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(Circulation. 2003;108:2336.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With ß-Blockade in Patients With Heart Failure

The ß-Blocker Evaluation of Survival Trial (BEST)

Eric J. Eichhorn, MD; Paul A. Grayburn, MD; Susan A. Mayer, MD; Martin St John Sutton, MD; Christopher Appleton, MD; Jonathan Plehn, MD; Jae Oh, MD; Barry Greenberg, MD; Anthony DeMaria, MD; Robert Frantz, MD; Heidi Krause-Steinrauf, MS, for the BEST Investigators

From the Department of Internal Medicine (Cardiology Division), the University of Texas Southwestern and Dallas VA Medical Centers, Dallas (E.J.E., P.A.G., S.A.M.); the University of Pennsylvania, Philadelphia (M.S.S.); the Mayo Clinic Scottsdale, Scottsdale, Ariz (C.A.); the Cardiovascular Branch of the National Institutes of Health and National Heart, Lung, and Blood Institute, Bethesda, Md (J.P.); the Mayo Clinic, Rochester, Minn (J.O., R.F.); the University of California at San Diego (B.G., A.D.); and the National Heart, Lung, and Blood Institute, Bethesda, Md, and the Department of Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif (H.K.-S.).

Correspondence to Eric J. Eichhorn, MD, Cardiopulmonary Research Science and Technology Institute, 7777 Forest Lane, Suite C-742, Dallas, TX 75230. E-mail eeichhorn{at}csant.com

Received August 19, 2002; de novo received April 8, 2003; revision received July 30, 2003; accepted August 1, 2003.

Background— ß-Blockers improve survival and reduce hospitalization in chronic heart failure (CHF) by biologically improving left ventricular ejection fraction (LVEF). However, a good predictor of improvement with this therapy has not been identified. This substudy of BEST examined whether myocardial contractile reserve, as determined by dobutamine stress echocardiography, predicts improvement in LVEF.

Methods and Results— Seventy-nine patients with class III/IV CHF underwent dobutamine stress echocardiography before treatment with bucindolol (n=41) or placebo (n=38). Regional wall motion score index (WMSI) was calculated as the sum of the scores in each segment divided by the total number of segments visualized. WMSI was compared with change in LVEF after 3 months of therapy as determined by gated radionuclide scan. Change in WMSI correlated inversely with change in LVEF after 3 months of bucindolol (r=-0.72, P<0.0001) and was the most significant multivariate predictor of change in LVEF (P=0.0002). Patients with contractile reserve had demographics similar to those of patients without contractile reserve, including RVEF, LVEF, systolic blood pressure, and CHF duration. However, patients without contractile reserve had higher baseline plasma norepinephrine levels (687±333 versus 420±246 pg/mL, P<0.05) and greater decrease in plasma norepinephrine in response to bucindolol (-249±171 versus -35±277 pg/mL, P<0.05).

Conclusions— This study suggests a direct relationship between contractile reserve and improvement in LVEF with ß-blocker therapy in patients with advanced CHF. Patients without contractile reserve have higher resting adrenergic drive, as reflected by plasma norepinephrine, and may experience greater sympatholytic effects from bucindolol.

Key Words: heart failure • receptors, adrenergic, beta • bucindolol • norepinephrine • contractility

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