# Biomarkers and genetic determinants of cardiac sarcoidosis: current status, the unmet needs and future perspectives

## TL;DR

This paper reviews the current state of biomarkers and genetic research for diagnosing cardiac sarcoidosis, highlighting the need for better non-invasive tools.

## Contribution

The paper identifies novel serum biomarkers and genetic factors that could improve cardiac sarcoidosis diagnosis and risk stratification.

## Key findings

- Contemporary imaging reveals up to 55% cardiac involvement in sarcoidosis patients.
- Current diagnostic methods for cardiac sarcoidosis are invasive, costly, and limited in accuracy.
- Emerging serum biomarkers and genomic studies offer potential for non-invasive and precise diagnosis.

## Abstract

Sarcoidosis is a systemic disorder driven by genetic predisposition, environmental exposures, and immune dysregulation, resulting in the formation of noncaseating granulomas across multiple organs. In cardiac sarcoidosis (CS), immune cell infiltration of the myocardium, epicardium, and endocardium may lead to conduction disturbances, ventricular arrhythmias, and heart failure. While overt cardiac involvement was historically considered rare, affecting only 5% of sarcoidosis patients, the wider availability and improved sensitivity of contemporary cardiac imaging have revealed a substantially higher burden, with cardiac involvement reaching up to 55% in selected, systematically screened populations. Current diagnostic approaches for CS, including endomyocardial biopsy (EMB), cardiovascular magnetic resonance (CMR), and fluorine-18 fluorodeoxyglucose–positron emission tomography (FDG-PET), offer valuable insights but are restricted by high costs, invasiveness, and limited sensitivity and specificity. These challenges, together with the disproportionate contribution of cardiac involvement to sarcoidosis-related mortality, underscore the need for innovative, non-invasive, and widely accessible diagnostic strategies. Emerging evidence suggests that novel serum biomarkers and genomic studies hold promise for transforming the diagnostic landscape of CS. Biomarkers may provide accessible, cost-effective tools to complement established diagnostic methods, while genetic insights could identify individuals at higher risk for cardiac involvement and stratify patients based on disease phenotype. This review examines current evidence on serum biomarkers and genetic studies in CS diagnosis, identifies critical knowledge gaps, and proposes future directions aimed at advancing diagnostic precision and improving clinical outcomes.