The impact of post-pulmonary embolism syndrome and its possible determinants

doi:10.1016/j.thromres.2018.09.048

Thrombosis Research

Volume 171, November 2018, Pages 84-91

https://doi.org/10.1016/j.thromres.2018.09.048 Get rights and content

Highlights

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Persistent dyspnea, reduced 6MWT and impaired HRQoL are independently associated.
•
Impaired post-PE recovery cannot simply be explained by patient comorbidities.
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Higher RV/LV-ratio at diagnosis predicted reduced 6MWT results.
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Unemployment and ongoing anticoagulation predicted impaired HRQoL.

Abstract

Introduction

Recent studies suggest that up to 50% of patients surviving pulmonary embolism (PE) may suffer from post-PE syndrome, which is defined by persistent dyspnea, impaired exercise capacity and/or decreased health-related quality of life (HRQoL). The possible determinants of post-PE syndrome are however not fully established.

Aims

To describe the differences between dyspneic and non-dyspneic PE-patients and to explore determinants of dyspnea, 6-min walking test (6MWT) and HRQoL.

Material and methods

In this cross-sectional study, consecutive patients diagnosed with PE between 2002 and 2011 at Østfold Hospital, Norway were identified from hospital registries. Patients were scheduled for clinical examination and a 6MWT. Dyspnea was assessed by the New York Heart Association (NYHA) classification. HRQoL was assessed with PEmb-QoL questionnaire. PE severity was assessed with PESI score, mean bilateral proximal extent of the clot and right-/left ventricle-ratio (RV/LV-ratio).

Results

203 patients participated in this study, of which 96 patients reported dyspnea (47%). Median time from diagnosis was 3.6 years (IQR 1.9–6.5). Patients without dyspnea performed better on 6MWT (488 m vs 413 m, p < 0.005) and had better HRQoL results (p < 0.005). None of the variables we examined, including Charlson comorbidity index, was independently associated with dyspnea. However, higher RV/LV ratio at diagnosis was significantly associated with reduced 6MWT at follow-up. Further, ongoing anticoagulation and unemployment were independently associated with impaired HRQoL.

Conclusions

PE-survivors complaining of dyspnea suffer from impaired HRQoL and reduced exercise capacity. Although PE-severity factors were associated with reduced exercise capacity, none of the examined factors were found to be independent determinants of dyspnea.

Introduction

Pulmonary embolism (PE) has classically been regarded as a curable disease with the majority of patients expected to fully recover without any sequelae. However, during the last decade several reports have revealed that up to 50% of long term PE survivors suffer from dyspnea, reduced health-related quality of life (HRQoL) and/or impaired exercise capacity, e.g. by 6-min walking test (6MWT) or cardiopulmonary exercise test [[1], [2], [3], [4]]. These observations have led to the proposition of a new syndrome called “post-PE syndrome” [5]. Although a clear definition of post-PE syndrome is still to be fully established, it is considered to be characterized by a combination of the following elements: persistent dyspnea, exercise capacity limitations and/or impaired HRQoL after a PE [5]. Chronic thromboembolic pulmonary hypertension (CTEPH), which also is suggested to fall under the post-PE syndromes umbrella, should be regarded as the most severe presentation of this ‘syndrome’ [6].

However, there are several knowledge gaps regarding post-PE syndrome. Firstly, the vast majority of studies reporting on possible long-term effects of PE have mainly focused on clinical outcome measures, e.g. recurrence, residual thrombosis and right ventricular dysfunction, rather than persistent dyspnea, which is the main manifestation of post-PE syndrome [7,8]. This is of particular clinical importance since it is the symptom of persistent dyspnea that mandates further evaluation in such patients [9,10]. Secondly, although associations between dyspnea, reduced exercise capacity and impaired HRQoL have been reported by previous studies, none have primarily aimed to evaluate independent associations between these measures. Thirdly, the pathophysiological basis and possible determinants of post-PE syndrome are still a subject of debate. Whereas some studies argue that the phenomenon is due to residual thrombosis, actual pathological remodeling of the pulmonary vasculature and the right side of the heart [11,12], other studies have suggested that the observed impairment is more likely due to patients' comorbidities and/or physical deconditioning [4,13,14]. From this perspective, there is a need for further research on post-PE recovery in order to better understand the impact, determinants and underlying pathophysiology of the post-PE syndrome.

The main purpose of this study was to characterize the post-PE syndrome. The specific objectives were: 1) To describe the differences in clinical, biochemical and radiological parameters as well as exercise capacity and HRQoL in patients with and without dyspnea; 2) To study whether there were independent associations between persistent dyspnea, reduced exercise capacity and impaired HRQoL; 3) To explore possible determinants of these measures; and 4) To evaluate if echocardiographic parameters were associated with either dyspnea and/or exercise capacity.

Section snippets

Study design

The details regarding inclusion and exclusion criteria of this cross-sectional study has previously been reported [3]. Briefly, patients who were objectively diagnosed with PE (i.e. by computed tomography pulmonary angiogram (CTPA) or high probability perfusion scintigraphy (V/Q-scan)) at Østfold Hospital Trust, Norway, between January 2002 and December 2011 and who were still alive in March 2012 were eligible for study participation. If patients had multiple separate episodes of PE between

Patients

The study flow chart is shown in Fig. 1. A total of 836 patients were identified for eligibility. After excluding 430 (51%) according to predefined exclusion criteria, 406 patients were found eligible and invited. Of these, 203 patients completed both the 6MWT and the HRQoL questionnaire. The index PE diagnosis was confirmed by CTPA in 186 patients and V/Q scan in 17 patients. Complete data for blood tests at follow up were obtained in 196 patients. Although the entire cohort was referred for

Discussion

In this study, we found that 47% of the patients had persistent dyspnea 3.6 years after an episode of PE. Patients with dyspnea had reduced exercise capacity and HRQoL compared to those without dyspnea. Further, an independent association was observed between these measures, hence objectively confirming the presence of the yet uncharacterized condition called post-PE syndrome. None of the predefined variables was found to be associated with dyspnea. However, we found that unemployment and

Conclusion

In conclusion, our study revealed that dyspnea is a frequent symptom in long-term PE survivors and that it is independently associated with limited exercise capacity and reduced HRQoL. These findings emphasize the existence and relevance of the post-PE syndrome and its impact on several aspects of the patients' well-being after PE. The underlying cause of post-PE syndrome seems, however, to be multifaceted and further research is needed in order to more clearly define this condition. Future

Conflict of interest

The authors state that they have no conflict of interest, except W. Ghanima, P.A. Sirnes and L.P. Jelsness-Jørgensen. W. Ghanima reports research grants from Bayer, Novartis and BMS and lecture and advisory board honoraria from Bayer, Amgen and Novartis. PA Sirnes reports lecture and advisory board honoraria from Novartis, Sanofi, Bayer and Merck Sharp & Dohme – none of which is relevant for the submitted work. L.P. Jelsness-Jørgensen reports unrestricted grants from Ferring pharmaceuticals and

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Acknowledgements

We would like to thank our study nurse Christina Roaldsnes for her immense efforts in recruiting the study patients.

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Health-related quality of life (QoL) impairment is common after pulmonary embolism (PE). Whether the severity of the initial PE has an impact on QoL is unknown.
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This was a convergent mixed-methods systematic review, including quantitative studies, using PROMs and qualitative studies with non-cancer-related PE patients. Items from each PROM and qualitative findings were categorised using an International Classification of Function linking process to allow for integrated synthesis.
A total of 68 studies using 34 different PROMs with 657 items and 13 qualitative studies with 408 findings were included. A total of 104 individual ICF codes were used, and subsequently sorted into 20 distinct categories representing patient concerns. Identified PROMs were found to adequately cover 17/20 categories, including anxiety, fear of bleeding, stress, depression, dizziness/nausea, sleep disturbance, pain, dyspnea, fatigue, activity levels, family and friends, socializing, outlook on life, and medical treatment. PROMs from the ICHOM core set covered the same categories, except for dizziness/nausea.
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Full Length ArticleThe impact of post-pulmonary embolism syndrome and its possible determinants

Highlights

Abstract

Introduction

Aims

Material and methods

Results

Conclusions

Introduction

Section snippets

Study design

Patients

Discussion

Conclusion

Conflict of interest

Funding

Acknowledgements

Eur. J. Intern. Med.

Chest

Chest

Blood Rev.

Thromb. Res.

Chest

J. Thromb. Haemost.

Respir. Med.

Respir. Med.

Am. J. Med.

J. Chronic Dis.

J. Thromb. Haemost.

J. Am. Soc. Echocardiogr.

J. Am. Soc. Echocardiogr.

Physiotherapy

Full Length Article
The impact of post-pulmonary embolism syndrome and its possible determinants