Myocardial fibrosis: biomedical research from bench to bedside

Abstract

Myocardial fibrosis refers to a variety of quantitative and qualitative changes in the interstitial myocardial collagen network that occur in response to cardiac ischaemic insults, systemic diseases, drugs, or any other harmful stimulus affecting the circulatory system or the heart itself. Myocardial fibrosis alters the architecture of the myocardium, facilitating the development of cardiac dysfunction, also inducing arrhythmias, influencing the clinical course and outcome of heart failure patients. Focusing on myocardial fibrosis may potentially improve patient care through the targeted diagnosis and treatment of emerging fibrotic pathways. The European Commission funded the FIBROTARGETS consortium as a multinational academic and industrial consortium with the primary aim of performing a systematic and collaborative search of targets of myocardial fibrosis, and then translating these mechanisms into individualized diagnostic tools and specific therapeutic pharmacological options for heart failure. This review focuses on those methodological and technological aspects considered and developed by the consortium to facilitate the transfer of the new mechanistic knowledge on myocardial fibrosis into potential biomedical applications.

Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure

“…The use of PIIINP as primary outcome measure was chosen for testing the primary hypothesis of the HOMAGE (‘Heart ’omics' in AGEing’) trial (NCT02556450) in which patients at high risk for developing HF are randomised to either spironolactone plus conventional therapy or conventional therapy alone to assess the effect of spironolactone on PIIINP changes from baseline to 9 months. The assessment of PICP changes as secondary outcome measure was based on the increasing body of evidence supporting the direct correlation of this biomarker with myocardial fibrosis 18. The evidence supporting the correlation of the other studied biomarkers with myocardial fibrosis is weaker and they were assessed as exploratory measures.…”

Direct thrombin inhibition with dabigatran attenuates pressure overload-induced cardiac fibrosis and dysfunction in mice

“…A dysregulation of the ECM synthesis along with a decreased degradation results in an heightened mechanical stiffness leading to diastolic dysfunction ultimately leading to heart failure (3). This fibrotic process is characterized by activation of cardiac fibroblasts (myofibroblasts), that synthesize and excrete excessive collagen-rich extracellular matrix (collagen I and III) into the cardiac interstitial and perivascular regions in response to a variety of stimuli such as hypertension, inflammation, hormones, cytokines, and growth factors (4) Progressive fibrotic remodeling may ultimately lead to cardiac dysfunction, abnormalities of coronary reserve, and fatal arrhythmias (5, 6). …”

The year in cardiology 2017: heart failure

“…Given the heterogeneity of HF and difficulty characterizing HF, in particular with preserved EF, multimarker personalized approaches to HF, as occurs in oncology, may improve characterization and classification in HF. 27,51 But EF remains the most commonly used classifier and the fact remains: EF 40-49% is not normal but there is no evidence based therapy, and further research is needed in this group, 1 48 and greater prognostic impact of chronic kidney disease. 52 Recent studies also suggest that standard HF therapy may be effective in HFmrEF.…”

“…[23][24][25] But given the many factors involved in CRT response and outcomes, predicting CRT response remains elusive and the potential for larger multi parametric big-data approaches should be considered for future trials. 26,27 The 2016 ESC guidelines recommend primary prevention ICD in both ischaemic and non-ischaemic cardiomyopathy. 1 This was called into doubt by DANISH, 28 where primary prevention ICD in nonischaemic cardiomyopathy reduced sudden cardiac death but not allcause death.…”