CLINICAL RESEARCH: HEART FAILURE
Effects of loop diuretics on myocardial fibrosis and collagen type I turnover in chronic heart failure
Begoña López, PhD*,
Ramón Querejeta, MD, PhD ,
Arantxa González, PhD*,
Eloy Sánchez, MD,
Mariano Larman, MD and
Javier Díez, MD, PhD* ,*
* Area of Cardiovascular Pathophysiology, Centre for Applied Medical Research, Pamplona, Spain
Department of Cardiology and Cardiovascular Surgery, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
Division of Cardiology, General Hospital, San Sebastián, Spain
Division of Hemodynamics, Guipuzcoa Policlinics, Donostia University Hospital, San Sebastián, Spain
Manuscript received November 6, 2003;
revised manuscript received December 18, 2003,
accepted December 23, 2003.
* Reprint requests and correspondence: Dr. Javier Díez, Area de Fisiopatología Cardiovascular, CIMA, Facultad de Medicina, C/Irunlarrea 1, 31080 Pamplona, Spain.
jadimar{at}unav.es
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 µg/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.
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Abbreviations and Acronyms
| | ACE | = angiotensin-converting enzyme | | CHF | = chronic heart failure | | CITP | = carboxy-terminal telopeptide of collagen type I | | CVF | = collagen volume fraction | | DT | = deceleration time | | EF | = ejection fraction | | KLV | = left ventricular chamber stiffness | | LVMI | = left ventricular mass index | | NYHA | = New York Heart Association | | PIP | = carboxy-terminal peptide of procollagen type I |
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