14.8% of gene-positive DCM and 14.3% of HCM patients did not meet UK testing criteria despite having pathogenic genotypes, highlighting a need for revised guidelines.
Does genetic testing identify pathogenic variants in patients with cardiomyopathies who do not meet current UK national testing criteria?
A significant minority (approximately 1 in 7) of patients with cardiomyopathy and a pathogenic genotype do not meet current UK testing criteria, suggesting a need to adopt wider ESC guidance.
Introduction Inherited cardiac conditions, including dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM), may have a monogenic cause identified through genetic testing (GT). Confirmation of pathogenic gene variants can have important implications for the patient and their relatives. The UK National Genomic Test Directory (NGTD) provides strict criteria on the indications for GT; however, the European Society of Cardiology (ESC) recommends wider GT. We reviewed the prevalence of pathogenic genotypes in patients undergoing GT who did not meet the NGTD criteria. Methods We conducted a retrospective analysis of patients who underwent GT with a confirmed diagnosis of HCM or DCM attending the Essex Inherited Cardiac Conditions Clinic between January 2023 and January 2025. Results 257 patients were included in the analysis, with 136 patients with DCM (52.9%) and 121 patients with HCM (47.1%). The diagnostic yield of GT was 19.9% in DCM and 17.4% in HCM. 14.8% of gene-positive patients with DCM and 14.3% of gene-positive patients with HCM did not meet current UK testing criteria, predominantly due to age of onset. All gene-positive patients in the DCM subgroup not meeting current NGTD criteria for testing had evidence of myocardial fibrosis. Conclusion A significant minority of patients (1 in 7) with cardiomyopathy and a pathogenic genotype did not meet current UK testing criteria; each patient has an average of 4 first-degree relatives at risk who will benefit from predictive GT. We propose the adoption of the wider ESC guidance, removing the strict age-related cut-offs and being guided more by the severity of the phenotype, particularly involving myocardial scarring.
Madu et al. (2026) studied this question. 14.8% of gene-positive DCM and 14.3% of HCM patients did not meet UK testing criteria despite having pathogenic genotypes, highlighting a need for revised guidelines.