Skip to main content

Patent foramen ovale revealed by COVID-19 pneumonia

Abstract

Background

Platypnea-orthodeoxia syndrome (POS) is a rare condition characterized by dyspnoea (platypnea) and arterial desaturation in the upright position resolved in the supine position (orthodeoxia). Intracardiac shunt, pulmonary ventilation–perfusion mismatch and others intrapulmonary abnormalities are involved.

Case presentation

We report a case of POS associated with two pathophysiological issues: one, cardiac POS caused by a patent foramen ovale (PFO) and second, pulmonary POS due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interstitial pneumonia. POS has resolved after recovery of coronavirus disease 2019 (COVID-19) pneumonia.

Conclusions

Right-to-left interatrial shunt and intrapulmonary shunt caused by SARS-CoV-2 pneumonia contributed to refractory hypoxemia and POS. Therefore, in case of COVID-19 patient with unexplained POS, the existence of PFO must be investigated.

Peer Review reports

Background

COVID-19 causes an atypical acute respiratory distress syndrome (ARDS) and becomes pandemic [1, 2]. Hypoxemia is the mean feature of SARS-CoV-2 pneumonia and results from several pathologic ways that are not completely understood [3].

Positional hypoxemia related to POS is caused by right-to-left shunting (RTLS) bypassing pulmonary oxygenation due to intracardiac or intrapulmonary abnormalities. It is defined by a drop in oxygen saturation greater than 5% from supine to upright position [4]. PFO is common in adult population and is harmless for most of the time except under pathologic conditions [5]. We present a COVID-19 patient who presented refractory positional hypoxemia associated with unknown PFO.

Case presentation

A 55-year-old man presented in emergency department with fever and dyspnoea for 1 week. His medical history was notable for kidney transplant 2 years ago and he was treated with tacrolimus (blood level on admission 13 µg/L, normal range 5–7 µg/L), mycophenolate mofetil (750 mg twice a day) and methylprednisolone (4 mg once a day).

The arterial blood gas analysis at room air showed PaO2 60 mmHg, PaCO2 22 mmHg, pH 7.40 and P/F ratio 286. Creatinine at admission was 1.63 mg/dL (normal range 0.70–1.20). ECG showed no abnormalities. The patient had a positive swab for SARS-CoV-2 by reverse transcriptase polymerase chain reaction (RT-PCR). Chest Computed tomography (CT) scan showed bilateral peripheral ground glass opacities with crazy paving patterns (Fig. 1). He was hospitalized in the Middle Care Unit and was treated with oxygen therapy and Boussignac continuous positive airway pressure (BCPAP, PEEP 3 cmH2O, FiO2 50%) and dexamethasone (6 mg once a day) for ten days.

Fig. 1
figure 1

CT scan on admission. a Bilateral ground glass opacities predominantly with a peripheral lung distribution. b Crazy paving pattern in the right middle lobe and in the inferior lobes bilaterally

A second chest CT was performed 2 weeks after because of the lack of respiratory improvement, which showed replacement of the ground glass opacities with enlarged inferior consolidating aeras and a worsening course of disease (Fig. 2). As opportunistic infection was suspected, the patient underwent bronchoalveolar lavage and empirical antibiotics (Piperacillin/tazobactam 4 g, 4 times a day) was started.

Fig. 2
figure 2

CT scan after 2 weeks of hospitalisation. In comparison with the initial CT scan, ground glass opacities have been replaced by much more extensive consolidation lesions, especially predominant at the bases. Majoration of bilateral consolidations present in the middle and inferior lobes

Given the isolation of Corynebacterium propinquum on a quantitative culture 104 colony forming unit /ml, antibiotics were continued for 7 days. Tocilizumab (8 mg/kg) and convalescent plasma (IgG titers > 1:320) were administered on day 10 and day 18 after admission respectively.

Nevertheless, the symptomatology of the patients didn’t improve and he still complained of breathlessness while sitting or standing and orthodeoxia was confirmed by SpO2 measurements (SpO2 98% on 5L/min O2 by Filtamask (FiO2 40%) in the supine position vs SpO2 89% on 5L/min O2 by Filtamask in the seated position).

Bubble-contrast transthoracic echocardiography revealed RTLS on Valsalva due to PFO (Fig. 3).

Fig. 3
figure 3

Bubble contrast echocardiography. Two-dimensional transthoracic echocardiography image showing a right-to-left shunt upon release of the Valsalva maneuver

Progressively general condition favourably improved, the patient was discharged 1 week later with oxygen therapy (1 L/min). The arterial blood gas analysis showed PaO2 76 mmHg, PaCO2 38 mmHg, pH 7.46 and P/F ratio 316. Two weeks after discharge, orthodeoxia disappeared and SpO2 was 95% in supine position and 95% in standing position without oxygen therapy.

Discussion

We report a case of POS which is a rare clinical syndrome defined by orthostatic dyspnoea and a quantified fall in arterial oxygen saturation of 5% or a PaO2 of 4 mmHg in upstand position [4, 6, 7]. Hypoxemia related to anatomical defect such as PFO requires a concomitant secondary functional dysfunction as pulmonary hypertension or increase of intrathoracic pressure (Valsalva) [8].

PFO is the most common congenital heart abnormality of foetal origin [5]. 25% of the adult population have a PFO which is not harmful in general as it was the case in our patient who performed a lot of sport activities [9]. Nonetheless, under pathologic conditions, PFO is capable to bypassing the pulmonary circulation as blood flow goes directly from the right to left atrium [5]. A number of pathological conditions have been associated with PFO such as stroke, or POS [9].

In ARDS, V/Q mismatch and right-to-left intrapulmonary shunting lead to hypoxaemia [10].

ARDS caused by SARS-CoV-2 is atypical and lead to different phenotypes in COVID-19 patients [1, 2]. Hypoxaemia in COVID-19 patients is not fully understood and seems to result from several pathogenic mechanisms such as alteration of hypoxic pulmonary vasoconstriction (HPV), coagulopathy and V/Q mismatch [11]. Lower lobes are commonly afflicted in COVID-19 patients and these are the gravitationally dependent lung compartments in upright positioning which is in favour of occurring of orthodeoxia also [11].

In this case, the patient presented several causes contributing to RTLS and POS.

First, in this case of unknown PFO, right-to-left interatrial shunt (RTLIAS) clearly can exacerbate hypoxaemia in a patient with COVID-19 pneumonia. In presence of abnormal elevated right atrial pressure caused by COVID-19 pneumonia, blood can pass across the interatrial communication [12].

Second, hypoxic lung diseases such as COVID-19 pneumonia is characterized by V/Q mismatch with regional differences in apical and basal regions of the lungs. In upright position, apical regions of the lungs act like a dead space, increasing V/Q mismatch and leading to a physiologic shunt and to POS. Furthermore, diffuse vascular damages and coagulopathy induced by SARS-CoV-2 disturb physiologic regulation of HPV and increases V/Q mismatch. Injured basal lungs are then pathologically hyperperfused in COVID-19 patients and contribute also to hypoxemia [11].

RTLIAS such as PFO is not the only cause of POS and other mechanisms that participate in decrease in lung oxygenation are also implicated in this case. Intrapulmonary shunt caused by SARS-CoV-2 pneumonia certainly contributed to refractory hypoxemia as well as V/Q mismatch. But the pulmonary hypertension due to HPV could also have triggered RTLS in a patient with an interatrial defect. Therefore, in case of COVID-19 patient with unexplained POS, the existence of PFO must be investigated.

Availability of data and materials

Not applicable.

Abbreviations

ARDS:

Acute respiratory distress syndrome

BAL:

Bronchoalveolar lavage:

BCPAP:

Boussignac continuous positive airway pressure

COVID-19:

Coronavirus disease 2019

CPAP:

Continuous positive airway pressure

CT:

Computed tomography

ECG:

Electrocardiogram

FiO2:

Fraction of inspired oxygen

HPV:

Hypoxic pulmonary vasoconstriction

PaO2:

Partial pressure of oxygen

PaCO2:

Partial pressure of carbon dioxide

PEEP:

Positive End Expiratory Pressure

PFO:

Patent foramen ovale

pH:

Potential of hydrogen

POS:

Platypnea-orthodeoxia syndrome

RTLIAS:

Right-to-left interatrial shunt

RTLS:

Right-to-left shunting

RT-PCR:

Reverse transcriptase polymerase chain reaction

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

SpO2:

Peripheral oxygen saturation

V/Q:

Ventilation–perfusion

References

  1. Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, et al. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020;46:1099–102.

    CAS  Article  Google Scholar 

  2. Rajendram R, Kharal GA, Mahmood N, Puri R, Kharal M. Rethinking the respiratory paradigm of COVID-19: a ‘hole’ in the argument. Intensive Care Med. 2020. https://doi.org/10.1007/s00134-020-06102-6.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Masi P, Bagate F, d’Humières T, Al-Assaad L, Abou Chakra L, Derumeaux G, et al. Is hypoxemia explained by intracardiac or intrapulmonary shunt in COVID-19-related acute respiratory distress syndrome? Ann Intensive Care. 2020;10:4–6.

    Article  Google Scholar 

  4. Tan GP, Ho S, Fan BE, Chotirmall SH, Tan CH, Lew SJW, et al. Reversible platypnea-orthodeoxia in COVID-19 acute respiratory distress syndrome survivors. Respir Physiol Neurobiol. 2020;282:103515.

    CAS  Article  Google Scholar 

  5. Calvert PA, Rana BS, Kydd AC, Shapiro LM. Patent foramen ovale: Anatomy, outcomes, and closure. Nat Rev Cardiol. 2011;8(3):148–60.

    Article  Google Scholar 

  6. Agrawal A, Palkar A, Talwar A. The multiple dimensions of Platypnea-Orthodeoxia syndrome: a review. Respir Med. 2017;129:31–8.

    Article  Google Scholar 

  7. De Vecchis R, Baldi C, Ariano C, Giasi A, Cioppa C. Platypnea–orthodeoxia syndrome: orthostatic dyspnea and possible pathophysiological substrates. Herz. 2017. https://doi.org/10.1007/s00059-016-4479-4.

    Article  PubMed  Google Scholar 

  8. Cheng TO. Platypnea-orthodeoxia syndrome: Etiology, differential diagnosis, and management. Catheter Cardiovasc Interv. 1999;47(1):64–6.

    CAS  Article  Google Scholar 

  9. Homma S, Messé SR, Rundek T, Sun YP, Franke J, Davidson K, et al. Patent foramen ovale. Nat Rev Dis Prim. 2016;2:15086.

    Article  Google Scholar 

  10. Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, et al. Acute respiratory distress syndrome. Nat Rev Dis Prim. 2018;5:18.

    Article  Google Scholar 

  11. Herrmann J, Mori V, Bates JHT, Suki B. Modeling lung perfusion abnormalities to explain early COVID-19 hypoxemia. Nat Commun. 2020;11:4883.

    CAS  Article  Google Scholar 

  12. Rajendram R, Kharal GA, Puri R. Covid-19 may be exacerbated by right-to-left interatrial shunt. Ann Thorac Surg. 2020. https://doi.org/10.1016/j.athoracsur.2020.05.013.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

No funding was obtained for this study.

Author information

Affiliations

Authors

Contributions

All authors have read and approved the manuscript, and significantly contributed to this paper. CV, OT, NS, OV, DL: conception and design, literature review, manuscript writing and correction, final approval of the final manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Charlotte Vanhomwegen.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Competing interest

None.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Vanhomwegen, C., Taton, O., Selvais, N. et al. Patent foramen ovale revealed by COVID-19 pneumonia. BMC Pulm Med 21, 126 (2021). https://doi.org/10.1186/s12890-021-01494-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12890-021-01494-7

Keywords

  • Hypoxemia
  • SARS-CoV-2
  • Patent foramen ovale
  • Pulmonary vasoconstriction
  • Ventilation inhomogeneity