Influencia neurohormonal y farmacológica en el fenotipo del síndrome de Brugada

Abstract

Introduction: Brugada síndrome (BS) is a channelopathy, or alteration of the heart's ionic channels, with a genetic origin, capable of producing sudden death in patients with structurally normal hearts. There is no ethiologic treatment, and the difficulty in its management resides in sudden death risk stratification for further automatic defibrillator implant. Though this indication is clear for patients who have suffered a recuperated sudden death, for the other patients the indication is unclear, and it is necessary to look for risk indicators in order to optimize the defibrillator use. Sudden death incidence is much higher in males, and its occurrence is more frequent during night hours, the mechanism for these asymmetries not having been established. Aims: 1. To develop a specific software for electrocardiographic signal averaging and analysis. 2. To study the differences in averaged signal between BS patients and a control group. 3. To analyze the QT interval behaviour for 24 h. 4. To study testosterone (TH) levels in BS patients, and to analyze its correlation with the phenotype. Methods: Inclusion of patients with spontaneous BS and of those who underwent a challenge test with flecainide for its diagnosis was carried out. Three sub-studies were performed: a) In patients who underwent flecainide test, analysis of averaged electrocardiographic signal, with the aim of studying flecainide action mechanism in these patients, and attempt to describe risk markers. To compare findings according to the test result. b) Study of the QT interval behaviour using 24h electrocardiographic recording, in order to investigate what causes that sudden death episodes are more frequent during night time. c) Description of testosterone levels in BS patients of both genders, and their correlation with the clinical expression, including their possible implication as a risk factor. Study of the penetrance in a genotyped sample. Results: a) An increase of filtered QRS, ST segment amplitude, and delayed activation parameters were observed in all the patients who underwent the test, compared to the control group. There were differences in ST segment amplitude increase and in its concavity between patients with positive or negative result. There were no differences in the other variables. b) A deficient adaptation of QT interval to heart rate was observed in BS patients, compared to the control group. This meant shorter mean intervals along the 24 hours in BS patients than in the control group, and also extremely short QT intervals at slow heart rates, as predicted by the regression line. c) BS patients show higher TH levels than the control group, though there were no differences when analysed by gender. TH standardization proved of no use to avoid the gender influence in the results. Conclusions: a) Flecainide produces a global delay in ventricular activation, both in BS and control patients. b) BS patients show a deficient QT interval adaptation to heart rate, which results in shorter mean QT intervals than in normal people. c) BS patients show higher testosterone levels than the control group, probably due to the gender asymmetry showed by the disease.