Platypnea-orthodeoxia syndrome is an intriguing condition that comprehends multiple pathologic phenomena. It requires a high clinical suspicion and is probably underdiagnosed. Its identification has therapeutic implications and can have a huge impact on the patient’s everyday life. We made a review of the literature and analyzed 188 cases described thus far, trying to identify the underlying mechanisms and risk factors. We propose that a separate entity is created within the spectrum of platypnea-orthodeoxia syndrome that is responsible for the majority of cases, namely platypnea-orthodeoxia disease, which would be defined as the existence of an interatrial communication, with a right-to-left shunt, normal pressure in the right atrium and, of course, platypnea and orthodeoxia. Most patients with this disease were submitted to percutaneous closure of the patent foramen ovale or atrial septal defect, with favorable results, making it the first-line therapeutic approach nowadays.

Keywords:
Atrial septal defect, Platypnea, Orthodeoxia, Patent foramen ovale
1.
Strunk BL, Cheitlin MD, Stulbarg MS, Schiller NB: Right-to-left interatrial shunting through a patent foramen ovale despite normal intracardiac pressures. Am J Cardiol 1987;60:413–415.
2.
Burchell HB, Helmholz HF Jr, Wood EH: Reflex orthostatic dyspnea associated with pulmonary hypotension. Am J Physiol 1949;159:563–564.
3.
Schnabel TG Jr, Ratto O, Kirby CK, Johnson J, Comroe JH: Postural cyanosis and angina pectoris following pneumonectomy: relief by closure of an interatrial septal defect. J Thorac Surg 1956;32:246–250.
4.
Altman M, Robin ED: Platypnea (diffuse zone I phenomenon?). N Engl J Med 1969;281:1347–1348.
5.
Robin ED, Laman D, Horn BR, Theodore J: Platypnea related to orthodeoxia caused by true vascular lung shunts. N Engl J Med 1976;294:941–943.
6.
Seward JB, Hayes DL, Smith HC, et al: Platypnea-orthodeoxia: clinical profile, diagnostic workup, management, and report of seven cases. Mayo Clin Proc 1984;59:221–231.
7.
Krowka MJ, Dickson ER, Cortese DA: Hepatopulmonary syndrome: clinical observations and lack of therapeutic response to somatostatin analogue. Chest 1993;104:515–521.
8.
Lange PA, Stoller JK: The hepatopulmonary syndrome. Ann Intern Med 1995;122:521–529.
9.
Sherlock S: Vasodilatation associated with hepatocellular disease: relation to functional organ failure. Gut 1990;31:365–367.
10.
Rodriguez-Roisin R, Roca J: Hepatopulmonary syndrome: the paradigm of liver-induced hypoxaemia. Baillieres Clin Gastroenterol 1997;11:387–406.
11.
Rodríguez-Roisin R, Krowka M: Hepatopulmonary syndrome – a liver-induced lung vascular disorder. N Engl J Med 2008;358:2378–2387.
12.
Luo B, Liu L, Tang L, et al: Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. J Hepatol 2003;38:556–563.
13.
Raffy O, Sleiman C, Vachiery F, et al: Refractory hypoxemia during liver cirrhosis. Hepatopulmonary syndrome or ‘primary’ pulmonary hypertension? Am J Respir Crit Care Med 1996;153:1169–1171.
14.
Hoeper MM, Krowka MJ, Strassburg CP: Portopulmonary hypertension and hepatopulmonary syndrome. Lancet 2004;363:1461–1468.
15.
Papiris SA, Maniati MA, Manoussakis MN, Constantopoulos SH: Orthodeoxia in amiodarone-induced acute reversible pulmonary damage. Chest 1994;105:965–966.
16.
Ferry TG, Naum CC: Orthodeoxia-platypnea due to diabetic autonomic neuropathy. Diabetes Care 1999;22:857–859.
17.
Fox JL, Brown E, Harrison JK, Williams J, Terry PB: Platypnea-orthodeoxia and progressive autonomic failure. Am Rev Respir Dis 1989;140:1802–1804.
18.
DesJardin JA, Martin RJ: Platypnea in the intensive care unit. A newly described cause. Chest 1993;104:1308–1309.
19.
Cheng TO: Platypnea-orthodeoxia syndrome: etiology, differential diagnosis, and management. Catheter Cardiovasc Interv 1999;47:64–66.
20.
Angelini M, Lambru G, Montepietra S, Riccardi M, Zanferrari C, Bortone E: Unexplained dyspnea in an old patient with recurrent stroke: platypnea-orthodeoxia syndrome and evidence of patent foramen ovale. Neurol Sci 2010;31:93–94.
21.
Lopez G: Platypnea-orthodeoxia syndrome. Medicina (B Aires) 2005;65:268–272.
22.
Cheng TO: Mechanisms of platypnea-orthodeoxia: what causes water to flow uphill? Circulation 2002;105:e47.
23.
Hagen PT, Scholz DG, Edwards WD: Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. Mayo Clin Proc 1984;59:17–20.
24.
Mügge A, Daniel WG, Angermann C, et al: Atrial septal aneurysm in adult patients. A multicenter study using transthoracic and transesophageal echocardiography. Circulation 1995;91:2785–2792.
25.
Franke A, Hanrath P: The role of atrial septal abnormalities in cryptogenic stroke – still questionable? Eur Heart J 2001;22:198–200.
26.
Silver MD, Dorsey JS: Aneurysms of the septum primum in adults. Arch Pathol Lab Med 1978;102:62–65.
27.
Fox ER, Picard MH, Chow CM, Levine RA, Schwamm L, Kerr AJ: Interatrial septal mobility predicts larger shunts across patent foramen ovales: an analysis with transmitral Doppler scanning. Am Heart J 2003;145:730–736.
28.
Acharya SS, Kartan R: A case of orthodeoxia caused by an atrial septal aneurysm. Chest 2000;118:871–874.
29.
Kedia G, Tobis J, Lee MS: Patent foramen ovale: clinical manifestations and treatment. Rev Cardiovasc Med 2008;9:168–173.
30.
Steiner MM, Di Tullio MR, Rundek T, et al: Patent foramen ovale size and embolic brain imaging findings among patients with ischemic stroke. Stroke 1998;29:944–948.
31.
Irwin B, Ray S: Patent foramen ovale – assessment and treatment. Cardiovasc Ther 2012;30:e128–e135.
32.
Bertaux G, Eicher JC, Petit A, Dobsák P, Wolf JE: Anatomic interaction between the aortic root and the atrial septum: a prospective echocardiographic study. J Am Soc Echocardiogr 2007;20:409–414.
33.
Godart F, Rey C: Platypnea-orthodeoxia syndrome: a probably underestimated syndrome? Chest 2001;119:1624–1625.
34.
Rao PS, Palacios IF, Bach RG, Bitar SR, Sideris EB: Platypnea-orthodeoxia: management by transcatheter buttoned device implantation. Catheter Cardiovasc Interv 2001;54:77–82.
35.
Delgado G, Inglessis I, Martin-Herrero F, et al: Management of platypnea-orthodeoxia syndrome by transcatheter closure of atrial communication: hemodynamic characteristics, clinical and echocardiographic outcome. J Invasive Cardiol 2004;16:578–582.
36.
Hashimoto M, Okawa Y, Baba H, Nishimura Y, Aoki M: Platypnea-orthodeoxia syndrome combined with constrictive pericarditis after coronary artery bypass surgery. J Thorac Cardiovasc Surg 2006;132:1225–1226.
37.
Adolph EA, Lacy WO, Hermoni YI, Wexler LF, Javaheri S: Reversible orthodeoxia and platypnea due to right-to-left intracardiac shunting related to pericardial effusion. Ann Intern Med 1992;116:138–139.
38.
Patel AD, Abo-Auda WS, Nekkanti R, et al: Platypnea-orthodeoxia in a patient with ostium primum atrial septal defect with normal right heart pressures. Echocardiography 2003;20:299–303.
39.
Wright RS, Simari RD, Orszulak TA, Edwards WD, Gleich GJ, Reeder GS: Eosinophilic endomyocardial disease presenting as cyanosis, platypnea, and orthodeoxia. Ann Intern Med 1992;117:482–483.
40.
Romero T, Covell J, Friedman WF: A comparison of pressure-volume relations of the fetal, newborn, and adult heart. Am J Physiol 1972;222:1285–1290.
41.
Mackenzie IM, Banning A, Dyar O: Pharmacologic exposure of an occult atrial septal defect. Crit Care Med 2001;29:1832–1834.
42.
Khouzaie TA, Busser JR: A rare cause of dyspnea and arterial hypoxemia. Chest 1997;112:1681–1682.
43.
Lynch JJ, Schuchard GH, Gross CM, Wann LS: Prevalence of right-to-left atrial shunting in a healthy population: detection by Valsalva maneuver contrast echocardiography. Am J Cardiol 1984;53:1478–1480.
44.
Kusunose K, Yamada H, Todoroki T, et al: Platypnea-orthodeoxia syndrome associated with patent foramen ovale and aortic ectasia. Echocardiography 2009;26:114–117
45.
Baptista R, da Silva AM, Castro G, Monteiro P, Providência LA: Ascending aortic aneurysm and patent foremen ovale: a rare cause of platypnea-orthodeoxia. Rev Port Cardiol 2011;30:445–450.
46.
Faller M, Kessler R, Chaouat A, Ehrhart M, Petit H, Weitzenblum E: Platypnea-orthodeoxia syndrome related to an aortic aneurysm combined with an aneurysm of the atrial septum. Chest 2000;118:553–557.
47.
Eicher J-C, Bonniaud P, Baudouin N, et al: Hypoxaemia associated with an enlarged aortic root: a new syndrome? Heart 2005;91:1030–1035.
48.
Bashour T, Kabbani S, Saalouke M, Cheng TO: Persistent Eustachian valve causing severe cyanosis in atrial septal defect with normal right atrial pressure. Angiology 1983;34:79–83.
49.
Shakur R, Ryding A, Timperley J, Becher H, Leeson P: Late emergence of platypnea orthodeoxia: Chiari network and atrial septal hypertrophy demonstrated with transoesophageal echocardiography. Eur J Echocardiogr 2008;9:694–696.
50.
Sanikommu V, Lasorda D, Poornima I: Anatomical factors triggering platypnea-orthodeoxia in adults. Clin Cardiol 2009;32:E55–E57.
51.
Teupe CH, Groenefeld GC: Platypnea-orthodeoxia due to osteoporosis and severe kyphosis: a rare cause for dyspnea and hypoxemia. Heart Int 2011;6:e13.
52.
Toffart AC, Bouvaist H, Feral V, Blin D, Pison C: Hypoxemia-orthodeoxia related to patent foramen ovale without pulmonary hypertension. Heart Lung 2008;37:385–389.
53.
Marini C, Miniati M, Ambrosino N, et al: Dyspnea and hypoxaemia after lung surgery: the role of interatrial right-to-left shunt. Eur Respir J 2006;28:174–181.
54.
Yalonetsky S, Nun AB, Shwartz Y, Lorber A: Transcatheter closure of a patent foramen ovale prior to a pneumonectomy to prevent platypnea syndrome. Eur J Cardiothorac Surg 2006;29:622–624.
55.
Roxas-Timonera M, Larracas C, Gersony D, Di Tullio M, Keller A, Homma S: Patent foramen ovale presenting as platypnea-orthodeoxia: diagnosis by transesophageal echocardiography. J Am Soc Echocardiogr 2001;14:1039–1041.
56.
Pitcher D, Fletcher P, Laszlo G, Keen G, Rees JR: Onset of right-to-left shunting through a foramen ovale in a 70-year-old woman: successful surgical treatment. Eur Heart J 1986;7:541–544.
57.
Godart F, Rey C, Prat A, et al: Atrial right-to-left shunting causing severe hypoxaemia despite normal right-sided pressures: report of 11 consecutive cases corrected by percutaneous closure. Eur Heart J 2000;21:483–489.
58.
Legras A, Dequin PF, Hazouard E, Doucet O, Tranquart F, Perrotin D: Right-to-left interatrial shunt in ARDS: dramatic improvement in prone position. Intensive Care Med 1999;25:412–414.
59.
Smeenk FW, Postmus PE: Interatrial right-to-left shunting developing after pulmonary resection in the absence of elevated right-sided heart pressures: review of the literature. Chest 1993;103:528–531.
60.
Herregods MC, Timmermans C, Frans E, Decramer M, Daenen W, De Geest H: Diagnostic value of transesophageal echocardiography in platypnea. J Am Soc Echocardiogr 1993;6:624–627.
61.
Drighil A, El Mosalami H, Elbadaoui N, Chraibi S, Bennis A: Patent foramen ovale: a new disease? Int J Cardiol 2007;122:1–9.
62.
DeSouza KA, Saraswat S, DeSouza SA, Rajaram V, Reddy PC, Mosley L, Tandon N: Platypnea-orthodeoxia syndrome: a diagnostic challenge. South Med J 2009;102:1046–1048.
63.
Otto CM: Textbook of Clinical Echocardiography. Philadelphia, Saunders, 2004.
64.
Kerut EK, Norfleet WT, Plotnick GD, Giles TD: Patent foramen ovale: a review of associated conditions and the impact of physiological size. J Am Coll Cardiol 2001;38:613–623.
65.
Angelini M, Lambru G, Montepietra S, Riccardi M, Zanferrari C, Bortone E: Unexplained dyspnea in an old patient with recurrent stroke: platypnea-orthodeoxia syndrome and evidence of patent foramen ovale. Neurol Sci 2010;31:93–94.
© 2012 S. Karger AG, Basel
2012
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.