Israel Medical Association Journal

Background: Familial dysautonomia is a hereditary disease characterized by dysfunction of the sensory and autonomic nervous systems. Studies in patients with familial dysautonomia have shown that abnormal cardiac autonomic denervation might influence repolarization. Autonomic tone also affects atrial conduction parameters and P-wave dispersion, which are predictive of atrial fibrillation.

Objectives: To examine the possible association of familial dysautonomia with abnormal atrial conduction and P-wave dispersion.

Methods: The study population included 12 patients with familial dysautonomia and age and sex-matched control subjects. All participants underwent a 12-lead electrocardiogram under strict conditions. P-wave lengths and P-wave dispersion were computed from a randomly selected beat and an averaged beat using designated computer software.

Results: There were no statistically significant differences between the groups in minimal, maximal, and average P-wave duration or P-wave dispersion for a randomly selected beat. P-wave dispersion for an averaged beat was also similar. During 6 months follow-up, no supraventricular arrhythmias were documented in either group.

Conclusions: We found that patients with familial dysautonomia had P-wave dispersion parameters not significantly different from those of controls. Further research is required to clarify the effects of dysautonomia on atrial conduction in familial dysautonomia.

Classic anticoagulant drugs, such as heparin and warfarin, are very effective. Although in use for more than 50 years, they have some clinical drawbacks. Heparin, now better termed unfractionated heparin, can only be used intravenously and its laboratory control is complicated. Warfarin is orally administered, but its therapeutic window is very narrow and patients need repeated laboratory tests. Moreover, both drugs are non-specific, as they inhibit the coagulation cascade at several steps. Pharmaceutic research has developed new drugs, some of which are already on the market, such as fondaparinux, a pentasaccharide that can interact with antithrombin, thus inhibiting factor Xa. This pentasaccharide is part of the parent heparin molecule and can be chemically synthesized, with the advantage of avoiding extractive compounds. Fondaparinux has a half-life compatible with once-a-day administration; modification of its structure (idraparinux) has led to more stable binding with antithrombin and to an increase in its half-life to allow once-a-week administration. Alternatives to oral anticoagulants have been developed following the study of some compounds like hirudin, which directly binds thrombin and blocks its catalytic site. One of these molecules, ximelagatran, is in advanced clinical development. Ximelagatran is converted into its active form, melagatran, in the circulation, and thrombin activity can be blocked by oral administration twice daily. There is no need for laboratory control and phase II and phase III studies are encouraging. The next few years should bring great changes in the treatment of patients with thromboembolic disorders.