Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

Abstract

Introduction: The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH).

Methods: Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years.

Results: Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET.

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

Trial registration: ClinicalTrials.gov: NCT00491309.

Figure 1

Individual changes in six-minute-walking distance (6MWD) after 3 and 15 weeks exercise training. Using the Wilcoxon rank test, P < 0.001 was obtained for the comparisons with baseline at week 3 (n = 21) and P = 0.003 for comparison to week 15 (n = 11). The dashed line indicates the mean change from baseline in 6MWD (67 ± 52 meters and 72 ± 35 meters).

Figure 2

Mean short-form Health Survey Questionnaire (SF-36) scores for quality of life subscales before and after exercise training. At baseline (straight line), mean SF-36 scores were significantly reduced in comparison to respective values from a normal population (dotted line). After 15 weeks (dashed line), 5 scales of the SF-36 questionnaire improved significantly: physical functioning, general health perception, social functioning, mental health and vitality. P-values are indicated vs. baseline. No significant improvement was found for role emotional (ROLEM), role physical (ROLPH) and bodily pain (PAIN) after training. With Bonferroni adjustment, values of P < 0.005 were considered statistically significant. Data were available and were included in the analyses for 21 patients studied at baseline and for 18 patients studied at 15 weeks.

Figure 3

Workload compared to the Borg scale. The figure shows a significant increase in workload after 3 and 15 weeks (P = 0.007 and P = 0.008). The Borg scale remained unchanged (P = 0.171 and P = 0.105, respectively) although significantly higher workloads and higher heart rates during exercise were attained. Values are indicated as the mean, and the bars represent standard deviation. The columns represent workload (measured in Watt) and the dotted line the Borg Scale.

Figure 4

Survival by Kaplan-Meier analysis. Within a follow-up period of 2.9 ± 1.9 years (25 ± 13 months), two patients died due to pulmonary hypertension (PH), one died due to carcinoma, and one patient underwent lung transplantation. The dashed line indicates mortality due to connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH), the straight line indicates overall survival, and the dotted line indicates transplantation-free survival. The Kaplan-Meier PAH-survival rate was 100% after 1, and 2 years, and 80% after 3 years. The overall survival rate was 100% after 1, and 2 years, and 73% after 3 years. The transplantation-free survival rate was 95% after 1 and 2 years.