Short QT Syndrome (SQTS)

Monogenic (Mendelian): a minority with a definite variant: gain-of-function KCNH2 (SQT1), KCNQ1, KCNJ2^[2]

Acquired: secondary short QT (hyperkalaemia, hypercalcaemia, acidosis, digoxin) is separate and reversible^[3]

Complex (likely polygenic): most cases are gene-elusive; the genetic architecture is incompletely defined^[2]

Inheritance: Autosomal dominant where a causal variant is found, which is a minority of patients; familial disease is present in 44% of kindreds, and some variants arise de novo^[5]. Male predominance (84% of patients in a European registry^[5]); estimated prevalence about 2.7 per 100,000 (~0.0027%), and an isolated short QTc on an ECG is commoner than clinical SQTS. First described by Gussak et al. in 2000^[4]; first genetic subtype identified by Ramon Brugada et al. in 2004.^[3]

Genetic yield: Low, about 15–20%: a causal variant was found in 14% of a 73-patient European registry^[5], so the large majority are genetically elusive. Nine genotypes described to date.

ClinGen-validated genes (Walsh et al, EHJ 2022, SQTS reappraisal)^[2]:

• KCNH2 (SQT1), Definitive: Gain-of-function in IKr channel (hERG/Kv11.1); accelerates repolarisation; paradoxically the same gene causes LQT2 when loss-of-function. Key mutations: N588K, T618I. Most evidence.^[7]
• KCNQ1 (SQT2), Strong: Gain-of-function in IKs channel (same gene as LQT1 when loss-of-function). Very few described variants (only 1 in ClinGen curation).
• KCNJ2 (SQT3), Moderate: Gain-of-function in IK1 channel (inward rectifier); same gene as Andersen-Tawil syndrome when loss-of-function. Very limited evidence (5 variants).
• SLC4A3, Moderate to strong (panel divided): Anion exchanger; evidence rests on a single variant.

Important caveat (Walsh et al 2022)^[2]: Evidence for most SQTS genes is derived from very few variants (5 in KCNJ2, 2 in KCNH2, 1 in KCNQ1/SLC4A3). Even KCNH2, the only definitive gene, rests on a few recurrent variants and scored lower than definitive genes in other conditions. Genetic results must be interpreted with extreme caution, low pre-test probability → high false-positive risk. Other reported genes (CACNA1C, CACNA2D1, CACNB2, SCN5A) are disputed: most reported carriers had Brugada syndrome with a relatively short QT rather than SQTS.

Pathophysiology: Accelerated K⁺ efflux (SQT1–3) or attenuated Ca²⁺ influx (proposed for calcium-channel genes whose link to SQTS is disputed^[2]) → shortened ventricular action potential → abbreviated QTc → shortened refractory period → susceptibility to re-entrant AF and VF.

Very rare, estimated at approximately 2.7 per 100,000 (~0.0027%), though estimates vary with the QTc threshold and clinical criteria used; first described by Gussak et al in 2000^[4][3]

Affects a wide age range, from neonates to elderly; the syndrome is present across all age groups from infancy to old age^[3]

Strongly associated with ventricular fibrillation and sudden cardiac death; paroxysmal AF is often an early manifestation

Genetic testing identifies a causal variant in only a minority, about 15–20% (14% in a European registry^[5]); the large majority remain genetically elusive; nine genetic subtypes described to date^[3]

Common mutations: KCNH2 (SQT1, gain-of-function, definitive), KCNQ1 (SQT2, strong), KCNJ2 (SQT3, moderate)^[3]

Diagnostic Criteria:

• Diagnosed (Class I): QTc ≤360 ms with at least one of: a pathogenic variant, a family history of SQTS, or survival of VT/VF in the absence of heart disease^[1]
• Should be considered (Class IIa): QTc ≤320 ms; or QTc 320–360 ms with arrhythmic syncope^[1]
• May be considered (Class IIb): QTc 320–360 ms with a family history of sudden death before 40 years^[1]
• Verify the QT measurement and exclude secondary causes of a short QT (for example hyperkalaemia, hypercalcaemia, acidosis, hyperthermia, digoxin effect) before applying these thresholds
• Gollob probability score (an older, pre-ESC scoring system, analogous to the Schwartz score for LQTS): weights ECG findings, clinical history, family history and genetics to classify low/intermediate/high probability; useful as contextual evidence but is a separate, older framework from the current ESC diagnostic classes above and the two should not be conflated as a single unified rule

NHS Genomic Medicine Service testing-eligibility criteria (R-codes) are a separate funding/eligibility framework for who qualifies for NHS-funded genetic testing, they are not themselves diagnostic criteria for SQTS.

ECG features (Pérez-Riera et al, J Electrocardiol 2024; Boulmpou et al, J Pers Med 2025)^[6][3]:

• Very short QTc (often <300 ms in symptomatic cases)
• Tall, narrow, peaked T waves: short isoelectric ST segment; rapid transition from J-point to T-wave peak
• T wave appears symmetric on 12-lead ECG, but vectorcardiogram confirms T loop asymmetry, efferent branch dashes are closer together (Pérez-Riera 2024)^[6]
• "Minus-plus T wave sign", described as a specific ECG marker
• Short atrial refractory period → paroxysmal AF (often first manifestation); Holter may capture AF spontaneously converting to sinus rhythm
• Short ventricular refractory period → VF susceptibility

Clinical Features:

• Wide age range, from neonates to elderly; presentations at any age from infancy to old age
• Often asymptomatic, incidental ECG finding
• Palpitations, presyncope, syncope
• Cardiac arrest (VF), may be first presentation
• Paroxysmal AF, often early onset (<40 years), may convert spontaneously
• Sudden infant death syndrome reported in SQTS families

1. General measures:

• Genetic counselling and family cascade testing, see the Genetic Testing page

2. Medical therapy:

• Hydroquinidine (preferred where available, prolongs QTc via IKr inhibition; most pharmacological evidence in SQTS^[3]): reduces arrhythmic events; first-line pharmacological option in high-risk patients unsuitable for ICD
• Quinidine (bisulfate formulation, alternative): may prolong QT interval and reduce VF inducibility; consider alongside ICD to reduce device therapies
• Quinidine may be considered (Class IIb) in asymptomatic patients with a family history of sudden cardiac death, and in those who qualify for an ICD but decline it or have a contraindication^[1]
• Atrial fibrillation: anticoagulation as per standard AF guidelines; quinidine/hydroquinidine may help AF control and simultaneously address arrhythmic risk

3. Device therapy:

• ICD: the therapy with the strongest evidence for secondary prevention, first-line in survivors of cardiac arrest^[1]
• An ICD should be considered after arrhythmic syncope (Class IIa)^[1]
• Sensing: tall, peaked T waves predispose to T-wave oversensing and inappropriate shocks; check sensing at implant and on exercise, and screen carefully before choosing a subcutaneous ICD^[3]

4. Acute management (electrical storm):

• Haemodynamically unstable or sustained arrhythmia: advanced life support with external cardioversion/defibrillation (Class I)^[1]
• Interrogate any ICD: T-wave oversensing causes inappropriate shocks in SQTS and is corrected by reprogramming (Class I)^[1][3]
• Sedation to reduce sympathetic tone (Class I)^[1]
• Isoprenaline IV may be considered (Class IIb)^[1]
• Quinidine (or hydroquinidine) is the best-supported antiarrhythmic; start or up-titrate, monitoring for excessive QT prolongation^[1]
• Stop QT-shortening drugs, e.g. nicorandil^[1]
• Refractory storm: deep sedation/intubation (Class IIa)^[1]

• VF and sudden cardiac death: possible from infancy, and no QTc threshold reliably predicts it^[1]
• Atrial fibrillation: often at a young age, and may be the presenting feature
• Inappropriate ICD shocks: from T-wave oversensing (tall, peaked T waves)

Quantitative natural history: In the largest natural-history cohort (73 patients; mean QTc 314 ms), cardiac arrest was frequently the sentinel event, and the estimated probability of a first arrhythmic event by age 40 was approximately 41% in probands. Crucially, QTc duration itself did not predict events, a very short QTc alone should not be used to reassure or to drive ICD decisions. Hydroquinidine prevented arrhythmia recurrence in all treated patients during follow-up.^[5]

High-risk features for SCD:

• Prior cardiac arrest or documented VF: the strongest independent predictor of recurrence^[5]
• Syncope (probable arrhythmic)
• Family history of sudden death <40 years
• Very short QTc (e.g. <320 ms), a diagnostic feature, but on its own a weak risk discriminator (see above)

ICD and monitoring:^[1]

• Class I: ICD after aborted cardiac arrest or documented spontaneous sustained VT
• Class IIa: ICD for arrhythmic syncope
• Class IIa: implantable loop recorder in young patients
• Class III: programmed electrical stimulation for risk stratification

mWHO class II–III or above: refer to a Pregnancy Heart Team before conception (see Pregnancy).

Based on ESC ventricular arrhythmia guidance and SQTS reviews^[1][3].

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

• Accurate QT measurement essential: manual measurement on repeated ECGs at heart rates near 60 bpm^[1]
• Exclude secondary causes of QT shortening (hypercalcemia, hyperkalemia, acidosis, digoxin)^[1]
• A very short QTc does not predict events on its own; history of cardiac arrest or arrhythmic syncope does^[5]
• Programmed stimulation is not recommended for risk stratification^[1]
• Tall T waves risk ICD oversensing: check sensing carefully^[3]
• Hydroquinidine or quinidine is the main drug option^[3]
• Family screening essential: autosomal dominant where a variant is found, and familial disease is common even when genetic testing is negative^[1][5]
• Avoid QT-shortening drugs if possible^[1]