ECG Pattern Of ST-segment Elevation Research Articles

0194: Flecainide and ajmaline challenge in Brugada syndrome patients under the age of 15 years

Brugada syndrome (BrS) is an inherited arrhythmia syndrome with increased risk of syncope and sudden death. The typical ECG pattern of ST-segment elevation in the right precordial leads can fluctuate. Sodium channel blockers, such as ajmaline or flecainide, are used to unmask the diagnostic ECG pattern of BrS in case of non-diagnostic basal ECG. There is no direct comparison of the electrocardiographic modification induced by these drugs in patients under the age of 15 years. The aim of this study is to relate our experience in our reference centre. Injections are performed by continuous infusion over a period of 10 minutes at 1mg/kg dose for ajmaline and 2 mg/kg for flecainide. Tests were performed in case of absence of type 1 aspect on the resting ECG and in absence of major conduction defects. The flecainide test (group F) was performed in 36 patients and ajmaline test (group A) in 11 patients. Mean age was 12±4 years in group F and 14±2 years in A (p=0.04). There was 14 girls in group F (39%) vs 4 in group A (36%), NS. All patients were in sinus rhythm in both groups. There was no difference between the two groups for heart rate 78±21 vs 72±15 bpm (p=0.35), PR 148±28 ms vs 138±22 ms (p=0.32), QRS 87±11 ms vs 91+/−10 ms (p=0.29) and QTc 412±40 vs 425±30 ms (p =0.31). During the test, HR increase in both groups 9±12 vs 6±7 bpm (p=0.52). There was no difference for PR 31±27 ms vs 32±22 ms (p=0.89). The QRS and QTc were slightly higher in F group (QRS 25±23 ms vs 13±12 ms, p=0.11 and QTc 32±40 vs 18±15 ms, p=0.25) even if the difference was not significant. The number of positive tests F 11/36 (31%) vs 3/11 (27%) were similar in both groups. During pharmacological test no arrhythmic complications has been observed. In patients under the age of 15 years and suspected of BrS, the results of Flecainide and Ajmaline challenge are similar for conduction parameters and positive results. The risk of ventricular arrhythmias appears very low.

Clinical spectrum of patients with a Brugada ECG

The Brugada syndrome continues to spark intensive investigation since its earliest description. New insight has been gained regarding the genetic, histopathologic, and metabolic mechanisms of this heritable channelopathy - a heterogeneity that is reflected in the diverse clinical presentation. In this review, we will focus on clinical spectrum of patients with a Brugada ECG pattern with a special focus on diagnosis and risk stratification. In the past year, multiple case reports have demonstrated that the Brugada ECG pattern is not limited to those with the diagnosed syndrome, with increasing evidence that an 'overlap' exists among inherited channelopathies, especially those involving the sodium and calcium channels. The clinical spectrum of patients with a Brugada ECG remains broad, reflecting the heterogeneity of the underlying pathophysiology. As the true prevalence of the disease unfolds, knowledge regarding the clinical spectrum of patients with a Brugada ECG is important to implement effective risk stratification and management. It may be proposed that the ECG pattern of ST-segment elevation in the right precordial leads should not be seen as a marker of a specific syndrome, but rather as a common electrical expression of structural abnormalities in the right ventricle that may have genetic, infective, or inflammatory origins.

Clinical Aspects and Prognosis of Brugada Syndrome in Children

Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and augmented risk of sudden cardiac death. Little is known about the clinical presentation and prognosis of this disease in children. Thirty children affected by Brugada syndrome who were <16 years of age (mean, 8+/-4 years) were included. All patients displayed a type I ECG pattern before or after drug provocation challenge. Diagnosis of Brugada syndrome was made under the following circumstances: aborted sudden death (n=1), syncope of unexplained origin (n=10), symptomatic supraventricular tachycardia (n=1), suspicious ECG (n=1), and family screening for Brugada syndrome (n=17). Syncope was precipitated by fever in 5 cases. Ten of 11 symptomatic patients displayed a spontaneous type I ECG. An implantable cardioverter-defibrillator was implanted in 5 children; 4 children were treated with hydroquinidine; and 1 child received a pacemaker because of symptomatic sick sinus syndrome. During a mean follow-up of 37+/-23 months, 1 child experienced sudden cardiac death, and 2 children received an appropriate implantable cardioverter-defibrillator shock; all of them were symptomatic and had manifested a type I ECG spontaneously. One child had a cardioverter-defibrillator infection that required explantation of the defibrillator. In the largest population of children affected by Brugada syndrome described to date, fever represented the most important precipitating factor for arrhythmic events, and as in the adult population, the risk of arrhythmic events was higher in previously symptomatic patients and in those displaying a spontaneous type I ECG.

Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome

The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia, and sudden cardiac death after long-term, high-dose propofol infusion has been referred to as propofol infusion syndrome (PRIS). The purpose of this study was to explore the ECG abnormalities observed in a patient with PRIS in order to identify possible pathophysiologic mechanisms of the syndrome. ECG changes in the index case were characterized by down-sloping ST-segment elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We subsequently assessed the relationship between this ECG pattern and the propofol infusion rate, the development of arrhythmias, and the occurrence of sudden death in a previously described cohort of 67 head-injured patients, seven of whom had been identified as having PRIS. Six of the PRIS patients developed the ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of irrecoverable electrical storm. This ECG pattern was the first aberration recorded hours before the death of these patients. ECGs that were available for 30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients developed ventricular arrhythmias. Our findings indicate that development of an acquired Brugada-like ECG pattern in severely head-injured patients is a sign of cardiac electrical instability that predicts imminent cardiac death. Future studies will determine whether such an ECG pattern also predicts imminent cardiac arrhythmia in other patient populations.

Structural Heart Disease, SCN5A Gene Mutations, and Brugada Syndrome

The report of the Second Consensus Conference, published in Circulation in 2005, defined the Brugada syndrome as ST-segment elevation in the right precordial ECG leads (so-called type 1 ECG) and a high incidence of sudden death in patients with structurally normal hearts.1 An autosomal dominant disease with incomplete penetrance, Brugada syndrome has been linked to mutations in SCN5A , the gene encoding the alpha subunit of the cardiac sodium channel.2 More than 80 mutations in SCN5A have been linked to this syndrome (references cited in Reference 1). Analysis of several of these mutations has consistently demonstrated a loss of function related to multiple mechanisms, including failure of sodium channel protein expression and changes in the voltage and time dependence of sodium channel current activation, inactivation, or reactivation.1 Still, SCN5A mutations have been reported in only &20% of patients with Brugada syndrome diagnosed on the basis of clinical criteria, suggesting that other genetic defects and/or other disease mechanisms may give rise to this clinical picture. To complicate matters further, SCN5A mutations have also been identified in patients with the long-QT syndrome. These mutations generally lead to a “gain of function” in the sodium channel, which prolongs the QT interval by increasing inward current. In fact, at least 3 human diseases have been linked to defects in this gene: Brugada syndrome, long-QT syndrome, and progressive conduction disturbances.2–4 Furthermore, there is considerable overlap of clinical profiles, so some patients with Brugada syndrome also have atrial fibrillation, conduction defects with sinus node abnormalities, or prolonged QT interval (reviewed in Reference 1). Thus, genotype-phenotype relationships in Brugada syndrome are highly complex and serve to underscore our incomplete knowledge of the pathogenesis of this type of inherited arrhythmogenic disease. Article p 3680 A similar area of increasing complexity and uncertainty has to …

Unmasking of Brugada Syndrome by Lithium

The characteristic ECG pattern of ST-segment elevation in V1 and V2 in the Brugada syndrome is dynamic; it is often intermittently present in affected individuals and can be unmasked by sodium channel blockers, including antiarrhythmic drugs and tricyclic antidepressants. We report here 2 patients who developed the Brugada ECG pattern after administration of lithium, a commonly used drug not previously reported to block cardiac sodium channels. Lithium induced transient ST-segment elevation (type 1 Brugada pattern) in right precordial leads at therapeutic concentrations in 2 patients with bipolar disorder. Lithium withdrawal in the patients resulted in reversion to type 2 or 3 Brugada patterns or resolution of ST-T abnormalities. In Chinese hamster ovary cells transfected with SCN5A, which encodes the cardiac sodium channel, lithium chloride caused concentration-dependent block of peak INa at levels well below the therapeutic range (IC50 of 6.8+/-0.4 micromol/L). The widely used drug lithium is a potent blocker of cardiac sodium channels and may unmask patients with the Brugada syndrome.

Long-term prognosis of individuals with right predordial ST-elevation - Brugada syndrome

Background: Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as the result of ventricular fibrillation. Controversy exits on risk stratification and therapeutic management in particular in asymptomatic individuals.

Intravenous drug challenge using flecainide and ajmaline in patients with Brugada syndrome

The purpose of this study was to compare the effect of intravenous flecainide and ajmaline with respect to their ability to induce or accentuate the typical ECG pattern of Brugada syndrome. Brugada syndrome is associated with a high incidence of sudden cardiac death. The typical ECG pattern of ST-segment elevation in the right precordial leads often is concealed, but it can be unmasked with sodium channel blockers such as flecainide and ajmaline. Little is known about the relative effectiveness of these provocative agents in unmasking Brugada syndrome. Intravenous pharmacologic challenge with flecainide and ajmaline was performed. Whole-cell patch clamp techniques were used to assess the relative potency of ajmaline and flecainide to inhibit the transient outward current (I(to)). A coved-type ST-segment elevation in the right precordial leads was induced or enhanced in 22 of 22 patients following ajmaline administration. Among the 22 patients, only 15 patients showed positive response to flecainide, resulting in a positive concordance of 68%. Both drugs produced equivalent changes in QRS and PQ intervals, suggesting similar effects on sodium channel current. Whole-cell patch clamp experiments revealed a reduction of the total charge provided by I(to) with an IC(50) of 216 and 15.2 microM for ajmaline and flecainide, respectively. Our data demonstrate disparate response of Brugada patients to flecainide and ajmaline, with a failure of flecainide in 7 of 22 cases (32%). Greater inhibition of I(to) by flecainide may render it less effective. These observations have important implication for identification of patients at risk for sudden death.

Long-Term Prognosis of Individuals With Right Precordial ST-Segment–Elevation Brugada Syndrome

Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of ST-segment elevation in the right precordial leads and an increased risk of sudden cardiac death as a result of ventricular fibrillation. Controversy exists with regard to risk stratification and therapeutic management, particularly in asymptomatic individuals. A total of 212 individuals (mean age, 45+/-6 years) with a type 1 Brugada ECG pattern were studied. Of these, 123 (58%) were asymptomatic, 65 (31%) had > or =1 syncope of unknown origin, and 24 (11%) had to be resuscitated because of ventricular fibrillation. In 125 individuals (59%), a spontaneous type 1 ECG was recorded. In the remaining, drug challenge with a class I antiarrhythmic agent unmasked a Brugada ECG. The mean ST elevation was 2.3+/-1.2 mm in symptomatic patients and 1.9+/-1.5 mm in asymptomatic individuals (P=0.04). During a mean follow-up of 40+/-50 months, 4 of the 24 patients (17%) with aborted sudden cardiac death and 4 of 65 (6%) with a prior syncope had a recurrent arrhythmic event, whereas only 1 of 123 asymptomatic individuals (0.8%) had a first arrhythmic event. Four of 9 patients with arrhythmic events during follow-up were not inducible during programmed electrical stimulation. A previous history of aborted sudden death or syncope and the presence of a spontaneous type 1 ECG were predictors of adverse outcome. The present study reports data on a large population of individuals with a type 1 Brugada ECG pattern with the longest follow-up reported so far. A very low incidence of severe arrhythmic events, particularly in asymptomatic individuals, was found during follow-up. In the presence of very few arrhythmic events on follow-up, programmed electrical stimulation showed very little accuracy in predicting outcome.