Short QT Syndrome

Short QT syndrome (SQTS) is a rare inherited channelopathy in which the QT interval is abnormally short, with a high risk of atrial fibrillation, ventricular tachycardia and fibrillation, syncope and sudden cardiac death at any age, including infancy.

It is diagnosed by a QTc of 320 ms or less, or a QTc of 360 ms or less with one or more of: a pathogenic variant, a family history of SQTS, a family history of sudden death under 40 years, or survival of ventricular tachycardia or fibrillation without structural heart disease. Earlier criteria used a QTc of 340 ms or less.

Genes include KCNH2 (SQT1, gain of IKr), KCNQ1 (SQT2, gain of IKs), KCNJ2 (SQT3, gain of IK1), CACNA1C and CACNB2 (SQT4 and SQT5, loss of L-type calcium current, with a Brugada overlap), CACNA2D1 and SLC4A3. Inheritance is autosomal dominant with high penetrance.

Pathophysiology. Gain of repolarising potassium current or loss of calcium current shortens the action potential and the effective refractory period in atrium and ventricle. Dispersion of repolarisation and short refractory periods allow re-entry, causing atrial fibrillation and ventricular fibrillation.

The QT interval fails to adapt to heart rate. Arrhythmia occurs at rest, during sleep and with exertion.

• Palpitations, syncope, cardiac arrest, and atrial fibrillation at a young age, including in infants.
• Family history of sudden death, including sudden infant death.
• Many patients are asymptomatic, and the finding is incidental.
• Examination is normal. ECG shows a short QT interval, little or no ST segment, tall, narrow, symmetrical peaked T waves and a short interval from the J point to the T peak (under 120 ms), with bradycardia.

Red flags.

• Syncope, resuscitated arrest or documented ventricular fibrillation
• Atrial fibrillation in a child or young adult
• QTc of 320 ms or less
• Sudden death or sudden infant death in a relative
• Family history of SQTS

• 12-lead ECG: measure the QT at heart rates under 80/min; correction formulas are unreliable at faster rates. Repeat on separate days.
• Gollob score:
  • ECG: QTc under 370 ms 1 point, under 350 ms 2, under 330 ms 3; J point to T peak interval under 120 ms 1.
  • Clinical history: cardiac arrest 2; documented polymorphic ventricular tachycardia or ventricular fibrillation 2; unexplained syncope 1; atrial fibrillation 1.
  • Family history: first or second degree relative with high probability SQTS 2; first or second degree relative with unexplained sudden cardiac death 1; sudden infant death syndrome 1.
  • Genotype: confirmed pathogenic genotype 2; variant of uncertain significance 1.
  • Interpretation: 4 or more high probability, 3 intermediate, 2 or less low.
• Ambulatory ECG and exercise testing: the QT fails to shorten with rate, and atrial and ventricular arrhythmia are documented.
• Genetic testing: KCNH2, KCNQ1, KCNJ2, CACNA1C, CACNB2 and SLC4A3, with cascade screening of relatives.
• Echocardiography or MRI: exclude structural heart disease. Laboratory: calcium, potassium, acid base state, thyroid function, and drug history.

Differential diagnosis.

• Acquired short QT from hypercalcaemia, hyperkalaemia, acidosis, hyperthermia, digoxin, anabolic steroids, or rufinamide
• Early repolarisation pattern
• Brugada syndrome
• Athlete's heart with relative bradycardia
• Overcorrection of QT at rapid heart rates
• Hyperthyroidism
• Familial atrial fibrillation
• Long QT syndrome with an incorrect measurement

• Implantable cardioverter defibrillator: indicated after cardiac arrest or documented sustained ventricular tachycardia. It is also considered with unexplained syncope. T wave oversensing causing inappropriate shocks is the main hazard, so test sensing before implantation, choose the lead position carefully and programme long detection durations and high rate zones. Subcutaneous devices carry a higher risk of oversensing.
• Quinidine prolongs the QT and refractory period and reduces arrhythmia: quinidine sulphate 200 to 300 mg orally every 8 hours (usual total 600 to 900 mg daily), maximum 1,200 mg daily in this setting, long term. Aim for a QTc over 360 ms. Monitor ECG, full blood count (thrombocytopenia), liver enzymes, and gastrointestinal symptoms (diarrhoea limits tolerance). Contraindicated in complete atrioventricular block without a pacemaker, myasthenia gravis, and a history of quinidine induced thrombocytopenia. It doubles digoxin levels (halve the digoxin dose), potentiates warfarin and interacts with CYP2D6 and CYP3A4 drugs. It is the best studied option and is effective in SQT1, in which sotalol and flecainide are not.
• Atrial fibrillation: anticoagulation is directed by individual stroke risk. Apixaban 5 mg orally twice daily, reduced to 2.5 mg twice daily when at least two of age 80 years or over, weight 60 kg or under and serum creatinine 133 micromol/L or over are present. Also 2.5 mg twice daily at creatinine clearance 15 to 29 mL/min, and avoided under 15 mL/min. Maximum 10 mg daily. Long term. Rhythm control is difficult, and ablation has limited data.
• Avoid drugs and states that shorten the QT: digoxin, hypercalcaemia, hyperkalaemia and acidosis.
• Asymptomatic gene carriers: follow up, avoidance of triggers, and quinidine considered case by case.

Special groups.

• Children and infants: ICD placement is technically demanding, and quinidine is used as a bridge.
• Pregnancy: continue quinidine with specialist supervision and device follow up.

Monitoring. Device interrogation every 3 to 6 months with remote monitoring. ECG yearly, and after each change in quinidine dose. Ambulatory ECG yearly for atrial fibrillation. Cascade screening of first degree relatives.

Referral and escalation. Refer to an inherited cardiac conditions centre. Urgent for syncope, ventricular arrhythmia or device shocks.