Is pleural effusion in Pulmonary Artery Hypertension (PAH) typically transudative or exudative, and are they usually unilateral or bilateral?

Pleural Effusion in Pulmonary Arterial Hypertension

Pleural effusions in pulmonary arterial hypertension (PAH) are typically transudative and bilateral, though they can present as unilateral (more commonly right-sided) in a significant minority of cases.

Transudate vs Exudate

Pleural effusions in PAH are predominantly transudative in nature, reflecting the underlying pathophysiology of right heart failure (RHF) with elevated right atrial pressures 1, 2. When thoracentesis was performed in PAH patients with isolated RHF, four of five patients had transudates 1. This aligns with the general principle that more than 80% of transudates are due to heart failure, with the fluid accumulating from increased hydrostatic pressure rather than inflammatory pleural membrane changes 3.

Important Caveat on Classification

Approximately 25-30% of heart failure-related transudates may be misclassified as exudates when using Light's criteria 4, 5. If Light's criteria suggest an exudate but PAH with RHF is clinically suspected, you should:

• Calculate the serum-effusion albumin gradient: a value >1.2 g/dL reclassifies the effusion as a transudate due to heart failure 3, 4
• Measure NT-proBNP in serum or pleural fluid: levels >1500 μg/mL confirm heart failure as the cause 3, 4

This distinction is critical because it prevents unnecessary invasive diagnostic procedures in PAH patients whose effusions are simply manifestations of their underlying RHF 3.

Unilateral vs Bilateral Distribution

The distribution pattern in PAH-related pleural effusions shows considerable variability:

Bilateral Effusions (Most Common)

• Bilateral effusions occur in approximately 51.7% of PAH patients with connective tissue disease 2
• In idiopathic/familial PAH, bilateral distribution accounts for 26.3% of cases 1
• When effusions develop during follow-up in PAH patients without alternative causes, 73.7% are bilateral 6

Unilateral Effusions

• Right-sided unilateral effusions are more common than left-sided when effusions are not bilateral 1, 6
• In idiopathic/familial PAH, 57.9% of effusions are right-sided 1
• Among incident effusions in PAH follow-up, 15.8% are right-sided and 10.5% are left-sided 6

Heart failure in general is more likely to present with bilateral effusions (53.5% of bilateral effusions are due to heart failure), but unilateral presentations do occur 3.

Size and Clinical Significance

The majority of PAH-related pleural effusions are trace to small in size (58.6-63.2% of cases) 1, 2. Despite their often modest size, these effusions carry significant prognostic implications 6.

Hemodynamic Correlates

Patients with PAH who develop pleural effusions have:

• Significantly higher mean right atrial pressures (16.0 ± 6.8 mm Hg vs 8.8 ± 5.5 mm Hg in those without effusions, p < 0.001) 1
• Lower cardiac indices (2.1 ± 0.6 L/min/m² vs 2.5 ± 0.7 L/min/m², p = 0.011) 2

The elevated right atrial pressure is the key hemodynamic driver, reflecting the systemic venous congestion that leads to transudative fluid accumulation 1, 2.

Prognostic Impact

Development of a new pleural effusion in PAH is associated with markedly attenuated survival (HR: 5.13; 95% CI: 1.86-14.16 in multivariate analysis) 6. This negative prognostic impact persists even after adjusting for concomitant pericardial effusion, indicating that pleural effusion represents an independent marker of disease severity and RHF progression 6.

Incidence and Prevalence

• Prevalence on initial assessment: 7.3% of PAH patients 6
• Cumulative incidence during follow-up: 27.5% of PAH patients develop effusions 6
• Incident rate: 38.6 cases per 1000 person-years in PAH patients without alternative causes 6
• Higher rates in PAH associated with connective tissue disease: 39.3% overall, with 45.1% in scleroderma patients 2

Diagnostic Approach

When evaluating pleural effusions in PAH patients:

1. Perform thoracentesis if the diagnosis is uncertain or if the effusion is large enough to warrant drainage for symptomatic relief 1

2. Apply Light's criteria to distinguish transudate from exudate, but recognize the 25% misclassification rate for heart failure-related effusions 3

3. If Light's criteria suggest exudate but RHF is clinically evident, calculate the albumin gradient (>1.2 g/dL confirms transudate) or measure NT-proBNP (>1500 μg/mL confirms heart failure) 3, 4

4. Exclude alternative causes: In PAH cohorts, 19-32% of pleural effusions have explanations other than RHF, including infection, malignancy, or CTD-related pleuritis 1, 2

5. Assess for associated findings: Eight of 19 patients (42%) with RHF-related effusions also had ascites, indicating more severe systemic venous congestion 1

Management Implications

Treat the underlying RHF with diuretics as the primary intervention 7. Most transudates respond successfully to diuretic therapy, making further invasive procedures unnecessary 3. Therapeutic thoracentesis may be required for very large effusions causing significant dyspnea 7, but the majority of PAH-related effusions are small and managed medically 1, 2.

The presence of pleural effusion should prompt intensification of PAH-directed therapy and optimization of RHF management, given the strong association with adverse outcomes 6.