Letter to the Editor regarding the article ‘Left atrial volume index in patients with heart failure and severely impaired left ventricular systolic function: the role of established echocardiographic parameters, circulating cystatin C and galectin-3’ by Zivlas et al. (2017)

We have read the article by Zivlas and colleagues in which the authors suggest a putative pathogenic role for cystatin C (Cys-C) and galectin-3 (Gal-3) in heart failure (HF) progression and cardiorenal syndrome. They even speculate on the possibility of targeting both molecules as a new therapeutic approach to address both processes.¹

We strongly disagree with this point of view. The authors seem to have missed important information concerning the pathophysiological role of these biomarkers in cardiovascular diseases.

Cys-C has been extensively studied in the context of HF. It is largely accepted nowadays that Cys-C is a fine surrogate marker of glomerular filtration rate (GFR),² and not involved in heart remodelling³ nor in the pathogenesis of cardiovascular diseases.⁴ Similarly, the initial hope with Gal-3, has been dismantled by studies showing that it is, again, merely a marker of GFR that does not add prognostic information after correcting for renal function,⁵ nor is it involved in the pathogenesis of fibrotic changes at a myocardial level in HF from hypertensive origin.⁶

Risk stratification remains a key point in HF,⁷ and for that purpose, Cys-C is an excellent option, especially for patients with a mild impairment in GFR, where it has been shown to reclassify up to 20% of patients.⁸

Further applications of both biomarkers, especially in the field of therapeutics remain largely speculative with little likelihood of reaching practical goals.