The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol

Rolf, Sascha; Bruns, Hans-Jürgen; Wichter, Thomas; Kirchhof, Paulus; Ribbing, Michael; Wasmer, Kristina; Paul, Matthias; Breithardt, Günter; Haverkamp, Wilhelm; Eckardt, Lars

doi:10.1016/s0195-668x(03)00195-7

Cited by 178 publications

(88 citation statements)

References 26 publications

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“…The intravenous administration of the sodium channel blocker ajmaline (1 mg/kg) provoked an increased STsegment elevation in the right precordial leads in all patients (positive ajmaline test). 15 Investigations during screening included noninvasive (echocardiography, stress, and rest ECGs) as well as invasive (coronary angiography, electrophysiological study, endomyocardial biopsy) techniques. 16 All patients underwent programmed electrical stimulation as reported previously.…”

Section: Patientsmentioning

confidence: 99%

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

et al. 2004

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Background— Life-threatening ventricular tachyarrhythmias can occur in young patients without structural heart disease (idiopathic forms). In many patients, these are typically triggered by an increased sympathetic tone, eg, by physical or mental stress. In contrast, in Brugada syndrome, ventricular tachyarrhythmias more often occur during rest or sleep when the vagal tone is predominant. Furthermore, adrenergic agonists can reduce the level of ST-segment elevation, whereas it is increased by parasympathetic agonists or adrenergic antagonists. The aim of this study was to investigate presynaptic and postsynaptic myocardial sympathetic function in patients with Brugada syndrome. Methods and Results— Nine patients with Brugada syndrome (6 male, 3 female; age, 41±13 years) were enrolled in this study. The cardiac autonomic nervous system was assessed noninvasively, quantifying myocardial presynaptic and postsynaptic sympathetic function by means of positron emission tomography with the norepinephrine analogue 11 C-Hydroxyephedrine ( 11 C-HED) and the nonselective β-blocker 11 C-CGP 12177 ( 11 C-CGP). Presynaptic sympathetic norepinephrine recycling, assessed by 11 C-HED, was globally increased in patients with Brugada syndrome compared with a group of age-matched healthy control subjects (92.9±16.2 mL/g versus 69.1±14.2 mL/g; P <0.05), whereas postsynaptic β-adrenoceptor density, assessed by 11 C-CGP, was similar in patients and control subjects (10.4±6.7 pmol/g versus 10.2±2.9 pmol/g; P =NS). Conclusions— The present study on autonomic innervation in Brugada syndrome describes an enhanced presynaptic norepinephrine recycling with preserved β-adrenoceptor density, further supporting the hypothesis of an autonomic dysfunction in Brugada syndrome. This is a further step toward the understanding of the pathophysiology of the disease with potential future impact on therapeutic strategies.

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Section: Patientsmentioning

confidence: 99%

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

et al. 2004

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“…Previous studies showed that an SCB test induced VTAs in 0% to 25% of patients and VF in up to 4% of patients with BrS 13, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34. The incidence of SCB‐induced VTAs increased if the subjects of the study included subjects with spontaneous type 1 ECG.…”

Section: Discussionmentioning

confidence: 94%

“…An SCB test is useful and safe for most patients, but some studies have shown that some patients develop severe VTAs requiring external defibrillation, implantable cardioverter‐defibrillator therapy, or an extracorporeal membrane oxygenator 6, 13, 15, 19, 23, 28, 31, 34. An SCB test should be performed during hospitalization, and continuous infusion of low‐dose isoproterenol after the test should be performed overnight for high‐risk patients.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome

Ueoka

Morita

Watanabe

et al. 2018

JAHA

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BackgroundA drug provocation test using a sodium channel blocker (SCB) can unmask a type 1 ECG pattern in patients with Brugada syndrome. However, the prognostic value of the results of an SCB challenge is limited in patients with non–type 1 ECG. We investigated the associations of future risk for ventricular fibrillation with SCB‐induced ECG changes and ventricular tachyarrhythmias (VTAs).Methods and ResultsWe administered intravenous pilsicainide to 245 consecutive patients with Brugada syndrome (181 patients with spontaneous type 1 ECG, 64 patients with non–type 1 ECG). ECG parameters before and after the test and occurrence of drug‐induced VTAs were evaluated. During a mean follow‐up period of 113±57 months, fatal VTA events occurred in 31 patients (sudden death: n=3, ventricular tachycardia/ventricular fibrillation: n=28). Symptomatic patients and spontaneous type 1 ECG were associated with future fatal arrhythmic events. Univariable analysis of ECG parameters after the test showed that long PQ and QRS intervals, high ST level, and SCB‐induced VTAs were associated with later VTA events during follow‐up. Multivariable analysis showed that symptomatic patients, high ST level (V1) ≥0.3 mV after the test, and SCB‐induced VTAs were independent predictors for future fatal arrhythmic events (hazard ratios: 3.28, 2.80, and 3.62, 95% confidence intervals: 1.54–7.47, 1.32–6.35, and 1.64–7.75, respectively; P<0.05).Conclusions SCB‐induced VTAs and ST‐segment augmentation are associated with an increased risk of the development of ventricular tachycardia/ventricular fibrillation events during follow‐up in patients with Brugada syndrome.

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“…19 If no spontaneous type I morphology was seen on the electrocardiogram (ECG), a standardized Ajmaline Challenge Test was performed conforming to current guidelines to unmask any concealed forms of BS. 20 In case of established BS, SCN5A genetic analysis was performed, according to the recommendations from the Heart Rhythm Society/European Heart Rhythm Association. 21 SCN5A variant detection in genomic DNA was carried out via high-resolution melting-curve analysis (HRMCA), followed by direct bidirectional Sanger sequencing analysis of aberrant HRMCA melting patterns and of exons and flanking intron regions for which HRMCA was not available.…”

Section: First Case/index Familymentioning

confidence: 99%

SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies

et al. 2015

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SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome. On the other hand, mutations in SCN4A encoding the α-subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with nondystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A-associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy (DMPK gene) and one family had a Thomsen disease myotonia congenita (CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.

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The ajmaline challenge in Brugada syndrome: Diagnostic impact, safety, and recommended protocol

Cited by 178 publications

References 26 publications

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

Abnormal Myocardial Presynaptic Norepinephrine Recycling in Patients With Brugada Syndrome

Prognostic Significance of the Sodium Channel Blocker Test in Patients With Brugada Syndrome

SCN4A variants and Brugada syndrome: phenotypic and genotypic overlap between cardiac and skeletal muscle sodium channelopathies

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