Introduction

Chronic thromboembolic pulmonary hypertension (CTEPH) leads to increased vascular resistance and progressive right heart failure resulting from occlusion of the proximal pulmonary arteries by fibrotic intravascular material in combination with secondary microvasculopathy of the vessels [1]. Patients with CTEPH are typically prone to exercise limitations and, in severe cases, are movement-restricted if not confined to bed rest because of reduced O₂ delivery to the periphery and impaired skeletal muscle diffusion capacity (i.e., the capacity to transport atmospheric oxygen into the mitochondria is limited) [2]. Pulmonary endarterectomy (PEA) is an elective procedure for the surgical treatment of CTEPH [3-14] and consists of the removal of chronic thromboembolic material from the entire pulmonary arterial tree via a median sternotomy utilizing cardiopulmonary bypass [8,15]. Successful surgery relies on three main principles: (1) the surgery must be performed on both lungs; (2) cardiopulmonary bypass with periods of circulatory arrest is essential to achieve adequate exposure in the face of copious bronchial blood flow; and (3) true endarterectomy in the plane of the media must be accomplished [8].

The first attempt to surgically remove clots from the pulmonary artery was described by Trendelenburg at the beginning of the 20th century [16]. Since the early 1970s to late 1980s [17-22], PEA has been increasingly performed in the Netherlands, Sweden, France, Japan, Mexico, Finland, South Africa, Germany, Austria, Italy, Chile, Spain, Israel, Denmark, the United Kingdom, Poland, China, Turkey, Belgium, the Czech Republic, Brazil, Canada, Taiwan, Korea, Russia, India, and Bulgaria [15,23-49]. The University of California, San Diego, serves as the international reference center [6,50,51] and has performed 5,000 procedures as of July 2024.

The in-hospital mortality rate of PEA is estimated to be <5%, with survival rates ≥90% at 3 years. To increase and preserve these figures, centers performing PEA should meet an annual volume of at least 50 procedures [1], with 33 cases to 40 cases per year defining high-volume centers [52]. Indeed, the 30-day mortality rates decrease as the number of procedures increases [53]. A carefully monitored postoperative rehabilitative intervention after PEA should be considered a standard of care according to the European Respiratory Society statement on CTEPH, and it is a viable option even in inoperable cases [1].

Data from the United States Chronic Thromboembolic Pulmonary Hypertension Registry, encompassing 750 patients, contribute to profiling the characteristics of patients undergoing PEA [54]. Five hundred and sixty-six out of 750 patients underwent PEA; the median age was 57 years (range, 44–67 years), 52.7% were male, and the body mass index (BMI) was 30.4 kg/m² (range, 26.1–36.3 kg/m²) [54]. Similarly, data from an international registry that included one Canadian and 26 European centers described the characteristics of 386 patients who underwent surgery; the median age was 60 years (range, 18–64 years), and 54.1% were males [55].

Although PEA is increasingly performed worldwide, information on the effects of acute and subacute postoperative rehabilitation in patients with CTEPH after PEA is scarce, and there is currently no special focus on the role of rehabilitation during postoperative recovery.

This study aimed to investigate the effects of acute and subacute postoperative rehabilitation on functional exercise capacity, dyspnea, and quality of life (QoL) in patients with CTEPH who underwent PEA.

Study design

This study was a systematic review of seven primary databases (Table 1). The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to design this review [56]. The databases were searched for articles published from database inception until February 2025. Two keyword entries, “pulmonary endarterectomy” and “rehabilitation,” were combined into a search string using the Boolean operator AND (Table 1). Filters for document types were applied, excluding letters to the editor, conference proceedings, and reviews. No filters were applied for age, sex, or publication date.

Inclusion and exclusion criteria

To be included, citations had to be published in English, French, Spanish, or Italian describing postoperative rehabilitation in adult patients who underwent PEA. Citations not describing postoperative rehabilitation and those involving patients aged <18 years were excluded.

After duplicates were removed, the remaining documents were screened for eligibility based on their abstracts. For articles with abstracts that met the inclusion criteria, full texts were screened for suitability, and confirmed citations were considered eligible for the final analysis. The search was completed on February 28, 2025.

Results

The initial search returned 152 articles, and 101 citations were screened after removing duplicates. At the end of the selection process, five documents were included in the final analysis (Fig. 1). One of the five articles was a prospective interventional study [57], one was a case report [58], and three were retrospective observational studies [59-61] (Table 2). Three of these five studies were conducted in Italy, one in Korea, and one in Germany. Of 204 patients, 95 (47%) were male (Table 2). In one study [61], the New York Heart Association (NYHA) class was determined pre- and post-PEA, and patients gained significant improvements postoperatively, with the majority (90%) dropping from NYHA class IV preoperatively to class II postoperatively. In another study [59], NYHA class was determined at the time rehabilitation commenced, with most patients (>70%) in classes III and IV.

Functional exercise capacity

The 6-minute walk test (6MWT) is used to measure response to medical interventions in patients with moderate-to-severe heart or lung disease, including pulmonary hypertension [62,63]. Although optimal reference values are not precisely defined in healthy adults, studies have determined that in adult men and women, the median 6-minute walk distance (6MWD) is 580 m and 500 m, respectively [62,64]. Similarly, the 6MWD was estimated to be 630 m among a population of 51 healthy individuals aged 50 to 85 years [62,65].

Data from the United States Chronic Thromboembolic Pulmonary Hypertension Registry indicate that the median 6MWD was 334 m (range, 235–406 m) before PEA [54]. Similarly, data from a European-Canadian Registry indicate that the median 6MWD was 341 m (range, 20–700 m) [55].

In a large cohort study of 499 patients (54.9% males) aged 57.5 years (range, 11–84 years) evaluating long-term outcomes after PEA, 257 patients could walk 346.1±127.3 m at the 6MWT preoperatively. At the 15-year follow-up, the 6MWD was 422.9±122.0 m in 173 patients [53].

It is estimated that 6MWD at 1 year after PEA can increase from 69%±4% to 87%±3%, correlating with the clinical and hemodynamic severity of CTEPH [66].

The present review determined that in patients with CTEPH pre-PEA, the 6MWD ranged between 284.7 m and 371.95 m (Table 3), as extracted from two studies involving 77 patients with a mean age of 57.6±12.4 years and 53.4±15.3 years, respectively (Table 3) [57,61]. To the same extent, it was extrapolated that at 6 to 12 weeks post-PEA, after having attended postoperative rehabilitation, patients could walk between 434.1 m and 483.6 m in the 6MWT. In comparison, at 22 weeks, patients could walk 493.4 m (Table 3) [57,61].

After a 3-week postoperative rehabilitation program in one study, most patients achieved a minimal clinically important difference in the 6MWT (Table 3) [59].

Although the 6MWT requires patients to walk unassisted and bear the effort of walking along an established path, the daily walk (DW) distance during rehabilitation or normal activities does not require patients to perform a specific motor task. Therefore, it has been assumed that the DW distance can be used to determine the motor abilities of patients who underwent PEA, particularly during acute postoperative recovery, when they may not be able to perform the 6MWT. In one study, it was found that after an extended stay of 9.5 days (range, 3–20 days), patients could achieve a DW distance of 750 m (range, 60–2,300 m) and that men, patients aged <60 years, and those with a BMI ≥25 kg/m² performed better than women, patients aged >60 years, and those with a BMI ≤25 kg/m², as shown in Table 3 [60]. Based on the available data, the 6MWD and DW pre- and/or post-PEA trends are shown in Fig. 2.

Postoperative rehabilitation also expedited and facilitated the functional recovery of patients with complications necessitating extracorporeal membrane oxygenation (ECMO) support after PEA (Table 3) [58]. The use of ECMO as rescue therapy for the management of perioperative complications during PEA (e.g., reperfusion pulmonary edema, endobronchial hemorrhage, and right ventricular failure) not amenable to conventional cardiorespiratory support or preoperatively as a bridge to PEA has been demonstrated to be an effective therapeutic option, with 5-year survival rate post-ECMO of >70% [67,68]. However, the rehabilitation of patients undergoing ECMO has become a standard of care, as highlighted in the literature [69,70], even during the coronavirus disease 2019 pandemic [71].

Dyspnea and perceived exertion after pulmonary endarterectomy

Exertional dyspnea or dyspnea at rest is a characteristic symptom in patients arriving for PEA preoperatively [2,8,54]. The patients included in the present review experienced relief from dyspnea postoperatively. Indeed, in two studies [57,61], the scores on both the Borg and visual analog scales improved after patients attended a postoperative rehabilitation program (Table 3). However, alternative instruments to quantify dyspnea in patients before and after PEA could be explored to verify whether, for example, the Modified Borg Scale [72] and Barthel Index Dyspnea (BI-d) [73] can provide more detailed information. Indeed, Modified Borg Scale scores 0–10, with lower scores indicating less dyspnea, can simplify the scoring, particularly during postoperative acute rehabilitation. In addition, BI-d provides more complex and detailed information on the intensity of symptoms during the execution of daily activities, and for this specific reason, could contribute to defining patients’ deterioration or progress with more precision. The BI-d score ranges from 0 (absence of dyspnea) to 100 (maximal dyspnea perceived), and it has been calculated that the minimal clinically important difference ranges from 6.5 to 9 points in patients with chronic obstructive pulmonary disease (COPD) without chronic respiratory failure and from 7.5 to 12 points in patients with COPD and chronic respiratory failure [74]. As dyspnea is a primary symptom in patients with CTEPH, similar to those with COPD, the administration of BI-d before and after PEA can help identify the aspects of daily activities that benefit most from surgery and postoperative rehabilitation.

Quality of life

In the present review, QoL was evaluated using Short Form-36 Health Survey (SF-36) at 3 weeks and 22 weeks post-PEA, and improvements were observed in both the physical component summary (PCS) and mental component summary (MCS) scores, as shown in Table 3. The SF-36 questionnaire comprises 36 questions organized into eight domains aggregated into two summary scores, the PCS and MCS. The SF-36 scores range from 0 to 100, with higher scores indicating better QoL [75]. Unlike the present review, where SF-36 was administered at 3 weeks and 22 weeks post-PEA, a study among 136 patients with a mean age of 49.4±12.7 years (42.6% women) who had undergone PEA reported SF-36 data available both preoperatively and at 1 year post-PEA [76]. In that study, significant differences were observed between SF-36 pre-PEA and at 1-year follow-up in both the PCS (34.33±7.30 vs. 42.59±9.42 points; p<0.001) and MCS (37.05±7.89 vs. 47.65±7.93; p<0.001). In the study by Kamenskaya et al. [76], QoL was better and sustained over a longer follow-up period than that shown in the SF-36 data in Table 3. However, no information was provided on rehabilitation, leaving room for further consideration, including to what extent QoL improvements are related to surgery alone or postoperative rehabilitation. This may require further analysis. The investigation encountered difficulties in delineating the specific domains of QoL that rehabilitation influenced during the postoperative phase. Effects on the mental components of QoL were less pronounced than those on motor function, complicating the derivation of conclusive insights into the overall impact of rehabilitation on QoL. Indeed, QoL in patients who underwent PEA is a matter of increasing interest, and recently, a single-center study provided further insights into this specific aspect [77]. In that research, 49 patients returned the RAND-36 questionnaire, which included the same items and eight domains as those in the SF-36 [78]; in addition, 47 participants returned the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR), a patient-reported outcome measure of QoL explicitly designed for patients with pulmonary hypertension [79]. The latter contains 65 items in three domains: symptoms, activity, and QoL, with higher scores indicating worse QoL and greater functional limitations [79,80]. For RAND-36, the mean time from PEA to evaluation was 8.5 years (range, 1–24 years), and the most affected domains were physical role and physical functioning [77]. For CAMPHOR, the mean time from PEA to evaluation was 5.9 years (range, 0.4–20 years), and the mean scores across domains were 4, 2.5, and 4 points for activity, QoL, and symptoms, respectively [77].

Rehabilitation before and after pulmonary endarterectomy

Given the increasing number of procedures performed, defining and quantifying the rehabilitative outcomes after PEA is of increasing interest. Patients who undergo PEA echo the cardiac surgery pathway and share preoperative functional limitations.

Postoperative rehabilitation after PEA is characterized by various aspects, depending on the care setting (Fig. 3). However, preoperative rehabilitation has not yet been explored in this patient population. In this regard, one crucial aspect that could be of interest for preoperative rehabilitation is the management of exertional dyspnea; therefore, there is potential for implementing respiratory techniques that enhance patient comfort (e.g., relaxed breathing and breathing control). Simultaneously, educational programs that concentrate on customizing motor activities to individual needs can assist patients in becoming accustomed to movement and in preparing better for surgery. Patients who have undergone PEA are still prone to postoperative peripheral oxygen desaturation and dyspnea on exertion, particularly during the initial recovery phase, when active mobilization and becoming accustomed to exercise are the primary goals. Muscle deconditioning is often observed in patients after PEA because of prolonged periods of inactivity or reduced mobility due to preoperative exertional dyspnea and peripheral oxygen desaturation.

Rehabilitation in the intensive care setting

Immediately after surgery, physiotherapy plays a crucial role in airway clearance in the intensive care unit (ICU) because of impaired mucus transport during mechanical ventilation and other pulmonary complications such as atelectasis, dysventilation phenomena, and impaired respiratory drive [81-84]. Manual techniques, including patient positioning, breathing control, chest wall vibration, postural drainage, and assisted coughing, can significantly contribute to expediting patient progression to intermediate care settings [85]. During the ICU stay, deep breathing exercises without mechanical devices are undoubtedly a viable option for reducing atelectasis, increasing lung volume, facilitating mucus clearance, and improving gas exchange. These exercises should be proposed to patients regardless of their layout because of the ease and flexibility of their execution [86]. During supervised deep breathing exercises, patients are instructed to inhale slowly and as deeply as possible, hold their breath, and exhale the air slowly through their mouths. A treatment session consists of five breaths to 15 breaths repeated up to three times, avoiding hyperinflation and fatigue [86]. Breathing exercises can also be performed using mechanical devices that provide positive expiratory pressure [86-88]. The use of mechanical (positive expiratory pressure devices) or manual techniques primarily depends on patient cooperation and sedation status in the ICU. Briefly, the initial postoperative recovery phase is dedicated to managing respiratory function and preventing or treating pulmonary complications; passive and active range of motion exercises are initiated concurrently [89].

Rehabilitation in the sub-intensive setting

As soon as patients are cleared to a sub-intensive setting, respiratory therapy still plays a crucial role, and incorporating respiratory techniques into motor activities contributes to maintaining and ensuring adequate oxygenation during this early recovery phase. In this review, two studies [60,61] described respiratory physiotherapy during the in-hospital subacute phase, focusing on lung ventilation and airway clearance. Additionally, it should be highlighted that during the first 3 weeks after PEA, the primary rehabilitative goal is motor reconditioning in the absence of complications. Physical reconditioning should be implemented, considering that cardiac and pulmonary remodeling can be achieved several weeks postoperatively. Therefore, fatigue and dyspnea on exertion may occur, and oxygen supplementation may be necessary during motor rehabilitation activities following surgery. During this phase, strengthening exercises targeting large muscle groups, such as the quadriceps, gluteus, and triceps, can be performed with or without assistive devices such as cycle ergometers [60]. Walking training and facilitating the resumption of daily activities are essential components of in-hospital postoperative rehabilitation to allow patients to become accustomed to motor exercises. At this stage, the frequency, intensity, and duration of rehabilitative sessions are approximately 1 hour twice per day, 5 to 6 days per week, for 2 to 3 weeks, depending on the length of hospital stay [57,60].

Long-term postoperative rehabilitation

At an advanced stage, post-acute functional recovery is achieved through rehabilitative programs (lasting 3 weeks, 5–6 days per week) that incorporate aerobic exercise training to achieve maximal functional exercise capacity [57,59,61].

However, the rehabilitative journey of patients who have undergone PEA could be further personalized in cases of inoperable or postoperative residual CTEPH, as in the presence of peripherally located thrombi (associated with lower improvements in pulmonary hemodynamics) [90]. There have been cases of inoperable patients or those in whom PEA is ineffective, resulting in residual CTEPH. Under these circumstances, rehabilitation can contribute to the preservation of residual motor function. Indeed, in a study involving eight patients (aged 64±12 years) with inoperable or residual CTEPH, a 12-week home-based pulmonary rehabilitation program improved functional exercise capacity and QoL [90]. The program included one in-hospital class per week in which patients performed 40 to 60 minutes of supervised exercises, including endurance training on a cycle ergometer. The home-based sessions consisted of lower and upper limb strength training, respiratory exercises, and walking. At the completion of rehabilitation, patients experienced significant improvements, walking an average of 415.4±57.0 m at 12 weeks compared to 382.1±45.4 m at baseline (p<0.01) in the 6MWT. In addition, significant changes were detected in QoL with the activity domain of the St. George’s Respiratory Questionnaire score improving from 65.0±10.6 points at baseline to 52.9±14.2 points at 12 weeks (p<0.05) [90].

In another study, 35 patients (aged 61±15 years) with inoperable or residual CTEPH participated in a program consisting of a 3-week inpatient rehabilitation period followed by 12 weeks of home-based exercise [91]. The program included interval bicycle ergometer training, strengthening exercises, walking, and respiratory training, 5 days per week. The 6MWD improved by 61±54 m at 3 weeks (p<0.001) and by 71±70 m at 15 weeks (p=0.001) relative to the baseline distance (408±108 m) [91].

Safety

Exercise in patients with pulmonary hypertension is not without risks, and close monitoring must be guaranteed during rehabilitative sessions. In a study of 183 patients with different types of pulmonary hypertension (idiopathic pulmonary arterial hypertension, heritable pulmonary arterial hypertension, associated pulmonary arterial hypertension, and CTEPH), 13.6% experienced adverse events, consisting of presyncope, syncope, supraventricular tachycardia, and hemoptysis, during a 3-week in-hospital training program [92]. In another study of 35 patients, of whom 33 had inoperable CTEPH and two had residual CTEPH after PEA, during a 3-week rehabilitation program, five patients had an adverse event, with two cases related to exercise (syncope and herpes zoster) [91].

Limitations

The present study has some limitations. First, a small number of citations and patients were included; however, it is worth noting that the number of procedures has increased recently, rising from 1,580 cases as of 2002 to 5,000 as of July 2024 at the highest-performing center in San Diego, California [51,93]. These figures are consistent with the assumption that PEA is a relatively new procedure; therefore, the available data on rehabilitation indicate that high-volume centers are still few [52]. Second, the inability to extrapolate comprehensive patient demographic information from the analyzed studies presents challenges in generalizing the results to a broader population. This limitation indicates that the conclusions drawn may not be universally applicable to all patients who undergo PEA. Third, in the present study, functional exercise capacity was measured using the 6MWT; therefore, comparisons with other methods (e.g., the 1-minute sit-to-stand test) were not possible.

Finally, the extent to which specific domains of QoL rehabilitation influence postoperative outcomes could be a matter of debate because the effects on mental components did not echo motor function, the former being less robust. Therefore, from this study, it is challenging to extrapolate absolute hypotheses, although, from the data analyzed here, QoL improved over time postoperatively.

Conclusion

This study confirms that postoperative rehabilitation after PEA can be divided into several phases. Acute in-hospital rehabilitation is crucial to help patients become accustomed to movement and prepare for more intense activities. The 6MWD and DW are the most effective instruments for detecting motor changes during recovery, with the latter being calculated even in the early postoperative phase. It was also found that patients could walk a median daily distance of 750 m and climb at least one flight of stairs at hospital discharge. After attending a 3- to 12-week subacute postoperative rehabilitation program, patients could walk a 6MWD that ranged from 434.1 to 483.6 m.

Contextually, significant progress in QoL can be expected in both physical and mental domains, although the physical components are most likely to display marked results linked to rehabilitation.

Another crucial aspect of this review is that exercise must be closely monitored, as adverse events (in particular, syncope and presyncope) related to motor activity are possible. However, fatal consequences were not reported.

This systematic review underscores the need for further research involving larger sample sizes and diverse methodologies to enhance our understanding of the effects of postoperative rehabilitation on functional exercise capacity, dyspnea, and QoL in patients who underwent PEA.

Article information

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Fig. 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart.

Fig. 2.

Six-minute walk distance and daily walk before and after pulmonary endarterectomy. ICU, intensive care unit; PEA, pulmonary endarterectomy; DW, daily walk; 6MWD, 6-minute walk distance.

Fig. 3.

Postoperative rehabilitation is divided into phases depending on the care setting. 1: Acute, typically intensive care unit (ICU). 2: Subacute, sub-intensive environment and cardiac ward. 3: Post-acute, rehabilitation facility. 4: Long-term, home or outpatient programs. ADL, activities of daily living.

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