ECGs were examined for the presence of type 1 Brugada pattern.. During 21 (16.4%) positive ajmaline tests, type 1 pattern was observed in lead V(2h) during 20 tests (95.2%) and in V(2) during 10 tests (47.6%). Type 1 pattern appeared in lead V(2-4) or V(2-5) in all tests when it was present in V(2) and in seven tests during which it was observed in lead V(2h) but not V(2) (17 tests [81%]). Type 1-like pattern was observed in lead V(2-4) or V(2-5) during two nonpositive tests (1.9%) and in one healthy subject (0.4%).. Bipolar leads V(2-4) and V(2-5) are more sensitive than lead V(2) for detection of the type 1 Brugada pattern.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Chi-Square Distribution; Electrocardiography; Electrodes; Female; Humans; Male; Sensitivity and Specificity

We sought to obtain new insights into the pathophysiologic basis of Brugada syndrome (BrS) by studying changes in various electrocardiographic depolarization and/or repolarization variables that occurred with the development of the signature type 1 BrS electrocardiogram (ECG) during ajmaline provocation testing.. BrS is associated with sudden cardiac death. Its pathophysiologic basis, although unresolved, is believed to reside in abnormal cardiac depolarization or abnormal repolarization.. Ajmaline provocation was performed in 269 patients suspected of having BrS with simultaneous recording of ECGs, vectorcardiograms, and 62-lead body surface potential maps.. A type 1 ECG was elicited in 91 patients (BrS patients), 162 patients had a negative test result (controls), and 16 patients had an abnormal test result. Depolarization abnormalities were more prominent in BrS patients and were mapped to the right ventricle (RV) by longer right precordial filtered QRS complex durations (142 +/- 23 ms vs. 125 +/- 14 ms, p < 0.01) and right terminal conduction delay (60 +/- 11 ms vs. 53 +/- 9 ms, p < 0.01). Repolarization abnormalities remained concordant with depolarization abnormalities as indicated by steady low nondipolar content (12 +/- 8% vs. 8 +/- 4%, p = NS), lower spatial QRS-T integrals (33 +/- 12 mV.ms vs. 40 +/- 16 mV.ms, p < 0.05), similar spatial QRS-T angles (92 +/- 39 degrees vs. 87 +/- 31 degrees , p = NS), similar T(peak)-T(end) interval (143 +/- 36 ms vs. 138 +/- 25 ms, p = NS), and similar T(peak)-T(end) dispersion (47 +/- 37 ms vs. 45 +/- 27 ms, p = NS).. The type 1 BrS ECG is characterized predominantly by localized depolarization abnormalities, notably (terminal) conduction delay in the RV, as assessed with complementary noninvasive electrocardiographic techniques. We could not define a separate role for repolarization abnormalities but suggest that the typical signs of repolarization derangements seen on the ECG are secondary to these depolarization abnormalities.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Body Surface Potential Mapping; Brugada Syndrome; Female; Humans; Male; Middle Aged

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; Electrocardiography; Humans

This case study shows a young male presenting a mixture of two disease entities: (1) Brugada syndrome with a nearly-normal baseline electrocardiogram and positive Ajmaline drug challenge as well as (2) idiopathic ventricular fibrillation including extremely short-coupled monomorphic ventricular premature beats (VPB) triggering ventricular fibrillation (coupling interval 318 ± 21 ms). In this phenotypic patient group-more suggestive of idiopathic ventricular fibrillation due to the ultra-short coupling interval of the VPBs-drug treatment with a class IA agent such as Quinidine might be an important option to implantable cardioverter-defibrillator and ablation therapy.

Topics: Adrenergic beta-Antagonists; Adult; Ajmaline; Anti-Arrhythmia Agents; Atrial Fibrillation; Brugada Syndrome; Bundle-Branch Block; Catheter Ablation; Defibrillators, Implantable; Electrocardiography; Humans; Male; Prosthesis Implantation; Quinidine; Treatment Outcome; Ventricular Fibrillation; Ventricular Premature Complexes

Ajmaline is a sodium channel blocking, class 1A anti-arrhythmic drug. It has gained renewed interest in the field of cardiology as a diagnostic agent to reveal the electrocardiographic characteristics in patients with suspected Brugada syndrome. We developed a simple and precise high-performance liquid chromatographic assay to determine ajmaline in serum of patients. The samples were pre-treated using protein precipitation with perchloric acid and the extract was injected into the chromatographic system. The system consisted of an end-capped octadecyl silica column with isocratic elution using perchloric acid in a water-acetonitrile mixture. Ajmaline was detected by fluorescence at 290 and 355 nm for excitation and emission, respectively. The assay was validated in a 21-5300 ng/ml concentration range, the lower limit of quantification was 25 ng/ml. Within day precisions were 1.3-3.9%, between day precisions 2-7% and accuracies were between 95 and 99% for the whole calibration range. The drug was shown to be chemically stable under all relevant conditions. This assay has been successfully applied to pharmacokinetic-pharmacodynamic evaluations of intravenous ajmaline administration to patients with suspected Brugada syndrome.

Topics: Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Calibration; Chromatography, Liquid; Drug Stability; Fluorescence; Humans; Male; Reproducibility of Results; Young Adult

The authors sought to assess the value of the high right precordial leads (RPL) to detect the Type I Brugada ECG pattern in patients suspected of carrying Brugada syndrome (BrS).. Ajmaline testing using 15-lead ECGs was performed in 183 patients suspected of carrying BrS. Standard 12-lead ECG with V1-V3 recorded from the fourth intercostal space and an additional three leads placed over V1-V3 recorded from the third intercostal space were analysed. ECGs were analysed for a Type I ECG pattern in either the standard or high RPLs.. Of the 183 tests, 31 (17%) were positive, and 152 were negative. In all positive studies, at least one high RPL became positive. In 13/31 (42%) cases, the Type I ECG pattern could be observed only in the high RPLs. Standard or high V3 were never positive before standard or high V1-V2. In seven patients, a Type I pattern was seen in one standard and one high RPL (vertical relationship).. The high RPLs are more sensitive than the conventional 12-lead ECG alone and initial observations suggest that they remain specific for BrS, while standard and high lead V3 offer redundant data. A vertical relationship of type 1 patterns may have a similar diagnostic value to that of a horizontal pair.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Case-Control Studies; Electrocardiography; Female; Humans; Male; Middle Aged

Current consensus documents on Brugada syndrome recommend the diagnostic intravenous administration of a Na-channel blocker to be stopped when the QRS prolongs to > or =130% of baseline, presumably because of increased arrhythmic risk.. This study sought to assess QRS prolongation during ajmaline testing and its relation to arrhythmic risk.. We analyzed an electrocardiographic (ECG) database collected during ajmaline testing in 148 patients (92 men, age 36 +/- 15 years). The QRS was measured at baseline and during the 1st to 7th, 10th, and 15th minute after the beginning of ajmaline administration.. The average QRS prolongation was 36% +/- 16% (range 9% to 88%), not significantly different between positive (n = 30) and negative (n = 118) tests. QRS prolonged to > or =130% during 16 (55%) positive and 71 (61%) negative tests (P = .50), with no clinical side effects. The incidence of ventricular arrhythmias was not significantly different between patients with and without QRS prolongation. Short runs (3 to 8 complexes) of nonsustained ventricular tachycardia occurred in 3 patients with QRS prolongation > or =130%. In 40% of positive tests, prolongation > or =130% occurred earlier by >1 minute than diagnostic Brugada ECG changes, i.e., early termination of the test could possibly have resulted in false-negative outcomes.. QRS prolongation > or =130% occurs in >50% of all tests. In 40% of positive tests it occurs before diagnostic ECG changes. Always terminating the test when QRS prolongs > or =130% could possibly result in loss of important diagnostic information. It is appropriate to adjust the criteria for early termination of the test to the baseline QRS and possibly other factors.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; Electrocardiography; Female; Follow-Up Studies; Heart Conduction System; Heart Rate; Humans; Male; Prognosis; Retrospective Studies

Topics: Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnosis, Differential; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Prognosis

Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb) leads have been reported ("atypical" Brugada syndrome [BS]), their incidence in patients investigated for BS is unknown.. We retrospectively analyzed an ECG database collected during ajmaline test in 143 patients (89 men) with suspected BS. In 42 patients, 12-lead ECGs were recorded, whereas in 101 patients, leads V1-V3 from the third intercostal space were also recorded. The presence of types 1, 2, and 3 Brugada pattern in each limb and precordial lead was noted and the PR, QRS, and QTc intervals were calculated.. There were 114 (79.7%) negative and 29 (20.3%) positive tests. Type 1 pattern developed in >or=1 limb lead in six patients (4.2%) (3/29 with positive tests, 10.3%); all of them were male, symptomatic, and/or with family history of BS or sudden cardiac death. Their pre- and posttest QRS were significantly longer compared with the rest with positive (n = 26) or negative (n = 111) test (pretest: 129 +/- 31 ms vs 101 +/- 11 ms and 97 +/- 12 ms, P < 0.001; posttest: 175 +/- 44 ms vs 134 +/- 14 ms and 131 +/- 19 ms, P < 0.001). The posttest QTc was longer in patients with peripheral changes compared with the rest (507 +/- 47 ms vs 453 +/- 22 ms and 447 +/- 24 ms, P < 0.001). The pretest QTc and pre- and posttest heart rate and PR intervals were not significantly different between the three groups.. Type 1 Brugada pattern in the peripheral leads was observed in 4.2% of patients during ajmaline test (10.3% of positive tests) and was associated with longer QRS and greater QTc prolongation compared with the rest of the patients.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Electrodes; Female; Humans; Incidence; Reproducibility of Results; Sensitivity and Specificity; United Kingdom

The sequences of activation and recovery of the heart have physiological and clinical relevance. We report on progress made over the last years in the method that images these timings based on an equivalent double layer on the myocardial surface serving as the equivalent source of cardiac activity, with local transmembrane potentials (TMP) acting as their strength. The TMP wave forms were described analytically by timing parameters, found by minimizing the difference between observed body surface potentials and those based on the source description. The parameter estimation procedure involved is non-linear, and consequently requires the specification of initial estimates of its solution. Those of the timing of depolarization were based on the fastest route algorithm, taking into account properties of anisotropic propagation inside the myocardium. Those of recovery were based on electrotonic effects. Body surface potentials and individual geometry were recorded on: a healthy subject, a WPW patient and a Brugada patient during an Ajmaline provocation test. In all three cases, the inversely estimated timing agreed entirely with available physiological knowledge. The improvements to the inverse procedure made are attributed to our use of initial estimates based on the general electrophysiology of propagation. The quality of the results and the required computation time permit the application of this inverse procedure in a clinical setting.

Topics: Ajmaline; Algorithms; Anti-Arrhythmia Agents; Brugada Syndrome; Diagnostic Imaging; Electrocardiography; Electrophysiologic Techniques, Cardiac; Heart; Humans; Myocardium

Topics: Ajmaline; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Brugada Syndrome; False Positive Reactions; Humans; Reproducibility of Results; United Kingdom

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Female; France; Germany; Humans; Injections, Intravenous; Male; Reproducibility of Results; Sensitivity and Specificity; Tachycardia, Ventricular

Topics: Aged; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Electrocardiography; Humans; Male; Middle Aged

A 24-year-old man without structural heart disease was admitted following recurrent syncopes. His baseline ECG revealed a right bundle-branch block (RBBB) pattern. Spontaneous monomorphic and polymorphic ventricular tachycardias (VT) were observed during monitoring. The provocation test by propafenone brought out recurrent spontaneous polymorphic VT and provocation by ajmaline caused an ST elevation in V2. Programmed ventricular stimulation test during the electrophysiologic study revealed both monomorphic and polymorphic VT. The patient received an internal cardioverter/defibrillator with the diagnosis of Brugada syndrome.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Brugada Syndrome; Bundle-Branch Block; Defibrillators, Implantable; Electrocardiography; Humans; Male; Propafenone; Tachycardia, Ventricular

Topics: Ajmaline; Alkaloids; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Heart Conduction System; Humans; Rauwolfia

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Catheterization; Cardiac Complexes, Premature; Cardiac Conduction System Disease; Digitalis Glycosides; Emergency Treatment; Heart Conduction System; Humans; Rauwolfia; Tachycardia

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Heart Conduction System; Hypnotics and Sedatives; Rauwolfia

Topics: Ajmaline; Alkaloids; Animals; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Dogs; Heart Conduction System; Rauwolfia

Topics: Ajmaline; Alkaloids; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Conduction System Disease; Heart Conduction System; Rauwolfia

Topics: Ajmaline; Arrhythmias, Cardiac; Brugada Syndrome; Cardiac Complexes, Premature; Cardiac Conduction System Disease; Heart Conduction System; Humans