Brugada syndrome and fever: Genetic and molecular characterization of patients carrying mutations

Abstract

The genetic background of BrS patients sensitive to fever is heterogeneous. Our experimental data suggest that the clinical manifestations of fever-exacerbated BrS may not be mutation specific.

A hot topic

“…Action potential modeling of the right ventricle shows that a 50% reduction in I Na in conjunction with elevated temperature results in premature termination of the action potential, consistent with the BrS phenotype. 18 Elevating temperature of a canine model of heart tissue also supports a non-mutation-specific mechanism of hyperthermic arrhythmias. 97 Morita et al demonstrate a temperature induced pro-arrhythmic state due to shortening of the action potential duration and creation of a large intramural dispersion gradient of action potential duration.…”

“…Temperature analysis of L325R failed to produce effects consistent with ECG abnormalities observed in BrS. Keller et al (2005) proposed that the autosomal dominant pattern of inheritance of BrS results in a dominant negative reduction in the number of functional sodium channels. Thus, it could be argued that febrile arrythmias are not mutation specific but instead are mediated through the inherent temperature sensitivity of wild-type channels in conjunction with reduced I Na .…”

“…14 Whether temperature affects the voltage dependence of gating in native channels is debatable. A large number of studies show little or no effect of temperature on the voltage of halfmaximal (V 1/2 ) steady-state activation, 10,[15][16][17][18][19][20] but Thomas et al (2009) shows a strong hyperpolarizing shift in the V 1/2 of activation with increased temeperature. 11 The V 1/2 of inactivation, specifically slow inactivation, seems to show stronger temperature sensitivity.…”

Right bundle branch block or Brugada syndrome?

“…2A and B). In addition to class 1 anti-arrhythmic drugs fever has also been shown to unmask or trigger the Brugada syndrome phenotype [3].…”

Short-coupled variant of torsade de pointes

“…Several reports are written on fever triggering or unmasking (previously unknown) Brugada syndrome, resulting in tachyarrhythmias. 10,11 We are not aware of studies linking fever to QTc-related arrhythmias, let alone this shortcoupled variant of TdP. Both hypokalaemia and ciprofloxacin are known causes of QTc prolongation, but, to the best of our knowledge, have never been described in relation to the short-coupled variant of TdP, in contrast to several other antibiotics which are associated with TdP, with or without a prolonged QTc interval.…”