Abstract 23241: Effects of Candesartan and Metoprolol on Myocardial Mass,Edema, and Fibrosis During Anthracycline Treatment in Early Breast Cancer: APRADA-CMR substudy
Background: Anthracycline treatment may cause myocardial damage with myocyte death and expansion of the myocardial extracellular volume (ECV) fraction by edema and fibrosis. We tested the hypotheses that adjuvant treatment with the anthracycline epirubicin is associated with a dose dependent increase in myocardial ECV fraction and a reduction in total myocardial cellular volume and mass, and that these changes could be prevented by concomitant angiotensin or beta-adrenergic blockade.
Methods: The PRevention of cArdiac Dysfunction during Adjuvant breast cancer therapy (PRADA) trial was a 2x2 factorial, placebo-controlled, double-blind trial. 120 women with early breast cancer and no serious comorbidities were randomized to receive candesartan cilexetil, metoprolol succinate, or matching placebos concomitantly with adjuvant anticancer therapy. In 69 patients, ECV fraction, total ECV and cellular volume, and myocardial mass were measured by cardiovascular magnetic resonance before and at the completion of anthracycline therapy.
Results: Overall, ECV fraction increased from 27.5±2.7% to 28.7±2.9 % (p=0.001). There was a dose dependent association between cumulative anthracycline dose (400 mg/ m2 vs. <400 mg/m2) and ECV fraction (mean change 3.2 % [95% confidence interval (CI) 1.0, 5.5] vs. 0.8% [95% CI 0.1, 1.5], p=0.009), as well as with increased total ECV (mean change 1.8 ml [95% CI 0.2, 3.5] vs. 0.2 ml [95% CI -0.5, 0.8], p=0.050). Candesartan treatment was associated with a decline in total cellular volume (mean change -3.5 ml [95% CI -4.7, -2.3]) and left ventricular mass (mean change -3.6 g [95% CI -5.2, -2.0]) (both p<0.001), and no change in total ECV; (mean change 0.1 ml [95% CI -0.9, 1.0], p=0.902). In contrast, in patients receiving no candesartan, total ECV increased (0.9 ml [95% CI 0.1, 1.7]; p=0.031) while total cellular volume (-0.7 ml [95% CI -2.2, 0.8]; p=0.366) and mass (0.2 g [95% CI -1.3, 1.7]; p=0.741) remained unchanged. There was no impact of metoprolol on ECV fraction, total ECV or cellular volume.
Conclusions: Anthracycline therapy is associated with a dose-dependent increase in ECV fraction and total ECV. Concomitant treatment with candesartan blunts the increase in total ECV and reduces left ventricular total cellular volume and mass.
Author Disclosures: S. Heck: None. G. Gulati: Honoraria; Modest; Novartis. P. Hoffmann: None. F. von Knobelsdorff-Brenkenhoff: None. T.H. Storås: None. A.H. Ree: None. B. Gravdehaug: None. H. Røsjø: None. K. Steine: None. J. Geisler: None. J. Schulz-Menger: Research Grant; Modest; Siemens. Other Research Support; Modest; Siemens, Circle. Consultant/Advisory Board; Modest; Bayer. Other; Modest; SCMR, President, ISMRM Board Member. T. Omland: Other Research Support; Significant; AstraZeneca, Abbott Diagnostics. Honoraria; Modest; Abbott Diagnostics, Roche Diagnostics, Novartis. Consultant/Advisory Board; Modest; Novartis.
- © 2016 by American Heart Association, Inc.