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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 3, May/June 2018
AFRICA
153
loss, rather than excessive collagen deposition secondary to
activation of Kallikrin–Kinin system, and thereby, of bradykinin,
which increases MMP activity, causing loss of collagen, and LV
dysfunction, as shown in an animal model.
29
The predominance
of degradation over synthesis results in loss and disruption
of the myocardial collagen scaffold and an associated decline
in matrix tensile strength, resulting in ventricular dilatation,
systolic dysfunction and ultimately death.
14
In this study, patients with CRMR had increased collagen
degradation, as suggested by increase in MMP activity and
normal levels of TIMPs and markers of collagen synthesis. This
finding supports the lack of myocardial fibrosis observed in our
study. These findings differ from the study by Banerjee
et al
. in
30 patients with CRMR, where they found an increased level
of biomarkers of synthesis and degradation.
13
The discrepancy
may be explained by: younger patients than in this study (mean
age 29.6
±
2 years), possible ongoing rheumatic activity, and the
inclusion of patients with atrial fibrillation, therefore resulting in
increased biomarker levels.
13
The use of anti-remodelling therapy was similar in our study
to that of Banerjee
et al
.
13
Thirty to 40% of their patients were
on anti-remodelling therapy with spironolactone and ACE
inhibitors, respectively, and 10% were on beta-blockers. In their
study, only biopsies of the leaflets were performed, not the
LV to assess the absence or presence of fibrosis. Furthermore,
they reported increased thickness of the leaflets and collagen
deposition in eight patients who underwent surgery. It is unclear,
however, as to whether the primary lesion was mitral stenosis or
MR in this subset of patients.
Moreover, there was increased MMP activity in their MR
patients compared to mitral stenosis, as well as increased
MMP-to-TIMP ratio. They acknowledge that the elevation
in PIP levels was lower than anticipated in their MR cohort,
and that markers of collagen degradation exceeded markers of
synthesis in their patients with CRMR.
The main limitation of this study was the small sample size. A
larger sample size would have reduced the probability of chance
accounting for the absence or presence of fibrosis. A study with a
larger sample size with isolated MR and one with co-morbidities
and MR may be required to account for the finding of fibrosis
secondary to isolated MR. T1 mapping was not used to exclude
the presence of microscopic fibrosis and LV biopsies were not
performed.
Conclusion
The occurrence of LV fibrosis by LGE imaging was low in
CRMR patients. This finding corroborates the increased level
of biomarkers of collagen degradation and normal levels of
biomarkers of collagen synthesis. These findings may have
implications in terms of therapy. Earlier surgical referral may
be of benefit before dissolution of the myocardial scaffold and
irreversible myocardial damage ensues, with resultant poor
postoperative LV function.
Dr Meel was the recipient of the Carnegie PhD Fellowship award (Carnegie
Corporation Grant No. b8749.r01). We thank Hiral Matioda and Claudia
dos Santos for their help in acquisition of echocardiographic images, Janet
Mazibuko for her help with meticulous processing and storage of blood samples,
and Raquel Duarte for procuring laboratory consumables and biomarker kits.
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