Platypnea

Etiology

The literature has broadly classified the etiology of POS into intracardiac and extracardiac shunts. Intracardiac shunting-related conditions most commonly associated with POS include PFO, ASD, and ASA.[3] Extracardiac pathologies are further divided into intrapulmonary and extrapulmonary shunts. Examples of intrapulmonary causes are PAVM and lung parenchymal disease. HPS produces extrapulmonary shunting that gives rise to POS. Other articles implicate fat embolism and Parkinson disease as possible causes of POS, though the precise mechanism giving rise to POS in these disorders remains controversial.[4]

Epidemiology

No data currently exists estimating the incidence of POS. Most cases go undetected unless clinicians specifically ask about the symptoms. Additionally, the degree of positional dyspnea or SaO₂ reduction is not routinely determined during physical examination. Therefore, positional oxygenation level alterations can be easily overlooked.[5][6]

Pathophysiology

The pathophysiology of POS is not entirely understood, but the condition is highly associated with positional intracardiac or intrapulmonary right-to-left shunting. The shunts may arise from congenital cardiac disorders like PFO and acquired ones like pulmonary hypertension, pulmonary embolism, pneumonectomy, and significant pericardial effusions.

POS may also result from worsening V/Q mismatch in patients with underlying lung disease, especially when the lung bases are most affected. This mechanism has been reported in cases of idiopathic pulmonary fibrosis (IPF) in the lung bases and severe basilar pneumonia. The same can develop in HPS, as the upright position causes more blood to flow to the lung bases.[7]

The shunt fraction of total cardiac output (Qs/Qt) can be calculated by supplying the patient with 100% oxygen for 20 to 30 minutes and then using this equation:[8]

Qs/Qt (Shunt Fraction): (CcO₂ - CaO₂) / (CcO₂ - CvO₂)

In this equation, CcO₂ is the end capillary O₂ content, CaO₂ is the arterial blood's oxygen content, and CvO₂ is the mixed venous blood's oxygen content. In healthy individuals, the physiologic shunt fraction is about 5%.

History and Physical

POS is a symptom and not a disease. History and physical examination should focus on determining the condition's underlying cause.[9] On history, patients may describe dyspnea precipitated by assuming an upright position that improves when reclining. A history of a longstanding primary or secondary cardiopulmonary condition and poor exercise tolerance may be elicited. The patient may likewise report associated symptoms like chest pain, palpitations, dizziness, and fainting spells.

Physical examination is notable for hypoxemia in the upright position, improving in the reclining position. Other findings depend on POS' underlying cause. Cardiac auscultation may reveal murmurs in patients with congenital heart anomalies, though individuals with PFO may have normal heart sounds. Positional hypoxemia in the presence of a right-to-left shunt may not respond to oxygen supplementation.[16] Abnormal breath sounds, cyanosis, and clubbing may be present in patients with either heart or lung pathology. Signs of chronic hepatic disease, such as spider nevi, palmar erythema, ascites, and anasarca, may be present in patients with HPS.

Evaluation

Laboratory tests should focus on determining POS' underlying etiology. Patients with PFO may have a normal electrocardiogram, chest x-rays, blood counts, and metabolic panels. However, echocardiography will reveal the pathology.

Agitated saline bubble echocardiography distinguishes intracardiac from extracardiac shunts, making it an excellent initial imaging tool for POS evaluation. The appearance of microbubbles in the left atrium during the first 3 beats after opacification of the right chambers suggests an intracardiac shunt. Meanwhile, microbubble appearance after 3 to 6 beats is more consistent with extracardiac shunting. The Valsalva maneuver may help intensify right-to-left shunting. Other tests that can help evaluate shunts include contrast-enhanced echocardiography, macroaggregated-albumin scintigraphy, and invasive angiography.[10]

Plain chest radiography is usually not sensitive but may show an underlying lung disease that can explain POS occurrence. PFO may be detectable on computed tomography (CT) without contrast (see Image. Patent Foramen Ovale Computed Tomography). CT with contrast is useful when looking for an arteriovenous malformation (AVM).[11]

Patients with hepatic disease will have abnormal liver enzyme levels and coagulation test results. HPS arises from the triad of liver disease, arterial deoxygenation from pulmonary gas-exchange abnormalities, and evidence of intrapulmonary vascular dilatations. The following are the diagnostic criteria for this condition:[12]

• The presence of liver disease, portal hypertension, or both
• An elevated room air alveolar-arterial oxygen gradient {P(A-a)O₂ gradient} >15 mm Hg or >20 mm Hg in individuals older than 65
• Evidence of intrapulmonary vascular dilatations in the basal parts of the lungs
• Absence of other significant cardiopulmonary disease

Referral to specialists, such as pulmonologists, cardiologists, hepatologists, or interventional radiologists, is essential to determine the need for other specific tests.

Treatment / Management

POS interventions should be directed toward addressing the underlying disorder. Detailed management of each disease is beyond the scope of this review, but persistent hypoxia warrants oxygen supplementation. Early referral to specialists like cardiologists or pulmonologists can help refine the evaluation and management strategies. 

Patients with a possible cardiac condition may be referred to a cardiologist. PFO usually does not require any treatment as it may be present in up to 25% of people. However, POS and concerns for a paradoxical embolic stroke warrant a referral to a cardiovascular surgeon for possible surgical closure.

Underlying lung diseases must be treated appropriately and in a timely fashion. Patients with pneumonia may be given antibiotics. A pulmonology referral is required to treat complex pulmonary conditions like ILD. Interventional radiologists may perform embolotherapy for large PAVMs.[13](B3)

Liver transplantation, performed by a liver transplant specialist, is warranted in cirrhosis with HPS. Supportive treatment may be given to patients while waiting for surgery.[14]

Differential Diagnosis

Positional dyspnea is a symptom of many disorders. The differential diagnosis of POS includes an extensive list but may be classified into the following:

• Intracardiac shunting: PFO, ASD, ASA, valvular heart disease, cardiomyopathy
• Pulmonary vascular disorders: PAVMs, pulmonary hypertension
• Respiratory conditions: COPD, pneumonia, ILD
• Extrapulmonary conditions: diaphragmatic hernia or paralysis, liver failure
• Miscellaneous: orthostatic hypotension from causes like severe dehydration and blood loss, sleep-related breathing disorders

POS is a rare condition requiring a multidisciplinary approach for complete evaluation and appropriate management.

Prognosis

The prognosis of POS mainly depends on the severity of the underlying condition and the appropriateness of management.[15] Outcomes are generally excellent if the underlying cause is treated promptly and the patient completes rehabilitation. Poor prognostic factors include delayed management, poor treatment response, suboptimal cardiac function, and the presence of systemic complications.

Complications

POS' underlying conditions cause complications, not POS itself. These complications include the following:

• Persistent hypoxemia, leading to chronic heart failure and multiple organ dysfunction
• Risk of thromboembolic events, which usually accompanies intracardiac shunts
• Reduced quality of life, which may be due to shortness of breath and related symptoms like fatigue and cognitive impairment
• Surgical complications, including anesthesia-induced reactions, bleeding, and infection, in conditions treated surgically
• Progression of the underlying conditions, which may ultimately lead to death, as in cases of liver and heart failure 

Accurate diagnosis and timely treatment are crucial in preventing or mitigating POS' potential complications.