Patients With Hypertrophic Cardiomyopathy and Normal Genetic Investigations Have Few Affected Relatives

• Published in: Journal of the American College of Cardiology 2023-10, Vol.82 (18), p.1751-1761
• Main Authors: Nielsen, Søren K., Hansen, Frederikke G., Rasmussen, Torsten B., Fischer, Thomas, Lassen, Jens F., Madsen, Trine, Møller, Dorthe S., Klausen, Ib C., Brodersen, John B., Jensen, Morten S.K., Mogensen, Jens
• Format: Article
• Language: English
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2023.08.041

BACKGROUNDCurrent guidelines recommend that relatives of index patients with hypertrophic cardiomyopathy (HCM) are offered clinical investigations to identify individuals at risk of adverse disease complications and sudden cardiac death. However, the value of family screening in relatives of index patients with a normal genetic investigation of recognized HCM genes is largely unknown.OBJECTIVESThe purpose of this study was to perform family screening among relatives of HCM index patients with a normal genetic investigation to establish the frequency of familial disease and the clinical characteristics of affected individuals.METHODSClinical and genetic investigations were performed in consecutive and unrelated HCM index patients. Relatives of index patients who did not carry pathogenic/likely pathogenic variants in recognized HCM genes were invited for clinical investigations.RESULTSIn total, 60% (270 of 453) of HCM index patients had a normal genetic investigation. A total of 80% of their relatives (751 of 938, median age 44 years) participated in the study. Of these, 5% (34 of 751) were diagnosed with HCM at baseline, whereas 0.3% (2 of 717 [751-34]) developed the condition during 5 years of follow-up. Their median age at diagnosis was 57 years (IQR: 51-70 years). Two-thirds (22 of 36) were diagnosed following family screening, whereas one-third (14 of 36) had been diagnosed previously because of cardiac symptoms, a murmur, or an abnormal electrocardiogram. None of the affected relatives experienced adverse disease complications. The risk of SCD was low.CONCLUSIONSSystematic family screening of index patients with HCM and normal genetic investigations was associated with a low frequency of affected relatives who appeared to have a favorable prognosis.