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Published on: June 14, 2016
Systemic inflammation is associated with myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy
Xinli Guo1, Jian Zhang2, Manyun Huang3
1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Insights
In hypertrophic cardiomyopathy (HCM), elevated levels of interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-α) correlate with increased myocardial fibrosis (MF). Early anti-inflammatory treatment may help slow MF progression in HCM patients.
Area of Science:
- Cardiology
- Immunology
- Pathology
Background:
- Chronic low-grade inflammation is a hallmark of hypertrophic cardiomyopathy (HCM).
- Inflammation is implicated in adverse ventricular remodeling and disease progression in HCM.
- The specific relationship between inflammatory markers and myocardial fibrosis (MF) in HCM requires further elucidation.
Purpose of the Study:
- To investigate the association between plasma inflammatory markers and the extent of myocardial fibrosis (MF) in patients with HCM.
- To determine if specific inflammatory markers predict the presence or severity of MF in HCM.
Main Methods:
- 102 HCM patients undergoing septal myectomy provided myocardial samples for Masson's trichrome staining to quantify MF.
- Plasma levels of various inflammatory markers, including IL-2, TNF-α, and IFN-α, were measured.
- Univariate and multivariate logistic regression analyses were used to assess the relationship between inflammatory markers and MF, adjusting for clinical and imaging variables.
Main Results:
- Higher levels of IL-2, TNF-α, and IFN-α were observed in patients with high MF compared to those with low MF.
- Multivariate analysis revealed that IL-2, IL-5, and TNF-α were significantly associated with increased interstitial MF.
- After adjustment for imaging indicators, IL-2 and TNF-α remained significant predictors of interstitial MF. No significant correlation was found between inflammatory markers and late gadolinium enhancement (LGE) on CMR.
Conclusions:
- Elevated IL-2 and TNF-α levels are associated with increased histopathological interstitial MF in HCM patients.
- These findings suggest a role for inflammation in the fibrotic process of HCM.
- Early anti-inflammatory interventions may be a potential strategy to mitigate MF progression in HCM.
Aims:
Chronic low-grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM.
Methods And Results:
This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9 years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean = 15.2 ± 8.1%, median = 13.0%, IQR = 9.9%-18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)-2, tumour necrosis factor (TNF)-α and interferon (IFN)-α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0 pg/mL, 3.1 vs. 3.9 pg/mL, 4.2 vs.4.7 pg/mL, respectively; all P < 0.05). In multivariate models adjusted for age, sex and other clinical features, IL-2, IL-5 and TNF-α, were correlated with increased interstitial MF [odds ratio (OR): 1.54, 95% confidence interval (CI): 1.10-2.14; OR: 1.42, 95% CI: 1.02-1.98; OR: 1.33, 95% CI: 1.04-1.70]. After additional adjustment for imaging indicators, IL-2 and TNF-α remained significant (OR: 1.49, 95% CI: 1.06-2.09, P = 0.021; OR:1.35, 95% CI: 1.01-1.80, P = 0.044). The correlation analysis between inflammation and replacement fibrosis assessed by CMR in 97 patients revealed that 72 (74.2%) showed late gadolinium enhancement (LGE). No significant correlation was found between inflammatory markers and the presence or extent of LGE.
Conclusions:
Higher levels of IL-2 and TNF-α were associated with increased histopathological interstitial MF in patients with HCM. Given the gradual progression of MF in HCM, initiating anti-inflammatory treatment in the early stages may delay its progression.
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