PMID- 29196542 OWN - NLM STAT- MEDLINE DCOM- 20190128 LR - 20220129 IS - 1468-201X (Electronic) IS - 1355-6037 (Print) IS - 1355-6037 (Linking) VI - 104 IP - 13 DP - 2018 Jul TI - Cardiac myosin-binding protein C is a novel marker of myocardial injury and fibrosis in aortic stenosis. PG - 1101-1108 LID - 10.1136/heartjnl-2017-312257 [doi] AB - OBJECTIVE: Cardiac myosin-binding protein C (cMyC) is an abundant sarcomeric protein and novel highly specific marker of myocardial injury. Myocyte death characterises the transition from hypertrophy to replacement myocardial fibrosis in advanced aortic stenosis. We hypothesised that serum cMyC concentrations would be associated with cardiac structure and outcomes in patients with aortic stenosis. METHODS: cMyC was measured in two cohorts in which serum had previously been prospectively collected: a mechanism cohort of patients with aortic stenosis (n=161) and healthy controls (n=46) who underwent cardiac MRI, and an outcome cohort with aortic stenosis (n=104) followed for a median of 11.3 years. RESULTS: In the mechanism cohort, cMyC concentration correlated with left ventricular mass (adjusted I(2)=11.0 g/m(2) per log unit increase in cMyC, P<0.001), fibrosis volume (adjusted I(2)=8.0 g, P<0.001) and extracellular volume (adjusted I(2)=1.3%, P=0.01) in patients with aortic stenosis but not in controls. In those with late gadolinium enhancement (LGE) indicative of myocardial fibrosis, cMyC concentrations were higher (32 (21-56) ng/L vs 17 (12-24) ng/L without LGE, P<0.001). cMyC was unrelated to coronary calcium scores. Unadjusted Cox proportional hazards analysis in the outcome cohort showed greater all-cause mortality (HR 1.49 per unit increase in log cMyC, 95% CI 1.11 to 2.01, P=0.009). CONCLUSIONS: Serum cMyC concentration is associated with myocardial hypertrophy, fibrosis and an increased risk of mortality in aortic stenosis. The quantification of serum sarcomeric protein concentrations provides objective measures of disease severity and their clinical utility to monitor the progression of aortic stenosis merits further study. CLINICAL TRIAL REGISTRATION: NCT1755936; Post-results. CI - (c) Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. FAU - Anand, Atul AU - Anand A AUID- ORCID: 0000-0002-6428-4554 AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Chin, Calvin AU - Chin C AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Shah, Anoop S V AU - Shah ASV AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Kwiecinski, Jacek AU - Kwiecinski J AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. AD - First Department of Cardiology, Poznan University of Medical Sciences, Poznan, Poland. FAU - Vesey, Alex AU - Vesey A AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Cowell, Joanna AU - Cowell J AD - Department of Geriatric Medicine, Royal Victoria Building, Edinburgh, UK. FAU - Weber, Ekkehard AU - Weber E AD - Institute of Physiological Chemistry, Martin Luther University Halle-Wittenberg, Halle, Germany. FAU - Kaier, Thomas AU - Kaier T AD - King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, London, UK. FAU - Newby, David E AU - Newby DE AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Dweck, Marc AU - Dweck M AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. FAU - Marber, Michael S AU - Marber MS AD - King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, London, UK. FAU - Mills, Nicholas L AU - Mills NL AD - BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. LA - eng SI - ClinicalTrials.gov/NCT01755936 GR - G1000737/MRC_/Medical Research Council/United Kingdom GR - FS/14/78/31020/BHF_/British Heart Foundation/United Kingdom GR - DH_/Department of Health/United Kingdom GR - TG/15/1/31518/BHF_/British Heart Foundation/United Kingdom GR - FS/15/13/31320/BHF_/British Heart Foundation/United Kingdom GR - FS/16/14/32023/BHF_/British Heart Foundation/United Kingdom GR - Wellcome Trust/United Kingdom GR - WT103782AIA/WT_/Wellcome Trust/United Kingdom GR - CH/9/002/BHF_/British Heart Foundation/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171201 PL - England TA - Heart JT - Heart (British Cardiac Society) JID - 9602087 RN - 0 (Biomarkers) RN - 0 (Carrier Proteins) RN - 0 (Contrast Media) RN - 0 (myosin-binding protein C) SB - IM MH - Aged MH - Aged, 80 and over MH - Aortic Valve Stenosis/*blood/diagnostic imaging/mortality/pathology MH - Biomarkers/blood MH - Cardiomegaly/*blood/diagnostic imaging/mortality/pathology MH - Carrier Proteins/*blood MH - Case-Control Studies MH - Cell Death MH - Contrast Media/administration & dosage MH - Female MH - Fibrosis MH - Humans MH - Magnetic Resonance Imaging MH - Male MH - Middle Aged MH - Myocardium/*pathology MH - Predictive Value of Tests MH - Prognosis MH - Risk Factors MH - Severity of Illness Index MH - Time Factors MH - Ventricular Remodeling PMC - PMC6031261 OTO - NOTNLM OT - aortic stenosis OT - cardiac magnetic resonance (CMR) imaging COIS- Competing interests: AA has received speaker fees from Abbott Laboratories. ASVS has acted as a consultant for Abbott Laboratories. NLM has acted as a consultant for Abbott Laboratories, Beckman-Coulter, Roche and Singulex. Singulex was contracted to undertake the analyses of cMyC on a fee-for-service basis and holds no commercial interest. MSM is named as an inventor on a patent held by King's College London for the detection of cardiac myosin-binding protein C as a biomarker of myocardial injury. All other authors have no conflicts of interest to declare. EDAT- 2017/12/03 06:00 MHDA- 2019/01/29 06:00 PMCR- 2018/07/04 CRDT- 2017/12/03 06:00 PHST- 2017/08/02 00:00 [received] PHST- 2017/11/15 00:00 [revised] PHST- 2017/11/16 00:00 [accepted] PHST- 2017/12/03 06:00 [pubmed] PHST- 2019/01/29 06:00 [medline] PHST- 2017/12/03 06:00 [entrez] PHST- 2018/07/04 00:00 [pmc-release] AID - heartjnl-2017-312257 [pii] AID - 10.1136/heartjnl-2017-312257 [doi] PST - ppublish SO - Heart. 2018 Jul;104(13):1101-1108. doi: 10.1136/heartjnl-2017-312257. Epub 2017 Dec 1.