“Pill-in-the-Pocket” Treatment of Propafenone Unmasks ECG Brugada Pattern in an Atrial Fibrillation Patient With a Common SCN5A R1193Q Polymorphism

Figures

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  FIGURE 1. (A) ECG of the patient before PIP treatment with propafenone. (B) ECG of the patient after PIP treatment with propafenone. ST segment of V1–V3 was significantly elevated after PIP approach.

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  FIGURE 2. (A) Current–voltage relationship of peak currents. (B) The voltage dependence of SSA. (C) The voltage dependence of SSI. Experimental data were fitted with Boltzman relationships to obtain the parameters (Table 1). (D) Recovery from inactivation was assessed by the double-pulse protocol shown in inset and fitted using a biexponential function. Time constants and relative weights on averaged data are shown in Table 1.

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  FIGURE 3. (A) Whole-cell current recordings of TB before and after propafenone perfusion (10 μmol/L). (B) Concentration dependence of TB by propafenone. Graph showed a peak current after drug application normalized to peak current in the absence of drug plotted against a function of drug concentration. IC50 values were 70.3 ± 9.3 μmol/L for WT (n = 6) and 54.9 ± 10.1 μmol/L for R1193Q (n = 6), respectively.

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  FIGURE 4. (A) Whole-cell current recordings of UDB showed representative current traces (1st, 15th, and 30th) that have been normalized to facilitate comparison of WT and R1193Q in the presence of propafenone (2 μmol/L). (B) Graph showed UDB for WT and R1193Q channel in the absence of propafenone at 1 and 2 Hz pacing. Plots of normalized peak Na+ current against the number of depolarizing pulse to –10 mV from a holding potential of –100 mV for 400 ms, n = 7 to 14 cells per condition. (C) Graph showed UDB for WT and R1193Q channel in the presence of propafenone (2 μmol/L) at 1 and 2 Hz pacing, n = 8–13 cells per condition. R1193Q exhibited more sensitive to propafenone; at 2 Hz pacing, the UDB of WT and R1193Q was 24.8 ± 3.5 and 44.2 ± 5.7%, respectively, P < 0.05. (D) Concentration dependence of UDB by propafenone at 1 Hz pacing, n = 6 for each concentration. IC50 values were 13.2 ± 2.6 μmol/L for WT and 6.2 ± 1.3 μmol/L for R1193Q. (E) Concentration dependence of UDB by propafenone at 2 Hz pacing, n = 6 for each concentration. IC50 values were 8.1 ± 1.8 μmol/L for WT and 2.9 ± 0.7 μmol/L for R1193Q.

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  FIGURE 5. Effects of propafenone (2 μmol/L) on the channel gating properties. (A) Effect of propafenone on SSI in WT, propafenone shifted the V1/2 of SSI by -1.85 mV (from -63.41 ± 0.93 to -65.26 ± 2.61 mV, n = 7–10 cells for each group; P > 0.05). (B) Effect of propafenone on SSI in R1193Q, propafenone shifted the V1/2 by -6.96 mV (from -62.83 ± 1.72 to -69.79 ± 1.90 mV, n = 7–8 cells for each group, P < 0.05). (C) Effect of propafenone on time course of recovery from inactivation (protocol in inset), normalized current was plotted against a recovery interval (n = 8–10 cells for each group), time constants and relative weights on averaged data were as follows: for WT, Tfast = 12.0 ms, Afast = 0.71, Tslow = 53.1 ms, Aslow = 0.29; for R1193Q, Tfast = 21.2 ms, Afast = 0.70, Tslow = 123.5 ms, Aslow = 0.30.