Clinical Diversity of Cardiac Fibrosis, Treatment Effects Need More Study, Researchers Say

Because cardiac fibrosis can develop under very diverse etiological circumstances, it is extremely heterogeneous.

To make the challenging transition from usual care to precision medicine in treating cardiac fibrosis, scientists must rely on biomarker-guided identification of the diverse histomolecular phenotypes and individualized anti-fibrotic therapies, according to an opinion paper published in ESC Cardiovascular Research.

Cardiac fibrosis is a key contributor to heart failure (HF) and the progression of HF, and it has important prognostic implications both in ischemic heart disease and non-ischemic cardiac diseases.

“In this regard, cardiac fibrosis is a major driver associated with the growing burden of HF, especially in older people,” authors Javier Díez and Rudolf A. de Boer wrote.. “However, integrating cardiac fibrosis in HF management is still an unmet medical need, which may be explained by its high tissue heterogeneity and clinical diversity, and, as a consequence, the very real limitations of its diagnosis and treatment.”

The authors summarized challenges and requirements in the clinical management of cardiac fibrosis in patients with HF.

Because cardiac fibrosis can develop under very diverse etiological circumstances, it is extremely heterogeneous. In other words, the diversity in the character or makeup of cardiac fibrosis is a result of various developments of the heart lesion. Additionally, multiple stages in the fibrotic process cause variable histomolecular expression and clinical behavior.

Another cause of the diversity is the different subpopulations of cardiac fibroblasts — the primary source of collagen fibers — and their high plasticity, allowing them to alter their behavioral response to the type of initiating injury. These factors lead to variable alterations in fibrillary collagen turnover and fibrotic deposits with varying functional impact and outcomes.

According to one investigation, identifying cardiac fibrosis features unique to specific patient networks offered a strategy for advancing precision medicine in cardiac fibrosis. However, the authors still wish to find an accurate, precise, and non-invasive diagnosis process for cardiac fibrosis.

“Detection of cardiac fibrosis using current cardiac imaging modalities or circulating biomarkers, usually separately, as has been done so far, does not ensure capture of the subtle aspects of this heterogeneous lesion,” they argued, adding that it does not evaluate histological or molecular characteristics.

Molecular imaging, omics, and non-coding RNA13 research may lead to the discovery of novel biomarkers and therefore increase accuracy and precision for cardiac fibrosis diagnosis in HF patients. Until those biomarkers are specified, imaging and circulating biomarkers (eg ECV and collagen type I-derived serum peptides) can help diagnose subtypes.

Cardiac fibrosis can be reversible in patients with HF, meaning the clinical effects of tailored and targeted treatments of the lesion need to be prioritized in research. Endpoints are not currently included in clinical trials

“As it is the case for the treatment of fibrosis in other organs, it can also be anticipated that cardiac fibrosis should be treated with combinations of anti-fibrotic drugs targeting the multiple mechanisms that, jointly, regress this lesion in each individual patient,” the authors said.


Díez J, de Boer RA. Management of cardiac fibrosis is the largest unmet medical need in heart failure. ESC Cardiovascular Research. Published online July 9, 2021. doi:10.1093/cvr/cvab228