title: A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype.
abstract: OBJECTIVE
  In hypertrophic cardiomyopathy (HCM), attempts to associate genotype with phenotype have largely been unsuccessful. More recently, cardiac magnetic resonance (CMR) imaging has enhanced myocardial fibrosis characterization, while next-generation sequencing (NGS) can identify pathogenic HCM mutations. We used CMR and NGS to explore the link between genotype and fibrotic phenotype in HCM.
  
  
  RESULTS
  One hundred and thirty-nine patients with HCM and 25 healthy controls underwent CMR to quantify regional myocardial fibrosis with late gadolinium enhancement (LGE) and diffuse myocardial fibrosis with post-contrast T1 mapping. Collagen content of myectomy specimens from nine HCM patients was determined. Fifty-six HCM patients underwent NGS for 65 cardiomyopathy genes, including 36 HCM-associated genes. Post-contrast myocardial T1 time correlated histologically with myocardial collagen content (r = -0.70, P = 0.03). Compared with controls, HCM patients had more LGE (4.6 ± 6.1 vs. 0%, P < 0.001) and lower post-contrast T1 time (483 ± 83 vs. 545 ± 49 ms, P < 0.001). LGE negatively correlated with left-ventricular (LV) ejection fraction and outflow tract obstruction, whereas lower post-contrast T1 time, suggestive of more diffuse myocardial fibrosis, was associated with LV diastolic impairment and dyspnoea. Patients with identifiable HCM mutations had more LGE (7.9 ± 8.6 vs. 3.1 ± 4.3%, P = 0.03), but higher post-contrast T1 time (498 ± 81 vs. 451 ± 70 ms, P = 0.03) than patients without.
  
  
  CONCLUSIONS
  In HCM, contrast-enhanced CMR with T1 mapping can non-invasively evaluate regional and diffuse patterns of myocardial fibrosis. These patterns of fibrosis occur independently of each other and exhibit distinct clinical associations. HCM patients with recognized genetic mutations have significantly more regional, but less diffuse myocardial fibrosis than those without.
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Andris H
authors.initials: AH
authors.lastname: Ellims
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Leah M
authors.initials: LM
authors.lastname: Iles
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Liang-han
authors.initials: LH
authors.lastname: Ling
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Chong
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Macciocca
authors.affiliation: GE Healthcare, Bethesda, USA.
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Slavin
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: James L
authors.initials: JL
authors.lastname: Hare
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Kaye
authors.affiliation: Cardiothoracic Surgery Unit, Alfred Hospital, Melbourne, Australia.
authors.forename: Silvana F
authors.initials: SF
authors.lastname: Marasco
authors.affiliation: Department of Anatomical Pathology, Alfred Hospital, Melbourne, Australia.
authors.forename: Catriona A
authors.initials: CA
authors.lastname: McLean
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Paul A
authors.initials: PA
authors.lastname: James
authors.affiliation: Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Desirée
authors.initials: D
authors.lastname: du Sart
authors.affiliation: Heart Centre, Alfred Hospital, Melbourne, Australia Baker IDI Heart and Diabetes Institute, Melbourne, Australia andrew.taylor@bakeridi.edu.au.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Taylor
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D003287:Contrast Media; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D019786:Gadolinium DTPA; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA
keywords: Genotyping; Hypertrophic cardiomyopathy; Magnetic resonance imaging; Myocardial fibrosis; T1 mapping