title: New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility.
abstract: BACKGROUND
  It is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α(1),β(1),β(2)-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions.
  
  
  RESULTS
  In 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II-IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF(c)). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF(c)-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF(c) relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months.
  
  
  CONCLUSIONS
  Despite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.
authors.affiliation: Section of Cardiology, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas 77030, USA. bbozkurt@bcm.tmc.edu
authors.forename: Biykem
authors.initials: B
authors.lastname: Bozkurt
authors.forename: Mariana
authors.initials: M
authors.lastname: Bolos
authors.forename: Anita
authors.initials: A
authors.lastname: Deswal
authors.forename: Sameer
authors.initials: S
authors.lastname: Ather
authors.forename: Wenyaw
authors.initials: W
authors.lastname: Chan
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Mann
authors.forename: Blase
authors.initials: B
authors.lastname: Carabello
mesh_terms: D000368:Aged; D002227:Carbazoles / Q000627:therapeutic use*; D000077261:Carvedilol; D002908:Chronic Disease; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D011412:Propanolamines / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left
chemical_list: D002227:Carbazoles; D011412:Propanolamines; D014665:Vasodilator Agents; D000077261:Carvedilol