Exercise-induced ECG changes in Brugada syndrome

Abstract

Background: Ventricular arrhythmia occurrence during exercise is reported in Brugada syndrome (BrS). Accordingly, experimental studies suggest that BrS-linked SCN5A mutations reduce sodium current more at fast heart rates. Yet, the effects of exercise on the BrS ECG phenotype have not been studied. We aimed to assess ECG responses to exercise in BrS and determine whether these responses are affected by the presence of an SCN5A mutation.

Methods and results: ECGs at baseline, at peak exercise, and during recovery were analyzed from 35 male control subjects, 25 BrS men without SCN5A mutation (BrS(SCN5A)(-)), and 25 BrS men with SCN5A mutation (BrS(SCN5A+); 15 with missense mutation and 10 with mutation leading to premature truncation of the protein). No differences existed in clinical phenotype between BrS groups. At baseline, BrS(SCN5A)(-) and BrS(SCN5A+) patients had lower heart rates, wider QRS, shorter QT(c), and higher peak J-point amplitudes than control subjects; BrS(SCN5A+) patients also had longer PR than BrS(SCN5A)(-) and control subjects. Exercise resulted in PR shortening in all groups, more QRS widening in BrS(SCN5A+) than in BrS(SCN5A)(-) and control subjects(,) and less QT shortening in BrS(SCN5A)(-) and BrS(SCN5A+) than in control subjects. The latter resulted in QT(c) shortening in control subjects but QT(c) prolongation in BrS(SCN5A)(-) and BrS(SCN5A+). Finally, the increase in peak J-point amplitude during exercise was similar in all 3 groups but resulted in a coved-type pattern only in BrS(SCN5A)(-) and BrS(SCN5A+).

Conclusions: Exercise aggravated the ECG phenotype in BrS. The presence of an SCN5A mutation was associated with further conduction slowing at fast heart rates. Possible mechanisms that may explain the observed ECG changes are discussed.