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

Abstract:

Aims 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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/ehjci/jey135

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; RDM Cardiovascular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; RDM Cardiovascular Medicine
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
RDM; RDM Cardiovascular Medicine
Role:
Author


More from this funder
Funding agency for:
Ariga, R
Lewandowski, AJ
Grant:
Clinical Research Training Fellowship: 098436/Z/12/Z
FS/18/3/33292
More from this funder
Funding agency for:
Watkins, H
Neubauer, S
Grant:
U01HL117006-01A1
U01HL117006-01A1
More from this funder
Funding agency for:
Watkins, H
Neubauer, S
Grant:
U01HL117006-01A1
U01HL117006-01A1
More from this funder
Funding agency for:
Rodgers, C
Grant:
Sir Henry Dale Fellowship: 098436/Z/12/B
More from this funder
Funding agency for:
Raman, B
Mahmod, M
Spartera, M
Chan, K
Grant:
Oxford Biomedical Research Centre
Oxford Biomedical Research Centre
Academic Clinical Fellowship


Publisher:
Oxford University Press
Journal:
European Heart Journal: Cardiovascular Imaging More from this journal
Volume:
20
Issue:
2
Pages:
157–167
Publication date:
2018-10-24
Acceptance date:
2018-09-05
DOI:
EISSN:
2047-2412
ISSN:
2047-2404


Keywords:
Pubs id:
pubs:935936
UUID:
uuid:c26a77fc-9c75-4d9b-8c4d-0ce1eb3c5696
Local pid:
pubs:935936
Deposit date:
2018-10-31

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