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Abstract
Platypnoea-orthodeoxia syndrome (POS) is a descriptive diagnosis of dyspnoea and arterial desaturation when changing from supine to upright position. It has many possible underlying conditions. We report a case of POS due to a right-to-left shunt which became apparent during a hospital admission with COVID-19 pneumonitis. Surprisingly, this shunt as well as the POS symptoms gradually disappeared during the ten months after discharge. We believe that fibrotic and vascular changes due to COVID-19 caused an intracardiac defect to become temporarily symptomatic. In case of discovery of POS which does not resolve after COVID-19, it may be necessary to look for the underlying cause of this syndrome.  

Introduction
Platypnoea-orthodeoxia syndrome (POS) is a rare clinical syndrome which is characterised by dyspnoea and arterial desaturation while in the upright position. The hypoxia in POS is caused by mixing of arterial and venous blood through a shunt.[1] This mechanism has various causes, broadly classified into intracardiac abnormalities, extracardiac abnormalities and miscellaneous. Intracardiac abnormalities such as patent foramen ovale (PFO) and atrial septal defect (ASD) are the most common causes (87%) of POS.[1] We report a case of POS most likely due to a transiently symptomatic intracardiac shunt in a patient who presented to our hospital with COVID-19 pneumonitis.

Case
A 58-year-old male with no medical history, who was previously asymptomatic and active, was referred to our hospital with symptoms of dyspnoea and coughing that had existed for 11 days, due to COVID-19 pneumonitis. A CT thorax was performed and pulmonary embolisms were excluded. He was treated by nasal high-flow-high-oxygen therapy and needed no mechanical ventilation during his admission. However, the hypoxaemia persisted and we were not able to diminish the oxygen therapy. After further examination, it struck us that our patient significantly desaturated while experiencing more dyspnoea when sitting up straight, consistent with the definition of POS. A transthoracic echocardiogram in the supine left lateral position was performed at admission day 12. It showed normal left and right atrial anatomy, normal left ventricular (LV) systolic function, normal right ventricular (RV) function, and there was no valvular dysfunction, and no signs of pulmonary hypertension. Pulmonary embolisms were excluded again by CT scan at day 16. Furthermore, there was no aortic pathology. Eventually, an agitated saline contrast echocardiography was performed at day 19, which showed an evident interatrial right-to-left shunt with large contrast flow. At day 23, our patient was discharged to the pulmonology ward, where he still suffered from POS. After a total of 36 days in our hospital, our patient went home and continued oxygen therapy there. Three months after discharge, he was still impaired by POS and not yet able to work. A transoesophageal echocardiogram was performed four months after discharge. These images were inconclusive. They showed no clear ASD or PFO, but during Valsalva manoeuvres agitated saline contrast could be seen crossing from the right to the left atrium. Cardiac magnetic resonance imaging with Gadolinium (1.5T Siemens Avanto Fit) was used to assess LV and RV function 10 months after discharge. Standard cine images, late gadolinium enhanced images and flow measurements were performed. The shunt ratio (Qp:Qs ratio), consisting of flow in the pulmonary artery (Qp) and flow in the aorta (Qs), was 0,99. An intracardiac defect was no longer visible. Our patient’s symptoms of dyspnoea had resolved and he was able to function normally in his daily working life. An expectant strategy was agreed upon.

Discussion
Intracardiac defects such as PFO or ASD are often asymptomatic. The way we discovered our patient’s intracardiac shunt was unusual. It became symptomatic in the form of POS during the disease process of COVID-19 pneumonitis, and symptoms and shunting disappeared after recovering. We will discuss possible mechanisms behind this development of right-to-left shunting.

The differential diagnosis of POS is quite extensive and can be divided into three groups: intracardiac shunting (table 1.1), extracardiac shunting (table 1.2) and miscellaneous mechanisms (table 1.3). Between these groups, intracardiac shunting is the most common cause. In case of intracardiac shunting, a second condition is present in the majority of patients to actually trigger the right-to-left shunting.[1,2] Generally, for blood to flow ‘uphill’, pressure in the right-sided heart should be higher than in the left-sided heart.[2] However, it is a well-known phenomenon that right-to-left shunting through an intracardiac defect might also occur in the absence of an interatrial pressure gradient.[3,4] This is explained by the hypothesis of a change in the direction of several flows of blood in the right atrium, without changes in pressure.[3]

In our patient, several mechanisms might have contributed to POS. On the CT scan no intrathoracic anatomic changes were visible. We believe that haemodynamic and pulmonary changes due to COVID-19 were the reason for his underlying condition to become temporarily symptomatic. We have several hypotheses regarding the mechanism.

Firstly, COVID-19 can be a cause of POS on its own.[5] Some COVID-19 patients suffer from POS, possibly because of a change in perfusion and ventilation causing a mismatch, or due to ARDS (extracardiac shunting). However, in most of these patients, POS resolves after several days to weeks, which did not happen in our patient.[5] This suggests that in case of persisting POS, an underlying condition is more likely.

Secondly, pulmonary vascular changes and (micro)thrombi can occur in COVID-19 pneumonitis, as has been shown in postmortem studies.[6,7] This could cause pulmonary hypertension and right-sided pressures (especially right atrial pressure) to elevate. It has been shown that pulmonary hypertension and right ventricular failure can develop very quickly after COVID-19 pneumonitis.[8] Pulmonary embolisms have also led to POS and subsequent discovery of intracardiac shunting.[9]

Thirdly, extracardiac shunting can aggravate intracardiac shunting, as was shown in patients where PFO was discovered after they developed pulmonary hypertension due to COPD.[10] Conditions such as ARDS, interstitial lung disease, fibrosis, and microthrombi can cause ‘pulmonary hypertension’, thereby inducing a right-to-left shunt that did not shunt before. Furthermore, hypoxic vasoconstriction can aggravate this process. Right-sided pressures might have been higher due to hypoxic vasoconstriction, not showing tricuspid regurgitation since it existed briefly. All of the above-mentioned changes can occur due to COVID-19 pneumonitis.[6] We consider it most likely that in our patient these changes played the largest role. Fortunately for our patient the pulmonary changes must have resolved after several months, since we saw no more evidence of shunting through the undefined intracardiac defect that was established at first. In addition the patient’s symptoms resolved after ten months.

Conclusion
POS is a rare syndrome that can be provoked by different conditions, in this case COVID-19 pneumonitis. COVID-19 pneumonitis can cause fibrotic and haemodynamic changes in the heart-lung axis, thus causing an asymptomatic intracardiac defect to become symptomatic. This case illustrates the need for further investigation in case of slow recovery from COVID-19 pneumonitis combined with POS. It is reassuring that the COVID-19 pneumonitis induced intracardiac shunt seems to be transient.

Disclosures
All authors declare no conflict of interest. No funding or financial support was received. Informed consent from the patient was obtained for the publication of this case report.

Written informed consent was obtained from the patient for the publication of this case report.