A 58-year-old man presents with progressive dyspnea, orthopnea, and peripheral edema. Echocardiography shows restrictive cardiomyopathy with increased wall thickness. Serum protein electrophoresis is normal. Which investigation is most appropriate to confirm the diagnosis of cardiac amyloidosis?

Question

Accepted Answer

A. Endomyocardial biopsy with Congo red staining and polarized light microscopy. ## Diagnosis of Cardiac Amyloidosis

**Key Point:** Endomyocardial biopsy with Congo red staining and polarized light microscopy (apple-green birefringence under cross-polarized light) is the gold standard confirmatory test for amyloidosis, including cardiac amyloidosis.

### Why Congo Red Staining?

Congo red is the pathognomonic stain for amyloid:
- Binds to amyloid fibrils with high affinity
- Produces characteristic **apple-green birefringence** under polarized light microscopy
- This birefringence is virtually diagnostic of amyloid and distinguishes it from other protein deposits
- Remains the reference standard for definitive diagnosis

### Role of Endomyocardial Biopsy

Endomyocardial biopsy is the **tissue diagnosis** of choice because:
1. Directly samples the affected organ (heart)
2. Allows histological confirmation with Congo red staining
3. Permits electron microscopy to visualize characteristic 7–10 nm unbranched fibrils
4. Enables amyloid typing (AL, ATTR, AA) via immunohistochemistry or mass spectrometry

### Diagnostic Pathway for Cardiac Amyloidosis

```mermaid
flowchart TD
  A[Restrictive cardiomyopathy suspected]:::outcome --> B{Echocardiography shows increased wall thickness}:::decision
  B -->|Yes| C[Serum/urine protein electrophoresis]:::action
  C --> D{Monoclonal protein present?}:::decision
  D -->|No| E[Consider ATTR amyloidosis]:::outcome
  D -->|Yes| F[Consider AL amyloidosis]:::outcome
  E --> G[Endomyocardial biopsy with Congo red staining]:::action
  F --> G
  G --> H[Apple-green birefringence under polarized light]:::outcome
  H --> I[Amyloidosis confirmed]:::outcome
```

**High-Yield:** Congo red staining with polarized light microscopy is the **single most specific** diagnostic test for amyloidosis and is required for definitive diagnosis before treatment.

**Clinical Pearl:** In cardiac amyloidosis, the restrictive pattern on echocardiography (increased wall thickness, restrictive filling) is suggestive, but tissue confirmation is mandatory because other infiltrative diseases (sarcoidosis, Fabry disease, hemochromatosis) can mimic this pattern.

[cite:Robbins 10e Ch 6]

Answer

B. Serum and urine immunofixation electrophoresis

Answer

C. Cardiac MRI with late gadolinium enhancement

Answer

D. Transesophageal echocardiography with tissue Doppler imaging

A 58-year-old man presents with progressive dyspnea, orthopnea, and peripheral edema. Echocardiography shows restrictive cardiomyopathy with increased wall thickness. Serum protein electrophoresis is normal. Which investigation is most appropriate to confirm the diagnosis of cardiac amyloidosis?

Explanation

Diagnosis of Cardiac Amyloidosis

Why Congo Red Staining?

Role of Endomyocardial Biopsy

Diagnostic Pathway for Cardiac Amyloidosis

Practice similar questions

Join our NEET PG community