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Previous Volume 346:1357-1365 May 2, 2002 Number 18 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Stevenson, L. W. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Beta-blocker therapy may improve cardiac function in patients with idiopathic dilated cardiomyopathy. We tested the hypothesis that beta-blocker therapy produces favorable functional effects in dilated cardiomyopathy by altering the expression of myocardial genes that regulate contractility and pathologic hypertrophy.

Methods We randomly assigned 53 patients with idiopathic dilated cardiomyopathy to treatment with a -adrenergic–receptor blocking agent (metoprolol or carvedilol) or placebo. The amount of messenger RNA (mRNA) for contractility-regulating genes (those encoding ₁- and ₂-adrenergic receptors, calcium ATPase in the sarcoplasmic reticulum, and - and -myosin heavy-chain isoforms) and of genes associated with pathologic hypertrophy (-myosin heavy chain and atrial natriuretic peptide) was measured with a quantitative reverse-transcription polymerase chain reaction in total RNA extracted from biopsy specimens of the right ventricular septal endomyocardium. Myocardial levels of -adrenergic receptors were also measured. Measurements were conducted at base line and after six months of treatment, and changes in gene expression were compared with changes in the left ventricular ejection fraction as measured by radionuclide ventriculography.

Results Twenty-six of 32 beta-blocker–treated patients (those with complete mRNA measurements) had an improvement in left ventricular ejection fraction of at least 5 ejection-fraction (EF) units (mean [±SE] increase, 18.8±1.8). As compared with the six beta-blocker–treated patients who did not have a response (mean change, a decrease of 2.5±1.8 EF units), those who did have a response had an increase in sarcoplasmic-reticulum calcium ATPase mRNA and -myosin heavy chain mRNA and a decrease in -myosin heavy chain mRNA. The change in sarcoplasmic-reticulum calcium ATPase was not present in the patients in the placebo group who had a spontaneous response. There were no differences between those who had a response and those who did not in terms of the change in mRNA or protein expression of -adrenergic receptors.

Conclusions In idiopathic dilated cardiomyopathy, functional improvement related to treatment with beta-blockers is associated with changes in myocardial gene expression.

Source Information

From the Division of Cardiology and the Cardiovascular Institute, University of Colorado Health Sciences Center, Denver (B.D.L., W.T.A., W.A.M., D.F., E.E.W., J.L., T.T., A.D.R., R.A.Q., M.R.B.); and the Division of Cardiology, University of Utah Health Sciences Center, Salt Lake City (E.M.G., P.L.).

Address reprint requests to Dr. Bristow at the Division of Cardiology, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Campus Box B139, Denver, CO 80262.

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