Isoproterenol stress-MRI did not correlate with exercise tolerance testing, despite reduced ejection fraction change under stress in MI (10.1%) and TAC (8.9%) mice vs sham (32.0%) at 4 weeks (P<0.001).
RCT
Randomized
Does isoproterenol-based cardiac reserve correlate with exercise tolerance in murine models of heart failure?
Isoproterenol stress-MRI cardiac indexes do not correlate with exercise tolerance in mouse models of heart failure, suggesting non-cardiac factors contribute to exercise intolerance.
Absolute Event Rate: 10.1% vs 32%
p-value: p=<0.001
The loss of cardiac reserve is, in part, responsible for exercise intolerance in late-stage heart failure (HF). Exercise tolerance testing (ETT) has been performed in mouse models of HF; however, treadmill performance and at-rest cardiac indexes determined by magnetic resonance imaging (MRI) rarely correlate. The present study adopted a stress-MRI technique for comparison with ETT in HF models, using isoproterenol (ISO) to evoke cardiac reserve responses. Male C57BL/6J mice were randomly subjected to myocardial infarction (MI), transverse aortic constriction (TAC), or sham surgery under general anesthesia. Mice underwent serial ETT on a graded treadmill with follow-up ISO stress-MRI. TAC mice showed consistent exercise intolerance, with a 16.2% reduction in peak oxygen consumption vs. sham at 15-wk postsurgery (WPS). MI and sham mice had similar peak oxygen consumption from 7 WPS onward. Time to a respiratory exchange ratio of 1.0 correlated with ETT distance (r = 0.64; P < 0.001). The change in ejection fraction under ISO stress was reduced in HF mice at 4 WPS 10.1 ± 3.9% change (Δ) and 8.9 ± 3.5%Δ in MI and TAC, respectively, compared with 32.0 ± 3.5%Δ in sham; P < 0.001. However, cardiac reserve differences between surgery groups were not observed at 16 WPS in terms of ejection fraction or cardiac output. In addition, ETT did not correlate with cardiac indexes under ISO stress. In conclusion, ISO stress was unable to reflect consistent differences in ETT between HF and healthy mice, suggesting cardiac-specific indexes are not the sole factors in defining exercise intolerance in mouse HF models.
Richards et al. (Fri,) conducted a rct in Heart failure. Isoproterenol stress-MRI and Exercise tolerance testing vs. Sham surgery was evaluated on Change in ejection fraction under isoproterenol stress at 4 weeks postsurgery (p=<0.001). Isoproterenol stress-MRI did not correlate with exercise tolerance testing, despite reduced ejection fraction change under stress in MI (10.1%) and TAC (8.9%) mice vs sham (32.0%) at 4 weeks (P<0.001).