It is noted that in

It is noted that in this study BrS patients had an abnormality of plasma K+ concentration which has been suggested to be a potential trigger of Brugada Syndrome episodes [11]. In the absence of renal dysfunction, the hyperkalemia may result from an abnormal phenotype in BrS characterized by mutation of potassium Z-IETD-FMK with increasing outward potassium currents (KCNE3, KCND3 and KCNJ8) [12–15]. A further molecular study in the patients in this study should be done to confirm this mechanism. Importantly, it is worth noting that in this study all subjects performed a graded exercise test which was vigorous exercise lasting a few minutes. With increases in plasma catecholamines and K+ concentrations, exercising at this intensity can be a potential problem even in healthy individuals. Within first few minutes after starting exercise, plasma K+ concentration increases [16] due to release from contracting skeletal muscles [17]. Furthermore, plasma pH can decrease by 0.4 units [18], and catecholamines can increase up to 15 fold (as high as 0.5–1µM at the level of the single ventricular myocyte) [19,20]. During exercise in healthy individuals, there is K+ uptake in non-contracting tissues which prevents an excessive increase in plasma K+ concentration [21–22], which reduces the overall increase in K+ concentrations. During exercise recovery, there is a transient hypokalemia [16] resulting from an increment in the skeletal muscle Na+–K+ ATPase activity which is stimulated via beta-2 adrenoceptors promoting K+ uptake [20]. During recovery there is also reported to be a marked vagal rebound [20]. The period of post-exercise hypokalemia may last 90min or longer depending upon the intensity of the exercise [23]. The reduction in hyperkalemia during the recovery period may be a beneficial effect of exercise in the BrS patients in this study. However, a disruption of this normal protective mechanism may cause SCD in BrS patients. This has been confirmed by previous studies suggesting that the increased vagal tone and/or the decreased sympathetic activity, together with ionic imbalance were important mechanisms in the arrhythmogenesis of BrS [24,25]. The reduction of nor-epinephrine in BrS could lead to an impaired stimulation of β-adrenoceptors. It could contribute to the reduction of cAMP and alter the subsequent signaling pathway having potential implications for arrhythmogenesis [24] and subsequent myocardial infarction [25]. In this study, sympathovagal and ionic imbalances during recovery after the exercise test were also found. In fact, a recent study reviewed the role of exercise stress testing in BrS [26]. It was found that an exercise test can worsen the ST abnormalities in BrS patients and can produce ventricular arrhythmias. The author suggested that BrS patients should not perform vigorous exercise. It is noted that we did not monitor the right precordial leads (V1 to V3) in which ST-segment elevation is important in identifying Brugada Syndrome. However, although we could not monitor Brugada-type ECG during the experiments, the post-experiment analysis of the recording made by the implanted cardioverter-defibrillators showed no Brugada ECG throughout the experiments. We measured ECG during the experiments with modified chest lead V4 (MCL4) [8] because we wished to investigate HRV in these patients and the measurement of HRV is most effectively done with a large R wave because it provides a more accurate determination of RR interval. Together with mild resting pre-exercise hyperkalemia this may imply that the patients in this study were not in a severe condition and had a good prognosis [27]. Nonetheless, a further research on BrS patients is needed to explore the ECG a few days after the exercise test. Moreover, it is unclear whether there are different responses to low- intensity and moderate-intensity exercise in BrS patients compared to controls. Thus, further research is needed to investigate the sympathovagal and cardio-respiratory changes after low-intensity and moderate-intensity exercise in order to provide further information as to whether the BrS patients may gain benefit from exercise training at one or more intensities.