Results
Forty patients were randomized after hospital discharge between September 2006 and October 2009 (21 patients in the training group and 19 patients in the control group) and then followed until 1 year after hospital discharge. A diagram summarizing the flow through the study is presented in Figure 1. One year after hospital discharge 18 patients in the intervention group and 16 patients in the control group were analyzed for the primary and secondary outcomes. Inclusion was terminated in October 2009 to finish the study at the scheduled completion date of November 2010. Baseline characteristics of participants are presented in Table 1. Anthropometric characteristics, the prevalence of underlying diagnoses, the moment of pretransplant assessments, the duration of hospital stay, the types of surgery performed and the presence of early acute rejection before hospital discharge were comparable between groups. Additional information on immunosuppressive drug regimens during the first year following transplantation is provided in Table S1.
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Figure 1.
Diagram showing the flow of participants through each stage of the randomized trial.
At least four full days of activity monitor data were collected for all patients during the four measurements (Pre-LTX, Baseline, 3 months and 1 year after hospital discharge). Severe limitations in daily physical activity, physical fitness and quality of life were observed before transplantation (Table 2, Table 3 and S5). Immediately following the exercise training intervention (3 months after hospital discharge) statistically significant differences between groups in daily walking time, movement intensity during walking and daily steps (Table 2) and in physical fitness (6-minute walking distance and quadriceps force [Table 3]) were observed. No statistically significant differences in handgrip force, respiratory muscle force, quality of life and mood status were observed at this stage (Tables S2, S5 and S7). Nine months later (12 months following hospital discharge) statistically significant differences were maintained. In addition, time spent in moderate intense (≥3METS) physical activity (Table 2), peak work rate during an incremental exercise test on a cycle ergometer (Table 3) and two items of the SF-36 health status questionnaire (physical functioning and role limitations due to physical functioning, Table S5) were significantly different between groups. No differences in mood status (Table S2) or any of the other parameters of participation in daily physical activity, physical fitness and quality of life were observed. Results of the broken line regression revealed that the evolution of quadriceps force was different during the two phases of the study. While the slopes were significantly different in favor of the intervention group during the first 3 months (intervention period; difference in slopes: β= 4.9, p = 0.001) this was not the case (difference in slopes: β=−0.2, p = 0.663) during the follow-up period (Figure 2). The slopes of daily walking time (Figure 2) were also significantly different in the first 3 months (β= 4.2, p = 0.011) and showed a trend to be different during the follow-up period (β= 1.5, p = 0.085). No significantly different slopes in either intervention or follow-up period were detected for other variables that showed statistically significant differences between groups at either 3-month or 12-month follow-up (e.g. 6MWD, Figure 2).
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Figure 2.
Progression of quadriceps force, 6-minute walking distance (6MWD) and daily walking time during the intervention period (Baseline to 3 months) and during the follow-up period (3 months to 1 year).*, significant difference between groups; #, significant difference in slopes between groups.
Significantly lower values for both average 24 h ambulatory diastolic and systolic blood pressure measurements were observed in the intervention group 1 year after hospital discharge (Table S6). More antihypertensive medication had to be prescribed in the control group (Table S3) and a lower incidence of patients that had to be treated for diabetes in the intervention group (1/18 [6%]) in comparison with the control group (4/16 [25%]) was observed. Due to the small sample size this clinically meaningful difference did however not reach statistical significance (Table S6). No differences in weight gain, blood lipid profiles and bone mineral density were observed between groups (Tables S4 and S6).