Platypnea-orthodeoxia syndrome developed with the progression of pulmonary parenchymal involvement: A case report

Abstract

Platypnea-orthodeoxia syndrome (POS) attributed to patent foramen ovale (PFO) can be caused by a variety of clinical conditions. A 70-year-old woman was admitted to our hospital for further evaluation of POS. Her symptoms developed along with the spread of infiltrative shadows in both lower lung fields during the preceding 2 years. Contrast transthoracic echocardiography with agitated saline revealed grade III intracardiac right-to-left shunting, presumably across a PFO. Transesophageal echocardiography demonstrated severe tricuspid regurgitation (TR) caused by the prolapse of the anterior leaflet. Bidirectional shunt flow, mainly from right-to-left across a PFO, that increased in the sitting position was also observed. She was diagnosed as having PFO associated with severe primary TR. Therefore, tricuspid valve repair and direct PFO closure were performed. Her symptoms resolved completely soon after the operation and her oxygen saturation was maintained. This patient's disease seemed to have worsened with the spread of pulmonary parenchymal involvement, which caused ventilation-perfusion mismatch and elevation of alveolar pressures. Echocardiography is an essential imaging modality in addition to other diagnostic examinations and imaging studies when assessing the pathogenesis in patients with POS.

Learning objective

Platypnea-orthodeoxia syndrome (POS) associated with patent foramen ovale may be caused by a variety of clinical conditions, and POS in our patient may be caused by the worsening of pulmonary parenchymal involvement. Examinations to evaluate all causes of POS are essential for making the diagnosis. Contrast transthoracic echocardiography was useful in assessing the cause of POS.

Introduction

Platypnea-orthodeoxia syndrome (POS) is a disease characterized by dyspnea and hypoxemia that is worse in the upright position than in the recumbent position [1]. POS is caused by a variety of structural abnormalities such as intracardiac shunt, pulmonary arteriovenous shunt, and parenchymal ventilation-perfusion mismatch seen in chronic obstructive pulmonary disease or parenchymal lung diseases [2]. Therefore, the duration from the occurrence of symptoms to diagnosis and treatment varies greatly [3]. It is essential to identify the pathological conditions altering the relationship between existing structures and underlying structural abnormalities. We describe a rare case of POS caused by patent foramen ovale (PFO) and severe tricuspid regurgitation (TR) that developed with the progression of lung disease in the lower lobes.

Case report

A 70-year-old woman with chronic airway symptoms for 5 years was suspected of having non-tuberculosis mycobacteriosis based on an abnormal shadow in the lung fields. The abnormal pulmonary shadow had continued to spread for 2 years. She presented with dyspnea that was worse in the sitting position. Thus, POS was suspected. She was admitted to our hospital for further evaluation. She had no history of smoking or allergies.

Physical examination revealed the following: height, 156 cm; weight, 44 kg; body mass index, 18 kg/m²; blood pressure, 145/87 mmHg; pulse, 112 beats/min and regular; and body temperature, 36.6 °C. Oxygen saturation on room air was 81 % in the sitting position, 93 % in the supine position, and 78 % after returning to the sitting position. Lung sounds were attenuated in both lower lung fields. There was a Levine II/VI systolic murmur best heard at the apex. No peripheral edema was noted.

Blood tests showed an elevated inflammatory response with white blood cell count of 11,600/μL (neutrophils 76.9 %, lymphocytes 17.0 %, and eosinophils 1.4 %) and C-reactive protein level of 0.93 mg/dL. Serum brain natriuretic peptide level was 155.1 pg/mL. Arterial blood gas revealed pH of 7.42, pO₂ of 89.9 mmHg, pCO₂ of 44.7 mmHg, and HCO₃⁻ of 28.8 mmoL/L. Serum anti-glycopeptidolipid-core immunoglobulin A antibody was positive. Biomarkers for viral hepatitis were negative and liver transaminase levels were not elevated.

The 12-lead electrocardiogram showed normal sinus rhythm with a heart rate of 83 beats/min, a normal axis, and low voltage in the limb leads (Fig. 1A). Chest radiography revealed a cardiothoracic ratio of 55 %, displacement of the cardiac silhouette to the right, and protrusion of the right second bow (Fig. 1B). The abnormal pulmonary shadow had gradually spread over the course of 5 years. Although chest computed tomography (CT) showed infiltrative shadows in both lower lung lobes that had gradually increased over the previous 2 years (Fig. 1C-E), no obvious shunts were observed on contrast-enhanced CT. Pulmonary function testing showed percentage forced vital capacity of 70.4 % and forced expiratory volume in 1 s of 85.4 %. Lung perfusion scintigraphy performed in the recumbent position showed a decrease in accumulation in the basal segments, which was consistent with non-tuberculosis mycobacteriosis. The right-to-left shunt ratio was calculated to be 6.3 %. Ventilation disorder in the middle lingual region and the lower lobes was observed during lung ventilation scintigraphy performed in the recumbent position. No apparent ventilation-perfusion mismatches were observed.

Fig. 1.

Twelve-lead electrocardiogram, chest radiograph on admission, and time course of plain thoracic computed tomography findings. Twelve-lead electrocardiogram (A) showed normal sinus rhythm with a normal axis and low voltage in the limb leads. Chest radiograph (B) showed a cardiothoracic ratio of 55 % and protrusion of the right second bow. Abnormal opacities were observed in both lower lung fields. A small infiltrative shadow was observed in right lower lung 7 years previously (C). Infiltrative shadows were observed in both lower lung lobes 2 years previously (D). These opacities worsened on admission (E). The upper and lower images of computed tomography are continuous cross-sectional images at each clinical time point.

We assessed the shunt ratio using the 100 % oxygen inhalation method in which the arterial blood gas analysis is derived based on the Fick principle after inhalation of 100 % oxygen for more than 20 min [4]. The shunt ratio differed by body position as follows: 7.9 % in the supine position, 7.1 % in Fowler's position, and 19.0 % in the sitting position. These findings supported the existence of an arteriovenous shunt. An intracardiac shunt was suspected.

On transthoracic echocardiography (TTE), severe TR with marked enlargement of the right-sided chambers was observed. Left ventricular contraction was normal and the same as 3 years previously. There was an atrial septum aneurysm. Although her echo window was limited due to mesocardia, subsequent contrast TTE with agitated saline revealed a grade III right-to-left intracardiac shunt, presumably across a PFO [5]. Transesophageal echocardiography (TEE) indicated that the severe TR was caused by prolapse of the anterior leaflet (Fig. 2A). At rest, bidirectional shunt flow, mainly right-to-left across a PFO, was observed (Fig. 2B, C, Video 1). In the sitting position, right-to-left shunt flow increased and oxygen saturation decreased from 98 % to 91 %.

Fig. 2.

Transesophageal echocardiography findings. Transesophageal echocardiography with Doppler color flow imaging showed severe TR caused by prolapse of the anterior leaflet (A). There was bidirectional shunt flow, mainly right-to-left flow across a PFO (B). Transesophageal echocardiography with agitated saline contrast revealed shunting of bubbles from the right atrium into the left atrium through a PFO (C).

LA, left atrium; PFO, patent foramen ovale; RA, right atrium; RV, right ventricle; TR, tricuspid regurgitation.

Her symptoms worsened along with worsening of the infiltrative shadows in both lower lung fields. Although the blood test was positive, the culture of sputum and bronchial lavage fluid did not meet the diagnostic criteria for non-tuberculosis mycobacteriosis. Therefore, the final diagnosis of her lung lesion was equivocal. Additional examinations and medications were not required at that time. The etiology of her TR was prolapse, i.e. primary TR. Therefore, surgical intervention was considered in addition to PFO closure (Fig. 3). Tricuspid valve repair and direct PFO closure were performed after discussion at the heart team conference. This patient's symptoms resolved completely soon after the operation. Her oxygen saturation was preserved. The patient was discharged and followed in the outpatient clinic. Home oxygen therapy that had been scheduled at the time of admission could also be discontinued.

Fig. 3.

Intraoperative findings. The surgeon's view from the right atrium. There was a large patent foramen ovale, through which forceps passed easily from the right atrial side (arrowheads) (A). The tricuspid valve was seen from the right atrial side (B). Prolapse of the thickened anterior leaflet was observed (arrows).

Discussion

POS is defined as postural dyspnea associated with oxygen desaturation that appears in the standing or sitting position and is relieved in the recumbent position due to the admixture of deoxygenated venous blood and arterial blood [1,2]. PFO is an important structure that can cause an intracardiac shunt. Although PFO has been reported in approximately 20 % to 25 % of the adult population [6,7], most people never develop any symptoms. One reason might be the higher pressure in the left atrium than the right atrium and the positional relationship between the septum primum and the septum secundum. This balance is lost when right atrial pressure exceeds left atrial pressure, i.e. pressure explanation or alterations in the position of the septa due to changes in the surrounding structures such as elongation of the aorta, abnormalities of the vertebral bodies, and displacement of the diaphragm. Some causes of pressure explanation are pulmonary hypertension, chronic obstructive pulmonary disease, and constructive pericarditis.

TR, especially acute-onset TR, is often reported to be associated with POS [8]. Acute TR due to a traffic accident that causes blunt trauma to the anterior chest might cause anatomical changes in the atrial septum and separation of the septa. In acute TR, a regurgitation jet often blows biasedly due to torn chordae or a damaged leaflet. The inclined jet might displace the atrial septa, which cause right-to-left jet flow. Right atrial pressure increases more than left atrial pressure in this situation. As a result, both pressure explanation and disjunction of the septa can lead to POS in the setting of acute TR. Although severe TR was observed in our patient, it did not occur suddenly. TR had been diagnosed 5 years prior to the onset of symptoms. TR was not considered the main cause of POS in this patient.

In our patient, pulmonary parenchymal involvement in the lower lobes worsened during the 2 years preceding admission. Blood flow increases in the lower lobes more than in the other lobes in the upright position due to gravity. Therefore, gas exchange takes place most effectively in the lower lobes. However, in the presence of pulmonary parenchymal involvement, as in our patient, ventilation-perfusion mismatch occurs, which increases alveolar pressures [9]. Occurrence of these phenomena during the 2 years before admission might have triggered POS in this patient. Although our patient's symptoms resolved soon after tricuspid valve repair and PFO closure, some patients still experience symptoms after PFO intervention [10]. The lack of improvement after PFO closure might occur in the presence of severe chronic obstructive pulmonary disease associated with pulmonary hypertension or other severe comorbidities such as hepato-pulmonary syndrome [10]. Therefore, it is desirable to rule out other causes of orthostatic dyspnea prior to PFO intervention.

Conclusion

POS associated with intracardiac shunting occurs due to a combination of the pressure balance between the atria and structural changes in atrial septa or any one of them. Our patient with PFO developed POS in the setting of increased pulmonary parenchymal involvement as well as severe TR.

The following is the supplementary data related to this article.

Video 1

Transesophageal echocardiography with agitated saline contrast

Agitated saline was injected into the right median cubital vein. Shunting of bubbles across the PFO was observed.

Consent statement

Written informed consent was obtained from the patient.

Declaration of competing interest

The authors declare that there is no conflict of interest.