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Feasibility and Outcomes of Ajmaline Provocation Testing for Brugada Syndrome in Children in a Specialist Paediatric Inherited Cardiovascular Diseases Centre

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Feasibility and Outcomes of Ajmaline Provocation Testing for Brugada Syndrome in Children in a Specialist Paediatric Inherited Cardiovascular Diseases Centre Arrhythmias and sudden death Open Heart: first published as 10.1136/openhrt-2013-000023 on 12 February 2014. Downloaded from Feasibility and outcomes of ajmaline provocation testing for Brugada syndrome in children in a specialist paediatric inherited cardiovascular diseases centre Merlin Ranald McMillan,1 Thomas George Day,1 Margarita Bartsota,1 Sarah Mead-Regan,1 Rory Bryant,1 Jasveer Mangat,1 Dominic Abrams,2 Martin Lowe,1 Juan Pablo Kaski1,3 To cite: McMillan MR, ABSTRACT sudden cardiac death (SCD) in adults and et al – Day TG, Bartsota M, . Objectives: Brugada syndrome (BrS) is an inherited children.1 3 It is characterised by a stereotyp- Feasibility and outcomes of arrhythmia syndrome that causes sudden cardiac death ajmaline provocation testing ical ECG pattern of cove-shaped ST segment in the young. The class Ia antiarrhythmic ajmaline can 14–6 for Brugada syndrome in elevation in the anterior chest leads, be used to provoke the diagnostic ECG pattern. Its use children in a specialist although this pattern is not always apparent, has been established in adults, but little data exist on paediatric inherited even in individuals with confirmed BrS. The the ajmaline provocation test in children. This study cardiovascular diseases prevalence of this pattern increases with age, centre. Open Heart 2014;1: aims to determine the safety and feasibility of ajmaline e000023. doi:10.1136/ provocation testing in a large paediatric cohort in a suggesting" that there are children with the openhrt-2013-000023 specialist paediatric inherited cardiac diseases centre. syndrome who will go on to develop a diag- Methods: 98 consecutive ajmaline tests were nostic ECG pattern. The diagnostic pattern 78 performed in 95 children between September 2004 and fluctuates and can also be unmasked by July 2012 for family history of BrS (n=46 (48%)); other factors such as fever and medications.9 family history of unexplained sudden cardiac death The use of class Ia antiarrhythmic agents ▸ Additional material is (n=39 (41%); symptoms with suspicious ECG such as flecainide and ajmaline to unmask http://openheart.bmj.com/ published online only. To abnormalities (n=9 (10%)). Three patients were view please visit the journal occult BrS in the adult population has been retested with age, due to the possibility of age-related 9–12 online (http://dx.doi.org/10. extensively reported. Ajmaline has been penetrance. ECG parameters were measured at baseline 1136/openhrt-2013-000023) selected as the agent of choice due to its and during maximal ajmaline effect. short half-life, established safety profile in Results: The mean patient age was 12.55 years, 43% Received 16 December 2013 adults and higher diagnostic yield compared Revised 8 January 2014 were female. Nineteen patients (20%) had a positive fl 13 Accepted 17 January 2014 ajmaline test. There were no arrhythmias or adverse with ecainide. However, little data exist on fi 14 events during testing. Ajmaline provoked significant its safety and ef cacy in children. This study aims to add further safety and feasibil- prolongation of the PR, QRS and QTc in all patients. on October 1, 2021 by guest. Protected copyright. Mean follow-up was 3.62 years with no adverse ity data on the diagnostic ajmaline provoca- outcomes reported in any patients with BrS. There tion test in children in a specialist paediatric were no predictors of a positive ajmaline provocation inherited cardiovascular diseases centre. test on multivariable analysis. One patient who tested negative at 12 years of age, subsequently tested positive at 15 years of age. METHODS Conclusions: Ajmaline testing appears safe and For numbered affiliations see Ajmaline test protocol feasible in children when performed in an appropriate end of article. All ajmaline tests were performed and inter- setting by an experienced team. Test positivity may preted by experienc""ed cardiologists with Correspondence to change with age in individuals, suggesting that the test Dr Juan Pablo Kaski, should be repeated in the late teenage years or early expertise in the evaluation and management Inherited Cardiovascular adulthood. of inherited cardiac conditions (ML, DA and Diseases Unit, Department JPK), with advanced cardiovascular resuscita- of Cardiology, Great Ormond tion equipment to hand. All patients (or Street Hospital NHS parents/guardians) gave informed consent Foundation Trust, Great Ormond Street, London INTRODUCTION to the test being performed, and signed an WC1N 3JH, UK; The Brugada syndrome (BrS) is an inherited appropriate form to record this. Patients [email protected] arrhythmia syndrome that is a cause of were intravenously cannulated and attached McMillan MR, Day TG, Bartsota M, et al. Open Heart 2014;1:e000023. doi:10.1136/openhrt-2013-000023 1 Open Heart Open Heart: first published as 10.1136/openhrt-2013-000023 on 12 February 2014. Downloaded from to continuous 12-lead ECG monitoring (using either a combinations of baseline HR, PR, QRS and QTc with age Mortara ECG machine via an Ultima CardiO2 worksta- and gender used as potential predictors. A value of tion or a Marquette MAC 5000 ECG machine). Baseline p<0.05 was considered significant in all cases. ECGs were taken after a period of rest. The ECGs were analysed at 1 min intervals throughout the duration of the test. Ajmaline was given intravenously as a phased RESULTS fi infusion over 5 min. A dose of 1 mg/kg up to a Ninety- ve consecutive patients aged 18 years or below – maximum of 50 mg was used. The infusion was discon- (12.55 years, SD 3.34; range 5 18 years and 4 months, 1 tinued if the ECGs became diagnostic or the QRS dur- outlier at 1 year 10 months) underwent ajmaline provo- ation increased by 150% or more.11 ECGs were cation testing in the Inherited Cardiovascular Diseases monitored until the PR interval and QRS durations had Unit at Great Ormond Street Hospital from the 1 normalised. A test was considered positive if there was J September 2004 to 31 July 2012. Forty-one patients were point elevation of ≥2 mms with coved ST elevation in female (43%). Three patients were retested in the more than one right precordial lead.611From 2011 department at an average of 5 years after the initial test, onwards, all patients undergoing ajmaline provocation due to the possibility of age-related penetrance. Baseline testing (n=24 (24%)) routinely had ECGs recorded in characteristics of these patients are presented in table 1. leads V1 and V2 in the high parasternal position in add- No patients had evidence of a spontaneous or fever- ition to the standard lead placement. induced type I Brugada ECG during follow-up. Individuals with a positive ajmaline provocation test The indication for ajmaline challenge was a family received advice in relation to fever management and history of BrS in 46 patients (48%), family history of fi avoidance of drugs with the potential to precipitate ven- unexplained SCD (without a con rmed family history of tricular arrhythmias in this population, and were advised BrS) in 39 (41%), symptoms with suspicious ECG abnor- to undergo an ECG during febrile episodes.15 All indivi- malities in 9 (9%; syncope, n=5; chest pain, n=1; palpita- duals were followed at 6–12 monthly intervals by the tions, n=3) and development of bradycardia with same team at our institution with a resting and/or abnormal ECG during general anaesthesia with propofol ambulatory ECG. in 1 patient. An infant was admitted following an appar- Structural heart disease was excluded in all patients ent life-threatening event after her brother had died in fi fi prior to testing using non-invasive imaging (echocardi- con rmed ventricular brillation (VF). This child ography and/or cardiac MRI) as has previously been underwent an ajmaline test in the catheter lab at the described.16 Genetic testing for mutations in the SCN5A age of 1 year and 10 months while having a loop gene was not routinely performed. recorder device implanted. One patient had evidence of sinus node dysfunction fl http://openheart.bmj.com/ ECG analysis and atrial utter at presentation; all other patients were Available ECGs were further analysed retrospectively by a in sinus rhythm, with no evidence of conduction disease single investigator (MRM) at pretest baseline and or atrial arrhythmia. maximal effect of ajmaline, defined by maximal pro- longation of ECG parameters. The PR, QRS, QT and RR Results of ajmaline provocation testing intervals were measured using vernier callipers (accurate A diagnostic type I response was reported in 19 indivi- to 0.02 mm) and averaged across three heart beats in duals (20%). Thirteen of the 46 patients (29%) who leads II and V5 (10,14). The QTc was calculated using underwent ajmaline provocation testing for a family ’ 17 fi history of BrS tested positive, compared with 5 of the 39 Bazett s formula. Patients were classi ed as having on October 1, 2021 by guest. Protected copyright. partial right bundle branch block (RBBB) if there was (13%) patients tested for a family history of SCD. The an RsrI pattern in V1 or V2 without prolongation of the remaining positive result was in an individual presenting QRS beyond 120 ms. No patients had a complete RBBB. with syncope and a suspicious ECG. Of the 13 patients with a positive ajmaline test referred because of a family Statistical analysis history of BrS, there was a history of SCD in a second All statistical analyses were performed using R V.12.2.1 degree relative in one family only. (R Foundation for Statistical Computing, Austria).18 Of the positive ajmaline tests, 12 patients’ ECGs Normally distributed, continuous data are presented as (63%) showed a diagnostic pattern within 4 min of the mean (± SD) with categorical data presented as n (%).
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