What is the cause of platypnea (shortness of breath that worsens in an upright position)?

From the Guidelines

Platypnea is a rare condition that requires prompt diagnosis and treatment to address the underlying cause, which is often related to liver disease or right-to-left cardiac shunts, and treatment should focus on addressing the underlying cause rather than the symptom itself. The pathogenesis of platypnea is multifactorial, involving the release of nitric oxide, endothelial activation of fractalkine, and increased expression and activity of nitric oxide synthase isoforms, as described in the EASL clinical practice guidelines for the management of patients with decompensated cirrhosis 1. The symptoms of platypnea are non-specific and mainly related to progressive right ventricular dysfunction, including shortness of breath, fatigue, weakness, angina, and syncope, as outlined in the 2015 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension 1.

The clinical presentation of platypnea may be modified by diseases that cause or are associated with the condition, as well as other concurrent diseases, and the physical signs of platypnea include left parasternal lift, an accentuated pulmonary component of the second heart sound, an RV third heart sound, a pansystolic murmur of tricuspid regurgitation, and a diastolic murmur of pulmonary regurgitation, as described in the 2015 ESC/ERS guidelines 1.

• Key points to consider in the diagnosis and treatment of platypnea include:
  • The importance of addressing the underlying cause rather than the symptom itself
  • The role of liver disease and right-to-left cardiac shunts in the pathogenesis of platypnea
  • The use of echocardiography with bubble study, CT scans, or pulmonary function tests to identify the underlying mechanism
  • The need for prompt treatment to improve symptoms and prevent complications
  • The potential benefits of liver transplantation in cases related to liver disease, as described in the EASL clinical practice guidelines 1
  • The potential benefits of closure of the defect via catheter-based procedures in patients with platypnea due to a PFO, as described in the example answer.

Proper diagnosis requires a high index of suspicion, and treatment should be individualized based on the underlying cause and severity of symptoms, as outlined in the ACC/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with chronic heart failure 1. Treatment should focus on addressing the underlying cause rather than the symptom itself, and patients should be advised to remain in positions that minimize their symptoms, typically lying down, while awaiting definitive treatment.

From the Research

Definition and Characteristics of Platypnea

• Platypnea is defined as shortness of breath that worsens in the upright position and improves when lying down 2, 3, 4.
• It is often associated with orthodeoxia, which represents hypoxemia that aggravates in the upright position 2, 3, 4.
• The causes of platypnea-orthodeoxia syndrome can be classified into intrapulmonary shunt, intracardiac shunt, and ventilation-perfusion mismatch 2.

Clinical Presentation and Diagnosis

• Patients with platypnea-orthodeoxia syndrome typically present with dyspnea and oxygen desaturation that worsens in the upright position and improves when lying down 2, 3.
• Diagnostic tests such as echocardiography, contrast-enhanced CT, and ventilation-perfusion scintigraphy can help identify the underlying cause of platypnea-orthodeoxia syndrome 3.
• Atrial septal defect (ASD) is a common cause of platypnea-orthodeoxia syndrome, and surgical or percutaneous closure of the defect can improve symptoms and oxygen saturation 2, 3.

Associated Conditions

• Platypnea-orthodeoxia syndrome can be associated with various conditions, including pulmonary embolism 4, hepatopulmonary syndrome 5, 6, and chronic obstructive pulmonary disease (COPD) 6.
• Hepatopulmonary syndrome is a pulmonary vascular complication of liver disease, characterized by intrapulmonary vascular dilatations and shunts, resulting in impaired gas exchange 5.
• Platypnea-orthodeoxia can be an effective diagnostic tool for hepatopulmonary syndrome, especially in patients with comorbid COPD 6.