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Hypertrophic cardiomyopathy
Original article
Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy
  1. Johanna Kuusisto1,6,
  2. Vesa Kärjä2,
  3. Petri Sipola3,6,
  4. Ivana Kholová4,
  5. Keijo Peuhkurinen1,
  6. Pertti Jääskeläinen1,
  7. Anita Naukkarinen2,
  8. Seppo Ylä-Herttuala4,
  9. Kari Punnonen5,
  10. Markku Laakso1,6
  1. 1Department of Medicine, Kuopio University Hospital, Kuopio, Finland
  2. 2Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland
  3. 3Department of Clinical Radiology, Kuopio University Hospital, Kuopio, Finland
  4. 4A.I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland
  5. 5Laboratory Center of Eastern Finland, Kuopio, Finland
  6. 6University of Eastern Finland, Kuopio, Finland
  1. Correspondence to Professor Johanna Kuusisto, Kuopio University Hospital, Department of Medicine/Center for Medicine and Clinical Research, Puijonlaaksontie 2, PO Box 1777, Kuopio FIN-70210, Finland; johanna.kuusisto{at}kuh.fi

Abstract

Objective To investigate the role of inflammation in the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy (HCM).

Design Clinical study.

Setting Kuopio University Hospital and University of Eastern Finland, Kuopio, Finland.

Subjects Twenty-four patients with a single HCM-causing mutation D175N in the α-tropomyosin gene and 17 control subjects.

Main outcome measures Endomyocardial biopsy samples taken from the patients with HCM were compared with matched myocardial autopsy specimens. Levels of high-sensitivity C-reactive protein (hsCRP) and proinflammatory cytokines were measured in patients and controls. Myocardial late gadolinium enhancement (LGE) in cardiac MRI (CMRI) was detected.

Results Endomyocardial samples in patients with HCM showed variable myocyte hypertrophy and size heterogeneity, myofibre disarray, fibrosis, inflammatory cell infiltration and nuclear factor kappa B (NF-κB) activation. Levels of hsCRP and interleukins (IL-1β, IL-1RA, IL-6, IL-10) were significantly higher in patients with HCM than in control subjects. In patients with HCM, there was a significant association between the degree of myocardial inflammatory cell infiltration, fibrosis in histopathological samples and myocardial LGE in CMRI. Levels of hsCRP were significantly associated with histopathological myocardial fibrosis. hsCRP, tumour necrosis factor α and IL-1RA levels had significant correlations with LGE in CMRI.

Conclusions A variable myocardial and systemic inflammatory response was demonstrated in patients with HCM attributable to an identified sarcometric mutation. Inflammatory response was associated with myocardial fibrosis, suggesting that myocardial fibrosis in HCM is an active process modified by an inflammatory response.

  • Hypertrophic cardiomyopathy
  • inflammation
  • fibrosis
  • genetics
  • late gadolinium enhancement
  • coronary angioplasty
  • aortic stenosis
  • invasive cardiology
  • coronary artery disease
  • cardiomyopathy hypertrophic
  • tissue characters
  • HCM
  • MRI
  • myocardial function
  • myocardial perfusion
  • myocardial ischaemia
  • myocardial infarction
  • arrhythmias
  • endocrinology

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

https://doi.org/10.1136/heartjnl-2011-300960

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    Supplementary materials

    Footnotes

    • See Editorial, p 965

    • VK, PS contributed equally.

    • Funding This study was supported by the Academy of Finland and the Finnish Heart Research Foundation (grants to JK.).

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval Provided by the ethics committee of the Kuopio University Hospital.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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