Efficacy of exercise training in pulmonary arterial hypertension associated with congenital heart disease

Abstract

Background

The objective of this prospective study was to assess the efficacy of exercise training as add-on to medical therapy in patients with congenital heart disease associated pulmonary arterial hypertension (CHD–APAH).

Methods

Patients with invasively confirmed CHD–APAH received in-hospital exercise training for 3 weeks and continued at home. Efficacy parameters were evaluated at baseline, after 3 and 15 weeks. Medical treatment remained unchanged. Worsening events and survival rate were assessed in a follow-up period of 21 ± 14 months.

Results

Twenty consecutive CHD–APAH patients (16 female, 4 male, mean pulmonary arterial pressure 60 ± 23 mm Hg) were included. Patients significantly improved the mean distance walked in 6 min compared to baseline by 63 ± 47 m after 3 weeks (p < 0.001) and by 67 ± 59 m after 15 weeks (p = 0.001). Quality of life-score (p = 0.05), peak oxygen consumption (p = 0.002) and maximal workload (p = 0.003) improved significantly by exercise training after 15 weeks. The 1- and 2‐year survival rates were 100%, the transplantation-free survival rate was 100% after 1 year and 93% after 2 years.

Conclusion

Exercise training as add-on to medical therapy may be effective in patients with CHD–APAH and improved work capacity, quality of life and further prognostic relevant parameters. It was associated with an excellent long-term survival. Further randomized controlled studies are needed to confirm these results.

Introduction

Congenital heart disease–associated pulmonary arterial hypertension (CHD–APAH) is an important subgroup of associated PAH (APAH) which accounts for approximately 11% of all patients with PAH [1]. In about 0.8–1 of 1000 live births relevant CHD has been diagnosed. Today, in Western countries more than 90% of these children reach adulthood, in some cases with significant pulmonary vascular disease [2]. The prevalence of APAH in CHD in Germany is not known. European registry data suggest a prevalence of APAH in about 4–10% of adult CHD-patients [1], [3], [4]; up to 25–50% develop an Eisenmenger syndrome (ES) [5]. Patients with CHD–APAH had identical histological findings as idiopathic PAH (IPAH) [6] and revealed a markedly reduced exercise capacity and quality of life [4], [7]. ES had the worst exercise capacity compared to other forms of CHD–APAH [7]. All-cause mortality risk was more than 2-fold higher for CHD-patients with APAH compared with those without [8]. Estimated 1-, 2-, and 3-year survival rates in CHD–APAH-patients were 97%, 89% and 77%, respectively [9].

In contrast to IPAH, only few randomized controlled trials on advanced, disease-targeted medical therapy have been performed in CHD–APAH including drugs as bosentan (BREATHE-5 study) [5] and tadalafil [10] showing significant improvements of pulmonary hemodynamics and exercise tolerance. Positive effects for exercise capacity were also described for sildenafil, epoprostenol and ambrisentan in small, uncontrolled studies [10], [11], [12], [13]. Only few data are available on combination therapies, including 2 to or more PAH-targeted drugs [14], [15], [16]. However, the effect of advanced medical therapy on exercise capacity and quality of life seems to be very limited in this subgroup. Thus, especially patients with CHD–APAH may need additional therapeutic tools addressing their exercise capacity and quality of life. It is unclear whether and to which extent CHD or CHD–APAH-patients should perform sports or exercise training, especially with respect that their hypoxemia usually rapidly deteriorates during exercise. In patients with IPAH and other forms of APAH exercise training as add-on to optimized medical treatment has been shown to increase exercise capacity, quality of life, peak oxygen consumption, WHO-functional class (WHO-FC) in a randomized, controlled study [17] and in single arm studies [18], [19], [20] and possibly improved clinical outcome [19]. There are only few small uncontrolled studies showing a benefit of exercise training for exercise capacity in CHD-patients without PAH [21], [22], [23]. Except one report with 4 CHD–APAH-patients receiving rehabilitation [24] up to now there is no study focusing on the acute and long-term effect of exercise training in this cohort. The aim of this study was to prospectively assess the effects of exercise training on safety and prognostic relevant factors such as exercise capacity and quality of life in a cohort of patients with severe CHD–APAH and to analyze the 1- and 2‐year survival rates.