**10. Clinical Implications**

Despite the paucity of mechanistic insights into the pathogenesis of *SCN5A*-mediated DCM, one can derive clinical repercussions from the aforementioned theories. In patients with known *SCN5A* variants, a review of the literature for the description of its functional properties is necessary for selection of optimal beta-blockers, since propranolol (but not metoprolol) blocks both the peak and the late (persistent) *I*Na [44]. This effect might alleviate the ventricular arrhythmias in gain-of-function *SCN5A* variant carriers, but can controversially provoke arrhythmias and cause or worsen cardiac conduction delays at different levels in those with loss-of-function variants. Likewise, the former group might also benefit from treatment with class Ic antiarrhythmic medications that block the sodium channel, such as flecainide, while its use in the latter group might elicit arrhythmias and cardiac conduction delay. These suggestions are however limited to patients with clearly pathogenic and previously studied *SCN5A* variants, and more functional studies are needed to expand our knowledge to more *SCN5A* variants. Perhaps the growing use of the automated patch clamp technique will help advance this process.
