Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance
Abstract Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histo...
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doaj-2d560d1a1d7b428cb22ea02dbd1d951e2020-12-20T12:36:34ZengBMCJournal of Cardiovascular Magnetic Resonance1532-429X2020-12-0122111210.1186/s12968-020-00674-4Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonanceBoyang Liu0Desley A. H. Neil1Monisha Premchand2Moninder Bhabra3Ramesh Patel4Thomas Barker5Nicolas Nikolaidis6J. Stephen Billing7Thomas A. Treibel8James C. Moon9Arantxa González10James Hodson11Nicola C. Edwards12Richard P. Steeds13Department of Cardiology, University Hospital BirminghamDepartment of Cellular Pathology, University Hospital BirminghamDepartment of Cardiology, University Hospital BirminghamDepartment of Cardiothoracic Surgery, University Hospital BirminghamDepartment of Cardiothoracic Surgery, University Hospital CoventryDepartment of Cardiothoracic Surgery, University Hospital CoventryDepartment of Cardiothoracic Surgery, New Cross HospitalDepartment of Cardiothoracic Surgery, New Cross HospitalInstitute for Cardiovascular Sciences, University College LondonInstitute for Cardiovascular Sciences, University College LondonProgram of Cardiovascular Diseases, CIMA Universidad de Navarra and IdiSNADepartment of Statistics, Institute of Translational Medicine, Queen Elizabeth Hospital BirminghamGreen Lane Cardiovascular Service, Department of Cardiology, Auckland City HospitalDepartment of Cardiology, University Hospital BirminghamAbstract Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVFmean 13.6% [6.3–18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418https://doi.org/10.1186/s12968-020-00674-4Mitral regurgitationHistological fibrosisExtracellular volumeLate gadolinium enhancementMyocardial strainExercise capacity |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Boyang Liu Desley A. H. Neil Monisha Premchand Moninder Bhabra Ramesh Patel Thomas Barker Nicolas Nikolaidis J. Stephen Billing Thomas A. Treibel James C. Moon Arantxa González James Hodson Nicola C. Edwards Richard P. Steeds |
spellingShingle |
Boyang Liu Desley A. H. Neil Monisha Premchand Moninder Bhabra Ramesh Patel Thomas Barker Nicolas Nikolaidis J. Stephen Billing Thomas A. Treibel James C. Moon Arantxa González James Hodson Nicola C. Edwards Richard P. Steeds Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance Journal of Cardiovascular Magnetic Resonance Mitral regurgitation Histological fibrosis Extracellular volume Late gadolinium enhancement Myocardial strain Exercise capacity |
author_facet |
Boyang Liu Desley A. H. Neil Monisha Premchand Moninder Bhabra Ramesh Patel Thomas Barker Nicolas Nikolaidis J. Stephen Billing Thomas A. Treibel James C. Moon Arantxa González James Hodson Nicola C. Edwards Richard P. Steeds |
author_sort |
Boyang Liu |
title |
Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
title_short |
Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
title_full |
Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
title_fullStr |
Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
title_full_unstemmed |
Myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
title_sort |
myocardial fibrosis in asymptomatic and symptomatic chronic severe primary mitral regurgitation and relationship to tissue characterisation and left ventricular function on cardiovascular magnetic resonance |
publisher |
BMC |
series |
Journal of Cardiovascular Magnetic Resonance |
issn |
1532-429X |
publishDate |
2020-12-01 |
description |
Abstract Background Myocardial fibrosis occurs in end-stage heart failure secondary to mitral regurgitation (MR), but it is not known whether this is present before onset of symptoms or myocardial dysfunction. This study aimed to characterise myocardial fibrosis in chronic severe primary MR on histology, compare this to tissue characterisation on cardiovascular magnetic resonance (CMR) imaging, and investigate associations with symptoms, left ventricular (LV) function, and exercise capacity. Methods Patients with class I or IIa indications for surgery underwent CMR and cardiopulmonary exercise testing. LV biopsies were taken at surgery and the extent of fibrosis was quantified on histology using collagen volume fraction (CVFmean) compared to autopsy controls without cardiac pathology. Results 120 consecutive patients (64 ± 13 years; 71% male) were recruited; 105 patients underwent MV repair while 15 chose conservative management. LV biopsies were obtained in 86 patients (234 biopsy samples in total). MR patients had more fibrosis compared to 8 autopsy controls (median: 14.6% [interquartile range 7.4–20.3] vs. 3.3% [2.6–6.1], P < 0.001); this difference persisted in the asymptomatic patients (CVFmean 13.6% [6.3–18.8], P < 0.001), but severity of fibrosis was not significantly higher in NYHA II-III symptomatic MR (CVFmean 15.7% [9.9–23.1] (P = 0.083). Fibrosis was patchy across biopsy sites (intraclass correlation 0.23, 95% CI 0.08–0.39, P = 0.001). No significant relationships were identified between CVFmean and CMR tissue characterisation [native T1, extracellular volume (ECV) or late gadolinium enhancement] or measures of LV function [LV ejection fraction (LVEF), global longitudinal strain (GLS)]. Although the range of ECV was small (27.3 ± 3.2%), ECV correlated with multiple measures of LV function (LVEF: Rho = − 0.22, P = 0.029, GLS: Rho = 0.29, P = 0.003), as well as NTproBNP (Rho = 0.54, P < 0.001) and exercise capacity (%PredVO2max: R = − 0.22, P = 0.030). Conclusions Patients with chronic primary MR have increased fibrosis before the onset of symptoms. Due to the patchy nature of fibrosis, CMR derived ECV may be a better marker of global myocardial status. Clinical trial registration Mitral FINDER study; Clinical Trials NCT02355418, Registered 4 February 2015, https://clinicaltrials.gov/ct2/show/NCT02355418 |
topic |
Mitral regurgitation Histological fibrosis Extracellular volume Late gadolinium enhancement Myocardial strain Exercise capacity |
url |
https://doi.org/10.1186/s12968-020-00674-4 |
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