Table 2.
Mean (standard deviation) echocardiographic values for rapamycin and placebo groups at baseline, 6 months, and 12 months into the study.
| Outcome measure | Treatment group | Baseline | 6 month mean (SD) | 6 month effect* | p-value** | Adjusted p-value*** | 12 month mean (SD) | 12 month effect* | p-value** | Adjusted p-value*** |
|---|---|---|---|---|---|---|---|---|---|---|
| Left atrial to aortic root ratio | Rapamycin | 1.159 (0.117) | 1.132 (0.144) | −0.18 (−0.32, 0–0.04) | 0.014 | 0.196 | 1.138 (0.112) | −0.166 (−0.321, −0.012) | 0.037 | 0.481 |
| Placebo | 1.195 (0.168) | 1.315 (0.127) | 1.304 (0.182) | |||||||
| Left atrial major diameter^ (cm) | Rapamycin | 3.58 (0.41) | 3.69 (0.42) | 0.06 (−0.33, 0.44) | 0.757 | 1 | 3.74 (0.43) | 0.292 (−0.113, 0.697) | 0.145 | 1 |
| Placebo | 3.42 (0.35) | 3.63 (0.30) | 3.45 (0.34) | |||||||
| Ejection fraction (%) | Rapamycin | 58.27 (11.86) | 62.33 (13.96) | 1.63 (−6.41, 9.67) | 0.692 | 1 | 58.77 (7.29) | 1.98 (−9.10, 12.99) | 0.707 | 1 |
| Placebo | 58.55 (8.10) | 59.15 (10.00) | 56.79 (13.47) | |||||||
| Fractional shortening (%) | Rapamycin | 30.08 (9.75) | 30.98 (7.65) | −2.91 (−9.60, 3.78) | 0.524 | 1 | 31.85 (6.12) | −0.513 (−7.062, 6.037) | 0.87 | 1 |
| Placebo | 32.21 (8.50) | 33.89 (4.74) | 32.37 (6.55) | |||||||
| LVIDdN | Rapamycin | 1.463 (0.093) | 1.420 (0.093) | 0.003 (−0.103, 0.110) | 0.948 | 1 | 1.444 (0.131) | −0.026 (−0.180, 0.128) | 0.721 | 1 |
| Placebo | 1.456 (0.171) | 1.417 (0.113) | 1.470 (0.166) | |||||||
| LVIDsN | Rapamycin | 0.953 (0.146) | 0.916 (0.133) | 0.04 (−0.08, 0.16) | 0.489 | 1 | 0.920 (0.145) | −0.014 (−0.055, 0.102) | 0.856 | 1 |
| Placebo | 0.921 (0.151) | 0.876 (0.093) | 0.934 (0.157) | |||||||
| Peak E-wave velocity (m/s) | Rapamycin | 0.65 (0.11) | 0.70 (0.12) | −0.05 (−0.19, 0.01) | 0.511 | 1 | 0.67 (0.10) | −0.004 (−0.113, 0.105) | 0.938 | 1 |
| Placebo | 0.66 (0.20) | 0.74 (0.16) | 0.68 (0.11) | |||||||
| E to A wave ratio | Rapamycin | 1.15 (0.30) | 1.10 (0.22) | −0.05 (−0.29, 0.19) | 0.688 | 1 | 1.19 (0.12) | 0.201 (0.054, 0.347) | 0.011 | 0.154 |
| Placebo | 0.98 (0.27) | 1.15 (0.24) | 0.99 (0.16) | |||||||
| IVRT (ms) | Rapamycin | 83.08 (12.28) | 79.39 (13.01) | −9.32 (−21.35, 2.72) | 0.119 | 1 | 85.33 (13.42) | 2.232 (−11.523, 15.988) | 0.734 | 1 |
| Placebo | 84.10 (9.74) | 88.71 (9.77) | 83.10 (13.12) | |||||||
| AV Vmax (m/s) | Rapamycin | 1.45 (0.26) | 1.57 (0.25) | 0.02 (−0.31, 0.28) | 0.89 | 1 | 1.44 (0.20) | 0.003 (−0.203, 0.196) | 0.972 | 1 |
| Placebo | 1.49 (0.24) | 1.59 (0.32) | 1.44 (0.19) | |||||||
| AV VTI (cm) | Rapamycin | 17.76 (4.66) | 16.50 (1.87) | −1.14 (−7.45, 0.82) | 0.018 | 0.234 | 17.85 (4.60) | 0.743 (−3.200, 4.685) | 0.694 | 1 |
| Placebo | 17.63 (3.21) | 20.64 (4.24) | 17.10 (2.62) | |||||||
| PV Vmax (m/s) | Rapamycin | 0.89 (0.22) | 1.02 (0.24) | 0.08 (−0.19, 0.34) | 0.544 | 1 | 0.95 (0.17) | 0.068 (−0.091, 0.226) | 0.375 | 1 |
| Placebo | 0.83 (0.22) | 0.94 (0.27) | 0.88 (0.13) | |||||||
| LVPWdN | Rapamycin | 0.462 (0.073) | 0.485 (0.044) | −0.010 (−0.044, 0.062) | 0.7 | 1 | 0.452 (0.042) | −0.016 (−0.059, 0.026) | 0.418 | 1 |
| Placebo | 0.473 (0.061) | 0.475 (0.057) | 0.469 (0.039) | |||||||
| QTc (ms) | Rapamycin | 206.57 (6.48) | 206.99 (13.82) | −7.19 (−21.06, 7.22) | 0.304 | 1 | 196.13 (15.62) | −3.22 (−23.38, 29.82) | 0.8 | 1 |
| Placebo | 216.10 (17.32) | 214.17 (14.01) | 192.91 (33.67) |
AV Vmax, peak aortic velocity; AV VTI, aortic velocity time integral; IVRT, isovolumic relaxation time; LVIDdN, normalized left ventricular internal dimension in diastole; LVIDsN, normalized left ventricular internal dimension in systole; LVPWdN, normalized left ventricular free wall thickness at end diastole; PV Vmax, peak pulmonic velocity.
^Does not include baseline measurement from dog 17, which was lost due to software error.
*Per unit difference in the measure (95% confidence interval) associated with rapamycin (compared to placebo).
**2-sided test of the null hypothesis of no difference between the rapamycin group compared to placebo.
***2-sided test of the null hypothesis of no difference between the rapamycin group compared to placebo, adjusted for multiple comparisons using the Holm-Bonferroni step-down method.