Abstract
Background
Platypnea-orthodeoxia syndrome (POS) is a rare condition with complex pathophysiology resulting from an anatomical site of shunting, mostly a patent foramen ovale (PFO), and factors promoting a right-to-left (R-L) shunt.
Case Summary
A 54-year-old man was referred to our center for unexplained respiratory failure, exacerbated by sitting. A suspicion of POS was raised, and transesophageal echocardiography demonstrated a wide stretched PFO with R-L shunting, related to the presence of an aortic root aneurysm and right hemidiaphragm elevation, both compressing the right atrium, as well as a prominent eustachian valve. The patient underwent valve-sparing aortic root replacement and concomitant PFO closure, with resolution of symptoms.
Take-Home Messages
Multiple factors promoting R-L shunt have been associated with POS. The treatment of choice is represented by the correction of the anatomical shunt. Multidisciplinary team discussion is paramount for the diagnosis and management of this complex condition.
Key words: ascending aorta aneurysm, hemidiaphragm elevation, patent foramen ovale, platypnea-orthodeoxia syndrome
Visual Summary
Platypnea-orthodeoxia syndrome (POS) is a relatively rare entity characterized by positional dyspnea and arterial desaturation exacerbated by the upright position. A reduction of arterial oxygen saturation of >5% or arterial partial oxygen pressure of >4 mm Hg has classically been accepted as its definition.1,2 POS presents a complex pathophysiology resulting from the interaction of multiple mechanisms. Indeed, it is related to the presence of right-to-left (R-L) shunts, with an intracardiac or extracardiac (generally pulmonary) location. The most common site of R-L shunting is intracardiac, mostly a patent foramen ovale (PFO). Even though the presence of an anatomical shunt is essential in the pathogenesis of intracardiac POS, additional factors promoting R-L shunting, particularly in the upright position, are required. Either factors facilitating blood flow redirection toward the shunt or—less commonly—rising right atrial pressure have been described (Table 1).1, 2, 3, 4 Herein, we describe a case of POS associated with aortic root aneurysm and right hemidiaphragm elevation (rHE).
Take-Home Messages
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Intracardiac POS results from an anatomical site of shunting, mostly a PFO, and factors that promote R-L shunt, facilitating blood flow redirection toward the shunt or rising right atrial pressure.
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Understanding the complex pathophysiology of POS and its contributing factors is an important step to establish the association between the PFO and the clinical manifestations.
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Multidisciplinary team discussion is paramount in the diagnosis and management of POS: Key steps include bubble-contrast TTE, both in the supine and upright positions, TEE, evaluation of contributory factors to POS, exclusion of other causes of respiratory failure, and right heart catheterization when needed.
Table 1.
Factors Associated With Platypnea-Orthodeoxia Syndrome
Factors associated with intracardiac POS
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Factors associated with extracardiac POS (pulmonary)
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Case Presentation
A 54-year-old man was referred to our center for unexplained respiratory failure, exacerbated by sitting, with suspected R-L shunt through a PFO and an incidentally detected aortic root aneurysm. The patient had a medical history significant for obesity, systemic arterial hypertension, and type 2 diabetes. He had been bedbound for an extended period after an initial hospital admission for bacterial right gonarthritis complicated by spondylodiscitis L4-S1, followed by hypocapnic hypoxic respiratory failure persisting after resolution of the infection. The patient presented with dyspnea at rest and arterial desaturation despite high-flow nasal cannula oxygen therapy, exacerbated by sitting and improved when lying on the left side. Computed tomography lung scan detected rHE with no evidence of lung parenchymal or vascular disease. Transthoracic echocardiography revealed an aortic root aneurysm and a suspected R-L shunt through a PFO, with no signs of pulmonary hypertension and normal biventricular systolic function. Transesophageal echocardiography (TEE) revealed a floppy hypermobile interatrial septum (IAS) bulging toward the left atrium with a wide stretched PFO (6 mm) and a significant basal R-L shunt (Figure 1). An aortic root aneurysm (60 mm at the sinus of Valsalva) was found, compressing the anterosuperior wall of the right atrium (RA). The RA inferior wall was compressed as well, probably owing to rHE. Moreover, we detected a flow acceleration with no significant gradient (mean gradient: 3 mmHg) along the compressed portion of the RA, with a prominent eustachian valve (EV) above it creating a functional compartmentalization between the compressed RA portion and the residual inferoposterior region (Figures 2 and 3). The inferior vena cava (IVC) was displaced toward the IAS, with IVC flow directed toward the PFO (Figure 4). A tricuspid aortic valve with a relatively preserved anatomy and mild regurgitation was also noted.
Visual Summary.
Transverse, Coronal, and Sagittal Planes
Schematic illustration showing in the (A) transverse, (B) coronal, and (C) sagittal planes the right atrial compression between the dilated aorta and right hemidiaphragm elevation, with consequent distortion of the interatrial septum and stretching of the patent foramen ovale (asterisk); a prominent eustachian valve (arrowhead) bordering the compressed area of the right atrium contributes to preferential blood flow from the inferior vena cava toward the patent foramen ovale. The dotted line and the associated faded yellow area represent the usual atrial anatomy without extrinsic compression. Ao = aorta; IVC = inferior vena cava; LA = left atrium; PA = pulmonary artery; RA = right atrium; rHE = right hemidiaphragm elevation; RV = right ventricle; SVC = superior vena cava; TV = tricuspid valve.
Figure 1.
Interatrial Septum Anatomic Distortion
Transesophageal echocardiography deep-esophageal 0° view showing interatrial septum distortion along the aneurysmatic aortic root (Ao), stretching the patent foramen ovale (arrowhead). LA = left atrium; RA = right atrium.
Figure 2.
Right Atrial Compression
Transesophageal echocardiography midesophageal 60° view showing color Doppler flow acceleration (arrow) in the compressed right atrial portion along the dilated aortic root (Ao). LA = left atrium; RA = right atrium.
Figure 3.
Relationship Between the Right Atrium, Aortic Root, and Interatrial Septum
(A) Transesophageal echocardiography midesophageal 60° 3D reconstruction showing a wide stretched patent foramen ovale (arrow) and a prominent eustachian valve (EV) above the right atrial (RA) compression along the dilated aortic root (Ao). (B) Corresponding 2D color Doppler view showing flow acceleration in the compressed RA region (arrowhead), with right-to-left shunting across the patent foramen ovale. IVC = inferior vena cava; LA = left atrium.
Figure 4.
Inferior Vena Cava Flow Directed Toward the Patent Foramen Ovale
Transesophageal echocardiography midesophageal 60° view showing preferential flow from the inferior vena cava (arrow) toward a bulging interatrial septum (arrowhead). Ao = aortic root; LA = left atrium; RA = right atrium.
Preoperative computed tomography angiography showed a 61-mm aortic root aneurysm extending to the proximal tubular aorta, with significant elongation and slight overangulation of the ascending aorta. Furthermore, it clearly depicted RA compression between the aortic root and rHE (Figure 5). Hence, we hypothesized that the aortic root aneurysm and rHE distorted the IAS and RA anatomy, promoting R-L shunting through the stretched PFO in association with a prominent EV. Coronary angiography was performed, demonstrating no significant coronary lesions. After multidisciplinary heart team discussion, the patient underwent valve-sparing aortic root replacement with David procedure using a 32-mm Valsalva Dacron graft and concomitant PFO closure by direct suturing. At surgical inspection, the presence of a wide stretched PFO was confirmed (Figure 6). The aortic valve showed only minimal pericommissural fenestrations and a slight redundancy of the right coronary cusp, whose free margin was therefore shortened with a central plication.
Figure 5.
Relationship Between the Right Hemidiaphragm Elevation, Aortic Aneurysm, and Right Atrium
(A) Coronal computed tomography view showing right atrial lumen (arrow) compressed between the dilated aortic root (Ao) and right hemidiaphragm elevation (rHE). (B) Corresponding 3D reconstruction showing severely dilated aortic root and significant elongation with slight overangulation of the ascending aorta.
Figure 6.
Intraoperative View of the Interatrial Septum
Intraoperative view of the interatrial septum revealing a wide stretched patent foramen ovale (asterisk).
After surgical intervention, the patient experienced prompt relief of dyspnea and a significant improvement in arterial saturation, with rapid weaning from high-flow nasal cannula. Postoperative TEE showed optimal results of valve-sparing aortic root replacement and no residual shunt through the IAS, despite a persistent flow acceleration along the EV (Figure 7). The postoperative course was complicated by a persistent complete atrioventricular block and atrial fibrillation, therefore the patient was started on antiarrhythmic therapy and long-term oral anticoagulation as well as undergoing dual-chamber pacemaker implantation after 5 days. Finally, he was transferred to a rehabilitation center for the treatment of diaphragmatic paralysis and controlled weight loss.
Figure 7.
Transthoracic Echocardiography After Surgery
Transthoracic echocardiography modified parasternal short-axis view with simultaneous color Doppler showing persistent flow acceleration (red color flow) along a prominent eustachian valve (arrowhead), with no residual shunt at the interatrial septum (arrow). Ao = aortic graft; IVC = inferior vena cava; LA = left atrium; RA = right atrium; TV = tricuspid valve.
Discussion
Ascending aorta aneurysms, elongation and horizontalization, a prominent EV, and rHE have been well described as contributory factors to POS, associated with normal RA pressure and preferential blood flow toward the PFO. In particular, it has been previously reported that ascending aortic abnormalities may cause compression, distortion, and hypermobility of the IAS, facilitating PFO opening and its alignment with the IVC flow.1,5,6 The rightward shift of the IAS puts it in closer proximity to the IVC, while the reduced length and looseness of the compressed IAS promote opening of the fossa ovalis flap.1,5,7 Consequently, the IVC flow directed toward the fossa ovalis may maintain the PFO wide opened and bulged toward the left atrium, as a “spinnaker effect.”1 Similarly, rHE may lead to similar modifications of the spatial configuration of the IAS and its relationship with the IVC, favoring PFO opening and blood flow from the IVC through the PFO.1,8 A prominent EV could contribute as well to flow redirection from the IVC to the IAS, as in fetal life. Of note, combined with atrial compression, it may functionally act as an acquired cor triatriatum dexter, compartmentalizing the RA.1 The combination of these mechanisms is well described in our case. In addition, an interesting finding is the postoperative persistence of the intra-atrial flow acceleration along the EV, despite the replacement of the aneurysmal ascending aorta. It underscores the complex pathogenesis of POS, related to the combined effect of multiple factors, whose relative weight is difficult to establish. Indeed, the multifactorial nature of POS is further supported by its low prevalence in relatively common conditions, such as PFO.9 Consequently, closure of the anatomic defect allowing R-L shunting represents the treatment of choice for POS.9, 10, 11 Recent European and international consensus recommend PFO closure when correlated with POS,10,11 despite the lack of large supporting studies given the small number of cases.9,12, 13, 14, 15
Hence, demonstrating a clear association between the presence of a PFO and clinical signs and symptoms suggestive of POS is paramount for its management.10,11 Firstly, a high degree of suspicion is a key factor in case of unexplained dyspnea and desaturation, in particular when exacerbated in the upright position.1,11 Objective demonstration of reduction in arterial saturation in the upright position is a key step in the diagnosis.1,2,11 The presence of known contributory factors further strengthens the suspicion of POS. PFO-related POS is a rule-out diagnosis, thus exclusion of other causes of respiratory failure is mandatory.1,11,12 However, POS should still be suspected even in the presence of other possible causes of hypoxemia, in particular when the clinical picture is disproportionate to other concomitant conditions or persists after their resolution.11 Transthoracic echocardiography represents the first diagnostic examination.1,2,11 The use of provocative maneuvers (eg, Valsalva maneuver) and agitated saline bubble contrast, which has to be performed in both supine and sitting positions, increases the sensitivity in detecting R-L shunting and PFO.16 Indeed, the presence of basal R-L shunting has been demonstrated even in the supine position in patients with POS,9 although dyspnea and arterial desaturation are exacerbated in the upright position. Therefore, performing transthoracic echocardiography with bubble contrast as well in the sitting position may facilitate the diagnosis. Notably, intravenous injection in the antecubital veins may lead to false-negative results when the IVC flow is preferentially directed toward the intracardiac shunt.11
In case of inconclusive or positive results for intracardiac shunts, TEE must be performed for confirmation of diagnosis and anatomical characterization of IAS.1,11 If TEE shows an intracardiac shunt with significant basal or induced R-L shunting, percutaneous closure should be considered. Surgical closure may be an alternative in case of other indications for cardiac surgery or if the atrial septal defect is not suitable for percutaneous closure. In case of absent or trivial R-L shunting, particularly when not associated with known contributory factors of POS (eg, ascending aorta abnormalities, rHE), extracardiac shunts or other uncommon causes of respiratory failure have to be extensively investigated. In this subset of patients without a clear association between PFO and POS, the benefit of percutaneous closure may be limited.11,12,14
In case of coexisting conditions that can potentially cause hypoxemia or in the presence of suspected concomitant extracardiac shunting, right heart catheterization can be particularly useful. Indeed, current European consensus suggests its employment whenever the pathogenetic role of PFO is not clear.11 Right heart catheterization can accurately assess the degree of intracardiac R-L shunting. In addition, a balloon occlusion test can show if closing the intracardiac shunt may lead to an effective increase in arterial saturation.11 However, invasive measurements obtained in the catheterization laboratory are influenced by several factors, in particular patient position.11 Although R-L shunting is commonly found even in the supine position, hemodynamic data may be different from ““real life” conditions, especially when R-L shunting through the PFO is intermittent and markedly dependent on patient position. Right heart catheterization can be valuable even when concern of significant right heart disease exists (ie pulmonary hypertension, right ventricle dysfunction, or restrictive physiology).11 In these conditions, PFO closure can lead to a significant increase in RA pressure and reduction of systemic cardiac output. In such cases, right heart catheterization may be extremely useful, providing precise measurements of intracardiac and pulmonary pressures; in addition, the ballon occlusion test may demonstrate the hemodynamic effect of PFO closure on RA pressure and cardiac output.17 A proposed diagnostic algorithm for intracardiac POS is described in Figure 8.
Figure 8.
Proposed Diagnostic Algorithm for the Management of Intracardiac Platypnea-Orthodeoxia Syndrome
∗Chest CT angiography and pulmonary angiography for pulmonary arteriovenous malformation (especially in patients with positive TTE bubble test for extracardiac shunt) and hepatopulmonary syndrome in patients with chronic liver disease (as evidenced by laboratory testing and liver ultrasound), high-resolution CT to evaluate lung parenchymal disease affecting predominantly lower lung regions and “zone 1 phenomena” (if not yet performed). ∗∗In case of suspected significant right heart disease or mixed etiology (ie, concomitant causes of hypoxemia or extracardiac platypnea-orthodeoxia syndrome). ∗∗∗Surgical closure in patients with other indications for cardiac surgery or atrial septal defect not amenable to percutaneous closure. CT = computed tomography; PFO = patent foramen ovale; POS = platypnea-orthodeoxia syndrome; RHC = right heart catheterization; R-L = right-to-left; TEE = transesophageal echocardiography; TTE = transthoracic echocardiography.
Future Directions
Demonstrating a clear association between the presence of a PFO and clinical manifestations of POS is essential in the diagnosis and management of this condition. A comprehensive multimodality assessment, including 3D TEE reconstruction and other imaging modalities when needed, is crucial to identify the contributing factors involved in the complex interplay underlying POS.
Conclusions
POS is a rare but serious condition, arising from the complex interplay of multiple factors. Closure of the anatomical shunt represents the treatment of choice. Therefore, a better understanding of the involved contributing factors, a comprehensive multimodality evaluation, and the exclusion of other concomitant causes after interdisciplinary discussion are paramount for a proper selection of patients amenable to closure.
Funding Support and Author Disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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