Cascade testing for inherited arrhythmia conditions: Experiences and attitudes of family communication approaches for a Canadian cohort

Abstract

Inherited arrhythmia conditions (IAC) can lead to sudden cardiac death at any age, and relatives of an affected person have up to a 50% chance of inheriting the condition and are at risk for developing features. Cascade testing is a stepwise approach for identifying relatives at risk for IACs through clinical screening and genetic testing. Early detection can reduce morbidity and mortality for affected individuals and determine potential risk mitigation strategies for relatives. However, cardiovascular genetic studies have reported an incomplete uptake of cascade testing in at-risk relatives. We explored patient perspectives on cascade testing for IACs and alternative approaches to family communication. Twelve semi-structured phone interviews were conducted with probands of the British Columbia Inherited Arrhythmia Program confirmed to carry a pathogenic or likely pathogenic variant in a gene associated with an IAC. Thematic analysis of transcripts through an iterative coding process revealed five main themes: (a) a stepwise approach is followed in disclosing risk to relatives, (b) relatives' autonomy in cascade testing is supported, (c) lived experience with the condition influences disclosure and uptake of cascade testing, (d) collaborative approach to informing relatives reduces negative impact of disclosure, and (e) direct contact from a healthcare provider is viewed as acceptable. The findings highlight this patient cohort's experiences and opinions with approaches to disclosure and demonstrate their understanding and acceptance of their relatives' approaches to cascade testing.In addition, while the notion of direct contact was generally accepted, a collaborative approach to contacting relatives between the proband and provider may be most effective.

Direct notification by health professionals of relatives at-risk of genetic conditions (with patient consent): views of the Australian public

“…One respondent in free-text comments with “a little concern” even recognised the benefits of knowing this risk information, noting that “benefit/risk outweighs the concern”. Similar findings emerged from a Canadian study [ 37 ], where a participant who had experienced sudden cardiac arrest before genetic testing stated, “you’d have to be an idiot not to be thankful for getting the information…[my family members] wouldn’t be worried about privacy if their health is a concern” (at 823). A participant in the same study compared direct contact in clinical genetics to common COVID-19 notification measures introduced during the pandemic for public health protection, stating, “especially now with this whole COVID thing, I wouldn’t mind getting notified by healthcare.…”

“…Despite some HPs expressing reservations about their ability to contact patients directly [ 36 ], or views that patients are better placed to communicate with relatives [ 19 ], this is often not true [ 4 , 32 ]. Further, HPs often do not know whether relatives ultimately receive the information [ 37 ]. These findings underscore the importance of providing each patient with the best tools for disseminating risk information within their family, including offering direct notification by a HP where appropriate.…”

Privacy Implications of Contacting the At-Risk Relatives of Patients with Medically Actionable Genetic Predisposition, with Patient Consent: A Hypothetical Australian Case Study

“…APP 3 prohibits the collection of personal information unless reasonably necessary for the entity’s functions. Facilitation of cascade testing of at-risk relatives is a core function of genetics services [ 12 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], and communication of risk information to relatives by patients directly is frequently inadequate [ 2 , 29 ]. Accordingly, collecting Darcy’s personal information for this purpose sits squarely within its core functions.…”

The safety of sports in children with inherited arrhythmia substrates

“…Evidence of disease progression and worse outcomes in 80 subjects with the TMEM43 p.S358L ACM mutation who participated in high-intensity exercise [>9 metabolic equivalent of task (MET)-hours/day] led to the recommendation that cascade screening be done earlier, to inform exercise choices reflective of the genotype ( 52 ). Cascade screening is a systematic approach of identifying family members of a proband who may be at risk for an inherited arrhythmia condition via clinical screening and genetic testing ( 53 ).…”