Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy

Signe Wiese; Andrei Voiosu; Jens D Hove; Karen V Danielsen; Theodor Voiosu; Henning Grønbaek; Holger Jon Møller; Federica Genovese; Alexander Lynge Reese-Petersen; Rajeshwar P Mookerjee; Jens Otto Clemmesen; Jens Peter Gøtze; Ove Andersen; Søren Møller; Flemming Bendtsen

doi:10.1111/apt.15812

Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy

Signe Wiese, Andrei Voiosu, Jens D Hove, Karen V Danielsen, Theodor Voiosu, Henning Grønbaek, Holger Jon Møller, Federica Genovese, Alexander Lynge Reese-Petersen, Rajeshwar P Mookerjee, Jens Otto Clemmesen, Jens Peter Gøtze, Ove Andersen, Søren Møller, Flemming Bendtsen

Research output: Contribution to journal › Journal article › Research › peer-review

21 Citations (Scopus)

Abstract

BACKGROUND: 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.

AIM: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation.

METHODS: 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).

RESULTS: 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).

CONCLUSION: 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.

Original language	English
Journal	Alimentary Pharmacology and Therapeutics
Volume	52
Issue number	2
Pages (from-to)	340-350
Number of pages	11
ISSN	0269-2813
DOIs	https://doi.org/10.1111/apt.15812
Publication status	Published - Jul 2020

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Wiese, S., Voiosu, A., Hove, J. D., Danielsen, K. V., Voiosu, T., Grønbaek, H., Møller, H. J., Genovese, F., Reese-Petersen, A. L., Mookerjee, R. P., Clemmesen, J. O., Gøtze, J. P., Andersen, O., Møller, S., & Bendtsen, F. (2020). Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy. Alimentary Pharmacology and Therapeutics, 52(2), 340-350. https://doi.org/10.1111/apt.15812

Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy. / Wiese, Signe; Voiosu, Andrei; Hove, Jens D; Danielsen, Karen V; Voiosu, Theodor; Grønbaek, Henning; Møller, Holger Jon; Genovese, Federica; Reese-Petersen, Alexander Lynge; Mookerjee, Rajeshwar P; Clemmesen, Jens Otto; Gøtze, Jens Peter; Andersen, Ove ; Møller, Søren ; Bendtsen, Flemming.

In: Alimentary Pharmacology and Therapeutics, Vol. 52, No. 2, 07.2020, p. 340-350.

Research output: Contribution to journal › Journal article › Research › peer-review

Wiese, S, Voiosu, A, Hove, JD, Danielsen, KV, Voiosu, T, Grønbaek, H, Møller, HJ, Genovese, F, Reese-Petersen, AL, Mookerjee, RP, Clemmesen, JO, Gøtze, JP, Andersen, O , Møller, S & Bendtsen, F 2020, 'Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy', Alimentary Pharmacology and Therapeutics, vol. 52, no. 2, pp. 340-350. https://doi.org/10.1111/apt.15812

Wiese, Signe ; Voiosu, Andrei ; Hove, Jens D ; Danielsen, Karen V ; Voiosu, Theodor ; Grønbaek, Henning ; Møller, Holger Jon ; Genovese, Federica ; Reese-Petersen, Alexander Lynge ; Mookerjee, Rajeshwar P ; Clemmesen, Jens Otto ; Gøtze, Jens Peter ; Andersen, Ove ; Møller, Søren ; Bendtsen, Flemming. / Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy. In: Alimentary Pharmacology and Therapeutics. 2020 ; Vol. 52, No. 2. pp. 340-350.

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title = "Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy",

abstract = "BACKGROUND: 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.AIM: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation.METHODS: 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).RESULTS: 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).CONCLUSION: 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.",

author = "Signe Wiese and Andrei Voiosu and Hove, {Jens D} and Danielsen, {Karen V} and Theodor Voiosu and Henning Gr{\o}nbaek and M{\o}ller, {Holger Jon} and Federica Genovese and Reese-Petersen, {Alexander Lynge} and Mookerjee, {Rajeshwar P} and Clemmesen, {Jens Otto} and G{\o}tze, {Jens Peter} and Ove Andersen and S{\o}ren M{\o}ller and Flemming Bendtsen",

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doi = "10.1111/apt.15812",

language = "English",

volume = "52",

pages = "340--350",

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TY - JOUR

T1 - Fibrogenesis and inflammation contribute to the pathogenesis of cirrhotic cardiomyopathy

AU - Wiese, Signe

AU - Voiosu, Andrei

AU - Hove, Jens D

AU - Danielsen, Karen V

AU - Voiosu, Theodor

AU - Grønbaek, Henning

AU - Møller, Holger Jon

AU - Genovese, Federica

AU - Reese-Petersen, Alexander Lynge

AU - Mookerjee, Rajeshwar P

AU - Clemmesen, Jens Otto

AU - Gøtze, Jens Peter

AU - Andersen, Ove

AU - Møller, Søren

AU - Bendtsen, Flemming

PY - 2020/7

Y1 - 2020/7

N2 - BACKGROUND: 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.AIM: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation.METHODS: 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).RESULTS: 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).CONCLUSION: 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.

AB - BACKGROUND: 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.AIM: To investigate the relationship between liver and cardiac ECV in cirrhosis and their association with collagen turnover and inflammation.METHODS: 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).RESULTS: 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).CONCLUSION: 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.

U2 - 10.1111/apt.15812

DO - 10.1111/apt.15812

M3 - Journal article

C2 - 32524673

VL - 52

SP - 340

EP - 350

JO - Alimentary Pharmacology and Therapeutics, Supplement

JF - Alimentary Pharmacology and Therapeutics, Supplement

SN - 0953-0673

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