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Carvedilol Improves Myocardial Contractility Compared With Metoprolol in Patients With Chronic Hibernating Myocardium After Revascularization

Division of Cardiology, Department of Medicine, University of Texas Medical Branch, Galveston, TX, Department of Cardiology, RWTH University Hospital, Aachen, Germany

Rajiv Gupta, MD

Division of Cardiology, Department of Medicine, University of Texas Medical Branch, Galveston, TX

Tu Phuong Diep, MD

Department of Cardiology, RWTH University Hospital, Aachen, Germany

Bernd Nowak, MD

Department of Nuclear Medicine, RWTH University Hospital, Aachen, Germany

Sawa Kostin, MD

Department of Experimental Cardiology, Max Planck-Institute, Bad Nauheim, Germany

Beate Grohmann, BS

Department of Experimental Cardiology, Max Planck-Institute, Bad Nauheim, Germany

Barry F. Uretsky, MD

Division of Cardiology, Department of Medicine, University of Texas Medical Branch, Galveston, TX

Jutta Schaper, MD, PhD

Department of Experimental Cardiology, Max Planck-Institute, Bad Nauheim, Germany

Background: We tested the hypothesis of whether carvedilol delays morphologic degeneration and improves functional outcome compared with metoprolol tartrate in patients with hibernating myocardium undergoing surgical revascularization. We have previously shown that patients with chronic hibernating myocardium undergo progressive cellular degeneration and fibrosis.

Methods: Twenty patients with multivessel coronary artery disease revascularization and hibernating myocardium as assessed by technetium-99m perfusion scintigraphy and fluorine-18-fluorodeoxyglucose positron emission tomography were randomized to receive either carvedilol or metoprolol tartrate for at least 2 months before surgery, and this was continued for 7 months postoperatively. Left ventricular ejection fraction and regional wall motion abnormalities were assessed by left ventriculography at baseline and 7 months postoperatively. Intraoperative transmural needle biopsy samples were obtained for microscopic analysis.

Results: Postoperatively, the ejection fraction increased from 31% ± 5% to 44% ± 4% (P < .005) in the carvedilol group (n = 10), and from 30% ± 6% to 40% ± 6% in the metoprolol tartrate group (P < .05 vs preoperatively and vs carvedilol). Wall motion abnormalities in the carvedilol group improved from -2.1 ± 0.4 to -0.6 ± 0.5 (P < .05) and from -2.3 ± 0.5 to -1.6 ± 0.6 in the metoprolol tartrate group (P < .05 vs preoperatively and vs carvedilol). Microscopic analysis after 72 ± 18 days of either treatment showed mild cardiomyocyte degeneration and moderate-to-severe fibrosis (28% ± 7%) in the carvedilol group compared with moderate cardiomyocyte degeneration and moderate-to-severe fibrosis (33% ± 6%) in the metoprolol tartrate group. Apoptosis, as assessed by the terminal deoxynucleotidyl transferase nick end labeling method, was observed in only 1 patient in each group.

Conclusions: Carvedilol treatment of hibernating myocardium results in improved functional recovery after revascularization compared with metoprolol tartrate, and this might partially be related to reduced cardiomyocyte degeneration.

Key Words: carvedilol • hibernating myocardium • myocardial function • apoptosis

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 10, No. 3, 181-190 (2005)
DOI: 10.1177/107424840501000306


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