Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure.

OBJECTIVES

This individually randomized, open-label, parallel-group pilot study was designed to test the hypothesis that the ability of loop diuretics to interfere with cardiac fibrosis in chronic heart failure (CHF) may be different between compounds.

BACKGROUND

The apparent mortality and cardiac benefits seen in studies comparing torasemide with furosemide in CHF suggest that torasemide may have beneficial effects beyond diuresis (e.g., on the process of cardiac fibrosis).

METHODS

Patients with New York Heart Association functional class II to IV CHF received diuretic therapy with either 10 to 20 mg/day oral torasemide (n = 19) or 20 to 40 mg/day oral furosemide (n = 17), in addition to their existing standard CHF therapy for eight months. At baseline and after eight months, right septal endomyocardial biopsies were obtained to quantify collagen volume fraction (CVF) with an automated image analysis system. Serum carboxy-terminal peptide of procollagen type I (PIP) and serum carboxy-terminal telopeptide of collagen type I (CITP), indexes of collagen type I synthesis and degradation, respectively, were measured by specific radioimmunoassays.

RESULTS

In torasemide-treated patients, CVF decreased from 7.96 +/- 0.54% to 4.48 +/- 0.26% (p < 0.01), and PIP decreased from 143 +/- 7 to 111 +/- 3 microg/l (p < 0.01). Neither CVF nor PIP changed significantly in furosemide-treated patients. In all patients, CVF was directly correlated with PIP (r = 0.88, p < 0.001) before and after treatment. No changes in CITP were observed with treatment in either group.

CONCLUSIONS

These findings suggest that loop diuretics possess different abilities to reverse myocardial fibrosis and reduce collagen type I synthesis in patients with CHF.