Electrocardiographic characteristics of definite drug induced Brugada patients

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Robert Lancaster Memorial Fund sponsored by McColl’s Research Group British Heart Foundation. BACKGROUND: Clinical, electrocardiographic, and genomic factors associated with the development of the drug induced type 1 Brugada pattern (DI-T1BP), in response to sodium channel blocker provocation (SCBP) have been investigated. However, these prior analyses have mostly been concerned with the prediction of the DI-T1BP rather than the strength or validity of the diagnosis of Brugada syndrome (BrS). We sought to analyse and compare the ECG response to SCBP with Ajmaline in a cohort of healthy subjects (Healthy Controls) and clinical patients with a DI-T1BP and a Shanghai Score (ShS) >3.5 (Definite-BrS group). METHODS: From an existing clinical cohort of consecutive patients investigated at our centre between 2010 - 2022, we identified those with a DI-T1BP and a ShS >3.5. Respondents to a national advertisement, completed an online medical questionnaire. Those fulfilling the inclusion criteria were invited to undergo further evaluation with eligible subjects being recruited to the healthy control group. All subjects received a diagnostic AP (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 controls and 166 patients with definite BrS were recruited, Table 1.0. This included 51 (31%) BrS probands. In the definite BrS group, the mean pre-ajmaline ShS was 2.1 (± 0.80) and mean final ShS was 4.3 (± 0.75). In comparison to healthy controls, the time to peak drug effect was significantly earlier in definite BrS patients, 05:18 (±02:05) vs. 05:59 (± 01:20). Whilst the increase in global QRS duration was greater in the definite BrS group, ∆37.78ms (± 18.16ms) vs. ∆25.66ms (±11.98) P<0.01, the increase in PR interval was greater in the healthy control group, ∆43.36ms (±17.27ms) vs. ∆20.77ms (±31.64ms), P<0.01. Compared to the healthy controls, the definite BrS group experienced a pronounced increase in anterior ST-J point amplitude ∆27.58µV (±27.70) vs. 115.37µV(±106.41), P<0.01, respectively. In contrast, whilst there was a reduction in inferior and lateral ST-J point amplitude in the definite BrS group, healthy controls demonstrated an increase in amplitude in these regions, Table 2.0. Mean QRS area was significantly greater at peak drug effect in the definite BrS group, ∆0.14V/s (±0.31) vs. ∆-0.20 (±0.18), P <0.01, whilst T wave area showed a reduction. CONCLUSION: In addition to the DI-T1BP patients with definite BrS experience a number of ECG characteristics that might allow for a quantitative refinement of the diagnosis. [Figure: see text] [Figure: see text]