Myocardial fibrosis in heart failure with preserved ejection fraction: integrating circulating collagen fragments and cardiac magnetic resonance mapping

Myocardial Interstitial fibrosis is a hallmark of cardiac aging and a central determinant of the increased tissue stiffness that characterizes heart failure with preserved ejection fraction (HFpEF).1,2 It reflects maladaptive extracellular-matrix (ECM) remodelling with interstitial expansion and accumulation of fibrillar type I collagen, a main contributor to matrix rigidity. Non-invasive strategies to assess myocardial fibrosis comprise circulating collagen-turnover biomarkers and cardiovascular magnetic resonance (CMR) metrics such as native T1 and extracellular volume (ECV) mapping.3–5 Both correlate with histological fibrosis, the reference standard,6 yet endomyocardial biopsies are invasive and subject to sampling error and processing artefacts. Non-invasive assessment is therefore needed, and combining CMR with circulating collagen fragments may improve accuracy over either alone. CMR mapping sequences offers in vivo whole-heart quantitative coverage, but myocardial T1 relaxation time can be prolonged by others tissue processes (e.g. inflammation or amyloid deposition) and distorted by susceptibility artefacts from stents or implanted devices. By contrast, circulating biomarkers provide fibrosis-specific readouts but may derive from extra-cardiac sources (e.g. liver and bone) and be affected by renal clearance.7 Because each method addresses different limitations, these approaches may be complementary, and combining organ-level imaging with mechanism-specific biomarkers may enable earlier, more specific detection of fibrotic remodelling and help refine selection for antifibrotic therapies. However, the data evaluating the correlation between circulating collagen fragments and CMR data are limited. Specifically, simultaneous profiling of collagen biomarkers and CMR-based fibrosis surrogates, and their association, has not been addressed in HFpEF.