Background: The ajmaline challenge is a key diagnostic tool for Brugada syndrome (BrS). Although ajmaline displays rapid distribution and short initial duration of action, the optimal timing to capture the diagnostic response remains under discussion. Previous studies suggest that peak ECG changes occur shortly after administration, yet this may not coincide with the appearance of the diagnostic type I pattern.
Methods: We prospectively analysed 67 patients referred for ajmaline challenge due to suspected BrS. All patients received intravenous ajmaline (1 mg/kg over 5 minutes). Serial ECGs were recorded up to 90 minutes. The “peak effect” was defined as the time point of maximum QRS and QTc prolongation, while a “positive response” was defined as the emergence of a type I Brugada pattern.
Results: Out of 67 patients, 27 (40%) had a positive test. Baseline characteristics were similar between groups (see Table 1). The mean time of peak ECG interval prolongation was 10 minutes after infusion onset, with a rapid QRS and QTc interval normalisation minutes. However, the emergence of the type I pattern occurred significantly later, with a mean of 11.5minutes. In 6 patients (22.2%) the positive response appeared after 10 minutes, which means after the completion of the ajmaline infusion and once the QRS and QTc intervals were already returning to normal [see figure 1]. Moreover, in one patient the positive response appeared at the 90-minute follow-up ECG, which lies beyond the ECG monitoring window defined by most protocols.
Discussion: Our findings highlight a temporal dissociation between peak pharmacodynamic effect and diagnostic manifestation. This is consistent with previous evidence of PK/PD hysteresis with ajmaline: its myocardial uptake lags peak plasma concentration, leading to a delayed ECG response. These results challenge the traditional assumption that diagnostic changes occur exclusively during or immediately after infusion.
Conclusion: While ajmaline’s electrophysiological effects tend to peak early, the diagnostic type I pattern may appear later—even after drug administration has ceased. These findings underscore the importance of maintaining continuous ECG monitoring for at least 20 minutes post-infusion, in order to optimise the sensitivity of the test. Extending the observation window may enhance BrS detection without compromising safety, given the short functional half-life of ajmaline.