Short QT Syndrome: a new primary electrical disease

Description

A series of descriptions and reports have helped to establish the short QT Sydrome as a new primary electrical disease. In 2000, the association of a short QT interval with familial atrial fibrillation was first described. Then there was a single unrelated case with sudden cardiac death put forward by Gussak et al. and subsequently the report of two European families with a significant familial history of atrial fibrillation, syncope and sudden cardiac death who have been associated with a short QT interval.(1,2)

Genetic screening of the latter two families enabled the identification of the first gain-of-function mutation of the rapid component of the delayed rectifier potassium current (IKr) which constitutes the Short QT-1 syndrome (SQT1).(3)
Two further gain-of-function mutations establishing the Short QT-2 and Short QT-3 syndrome demonstrate the fact that we are dealing with a genetically heterogeneous disease (SQT2 and SQT3).(4,5)

Risks of the short QT syndrome

In patients with a short QT syndrome, the risk for an arrhythmic event such as syncope and/or sudden cardiac death due to ventricular tachyarrhythmias is high. A relevant number of sudden cardiac deaths occurred in three - respectively four generations- in the two reported families with a short QT interval.(2)
However, in demonstrating a clinical heterogeneity in the first described family, the same mutation (SQT-1) was found but no sudden cardiac death was reported.(6)
Nevertheless, sudden cardiac death may be the first presentation of the disease with no preceding syncope since four of the sudden cardiac deaths had no history of prior syncope or other arrhythmic events.

Screening for patients with the short QT syndrome

The incidence of atrial fibrillation is high in patients with a short QT syndrome. Approximately 70% of patients with a short QT syndrome had either paroxysmal or permanent atrial fibrillation. In 50% of the patients, the first symptom was atrial fibrillation. Thus especially in young patients with “lone” atrial fibrillation, one must screen for  short QT syndrome. The electrocardiogram is characterised by absolute QT intervals below 300-320 ms. The QT interval should be measured and corrected for heart rate at rates < 80 bpm. A tall, symmetrical peaking T wave in the right precordial leads (figure 1) is often striking. However, this has not been observed in every patient and asymmetrical T-waves have also been described.(5)
All patients, during programmed atrial and ventricular stimulation, demonstrated very short atrial and ventricular effective refractory periods ranging from 120 to 180 ms. Ventricular fibrillation was inducible in 90 % of the patients. However, individual risk assessment of patients with a short QT syndrome is still difficult due to the genetic and clinical heterogeneity and low numbers of patients with a short follow-up period.

Pharmaceutical treatment

The response to drugs has been studied only in SQT1 patients with a mutation in KCNH2 (HERG). Quinidine prolonged the QT-interval into the normal range and prevented inducibility of ventricular fibrillation in four out of four patients.(7,8)
Thus, pharmacological treatment of patients with a short QT-1 syndrome may be considered in view to suppress atrial fibrillation. Pharmaceutical treatment should be reserved only for the treatment or prevention of ventricular tachyarrhythmias if a defibrillator implant, which is at present the therapy option in symptomatic patients and patients with a family history of sudden cardiac death, is denied or impossible for other reasons.(9)

Figure

ECG from a 71 year old patient with a short QT syndrome and atrial fibrillation (QT interval 240 ms, QTc 290 ms, paper speed 25 mm/sec).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.