Myocardial Fibrosis in Heart Failure: Anti-Fibrotic Therapies and the Role of Cardiovascular Magnetic Resonance in Drug Trials

Abstract

All heart muscle diseases that cause chronic heart failure finally converge into one dreaded pathological process that is myocardial fibrosis. Myocardial fibrosis predicts major adverse cardiovascular events and death, yet we are still missing the targeted therapies capable of halting and/or reversing its progression. Fundamentally it is a problem of disproportionate extracellular collagen accumulation that is part of normal myocardial ageing and accentuated in certain disease states. In this article we discuss the role of cardiovascular magnetic resonance (CMR) imaging biomarkers to track fibrosis and collate results from the most promising animal and human trials of anti-fibrotic therapies to date. We underscore the ever-growing role of CMR in determining the efficacy of such drugs and encourage future trialists to turn to CMR when designing their surrogate study endpoints.

Keywords: Anti-fibrotic therapies; Cardiac magnetic resonance imaging; Extracellular volume; Myocardial fibrosis; T1 mapping.

Fig. 1

The value of CMR tissue characterisation in distinguishing the underlying cause for LVH phenotypes. Panel a shows a patient with familial HCM caused by a pathogenic MYBPC3 mutation. There is asymmetric septal hypertrophy and extensive diffuse and patchy LGE in the hypertrophied segments with corresponding high native myocardial T₁ in these areas of fibrosis. Panel b shows a male patient with LVH secondary to myocardial glycosphingolipid accumulation in Fabry disease as a result of which myocardial T₁ times are low and there is the classic patch of subepicardial fibrosis in the inferolateral wall. b/m/aSAX basal/mid/apical short axis, 4/2C 4/2-chamber, HCM hypertrophic cardiomyopathy, LGE late gadolinium enhancement, LVH left ventricular hypertrophy, MOCO motion-corrected, MOLLI modified Look-Locker inversion recovery, MYBPC3 myosin-binding protein C3, PSIR phase-sensitive inversion recovery, ShMOLLI shortened MOLLI, SSFP steady-state free precession

Fig. 2

Schema representing the development of myocardial fibrosis and sites of action of potential therapeutic targets. RAAS renin–angiotensin–aldosterone system, TGFβ tissue growth factor-β, TNFα tumour necrosis factor-α, CTGF connective tissue growth factor, IL-11 interleukin-11, miRNA microRNA, MMP matrix metalloproteinases, Gal-3 galectin-3