PMID- 22447464 OWN - NLM STAT- MEDLINE DCOM- 20120807 LR - 20220408 IS - 1468-201X (Electronic) IS - 1355-6037 (Print) IS - 1355-6037 (Linking) VI - 98 IP - 13 DP - 2012 Jul TI - Low-grade inflammation and the phenotypic expression of myocardial fibrosis in hypertrophic cardiomyopathy. PG - 1007-13 LID - 10.1136/heartjnl-2011-300960 [doi] AB - 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 alpha-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-kappaB) activation. Levels of hsCRP and interleukins (IL-1beta, 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 alpha 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. FAU - Kuusisto, Johanna AU - Kuusisto J AD - Kuopio University Hospital, Department of Medicine/Center for Medicine and Clinical Research, Puijonlaaksontie 2, Finland. johanna.kuusisto@kuh.fi FAU - Karja, Vesa AU - Karja V FAU - Sipola, Petri AU - Sipola P FAU - Kholova, Ivana AU - Kholova I FAU - Peuhkurinen, Keijo AU - Peuhkurinen K FAU - Jaaskelainen, Pertti AU - Jaaskelainen P FAU - Naukkarinen, Anita AU - Naukkarinen A FAU - Yla-Herttuala, Seppo AU - Yla-Herttuala S FAU - Punnonen, Kari AU - Punnonen K FAU - Laakso, Markku AU - Laakso M LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120324 PL - England TA - Heart JT - Heart (British Cardiac Society) JID - 9602087 RN - 0 (TPM1 protein, human) RN - 0 (Tropomyosin) RN - 9007-49-2 (DNA) SB - IM CIN - Heart. 2012 Jul;98(13):965-6. PMID: 22668864 MH - Adolescent MH - Adult MH - Aged MH - Biopsy MH - Cardiomyopathy, Hypertrophic/*complications/diagnosis/genetics MH - Coronary Angiography MH - DNA/*genetics MH - Echocardiography MH - Electrocardiography MH - Female MH - Fibrosis/diagnosis/etiology/genetics MH - Humans MH - Immunohistochemistry MH - Inflammation/*complications/diagnosis/genetics MH - Magnetic Resonance Imaging, Cine MH - Male MH - Middle Aged MH - *Mutation MH - Myocardium/*pathology MH - Phenotype MH - Severity of Illness Index MH - Tropomyosin/biosynthesis/*genetics MH - Young Adult PMC - PMC3368494 COIS- Competing interests: None declared. EDAT- 2012/03/27 06:00 MHDA- 2012/08/08 06:00 PMCR- 2012/03/24 CRDT- 2012/03/27 06:00 PHST- 2012/03/27 06:00 [entrez] PHST- 2012/03/27 06:00 [pubmed] PHST- 2012/08/08 06:00 [medline] PHST- 2012/03/24 00:00 [pmc-release] AID - heartjnl-2011-300960 [pii] AID - 10.1136/heartjnl-2011-300960 [doi] PST - ppublish SO - Heart. 2012 Jul;98(13):1007-13. doi: 10.1136/heartjnl-2011-300960. Epub 2012 Mar 24.