Myocardial contractile reserve by dobutamine stress echocardiography predicts improvement in ejection fraction with β-blocker in patients with heart failure. the β-blocker evaluation of survival trial (best)

or other syndromes surrounding acute coronary artery syndromes. WA

patients incorporating endpoints of not just improved function but also tolerance to beta-blocker therapy. WA

Myocardial Contractile Reserve by Dobutamine Stress Echocardiography Predicts Improvement in Ejection Fraction With ␤-Blocker in Patients With Heart Failure. The ␤-Blocker Evaluation of Survival Trial (BEST)

Gadolinium Cardiovascular Magnetic Resonance Predicts Reversible Myocardial Dysfunction and Remodeling in Patients With Heart Failure Undergoing ␤-Blocker Therapy Bello D, Shah DJ, Farah GM, et al. Circulation 2003;108:1945– 53.

Eichhorn EJ, Grayburn PA, Mayer SA, et al. Circulation 2003;108: 2336 – 41.

Study Question: To evaluate with Gadolinium cardiovascular magnetic resonance imaging (CMR) the relationship of remodeling and improved systolic function in patients with congestive heart failure undergoing ␤-blocker therapy. Methods: CMR was performed in 45 patients with chronic CHF, 35 of whom completed 6 months of ␤-blocker therapy and had repeat CMR for LV function and extent of scar (hyperenhancement). Results: The etiology of CHF was ischemic in 23 and nonischemic in 12 patients. Hyperenhancement indicating scar was noted in 28 of 28 patients with ischemic disease and in only two of 17 (12%) with a nonischemic etiology. There was an inverse relationship between the extent of scar at baseline and contractile improvement at 6 months (p⬍0.001). Improved contractility was noted in 674 of 1307 (56%) segments without scar but in only eight of 232 (3%) with ⬎75% scar. After 6 months of ␤-blocker therapy, improvement in contractile function and remodeling was greater in the nonischemic than in the ischemic group (p⫽NS). On multivariate analysis the amount of viable, dysfunctional myocardium by CMR independently predicted an increase in ejection fraction (p⫽0.01), wall motion score (p⫽0.0007) and LV diastolic and systolic volume index (pⱕ0.007). Conclusion: Gadolinium-enhanced CMR accurately identifies responders and non-responders to ␤-blocker therapy based on detection and extent of scar. Perspective: This is one of several recent publications outlining the clinical utility of contrast enhanced CMR for identifying myocardial scar in patients with CHF and further stratifying them with respect to viability. This study nicely demonstrates that patients with greater extent of scar are less likely to have improvement in a variety of parameters of left ventricular remodeling and systolic function than are those with no or lesser degrees of scar. While this study nicely demonstrates the ability of CMR to identify small cohort responders to ␤-blocker therapy when the end point is improved LV function and remodeling, it does not address issues of functional status or survival, which may be improved in the absence of favorable remodeling. WA

Study Question: To evaluate the relationship of contractile reserve at the time of dobutamine stress echocardiography (DSE) to improvement in left ventricular ejection fraction (LVEF) after treatment with ␤-Blocker (BB) (bucindolol) in patients with advanced congested heart failure (CHF). Methods: This was a substudy of the ␤-Blocker Evaluation of Survival Trial (BEST) in which 79 patients with class 3/4 CHF underwent DSE before randomization to BB (n⫽41) or placebo (n⫽38). Contractile reserve was defined as a decrease of wall motion score index (WMSI) of at least 0.2. Results: There were no statistically significant differences in baseline characteristics of patients receiving placebo or BB, including age, ischemic vs. nonischemic etiology, resting heart rate, LVEF or plasma norepinephrine (PNE). Patients with contractile reserve more often had an ischemic etiology. Clinical descriptors did not distinguish between presence or absence of contractile reserve. Change in WSMI during DSE correlated with improvement in LVEF after three months of treatment (r⫽⫺0.72, p⬍0.0001) and the regression equation suggested a LVEF improvement of 5.0 EF units per WMSI ⌬⫺0.2 in patients receiving BB. There was no similar relationship in placebo patients. ⌬WMSI was the only multivariate predictor of improvement in LVEF during BB therapy. Conclusion: Demonstration of contractile reserve with DSE predicts improvement in LVEF in patients with advanced CHF undergoing BB therapy with bucindolol. Perspective: This substudy from the BEST trial provides further information that may allow prediction of a beneficial BB therapy. In addition to the measures discussed above, there were statistically significant differences in the neurohormonal profile of patients who were BB responders vs. not responders and lower PNE levels seen in those with contractile reserve vs. no contractile reserve. It should be emphasized that this was a relatively limited randomized trial using only one BB and the results may not extrapolate to other BB. Identification of a favorable response to betablockade is crucial because of the potential for this therapy to result in worsening LV function in susceptible individuals and, hence, worsened outcome. A natural outcome of this study would be evaluation of a larger population of

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