Author + information
- Thomas E. Callis,
- Rebecca Truty,
- Edward D. Esplin,
- Ana Morales,
- Matteo Vatta,
- Lisa Salberg and
- Robert Nussbaum
Genetic evaluation is recommended to improve the diagnosis and management of cardiomyopathy patients and family members. The number of genetic tests is growing rapidly and includes FDA-authorized direct-to-consumer (DTC) tests and hybrid models where consumers order laboratory-developed tests (LDTs) with physician support. Across the spectrum of tests, methods vary and the associated clinical limitations are not well-understood by non-specialists nor precisely defined among specialists. Recently, a limited variant screening strategy for 9 pathogenic or likely pathogenic (P/LP) cardiomyopathy variants in MYH7 and MYBPC3 was made available to consumers as a LDT through a hybrid ordering model. Here, we determine how often screening for only the 9 variants would miss other P/LP variants and falsely reassure individuals at risk for cardiomyopathy.
We analyzed de-identified data from two cohorts referred by healthcare providers for clinical genetic testing: 1) 5743 patients referred for hypertrophic cardiomyopathy (HCM) testing of up to 60 genes and 2) 8754 patients referred for comprehensive cardiomyopathy testing of up to 106 genes. Testing consisted of full-gene sequencing and deletion/duplication analysis using next-generation sequencing (NGS). We calculated the fraction of patients with any positive result that would have been detected if only the 9 variant cardiomyopathy screen had been used.
The yield of clinical testing was 22.4% (1286/5743) in the HCM group and 19.1% (1673/8754) in the comprehensive cardiomyopathy group for P/LP variants within the genes analyzed. In contrast, the yield of a genotyping screen reporting 9 specific variants in these same groups was, respectively, 1.5% (87/5743) and 0.4% (33/8754).
These results predict that 96% of individuals with genetically-positive cardiomyopathy would be falsely reassured by a negative result through a limited genotyping testing strategy. It is paramount for clinicians to avoid interpreting such uninformative results as an “all-clear” that would preclude patients and at-risk family members from receiving appropriate care and monitoring based on their true risk.
Sunday, March 29, 2020, 8:38 a.m.-8:48 a.m.
Session Title: Highlighted Original Research: Heart Failure and Cardiomyopathies and the Year in Review
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 902-08
- 2020 American College of Cardiology Foundation