title: Mechanisms underlying improvements in ejection fraction with carvedilol in heart failure.
abstract: 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.
  
  
  RESULTS
  Twenty-nine patients (63+/-12 years old) with New York Heart Association class II-III heart failure underwent serial measurements of left ventricular volumes using 3-dimensional echocardiography and blood pressures by sphygmomanometry at baseline, 2 weeks, 2, 6, and 12 months after initiation of carvedilol. From these parameters, left ventricular contractility (indexed by the end-systolic pressure-volume ratio), total peripheral resistance, and effective arterial elastance (E(a)) 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 total peripheral resistance (P<0.003 in each case). In those patients whose EF increased at least 5 points, approximately 60% of the increase was due to HR reduction, approximately 30% was due to increased contractility, and <20% was due to the decrease in total peripheral resistance.
  
  
  CONCLUSIONS
  Decreased HR, improved chamber contractility and afterload reduction each contributed significantly to improved EF with carvedilol.
authors.affiliation: Division of Cardiology, Columbia Presbyterian Medical Center, New York, NY, USA.
authors.forename: Mathew S
authors.initials: MS
authors.lastname: Maurer
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Sackner-Bernstein
authors.forename: Lyna
authors.initials: L
authors.lastname: El-Khoury Rumbarger
authors.forename: Madeline
authors.initials: M
authors.lastname: Yushak
authors.forename: Donald L
authors.initials: DL
authors.lastname: King
authors.forename: Daniel
authors.initials: D
authors.lastname: Burkhoff
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D019560:Echocardiography, Three-Dimensional; D004548:Elasticity; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000627:therapeutic use*; D012720:Severity of Illness Index; D019722:Sphygmomanometers; D013318:Stroke Volume / Q000187:drug effects*; D016896:Treatment Outcome; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol