Pulmonary hypertension and exercise training: a synopsis on the more recent evidences

Abstract

The benefits of exercise training in virtually all humans, including those with a clinically stable chronic disease are numerous. The potential value lies in the fact that functional capacity is oftentimes significantly compromised. Exercise training not only play a role in reversing some of the pathophysiologic processes associated with chronic diseases but also improves clinical trajectory. Given the significant pathologic consequences associated with pulmonary hypertension and its implications for deteriorating right ventricular function as well as the perceived potential for a precipitous and possibly critical drop in cardiac output during periods of physical exertion, exercise training was historically not recommended for these patients. More recently, a promising body of literature demonstrating the safety and efficacy of exercise training (with benefit on exercise capacity, peak oxygen consumption and quality of life) in pulmonary hypertension patients has emerged, but the conclusion about the effects of exercise training were non-exhaustive and therefore there is still a lack of knowledge regarding exercise training for these patients. Thus, we aim to ascertain the current effectiveness of exercise rehabilitation for pulmonary hypertension by performing a brief overview on the latest currently available evidences in such an “at a glance” synopsis addressed to summarize/quantify the more recent existing body of literature.

KEY MESSAGES

• Exercise training was historically not recommended in pulmonary hypertension.

• Recently, exercise training safety-efficacy in pulmonary hypertension has emerged.

• Exercise training should be recommended in addition to optimal medical therapy.

Keywords:

• Pulmonary hypertension
• exercise training
• rehabilitation

Introduction

The benefits of exercise training in virtually all humans, including those diagnosed with a clinically stable chronic disease, are numerous [1–4]. The potential value of exercise training for patients diagnosed with a chronic disease lies in the fact that functional capacity is oftentimes significantly compromised. The underlying concept behind exercise training is that it plays a role in reversing some of the pathophysiologic processes associated with chronic disease and improves clinical trajectory (i.e. functional capacity, quality of life and prognosis). Perhaps the chronic disease population where the benefits of exercise training and its clinical acceptance, are most well established is in patients with heart failure [3–5]. Patients with pulmonary hypertension comprise another chronic disease population where the deficits in exercise capacity and prognostic outlook are comparable to, if not worse than, those seen in patients with heart failure [6–8]. Pulmonary hypertension is a chronic disease precipitated by one of several pathologic mechanisms, including idiopathic, genetic, congenital and associated connective tissue diseases such as scleroderma [9]. The gold standard for the diagnosis of pulmonary hypertension is a mean resting pulmonary artery pressure, measured by right heart catheterization, of 25 mmHg or more with a concomitant pulmonary capillary wedge pressure of 15 mmHg or less [9,10].

Because of the significant pathologic consequences associated with pulmonary hypertension and its implications for deteriorating right ventricular function as well as the perceived potential for a precipitous and possibly life threatening drop in cardiac output during periods of physical exertion, exercise training was historically not recommended for these patients. More recently, however, a promising body of literature demonstrating the safety and efficacy of exercise training in patients with pulmonary hypertension has emerged. The initial positive findings have increased enthusiasm and interest in this area, resulting in an acceleration of scientific inquiry; however, the conclusions about the effects of exercise training were non-exhaustive and therefore there is still a lack of knowledge regarding exercise training for patients with pulmonary hypertension.

Additionally, the recent European Society of Cardiology (ESC) / European Respiratory Society (ERS) Guidelines for the diagnosis and treatment of pulmonary hypertension stated that supervised exercise training should be considered in physically deconditioned patients with pulmonary hypertension under medical therapy. Thus, we aim to ascertain the current effectiveness of exercise rehabilitation for pulmonary hypertension by performing a brief overview on the latest currently available evidence in such an “at a glance” synopsis addressed to summarize and quantify the more recent existing body of literature. Our review is properly ranging from the Guidelines Publication date themselves (January 2016), in the aim to test at the same time the hypothesis that the Guidelines recommendations regarding supervised exercise training promotion in physically de-conditioned patients with pulmonary arterial hypertension whose status is clinically stable and on optimal pharmacological treatment could have increased the interest of the scientific community.

Methods

We conducted a systematic literature search in the electronic PubMed database using the medical subject heading keywords “exercise training” or “rehabilitation” and “pulmonary hypertension”. The search was limited to English language articles published from 1 January 2016 to 1 October 2017 and the results were filtered by “clinical trials” and “review”. From this search, we only included articles specifically addressing the effects of a supervised exercise training program in patients with pulmonary hypertension. All clinical trials and reviews published in a peer-reviewed journal concerning exercise training (aerobic, resistance, inspiratory muscle training or combinations of these) as an intervention for patients with pulmonary hypertension delivered through any setting (i.e. hospital, home, community or a combination of them), were included. In the aim to provide a broad cutting-edge outline of the state-of-the-art scientific remarks, no more specific inclusion and exclusion criteria were adopted.

Results

Literature search

The literature search resulted in a total of 549 potentially relevant studies from which a total of 14 articles were finally included in the review [11–24]: a summary of the included studies is provided in Table 1. Of the 14 studies retrieved, two were randomized controlled trials [15,24], one was a non-randomized controlled trial [20], three were single group pre/post design studies (i.e. retrospective analysis, pre/post test case series or prospective cohort study) [14,17,21] and eight were reviews [11–13,16,18,19,22,23].

Table 1. Summary of studies selected and included in the review.

Authors and year	Design	Main conclusion
González-Saiz et al. [15]	Randomized controlled trial (n = 20–20)	An eight-week exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables.
Ehlken et al. [24]	Randomized controlled Trial (n = 46–41)	Exercise training significantly improved peak oxygen consumption, hemodynamics and further clinically relevant parameters. The improvements of cardiac index indicate that exercise training may improve the right ventricular function.
Fukui et al. [20]	Prospective controlled study (n = 17–24)	The combination of balloon pulmonary angioplasty and subsequent cardiac rehabilitation is a new treatment strategy for inoperable chronic thromboembolic pulmonary hypertension to improve exercise capacity to near-normal levels and heart failure symptoms, with a good safety profile.
Bussotti et al. [17]	Pre/post test case series (n = 15)	Cardiorespiratory training is a suitable option for patients with pulmonary arterial hypertension in WHO functional class II/III thanks to improved exercise capacity and quality of life, which may allow them to achieve better outcomes.
Matura et al. [21]	Prospective cohort study (n = 15)	Women with pulmonary arterial hypertension may spend most of their time being sedentary and lower self-reported energy levels are associated with less daily activity. Interventions to improve symptoms such as fatigue may also increase physical activity levels in pulmonary arterial hypertension.
Talwar et al. [14]	Retrospective analysis (n = 18)	Patients with pulmonary hypertension benefit from a structured pulmonary rehabilitation program to improve their exercise capacity and should be enrolled in pulmonary rehabilitation programs as part of their management.
Morris et al. [16]	Systematic review with meta-analysis	In patients with pulmonary hypertension, exercise-based rehabilitation results in clinically relevant improvements in exercise capacity. Exercise training was not associated with any serious adverse events.
Babu et al. [22]	Systematic review without meta-analysis	There is evidence to recommend the use of exercise training as an adjunct to medical treatment in pulmonary arterial hypertension.
Leggio et al. [11]	Narrative/commentary extensive review with a specific focus	Exercise training could represent a reliable and effective unique therapy for both pulmonary and systemic hypertension although their significant differences in terms of etiology, physiopathology, consequences and treatment strategy.
Richter et al. [13]	Narrative/commentary extensive review with a specific focus	Exercise training is emerging as a promising additional therapy option for patients with pulmonary hypertension. Besides the impact of exercise training on functional capacity and pulmonary hemodynamics, recent studies have suggested that exercise training has anti-inflammatory effects.
Chia et al. [19]	Narrative/commentary extensive review	Exercise training in patients with pulmonary hypertension appears to have significant benefits on endurance, peak oxygen consumption, hemodynamics and skeletal muscle function.
Arena et al. [23]	Narrative/commentary extensive review	Clearly, exercise training is now recognized as a valuable medical intervention in virtually all patient populations, including those diagnosed with the left-sided heart disease-pulmonary hypertension phenotype.
Keusch et al. [12]	Straight/focused mini review	Pulmonary rehabilitation patients with pulmonary arterial hypertension is a recommended therapy in addition to optimal medical therapy with targeted drugs, if performed in a highly experienced team under expert supervision.
Madonna et al. [18]	Straight/focused mini review	Preclinical studies and clinical trials now support the concept that one new prescription for patients with pulmonary arterial hypertension should be exercise training.

Characteristics of all included studies

Considering the two randomized controlled trials and the non-randomized controlled trial [15,20,24], the exercise intervention and control groups consisted of 83 and 85 participants, respectively. Study duration ranged between 8–15 weeks and the exercise training line-up was a combination of supervised in-hospital and home-based outpatient training programs. The interventions included aerobic, muscle resistance and specific inspiratory muscle training [15], walking, bicycle ergometer and low-intensity resistance training of the lower limbs without specific training of respiratory muscles or upper limb muscles [20] and interval cycle ergometer training at low workloads, walking, dumbbell training of single muscle groups using low weights (500–1000 g) and respiratory training [24]; in the study by Ehlken et al. [24] mental training to improve their perception of their individual physical abilities and limits and psychological support was also offered; the study by Fukui et al. [20] was specifically aimed to determine safety and efficacy of cardiac rehabilitation initiated immediately following balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension. The frequency of exercise training was five sessions weekly (median), with a duration per session ranging from 20–40 [15] to 90 min (in intervals distributed over the day) [24]. In regard to outcome measures, brain natriuretic peptide levels, cardiopulmonary exercise testing variables, 6 min walking distance, health-related quality of life and functional class/status were assessed as endpoints in all these three studies, whereas right heart catheterization was performed only in two studies [20,24].

In the three single group pre/post design studies [14,17,21], a total of 48 participants were included. The exercise training line-up was a combination of supervised in-hospital and home-based outpatient training program only in one study [14] in which exercise tolerance was recorded as speed attainable on a treadmill and duration of exercise in minutes, but the most complete intervention description (i.e. sessions of aerobic and resistance exercise, inspiratory muscle reinforcement, slow breathing, relaxation and psychological support) and outcome evaluation (i.e. brain natriuretic peptide levels, cardiopulmonary exercise testing variables, 6 min walking distance, health-related quality of life and functional class/status) was provided in the pre-/post-test outpatient case series by Bussotti et al. [17]. In the third of these studies [21], daily physical activity was measured by accelerometry, brain natriuretic peptide levels were collected from the medical record and 6 min walking distance was measured only at baseline. Of note, it must be reminded that the retrospective analysis by Talwar et al. [14] could be affected by a potential selection bias, occurring if selection of subjects is somehow related to the outcome.

Of the eight reviews [11–13,16,18,19,22,23], one was a systematic review with meta-analysis [16], another one a systematic review without meta-analysis [22] and the other six consisted of four narrative/commentary extensive reviews [11,13,19,23] and two straight/focused mini reviews [12,18]. Of note, two extensive reviews were characterized by a specific focus: the suggestion of our study [11] was to examine and summarize the benefit of exercise training for both pulmonary and systemic hypertension and the study of Richter et al. [13] addressed the hypothesis that exercise training could have anti-inflammatory effects that could directly contribute to the therapeutic benefits in pulmonary hypertension.

Discussion

The idea that exercise training programs may potentially be beneficial for patients with pulmonary hypertension has become accepted only recently and the recent ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension stated that supervised exercise training should be considered in physically deconditioned patients with pulmonary hypertension under medical therapy (Class IIa – Level of Evidence B Recommendation) [11,25]. Of note, it could be speculated that the Guidelines recommendations regarding supervised exercise training promotion in physically de-conditioned patients with pulmonary arterial hypertension whose status is clinically stable and on optimal pharmacological treatment could have also promoted and increased the interest of the scientific community. Indeed, in spite of a relatively small time period, the literature search resulted in a total of 549 potentially relevant studies from which a total of 14 articles were finally included in the review [11–24]. Exercise-based rehabilitation for patients with pulmonary hypertension is now considered as a new adjunct treatment option in order to improve their functional capacity and quality of life. As a consequence, some proof of concept studies have been performed; most of them showing significant beneficial effects of exercise training, but the existing evidence appears still inconclusive and insufficient to result in the implementation of exercise programs in routine clinical care for patients with pulmonary hypertension. Our review is focused only on the more recent literature suggestions, in the aim to recapitulate and sum up the current knowledge. Hence, even if most of the included studies were observational studies and reviews, this review represents, however, most of the more recently published experience of exercise training in patients with pulmonary hypertension.

The more recent randomized controlled trial is the “WHOLEi +12” trial [15], aimed to determine the effects of an eight week intervention combining muscle resistance, aerobic and inspiratory pressure-load exercises on upper/lower-body muscle power and other functional variables in patients with pulmonary arterial hypertension and chronic thrombo-embolic pulmonary hypertension. Participants were allocated to a control (standard care) or intervention (exercise) group (n = 20 each) and the intervention included five, three and six supervised (in-hospital) sessions/week of aerobic, resistance and inspiratory muscle training, respectively. The primary endpoint was peak muscle power during bench/leg press; secondary outcomes included N-terminal pro-brain natriuretic peptide levels, 6 min walking distance, five-repetition sit-to-stand test, maximal inspiratory pressure, cardiopulmonary exercise testing variables (e.g. peak oxygen consumption), health-related quality of life, physical activity levels and safety. Adherence to training sessions was good and analysis of variance showed a significant interaction (group × time) effect for leg/bench press (p < .001/p = .002), with both tests showing an improvement in the exercise group (p < .001) but not in controls (p > .1) and also for five-repetition sit-to-stand test, maximal inspiratory pressure and peak oxygen consumption (p < .001 for all), indicating a training-induced improvement. No major adverse event was noted due to exercise. The main finding of this study is that relatively short-duration (eight weeks) but “complete” exercise intervention including aerobic, resistance and specific inspiratory muscle training is safe for patients with pulmonary arterial hypertension and yields significant improvements in muscle power and other functional variables, even if some methodological limitations should be noted, such as the fact that exercise effects on hemodynamics were not assessed and that the program failed to induce a significant improvement in several secondary endpoints including 6 min walking distance.

The other randomized controlled trial provided by Ehlken et al. [24] investigated the impact of exercise training (interval cycle ergometer training at low workloads at seven days a week, walking, dumbbell training of single muscle groups using low weights and respiratory training started in-hospital for three weeks and continued at home for the following 12 weeks) on peak oxygen consumption, as an important prognostic factor in patients with severe pulmonary arterial hypertension and chronic thrombo-embolic pulmonary hypertension and right heart failure; this trial was also aimed to provide insights into the effects of exercise training on invasively measured hemodynamics. Eighty-seven patients with pulmonary arterial hypertension and inoperable chronic thrombo-embolic pulmonary hypertension on stable disease-targeted medication (unchanged during the study period) were randomly assigned to a control and training group. Non-invasive assessments and right heart catheterization at rest and during exercise were performed at baseline and after 15 weeks. Primary endpoint was the change in peak oxygen consumption. Secondary endpoints included changes in hemodynamics. The study results showed a significant improvement of peak oxygen consumption in the training group (p < .001). Cardiac index at rest and during exercise, mean pulmonary arterial pressure, pulmonary vascular resistance, 6 min walking distance, quality of life and exercise capacity also significantly improved by exercise training. Bearing in mind that right heart catheterization was an optional assessment in this study, low-dose exercise training at 4–7 days/week as add-on to pulmonary arterial hypertension-targeted medication significantly improved peak oxygen consumption and cardiopulmonary parameters such as pulmonary vascular resistance and cardiac index at rest and during exercise, leading to an increase in exercise capacity and quality of life, suggesting that this therapy can improve right ventricular function and other important prognostic parameters.

The non-randomized controlled trial [20] included in this review addresses the important issue to determine safety and efficacy of cardiac rehabilitation initiated immediately following balloon pulmonary angioplasty in patients with inoperable chronic thrombo-embolic pulmonary hypertension who presented with continuing exercise intolerance and symptoms on effort. Forty-one consecutive patients with inoperable chronic thrombo-embolic pulmonary hypertension who underwent their final balloon pulmonary angioplasty with improved resting mean pulmonary arterial pressure and who suffered from remaining exercise intolerance were divided in a cardiac rehabilitation group participating in a 12-week program of one-week in-hospital training followed by an 11-week outpatient plan and in a control group. Cardiopulmonary exercise testing, hemodynamics and quality of life were assessed before and after the program. At week 12, peak oxygen consumption, percent predicted peak oxygen consumption, peak workload, and oxygen pulse significantly improved in the cardiac rehabilitation group compared to the control group, with a tendency towards improvement in mental health-related quality of life. Quadriceps strength and heart failure symptoms significantly improved in the cardiac rehabilitation group and during the program no patient experienced adverse events or deterioration of right-sided heart failure or hemodynamics as confirmed via catheterization. Even if this study lacked randomization during group assignment although it was prospectively designed with a control group, it provides evidence that the combination of balloon pulmonary angioplasty and subsequent cardiac rehabilitation could represent a new treatment strategy for inoperable chronic thrombo-embolic pulmonary hypertension to improve exercise capacity to near-normal levels and heart failure symptoms, with a good safety profile.

In regard to the three single group pre/post design studies [14,17,21], the retrospective analysis by Talwar et al. [14] showed that patients with all types of pulmonary hypertension and varying functional class show improvement as measured by treadmill exercise speed and median exercise duration from a structured pulmonary rehabilitation program, suggesting that all these patients should be enrolled in rehabilitation programs as part of their management in addition to pharmacological therapy and regardless of their functional class. Accordingly, the pre/post test case series by Bussotti et al. [17] indicated cardiorespiratory training in an outpatient service as a suitable option for patients with pulmonary arterial hypertension in advanced functional class due to improved exercise capacity and quality of life, which may allow them to achieve better outcomes. The prospective cohort pilot study by Matura et al. [21], even if with a small sample size of women, concluded that patients with pulmonary arterial hypertension may spend most of their time being sedentary and that lower self-reported energy levels are associated with less daily activity, hence suggesting that interventions to improve symptoms such as fatigue may also increase physical activity levels, although it must be reminded that higher physical activity levels could increase the energy level of individuals as well.

The systematic review with meta-analysis provided by Morris et al. [16] was aimed to assess the efficacy and safety of exercise-based rehabilitation for patients with pulmonary hypertension. Primary outcomes were exercise capacity, adverse events during the intervention period and health-related quality of life. Secondary outcomes included cardiopulmonary hemodynamics, functional class, clinical worsening during follow-up, mortality and changes in B-type natriuretic peptide. All randomized controlled trials focusing on exercise-based rehabilitation programs for pulmonary hypertension were included and the results suggested that supervised exercise-based rehabilitation is likely to be safe for patients with pulmonary hypertension whose status is stable on medical therapy. Moreover, the rehabilitation can lead to meaningful improvements in exercise capacity, whilst clinical importance of improvements in health-related quality of life is less clear. Similarly, the systematic review without meta-analysis due to data heterogeneity by Babu et al. [22] systematically analyzed the effects of exercise training on exercise capacity in pulmonary arterial hypertension and the conclusion was that exercise training appears to be a promising intervention as an adjunct to medical therapy though close monitoring is required while evaluating exercise capacity.

Lastly, to briefly summarize the conclusion of the six narrative extensive/mini reviews [11–13,18,19,23], their findings consistently suggested that an exercise training program positively influences exercise tolerance and functional capacity in patients with pulmonary hypertension and that physicians need to become aware of the positive effects of this non-pharmacological intervention that can improve the integrated care of these patients. In regard to the two extensive reviews characterized by a specific focus, our study [11] was aimed to examine and summarize the benefit of exercise training for both pulmonary and systemic hypertension. In conclusion, our compelling hypothesis that the exercise training could represent a reliable and effective unique therapy for both pulmonary and systemic hypertension, although their significant differences (i.e. etiology, physiopathology, consequences and treatment strategy), seems to be supported and confirmed by a large body of clinical data and experimental evidences. The study of Richter et al. [13] addressed the hypothesis that exercise training could have anti-inflammatory effects that could directly contribute to the therapeutic benefits in pulmonary hypertension. The very interesting conclusion was that, besides the impact of exercise training on functional capacity and pulmonary hemodynamics, recent studies have suggested it to also have anti-inflammatory effects, although it is not yet known if these effects contribute to the therapeutic benefits of exercise training in pulmonary hypertension.

In light of these data and previous information, it appears that pulmonary rehabilitation in pulmonary hypertension patients should be considered a recommended therapy in addition to optimal medical therapy, if performed in a highly experienced team under expert supervision [11,12]. Supervised rehabilitation should be implemented by centers experienced in both pulmonary hypertension patient care and rehabilitation of compromised patients and be especially tailored to groups of pulmonary hypertension patients. It leads to significant improvements in symptoms, exercise capacity and quality of life, even if the pathomechanisms are not yet fully understood. Patients starting exercise training have to be in stable condition on optimized medical therapy [11,12]. In close collaboration with and supervision by a pulmonary hypertension expert center, specially tailored exercise training for pulmonary hypertension patients is relatively safe. It is essential to use a low workload exercise protocol with careful individual adjustments, to avoid overloading of patients. Ideally, patients should fully participate in a comprehensive exercise training program that is individually tailored to optimally improve physiologic function and clinical outcomes [11,12]. It is also important to recognize that “something is better than nothing” and a primary goal, particularly at the onset, is the transition from a completely sedentary lifestyle to some level of routine physical activity that is sustainable over the long-term [11,23]. Moreover, a key issue that has not been thoroughly addressed to this point is the impact of exercise training on the pulmonary arterial system itself, which directly ties to lifestyle intervention and its potential to lower pulmonary artery pressure in patients with pulmonary hypertension. This is a highly relevant question for this field of research: does exercise training, through an improvement in pulmonary arterial vasorelaxation and/or architecture, elicit a significant reduction in pulmonary artery pressure that could potentially contribute to altering the clinical trajectory of patients with pulmonary hypertension in a favorable manner? These hypotheses need to be confirmed by a large body of clinical data and experimental evidences and further future in-depth large clinical studies with longer follow-up duration are required to determine whether exercise training can be used to improve long-term clinical outcomes among these patients in the real world.

Conclusions

This brief overview on the latest evidence largely confirm that exercise training in patients with pulmonary hypertension appears to have significant benefits on endurance, peak oxygen consumption, hemodynamics and skeletal muscle function and still represents a very actual and attractive scientific topic with constantly growing interest and body of evidences. The magnitude of improvement in 6 min walking distance is similar to that seen with pharmacotherapy. All pulmonary hypertension patients should undergo a thorough medical assessment prior to exercise and have access to experienced clinicians during the exercise period. Although an intensive inpatient exercise training program has been shown to be beneficial, such program is often not available. A less intensive outpatient program may be more accessible, but its effectiveness requires further investigation. Components of a suitable exercise program that require further investigation include strength training, aerobic/endurance training and respiratory muscle training. Despite these limitations, exercise training in pulmonary hypertension has a good safety profile with few serious adverse effects and should be encouraged as part of a multidisciplinary treatment program. Finally, even if exercise training is associated with significant improvement in exercise capacity, cardiorespiratory fitness and quality of life among patients with pulmonary hypertension, future studies with longer follow-up duration are needed to determine whether exercise training can be used to improve long-term clinical outcomes among these patients in the clinical, real-world setting.

There is no doubt that physical activity is one of the most important modifiable factors of our lifestyle and that it also has important beneficial effects on preventing and treating cardiovascular diseases [11]. Even small improvements in the habitual physical activity level may have favorable effects on health [11]. Comparatively, physical activity could be characterized by a pharmacological powerful and beneficial effect, at any age [11].

In summary, the results of our brief overview on the latest currently available evidence addressed to summarize the more recent existing body of literature largely confirm, extend and amplify the concept that exercise training in patients with pulmonary hypertension appears to have significant benefits. The recent ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension Guidelines recommendations regarding supervised exercise training promotion in physically de-conditioned patients with pulmonary arterial hypertension whose status is clinically stable and on optimal pharmacological treatment surely could have also promoted and increased the interest of the scientific community as well. Supervised exercise-based rehabilitation is likely to be safe for patients with pulmonary hypertension whose status is stable on medical therapy and can lead to meaningful improvements in exercise capacity. Clinical importance of improvements in health-related quality of life is less clear. Although it is possible that programs with an inpatient component may confer a greater magnitude of benefits, it must be acknowledged that these are not available in many parts of the world and some have speculated that clinically meaningful benefits could be still achieved with outpatient programs: while logical, large randomized controlled trials are necessary to compare these rehabilitation settings. It is also possible that patients with pulmonary hypertension could safely undertake rehabilitation in standard pulmonary or heart failure rehabilitation programs, although different exercise prescription and monitoring practices appear necessary. Nonetheless, rehabilitation in patients with pulmonary hypertension is a recommended therapy in addition to optimal medical therapy with targeted drugs if performed in a highly experienced team under expert supervision and should be implemented by centers experienced in both pulmonary hypertension patient care and rehabilitation of compromised patients.

Exercise training definitely appears to be a promising intervention as an adjunct to medical therapy though close monitoring is required while evaluating exercise capacity. Considering the lack of methodological rigor and duration, better quality evidence and long-term trials are required, if exercise training is to become a part of the evidence-based recommendations for management of patients with pulmonary hypertension.

Disclosure statement

No potential conflict of interest was reported by the authors.