Effects of early, late, and long-term nonselective β-blockade on left ventricular remodeling, function, and survival in chronic organic mitral regurgitation

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.