Background: Short QT Syndrome (SQTS) is one of the rarest and most lethal inherited arrhythmogenic syndromes. Preliminary data have shown that hydroquinidine (HQ) is effective in prolonging the duration of QT interval and in preventing the induction of ventricular arrhythmias during programmed electrical stimulation in SQTS patients. No data exist regarding the efficacy of HQ in reducing cardiac events in SQTS patients.
Objective: To determine whether HQ reduces the occurrence of Life-threatening Arrhythmic Events (LAE), defined as aborted cardiac arrest and sudden cardiac death, in SQTS patients.
Methods: Cohort study on consecutive SQTS patients referred to our center and treated with HQ. The endpoint was to evaluate the antiarrhythmic efficacy of HQ, by comparing the percentage of patients with LAE, the number of LAE per patient and the annual rate of LAE before and after the beginning of therapy with HQ (mean duration of therapy 6±1 years).
Results: The study population was comprised of 17 SQTS patients with the following characteristics: 13 (76%) males, age at beginning of therapy with HQ 29±3 years, QTc interval before treatment 331±3 ms. Therapy with HQ was ceased in 2 cases (12%) after 1 week due to gastrointestinal intolerance, while in the remaining 15 patients HQ was administered continuously for 6±1 years, at an average dose of 528±42 mg per day (7±0.6 mg/kg/day). HQ significantly prolonged the QTc interval in all patients, by a mean of 60±6 ms (p<0.001). HQ reduced to zero the percentage of patients with LAE (from 40% to 0%, p=0.03), the mean number of LAE per patient (from 0.73±0.3 to 0, p=0.026) and the annual rate of LAE (from 12.2% to 0%, p=0.028).
Conclusions: We showed for the first time that HQ, besides normalizing the duration of the QT interval, is associated with a major reduction of life-threatening arrhythmic events in SQTS patients, thus representing an efficacious therapeutic approach in this group of individuals. Early discontinuation due to gastrointestinal intolerance occurred in 12% of patients.