Editorial Comment

Platypnea-OrthodeoxiaSyndrome: Etiology, DifferentialDiagnosis, and Management

Tsung O. Cheng, MD

George Washington UniversitySchool of Medicine and Health Sciences,Washington, D.C.

The platypnea-orthodeoxia syndrome appears to beexceedingly rare. According to a 1997 editorial by Robinand McCauley [1], only 19 cases had been reported. The20 more cases I found in a cursory review of the literature[2–13] and the additional case reported by Iskander et al.in this issue make a total of 40 cases up to date.

The original description of patients with platypnea-orthodeoxia syndrome dates back to 1949 when Burchellet al. [14] described a patient with a posttraumaticintrathoracic venous-arterial type of blood shunt whoexhibited a threefold increase in ventilation and a 15-point decrease in arterial oxygen saturation whenever hewas in an upright position. The termsplatypnea(flatbreathing), defined as dyspnea induced by upright postureand relieved by recumbency, andorthodeoxia, defined asarterial oxygen desaturation accentuated by upright pos-ture and improved by recumbency, were actually not usedto describe the manifestations of this syndrome until 1969[15] and 1976 [16], respectively. Patients with thissyndrome may or may not have a decubitus preference(‘‘trepopnea’’) [12].

Although the precise mechanisms for both platypneaand orthodeoxia are not yet known, several postulationshave been advanced. The conditions under which platy-pnea-orthodeoxia have been associated with are listed inTable I.

The most common etiologic association is an interatrialright-to-left shunt through a patent foramen ovale, or anatrial septal defect or an atrial septal aneurysm. Right-to-left interatrial shunting is usually associated with sponta-neous [17] or induced [18] pulmonary hypertension. Inthe absence of pulmonary hypertension and, therefore, inthe absence of a right-to-left pressure gradient, what is themechanism for a right-to-left shunt? Or put in anotherway, what causes water to flow uphill [1]? A persistentEustachian valve can cause interatrial right-to-left shunt-ing with a normal right atrial pressure [19]. Platypnea-

orthodeoxia could be explained on the basis of positionalmodification of abnormal shunting. Standing uprightcould stretch the interatrial communication, be it a patentforamen ovale, an atrial septal defect, or a fenestratedatrial septal aneurysm, thus allowing more streaming ofvenous blood from inferior vena cava through the defect,whether or not a persistent Eustachian valve coexists[20,21]. This redirection of flow caused by an anatomicdistortion of the right atrium or the atrial septum alsomight occur from a loculated pericardial effusion [4] or anaortic aneurysm [13].

The mechanism for platypnea in constrictive pericardi-tis is not well understood. One possible explanation isthat with constrictive pericarditis a high filling pressure isrequired to maintain an adequate cardiac output. With thepatient in the upright position the right ventricularpreload diminished, resulting in decreased right-sidedcardiac output. This would cause diminished pulmonaryarteriolar pressures and a greater proportion of Zone Ihemodynamics. As a result, there would be an increase inV̇/Q̇ mismatch, increased work of breathing, and dys-pnea. This cascade would be reversed in the recumbentposition, with a return to higher filling pressures in theright side of the heart [8].

Platypnea-orthodeoxia may occur in rare patients withpulmonary emphysema [16]. Because the capillary pres-sure at the top of the lung in normal man in the uprightposition is not as high as the alveolar pressure, the apex ofthe lung receives no appreciable blood flow when thesubject is upright [22]. Because of high alveolar pressurein patients with emphysema, a further decrease in theperfusion of the apex of the lung in the upright posture,unaccompanied by a comparable decrease in ventilation,should cause an increase in the pulmonary dead spacecausing hyperventilation and dyspnea [22]. In platypnea-orthodeoxia associated with pulmonary arteriovenouscommunications, the latter were largely basal in location[16]. When the patient assumed a sitting or standingposition, gravity increased basal pulmonary blood flow[22], in turn increasing blood flow through basal shunts inthe sitting or standing position. Similarly, in patients withthe rare combination of pneumonectomy and atrial septaldefect or patent foramen ovale, platypnea-orthodeoxiawas related to the detrimental effect of the verticalposition on cardiac output and to the generation of apressure gradient across the atrial septal defect or patentforamen ovale caused by restriction of the pulmonary

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vascular bed (pneumonectomy) and by postpneumonec-tomy fluid filling of the hemithorax [16].

Pulmonary toxicity is the most serious side effect ofamiodarone. Possible mechanisms include metabolic dis-turbance (lipid storage disorder), hypersensitivity reac-tion, and a combination of both [9]. Amiodarone pulmo-nary toxicity is usually dose-related: a dosage greaterthan 400 mg daily for months or years is usually requiredto develop toxic effects. Only one other case has beenreported of orthodeoxia as a manifestation of amiodaronepulmonary toxicity [9]. The case report by Iskander et al.in this issue is the second such case. Two differentmechanisms may be implicated in this phenomenon:failure of the local vasoconstrictive control, and obligategravitational perfusion to the basal alveolar units, withexaggeration of the ventilation-perfusion mismatch [9].

Two abdominal causes of platypnea-orthodeoxia arecirrhosis of the liver [5,16] and ileus [7]. In cirrhosis, trueanatomic intrapulmonary arteriovenous shunts can occurat the lung bases [16]. In the upright position, blood flowfollows gravity to the bases, increases intrapulmonaryshunt, and creates hypoxemia unresponsive to the supple-mental oxygen. Alternatively, due to the basilar dilatationof intrapulmonary precapillary and capillary blood ves-sels, a central stream of venous blood may be created.This central blood may remain unoxygenated due to theincreased distance from the alveolar epithelium in thesetting of a decreased transit time [23]. DesJardin andMartin [7] postulated that in their patient with chronicobstructive pulmonary disease, impaired abdominalmuscle contraction in the upright position secondary toileus was responsible for the development of platypnea.

Fox et al. [24] reported a case of platypnea-orthodeoxiain a patient with minimal obstructive airway disease andprogressive autonomic failure. In their proposed mecha-nism, a basilar ventilation-perfusion mismatch existsbecause of air trapping. When supine, venous return andpulmonary vascular pressures are sufficient to perfusewell-ventilated regions of the lung and prevent hypox-emia. When erect, the underlying autonomic failure

produces inadequate pulmonary vascular perfusion, ZoneI proliferation, and, ultimately, in combination with thebasilar ventilation-perfusion mismatch, hypoxemia. Thecorrection of their patient’s platypnea-orthodeoxia bypostural changes alone and its successful management byincreasing intravascular volume support this hypothesis.

Treatment of platypnea-orthodeoxia should always bedirected at the underlying source of vascular shunting. Inthe case of interatrial shunting, it is not always necessaryto repair the patent foramen ovale or atrial septal defectby open heart surgery. Current recommendation calls forpercutaneous transcatheter closure [11], which avoids themorbidity, mortality, and increased expenses associatedwith open heart surgical procedures [25,26] and should beconsidered the procedure of choice for relief of platypnea-orthodeoxia due to interatrial right-to-left shunting [11].

REFERENCES

1. Robin ED, McCauley RF. An analysis of platypnea-orthodeoxiasyndrome including a ‘‘new’’ therapeutic approach. Chest 1997;112:1449–1951.

2. Sorrentino M, Resnekov L. Patent foramen ovale associated withplatypnea and orthodeoxia. Chest 1991;100:1157–1158.

3. Murray KD, Kalanges LK, Weiland JE, Binkley PF, Howanitz EP,Galbraith TA, Myerowitz PD. Platypnea-orthodeoxia: an unusualindication for surgical closure of a patent foramen ovale. J CardSurg 1991;6:62–67.

4. Adolph EA, Lacy WO, Hermoni YI, Wexler LF, Javaheri S.Reversible orthodeoxia and platypnea due to right-to-left intracar-diac shunting related to pericardial effusion. Ann Intern Med1992;116:138–139.

5. Byrd RP Jr, Lopez PR, Joyce BW, Roy TM. Platypnea, orthode-oxia and cirrhosis. J Ky Med Assoc 1992;90:189–192.

6. Timmermans C, Frans E, Herregods C, Decramer M, Daenen W,De Geest H. Platypnea-orthodeoxia syndrome: a report of twocases. Acta Cardiologica 1993;48:583–590.

7. DesJardin JA, Martin RJ. Platypnea in the intensive care unit: anewly described cause. Chest 1993;104:1308–1309.

8. Mashman WF, Silverman ME. Platypnea related to constrictivepericarditis. Chest 1994;105:636–637.

9. Papiris SA, Maniati MA, Manoussakis MN, Constantopoulos SH.Orthodeoxia in amiodarone-induced acute reversible pulmonarydamage. Chest 1994;105:965–966.

10. Bourke SJ, Munro NC, White JES, Gibson GJ, Ashcroft T, CorrisPA. Platypnea-orthodeoxia in cryptogenic fibrosing alveolitis.Respir Med 1995;89:387–389.

11. Landzberg MJ, Sloss LJ, Faherty CE, Morrison BJ, Bittl JA,Bridges ND, Casale PN, Keane JF, Lock JE. Orthodeoxia-platypnea due to intracardiac shunting: relief with transcatheterdouble umbrella closure. Cathet Cardiovasc Diagn 1995;36:247–250.

12. Dear WE, Chen P, Barasch E, Anderson HV, Varughese AT, MacrisMP. Sixty-eight-year-old woman with intermittent hypoxemia.Circulation 1995;91:2284–2289.

13. Laybourn KA, Martin ET, Cooper RAS, Holman WL. Platypneaand orthodeoxia: shunting associated with an aortic aneurysm. JThorac Cardiovasc Surg 1997;113:955–956.

14. Burchell HB, Helmholz HF Jr, Wood EH. Reflex orthostaticdyspnea associated with pulmonary hypotension. Am J Physiol1949;159:563–564.

TABLE I. Differential Di agnosis of Platypnea-Orthodeoxia

Cardiac Patent foramen ovaleAtrial septal defectAtrial septal aneurysmPericardial effusionConstrictive pericarditisAortic aneurysm

Pulmonary EmphysemaArteriovenous communicationsPneumonectomyAmiodarone toxicity

Abdominal Hepatic cirrhosisIleus

Autonomic dysfunction

Platypnea-Orthodeoxia Syndrome 65

15. Altman M. Robin ED. Platypnea (diffuse Zone I phenomenon)? NEngl J Med 1969;281:1347–1348.

16. Robin ED, Laman D, Horn BR, Theodore J. Platypnea related toorthodeoxia caused by true vascular lung shunts. N Engl J Med1976;294:941–943.

17. Cheng TO. Right-to-left atrial shunting. Chest 1991;99:526–527.18. Cheng TO. Paradoxical embolism: a diagnostic challenge and its

detection during life. Circulation 1976;53:565–568.19. Bashour T, Kabbani S, Saalouke M, Cheng TO. Persistent Eusta-

chian valve causing severe cyanosis in atrial septal defect withnormal right heart pressures. Angiology 1983;34:79–83.

20. Cheng TO. Reversible orthodeoxia. Ann Intern Med 1992;116:875.

21. Cheng TO. Platypnea-orthodeoxia due to interatrial right-to-leftshunting. Acta Cardiologica 1994;49:217.

22. Riley RL, Permutt S, Said S, Godfrey M, Cheng TO, Howell JBL,Shepard RH. Effect of posture on pulmonary dead space in man. JAppl Physiol 1959;14:339–344.

23. Vora SG, Nierman DM. Platypnea related to constrictive pericardi-tis. Chest 1995;107:887.

24. Fox JL, Brown E, Harrison JK, Williams J, Terry PB. Platypnea-orthodeoxia and progressive autonomic failure. Am Rev RespirDis 1989;140:1802–1804.

25. Cheng TO. Impending paradoxical embolism: a rare but importantdiagnosis. Br Heart J 1991;66:258.

26. Cheng TO. Paradoxic embolism. Am Heart J 1996;131:1238.

66 Cheng