Presentation: Adult with arrhythmogenic right ventricular cardiomyopathy

A 30-year-old woman is referred for assessment due to multiple episodes of palpitations that cause her to feel lightheaded. She has had one episode of blackout. An electrocardiogram (ECG) demonstrates inverted T-waves in leads V1 to V3. Cardiac MRI shows reduced right ventricular function with features of fibrous-fatty infiltration of the heart muscle. Her sister has an implantable cardioverter-defibrillator device in her chest following a resuscitated cardiac arrest.

• Genomic testing is recommended in the following situations:
  • an individual meets a definite diagnosis according to the modified task force criteria, with age of onset below 50 years; or
  • a deceased individual had pathologically confirmed arrhythmogenic right ventricular cardiomyopathy (ARVC) and has relatives who will benefit from cascade testing in the event of a genetic diagnosis; or
  • identification of a pathogenic or likely pathogenic variant in an ARVC-associated gene would complete diagnostic task force criteria for ARVC.
• 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.
• Bear in mind that the phenotype may represent another form of arrhythmogenic cardiomyopathy (ACM) – for example, left ventricular or biventricular involvement or features of dilated cardiomyopathy (DCM).

• 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 adults with suspected ARVC is:
  • R133 Arrhythmogenic right ventricular cardiomyopathy. This indication comprises small gene panel sequencing.
• 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.

For clinicians

• NHS England: National Genomic Test Directory

References:

• Corrado D, van Tintelen PJ, McKenna WJ and others. ‘Arrhythmogenic right ventricular cardiomyopathy: Evaluation of the current diagnostic criteria and differential diagnosis’. European Heart Journal 2020: volume 41, issue 14, pages 1,414–1,429. DOI: 10.1093/eurheartj/ehz669
• Marcus FI, McKenna WJ, Sherrill D and others. ‘Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: Proposed modification of the Task Force Criteria’. European Heart Journal 2010: volume 31, issue 7, pages 806–814. DOI: 10.1093/eurheartj/ehq025

For patients

• British Heart Foundation: Arrhythmogenic cardiomyopathy
• Cardiomyopathy UK: Arrhythmogenic cardiomyopathy
• Cardiac Risk in the Young
• NHS Health A to Z: Cardiomyopathy
• SADS Foundation: ARVC/ACM