KEY TEACHING POINTS

•Short QT syndrome is an inherited channelopathy that predisposes patients to life-threatening arrhythmias. Most patients who have been genotyped carry a mutation in the KCNH2 gene. An implantable cardioverter-defibrillator is the treatment of choice in individuals who have experienced cardiac arrest or syncope. •Clinical studies on a limited number of subjects have demonstrated the efficacy of long-term prophylactic treatment with hydroquinidine in prolonging the QT interval and preventing atrial and ventricular arrhythmias in both symptomatic and asymptomatic SQTS patients, regardless of their genotype. Other antiarrhythmic drugs, including flecainide, sotalol, and ibutilide, have been tried in patients with the KCNH2-N588K mutation and did not show any efficacy. •An in vitro study suggested a possible role for pharmacologic therapy with sotalol in SQTS patients with the KCNH2-T618I mutation. In this first in vivo report, this drug did not prove to be effective. Further evidence is needed before its use in the setting of SQTS can be recommended.