Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy.

Abstract

Fibrogenesis and inflammation contribute to the progression of cirrhosis. However, it is unknown if these processes also contribute to the development of cirrhotic cardiomyopathy (CCM). Novel magnetic resonance imaging with quantification of the extracellular volume (ECV) provides an estimate of the fibrotic remodelling in the liver and heart. To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation. A prospective study of 52 patients with cirrhosis and 14 healthy controls. All patients underwent contrast-enhanced MRI with T1-mapping and quantification of myocardial and liver ECV, biochemical assessments of collagen turnover (PRO-C3, PRO-C5, PRO-C6, collagen type IV degradation fragment, collagen type V degradation fragment, LG1M) and inflammation (TNFα, IL-1β, IL-6, IL-8, IL-18, SDF1α, sCD163, sMR, soluble macrophage mannose receptor). Myocardial and liver ECV were increased in patients compared with healthy controls (myocardial ECV 31.2±5.5% vs 27.4±2.9%, P=0.037; liver ECV 44.1±9.6% vs 33.7±6.7%, P<0.001). Myocardial ECV correlated strongly with liver ECV (r=0.48, P=0.001) and biomarkers of collagen formation and inflammation (P<0.005). Similarly, liver ECV correlated with biomarkers of collagen formation and inflammation (P<0.003). In a multivariate analysis, liver ECV was predicted by biomarkers of collagen formation (PRO-C3 and PRO-C6), whereas myocardial ECV was predicted by biomarkers of collagen formation (PRO-C6) and inflammation (IL-6 and sMR). Structural myocardial changes seem closely related to liver fibrosis in patients with cirrhosis. The strong associations with biomarkers of collagen formation and inflammation provide new insight into the role of inflammation and fibrogenesis in the development of structural cardiac abnormalities, potentially leading to CCM.