Published Online
on April 14, 2009

A more recent version of this article appeared on May 1, 2009

This Article Full Text (PDF) Data Supplement All Versions of this Article: 2/3/189    most recent CIRCHEARTFAILURE.108.806240v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maurer, M. S. Articles by Burkhoff, D. Search for Related Content PubMed PubMed Citation Articles by Maurer, M. S. Articles by Burkhoff, D. Related Collections Contractile function Other heart failure Congestive

Original Article

Mechanisms Underlying Improvements in Ejection Fraction with Carvedilol in Heart Failure

Mathew S. Maurer¹; Jonathan D. Sackner-Bernstein^2,3; Lyna El-Khoury Rumbarger¹; Madeline Yushak¹; Donald L. King¹ and Daniel Burkhoff¹

¹ Columbia Presbyterian Medical Center, New York, NY;
² Clinilabs Inc., New York, NY

³ E-mail: jonathansb{at}yahoo.com

Background—Reductions in heart rate (HR) with beta-blocker therapy have been associated with improvements in ejection fraction (EF). However, the relative contributions of HR reduction, positive inotropism, afterload reduction and reverse remodeling to improvements in EF are unknown.

Methods and Results—29 patients (63±12 years old) with NYHA II-III heart failure underwent serial measurements of LV volumes using three-dimensional echocardiography and blood pressures by sphygmomanometry at baseline, 2 weeks, 2, 6 and 12 months after initiation of carvedilol. From these parameters, LV contractility (indexed by the end-systolic pressure-volume ratio), total peripheral resistance (TPR) and effective arterial elastance (Ea) were derived. Overall, EF increased by 7-percentage points after 6 months of therapy (from 25±9 to 32±9, p <0.0001). This change was due to an increase in stroke volume (p<0.001) with no significant change in end-diastolic volume (p=0.15). The EF change correlated with increased contractility, decreased HR and decreased TPR (p<0.003 in each case). In those patients whose EF increased at least 5 points, ~60% of the increase was due to HR reduction, ~30% was due to increased contractility and <20% was due to the decrease in TPR.

Conclusions—Decreased HR, improved chamber contractility and afterload reduction each contributed significantly to improved EF with carvedilol.

Key Words: contractility • heart failure • heart rate • vasodilation • ejection fraction

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