Can right pleural effusion occur in cardiac amyloidosis?

Right Pleural Effusion in Cardiac Amyloidosis

Yes, right pleural effusion can occur in cardiac amyloidosis, and it may be due to both cardiac dysfunction and direct pleural infiltration by amyloid deposits. 1

Mechanisms of Pleural Effusion in Cardiac Amyloidosis

Pleural effusions in cardiac amyloidosis can develop through several mechanisms:

1. Heart failure-related mechanisms:

   • Increased hydrostatic pressure due to restrictive cardiomyopathy
   • Biventricular dysfunction, particularly right ventricular dysfunction
   • Elevated central venous pressure

2. Direct amyloid infiltration:

   • Pleural involvement with amyloid deposits 2
   • Disruption of pleural function by amyloid proteins
   • Impaired lymphatic drainage

3. Vascular mechanisms:

   • Vascular endothelial growth factor (VEGF) mediated effusions 3
   • Vascular amyloid infiltration

Clinical Presentation and Characteristics

• Pleural effusions in cardiac amyloidosis can be:

  • Unilateral (right-sided) or bilateral
  • Transudative (most common) or occasionally exudative
  • Refractory to standard heart failure treatment
  • Associated with poorer prognosis, especially in AL amyloidosis 4

• Right-sided pleural effusions may be more common due to:

  • Right ventricular dysfunction, which is frequently seen in cardiac amyloidosis 1
  • Direct pleural infiltration, which can affect either side

Diagnostic Approach

When a patient with known or suspected cardiac amyloidosis presents with pleural effusion:

1. Cardiac evaluation:

   • Echocardiography to assess for typical features of cardiac amyloidosis:
     • Increased left ventricular wall thickness
     • Restrictive filling pattern
     • Biventricular dysfunction
     • "Sparkling" or granular appearance of myocardium
     • Apical sparing on longitudinal strain imaging 1

2. Pleural fluid analysis (if thoracentesis performed):

   • Usually transudative but may be exudative
   • Low protein values may be seen
   • Negative for malignant cells

3. Consider pleural biopsy if:

   • Effusion is refractory to diuretics and thoracentesis
   • Suspicion of direct pleural involvement 2

Management Considerations

1. Optimize heart failure therapy:

   • Diuretic management (loop diuretics, often at high doses)
   • Careful use of guideline-directed medical therapy for heart failure
   • Monitor for hypotension, which is common in cardiac amyloidosis 1, 5

2. For refractory pleural effusions:

   • Consider thoracentesis for symptomatic relief
   • Indwelling pleural catheter may be needed for recurrent effusions
   • Pleurodesis can be considered in selected cases 2

3. Disease-modifying treatment:

   • For AL amyloidosis: chemotherapy regimens targeting the underlying plasma cell dyscrasia
   • For ATTR amyloidosis: TTR stabilizers or silencers based on type and clinical presentation 1

4. Novel approaches for refractory cases:

   • Anti-VEGF therapy (bevacizumab) has been reported in case studies for refractory pleural effusions 3

Prognostic Implications

• The presence of pleural effusion in cardiac amyloidosis, particularly in AL type, is associated with:

  • Worse right ventricular function 4
  • Poorer overall survival (median survival of untreated patients with persistent pleural effusions is approximately 1.8 months) 2
  • Higher disease burden

• Pleural effusions that respond to treatment of the underlying amyloidosis have better outcomes than those that remain refractory 6

Clinical Pearls and Pitfalls

• Pearl: Right-sided or bilateral pleural effusions in a patient with unexplained heart failure with preserved ejection fraction should raise suspicion for cardiac amyloidosis.

• Pitfall: Not all pleural effusions in cardiac amyloidosis are due to heart failure; direct pleural involvement should be considered in refractory cases.

• Pearl: Response of pleural effusions to treatment may serve as a marker of overall treatment response in systemic amyloidosis.

• Pitfall: Aggressive diuresis without addressing the underlying amyloidosis is often ineffective for persistent pleural effusions.