Exercise training improves exercise capacity and quality of life in patients with inoperable or residual chronic thromboembolic pulmonary hypertension

Abstract

Background: Aim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).

Methods: Thirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline, after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6-46.6 months).

Results: All patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year survival rate was 94% and the 3-year-survival 86% respectively.

Conclusion: Training as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results.

Trial registration: ClinicalTrials.gov NCT01398345.

Figure 1. Individual changes in Six-Minute-Walking Distance (6MWD) after 3 and 15 weeks exercise training.

With the use of Wilcoxon Rank Test according to baseline walking distance, p<0.001 was obtained for the comparison to baseline with weeks 3 (n = 35) and p = 0.001 with week 15 (n = 22). The dotted line indicates the mean change from baseline in 6MWD (61±54 meters and 71±70 meters).

Figure 2. Mean SF-36 scores of Quality of life Subscales (SF-36 questionnaire) before and after Exercise Training.

At baseline (straight line), mean SF-36 scores were significantly reduced in comparison to respective values of a normal population (dotted line). After 15 weeks (dashed line), the 2 subscales of the SF-36 questionnaire physical functioning and vitality improved significantly. P-values are indicated vs. baseline. No significant improvement was found for role emotional (ROLEM), role physical (ROLPH), general health (GH), social functioning (SF), mental health (MH), bodily pain (PAIN) after training. With Bonferroni adjustment, values of p<0.005 preserve statistical significance. At baseline data of 28 patients, after 15 weeks of 23 patients were available and included.

Figure 3. Survival by Kaplan Meier Analysis.

Within a follow-up period of median 36.4 months (interquartile range 26.6–46.6 months) 6 patients deceased, 4 due to PH. One patient died due to lung cancer >4 years after baseline. In one patient cause of death remained unknown. The straight line indicates overall survival, with 97% after 1-year, 94% after 2-years and 86% after 3 years. The dashed line indicates 95% Confidence interval.