Diffuse Myocardial Fibrosis on Cardiac Magnetic Resonance Imaging Is Related to Galectin-3 and Predicts Outcome in Heart Failure

Abstract

Aims: Ongoing adverse remodeling is a hallmark of heart failure (HF), which might be reflected by either focal or diffuse myocardial fibrosis. Therefore, in (pre)clinical settings, we used immunohistochemistry or cardiac magnetic resonance imaging (CMR) to investigate the association of (focal or diffuse) fibrosis with cardiac biomarkers and adverse events in HF. Methods and results: In C57Bl/6J mice, we determined the presence and extent of myocardial fibrosis 6 weeks post-myocardial infarction (MI). Furthermore, we studied 159 outpatient HF patients who underwent CMR, and determined focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium, respectively. HF patients were categorized based on the presence of LGE, and by the median post-contrast T1 time. Kaplan–Meier and Cox regression analyses were used to determine the association of fibrosis with HF hospitalization and all-cause mortality. LGE was detected in 61 (38%) patients. Cardiac biomarker levels were comparable between LGE-positive and LGE-negative patients. LGE-positive patients with a short T1 time had elevated levels of both NT-proBNP and galectin-3 (1611 vs. 453 ng/L, p = 0.026 and 20 vs. 15 μg/L, p = 0.004, respectively). This was not observed in LGE-negative patients. Furthermore, a short T1 time in LGE-positive patients was associated with a higher risk of adverse events (log-rank p = 0.01). Conclusion: This study implies that cardiac biomarkers reflect active remodeling of the non-infarcted myocardium of patients with focal myocardial scarring. Diffuse fibrosis, in contrast to focal scarring, might have a higher prognostic value regarding adverse outcomes in HF patients.

Efficacy and Safety of Kuoxin Formula in the Treatment of Dilated Cardiomyopathy-Related Heart Failure: Study Protocol of a Randomized, Double-Blind, Placebo-Controlled, Multi-Center Clinical Trial

“…33,34 TGF-β, a principal fibrillogenic factor, plays a significant role in myocardial fibrosis by promoting cardiac fibroblast proliferation and collagen synthesis, thus triggering the TGF-β/Smad pathway and contributing to ventricular remodeling. 35,36 Additionally, Galectin-3, a proinflammatory factor, is crucial in various pathological processes like cell growth, apoptosis, and inflammatory responses, acting as a key mediator in cardiac remodeling and the progression of heart failure. 37 Furthermore, Type I procollagen carboxyterminal peptide (PICP) and Type I collagen carboxyterminal crosslinked peptide (CITP) are valuable markers for assessing fibrosis.…”

Evaluation of right ventricular diastolic function, systolic function, and circulating galectin‐3 concentrations in dogs with pulmonary stenosis

“…Circulating Gal-3 has been experimentally validated as a marker of myocardial fibrosis in a number of veterinary species, 56,57 and it also has been correlated with the presence of myocardial fibrosis in humans detected by either cardiac magnetic resonance imaging (cMR) or histopathology. 29,58 Right ventricular myocardial fibrosis has been identified by histopathology in a client-owned dog with PS and in an experimental model with increased RV afterload. 59,60 Right ventricular myocardial fibrosis also has been identified in humans with PS using cMR, 16 and a similar study in dogs with PS identified increased right ventricular stiffness using cMR.…”

The Role of Galectin-3 in Heart Failure—The Diagnostic, Prognostic and Therapeutic Potential—Where Do We Stand?

“…CMR allows for the determination of focal and diffuse fibrosis by late gadolinium enhancement (LGE) and post-contrast T1 time of the non-LGE myocardium. Recently Screever EM et al demonstrated in a MI murine model and a well-characterized cohort of HF patients that diffused myocardial fibrosis on CMR was related to Gal-3 levels [105].…”

“…There are some data that Gal-3 is related to diffuse fibrosis. The role of diffuse fibrosis and its usefulness regarding prognosis might differ between different HF etiologies [105]. The type of fibrosis determines whether this process is reversible, at least to some point.…”