Platypnea–Orthodeoxia Syndrome Due to a Functional Patent Foramen Ovale: Aortic Dilatation and Possible Contribution of Obstructive Sleep Apnea

Abstract

Platypnea–orthodeoxia syndrome (POS) is an uncommon and underrecognized cause of positional hypoxemia, usually related to dynamic right-to-left shunting. We report the case of a 74-year-old man with obesity and unexplained presyncopal episodes associated with severe positional oxygen desaturation. Initial transthoracic echocardiography with agitated saline contrast performed in the supine position was negative. However, contrast-enhanced transesophageal echocardiography performed in the sitting position revealed a patent foramen ovale with a dynamic right-to-left shunt associated with aortic root dilatation and interatrial septal distortion. Percutaneous closure using a NobleStitch system resulted in immediate improvement in oxygenation. Subsequent respiratory polygraphy identified moderate obstructive sleep apnea, interpreted as a possible contributing factor rather than a proven mechanism. This case highlights the importance of considering POS in unexplained positional hypoxemia and emphasizes that a negative supine transthoracic contrast study does not exclude a dynamic intracardiac shunt.

Resumen

El síndrome de platipnea-ortodeoxia (SPO) es una causa infrecuente y a menudo infradiagnosticada de hipoxemia posicional, relacionada con un cortocircuito dinámico de derecha a izquierda. Presentamos un varón de 74 años con obesidad y episodios presincopales de etiología no filiada, asociados a desaturación de oxígeno al adoptar la posición erguida. La ecocardiografía transtorácica inicial con contraste de suero salino agitado realizada en decúbito supino fue negativa. La ecocardiografía transesofágica con contraste efectuada en sedestación evidenció la presencia de un foramen oval permeable con un cortocircuito dinámico de derecha a izquierda, asociado a dilatación de la raíz aórtica y deformación del septo interauricular. El cierre percutáneo mediante el sistema NobleStitch produjo una mejoría inmediata de la oxigenación. Posteriormente, la poligrafía respiratoria identificó un síndrome de apnea obstructiva del sueño de grado moderado, interpretado como un posible factor contribuyente más que como un mecanismo causal demostrado. Resaltamos la importancia de considerar el SPO ante cuadros de hipoxemia posicional no explicada y pone de manifiesto que una ecocardiografía transtorácica con contraste negativa en decúbito supino no excluye la existencia de un cortocircuito intracardíaco dinámico.

Platypnea–orthodeoxia syndrome (POS) is an uncommon clinical condition characterized by the development of dyspnea and/or hypoxemia upon assuming the sitting or upright position, with prompt resolution in the recumbent posture.¹ Although its prevalence is low, POS represents a potentially reversible cause of hypoxemia that is often clinically challenging to interpret.^1,2

From a pathophysiological perspective, POS arises from a right-to-left shunt of either intracardiac or intrapulmonary origin.² Intracardiac causes, most commonly patent foramen ovale (PFO) and atrial septal defect account for the majority of cases.² However, the mere presence of a PFO is rarely sufficient to produce the syndrome, and the coexistence of additional anatomical or functional factors that alter intracardiac flow direction is usually required.^2,3

We describe the case of a 74-year-old man, a former smoker (60 pack-years, quit 15 years earlier), with obesity (BMI 31 kg/m²), who presented with unexplained presyncopal episodes over a two-month period. At his primary care center, marked hypoxemia was detected (SpO₂ 83% on room air) in the absence of dyspnea at rest, prompting referral to the emergency department.

On admission, he exhibited severe arterial hypertension (220/116 mmHg) and sinus tachycardia (127 bpm). Initial arterial blood gas analysis, performed with an FiO₂ of 35%, showed a PaO₂/FiO₂ ratio of 171 mmHg. Respiratory support was escalated to high-flow nasal cannula therapy, with a maximum FiO₂ of 60%. Laboratory testing ruled out infectious or inflammatory processes. Electrocardiography, myocardial injury markers, and markers of cardiac overload were unremarkable.

Aortic root dilatation (43 mm) was noted on transthoracic echocardiography, without evidence of pulmonary hypertension or right ventricular overload (Fig. 1A). Computed tomography pulmonary angiography excluded acute pulmonary vascular disease and showed centrilobular and paraseptal emphysema predominantly affecting the upper lobes (Fig. 1B).

Fig. 1.

(A) Transthoracic echocardiography showing aortic root dilatation (yellow line) and the presence of a patent foramen ovale (PFO) (*). (B) Lung window showing no clinically significant parenchymal abnormalities. (C) Transthoracic echocardiography with agitated saline contrast performed in the supine position, showing no evidence of right-to-left shunting at the interatrial septum (arrow). (D) Contrast-enhanced transesophageal echocardiography performed in the sitting position, demonstrating marked right-to-left shunting through a patent foramen ovale (arrows). (E) Transesophageal echocardiography with color Doppler imaging showing a large patent foramen ovale with right-to-left flow (arrow). (*) Suspected interatrial septal defect/PFO region (depending on your image labeling).

The patient was admitted to the Intermediate Respiratory Care Unit, where significant oxygen desaturation was observed upon assuming the sitting position, with SpO₂ decreasing from 92% to 86%. Positional desaturation was associated predominantly with presyncopal symptoms rather than overt platypnea. This positional oxygen desaturation raised suspicion of platypnea–orthodeoxia syndrome. Additionally, episodes of snoring and sleep apnea were observed, associated with nocturnal oxygen desaturation during monitoring. Orthodeoxia testing demonstrated a reproducible decrease in PaO₂ from 64 mmHg in the supine position to 58 mmHg when sitting upright, associated with positional oxygen desaturation.

As part of the etiological evaluation, transthoracic echocardiography with agitated saline contrast performed in the supine position was unremarkable (Fig. 1C). It is important to note that the patient exhibited a poor transthoracic acoustic window. Further investigations, including ^99mTc-macroaggregated albumin lung perfusion scintigraphy and abdominal ultrasound, were performed to exclude alternative causes of right-to-left shunting, including intrapulmonary shunt and hepatopulmonary syndrome.

Contrast-enhanced transesophageal echocardiography performed in the sitting position revealed a patent foramen ovale with a systodiastolic right-to-left shunt, a defect measuring 7–8 mm, distortion of the interatrial septum, and dilatation of the aortic root (Fig. 1D, E). Percutaneous closure of the PFO was performed using a NobleStitch suture-mediated closure system, selected by the interventional cardiology team as an alternative to permanent metallic device implantation, resulting in immediate improvement in oxygenation, with oxygen saturation exceeding 95% on room air.

In a stable phase, overnight respiratory polygraphy confirmed the diagnosis of moderate obstructive sleep apnea (apnea–hypopnea index 20.7 events/h; CT90 3.9%). Given the clinical context, including the presence of obesity, snoring, apneic episodes, and cardiovascular comorbidities, nocturnal CPAP therapy was initiated at a pressure of 7 cmH₂O via a nasal mask, with good tolerance and effective control of the obstructive events.

At six-week follow-up, the patient remained asymptomatic, with pulmonary function tests (FEV₁ 2.77 L, 95.2%, z-score −0.28; DLCO 76.8%, z-score −1.68) and the six-minute walk test were within normal limits.

We present a case of platypnea–orthodeoxia syndrome attributable to a functional patent foramen ovale, in which the interplay between anatomical and functional factors resulted in initially unexplained hypoxemia that resolved after percutaneous closure of the interatrial defect.

From a pathophysiological perspective, cardiac POS does not depend solely on the presence of a septal defect but rather on the coexistence of mechanisms that promote a dynamic right-to-left shunt.³ In this setting, dilatation or elongation of the ascending aorta may contribute to interatrial septal distortion and flow redirection toward the foramen ovale, resulting in position-dependent shunting.^3,4 This flow redirection may occur even in the absence of sustained elevation of right atrial pressures.^2,3

From a pulmonologist's perspective, POS should be suspected in patients with unexplained positional hypoxemia disproportionate to pulmonary findings. Because the shunt may be dynamic, a negative supine transthoracic echocardiography does not exclude the diagnosis, and transesophageal echocardiography in the sitting position may be required. Although the absolute PaO₂ difference was modest, the positional desaturation was reproducible and clinically significant in the context of unexplained hypoxemia and orthostatic oxygen saturation changes. Despite mild emphysematous changes on computed tomography, pulmonary function tests showed no significant functional impairment, making a primary pulmonary cause of hypoxemia less likely.

The initial negative result of transthoracic echocardiography with agitated saline contrast can be explained by the dynamic and position-dependent nature of the shunt; however, the absence of an adequate transthoracic acoustic window and the lack of positional provocation should not be underestimated.⁴ It has been reported that saline administration via the femoral vein has greater sensitivity for the diagnosis of PFO compared with the brachial route; however, the femoral approach is not recommended.⁵ Right-to-left passage is not determined solely by the size of the PFO but also by septal alignment and venous flow direction.^3,4 In the supine position, oblique inferior vena cava flow and low right-sided pressures may prevent contrast passage; however, upon sitting upright, aortic dilatation-induced septal distortion facilitates direct flow alignment toward the defect, unmasking the shunt.^2,4 This mechanism accounts for false-negative conventional transthoracic echocardiography findings and underscores the need for contrast studies performed in the sitting position or dynamic transesophageal echocardiography.⁴

In our patient, obstructive sleep apnea may have contributed to transient shunt amplification through negative intrathoracic pressure generation. Recurrent inspiratory efforts against a collapsed upper airway generate marked negative intrathoracic pressures, transiently altering intracardiac pressure and flow relationships and promoting functional opening of the PFO.^6,7 Several studies have demonstrated a higher prevalence of right-to-left shunts and more pronounced nocturnal oxygen desaturation in patients with OSA and clinically significant PFO compared with those without relevant shunting.^7,8 However, because respiratory polygraphy was performed after PFO closure, OSA should be interpreted as a plausible contributing factor rather than a proven mechanism.

This case exemplifies the concept of a functional patent foramen ovale, whereby the clinical significance of the shunt depends less on the anatomical size of the defect than on dynamic anatomical and physiological conditions.^2,3 In this context, percutaneous PFO closure is associated with rapid normalization of oxygenation and favorable clinical outcomes.⁹

In conclusion, the coexistence of aortic dilatation and patent foramen ovale, potentially facilitated by coexisting obstructive sleep apnea, may represent a permissive substrate for the development of platypnea–orthodeoxia syndrome.^3,4 Recognition of this mechanism may prevent diagnostic delays and enable effective and definitive therapeutic intervention.

Ethical considerations

This case report did not require formal approval from an ethics committee according to institutional policies. Patient confidentiality and anonymity were maintained at all times.

Artificial intelligence involvement

The authors disclose not to have produced partially or totally any of the material with the help of any artificial intelligence software or tool.

Informed consent

Informed consent has been obtained from the patient for the publication of their clinical data and images.

Funding

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

Authors’ contributions

All authors have contributed to the drafting, supervision, and critical revision of the manuscript, and have approved its final version for submission.

Conflicts of interest

The authors declare not to have any conflicts of interest that may be considered to influence directly or indirectly the content of the manuscript.