ajmaline and Death--Sudden--Cardiac

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

The Wolff-Parkinson-White syndrome is a current debated clinical issue. Although the anatomical characteristics, polymorphic electrocardiographic features, and electrophysiological mechanisms of arrhythmias and sudden cardiac death are well known, the identification of patients at risk of sudden cardiac death remains challenging. Owing to the lack of effective therapeutic strategies, in the pre-ablation era many studies have been conducted to define the prognostic value of clinical and instrumental tests, and to define the actual risk of sudden cardiac death in patients with ventricular preexcitation. Nowadays, radiofrequency transcatheter ablation of anomalous atrioventricular pathways is a strong therapeutic option for all patients, independent of the risk of sudden cardiac death. However, radiofrequency ablation is associated with serious complications, but many studies confirm an overall good prognosis for most of the patients with electrocardiographic pattern of ventricular preexcitation. The aim of this review is to assess the prognostic value of clinical and instrumental tests in patients with ventricular preexcitation, referring to the latest knowledge.

Topics: Adolescent; Adult; Age Distribution; Ajmaline; Atrioventricular Node; Catheter Ablation; Child; Child, Preschool; Clinical Trials as Topic; Death, Sudden, Cardiac; Electrocardiography; Exercise Test; Feasibility Studies; Female; Heart Function Tests; Humans; Male; Middle Aged; Procainamide; Prognosis; Propafenone; Risk Assessment; Sex Distribution; Wolff-Parkinson-White Syndrome; Young Adult

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

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

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

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

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

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

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

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

The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear.. We analyzed 12-lead ECGs of 401 first-degree relatives of individuals who had died from SADS. The prevalence of ER patterns was compared with family-clustered controls. ER was more common in SADS family members than in controls (21% versus 8%; odds ratio: 5.14; 95% confidence interval, 3.37-7.84) independent of the presence of a familial cardiac diagnosis. Both ascending and horizontal ER patterns were more common. In addition, ER was investigated for associations with findings from ajmaline provocation (n=332), exercise ECG (n=304), and signal-averaged ECG (n=118) when performed. ER was associated with a trend toward late depolarization, in general was suppressed with exercise and was unaffected by ajmaline. Inferior and horizontal patterns were, however, more likely to persist during exercise. Augmentation of ER with ajmaline was rare.. The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology. The differing response of ER subtypes to exercise and ajmaline provocation suggests underlying mechanisms of both abnormal repolarization and depolarization.

Topics: Adult; Ajmaline; Arrhythmias, Cardiac; Case-Control Studies; Death, Sudden; Death, Sudden, Cardiac; Electrocardiography; Female; Humans; Male; Prevalence; Risk Factors

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

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

The aim of the present study was to elucidate the molecular mechanism underlying the concomitant occurrence of cardiac conduction disease and long QT syndrome (LQT3), two SCN5A channelopathies that are explained by loss-of-function and gain-of-function, respectively, in the cardiac Na+ channel.. A Caucasian family with prolonged QT interval, intermittent bundle-branch block, sudden cardiac death, and syncope was investigated. Lidocaine (1 mg/kg i.v.) normalized the prolonged QT interval and rescued bundle-branch block. An SCN5A mutation analysis was performed that revealed a C-to-A mutation at position 4859 (exon 28), predicted to change a highly conserved threonine for a lysine at position 1620. Mutant channels were characterized both in Xenopus oocytes and HEK293 cells. The T1620K mutation remarkably altered the properties of Nav1.5 channels. In particular, the voltage-dependence of the current decay time constants was largely lost. As a consequence, mutant channels inactivated faster than wild-type channels at potentials negative to -30 mV, resulting in less Na+ inward current (loss-of-function), but significantly slower at potentials positive to -30 mV, resulting in an increased Na+ inward current (gain-of-function). Moreover, we found a hyperpolarized shift of steady-state activation and an accelerated recovery from inactivation (gain-of-function). At the same time, channel availability was significantly reduced at the resting membrane potential (loss-of-function).. We conclude that lysine at position 1620 leads to both loss-of-function and gain-of-function properties in hNav1.5 channels, which may consequently cause in the same individuals impaired impulse propagation in the conduction system and prolonged QTc intervals, respectively.

Topics: Action Potentials; Adolescent; Adult; Ajmaline; Animals; Anti-Arrhythmia Agents; Bundle-Branch Block; Cell Line; Child; Death, Sudden, Cardiac; DNA Mutational Analysis; Electrocardiography; Female; Gene Transfer Techniques; Genetic Predisposition to Disease; Humans; Kinetics; Lidocaine; Long QT Syndrome; Lysine; Male; Muscle Proteins; Mutation; Myocardium; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Pedigree; Sodium; Sodium Channels; Syncope; Threonine; Xenopus laevis

A patient with a family history of sudden cardiac death and a structurally normal heart presented with a resting ECG intermittently displaying a saddle-type Brugada-ECG, which could be reproducibly converted to a coved-type ECG pattern suggestive of Brugada syndrome. However, no ST-segment changes occurred in the presence of a true right bundle branch block (RBBB) in the same patient. In consideration of the inalienable diagnostic criterion of dynamic ECG abnormalities in the right precordial leads in Brugada syndrome, setting the diagnosis in patients with true RBBB may be unattainable.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Bundle-Branch Block; Death, Sudden, Cardiac; Diagnosis, Differential; Electrocardiography; Humans; Male; Syndrome

The mechanisms responsible for the undulating pattern of ST-segment elevations in the Brugada syndrome are still a matter of discussion. This report describes a young man with a Brugada-like electrocardiographic pattern. The specific ST-segment elevations were unmasked during an episode of anemia due to a duodenal ulcer.

Topics: Adult; Ajmaline; Anemia; Anti-Arrhythmia Agents; Bundle-Branch Block; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Duodenal Ulcer; Electrocardiography; Electrocardiography, Ambulatory; Helicobacter Infections; Helicobacter pylori; Humans; Male; Peptic Ulcer Hemorrhage; Risk Factors; Syndrome; Ventricular Fibrillation

Brugada syndrome (BS) is an electrical cardiac disorder with a right bundle branch block and ST segment elevation in leads V1 to V3 on surface electrocardiograms (ECGs), and is a syndrome that may lead to sudden cardiac death.. The aim of the present study was to screen for mutations in the SCN5A gene in a family with BS, and to characterize the consequences of the mutation on channel function.. A heterozygous nonsense SCN5A mutation (W822X) was identified in the index patient. The mutation was confirmed in the patient's asymptomatic 16-year-old brother and 48-year-old father. The mutation was absent in the index patient's sister and mother. The ECG of the index patient showed a BS type 2 ECG phenotype, which converted into a type 1 ECG phenotype in the presence of flecainide. The ECG of the patient's brother was not typical for BS, but ajmaline treatment unmasked a type 1 ECG phenotype. The ECG of the asymptomatic father was normal at baseline and in the presence of ajmaline. No Na+ currents could be measured in tsA201 cells transfected with W822X mutant channels. Heterozygote expression showed a nearly 50% reduction in Na+ current amplitude with no significant alterations of biophysical properties, indicating a loss of functional Na+ channels, obviously without any dominant-negative activity on wild type channels.. The haploinsufficiency of the Nav1.5 protein is the plausible explanation for the clinical BS phenotype in this family. Because the heterozygous W822X mutation theoretically leads to channel expression at one-half of the normal level, the authors suggest that a modifier gene may influence or rescue the phenotype in the asymptomatic family members.

Topics: Adolescent; Adult; Ajmaline; Anti-Arrhythmia Agents; Bundle-Branch Block; Cell Line; Codon, Nonsense; Death, Sudden, Cardiac; Electrocardiography; Female; Heart Diseases; Humans; Male; Microscopy, Fluorescence; Middle Aged; Molecular Biology; Muscle Proteins; Mutagenesis; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Pedigree; Phenotype; Sodium Channels; Syndrome; Transfection

The diagnostic ECG pattern in Brugada syndrome (BS) can transiently normalize and may be unmasked by sodium channel blockers such as ajmaline. Proarrhythmic effects of the drug have been well documented in the literature. A detailed protocol for the ajmaline challenge in Brugada syndrome has not yet been described. Therefore, we prospectively studied the risks of a standardized ajmaline test.. During a period of 60 months, 158 patients underwent the ajmaline test in our institution. Ajmaline was given intravenously in fractions (10mg every two minutes) up to a target dose of 1mg/kg. In 37 patients (23%) the typical coved-type ECG pattern of BS was unmasked. During the test, symptomatic VT appeared in 2 patients (1.3%). In all other patients, the drug challenge did not induce VT if the target dose, QRS prolongation >30%, presence/appearance of the typical ECG, or the occurrence of premature ventricular ectopy were considered as end points of the test. A positive response to ajmaline was induced in 2 of 94 patients (2%) with a normal baseline ECG, who underwent evaluation solely for syncope of unknown origin.. The ajmaline challenge using a protocol with fractionated drug administration is a safe method to diagnose BS. Because of the potential induction of VT, it should be performed under continuous medical surveillance with advanced life-support facilities. Due to the prognostic importance all patients with aborted sudden death or unexplained syncope without demonstrable structural heart disease and family members of affected individuals should presently undergo drug testing for unmasking BS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ajmaline; Anti-Arrhythmia Agents; Bundle-Branch Block; Child; Clinical Protocols; Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Electrocardiography; Humans; Infusions, Intravenous; Middle Aged; Syncope; Syndrome

We present a Brugada syndrome patient who suffered an aborted sudden death. The ajmaline test (1 mg/kg body weight) induced accentuated alternans ST-segment elevation in V1-V2 without ventricular arrhythmias. It could represent silent ischaemia not detected before, failure of myocardial regions to repolarize in alternate beats due to transmural dispersion of conduction and refractoriness in the right ventricular outflow tract or a rate dependent sodium channel block by ajmaline. We need more studies to know whether this electrocardiographic sign is a risk factor for life-threatening ventricular arrhythmias in Brugada syndrome patients.

Topics: Ajmaline; Anti-Arrhythmia Agents; Bundle-Branch Block; Death, Sudden, Cardiac; Electrocardiography; Electrophysiologic Techniques, Cardiac; Humans; Syndrome; Ventricular Fibrillation

We report a 37-year-old man with documented aborted sudden death. After resuscitation, the patient showed no structural heart disease but the ECG showed a right bundle-branch block with a descending ST segment elevation in leads V(1) and V(2). After transient normalization of the ECG, the administration of ajmaline led to spontaneous development of the distinct descending ST segment elevation in the right precordial leads and therefore to the diagnosis of Brugada syndrome. The incidence of sudden cardiac death among these patients is high. The only treatment is an implantable cardioverter-defibrillator (ICD). The Brugada syndrome should therefore be borne in mind in the differential diagnosis of sudden death.

Topics: Adult; Ajmaline; Anti-Arrhythmia Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Diagnosis, Differential; Electrocardiography; Humans; Male; Myocardial Infarction; Resuscitation

The syndrome with an electrocardiographic pattern of right bundle branch block, ST segment elevation in leads V(1)to V(3)and sudden death is genetically determined and caused by mutations in the cardiac sodium channel. The inheritance of the disease is autosomal dominant. Sudden death may, however, occur from a variety of causes in relatives and patients with this syndrome.. Twenty-five Flemish families with this syndrome with a total of 334 members were studied. Affected members were recognized by means of a typical electrocardiogram either occurring spontaneously or after the intravenous administration of antiarrhythmic drugs. Sudden deaths in these families were classified as related or not to the syndrome by analysis of the data at the time of the event, mode of inheritance of the disease, and data provided by survivors. Results Of the 25 families with the syndrome, 18 were symptomatic (at least one sudden death related to the syndrome) and seven were asymptomatic (no sudden deaths related to the syndrome). In total, there were 42 sudden cardiac deaths (12% incidence). Twenty-four sudden deaths were related to the syndrome and all occurred in symptomatic families. Eighteen sudden deaths (43% of total sudden deaths) were not related to the syndrome (nine cases) or were of unclear cause (nine cases). Three of them occurred in two asymptomatic families and the remaining 15 in five symptomatic families. Twenty-four of the 50 affected members (47%) suffered (aborted) sudden death and 18 of the 284 unaffected members (6%). This difference in the incidence of sudden death was statistically significant (P<0.0001). Patients with (aborted) sudden death caused by the syndrome were younger than patients with sudden death of other or unclear causes (38+/-4 years vs 59+/-3 years respectively, P=0.0003).. In families at high risk of sudden death because of genetically determined diseases, the main cause of sudden death remains the disease. However, almost the half of sudden deaths are caused by unrelated diseases or are of unclear cause. Accurate classification of the causes of sudden death is mandatory for appropriate analysis of the causes of death when designing preventive treatments.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Ajmaline; Anti-Arrhythmia Agents; Belgium; Bundle-Branch Block; Child; Child, Preschool; Death, Sudden, Cardiac; Electrocardiography; Female; Heart Conduction System; Humans; Infant; Male; Middle Aged; Prospective Studies; Syndrome

Dynamic variations in electrophysiologic phenomena inherent to the Brugada syndrome may complicate therapy with implantable cardioverter defibrillators (ICDs).. Between 1997 and 1999, 3 of 7 patients with Brugada syndrome (1 man and 2 women, mean age 42 years) received an ICD. During follow-up, 2 patients experienced multiple inappropriate shocks. Simultaneously with dynamic changes in the surface ECG, endocardial ECGs revealed a dynamic decrease in the right ventricular R wave and an increase in the corresponding T wave, resulting in T wave oversensing. With ajmaline administration, these dynamic changes in endocardial signals were reproducible at different right ventricular sites, whereas left ventricular epicardial signals remained stable. Incremental AAI pacing and exercise stress testing resulted in similar changes in right ventricular endocardial signals, but normalization of the surface ECG apart from progressively increasing S waves in leads II, V5, and V6. Orciprenaline administration had no effect on ECG phenomena. After implantation of a left ventricular epicardial lead for sensing and pacing, no inappropriate tachycardia detection recurred.. These findings demonstrate that, in Brugada syndrome, spontaneous or ajmaline-induced changes in the surface ECG may be paralleled by significant variations in the right ventricular endocardial electrogram that may result in ICD malfunction. Implantation of a left ventricular epicardial lead for sensing and pacing may be the ultimate successful approach in certain patients. To assure proper ICD function, ajmaline testing during ICD implantation appears to be helpful.

Topics: Adrenergic beta-Agonists; Adult; Ajmaline; Anti-Arrhythmia Agents; Bundle-Branch Block; Cardiac Pacing, Artificial; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Exercise Test; Female; Flecainide; Humans; Injections, Intravenous; Male; Metaproterenol; Middle Aged; Recurrence; Syndrome; Ventricular Fibrillation