Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with beta-blockade in patients with heart failure: the Beta-Blocker Evaluation of Survival Trial (BEST).
BACKGROUND
beta-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.


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 beta-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.
Department of Internal Medicine, Cardiology Division, the University of Texas Southwestern and Dallas VA Medical Centers, Dallas, USA. eeichhorn@csant.com
Eric J
EJ
Eichhorn
Paul A
PA
Grayburn
Susan A
SA
Mayer
Martin
M
St John Sutton
Christopher
C
Appleton
Jonathan
J
Plehn
Jae
J
Oh
Barry
B
Greenberg
Anthony
A
DeMaria
Robert
R
Frantz
Heidi
H
Krause-Steinrauf
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004280:Dobutamine / Q000008:administration & dosage / Q000009:adverse effects; D025401:Echocardiography, Stress; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D011877:Radionuclide Imaging; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D004280:Dobutamine; C024307:bucindolol; D009638:Norepinephrine