Genetic testing for diagnosis of inheritable cardiac rhythm disorders

Newton S, Mittal R, Hill H, Carter D, Schubert C
Record ID 32018002419
Original Title: MSAC application 1598
Authors' objectives: To assess the safety, clinical effectiveness and cost effectiveness of genetic testing for the diagnosis of inheritable cardiac rhythm disorders. The proposed use of the test was in affected individuals (patients with clinical suspicion of inheritable cardiac arrhythmia syndrome), and cascade testing in biological relatives of affected individuals with a positive genetic diagnosis. The test comprised a panel of at least 20 genes implicated in inherited cardiac arrhythmias or channelopathies. This HTA was undertaken for the Australian Government to inform their decision making around publicly funding the test via the Medicare Benefits Schedule.
Authors' results and conclusions: Safety: Genetic testing has non-inferior safety compared to no testing in both affected individuals and family members. It was found that the clinical diagnosis of a cardiac arrrhythmia may adversely affect mental health status. Clinical Effectiveness: With regard to analytical performance, NGS panels were found to be highly accurate for detecting pathogenic variants in long QT syndrome (LQTS), when compared to Sanger sequencing. A benefit in clinical validity was shown by genetic testing, with a small proportion of patients receiving a changed diagnosis after testing. Genetic testing was also superior to clinical assessment alone at determining the subtype of LQTS, which is important as it impacts on prognosis. With regard to clinical utility, an important benefit was identified for family members of individuals with at least one pathogenic variant, as they can be safely discharged from further surveillance if they do not carry the variant. Conversely, those identified with the variant can receive appropriate surveillance and treatment, such as prophylactic measures. However it is difficult to quantify the benefit, as it is not known to what degree family members comply with current surveillance recommendations in the absence of genetic testing. For some affected individuals, knowing the genotype can help to modify treatment recommendations, especially with regard to avoiding triggers. The main ethical issues raised in the literature relate to insurance discrimination, equity of access to testing, patient motivations to test or not test, reproductive decision making, and issues of personal identity and coping. Furthermore, cascade testing raises a host of ethical issues, particularly who ought to share the information with relatives (the proband or the doctor), how and why they ought to share it, what helps and hinders the information sharing, and under what circumstances the doctor might be ethically justified in breaching confidentiality with the proband. Cost effectiveness: Genetic testing results in cost-savings due to unneccesary surveillance avoided in genotype-negative family members, and informs about variant status for index cases and family members tested. Sensitivity analyses shows that the cost savings were higher when diagnostic yield was higher and when more family members per index case were tested; cost savings decreased with decreases in these variables. Overall: For affected individuals, on the basis of the evidence, it is suggested that, relative to clinical assessment alone, genetic testing for inheritable cardiac arrhythmias and channelopathies and associated interventions has non-inferior safety and non-inferior effectiveness. For family members, on the basis of the evidence, it is suggested that, relative to clinical assessment alone, genetic testing for inheritable cardiac arrhythmias and channelopathies and associated interventions has non-inferior safety and superior effectiveness. The test for both affected individuals and cascade testing in biological relatives was recommended for funding at the MSAC meeting in November 2020.
Authors' methods: A systematic review was undertaken to investigate the research questions. The review was guided by PPICO criteria. A linked evidence approach that considered analytical validity, clinical validity, clinical utility was applied. A review of relevant ethical, legal and social implications was also undertaken. A cost-effectiveness and cost-comparison analysis was undertaken. Sensitivity analyses around the areas of uncertainty in the model were undertaken.
Project Status: Completed
Year Published: 2020
English language abstract: An English language summary is available
Publication Type: Not Assigned
Country: Australia
MeSH Terms
  • Genetic Testing
  • Atrial Fibrillation
  • Genetic Predisposition to Disease
  • Arrhythmias, Cardiac
  • genetic testing
  • genotyping
  • long QT syndrome
  • channelopathies
  • inherited cardiac arrhythmias
  • Jervell and Lange-Nielsen syndrome
  • Brugada syndrome
  • catecholaminergic polymorphic ventricular tachycardia
Organisation Name: Adelaide Health Technology Assessment
Contact Address: School of Public Health, Mail Drop 545, University of Adelaide, Adelaide SA 5005, AUSTRALIA, Tel: +61 8 8313 4617
Contact Name:
Contact Email:

Adelaide Health Technology Assessment (AHTA) on behalf of NICS

This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.