Sex Differences in Autonomic Response to Exercise Testing in Patients with Brugada Syndrome

Cardiac events in patients with Brugada syndrome (BS) typically occur at rest and mainly during sleep, suggesting that changes in autonomic modulation play an important role in the arrhythmogenesis of the disease. Moreover, sex differences in clinical manifestations of BS have been reported, identifying male patients with worse prognosis. The aim of our work was to assess and compare, according to sex, autonomic response to exercise in a clinical series including 105 BS patients.

Standard 12-lead electrocardiogram recordings were collected during a physical stress test divided into four phases: warm-up, incremental exercise, active recovery, and passive recovery. Spectral non-stationary heart rate variability indicators were extracted by means of a smoothed pseudo Wigner-Ville distribution approach that adapts frequency bands to respiratory information. These indicators were then averaged in non-overlapped windows of 1 min for each patient to compare groups at each minute of the physical stress test.

From the last minute of warm-up and until the third minute of incremental exercise, asymptomatic male patients presented significantly greater low-frequency (LF) values ([Formula: see text]: p = 0.015;[Formula: see text]: p = 0.024; [Formula: see text]: p = 0.011; [Formula: see text]: p = 0.002) than asymptomatic females. Conversely, asymptomatic women showed increased vagal modulation during the first minutes of incremental exercise ([Formula: see text]: p = 0.031; [Formula: see text]: p = 0.001). However, no significant differences were observed between symptomatic male and female patients.

As previously reported in healthy subjects, enhanced parasympathetic and decreased sympathetic tones appear to be not only greater in women but also defensive during cardiac stress. Based on the results, asymptomatic patients presented same-sex tendencies. However, we observed that symptomatic males developed a more female-like autonomic modulation, probably related to a more protective autonomic response to exercise. These results could be a step forward toward the understanding of the autonomic function in BS along with a potential impact on risk stratification.