Expanded Access to Genetic Testing for Cardiomyopathy Is Cost Effective

Expansion of genetic testing in asymptomatic relatives of patients with dilated cardiomyopathy (DCM) to guide clinical surveillance is cost-effective, according to a study published in Genetics in Medicine. The authors call for greater access to called cascade testing, rather than just periodic clinical surveillance.

"As the DCM pathogenic variant detection rate rises and new evidence for personalized treatment of at-risk individuals becomes available, the cost-effectiveness of cascade testing will further increase," write the authors led by Max Catchpool, from the University of Melbourne in Australia. "This has important implications for the evaluation of DCM and suggests that those with a family history of the condition should have improved access to specialized cardiac genetic services."

Asymptomatic DCM is estimated to affect more than one in 250 individuals. Yet, international professional associations do not routinely recommend genetic testing for all patients diagnosed with DCM and their relatives. The eight-year old recommendations call for testing only among patients with significant cardiac conduction disease and/or a family history of premature unexpected sudden death, but do call for periodic clinical surveillance (every 1 to 5 years) for relatives (e.g., physical examination, electrocardiography, and echocardiography).

The researchers built a model that incorporated findings from 87 patients with idiopathic DCM or other nonhypertrophic cardiomyopathies who underwent exome sequencing between April 2016 and September 2017. Eligible participants were either diagnosed younger than 40 years or had a family history of DCM (more than 2 relatives) and/or early sudden unexplained death before 35 years. A multidisciplinary team of clinical geneticists, cardiologists, genetic counselors, medical scientists, and bioinformaticians reviewed variant classifications.

The model assumed

• 40 percent of relatives to accept cascade testing
• Identification of a pathogenic variant means lifetime periodical clinical surveillance, whereas identification of no variants exempted relatives from clinical surveillance
• Familial DCM occurs in 35 percent of idiopathic DCM cases and in a cohort of first-degree relatives about 7 percent would have an identifiable variant
• 7 percent diagnostic rate
• Cost of performing exome sequencing (analysis of up to 100 genes) in a proband was $1,200 with initial and follow-up genetic counseling costs of $184 and $147, respectively
• Clinical surveillance occurred every 2 years

The researchers found that the incremental cost per additional quality-adjusted life year (QALY) for cascade genetic testing prior to periodical clinical surveillance of first-degree relatives was AUD $6,100. At the standard threshold of $50,000 per QALY, the probability that genetic testing-guided clinical surveillance is cost-effective versus clinical surveillance alone was 90 percent. The results were similar even with the addition of second-degree relatives and when the costs were raised to $2,400.

While the authors do urge expansion of DCM genetic testing beyond current recommendations, they do caution that evidence is lacking that shows improved clinical outcomes as a result of pathogenic variant identification.

"Our findings indicate that genetic testing in patients with DCM is very likely to be cost-effective and thus should be offered to more patients with DCM than is currently recommended," write the authors. "Similarities in the cost of genetic testing and the management guidelines for the treatment of DCM, as well as extensive sensitivity analyses conducted as part of the economic evaluation, are likely to support the generalizability of our findings to other contexts, such as the United States and Europe."

Takeaway: Clinical surveillance that is guided by genetic testing is cost effective among asymptomatic relatives of DCM patients.