Quantification of diffuse myocardial fibrosis using CMR extracellular volume fraction and serum biomarkers of collagen turnover with histologic quantification as standard of reference

Purpose: To compare the assessment of diffuse interstitial myocardial fibrosis in valvular diseases using cardiac magnetic resonance (CMR) extracellular volume fraction (ECV) quantification and serum biomarkers of collagen turnover using results of myocardial biopsy as standard of reference.

Materials and methods: This prospective monocentric study included consecutive patients before aortic valvular replacement. All patients underwent: i), 1.5T CMR with pre and post contrast T₁ mapping sequence and ECV computation; ii), serum quantification of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) and iii), myocardial biopsies were collected during surgery to assess collagen volume fraction (CVF). Patients with coronary artery disease were excluded. Correlation between native T1, ECV, CVF and serum biomarkers were assessed using Pearson correlation test. Agreement between basal anteroseptal ECV with global ECV was assessed using Bland-Altman test.

Results: Twenty-one patients, 16 with aortic stenosis and 5 with aortic regurgitation were included. There were 12 men and 9 women with a mean age of 74.1±6.8 (SD) years (range: 32-84 years). Mean global ECV value was 26.7±2.7 (SD) % (range: 23.4-32.5%) and mean CVF value was 12.4±9.7% (range: 3.2-25.7%). ECV assessed at the basal anteroseptal segment correlated moderately with CVF (r=0.6; P=0.0026). There was a strong correlation and agreement between basal anteroseptal ECV and global ECV, (r=0.8; P<0.0001; bias 5.4±6.1%) but no correlation between global ECV and CVF (r=0.5; P=0.10). Global ECV poorly correlated with serum TIMP-1 (r=0.4; P=0.037) and MMP-2 (r=0.4; P=0.047). No correlation was found between serum biomarkers and basal anteroseptal- ECV or native T1.

Conclusion: In patients with severe aortic valvulopathy, diffuse myocardial fibrosis assessed by anterosepto-basal ECV correlates with histological myocardial fibrosis. Anteroseptobasal ECV strongly correlates with global ECV, which poorly correlates with TIMP-1 and MMP-2, serum biomarkers involved in the progression of heart failure.