Presentation: Adult with long QT syndrome

A 30-year-old offshore worker is referred to a cardiology clinic after undergoing a routine work medical, during which an electrocardiogram (ECG) shows a QTc interval of 520 ms. He is fit and well and not on any regular medications.

• Consider genomic testing if there is a firm clinical diagnosis of long QT syndrome (LQTS) as indicated by either:
  • QTc ≥500 ms in repeated 12-lead ECGs;
  • LQTS risk >3.5;
  • QTc ≥480 ms in repeated 12-lead ECGs and an unexplained syncopal episode; or
  • QTc ≥480 ms in repeated 12-lead ECGs and a history of sudden unexplained death under 60 years of age in a first- or second-degree relative.
• A secondary cause for QT prolongation should be excluded first. Secondary causes include QT-prolonging medications and electrolyte anomalies, particularly hypokalaemia and hypomagnesaemia.
• Genomic testing should be carried out in parallel with expert phenotypic assessment – for example, in an inherited cardiac conditions (ICC) clinic – and with support from clinical genetics services. Note that testing may occasionally be appropriate outside these criteria, following discussion in an ICC multidisciplinary team meeting.
• Referrals for genomic testing will be triaged by a genomic laboratory. Testing should be targeted at those in whom a genetic or genomic diagnosis will guide management for the proband or their family.
• Testing should also be considered in first-degree relatives of a patient with confirmed LQTS whose condition is associated with an identified familial variant.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from the eligibility criteria in the National Genomic Test Directory, it is appropriate to refer to an ICC clinic for further assessment.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see our dedicated Knowledge Hub resource.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• If the relevant eligibility criteria are met, discuss the case with or refer it to your local ICC clinical service for genomic testing and family screening. You will need to provide details confirming that the patient fulfils the criteria.
• The relevant clinical indication for long QT syndrome is:
  • R127 Long QT syndrome: This indication comprises small gene panel sequencing.
• For tests that do not include whole genome sequencing, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub; and
  • include details of the phenotype in the test order form (refer to human phenotype ontology (HPO) terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• These tests are DNA based, and an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

• Crediblemeds
• NHS England: National Genomic Test Directory

References:

• Schwartz PJ and Crotti L. ‘QTc behavior during exercise and genetic testing for the long-QT syndrome’. Circulation 2011: volume 124, issue 20, pages 2,181–2,184. DOI: 10.1161/CIRCULATIONAHA.111.062182
• Zeppenfeld K, Tfelt-Hansen J, de Riva M and others. ‘2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)’. European Heart Journal 2022: volume 43, issue 40, pages 3,997–4,126. DOI: 10.1093/eurheartj/ehac262

Resources for patients

• Arrhythmia Alliance: Long QT syndrome
• British Heart Foundation: Life with sudden arrhythmic death syndrome
• British Heart Foundation: Long QT syndrome
• Cardiac Risk in the Young: Long QT syndrome
• NHS Health A to Z: Long QT syndrome
• SADS Foundation: Long QT syndrome