Sodium Channel Blocker Challenge Research Articles

The yield of a comprehensive investigation protocol for the diagnosis of true idiopathic ventricular fibrillation in a real-life clinical setting

Traditionally, aborted cardiac arrest (ACA) due to documented ventricular fibrillation (VF) in the absence of structural heart disease has been termed idiopathic VF. By careful evaluation, a specific etiology can be found in a substantial proportion of patients. The aim of this survey was to assess the yield of an advanced diagnostic work-up to reveal a causative etiology in a real-life clinical setting. Patients from the University Hospital Brno’s ACA database were analyzed (514 patients in total). Forty-six patients (31 males) fulfilled the inclusion criteria, which were: (1) absence of structural pathology on echocardiography; (2) absence of coronary artery disease; and (3) absence of reversible cause of ACA. The diagnostic work-up consisted in cardiac magnetic resonance imaging, stress testing, sodium channel blocker challenge, and genetic testing according to the availability of the method and patient compliance. A specific disease was found in 17 individuals (37.0%), although at least one diagnostic step was refused by 13 patients (28.3%). True idiopathic VF was confirmed in 7 patients (15.2%), for whom the entire diagnostic work-up did not reveal any specific pathology. Our real-life survey shows that, even with an incomplete diagnostic work-up (due to the unavailability of a particular method or variable patient compliance), a specific diagnosis can be identified in more than one third of the cases of “idiopathic” VF, which can thus enable targeted treatment and family screening.

Investigation of Unexplained Cardiac Arrest: Phenotyping and Genetic Testing.

Unexplained cardiac arrest (UCA) is a working diagnosis that should be replaced by a final diagnosis once evaluation is completed. Complete evaluation of UCA should include high-yield tests like cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge to identify latent causes of UCA. If no clear etiology is revealed after complete evaluation, idiopathic ventricular fibrillation may be diagnosed, and the strength of its diagnosis can be divided into definitive, probable, and possible based on the number of high-yield tests performed. Care should be provided by a multidisciplinary team with expertise in this area.

Abstract 12307: Exercise-Induced Ventricular Fibrillation in Patients with Brugada Syndrome Phenotype

Introduction: Ventricular fibrillation (VF) in Brugada syndrome (BS) patients are thought to be triggered by vagal nerve activation, which leads to sudden cardiac arrest (SCA) at rest or while asleep. Generally, exercise is not considered as trigger of SCA in BS patients. Aim: To report 2 rare cases of patients with BS phenotype developing exercise-induced ventricular (VF). Case reports: Case 1: 48 year-old male developed SCA during marathon running and was successfully resuscitated with cardiopulmonary resuscitation (CPR). The stored automatic external defibrillator (AED) electrogram (ECG) showed VF. The 12-lead ECG did not show abnormal morphology, however sodium channel blocker challenge test (intravenous injection of pilsicainide, a pure sodium channel blocker 1mg/Kg) unmasked typical type-1 BS ECG. The treadmill stress test induced single premature ventricular contraction by Bruce protocol, and ventricular tachycardia by a flat-out dash without a run-up. Genetic analysis did not show mutation of SCN5A gene. Case 2: 18 year-old male experienced SCA while playing basketball and was successfully resuscitated with CPR. The stored ECG record of AED showed VF. The 12-lead ECG showed normal result, then we performed the drug challenge test. Pilsicainide unmasked typical type-1 BS ECG. He also had exercise-induced atrial fibrillation (AF) and experienced inappropriate shock delivery from implantable cardioverter defibrillator. The treadmill stress test by Bruce protocol did not induce any ventricular arrhythmias. We avoided a flat-out dash protocol because of possibility of exercise-induced AF. Genetic analysis did not show SCN5A mutation. Conclusion: These 2 rare cases of drug-induced BS phenotype developing exercise-induced VF highlight important role of exercise testing as risk stratification tool in certain BS patients.

Nine reasons for performing an electrophysiology study in patients with apparently idiopathic ventricular fibrillation.

Idiopathic ventricular fibrillation (IVF) occurs in approximately 10% of patients resuscitated from cardiac arrest.1 When magnetic resonance imaging, exercise stress or epinephrine testing, and sodium channel blocker challenge are normal, there is a strong suspicion of IVF diagnosis,2 and many cardiac electrophysiologists are proceeding with implantable cardioverter-defibrillator (ICD) implantation without performing a diagnostic electrophysiology study (EPS) (“knee-jerk” ICD implantation).

Brugada Syndrome

Brugada syndrome (BrS) is an "inherited" condition characterized by predisposition to syncope and cardiac arrest, predominantly during sleep. The prevalence is ∼1:2,000, and is more commonly diagnosed in young to middle-aged males, although patient sex does not appear to impact prognosis. Despite the perception of BrS being an inherited arrhythmia syndrome, most cases are not associated with a single causative gene variant. Electrocardiogram (ECG) findings support variable extent of depolarization and repolarization changes, with coved ST-segment elevation ≥2 mm and a negative T-wave in the right precordial leads. These ECG changes are often intermittent, and may be provoked by fever or sodium channel blocker challenge. Growing evidence from cardiac imaging, epicardial ablation, and pathology studies suggests the presence of an epicardial arrhythmic substrate within the right ventricular outflow tract. Risk stratification aims to identify those who are at increased risk of sudden cardiac death, with well-established factors being the presence of spontaneous ECG changes and a history of cardiac arrest or cardiogenic syncope. Current management involves conservative measures in asymptomatic patients, including fever management and drug avoidance. Symptomatic patients typically undergo implantable cardioverter defibrillator insertion, with quinidine and epicardial ablation used for patients with recurrent arrhythmia. This review summarizes our current understanding of BrS and provides clinicians with a practical approach to diagnosis and management.

Radiofrequency ablation in Brugada syndrome.

Radiofrequency ablation in Brugada syndrome.

Defining idiopathic ventricular fibrillation: A systematic review of diagnostic testing yield in apparently unexplained cardiac arrest

Idiopathic ventricular fibrillation (IVF) is diagnosed in patients with apparently unexplained cardiac arrest (UCA) after varying degrees of evaluation. This is largely due to the lack of a standardized approach to UCA. We sought to develop an evidence-based diagnostic algorithm for IVF by systematically examining the yield of diagnostic testing in UCA probands. Studies reporting the yield of diagnostic testing in UCA were identified in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and conference abstracts. Their methodological quality was assessed by the National Institutes of Health quality assessment tool. Meta-analyses were performed using the random effects model. A total of 21 studies were included. The pooled comprehensive diagnostic testing yield was 43% (95% confidence interval 39%-48%). A lower yield was seen when only definite diagnoses based on the prespecified criteria were used (32% vs 47%; P = .15). Epinephrine challenge, Holter monitoring, and family screening were associated with low yield (<5%), whereas cardiac magnetic resonance imaging, exercise treadmill test, and sodium-channel blocker challenge were associated with high yield (≥5%). Coronary spasm provocation, electrophysiology study, and systematic genetic testing were reported to be abnormal in a high proportion of UCA probands (>10%). We developed a stepwise algorithm for UCA evaluation and criteria to assess the strength of IVF diagnosis on the basis of the diagnostic yield of UCA testing.

Value of the sodium-channel blocker challenge in Brugada syndrome

AimsIntravenous 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. MethodsAll 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. ResultsAmong 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. ConclusionWe 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.

Sodium-channel blocker challenge in the familial screening of Brugada syndrome: Safety and predictors of positivity

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 V5 (OR 3.71; 95% CI 2.54-5.44) as predictors of a positive SCBC (P < .0001). Eleven patients (1.6%) presented complications (10 ventricular arrhythmias and 1 atrial flutter), but no deaths occurred. Familial history of complications (OR 41; lower quartile, upper quartile 10, 203; P < .0001), young age (P = .04), and decreased electrocardiographic conduction parameters at baseline (P = .04) were predictors of complications. QRS enlargement during SCBC was not associated with complications. During a median follow-up of 106 months (lower quartile, upper quartile 54, 143 months), 11 life-threatening arrhythmias occurred. 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.

New Insights Into the Genetic Basis of Inherited Arrhythmia Syndromes.

Inherited arrhythmia syndromes encompass several different diseases, including long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), and progressive cardiac conduction system disease (PCCD).1 The heart is typically structurally normal with no evidence of disease macroscopically. They are an important cause for sudden cardiac death in the young, and an autopsy is typically negative.2,3 Ventricular arrhythmias are caused by mutations of ion channels and their interacting proteins, predominantly involving potassium, sodium, and calcium handling.4 Genetic studies have identified the specific genetic abnormalities that underpin these diseases, even permitting diagnosis in the deceased using postmortem genetic testing (the molecular autopsy).3 Most arrhythmia syndromes are inherited in an autosomal dominant manner, such that first-degree family members have a 50% chance of inheriting the disease. Identification of the mutation allows for predictive genetic testing in other living family members.4 Variable penetrance is common in all arrhythmia syndromes, the same mutation in the same family causing wide variation in phenotype.4 This suggests that other factors such as genetic modifiers and environmental factors may influence the phenotype. This review will highlight the latest developments in understanding the genetic basis of inherited arrhythmia syndromes and discusses the new opportunities and challenges faced with evolving genetic technologies including determining pathogenicity and the utility of large genetic databases. Finally, we will discuss newly described entities that continue the evolving theme of genetic syndromes with phenotypic overlap. Early views that a single genotype associates with a particular phenotype continue to be challenged by our greater understanding of the genotype–phenotype relationship. ### Long QT Syndrome Congenital LQTS is diagnosed in the presence of a prolonged corrected QT (QTc) interval after secondary causes (eg, QT-prolonging medications or electrolyte abnormalities) are excluded.1 The 2013 Heart Rhythm …

THE UTILITY AND INCREMENTAL VALUE OF THE SIGNAL AVERAGED ECG: A NOVEL MODEL FOR STRATIFYING PATIENTS WITH SUSPECTED BRUGADA SYNDROME

Patients with suspected Brugada syndrome often undergo a procainamide challenge to stratify their risk for sudden death and arrhythmic events. Patients that develop a Type 1 Brugada pattern during procainamide infusion are at greater risk for cardiac arrest. The signal-averaged ECG (SAECG) can detect late potentials in Brugada syndrome, which may have prognostic significance. We used historical and clinical features, and the SAECG to predict the yield of the procainamide and ajmaline tests in patients with suspected Brugada syndrome. 251 patients were enrolled across Canada with a procainamide challenge and standard, high precordial, and signal-averaged ECGs. A second cohort of 97 patients were enrolled in the United Kingdom, undergoing ajmaline challenge. We evaluated 6 variables including: sex, syncope, palpitations, previous cardiac arrest, baseline ST-elevation (STE; Type 2 or 3 Brugada pattern), and abnormal SAECG. We derived and validated a parsimonious model to predict the outcome of the sodium channel blocker challenge. The average age was 43±15 years (61% male). 100 patients (40%) had a cardiac arrest, 54 (22%) had syncope, and 24 (10%) had palpitations prior to assessment. 83 patients (33%) had baseline STE and 20 patients (8%) had a positive procainamide challenge. Univariate and multivariate analysis identified baseline STE (OR 50.7) and SAECG (OR 1.84 per parameter) to be associated with a positive procainamide challenge (see Table). A simple 2-factor, 6-point model derived using baseline STE (3 points) and SAECG (1 point per parameter) was strongly predictive of the procainamide challenge (AUC 0.876). This model was validated in a second cohort, and found to be moderately predictive of the ajmaline challenge (AUC 0.730). Patients that scored 0 were unlikely to have a positive test (100% sensitivity), and patients that scored 6 were very likely to have a positive test (93% specificity). In this combined cohort of 348 patients, we derived and validated a simple 2-factor, 6-point score that can be effectively used to triage the role of the procainamide and ajmaline challenge in patients with suspected Brugada syndrome. Our findings also highlight the utility and incremental value of the SAECG in stratifying patients with suspected Brugada syndrome, prior to a sodium channel blocker test. We identified two populations where the sodium channel blocker test could be avoided to prevent adverse events and ensure appropriate use of resources.

Brugada ECG Sign &amp; Chest Pain Mimicking ST Elevation Myocardial Infarction

Background: Management of patients with the brugada ECG sign who have no previous history of syncope is still negotiable. We present a case of a 57 year-old Caucasian lady who presented to the emergency department with substernal chest pain. Results: Her past medical history showed that she had two previous episodes of lightheadedness, but no syncope. She had a family history of sudden death secon­dary to unknown cause in her aunt at the age of 61. Physical exam was unremarkable except for diaphoresis. Electrocardiography (ECG) showed ST elevation in the right precordial leads (V1-V2) with T inversion, mimicking a STEMI. Emergent cardiac catheterization revealed normal coronary arteries. Echocardiogram was normal. Again, interpretation of ECG revealed a Brugada type 1 pattern, characterized by coved-type, gradually descending ST-T segment, elevated J point of more than 2 mm and T wave inversion. Electrophysiological (EPS) testing with a Sodium channel blocker challenge showed a persistent Brugada type 1 pattern with non-inducible ventricular tachycardia. This patient had Brugada type 1 ECG pattern with no previous history of syncope (asymptomatic). Thus she was considered at low risk of developing a serious arrhythmogenic event in the future. Conclusion: A history of syncope remains the best available predictor for arrhythmogenic events. EPS testing in such patients, to stratify the risk and predict for any future events, is still controversial. It is still unjustified to place an implantable cardioverter-defibrillator in asymptomatic non-inducible individuals with the Brugada pattern. These patients should follow up closely with a cardiologist and be aware of the risk of possible triggers of ventricular arrhythmias.

Letter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization”

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 5, No. 2Letter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Casado-Arroyo et al Regarding Article, “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” Rubén Casado-Arroyo, MD, Moisés Rodriguez-Mañero, MD, Andrea Sarkozy, MD, PhD and Pedro Brugada, MD, PhD Rubén Casado-ArroyoRubén Casado-Arroyo Search for more papers by this author , Moisés Rodriguez-MañeroMoisés Rodriguez-Mañero Search for more papers by this author , Andrea SarkozyAndrea Sarkozy Search for more papers by this author and Pedro BrugadaPedro Brugada Search for more papers by this author Originally published1 Apr 2012https://doi.org/10.1161/CIRCEP.112.970673Circulation: Arrhythmia and Electrophysiology. 2012;5:e59To the Editor:We have read “Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization” by Watanabe and colleagues1 with great interest and congratulate the authors for their publication. However, there are some aspects that in our opinion should be clarified.The authors state in the “Methods” section, “Patients with Brugada type ST-segment elevations at baseline or after sodium channel blocker challenge were excluded.”1 As has been previously published, the diagnosis of Brugada syndrome (BS) should be strongly considered if there is appearance of Type 1 ST segment elevation (coved type) in at least 1 of the precordial leads or in the inferior leads in the presence or absence of a sodium channel blocker plus at least 1 clinical symptom.2,3We disagree with the electrocardiographic interpretation in Patient 1 (Figure 2B): the basal electrocardiogram shows a spontaneous Type I Brugada pattern in lead V2. After pilsicainide, the patient presents an inferior–lateral early repolarization pattern. This pattern and the response to sodium channel blockers are specific of patients with BS and interestingly have been associated with a more severe phenotype.3 Patient 2 (Figure 2C) illustrates a classical coved-type electrocardiographic pattern after the infusion of the drug in lead V2. These 2 patients presented spontaneous ventricular fibrillation after the infusion of the drug and also during programmed stimulation, because it has been previously described in patients with BS.3,4 On the other hand, the third patient presents a typical case of spontaneous Type 1 at baseline in lead V2 (Figure 2E). Accordingly, it is important to mention that the SCN5A mutation (R367H) had been previously described in patients with BS, specifically in a large European family with 18 members4 and is internationally recognized as a mutation causative of BS.5 This amino acid substitution is associated with high incidence of spontaneous Type 1, as is the case in the third patient.Although differentiation between idiopathic ventricular fibrillation and BS may be difficult, frequent overlap between these 2 entities is possible. From our point of view, BS has not been properly excluded. These patients discussed by Wanatabe et al fit all phenotype and genotype characteristics of BS.Rubén Casado-Arroyo, MDMoisés Rodriguez-Mañero, MDAndrea Sarkozy, MD, PhDPedro Brugada, MD, PhD Heart Rhythm Management Center Cardiovascular Division Free University of Brussels (UZ Brussel) VUB Brussels, BelgiumSources of FundingFunded by a grant for international research post-residency, Spanish Society of Cardiology (R.C.-A.).DisclosuresNone.

Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization

Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. This study included 50 patients (44 men; age, 45 ± 17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

Clinical and electrocardiographic predictors of positive response to the intravenous sodium channel blockers in patients suspected of the Brugada syndrome

Background/objectivesSodium channel blockers are used to unmask the diagnostic ECG pattern of the Brugada syndrome (BrS) in case of a non-diagnostic baseline ECG. The aim of the study was to determine clinical and ECG predictors of a positive challenge test in patients suspected to the BrS. MethodsA total of 106 consecutive patients (91 men; mean age, 35±12years) suspected of the BrS underwent the intravenous sodium channel blocker challenge test with procainamide or flecainide. ResultsOf the 106 patients, positive tests were detected in 20 (19%) patients. During test, a transient episode of a second-degree atrioventricular block and isolated ventricular ectopies were observed in 1 (0.9%) and 2 (1.9%) patients, respectively. A QRS prolongation ≥30% was observed in 4 (3.8%) patients. Baseline QRS duration in V1≥110ms had a sensitivity of 70% and a specificity of 80% for a positive response. An ST-segment elevation ≥0.17mV in V2 had a sensitivity of 60% and a specificity of 82% for a positive response. Of the multiple clinical and ECG variables entered into a binary logistic regression analysis, a history of syncope (P=0.001), previous cardiac arrest (P=0.001), baseline QRS duration in V1≥110ms (P=0.001), and baseline ST-segment elevation in V2≥0.17mV (P=0.012) emerged as the independent predictors of a positive response to the intravenous challenge with sodium channel blockers. ConclusionThe results of the sodium channel blocker challenge test can be predicted by clinical presentation and baseline ECG features.

The ajmaline challenge and a strange ECG: reply

We have read with interest the letter by Dr Martini and we are grateful for his comments. We would like to reply to some of the issues raised by Dr Martini in his letter. The authors are aware that ajmaline was used as a diagnostic tool in the past to unmask intraventricular conduction delays. However, nowadays sodium channel blocker challenge is an accepted and established tool to unmask the ECG pattern diagnostic of the Brugada syndrome.1 This test is especially important in the circumstance when the …

Sodium channel blocker tests allow a clear distinction of electrophysiological characteristics and prognosis in patients with a type 2 or 3 Brugada electrocardiogram pattern

Patients with a type 2 or 3 Brugada syndrome (BS) pattern and a negative sodium channel blocker challenge (SCBC) are not considered as affected. Their arrhythmic prognosis is generally considered good, but it has never been specifically evaluated. The purpose of this study was to evaluate the arrhythmic prognosis in patients with a type 2 or 3 electrocardiogram (ECG) not converted to type 1 ECG during an SCBC. Clinical data, 12-lead ECG, results of the SCBC and electrophysiological study (EPS), and follow-up were collected. Among the 500 patients who underwent an SCBC in our institution, 158 displayed a type 2 or 3 ECG. After the SCBC, 93 (59%) had a type 1 ECG (positive group [PG]), whereas 65 (41%) remained negative (negative group [NG]). An EPS was performed in 31 (33%) PG patients and 15 (23%) NG patients. Ventricular fibrillation was induced in 21 PG patients (67%), whereas no patient in the NG was inducible (P <.001). During a follow-up of 37 +/- 17 months, no sudden death occurred. Three syncopes were observed in the NG versus one syncope, two ventricular tachycardias, and one appropriate shock in the PG. This study demonstrates that the presence or absence of coved type ST-segment elevation during the SCBC denotes a profound electrophysiological difference as demonstrated by the absence of inducibility during EPS in the NG that may be responsible for the good prognosis of patients with a type 2 or 3 ECG pattern not converted to type 1.

Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome

ObjectivesWe administered pilsicainide chloride, a class Ic pure sodium channel blocker, to patients with Brugada syndrome (BS) and evaluated the occurrence of ventricular arrhythmia (VA) and T-wave alternans (TWA). BackgroundVentricular arrhythmia and TWA are sometimes induced by a sodium channel blocker challenge test in BS patients, but the significance of the induced VA and TWA is not known. MethodsPilsicainide was administered to 65 patients with BS (10 symptomatic and 55 asymptomatic patients), and the occurrence of VA, TWA, and change of electrocardiogram were evaluated. Electrophysiologic study was performed in 57 patients, and the induction of VA by programmed electrical stimulation (PES) was evaluated. ResultsVentricular arrhythmia was not induced by administration of pilsicainide in 55 patients (no-VA group). Administration of pilsicainide-induced VA in 10 patients (Pil-VA group) and polymorphic ventricular tachycardia in four patients. Pilsicainide-induced VA in 60% of the symptomatic patients but in only 7% of asymptomatic patients (p < 0.01). ST level, QTc, and indexes of cardiac conduction in the Pil-VA group were not different from those in the no-VA group. Ventricular fibrillation was induced by PES in 67% of the patients in the Pil-VA group and in 33% of the patients in the no-VA group. In six cases, macroscopic TWA occurred in association with pilsicainide-induced VA, but TWA occurred in only one patient without pilsicainide-induced arrhythmia. ConclusionsAdministration of a sodium channel blocker results in induction of not only ST-elevation but also VA and TWA in patients with BS.

Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome: A Prospective Evaluation of 52 Families. Priori SG, Napolitano C, Gasparini M, et al. Circulation 2000;102:2509–15

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.