Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Abstract

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.