The Response To Ajmaline Provocation in Healthy Subjects
Research type
Research Study
Full title
An observational study into the variety of electrocardiographic responses to an ajmaline Provocation in healthy subjects. What are the genetic and structural variations dictating this response ?
IRAS ID
139794
Contact name
Elijah Behr
Contact email
Sponsor organisation
St George's University of London
Eudract number
2016-004277-41
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 7 months, 1 days
Research summary
Research Summary:
Ajmaline is used to aid the diagnosis of a life threatening condition, Brugada syndrome (BrS). Brugada syndrome (BrS), is a rare inherited cardiac condition that can lead to life threatening arrhythmias and sudden cardiac death in otherwise healthy young adults. It is characterised by the presence or inducibility of a characteristic right bundle branch pattern on the ECG.
Ajmaline is used to uncover a diagnostic electrocardiographic (ECG) pattern. In doing so a diagnosis of concealed Brugada syndrome is possible.This is an interventional study of the various electrocardiographic changes that can occur during sodium channel provocation with Ajmaline in the healthy subject in comparison to those changes observed in a clinical cohort being assessed for concealed Brugada syndrome.
Our own existing historical data is used for comparison given the extremely rare nature of this condition. We have a cohort of 1200 patients who have undergone ajmaline provocation in the clinical setting, in excess of 270 have been found to have concealed Brugada syndrome.
We are interested in exploring the different ECG changes that can be produced in response to Ajmaline in healthy individuals who do not have Brugada Syndrome. We will measure a number of electrocardiographic parameters during provocation using validated and novel computerised measurement tools.
We aim to identify and better understand the ‘normal response’ to Ajmaline. We feel this information is vital in providing a more accurate diagnosis in the clinical setting. Additionally prediction of future risk is likely to be enhanced by understanding which genetic variations are associated with high risk clinical features. This is currently lacking as there are no similar studies in a healthy cohort.
We are also interested in identifying potential structural and genetic determinants of the ECG response.
Summary of Results:
Count Percentage
Number completing online questionnaire 416
Number invited for pre-screening 276
Number attending pre-screening 108 73.21%
Number undergoing intervention 100 95.35%
Mean Age (Standard Deviation) 27 (5.4)
Male 52 52%
Female 48 48%
Positive study = Type 1 BRS Pattern 3 3%
Negative study = No Type 1 BRS Pattern 97 97 %
Mean change in QRS duration in milliseconds (SD) 25.66 (11.98)
Mean change in PR interval in milliseconds (SD) 43.36 (17.27)
Mean change in QT interval in milliseconds (SD) 5.72 (18.62)
Mean change in T wave durations in milliseconds (SD) 15.00 (20.53)
Mean change in P wave duration in milliseconds (SD) 19.04 (15.38)One hundred pre-screened individuals underwent sodium channel provocation without complication. Mean age 27 (SD = 5.4). Three individuals (3% of cohort) developed the type 1 BRS pattern. There were no arrhythmic complications.
Previous reports suggested the yield of the Type 1 BRS pattern could be as high as 40% in those without a family history of sudden arrhythmic death (2).
Aside from the type 1 BRS pattern, the electrophysiological response to Ajmaline provocation has not been described in healthy controls, in the clinical setting, an increase in QRS duration and PR interval is observed. In this study a similar pattern was noted with mean PR interval and QRS duration at peak drug effect demonstrating the most profound change from the baseline measure.
This healthy cohort will serve as a control group for further work comparing the electrophysiological response to Ajmaline across a variety of clinical scenarios, thereby defining the pathological response more accurately.
REC name
London - South East Research Ethics Committee
REC reference
16/LO/2173
Date of REC Opinion
3 Jan 2017
REC opinion
Favourable Opinion