A comprehensive evaluation of myocardial fibrosis in hypertrophic cardiomyopathy with cardiac magnetic resonance imaging: linking genotype with fibrotic phenotype

Aims 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. Methods and 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. Conclusion 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.