Clinical trial report: the electrocardiographic response to ajmaline provocation in healthy subjects

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Foundation. Main funding source(s): British Heart Foundation The Robert Lancaster Memorial Fund sponsored by McColl’s Research Group BACKGROUND: The electrocardiographic (ECG) response to diagnostic ajmaline provocation (AP) testing has been studied extensively in clinical cohorts. However, the healthy ECG response has not been described. We undertook a trial examining ECG changes in response to AP in a cohort of systematically recruited asymptomatic Caucasian healthy subjects with no family history of sudden death and normal baseline ECG and echocardiogram. METHODS: Applicants responded to a national recruitment advertisement and completed an online medical questionnaire. Those fulfilling inclusion criteria were invited to undergo further evaluation with eligible subjects undergoing a diagnostic ajmaline challenge (1mg/kg, max. 100mg over 5 minutes). A continuous ECG was recorded in the standard and high right precordial lead (HRPL) position. Automated analysis of conventional and novel ECG measurements were made at baseline and at peak drug effect, which was defined as the point of maximum QRS duration (excluding precordial leads). RESULTS: One hundred healthy Caucasian subjects underwent AP. The mean age was 26.84 years (SD ± 8.01 years) and 52% were male. A drug induced type 1 Brugada pattern (DI-T1BP) was observed in 3/100 (3%) of the cohort. We performed a paired comparison of ECG measures at baseline versus peak drug effect (Table 1). AP had a similar effect on global QRS duration and global PR interval, with both increasing by 28%, mean ∆ 25.66ms and mean ∆ 43.36ms respectively. Changes in S wave parameters in lead II were pronounced, with a 97% increase in S wave duration and a 101% increase in S wave negative amplitude. ST-J point elevation in the anterior, inferior, and lateral regions was comparable, with a 57%, 51% and 57% increase in ST-J amplitude respectively. AP had a greater effect on cardiac conduction in females compared to males (Table 2). In contrast, changes in STJ point amplitude and combined and segmented QRST segment area were greater in males. CONCLUSION: The healthy ECG response to AP elicits a pronounced effect on cardiac conduction, more so in females compared to males, whilst changes in STJ point amplitude and QRST area were greater in male subjects. The DI-T1BP is part of the healthy response to AP. [Figure: see text] [Figure: see text]