Author + information
- Andris H. Ellims,
- Leah Iles,
- Liang-han Ling,
- Belinda Chong,
- James L. Hare,
- David Kaye,
- Desiree Du Sart and
- Andrew Taylor
Mutations affecting at least 14 sarcomeric genes are associated with hypertrophic cardiomyopathy (HCM). Previous attempts to discover links between genotype and phenotype in this heterogeneous condition have largely been unsuccessful. More recently, advances in both genetic testing and myocardial tissue characterization using cardiac magnetic resonance (CMR) imaging have been described. This study utilized next-generation sequencing (NGS) and CMR with T1 mapping to explore the relationship between specific pathogenic mutations and phenotypic manifestations in HCM.
20 patients with HCM underwent chip-based genetic testing, CMR and echocardiography. The genetic testing was capture NGS for 70 cardiac-associated genes, including at least 30 genes associated with HCM. In addition to standard volumetric measurements, the CMR protocol included quantitative assessments of both regional (by late gadolinium enhancement [LGE]) and diffuse (by post-contrast T1 mapping) myocardial fibrosis. Patients with a pathogenic mutation involving a common HCM gene, myosin-binding protein C (MYBPC3), were compared to those without.
A pathogenic HCM mutation was identified in 16 of 20 (80%) patients – 6 of these had a MYBPC3 mutation. MYBPC3-positive patients had similar left ventricular (LV) wall thickness, end-diastolic volume, ejection fraction, mass and diastolic function compared to MYBPC3-negative patients. However, patients with MYBPC3 mutations had significantly more LGE (% of total LV mass: median 17.6% [IQR 7.7 – 26.4%] vs. median 2.4% [IQR 0.8 – 11.3%], p < 0.05) and higher basal LV T1 times (489 ± 19 ms vs. 429 ± 62 ms, p < 0.05), consistent with less diffuse myocardial fibrosis at this level.
HCM patients with pathogenic mutations involving MYPBC3 have significantly more regional myocardial scar, but less basal diffuse myocardial fibrosis, than MYBPC3-negative patients. Further research using these contemporary genetic testing and cardiac imaging techniques may facilitate an improved understanding of the genetic basis of this diverse condition.
Moderated Poster Contributions
Poster Sessions, Expo North
Saturday, March 09, 2013, 10:00 a.m.-10:45 a.m.
Session Title: Hypertrophic Cardiomyopathy: MRI-Based Phenotyping
Abstract Category: 23. Pericardial/Myocardial Disease
Presentation Number: 1121M-141
- 2013 American College of Cardiology Foundation