Presentation: Adult with dilated (including arrhythmogenic) cardiomyopathy

A 40-year-old man is referred for assessment due to a progressive shortness of breath, intermittent palpitations and impaired exercise capacity. An electrocardiogram (ECG) demonstrates inverted T-waves in V1–V3 and a chest X-ray shows evidence of cardiomegaly with pulmonary oedema.

• Consider genomic testing in the presence of a firm clinical diagnosis of dilated cardiomyopathy (DCM) or arrhythmogenic cardiomyopathy (ACM), as indicated by either:
  • a left or biventricular cardiomyopathy associated with variable degrees of myocardial dysfunction and/or myocardial fibrosis as well as ventricular arrhythmias (including prior cardiac arrest) following exclusion of other aetiologies (including inflammatory conditions);
  • a deceased individual with pathologically confirmed DCM or ACM with an age of onset below 50 years (they would be suitable for post-mortem DNA analysis);
  • a patient (any age) with a first-degree relative with a confirmed diagnosis of either DCM or ACM; or
  • a left ventricular end-diastolic diameter greater than two standard deviations, with:
  • • an ejection fraction reduced to less than 45%, adjusted for age and sex, with an age of onset below 50 years; or
  • • DCM with conduction defects, with an age of onset below 65 years.
• Genomic testing is recommended for patients who meet the above criteria and have:
  • relatives who will benefit from cascade testing in the event of a genetic diagnosis; and/or
  • features suggestive of an increased risk of sudden death, including:
  • • conduction defects;
  • • atrial arrhythmia;
  • • extensive myocardial fibrosis; and/or
  • • a family history of sudden death.
• Patients with ventricular dilatation secondary to coronary artery disease or pressure or volume overload should not be tested.
• Patients with DCM due to other precipitants (including myocarditis, alcohol, peripartum or chemotherapy) should only be tested after consultation with an expert.
• 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.

• 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.
• 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.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from 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 DCM or ACM is:
  • R132 Dilated and arrhythmogenic cardiomyopathy: This indication comprises whole exome sequencing or medium gene panel sequencing and multiplex ligation-dependent probe amplification (MLPA).
• 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.

• European Society of Cardiology: 2023 ESC guidelines for the management of cardiomyopathies
• NHS England: National Genomic Test Directory

References:

• McDonagh TA, Metra M, Adamo M and others. ‘2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC’. European Heart Journal 2021: volume 42, issue 48, page 4,901. DOI: 10.1093/eurheartj/ehab670

For patients

• British Heart Foundation: Arrhythmogenic cardiomyopathy
• British Heart Foundation: Dilated cardiomyopathy
• British Heart Foundation: Life with dilated cardiomyopathy
• Cardiac Risk in the Young
• Cardiomyopathy UK: Arrhythmogenic cardiomyopathy
• Cardiomyopathy UK: Dilated cardiomyopathy
• myheart: Dilated cardiomyopathy