Author + information
- Jodie Inglesa,b,
- Charlotte Burnsa,b,
- Richard Bagnalla,b,
- Lien Lama,b,
- Laura Yeatesa,b,
- Tanya Sarinaa,b,
- Raj Puranika,b,
- Tom Briffaa,b,
- John Athertona,b,
- Tim Driscolla,b and
- Christopher Semsariana,b
Background: The yield of positive sarcomere mutations in hypertrophic cardiomyopathy (HCM) is increased in probands with a family history of disease, younger age and asymmetric septal morphology, suggesting different clinical subgroups of disease occur. We hypothesized probands with no family history of disease and no sarcomere mutations represent a non-familial subgroup of HCM. We sought to determine the prevalence, natural history and potential clinical implications of this non-familial subgroup of HCM.
Methods and Results: There were 413 unrelated probands with clinically diagnosed HCM and genetic testing performed seen in a specialized HCM center from 2002 to 2015, included in this retrospective cohort study. There were 251 (61%) with no reported family history of HCM, including 166 (40% of total) with no sarcomere mutation, i.e. non-familial HCM. Quantified family pedigree data revealed no difference in mean number of first-degree relatives screened between non-familial and sarcomere positive groups. Adjusted predictors of non-familial status were older age (OR 1.04, 95%CI 1.02-1.06, p=0.0001), male gender (OR 1.96, 1.11-3.45, p=0.02), hypertension (OR 2.80, 95%CI 1.57-5.00, p=0.0005) and non-asymmetric septal morphology (OR 3.41, 95%CI 1.64-7.08, p=0.001). They had a less severe clinical course with greater event-free survival from death/major cardiac events (p=0.02) compared to sarcomere-positive HCM probands. Genotype prediction scores showed good performance in identifying genotype positive patients (AUC 0.71-0.75), and in combination with pedigree characteristics were further improved.
Conclusions: Non-familial HCM occurs in 40% of probands, with later disease onset and less severe clinical course. We propose a revised clinical pathway for management of HCM patients, highlighting the role of genetic testing, a detailed pedigree and refined clinical surveillance recommendations for family members.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Advances in HCM, PPCM and Other Cardiomyopathies
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 1201-279
- 2017 American College of Cardiology Foundation