Circulating Biomarkers of Cardiac Fibrosis

C ardiac fibrosis is common to the pathophysiology under- pinning the majority of cardiovascular conditions that predispose to heart failure.Acute conditions such acute myocardial infarction and myocarditis as well as chronic challenges including systemic arterial hypertension and cardiac valvular disease all potentially induce abnormal and adverse cardiac fibrosis.This manifests as an excess of generation over degradation of collagen types I and III with increased extracellular deposition of collagen.This process is associated with an increase in the ratio of the larger type I collagen to the smaller type III collagen fibrils and enhanced cross-linking between collagen fibrils, all resulting in interstitial fibrosis.In the context of infarction, defined segments of the myocardium become necrotic followed by scarring, designated replacement fibrosis, whereas chronic global challenges to the ventricle such as hypertension and other causes of sustained increased cardiac load induce diffuse interstitial or reactive fibrosis.1 Notably, the global adverse remodeling of the left ventricle (LV), which may follow focal myocardial infarction, incorporates diffuse reactive fibrosis of myocardium remote from the infarct concurrent with localized infarct-specific replacement fibrosis.Sufficiently extensive diffuse reactive fibrosis impinges adversely on cardiac structure and function through increased ventricular stiffness with consequently impaired diastolic and systolic function, reduced coronary flow reserve, and a propensity to arrhythmia.These disadvantageous effects predispose to progression through stages B to D of heart failure with the attendant severe morbidity and mortality.Given the pivotal role of cardiac fibrosis in the natural history of many forms of heart disease, clinically accessible markers reliably reflecting the degree of existing fibrosis as well as rising and falling in dynamic parallel to progression or regression of fibrosis would be invaluable.Such markers would find application in diagnosis, risk stratification, and for monitoring the efficacy of therapy.