Eur opean Rev iew for Med ical and Pharmacol ogical Sci ences 2014; 18 2599-2604 The platypnea-orthodeoxia syndrome

E. AKIN, U. KRÜGER, P. BRAUN, E. STROH, I. JANICKE, R. REZWANIAN, I. AKIN 1, W.H. SCHÖLS

Herzzentrum Duisburg, Duisburg (Akademisches Lehrkrankenhaus der Heinrich-Heine-Universität Düsseldorf), Germany 1Medizinische Fakultät Mannheim, Universität Heidelberg, Mannheim, Germany

Abstract. The platypnea orthodeoxia syn - right position. Different underlying conditions drome (POS) is a rare condition characterized are cardiac, pulmonary or hepatic diseases 3,4 . by dyspnea and hypoxia in upright position. Pathopysiologic underlying mechanisms are Even though POS isn’t common, the incidence is 5 determined by an atrial right-to-left shunt. Co - probably underestimated . The syndrome occurs existing conditions that evolve POS can be of in a variety of clinical settings. Knowledge of anatomical nature causing interatrial communi - epidemiology, clinic, diagnostics and therapy cation or of functional nature producing a de - helps clinic practitioners to identify the some - formity of the atrial septum in upright position. times initially mysterious appearing disease. Diagnosis is difficult, as it needs to mention about POS. Classically, transthoracic and trans - esophageal echocardiography in supine and Definition upright position with use of contrast medium Platypnea is a breathlessness, which is trig - and/or Doppler will point the diagnosis. Treat - gered by orthostatism. Orthodeoxia is recognized ment is predominantly carried out by interven - as in the upright position. Symptoms tional closure of that are clinical observable as well as a decrease in ar - promptly resolves clinical symptoms. terial blood oxygen saturation in a sitting or standing position. Most patients exhibit interatrial Key words: communication with and surprisingly without in - Platypnea, PFO, Occluder, Dyspnea. creased right atrium pressures, what could explain right-left-shunting 5,6 . Underlying conditions are a PFO, atrial septal defect (ASD) and atrial septal Abbreviations aneurism (ASA) with septal fenestration (Figures 1, 2). Few other mechanisms can cause a reversal ASA = atrial septal aneurism; ASD = atrial septal defect; of blood-flow through the interatrial septum. In - PFO = persistent foramen ovale; POS = platypnea orth - volved conditions are pericardial effusion or con - odeoxia syndrome. striction, pulmonary hypertension, pulmonary emphysema, pulmonary arteriovenous malforma - Introduction tion, cirrhosis of the liver and aortic aneurysm 5,6-8 . Additional factors are a prominent eustachian Platypnea Orthodeoxia Syndrome (POS) is a valve and alterations of atrial geometry that af - relative rare but striking condition with clinically fects atrial pressures possibly because of right observed dyspnea and hypoxia in upright posi - atrial remodeling. Underlying alterations of af - tion. Symptoms resolve typically in lying posi - fected patients may be due to aneurismal expan - tion. First reported in 1949, a number of car - sion and elongation of the ascending aorta 6. Man - diopulmonary processes cause the condition due ifestation of POS can result as a consequence of to desoxygenation of blood 1. The syndrome anatomic changes after pulmonary surgery (pneu - bases on an atrial right-to-left shunting. A major - moectomy or lobectomy) (Figure 3) as well as de - ity of cases are affected by an opening of the in - velopment of kyphoscoliosis 9. teratrial septum, mostly because of a patent fora - Basically three types of causes can lead to men ovale (PFO) 2. Coexisting conditions that POS: cardiac, pulmonary and hepatic causes, evolve POS can be of anatomical nature causing namely intracardiac shunts, pulmonary arteriove - interatrial communication or of functional nature nous shunts and ventilation/perfusion mismatch producing a deformity of the atrial septum in up - (Table I) 5.

Corresponding Author: Ibrahim Akin, MD; e-mail: [email protected] 2599 E. Akin, U. Krüger, P. Braun, E. Stroh, I. Janicke, R. Rezwanian, I. Akin, W.H. Schöls

Figure 1. Interatrial septal aneurysm determined by trans - esophageal echocardiography.

Figure 3. MRI of a patient with right-sided pneumectomy with deformation of heart and vasculature structure.

Pathophysiology The detailed physiologic mechanism responsi - ble for the positional nature of shunting is not fully understood.

Intracardiac Right-to-Left Shunt Atrial communication can be a residue of em - bryonic development, when septa did not fuse un - Figure 2. Interatrial shunt due to perforation in septal til after birth and closure is only functional. The aneurysm.

Table I. Possible causes of platypnea-orthodeoxia syndrome. (Modified according to 2,5).

Intracardiac shunt R-L shunt without elevated Compression of RA by aortic dilatation or aneurysm PFO R-L pressure gradient Pericardial effusion or constrictive pericarditis ASD Postpneumectomy 1 ASA Decreased RA compliance (after myocardial infarction) Eosinophilic endomyocardial disease Abnormally lying Eustachian valve or Chiari network Kyphosis RA lipomatosis hypertrophy RA myxoma R-L shunt with Pulmonary thromboembolism R-L pressure gradient Idiopathic pulmonary hypertension Right hydrothorax Long-duration lung diseases causing pulmonary hypertension Postpneumectomy Pulmonal parenchymal Emphysema, COPD, parenchymal lung diseases ventilation/perfusion Other causes of ventilation/perfusion mismatch (autonomic dysfunction, amiodarone toxicity, mismatch hepatopulmonary syndrome) Pulmonary arteriovenous Hepatopulmonary syndrome shunt Pulmonary arteriovenous malformations or fistulae Osler-Weber-Rendu syndrome

R-I = Right-to-left; RA = right atrium; COPD = chronic obstructive pulmonary disease. 1Postpneumectomy shunt can be pre - sent with or without elevated right atrium pressure.

2600 Platypnea syndrome resulting PFO is common and affects at least 25 increased alveolar pressures can be the result in percent of the general population 5,9 . The rarer ASD patients with various lung diseases. In upright with lack of atrial septal tissue is caused by ostium position, especially in the apical regions of the primum, ostium secundum or sinus venous defect. lung, the situation aggravates. The pulmonary ASA is a result of interatrial septum displacement artery pressure drops and leads to pulmonary into the atrium due to enlargement of the mobile capillary compression. This situation can lead to septum (Figure 1, 2). There is a coexistence be - a cessation of blood flow and a respiratory dead tween PFO and ASA in cases with POS 5. space in apical areas of the lungs. A vicious cir - Of course, most people with PFO never devel - cle begins (diffuse Zone 1 phenomenon): the op symptoms of POS, because left atrium pres - dead space causes dyspnea and , sure is 5-8 mmHg higher than right atrium pres - what increases the dead space and air trapping as sure and atrial septum is functionally closed. well as alveolar pressure 5,9 . Thus, this pressure difference is thought to pro - hibit right-to-left shunting through a PFO or Epidemiology small ASD. Right-to-left shunt can occur because POS is a rare described condition. Ten years of a transient pressure elevation in the right atri - ago only 40 cases were published. By 2009 about um (hemodynamic causes) and/or a flow-phe - 130 patients with the disorder were identified. nomenon (anatomical distortion) 5,10 . Given the But etiology of POS remained in too many cases large difference between the prevalence of PFO unclear. A review of 2012 found 105 articles with and POS, it appears that this interatrial defect is a total of 188 patients, each of whom with ac - itself not sufficient to produce clinically evidence cepted true platypnea and orthodeoxia 5,11 . issues in most cases 11,12 . It is suspected that POS is present in patients with an existing PFO in Clinical Picture whom there is an additional disease process that Affected patients suffer from variable dyspnea increases right heart pressures. or/and hypoxemia dependent on posture. Pa - tients complain of dyspnea in upright position Pulmonary Arteriovenous Shunts (sitting and standing) with or without . and Ventilation/Perfusion Missmatch The history of symptoms can be short and symp - Another cause of POS can be a blood-flow of toms can emerge acute, worsen rapidly and be desoxygenated blood through arteriovenous com - progressive within few days. Flat lying relieves munications mostly in the bases of lungs 13,14 . The dyspnea and cyanosis, but not in all cases 11 . Pa - increased blood flow in upright position increas - tients don’t respond to classical therapies of es the shunt and produces symptoms. This phe - chronic pulmonary disease, ischemic heart dis - nomenon is mostly observed in patients with ad - ease or left ventricular dysfunction. Case reports vanced hepatopulmonary syndrome (HPS), when show, that affected patients have different addi - dilated capillary vessels cause ventilation-perfu - tional symptoms: tachycardia, , drop sion mismatch, arteriovenous pulmonary shunt of systolic pressure in upright posture 9, drop of and decreased alveolar-arterial oxygen diffusion. oxygen saturation in upright position, even if 13 to 47% of these patients are hypoxemic with - 100 percent oxygen is applied 10 . out identifiable lung or heart disease 5,9,15 . Normally in health gravity causes that the Investigations blood flow of lung bases is greater than in apical POS is a differential diagnosis of patients with lung regions. However, the alveolar pressure dyspnea and refractory hypoxemia. Diagnosis of keeps constant in the complete organ. However, right-to-left shunting is challenging. Initial as -

Table II. Possible criteria for platypnea-orthodeoxia syndrome. (Modified according to 2,5).

• Existence of an interatrial communication • Right-to-left shunt • No pulmonary hypertension or elevation of right atrial pressure

• Orthodeoxia (sPO 2 < 90% or pO 2 < 60 mmhg in upright position, normalization in lying position) • Dyspnea with taking upright position that disappears with lying

POD = Platypnea-orthodeoxia Syndrome; sPO 2 = oxygen saturation; pO 2 = partial pressure of oxygen.

2601 E. Akin, U. Krüger, P. Braun, E. Stroh, I. Janicke, R. Rezwanian, I. Akin, W.H. Schöls sessment should be the proof of a possible asso - latations. Contrast-enhanced echocardiography, ciation between breathlessness and upright posi - perfusion scan (scintigraphy) with macroaggre - tion. Following oxygen saturation and blood gas gated albumin and pulmonary arteriography 9,15 . analysis (pulse oximetry) in lying and upright Contrast echocardiography is the most sensitive position exhibits an orthostatic desaturation 5,9 . In choice and, moreover, less invasive than arteriog - hepatopulmonary syndrome a decrease in the raphy. Is direct arteriovenous communication partial atrial pressure of oxygen in upright posi - suspected and the response to therapy poor an - tion of about 5% or at least 4 mmHg was giography is reasonable. In contrast to intracar - defined 12,15 . One author notes that intracardiac diac communication in hepatopulmonary syn - shunting is not in all patients presented with clear drome, the passage of microbubbles during con - postural changes in blood oxygenation. Supple - trast echocardiography through the dilated pul - mental oxygen therapy may aid the identification monary vessels to the left atrium shows a delay of the disease, because the right-to-left atrial of three to six heart beats 5,9,15 . shunt prevents systemic oxygen saturation reach - ing 100 percent 6,11 . Treatment For definitive establishment of diagnosis Treatment depends on the cause of POS. In echocardiography with Doppler mode and con - cases of intracardiac communication without pul - junct contrast-enhanced echocardiography is im - monary hypertension closure of the defect is a portant. Both examinations ideally are performed causative therapy with a prompt improvement of in lying and upright position. These examinations symptoms. Closure can be surgical or percuta - may allow to localize, visualize and semiquanti - neous 5,10,17-20 . Nowadays, preferable is the percu - tate the shunt at the atrial level, because of the taneous approach with cardiac catheterization to passage of microbubbles to the left atrium in the close PFO (Figure 4, 5). Coexisting anatomic de - first three beats after right-cavity opacification. fects such as aortic elongation, aortic aneurysm, Another simple and the most sensitive examina - constrictive pericarditis or myxoma, however, re - tion is contrast tilt-table transesophageal echocar - quire surgical intervention 2,4,7 . diography in lying and upright position. Maybe Percutaneous closure of PFO or ASD can be per - in rare cases the shunt is seen only on Valsava formed with a buttoned device, CardioSEAL Septal maneuvers 11,16 . In one case of an occult atrial Occlusion System and Amplatzer Septal Occluder septum defect the shunt could be delineated with devices or Amplatzer PFO Occluder (Figure 4, 5). IV metaraminol, while transthoracic echocardio - After closure, aortic oxygen saturation and systemic graphy was without a result. Rodrigues et al 5 blood saturation have to be monitored. Residual found in a review of the literature evidence that shunt can be identified by echocardiography. Anti - transthoracic echocardiography can also be sensi - coagulation with acetylsalicylic acid should last tive and transthoracic Doppler echocadiography three month following implantation. Transcatheter is possibly just as effective as transoesophageal closure results in immediately enhanced oxygen echocardiography 5,6,9,12 . saturation in upright position after the procedure. If an intracardiac shunt is not confirmed, an Platypnea resolves complete 7,10,12 . intrapulmonary shunt can exist. Three image In patients with hepatopulmonary syndrome techniques can show intrapulmonary vascular di - (HPS) advanced liver disease is the cause of POS

Figure 4. Interventional closure of patent interatrial septal cummunication by PFO-occluder.

2602 Platypnea syndrome

Figure 5. Transesophageal echocardiog - raphy in a patient with PFO-occluder im - plantation.

––––––––––––– –– –– –––– and liver transplantation is the only causal therapy. Conflict of interest No other treatment like almitrine bismesylate, so - The Authors declare that they have no conflict of interests. matostatin analog, indomethacin or plasmaphere - sis had been effective. First management can be oxygen therapy, bed rest, salt restriction and di - uretics. After transplantantion in 80% of patients Reference oxygenation improves, but severe hypoxemia is a 4,8 leading cause of perioperative mortality . 1) BURCHELL HB, H ELMHOLZ HF, W OOD EH. Reflex Underlying pulmonary diseases must be treat - Orthostatic dyspnea associated with pulmonary ed to improve ventilation-perfusion matching. hypertension. Am J Physiol 1949; 159: 563- 564. 2) CHENG TO. Platypnea-orthodeoxia syndrome: eti - ology, differential diagnosis, and management. Conclusions Cathet Cardiovasc Interv 1999; 47: 64-66. 3) BAKRIS NC, S IDDIQI AJ, F RASER CD J R, M EHTA AC. POS is still a relative rare condition, that often Right-to-left interatrial shunt after pneumectomy. develops acute and shortly, but incidence is pos - Ann Thorac Surg 1997; 63: 198-201. sibly underestimated. Shunting blood from the 4) BELLATO V, B RUSA S, B ALAZOVA J, M ARESCOTTI S, D E CARIA right to the left heart is the most common cause D, B ORDONE G. Platypnea-orthodeoxia syndrome in of the disease. Most patients suffer from PFO interatrial right to left shunt postpneumonectomy. and the causative therapy is obvious, namely Minerva Anestesiol 2008; 74: 271-275. closing of PFO. Other defects of the interatrial 5) RODRIGUES P, P ALMA P, S OUSA -P EREIRA L. Platypnea- septum also need percutaneous or surgical treat - Orthodeoxia Syndrome in review: Defining a new disease. Cardiology 2012; 123: 15-23. ment. Probably, there are additional anatomic 6) PTASZEK MP, S ALDANA F, P ALACIOS IF. Platypnea-Orth - changes that finally lead to POS. These changes odeoxia Syndrome in two previously healthy can follow lung surgery and malformations like adults. A case-based review. Clin Med Cardiol kyphoscoliosis or they develop age-related. The 2009; 3: 37-43. concrete triggers of POS and the role of anatom - 7) ADOLPH EA, L ACY WO, H ERMONI YI, W EXLER LF, J AVA - ic changes remain unclear and are possibly more HERI S. Reversible orthodeoxia and platypnea due individual. Nevertheless, increasing reports and to right-to-left intracardiac shunting related to case reports of POS call for attention and physi - pericardial effusion. Ann Intern Med 1992; 116: 138-139. cians should be attentive of patients with unex - 8) LAYBOURN KA, M ARTIN ET, C OOPER RA, H OLMAN WL. plained or paroxysmal hypoxia. Diagnosis is Platypnea and orthodeaxia: shunting associated easy, if the track is followed in the right direc - with an aortic aneurysm. J Thorac Cardiovasc tion. Surg 1997; 113: 955-956.

2603 E. Akin, U. Krüger, P. Braun, E. Stroh, I. Janicke, R. Rezwanian, I. Akin, W.H. Schöls

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