Exercise-Induced ECG Changes in Brugada Syndrome

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 (BrSSCN5A-), and 25 BrS men with SCN5A mutation (BrSSCN5A+; 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, BrSSCN5A- and BrSSCN5A+ patients had lower heart rates, wider QRS, shorter QT(c), and higher peak J-point amplitudes than control subjects; BrSSCN5A+ patients also had longer PR than BrSSCN5A- and control subjects. Exercise resulted in PR shortening in all groups, more QRS widening in BrSSCN5A+ than in BrSSCN5A- and control subjects, and less QT shortening in BrSSCN5A- and BrSSCN5A- than in control subjects. The latter resulted in QTc shortening in control subjects but QTc prolongation in BrSSCN5A- and BrSSCN5A+. 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 BrSSCN5A- and BrSSCN5A+. 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. (Circ Arrhythmia Electrophysiol. 2009; 2: 531-539.)