What is measured by cardiac fibrosis biomarkers and imaging?

C ardiac fibrosis is the consequence of extracellular cardiac matrix remodeling resulting from pathological processes, including ischemia, stretch, inflammation, and neurohormonal activation. Fibrosis can be reparative or reactive. At the site of a transmural myocardial infarction, fibrotic scarring provides protective strength and prevents myocardial rupture. Diffuse reactive fibrosis occurs remotely from the ischemic scar. It is associated with myocyte hypertrophy and contributes to the detrimental process of remodeling, increased ventricu-lar stiffness, tissue disarray with consequent contractile het-erogeneity, reduced contractile reserve, and arrhythmogenic anisotropy. Although most commonly found in the setting of ischemic heart disease, where it acts as a precursor to heart failure (HF), the more diffuse type of fibrosis is also an essential feature of idiopathic dilated cardiomyopathy, diabetic cardiomyopathy, hypertensive heart disease, and hypertrophic cardiomyopathy (HCM). Cardiac fibrosis results in an accumulation of proteins including collagen in the extracellular space, damage that has previously been considered irreversible in many cardiovascular (CV) diseases. It is now emerging as an important novel target for future CV antifibrotic therapies. Promising therapeutic candidates include antihyper-tensive therapies, antialdosterone agents, anti-inflammatory and antioxidant agents, growth factor inhibitors, matricellular proteins, and key miRNAs, as well as cell therapy or genetic interventions. It is therefore important to noninvasively identify , measure, image, and monitor the degree of cardiac fibro-sis to better understand its pathophysiology and select optimal patients for antifibrotic therapy trials. Furthermore, noninva-sive surrogate end points such as circulating biomarkers or magnetic resonance and molecular imaging should allow for larger proof-of-concept clinical trials than previously possible with endomyocardial biopsies. Detection of cardiac fibrosis is based on the quantification of a diffuse excess of collagen fiber deposition in the inter-stitial space, as assessed by staining techniques. Fibrosis may also be monitored noninvasively using biochemical assessments at circulating levels of collagen substrates, enzymatic complexes, or end products. It may also be assessed using bioimaging. Both methods have relative merits and limitations; thus, they can be used in conjunction. 3 Some degree of inference is required in the interpretation of these tests because they are noninvasive and have not always been validated against myocardial biopsy studies. Cardiac fibrosis has also been assessed indirectly by the evaluation of its functional consequences (ie, cardiac dysfunction, loss of contractile reserve, and abnormal myocardial stiffness). However, these functional tests may be heavily confounded by nonextracellular matrix (ECM)–related factors. Circulating cardiac fibrosis biomarkers have been developed, and many are associated with relevant clinical …