TOPLINE:

Relatives with a pathogenic sarcomere gene variant had milder thickening of the interventricular septum and a lower risk for serious cardiac events than patients originally diagnosed with hypertrophic cardiomyopathy but a higher risk than relatives without the gene variant.

METHODOLOGY:

• Researchers retrospectively reviewed records from a UK centre to describe outcomes in relatives who underwent cascade genetic testing after one family member (proband) was diagnosed with hypertrophic cardiomyopathy.
• They included 276 adults from 64 families referred between January 2010 and December 2018. Mean ages at initial evaluation ranged between 39.9 and 59.0 years, and 50%-71% were men.
• Adults were classified into four groups: probands with a disease-causing sarcomere gene variant, probands without the variant, carrier relatives with the variant, and non-carrier relatives without the variant.
• The primary endpoint was the onset of a new or subsequent major adverse cardiac event (MACE), such as the implantation of heart devices, heart failure, arrhythmias, and death.
• The mean follow-up duration was 8.9 years after identification.

TAKEAWAY:

• At baseline, 26.6% of relatives who underwent cascade genetic testing showed an uneven thickening of the interventricular septum on echocardiography.
• Probands with the disease-causing sarcomere gene variant had an adjusted marginal mean septal thickness of 22.1 mm, which was greater than that in carrier relatives (13.9 mm) and non-carrier relatives (12.3 mm; P < .001 for both).
• Probands with the gene variant had a fourfold higher risk for new MACEs than carrier relatives (adjusted hazard ratio [HR], 4.0; P < .001), and carrier relatives had about a fivefold higher risk than non-carrier relatives in an unadjusted analysis (HR, 4.9; P < .001).
• Among carrier relatives, the presence of asymmetrical hypertrophy at baseline was linked to an increased risk for repeat MACEs (P = .005).

IN PRACTICE:

"Genotype positive cascade-tested relatives possess a milder degree of hypertrophy and a lower incidence of repeat cardiac events compared with their proband counterparts. However, these patients still retain cardiac complications, justifying their inclusion in screening and clinical follow-up," the researchers concluded.

SOURCE:

This study was led by Wajeeh Raza Chaudhry, University of Dundee, Dundee, Scotland. It was published online on February 26, 2026, in Open Heart.

LIMITATIONS:

No limitations were explicitly mentioned for this study.

DISCLOSURES:

This study did not receive any specific funding. The authors did not declare any competing interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.