BACKGROUND: Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. METHODS AND RESULTS:Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308 ± 25 versus 351 ± 31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2 ± 0.7 versus 1.59 ± 0.6 mL; P<0.001), end-systolic volumes (0.72 ± 0.42 versus 0.40 ± 0.19 mL; P<0.001), and mass index (2.40 ± 0.55 versus 2.06 ± 0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33 ± 7% versus 38 ± 7%; P<0.001) and ejection fraction (69 ± 11% versus 75 ± 7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114 ± 10 versus 93 ± 12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). CONCLUSIONS: Early and long-term nonselective β-blockade was associated with adverse left ventricular remodeling, systolic dysfunction, and a reduction in survival in the experimental rat model of organic MR.
RCT Entities:
BACKGROUND:Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. METHODS AND RESULTS: Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308 ± 25 versus 351 ± 31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2 ± 0.7 versus 1.59 ± 0.6 mL; P<0.001), end-systolic volumes (0.72 ± 0.42 versus 0.40 ± 0.19 mL; P<0.001), and mass index (2.40 ± 0.55 versus 2.06 ± 0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33 ± 7% versus 38 ± 7%; P<0.001) and ejection fraction (69 ± 11% versus 75 ± 7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114 ± 10 versus 93 ± 12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). CONCLUSIONS: Early and long-term nonselective β-blockade was associated with adverse left ventricular remodeling, systolic dysfunction, and a reduction in survival in the experimental rat model of organic MR.
Entities:
Keywords:
left ventricular function; left ventricular remodeling; mitral regurgitation; β-blocker
Authors: Robert A Levine; Albert A Hagége; Daniel P Judge; Muralidhar Padala; Jacob P Dal-Bianco; Elena Aikawa; Jonathan Beaudoin; Joyce Bischoff; Nabila Bouatia-Naji; Patrick Bruneval; Jonathan T Butcher; Alain Carpentier; Miguel Chaput; Adrian H Chester; Catherine Clusel; Francesca N Delling; Harry C Dietz; Christian Dina; Ronen Durst; Leticia Fernandez-Friera; Mark D Handschumacher; Morten O Jensen; Xavier P Jeunemaitre; Hervé Le Marec; Thierry Le Tourneau; Roger R Markwald; Jean Mérot; Emmanuel Messas; David P Milan; Tui Neri; Russell A Norris; David Peal; Maelle Perrocheau; Vincent Probst; Michael Pucéat; Nadia Rosenthal; Jorge Solis; Jean-Jacques Schott; Ehud Schwammenthal; Susan A Slaugenhaupt; Jae-Kwan Song; Magdi H Yacoub Journal: Nat Rev Cardiol Date: 2015-10-20 Impact factor: 32.419