Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis

Ludovica Anna Cimini^{1

2}, Dieuwke Luijten^{3

2}, Stefano Barco⁴, Waleed Ghanima^{5

6

7}, Øyvind Jervan^{5

6}, Susan R Kahn^{8

9}, Stavros Konstantinides¹⁰, Daniel Lachant¹¹, Yoshihisa Nakano^{12

13}, Maarten Ninaber¹⁴, Josien van Es^{15

16}, Thijs van Mens³, Anton Vonk Noordegraaf¹⁵, Cecilia Becattini¹, Frederikus A Klok³

Affiliations

¹ Vascular and Emergency Medicine, University of Perugia, Perugia, Italy.
² L.A. Cimini and D. Luijten contributed equally and share first authorship.
³ Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Centre, Leiden, The Netherlands.
⁴ Department of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Internal Medicine, Østfold Hospital Trust, Grålum, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Haematology, Oslo University Hospital, Oslo, Norway.
⁸ Department of Medicine, McGill University, Montreal, QC, Canada.
⁹ Division of Internal Medicine and Division of Clinical Epidemiology, Jewish General Hospital/Lady Davis Institute, Montreal, QC, Canada.
¹⁰ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹¹ Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA.
¹² Department of Cardiology, Nagoya University Hospital, Nagoya, Japan.
¹³ Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁴ Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Department of Pulmonology, Amsterdam UMC, Cardiovascular sciences, VU University Amsterdam, Amsterdam, The Netherlands.
¹⁶ Department of Pulmonology, OLVG, Amsterdam, The Netherlands.

PMID: 39076522
PMCID: PMC11284598
DOI: 10.1183/23120541.01010-2023

Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis

Ludovica Anna Cimini et al. ERJ Open Res. 2024.

. 2024 Jul 29;10(4):01010-2023.

doi: 10.1183/23120541.01010-2023. eCollection 2024 Jul.

Authors

Affiliations

¹ Vascular and Emergency Medicine, University of Perugia, Perugia, Italy.
² L.A. Cimini and D. Luijten contributed equally and share first authorship.
³ Department of Medicine - Thrombosis and Hemostasis, Leiden University Medical Centre, Leiden, The Netherlands.
⁴ Department of Angiology, University Hospital Zurich, Zurich, Switzerland.
⁵ Department of Internal Medicine, Østfold Hospital Trust, Grålum, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁷ Department of Haematology, Oslo University Hospital, Oslo, Norway.
⁸ Department of Medicine, McGill University, Montreal, QC, Canada.
⁹ Division of Internal Medicine and Division of Clinical Epidemiology, Jewish General Hospital/Lady Davis Institute, Montreal, QC, Canada.
¹⁰ Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
¹¹ Division of Pulmonary and Critical Care Medicine, University of Rochester Medical Center, Rochester, NY, USA.
¹² Department of Cardiology, Nagoya University Hospital, Nagoya, Japan.
¹³ Department of Public Health and Health Systems, Nagoya University Graduate School of Medicine, Nagoya, Japan.
¹⁴ Department of Pulmonology, Leiden University Medical Center, Leiden, The Netherlands.
¹⁵ Department of Pulmonology, Amsterdam UMC, Cardiovascular sciences, VU University Amsterdam, Amsterdam, The Netherlands.
¹⁶ Department of Pulmonology, OLVG, Amsterdam, The Netherlands.

PMID: 39076522
PMCID: PMC11284598
DOI: 10.1183/23120541.01010-2023

Abstract

Introduction: Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE.

Methods: We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery (i.e. persistent symptoms, quality of life, exercise endurance). An odds ratio was pooled for perfusion defects or residual vascular obstruction and persistent symptoms using a random-effect model.

Results: 12 studies were included totalling 1888 PE patients; at a median of 6 months after PE (range 2-72 months), 34% had perfusion defects or residual vascular obstruction and 37% reported persistent symptoms. Among patients with perfusion defects or residual vascular obstruction, 48% (95% CI 37-60%, I²=82%) remained symptomatic during follow-up, compared to 34% (95% CI 20-51%, I²=96%) of patients without such defects. Presence of perfusion defects or residual vascular obstruction was associated with persistent symptoms (OR 2.15, 95% CI 1.66-2.78; I²=0%, τ=0). Notably, there was no association between these defects and quality of life or cardiopulmonary exercise test parameters.

Conclusion: While the odds of having persistent symptoms was higher in patients with perfusion defects or residual vascular obstruction after acute PE, a significant proportion of these patients reported no limitations. A possible causality between perfusion defects or residual vascular obstruction and residual functional limitation therefore remains to be proven.

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Conflict of interest statement

Conflict of interest: W. Ghanima reports receiving fees for participation in advisory boards from Amgen, Novartis, Pfizer, Principia Biopharma Inc. (a Sanofi Company), Sanofi, SOBI, Grifols, UCB, Argenx, Cellphire, Alpine, Kedrion, HiBio and Hutchmed, outside the submitted work; lecture honoraria from Amgen, Novartis, Pfizer, Bristol Myers Squibb, SOBI, Grifols, Sanofi and Bayer, outside the submitted work; and research grants from Bayer, BMS/Pfizer and UCB, outside the submitted work. Conflict of interest: Y. Nakano received speaker and lecturer fees from Bayer, Daiichi-Sankyo, Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Conflict of interest: F.A. Klok has received research support from Bayer, BMS, BSCI, AstraZeneca, MSD, Leo Pharma, Actelion, Farm-X, The Netherlands Organisation for Health Research and Development, The Dutch Thrombosis Foundation, The Dutch Heart Foundation, and the Horizon Europe Program, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose.

Figures

None — PE: pulmonary embolism; V′/Q′: ventilation/perfusion; CTPA: computed tomography pulmonary angiography. ^#: no meta-analysis performed due to heterogeneity.

**FIGURE 1**
Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram of the study. CTPA: computed tomography pulmonary angiogram; V′/Q′: ventilation/perfusion.

**FIGURE 2**
Presence of pulmonary perfusion defects or residual vascular obstruction and persistent symptoms during follow-up. CTPA: computed tomography pulmonary angiogram.

See this image and copyright information in PMC

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Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis

Affiliations

Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

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