Short QT syndrome

Overview

Short QT syndrome (SQTS) is a rare, inherited cardiac channelopathy characterized by abnormally short QT intervals on an electrocardiogram (ECG) and an increased risk of life-threatening arrhythmias, including atrial fibrillation, ventricular tachycardia, and sudden cardiac arrest. The QT interval represents the time it takes for the heart's electrical system to recharge between beats. In SQTS, this interval is shorter than normal, resulting in inadequate ventricular repolarization and increased arrhythmogenic potential. SQTS can affect individuals of all ages, and sudden death may be the first manifestation, especially in young, otherwise healthy individuals.

Causes

Short QT syndrome is primarily caused by mutations in genes that regulate cardiac ion channels, leading to accelerated repolarization of the heart. These genetic mutations affect potassium and calcium channels involved in the cardiac action potential. Known genes associated with SQTS include:

• KCNH2 (SQT1): Encodes the HERG potassium channel

• KCNQ1 (SQT2): Affects the slow delayed rectifier potassium current

• KCNJ2 (SQT3): Encodes the inward rectifier potassium channel

• Other rare mutations: May affect calcium channel function (e.g., CACNA1C)

The condition follows an autosomal dominant inheritance pattern, meaning only one copy of the mutated gene is needed to cause the disorder. In some cases, no genetic mutation is identified, and the cause remains idiopathic.

Symptoms

The clinical presentation of Short QT syndrome can vary widely. Some individuals remain asymptomatic, while others may experience serious arrhythmic events. Common symptoms and clinical findings include:

• Palpitations: Sensation of rapid or irregular heartbeat

• Syncope: Fainting episodes due to sudden arrhythmias

• Seizures: May occur as a result of cerebral hypoperfusion during cardiac arrest

• Sudden cardiac arrest: Particularly in infants, children, or young adults, often during rest or sleep

• Atrial fibrillation: May be the first presentation in some patients

Family history of sudden unexplained death, especially at a young age, is a critical clue for identifying individuals at risk for SQTS.

Diagnosis

Diagnosis of Short QT syndrome is based on clinical criteria, ECG findings, and genetic testing. Key steps include:

Electrocardiogram (ECG):

• QT interval corrected for heart rate (QTc) of ≤ 330 ms is highly suggestive

• QTc between 330–360 ms in the presence of symptoms or family history may support diagnosis

• T waves may appear tall and peaked, and PR intervals may be shortened

Clinical Criteria:

• Personal history of syncope, atrial fibrillation, or ventricular arrhythmias

• Family history of sudden cardiac death at a young age

• History of cardiac arrest or documented ventricular fibrillation

Genetic Testing:

• Used to identify pathogenic mutations in known SQTS genes

• Helps in confirming diagnosis and guiding family screening

Electrophysiological Study (EPS):

• May be used to assess arrhythmic risk and inducibility of ventricular arrhythmias

Treatment

Management of Short QT syndrome is centered on preventing sudden cardiac death and controlling arrhythmias. Treatment strategies may include:

Implantable Cardioverter-Defibrillator (ICD):

• Primary treatment for individuals at high risk (history of cardiac arrest, syncope, documented VT/VF)

• Can terminate life-threatening arrhythmias in real time

Pharmacologic Therapy:

• Quinidine: Most studied antiarrhythmic for SQTS; prolongs QT interval and may prevent arrhythmias

• Sotalol or other class III antiarrhythmics: Sometimes used but with less evidence of efficacy

• Beta-blockers: May help in selected cases but not effective in significantly prolonging QT

Lifestyle and Monitoring:

• Regular cardiac follow-up with ECGs and Holter monitoring

• Screening of first-degree relatives with ECG and genetic testing when applicable

• Avoidance of medications that further shorten the QT interval

Prognosis

The prognosis for individuals with Short QT syndrome depends on the severity of symptoms, the presence of high-risk features (e.g., history of cardiac arrest), and effectiveness of therapy. Without treatment, the risk of sudden cardiac death is significant. However, with timely diagnosis and management, particularly with ICD placement and/or quinidine therapy, long-term survival improves substantially.

Family screening and early intervention are crucial for preventing fatal arrhythmic events in affected relatives. Continued research and registries are important to better understand this rare but serious condition and improve outcomes through early detection and targeted therapy.