OBJECTIVES: The aim of this study was to investigate the clinical 
characteristics and the long-term course of a large cohort of patients with 
short QT syndrome (SQTS).
BACKGROUND: SQTS is a rare channelopathy characterized by an increased risk of 
sudden death. Data on the long-term outcome of SQTS patients are not available.
METHODS: Fifty-three patients from the European Short QT Registry (75% males; 
median age: 26 years) were followed up for 64 ± 27 months.
RESULTS: A familial or personal history of cardiac arrest was present in 89%. 
Sudden death was the clinical presentation in 32%. The average QTc was 314 ± 23 
ms. A mutation in genes related to SQTS was found in 23% of the probands; most 
of them had a gain of function mutation in HERG (SQTS1). Twenty-four patients 
received an implantable cardioverter defibrillator, and 12 patients received 
long-term prophylaxis with hydroquinidine (HQ), which was effective in 
preventing the induction of ventricular arrhythmias. Patients with a HERG 
mutation had shorter QTc at baseline and a greater QTc prolongation after 
treatment with HQ. During follow-up, 2 already symptomatic patients received 
appropriate implantable cardioverter defibrillator shocks and 1 had syncope. 
Nonsustained polymorphic ventricular tachycardia was recorded in 3 patients. The 
event rate was 4.9% per year in the patients without antiarrhythmic therapy. No 
arrhythmic events occurred in patients receiving HQ.
CONCLUSIONS: SQTS carries a high risk of sudden death in all age groups. 
Symptomatic patients have a high risk of recurrent arrhythmic events. HQ is 
effective in preventing ventricular tachyarrhythmia induction and arrhythmic 
events during long-term follow-up.