The results of our study indicate a substantial
elevation in serum MMP-9 levels in HCM patients
exhibiting myocardial fibrosis detected by CMR in
comparison to those who did not display fibrosis.
Additionally, a noteworthy correlation was found
between interventricular septum thickness, as
identified by CMR, and cardiac fibrosis. Furthermore,
the study demonstrated a positive correlation between
the serum MMP-9 level and the quantity of myocardial
fibrosis of the left ventricle.
Hypertrophic cardiomyopathy is a hereditary
cardiovascular disease characterized by myocardial
hypertrophy and impaired diastolic function, which can result in adverse clinical outcomes, including
heart failure, arrhythmias, and sudden cardiac
death.[1] Myocardial fibrosis, the deposition of excess
collagen in the myocardial interstitium, is a common
feature of HCM and contributes to the progression
of disease.[2] Cardiac magnetic resonance imaging
has emerged as a reliable tool for detecting and
quantifying myocardial fibrosis in HCM patients,
and its role in risk stratification and management
has been well-established.[3] The presence and extent
of myocardial fibrosis detected by CMR have been
shown to correlate with poor clinical outcomes,
including heart failure, ventricular arrhythmias, and
sudden cardiac death, providing important prognostic
information for HCM patients.[4] Consequently,
the identification of fibrosis-related factors has
become a major research focus, as these may serve
as potential therapeutic targets to mitigate disease
progression and improve patient outcomes. Current
guidelines recommend the use of CMR to assess the
presence and extent of myocardial fibrosis in HCM
patients, with fibrosis over 15% indicating a high
risk of sudden cardiac death and consideration for
implantable cardioverter-defibrillator placement.[5] As
a consequence, there has been an escalation in the
significance attributed to factors related to fibrosis,
alongside an increase in efforts aimed at identifying
the parameters that could predict the presence and
extent of myocardial fibrosis in HCM patients.
Matrix metalloproteinases are a group of
endopeptidases that require zinc and are involved
in tissue remodeling processes that include the
degradation of the collagen network in cardiovascular
disease. Among the MMPs, MMP-9, also called
type IV collagenase or gelatinase B, is a key player
in the tissue remodeling of the extracellular matrix,
particularly in the migration of cardiac fibroblasts. Prior
research has revealed a relationship between MMP-9
levels and cardiovascular events, including heart
failure, atherosclerosis, and myocardial infarction.[6-9]
Specifically, Roldán et al.[10] discovered a correlation
between cardiac fibrosis and serum MMP-9 levels.
Other investigations have also reported a connection
between MMP-9 levels and heart failure severity,
clinical status deterioration, and atherosclerotic plaque
formation and destabilization.[11,12] Additionally,
macrophages have been identified as a strong source of
MMP-9, and patients with acute myocardial infarction
or stable angina exhibited higher levels of MMP-9 in
macrophages than those in control groups.[13-15]
Previous research has demonstrated that MMP-9
activity is significantly higher in high-pressure
arteries compared to normal-pressure arteries.[16,17]
Hypertension-induced cardiac hypertrophy is a
key risk factor for various cardiovascular disorders,
including diastolic and systolic heart failure,
atrial fibrillation, and sudden cardiac death.[18] An
association has been reported between increased
MMP-9 activity and compensatory hypertrophy of
the heart. Specifically, Li et al.[16] observed elevated
MMP-9 activity during compensatory hypertrophy
in rats with spontaneously elevated blood pressure.
Consistent with our results, Münch et al.[19] also
found a correlation between MMP-9 and myocardial
fibrosis in female HCM patients.
The main limitation of our study is the limited
number of patients. Additionally, the visual
evaluation of the existence of LGE without using
software may be considered another limitation. It
should be noted that not all molecules in circulation
reflect changes in collagen metabolism at the cardiac
level, as collagen is the most abundant protein in the
body. Another potential limitation is that we did not
evaluate the cardiac tissue concentration of MMPs
in our study. Further research with a larger cohort
should analyze a broad panel or marker cassette for
validation.
In conclusion, the degree of interventricular
septum thickness is an important indicator of HCM.
Similar to the findings of our study, previous studies
have shown that there is a positive correlation
between the degree of interventricular septal
thickness and the extent of myocardial fibrosis in
HCM patients. Specifically, HCM patients with
greater degrees of interventricular septal thickness
tend to have more extensive myocardial fibrosis.
This relationship highlights the importance of
monitoring both interventricular septal thickness
and the presence of myocardial fibrosis in HCM
patients, as both parameters can provide important
information for risk stratification and management
of the disease.
Data Sharing Statement: The data that support the
findings of this study are available from the corresponding
author upon reasonable request.
Author Contributions: Idea/concept, writing the
article: S.S.; Design: Ö.Ç.; Control/supervision: A.R.D.;
Data collection/processing: H.K.; Analysis/interpretation:
M.A.; Literature rewiew: S.T.K.; Critical rewiews: A.R.D.;
References and fundings: M.C.; Materials: Y.Ö.
Conflict of Interest: The authors declared no conflicts
of interest with respect to the authorship and/or publication
of this article.
Funding: The authors received no financial support for
the research and/or authorship of this article.
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