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 520ms. 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 ≥500ms on repeated 12-lead ECGs;
  • LQTS risk >3.5 Schwartz score (noted in Schwartz and Crotti);
  • QTc ≥480ms on repeated 12-lead ECGs in the context of concerning symptoms such as unexplained syncopal episode; or
  • QTc ≥480ms 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 abnormalities, particularly hypokalaemia and hypomagnesaemia.
• Genomic testing should be carried out in parallel with expert phenotypic assessment – for example in an inherited cardiac conditions (ICC) service with multidisciplinary team (MDT) approach, including support from clinical genetics services.
• Occasionally, testing may be appropriate outside these circumstances and should be discussed in an ICC MDT setting.
• 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 and/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. This requires prior genetic counselling.

• 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 of all available tests.
  • For information about how to arrange testing in Wales, Scotland or Northern Ireland, see Genomic testing in the devolved nations.
• For information on the genes that are included on different gene panels, see the NHS Genomic Medicine Service (GMS) Signed Off Panels Resource.
• If eligibility criteria are met, discuss with/refer to your local ICC clinical service for genomic testing and family screening, including details of confirmation that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in other published guidelines, but these guidelines differ to the eligibility criteria in the test directory, it is appropriate to refer to an ICC clinic for further assessment.
• The relevant clinical indication for long QT syndrome is:
  • R127 Long QT syndrome: This indication comprises small gene panel sequencing.
• Predictive testing for first-degree relatives of a patient with a known causative variant should be requested via:
  • R242 Predictive testing for known familial variant(s).
• None of the tests outlined above use whole genome sequencing, so you should use your local Genomic Laboratory Hub test order form and consent (record of discussion) form.
• Most tests are DNA based, and an EDTA sample (typically a purple-topped tube) is required. There are a few tests for which a different type of tube is used; see Samples for genomic testing in rare disease.
• If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
• 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 (search ‘QTdrugs Lists’ for, for instance, QT-prolonging medications)
• 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: Long QT syndrome
• Cardiac Risk in the Young: Long QT syndrome
• NHS Health A to Z: Long QT syndrome
• SADS Foundation: Long QT syndrome