Ajmaline Test Research Articles

Haemochromatosis, sinus node dysfunction and Brugada syndrome – a ménage à trois of findings in one and the same patient: coincidence or causality?

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

Response to the Letter by Kattygnarath et al

We want to answer the letter Olesen et al addressed to Circulation: Cardiovascular Genetics after the publication of our report on MOG1 as a new susceptibility gene for Brugada syndrome (BrS). Olesen et al1 screened MOG1 in 23 patients with BrS and in 197 patients with early-onset lone atrial fibrillation, and they identified the nonsense variation c.181G>T (p.E61X) in 4 patients with atrial fibrillation, resulting in a premature stop codon that truncates the protein upstream of the region that interacts with Nav1.5. They also identified this variant in 2 of 488 healthy individuals (ie, in 0.4% of control subjects vs 1.8% of patients). As indicated by Olesen et al, we reported this nonsense variant at the American Heart Association 2009 scientific sessions,2 in an asymptomatic male patient with a type 1 BrS ECG. This variant was thought to be relevant because it had not been found in 100 control individuals. We later found it in 3 other BrS probands, positive or negative for the SCN5A mutation, and in some family members; in addition, we found it in …

The Eternal Dilemma Between Supraventricular and Ventricular Tachycardias in a Patient With Brugada Syndrome

![Figure][1] The image shows the result of an ajmaline test in a 42-year-old patient with a diagnosis of Brugada syndrome. A shows the transition from sinus rhythm to a right bundle branch block tachycardia with a heart rate of 140 beats/min, with a wide QRS complex (220 ms) and a right axis

Ajmaline Challenge in Young Individuals with Suspected Brugada Syndrome

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

Brugada-like ECG pattern induced by tricyclic antidepressants

We present the case report of a 57-year-old woman with severe monointoxication with dosulepine (Prothiaden) who developed a Brugada-like electrocardiographic pattern. In tricyclic antidepressants (TCAs) poisoning the Brugada-like pattern on electrocardiogram is a characteristic albeit rare manifestation of the frequently occurring conduction abnormalities in the myocardium and its recognition is imperative as it is associated with a higher degree of morbidity and mortality. An overview of the literature is given and recommendations concerning treatment of TCA-induced arrhythmias are provided. After successful treatment, the electrocardiogram in the patient normalized. However, 4 days after intoxication, the ajmaline test was positive (pharmacological induction of a type I Brugada-like pattern), but a subsequent one, repeated after 11 days, was reportedly normal, probably because of the slow clearance of dosulepine. This raises questions about the specificity of ajmaline testing for Brugada syndrome in patients taking dosulepine and perhaps other TCAs and neuroleptic agents.

Utility of high and standard right precordial leads during ajmaline testing for the diagnosis of Brugada syndrome

AimsThe authors sought to assess the value of the high right precordial leads (RPL) to detect the Type I Brugada ECG pattern in patients suspected of carrying Brugada syndrome (BrS).MethodsAjmaline...

Active Cascade Screening in Primary Inherited Arrhythmia Syndromes: Does It Lead to Prophylactic Treatment?

The purpose of this study was to investigate the follow-up and treatment of the mutation-carrying relatives of a proband with an inherited arrhythmia syndrome.The congenital long QT syndrome (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) are primary inherited arrhythmia syndromes that may cause syncope and sudden cardiac death in young individuals. After establishing the disease-causing deoxyribonucleic acid (DNA) mutation in probands, we actively conducted cascade screening to identify, most often asymptomatic, relatives who are also at risk of life-threatening arrhythmias.We retrospectively collected data from our cardiogenetics database and patient records and analyzed whether the identified carriers received prophylactic treatment.From 1996 to 2008, 130 probands with a disease-causing mutation in one of the involved genes were identified, and 509 relatives tested positive for the disease-causing familial mutation. These subjects subsequently underwent cardiologic investigation (electrocardiography, exercise testing, Holter monitoring, ajmaline testing, echocardiography, where appropriate). After a mean follow-up of 69 +/- 31 months (LQTS), 60 +/- 19 months (CPVT), and 56 +/- 21 months (BrS), treatment was initiated and ongoing in 65% (199 of 308), 71% (85 of 120), and 6% (5 of 81) of the relatives in the LQTS, CPVT, and BrS families, respectively. Eight carriers were lost to follow-up. Treatment included drug treatment (n = 249) or implantation of pacemakers (n = 26) or cardioverter-defibrillators (n = 14). All mutation carriers received lifestyle instructions and a list of drugs to be avoided.Cascade screening in families with LQTS, BrS, or CPVT, which was based on DNA mutation carrying and subsequent cardiologic investigation, resulted in immediate prophylactic treatment in a substantial proportion of carriers, although these proportions varied significantly between the different diseases.

Unusual unmasking of Brugada syndrome electrocardiographic pattern during ajmaline test by leaning forward: a case report

A 71-year-old male consulted us because of recurrent episodes of irregular paroxysmal palpitations associated with chest pain. The patient had a family history of Brugada syndrome (the mother died suddenly at the age of 40 years and a daughter was diagnosed as a carrier of Brugada syndrome). The cardiac evaluation revealed a structurally normal heart. A coronary angiography excluded the presence of coronary artery abnormalities. Atrial fibrillation was already diagnosed 12 years before the present consultation. He had two successful external electrical cardioversions and sinus rhythm was maintained until our consultation with the administration of sotalol, at a dosage of 240 …

219 Follow-up of Brugada syndrome patients without implantable cardioverter-defibrillator: the “Achilles’ heel” of current studies?

Risk stratification for sudden cardiac death in asymptomatic Brugada syndrome (BS) patients is not perfect. Although follow-up of patients with an implantable cardio-defibrillator (ICD) is reliable, follow-up for patients without an ICD is less accurate. All patients seen at the Bordeaux CHU between 1999 and 2009 with BS (spontaneous type 1 or after flecainide or ajmaline test) were included prospectively in the database, i.e. 187 patients (76% men, 44 ±12 years). Follow-up of non-implanted patients was carried out by consultation or annual telephone contact. All patients seen over the last 6 months were recontacted for this study. One hundred and two patients (55% BS, 76% men, 43 ±13 years) did not have an ICD. In 50% of cases the BS had been discovered by chance, after lipothymia or syncope in 32% of cases and during family assessment in 18% of cases. A spontaneous type 1 was present in 68%. Electrophysiological Study (EPS) had been carried out in 79% of patients (Negative in 75 pts and positive in 5pts who had refused the ICD). Average follow-up was 52 ±37 months, and no subject was lost to follow-up (follow-up<6months for all patients), 89 were asymptomatic, 7 presented with lipothymia, 1 with syncope (without arrhythmia on loop recorder), 1 had supra-ventricular tachycardia and 3 had died (septic shock, overdose, and one young patient called in for a family assessment died suddenly, even though his EPS was negative). After an exhaustive 4.3 year follow-up, 3/102 patients with BS and with no ICD had died, 1 suddenly, despite following risk stratification recommendations.

Diagnostic utility of bipolar precordial leads during ajmaline testing for suspected Brugada syndrome

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

The ajmaline challenge and a strange ECG

In the early years of invasive electrophysiology, the ajmaline test was introduced to induce or enhance intra-ventricular conduction delays in patients with fascicular block, because of its intrinsic pharmacological properties on the HV interval and QRS duration. Nowadays, a new ajmaline challenge has become a very popular test (both in tertiary and primary centres), because of the induction of a coved ST-segment elevation in the precordial leads, erroneously ascribed to a repolarization abnormality. Much evidence (simply recording late potentials during the infusion) has documented that a depolarization abnormality is what is obtained after the infusion. The induced ECG is similar …

Response to intravenous ajmaline: a retrospective analysis of 677 ajmaline challenges

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

YIA Abstracts: Best abstracts on clinical studies

YIA Abstracts: Best abstracts on clinical studies

Brugada‐Like Changes in the Peripheral Leads during Diagnostic Ajmaline Test in Patients with Suspected Brugada Syndrome

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

Significance of QRS prolongation during diagnostic ajmaline test in patients with suspected Brugada syndrome

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

The Significance of QRS Prolongation During Ajmaline Testing in Patients Suspected of Brugada Syndrome

The Significance of QRS Prolongation During Ajmaline Testing in Patients Suspected of Brugada Syndrome

Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families

At least 4% of sudden deaths are unexplained at autopsy [sudden arrhythmic death syndrome (SADS)] and a quarter may be due to inherited cardiac disease. We hypothesized that comprehensive clinical investigation of SADS families would identify more susceptible individuals and causes of death. Fifty seven consecutively referred families with SADS death underwent evaluation including resting 12 lead, 24 h and exercise ECG and 2D echocardiography. Other investigations included signal averaged ECG, ajmaline testing, cardiac magnetic resonance imaging, and mutation analysis. First-degree relatives [184/262 (70%)] underwent evaluation, 13 (7%) reporting unexplained syncope. Seventeen (30%) families had a history of additional unexplained premature sudden death(s). Thirty families (53%) were diagnosed with inheritable heart disease: 13 definite long QT syndrome (LQTS), three possible/probable LQTS, five Brugada syndrome, five arrhythmogenic right ventricular cardiomyopathy (ARVC), and four other cardiomyopathies. One SCN5A and four KCNH2 mutations (38%) were identified in 13 definite LQTS families, one SCN5A mutation (20%) in five Brugada syndrome families and one (25%) PKP2 (plakophyllin2) mutation in four ARVC families. Over half of SADS deaths were likely to be due to inherited heart disease; accurate identification is vital for appropriate prophylaxis amongst relatives who should undergo comprehensive cardiological evaluation, guided and confirmed by mutation analysis.

The clinical significance of the ajmaline test in the noninvasive diagnosis of the Wolff-Parkinson-White syndrome

A knowledge of electrophysiological parameters of accessory atrioventricular conduction pathways, such as effective refractory time and high conduction capacity in atrial fibrillation, make it possible to detect those patients who are at risk of life-threatening ventricular tachyarrhythmias. One criterion to identify these electrophysiological parameters is persistent pre-excitation after intravenous administration of ajmaline in Wolff-Parkinson-White (WPW) syndrome. Sensitivity and specificity of the ajmaline test in detecting patients at risk of life-threatening ventricular tachyarrhythmias were evaluated in 58 consecutive patients (22 females, 36 males; mean age 40.2 +/- 13 years) with the WPW syndrome. Pre-excitation was blocked after ajmaline in 43 patients (74%), pre-excitation persisting in 15 (26%). In 26 of the 43 patients with blocked pre-excitation the ajmaline test indicated short effective refractory time (< 270 ms) of the accessory pathway, and a high conduction capacity in 19 (minimal pre-excitation R-R interval during atrial fibrillation of < 250 ms). Sensitivity of the ajmaline test in the detection of a short refractory time was 33.3%, specificity 89.4%, while the corresponding values were 40.6% and 92.3% for the detection of accessory pathways with high conduction capacity in atrial fibrillation. These data show that the ajmaline test is not useful for estimating the electrophysiological characteristics of the accessory pathways. It is thus of only subordinate diagnostic value in predicting how much patients with the WPW syndrome are at risk of serious ventricular tachyarrhythmias.

Brugada Syndrome in Pure Black Africans

Although all races are concerned with the Brugada syndrome, no case has ever been reported among black Africans. We describe five different cases in this specific group of populations. In all patients, Brugada syndrome was identified after detailed noninvasive and invasive evaluations. Sex ratio was four males for one female. Convulsive syncope was noticed in 1 patient with a family history of sudden death. Diagnostic coved-type pattern was observed spontaneously in the normal position of right precordial leads in 3 patients and in a higher position of leads in 3 patients. Sixty percent had first-degree atrioventricular block. An ajmaline test was performed in 4 patients and was positive either in normal position of leads or in superior position in all of them. Sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) was inducible during programmed ventricular stimulation in 3 patients. Right ventricular cineangiography found localized apical hypokinesia with preserved systolic function in 1 patient. Automatic cardioverter defibrillator was implanted in 2 patients. SCN5A was not found in any of the patients. These observations demonstrate that Brugada syndrome is also present in black African populations, and increasingly reported cases of apparent sudden death in the sub-Saharan part of the world need to rule out cardiac electrical disturbance such as Brugada syndrome.

Abstract 2250: Active Cascade Screening in Primary Inherited Arrhythmia Syndromes; Does it Lead to Prophylactic Treatment?

Introduction The congenital long QT syndrome (LQTS), Brugada syndrome (BrS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) are primary inherited cardiac arrhythmia syndromes which may cause syncope and sudden cardiac death in young individuals. After establishing the disease-causing DNA mutation in probands, we actively conducted cascade screening to identify relatives who are also at risk of life-threatening arrhythmias. We studied how often this led to prophylactic treatment. Methods and Results We retrospectively collected data from our Cardiogenetics database and patient records. In 1996–2006, 118 probands with a disease causing mutation in one of the involved genes were identified and 446 relatives were tested positive for the disease causing mutation found in their family. These subjects subsequently underwent cardiologic investigation (ECG, exercise testing, Holter, ajmaline testing, echocardiography, where appropriate). We analyzed the numbers and percentages of identified carriers needing prophylactic treatment. Treatment was deemed necessary based on the results of cardiologic investigation, type of disease, previously reported properties (clinical and/or biophysical) of the mutation, familial occurrence of unexplained sudden death, and age of the subject. Treatment was initiated in 69% (197/285), 9% (5/54) and 71% (76/107) relatives in the LQTS, BrS, and CPVT families, respectively. Twenty-six carriers were lost to follow-up. Treatment included drug treatment (n=244) and implantation of pacemakers (n=26) or ICDs (n=8). Conclusions Cascade screening in families with LQTS, BrS or CPVT, which was based on DNA mutation carriership and subsequent cardiologic investigation, resulted in immediate prophylactic treatment in a substantial proportion of carriers (278/446, 62%), although it varies significantly between the different disease entities.