What is the probable cause of orthopnea and elevated JVP in a patient with ruled out cardiac and pulmonary causes?

Probable Causes of Orthopnea and Elevated JVP with Cardiac and Pulmonary Causes Ruled Out

When cardiac and pulmonary causes are definitively excluded, consider hepatic congestion from cirrhosis, superior vena cava syndrome, constrictive pericarditis (if not fully evaluated), severe obesity with expiratory flow limitation, orthostatic hypotension, or rarely intracardiac/intrapulmonary shunting without structural heart disease. 1, 2, 3

Systematic Approach to Alternative Diagnoses

Hepatic and Abdominal Causes

Cirrhosis with portal hypertension can present with elevated JVP and orthopnea through a distinct mechanism from primary cardiac disease 1:

• Portal hypertension triggers splanchnic vasodilation, creating a hyperdynamic circulatory state with increased cardiac output, elevated heart rate, and decreased systemic vascular resistance 1
• This activates neurohumoral systems causing sodium and water retention, increased blood volume, and hypervolemia that can elevate central venous pressures 1
• However, elevated JVP in cirrhotic patients more commonly reflects concurrent right heart dysfunction rather than being a direct consequence of portal hypertension itself 1
• Key distinguishing feature: Peripheral edema in cirrhosis is typically due to low plasma oncotic pressure and portal hypertension, not elevated right atrial pressure—but an elevated JVP in the presence of edema improves specificity that volume overload is contributing 1

Assess for: Stigmata of chronic liver disease (spider angiomata, palmar erythema, ascites), hepatomegaly, splenomegaly, and laboratory evidence of hepatic dysfunction 1

Obesity-Related Mechanisms

Severe obesity (BMI >40 kg/m²) can cause orthopnea through expiratory flow limitation independent of cardiac or primary pulmonary disease 2:

• Morbidly obese subjects breathe at low lung volumes with reduced expiratory reserve volume (ERV) 2
• In the supine position, functional residual capacity decreases due to gravitational effects of abdominal contents, promoting expiratory flow limitation 2
• Orthopnea in obesity is associated with lower seated ERV values and development of supine expiratory flow limitation, suggesting dynamic pulmonary hyperinflation and intrinsic positive end-expiratory pressure as mechanisms 2
• This occurs even with normal spirometry (FEV₁) and can present with elevated JVP from increased intrathoracic pressures 2

Assess for: BMI >40 kg/m², low seated ERV on pulmonary function testing, and improvement of symptoms with weight loss or non-invasive positive pressure ventilation 2

Orthostatic Hypotension

Orthostatic hypotension is a rarely considered but documented cause of orthostatic dyspnea 3:

• Dyspnea occurs in 30% of patients with orthostatic hypotension compared to 10% without it 3
• Shortness of breath coincides with blood pressure falls during postural changes in 25% of symptomatic patients 3
• The mechanism is likely ventilation-perfusion mismatch due to inadequate perfusion of ventilated lung apices when upright 3
• Critical distinction: This causes dyspnea when upright (opposite of typical orthopnea), but can be confused with orthopnea if the patient's description is imprecise 3

Assess for: Blood pressure and heart rate measurements in supine and standing positions (3-minute stand test), symptoms occurring with standing rather than lying down, and autonomic dysfunction history 3

Intracardiac or Intrapulmonary Shunting

Patent foramen ovale or pulmonary arteriovenous malformations can cause positional dyspnea without overt structural heart disease 4, 5:

• Right-to-left shunting across a patent foramen ovale occurs in approximately 20% of patients with pulmonary vascular disease and elevated right-sided pressures 4
• Platypnea-orthodeoxia syndrome (dyspnea and desaturation when upright, improving when supine) can occur with intracardiac or intrapulmonary shunts 5
• This presents as the opposite of typical orthopnea but involves positional dyspnea that may be mislabeled 5

Assess for: Oxygen saturation changes with position, contrast echocardiography (bubble study) to detect shunts, and consideration of CT pulmonary angiography if pulmonary arteriovenous malformations suspected 5

Constrictive Physiology

Constrictive pericarditis may be missed if echocardiography alone was performed without cardiac catheterization or cardiac MRI 4:

• Presents with elevated JVP, orthopnea, and signs of congestion similar to heart failure 4
• Echocardiography may appear relatively normal or show only subtle findings 4
• Requires specific evaluation: Cardiac catheterization showing equalization of diastolic pressures, cardiac MRI showing pericardial thickening, or CT showing pericardial calcification 4

Assess for: History of pericarditis, cardiac surgery, radiation therapy, tuberculosis exposure, and Kussmaul's sign (JVP rise with inspiration) 4

Superior Vena Cava Syndrome

SVC obstruction from mediastinal masses, thrombosis, or fibrosis causes elevated JVP and dyspnea 6:

• Presents with facial and upper extremity edema, dilated chest wall veins, and elevated JVP 6
• Orthopnea occurs from increased venous return and airway edema when supine 6

Assess for: Facial plethora, upper extremity swelling, dilated chest wall collateral veins, and contrast-enhanced chest CT to visualize SVC 6

Diagnostic Algorithm

1. Measure JVP accurately at 30-45 degrees elevation; normal is ≤8 cm H₂O above right atrium 6, 7

2. Assess for hepatic disease: Liver function tests, albumin, coagulation studies, abdominal ultrasound for cirrhosis and portal hypertension 1

3. Evaluate for severe obesity: Calculate BMI, perform pulmonary function tests including ERV measurement, assess for expiratory flow limitation 2

4. Test for orthostatic hypotension: Blood pressure supine and after 3 minutes standing; drop ≥20 mmHg systolic or ≥10 mmHg diastolic is diagnostic 3

5. Consider shunt evaluation: Contrast echocardiography (bubble study) to detect intracardiac or intrapulmonary shunts, with positional oxygen saturation measurements 5

6. Reassess for constrictive physiology: If not already done, cardiac MRI or CT for pericardial evaluation, consider cardiac catheterization if high suspicion 4

7. Evaluate mediastinum: Contrast-enhanced chest CT if SVC syndrome suspected based on physical examination 6

Common Pitfalls

• Assuming all orthopnea is cardiac: Obesity, liver disease, and positional hypotension are frequently overlooked 1, 3, 2
• Incomplete cardiac evaluation: Constrictive pericarditis requires more than echocardiography for diagnosis 4
• Confusing platypnea with orthopnea: Carefully clarify whether dyspnea worsens when lying down (orthopnea) or standing up (platypnea) 3, 5
• Missing JVP in obese patients: JVP measurement is challenging in obesity; consider hepatojugular reflux as alternative assessment 4, 6
• Overlooking cirrhosis contribution: Elevated JVP in cirrhotic patients warrants evaluation for concurrent cardiac disease, not dismissal as purely hepatic 1