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 SCN5AϪ ), and 25 BrS men with SCN5A mutation (BrS SCN5Aϩ ; 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 SCN5AϪ and BrS SCN5Aϩ patients had lower heart rates, wider QRS, shorter QT c , and higher peak J-point amplitudes than control subjects; BrS SCN5Aϩ patients also had longer PR than BrS SCN5AϪ and control subjects. Exercise resulted in PR shortening in all groups, more QRS widening in BrS SCN5Aϩ than in BrS SCN5AϪ and control subjects , and less QT shortening in BrS SCN5AϪ and BrS SCN5Aϩ than in control subjects. The latter resulted in QT c shortening in control subjects but QT c prolongation in BrS SCN5AϪ and BrS SCN5Aϩ . 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 SCN5AϪ and BrS SCN5Aϩ . 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.)

PurposeArrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a myocardial disease that predominantly affects the right ventricle (RV). Its hallmark feature is fibro-fatty replacement of RV myocardium. However, patchy inflammatory infiltrates in the RV are also consistently reported using autopsy and myocardial biopsy. Although the role of inflammation in ARVC/D is unresolved, the ability to assess inflammation non-invasively may aid in the diagnostic process. We aimed to establish whether cardiac inflammation can be assessed non-invasively in ARVC/D patients.MethodsIn eight ARVC/D patients and nine controls (haematology/oncology patients), the level of inflammatory activation was assessed by measuring plasma levels of inflammatory cytokines. Regional myocardial inflammation was assessed with 67Ga scintigraphy.ResultsARVC/D patients had higher plasma levels than controls of the pro-inflammatory cytokines interleukin (IL)-1β (1.22 ± 0.07 vs 0.08 ± 0.01 pg/ml, p < 0.0001), IL-6 (3.16 ± 0.44 vs 0.38 ± 0.04 pg/ml, p < 0.0001) and tumour necrosis factor (TNF)-α (9.16 ± 0.90 vs 0.40 ± 0.06 pg/ml, p < 0.0001), while levels of the anti-inflammatory cytokine IL-10 were not significantly different (1.36 ± 0.15 vs 1.20 ± 0.30 pg/ml, p = 0.74). 67Ga uptake in the RV was higher in ARVC/D patients than in controls. In ARVC/D patients, 67Ga uptake in the RV wall was higher than in the interventricular septum or left ventricular wall.ConclusionInflammation in the RV wall of ARVC/D patients can be detected non-invasively with the combined analysis of plasma levels of inflammatory cytokines and cardiac 67Ga scintigraphy.