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Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.

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cam.issuedOnline2018-10-24
dc.contributor.authorRaman, Betty
dc.contributor.authorAriga, Rina
dc.contributor.authorSpartera, Marco
dc.contributor.authorSivalokanathan, Sanjay
dc.contributor.authorChan, Kenneth
dc.contributor.authorDass, Sairia
dc.contributor.authorPetersen, Steffen E
dc.contributor.authorDaniels, Matthew J
dc.contributor.authorFrancis, Jane
dc.contributor.authorSmillie, Robert
dc.contributor.authorLewandowski, Adam J
dc.contributor.authorOhuma, Eric O
dc.contributor.authorRodgers, Christopher
dc.contributor.authorKramer, Christopher M
dc.contributor.authorMahmod, Masliza
dc.contributor.authorWatkins, Hugh
dc.contributor.authorNeubauer, Stefan
dc.contributor.orcidRodgers, Christopher [0000-0003-1275-1197]
dc.date.accessioned2019-01-12T00:31:23Z
dc.date.available2019-01-12T00:31:23Z
dc.date.issued2019-02-01
dc.description.abstractAIMS: Myocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications. METHODS AND RESULTS: Seventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97-13.48 g] to 6.30 g (IQR 1.38-17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85-13.79; P = 0.002). CONCLUSION: Myocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.
dc.description.sponsorshipThis study was funded by the National Institute of Health Research (NIHR) Oxford Biomedical Research Centre and the British Heart Foundation. BR, MM, MS were funded by National Institute of Health Research Oxford Biomedical Research Centre. RA was funded by a British Heart Foundation Clinical Research Training Fellowship grant (RA: 098436/Z/12/Z). K.C was supported by an NIHR academic clinical fellowship. CTR is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society [098436/Z/12/B].SEP acknowledges support from the NIHR Barts Biomedical Research Centre. MJD is supported by the Wellcome Trust (WT098519MA). AJL is supported by the British Heart Foundation (FS/18/3/33292). EOO acknowledges support from Cancer Research UK. SN and HW acknowledge support from the Oxford British Heart Foundation Center of Research Excellence. CMK, SN and HW are supported by U.S. NIH Grant/Contract (U01HL117006-01A1).
dc.format.mediumPrint
dc.identifier.doi10.17863/CAM.35215
dc.identifier.eissn2047-2412
dc.identifier.issn2047-2404
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287902
dc.languageeng
dc.language.isoeng
dc.publisherOxford University Press (OUP)
dc.publisher.urlhttp://dx.doi.org/10.1093/ehjci/jey135
dc.subjectCardiomyopathy, Hypertrophic
dc.subjectContrast Media
dc.subjectDisease Progression
dc.subjectFemale
dc.subjectFibrosis
dc.subjectGadolinium DTPA
dc.subjectHumans
dc.subjectMagnetic Resonance Imaging, Cine
dc.subjectMale
dc.subjectMeglumine
dc.subjectMiddle Aged
dc.subjectMyocardium
dc.subjectOrganometallic Compounds
dc.subjectPrognosis
dc.subjectRetrospective Studies
dc.subjectRisk Factors
dc.titleProgression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.
dc.typeArticle
dcterms.dateAccepted2018-09-05
prism.endingPage167
prism.issueIdentifier2
prism.publicationDate2019
prism.publicationNameEur Heart J Cardiovasc Imaging
prism.startingPage157
prism.volume20
pubs.funder-project-idWellcome Trust (Unknown)
pubs.funder-project-idWellcome Trust (098436/Z/12/B)
pubs.funder-project-idWellcome Trust (098436/Z/12/Z)
rioxxterms.licenseref.startdate2019-02
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1093/ehjci/jey135

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