“Rehab for all!” Is it too early in pulmonary arterial hypertension?

To the Editor:

Chronic pulmonary hypertension shares abnormalities found in chronic left heart failure and chronic respiratory failure, in which rehabilitation has been proposed [1, 2]. In a recent statement endorsed by the European Respiratory Society, Grünig et al. [3] proposed an exhaustive review of available data on rehabilitation in the setting of chronic pulmonary hypertension. The main messages proposed are “Specialised exercise training in patients with pulmonary hypertension appears to be effective, cost-efficient and safe.”

The task force should to be warmly thanked for this important document. However, while we fully share the hope that rehabilitation programmes may improve the lives of patients with pulmonary hypertension, we also believe that more data are needed to transform these experts' opinions into recommendations with a high level of evidence.

The current gold standard to assess the efficacy of any therapeutic intervention remains a randomised controlled trial, designed specifically to avoid related potential bias. As quoted by the authors, most of the current available evidence was provided by a single centre, questioning the scalability thereof to general practice. Moreover, all the current trials suffer from a high risk of bias (mainly performance bias and reporting bias), as illustrated in the last Cochrane review [4]. Although functional exercise capacities may improve with rehabilitation in patients with pulmonary hypertension as reported in chronic heart and respiratory failure, the results remain frail. The major limitation is related to the absence of controlled trials. Lack of long-term data following the rehabilitation programme is another limitation, as the potential effect of rehabilitation depends on the continuation of exercise.

The safety of each intervention is as important as its efficacy. Exercise occupies a paradoxical position in the field of pulmonary hypertension, particularly in patients with pulmonary arterial hypertension (PAH). For instance, the 2015 European guidelines [5] recommend supervised exercise training (IIB), but also advise against physical activity leading to distressing symptoms (recommendation IIIC). Although no concerns were raised from previous studies, the safety results are questioned in multicentre studies.

The common reluctance with rehabilitation is the potential deleterious haemodynamic effect. To date, only one study provides data on the haemodynamic effect of rehabilitation in patients with PAH [6]. Surprisingly, rehabilitation (performed in a single centre) was associated with improved haemodynamics, including cardiac output. These results call for a multicentre validation.

It also seems premature to us to conclude on the cost-effectiveness of rehabilitation, as there are still doubts as to its long-term efficacy and safety. The cost may differ from one country to another, but also from one organisation and one programme to another (inpatient rehabilitation in one or more centres; home-based rehabilitation programmes?)

We then hope that the on-going prospective, randomised trial (FONCE-HTAP trial, NCT02579954) will help to better assess the efficacy and safety of rehabilitation programme in the field of PAH, by addressing some of the questions raised in this correspondence. This trial includes a Zelen method also known as the “two-stage randomised consent design” [7] in order to build comparable groups, with the control group being unaware of the intervention group. This design protects the trial from a disappointment bias, which may lead to a pollution of the control group by the intervention (in this setting, an unsupervised auto-rehabilitation programme of patients randomised to the control group). Our multicentre trial also includes long-term training (52 weeks), with a home-based programme following hospital-supervised rehabilitation for the first 12 weeks. Haemodynamic assessment with right heart catheterisation during the study will allow us to confirm the safety of the intervention.

In conclusion, we share with the panellists the opinion that rehabilitation may significantly improve the functional capacity of patients, hopefully without a negative haemodynamic impact; however, we do consider that the evidence currently available is not sufficient to propose a grade I-A level of evidence.

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