Novel DAMP markers advance myocardial contusion detection

Researchers are exploring a new generation of biochemical markers that may help clinicians detect myocardial contusion. A frequently overlooked form of heart injury caused by blunt chest trauma, earlier and more accurately. The review highlights the diagnostic potential of damage-associated molecular patterns (DAMPs), including HMGB1 protein and circulating histones, which are released during post-traumatic inflammation.

Blunt chest trauma is a common consequence of traffic accidents, falls, and high-impact injuries. Although myocardial contusion is one of the most frequent cardiac complications, it often goes undiagnosed because symptoms can be nonspecific and current diagnostic criteria remain unclear. Today, clinicians rely primarily on electrocardiography (ECG) and troponin testing, yet these tools do not always distinguish cardiac contusion from other stress-related conditions.

Searching for more precise biomarkers

The authors reviewed emerging evidence suggesting that molecules released during sterile inflammation, known as DAMPs — may provide additional diagnostic insight. These molecules are produced when cells are damaged by trauma and activate immune pathways even in the absence of infection.

Among the most promising candidates is high mobility group box 1 (HMGB1), a nuclear protein that enters the bloodstream rapidly after injury and triggers inflammatory signalling. Studies show that HMGB1 levels can increase dramatically within hours of trauma, potentially reflecting the severity of tissue damage and cardiac stress.

Histones, another class of intracellular proteins, may also play a role. Once released into circulation, they can contribute to inflammation, thrombosis, and cardiodepressive effects. Elevated histone levels have been observed in patients with severe trauma and may correlate with systemic complications.

Together, these molecules could complement existing biomarkers by providing information not only about structural damage to the heart but also about the immune response driving secondary injury.

Why myocardial contusion is difficult to diagnose

Unlike myocardial infarction, myocardial contusion lacks clear clinical criteria. Patients may present with arrhythmias, hemodynamic instability, or subtle ECG changes that mimic ischemia. Because symptoms can appear hours or days after injury, delayed diagnosis may increase the risk of complications such as cardiogenic shock or sudden cardiac arrest.

Current trauma guidelines recommend ECG monitoring and measurement of cardiac troponins, but these markers can also rise in non-cardiac conditions such as hypoxia, traumatic brain injury, or systemic shock. This limited specificity has motivated researchers to investigate alternative molecular indicators.

From inflammation biology to clinical practice

The review outlines how trauma initiates a cascade of immune responses known as sterile inflammation. Tissue injury releases DAMPs, which bind to pattern recognition receptors on immune cells and trigger cytokine release, complement activation, and coagulation changes. While these processes help initiate healing, excessive activation may contribute to organ dysfunction, including cardiac injury.

However, translating DAMPs into clinical diagnostics presents challenges. HMGB1 and histones are elevated in various diseases, from autoimmune disorders to cancer — making it difficult to distinguish trauma-specific changes without dynamic monitoring over time. Standardized measurement techniques and clearly defined diagnostic thresholds will be essential before these biomarkers can be integrated into emergency protocols.

Future directions

Beyond diagnosis, targeting DAMP-mediated pathways may also open therapeutic possibilities. Experimental studies suggest that blocking HMGB1 signalling can reduce inflammation and organ damage in animal models of trauma. Yet researchers emphasize that HMGB1 may have both harmful and protective effects depending on its cellular location and signalling balance, underscoring the need for carefully designed clinical studies.

The authors conclude that while ECG and troponin testing remain central to trauma assessment, combining them with molecular markers of inflammation could improve risk stratification and early detection of myocardial contusion. Large-scale clinical trials comparing DAMP levels across different trauma scenarios are expected to clarify their prognostic value.