A comprehensive evaluation of myocardial fibrosis in hypertrophic cardio myopathy with cardiacmagnetic resonance imaging: Linking genotype with fibrotic phenotype

Aims In hypertrophic cardio myopathy (HCM), attempts to associate genotype with phenotype have largely been unsuccessful. More recently, cardiac magnetic resonance(CMR)imaging has enhancedmyocardial fibrosis characterization, while nextgeneration 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 Onehund red and thirty-nine patients with HCM and 25 healthy control sunder went CMR to quantify regional myocardial fibrosis with late gadolinium enhancement (LGE) and diffuse myocardial fibrosis with post-contrast T₁ mapping.Collagen content of myecto my specimens from nine HCM patients was determined. Fifty-six HCM patients under went NGS for 65 cardio myopathy genes, including 36 HCM-associated genes. Post-contrast myocardial T1 time correlated histologi cally with myocardial collagen content (r = 20.70, 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 InHCM,contrast-enhancedCMRwithT1 mapping can non-invasively evaluate regional and diffuse patterns ofmyocardial 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. Published on behalf of the European Society of Cardiology. All rights reserved.