Subclinical Inflammation in Ischemic Heart Disease and Its Role in the Transition to Heart Failure

Ischemic heart disease (IHD) remains the leading cause of chronic heart failure (HF) worldwide, yet the biological processes underlying this transition are not fully elucidated. Growing evidence indicates that chronic, low-grade inflammation acts as a pivotal link between ischemic injury and progressive myocardial dysfunction. Our review is the most up-to-date and structured synthesis on the pathophysiological pathways, biomarkers, and therapeutic implications of subclinical inflammation in patients with IHD at risk of developing HF. Following acute or repetitive ischemic episodes, persistent immune activation—mediated through interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α)—promotes endothelial dysfunction, microvascular instability, and extracellular matrix remodeling. These mechanisms culminate in ventricular stiffness, diastolic impairment, and adverse structural remodeling, even when left ventricular ejection fraction is preserved. Biomarkers such as Galectin-3, cancer antigen 125 (CA125), and high-sensitivity C-reactive protein (hsCRP) provide valuable insight into the interplay between fibrosis, congestion, and systemic inflammatory load, supporting early detection of subclinical myocardial injury. Advanced imaging modalities, including strain echocardiography and cardiac magnetic resonance imaging (MRI) mapping, enhance the phenotypic characterization of inflammatory cardiomyopathy. Understanding and targeting these inflammatory pathways may open new avenues for precision-based prevention and treatment, ultimately improving outcomes across the IHD–HF continuum.