The scope of PE can range from a small, clinically undetectable subsegmental embolism, which occurs in over 50% of patients with proximal deep vein thrombosis (DVT), to bilateral high-grade vascular occlusion with circulatory instability [6].

Untreated, the mortality rate of PE is 25% to 30%. The 30-day mortality rate is 6.2% for central PE and 3.7% for distal, i.e. segmental or subsegmental, PE, amounting to 5.4% overall [7]. One-year mortality is 8.1%, with a wide variation between countries [8].

In addition to the acute thromboembolic event, PE can have serious long-term health consequences [9]. These include reduced physical performance, psychosocial effects, and significant limitations in health-related quality of life (HRQoL) [8][10]. The risk of recurrence is significant, as is the risk of developing chronic consequences, including chronic thromboembolic pulmonary hypertension (CTEPH).

In CTEPH, a scarred remodelling of the embolic material leads to obstruction of part of the pulmonary circulation and to an increase in pulmonary vascular resistance. Around 3% of survivors of an acute pulmonary embolism develop this clinical condition which should definitely be diagnosed since targeted treatment options are now available [11][12].

The current guidelines recommend diagnosing pulmonary hypertension after at least 3 months of effective anticoagulation [5][13]-[15].

Post-pulmonary embolism syndrome (PPES) was defined around 10 years ago [9][16]. More than 50% of all patients who have survived a pulmonary embolism complain of persistent shortness of breath or symptoms of fatigue after at least 3 months of effective anticoagulation. This cannot be explained by signs of pulmonary hypertension or other lung changes. These symptoms are clear, but less pronounced than in CTEPH, and can persist for up to 10 years. A structured follow-up is necessary in order to identify the presence of PPES [17][18].

In a prospective multicentre observational cohort study, 1,017 patients were followed up at 3, 12 and 24 months after acute symptomatic pulmonary embolism. CTEPH was diagnosed in 1.6% of patients after a median of 129 days (estimated cumulative 2-year incidence 2.3 (1.2 - 4.4)%). The cumulative incidence of PPES was 17% (12.8% - 20.8%). Patients with PPES had a higher risk of rehospitalization and death, and a poorer quality of life (QoL) than patients without PPES. Thus, every 6th patient or more was still symptomatic after two years [19].

A follow-up examination of all patients 3 - 6 months after the event clarifies whether dyspnea or other functional limitations that were not present before the event are still present. If this is the case, a (repeat) echocardiogram is recommended. In any case, it should be ascertained whether criteria for CTEPH are present [6][20][21].

Despite its frequent occurrence and potential physical and psychosocial consequences for those affected, there are no structured aftercare or rehabilitation programs in the first year after PE, apart from a few follow-up appointments. Moreover, there is a lack of detailed patient information, such as brochures or tutorials (exception: [22]). This is in contrast to global follow-up care, for example, post-myocardial infarction. The current ESC/ERS guidelines provide a class 1C recommendation for an “integrated patient care program” based on country-specific infrastructures [6]. The program should integrate interdisciplinary outpatient and inpatient care by physicians and nursing staff using standardized treatment protocols. Patient education, including a positive influence on persistent risk factors (especially smoking, obesity and a lack of exercise) should be part of the program. Personal preferences, the family, and the social and professional environment should all be taken into account. This concept was confirmed by the results of a study of 42 CTEPH patients [23].

The German guideline recommends cardiac rehabilitation (CR) after PE [24][25]. Early, symptom-adapted mobilization and activating therapies reduce the likelihood of post-thrombotic syndrome in patients with PE and DVT [17]. The use of muscle pumps promotes venous decongestion of the affected extremity and effectuates (possibly complete) symptom relief [26]. Immobilization has a negative effect on the reduction of edema in the leg and patient symptoms [17].

Only a few studies have focused on the effects of a structured rehabilitation or aftercare program following PE. Studies on the safety and effectiveness of prevention and relief of post-thrombotic symptoms in patients with DVT are presented in a recent systematic review [27]. Specific rehabilitation programs for DVT and PE-patients are not yet available.

The aim of this review is to summarize and evaluate the available evidence on the feasibility, safety and effectiveness of exercise-based (CR) or pulmonary rehabilitation (PR) for these patients in order to gain insights for the establishment of such interventions.

In a first prospective randomized study, the safety and efficacy of early physical exercise in DVT and PE patients were evaluated over a period of 12 weeks. In the intervention group, maximum oxygen uptake (peak VO₂) and total weekly physical activity improved significantly. No clinical adverse events occurred under therapeutic anticoagulation [29].

Results of a retrospective cohort study (N = 422) showed no adverse events during a 3-week inpatient CR, especially in direct relation to physical activity and recent PE. In this feasibility-study, the PE-patients did not receive a specific program, but completed the multimodal CR together with other patients who were mainly attending CR due to coronary artery disease (CAD) [32].

In order to evaluate the prognosis of PE-patients during a 3-week CR, and in the first 12 months after completion of CR, a prospective cohort study was conducted by the same researcher. The rehospitalization rate was 3.9% during CR, and 28.6% in the follow-up phase. The mortality rate was 5.7% [33].

A retrospective study evaluated the effectiveness of participation in a 6-week outpatient exercise-based PR in 22 PE-patients with persistent exertional dyspnea (NYHA classification > 2), defined as PPES [28]. The median follow-up time was 39 months. Participation led to significant extension of the 6MWD. In addition, significant improvements were observed Pi_max, Watt_max, maximum strength of the upper and of the lower extremities. After an average follow-up period of 39 months after PR, 78% of patients reported an improved health status [28].

A small single-center RCT in 24 intermediate–high-risk acute PE-patients demonstrated that high-intensity-interval-training (HIIT) within a CR setting can be leveraged for acute PE patients as a safe and effective modality improving exercise capacity, pulmonary and RV function, as well as HRQoL significantly [31].

In the first multicenter randomized clinical trial, 140 PE-patients were randomly assigned to IG and CG [34]. The IG participated in an eight-week supervised home-based rehabilitation, starting 2 - 3 weeks following hospital discharge. Monitoring was carried out by telephone and through personal visits. The CG received one or more telephone consultations from specialized nursing staff. No relevant adverse events related to physical activity were observed. No significant benefits of the intervention were observed with regard to the primary endpoint or secondary endpoints. Reasons for this may include low comorbidity among PE-patients and the influence of the CG towards an active lifestyle due to the detailed examinations at the study entry. The latter may have reduced the CG's fear of physical activity after a severe acute illness [34].

In 27 PPES patients, participation in a 12-week outpatient rehabilitation led to a significant improvement in exercise intensity, PE-specific quality of life (PEQoL) and the extent of fatigue [37].

An analysis of cardiac magnetic resonance parameters in 26 PE-patients after an 8-week PR revealed, despite a significant improvement in dyspnea, only a non-significant reduction in the absolute longitudinal strain of the right ventricle and right ventricular mass, while the remaining parameters remained unchanged. The effects of PR were therefore not primarily attributable to cardiac adaptation. [41].

The results of a RCT involving 211 PE-patients suffering from persistent dyspnea 6 to 72 months after the event revealed that participation in an 8-week rehabilitation led to an improvement in physical performance and PEQoL. but it did not show superiority on its primary endpoint (with a non-significant difference in the Incremental Shuttle Walk Test (ISWT) of +53.0 m (p = .035)). No relevant adverse events occurred during the study [38]. These results were sustained and confirmed in a follow-up examination six months later. This confirms long-term health benefits of rehabilitation participation for PE-patients [43].

In a randomized pilot study, the IG participated in an 8-week home-based-exercise-program, while the CG received general recommendations on physical activity. Significant improvements in 6MWD, QoL and physical activity were observed in both groups, with no significant group differences. With regard to the primary endpoint of safety (defined as new or worsening pulmonary artery embolism during the eight-week program, syncope, hospital admission), the program was confirmed to be safe [39].

Recently published preliminary data on 225 PE-patients who began a 4-week inpatient exercise-based rehabilitation 8 days after the acute event are of interest. In all patients, treatment led to improvements in dyspnea and exercise capacity, regardless of the initial treatment for PE. However, the degree of improvement showed a clear correlation with existing comorbidities, particularly obesity and chronic obstructive pulmonary disease (COPD). There were no side effects from rehabilitation. All patients underwent a final echocardiography and pulmonary CT angiography after 4 weeks: the results showed normalization of right heart geometry and function in 93% and almost complete resolution of pulmonary artery thrombi in group 1. In group 2, significant residual thrombi remained in 61% of patients. After pharmacological or mechanical revascularization, the echocardiographic findings normalized after the first week of rehabilitation. The authors conclude that timely inpatient rehabilitation is suitable for high- and medium-risk patients. It is also suitable for low-risk patients, but they can participate on an outpatient basis [42].

41 CTEPH patients who had previously undergone balloon angioplasty due to inoperability were randomly assigned to an IG with immediate 12-week CR and a CG with usual care. The remaining mean pulmonary artery pressure was 24.7 ± 5.5 mmHg, and physical performance remained impaired. After 12 weeks, maximum oxygen uptake (VO₂), percentage of maximum oxygen uptake, oxygen pulse, and maximum power in watts had improved significantly in the IG compared to the CG. No adverse clinical events or worsening hemodynamics were observed [30].

A sample of 45 patients who had previously undergone pulmonary endarterectomy (PEA) due to CTEPH participated in a three-week inpatient CR, followed by a 16-week home-based exercise. The exercise program was well tolerated and no serious side effects were documented. Within the first three weeks and over the following 19 weeks, there was a consistent improvement in physical performance, peakVO₂ and hemodynamic parameters, including right heart catheterization results [35].

In an RCT involving 12 patients with pulmonary arterial hypertension (PAH), including 2 patients with CTEPH, an 8-week inspiratory muscle training (IMT) significantly improved 6MWD but not peakVO₂ [36].

A three-week structured multidisciplinary CR in 84 patients after pulmonary endarterectomy (PAE), involving exercise, education, nutritional and psychosocial counseling, improved 6MWD, echocardiographic hemodynamic parameters and arterial oxygen saturation [40].

The results of a meta-analysis show that exercise is well tolerated by CTEPH patients and can improve physical performance, mean pulmonary artery pressure (mPAP) and quality of life. Larger multicenter studies are needed to confirm the efficacy and safety of exercise in these patients [44].