Investigating a Biomarker-Driven Approach to Target Collagen Turnover in Diabetic Heart Failure with Preserved Ejection Fraction Patients. Effect of Torasemide Versus Furosemide on Serum C-Terminal Propeptide of Procollagen Type I (DROP-PIP trial)

AIM: Heart failure with preserved ejection fraction (HFpEF) is associated with myocardial remodelling including severe pro-fibrotic changes contributing to an increase in left ventricular stiffness and diastolic dysfunction. Serum C-terminal propeptide of procollagen type I (PIP) strongly correlates with the turnover of extracellular cardiac matrix proteins and fibrosis. Torasemide, but not furosemide, was described to reduce collagen type I synthesis in clinically unstable patients with heart failure with reduced ejection fraction. We evaluated whether its effect translated to HFpEF patients with type 2 diabetes mellitus (T2DM) and abnormal basal PIP levels. METHODS AND RESULTS: with a NT-proBNP of 174 ng/L and a 6-minute walk distance of 421 m. Mean per cent change in PIP was 2.63 ± 5.68% (±SEM) in torasemide vs. 2.74 ± 6.49% in furosemide (P = 0.9898) treated patients. Torasemide was not superior to furosemide in improving functional capacity, diastolic function, quality of life, or neuroendocrine activation. CONCLUSION: In this hypothesis-generating, mechanistic trial in stable HFpEF patients with T2DM, neither long-term administration of torasemide nor furosemide was associated with a significant effect on myocardial fibrosis, as assessed by serum PIP. Further studies are urgently needed in this field. More specific diuretic and anti-fibrotic treatment strategies in T2DM and/or HFpEF are warranted.