Cardiac remodelling – Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology

Abstract

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers. At a cellular and molecular level, remodelling involves all components of cardiac tissue: cardiomyocytes, fibroblasts, endothelial cells and leucocytes. The molecular, cellular and histological signatures of remodelling may differ according to the cause and severity of cardiac damage, and clearly to the global trend toward worsening or recovery. These processes cannot be routinely evaluated through endomyocardial biopsies, but may be reflected by circulating levels of several biomarkers. Different classes of biomarkers (e.g. proteins, non-coding RNAs, metabolites and/or epigenetic modifications) and several biomarkers of each class might inform on some aspects on HF development, progression and long-term outcomes, but most have failed to enter clinical practice. This may be due to the biological complexity of remodelling, so that no single biomarker could provide great insight on remodelling when assessed alone. Another possible reason is a still incomplete understanding of the role of biomarkers in the pathophysiology of cardiac remodelling. Such role will be investigated in the first part of this review paper on biomarkers of cardiac remodelling.

Biomarkers in heart failure clinical trials. A review from the Biomarkers Working Group of the Heart Failure Association of the European Society of Cardiology

“…5,6 A 2019 FDA guidance document indicates that biomarkers have potential utility to enrol heart failure (HF) patients with a greater event risk, stratify patients based on their predicted prognosis, and allow early proof of concept and dose selection studies. 7 Despite the almost exclusive focus on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), many biomarkers reflecting different elements of HF pathophysiology exist, [8][9][10][11] and the identification of specific biomarkers for each drug has been proposed. 1 Building on the FDA document and some authoritative papers, 1,6,12,13 this review article provides specific suggestions for biomarker use in HF clinical trials.…”

June 2022 at a glance: prevention, outcomes and treatment

“…Remodelling refers to the cardiac structural and functional changes leading to the development and progression of HF 12,13 . A two‐part review by the Heart Failure Association summarizes all the aspects of left ventricular remodelling, including pathophysiological mechanisms, the role of biomarkers and imaging and its clinical implications 14,15 . The role of left atrial function has also been recently pointed out 16,17 .…”

“…12,13 A two-part review by the Heart Failure Association summarizes all the aspects of left ventricular remodelling, including pathophysiological mechanisms, the role of biomarkers and imaging and its clinical implications. 14,15 The role of left atrial function has also been recently pointed out. 16,17 Left atrial remodelling across different stages of HF development, its clinical implications and therapeutic options are also reviewed in this issue.…”

Signaling Pathways and Potential Therapeutic Strategies in Cardiac Fibrosis

“…Consequently, it can be difficult to interpret MMP/TIMP as an imbalance in terms of collagen degradation or synthesis activity. Indeed, elevated circulating levels of MMP1 and TIMP1 are associated with poor outcomes in HF, and the C1TP/MMP1 ratio is inversely associated with cardiac complications in HF patients [ 107 ].…”