Cardiovascular Journal of Africa: Vol 29 No 3 (May/Junel 2018)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018

150

AFRICA

Assessment of myocardial fibrosis by late gadolinium

enhancement imaging and biomarkers of collagen

metabolism in chronic rheumatic mitral regurgitation

Ruchika Meel, Richard Nethononda, Elena Libhaber, Therese Dix-Peek, Ferande Peters, Mohammed Essop

Abstract

Background:

In chronic rheumatic mitral regurgitation

(CRMR), involvement of the myocardium in the rheumatic

process has been controversial. Therefore, we sought to study

the presence of fibrosis using late gadolinium enhance-

ment cardiac magnetic resonance imaging (LGE-CMR) and

biomarkers of collagen turnover in CRMR.

Methods:

Twenty-two patients with CRMR underwent CMR

and echocardiography. Serum concentrations of matrix metal-

loproteinase-1 (MMP-1), tissue inhibitor of MMP-1 (TIMP-

1), MMP-1-to-TIMP-1 ratio, procollagen III N-terminal

pro-peptide (PIIINP) and procollagen type IC peptide (PIP)

were measured.

Results:

Four patients had fibrosis on LGE-CMR. PIP and

PIIINP concentrations were similar to those of the controls,

however MMP-1 concentration was increased compared to

that of the controls (log MMP-1 3.5

0.7 vs 2.7

0.9,

0.02). There was increased MMP-1 activity as the MMP-1-to-

TIMP-1 ratio was higher in CRMR patients compared to the

controls (–1.2

0.6 vs –2.1

0.89,

0.002).

Conclusion:

Myocardial fibrosis was rare in CRMR patients.

CRMR is likely a disease characterised by the predominance

of collagen degradation rather than increased synthesis and

myocardial fibrosis.

Keywords:

chronic rheumatic mitral regurgitation, cardiac

magnetic resonance, late gadolinium enhancement, biomarkers

Submitted 21/1/17, accepted 19/12/17

Published online 6/2/18

Cardiovasc J Afr

2018;

: 150–154

www.cvja.co.za

DOI: 10.5830/CVJA-2018-002

Myocardial fibrosis can be reliably detected non-invasively

using late gadolinium enhancement (LGE-CMR) or contrast

enhancement cardiac magnetic resonance (CE-CMR) imaging.

CE-CMR is a useful non-invasive correlate of myocardial

fibrosis on histology.

Fibrosis represents an end-stage process in

various cardiac conditions, irrespective of aetiology and denotes

adverse outcomes.

Limited recent studies have shown the value

of CMR in valvular heart disease, such as degenerative MR and

aortic stenosis, in predicting the prognosis based on the presence

of fibrosis.

2,4,5

Studies pertaining to the possible involvement of the left

ventricle (LV) in the rheumatic process have yielded equivocal

results.

In chronic rheumatic mitral regurgitation (CRMR)

there may be involvement of the LV in the rheumatic process,

especially in the posterobasal region of the LV.

7-9

Sepulveda

al.

reported diffuse, mesocardial and heterogenous enhancement

of the myocardium in acute rheumatic fever using LGE.

The possible resultant fibrosis may therefore be studied by

LGE and have prognostic value similar to that in degenerative

MR. Furthermore, data concerning biomarkers of collagen

degradation and formation in MR are limited and mostly

comprise animal studies in degenerative MR.

11,12

In a recent study in rheumatic MR, an increase in biomarkers

of collagen synthesis and degradation was reported.

Biomarkers

of collagen turnover may serve as non-invasive tools for

identification of myocardial remodelling and add an incremental

value in risk stratification for surgery or institution of aggressive

medical treatment at an early stage.

14-16

Procollagen III N-terminal pro-peptide (PIIINP) and

procollagen IC peptide (PIP) are released into the circulation

during collagen synthesis, while the turnover of collagen is

controlled by matrix metalloproteinases (MMPs) and their

inhibitors, the tissue inhibitors of metalloproteinases (TIMPs).

These markers are therefore an excellent model to study collagen

turnover. Therefore we sought to assess the presence of LV

fibrosis in CRMR using cardiac MRI and biomarkers of collagen

degradation and synthesis.

Methods

This study was part of a prospective, cross-sectional study at

Chris Hani Baragwanath Academic Hospital. Patients were

enrolled from January to October 2014. All patients were

screened and those deemed to have moderate or severe CRMR

were referred for possible inclusion in the study.

The inclusion criteria were patients aged 18 years or older

with echocardiographic features of moderate or severe CRMR.

Patients were excluded if they had co-morbidities, significant

aortic valve disease, concurrent mitral stenosis with a valve

area of less than 2.0 cm

, documented ischaemic heart disease,

pre-existing non-valvular cardiomyopathy, prior cardiac surgery,

congenital or pericardial disease, pregnancy, severe anaemia

(haemoglobin

10 g/dl), presence of a pacemaker or defibrillator,

claustrophobia, renal dysfunction (estimated glomerular filtration

rate, eGFR

60 ml/min), or refusal to undergo CMR.

Division of Cardiology, Chris Hani Baragwanath

Academic Hospital and University of the Witwatersrand,

Johannesburg, South Africa

Ruchika Meel, PhD,

ruchikameel@gmail.com

Richard Nethononda, DPhil

Elena Libhaber, PhD

Therese Dix-Peek, MSc

Ferande Peters, MD

Mohammed Essop, MD