Is rheumatoid arthritis (RA) a cause for suspicion in cardiac amyloidosis?

Rheumatoid Arthritis as a Cause for Suspicion in Cardiac Amyloidosis

Rheumatoid arthritis (RA) is a recognized cause for suspicion of cardiac amyloidosis, particularly AA amyloidosis, though it is less common than other presentations of cardiac amyloidosis. 1, 2

Types of Amyloidosis Associated with RA

AA Amyloidosis

• Secondary to chronic inflammation in RA
• Prevalence of subclinical AA amyloidosis in RA patients is significant (21.5% by abdominal fat aspiration biopsy) 3
• Cardiac involvement in AA amyloidosis is less common than renal involvement but should be considered in RA patients with unexplained cardiac symptoms

ATTR Amyloidosis

• Can coexist with RA as a separate entity
• Cases of wild-type transthyretin (ATTRwt) cardiac amyloidosis have been reported in patients with RA 4

Clinical Indicators for Suspicion

When evaluating RA patients for possible cardiac amyloidosis, consider:

1. Disease characteristics associated with higher risk:

   • Longer time to diagnosis of RA 3
   • Presence of extraarticular manifestations 3
   • Proteinuria >0.3 g/24h 3
   • Rheumatoid factor seropositivity 1
   • Persistently elevated inflammatory markers (ESR, CRP) 1

2. Cardiac manifestations warranting investigation:

   • Unexplained left ventricular hypertrophy 5
   • Heart failure disproportionate to traditional risk factors 1
   • Reduced left ventricular systolic function without clear cause 5
   • Conduction abnormalities, particularly atrioventricular block 4
   • Discordance between wall thickness on echocardiogram and QRS voltage on ECG 1

Diagnostic Approach

For RA patients with suspected cardiac amyloidosis:

1. Initial screening:

   • Serum and urine monoclonal light chains with immunofixation electrophoresis and serum free light chain assay 1, 6
   • NT-proBNP and troponin levels (often elevated disproportionately to heart failure severity) 1

2. If negative for monoclonal proteins:

   • Bone scintigraphy (99mTc-PYP/DPD/HMDP) to evaluate for ATTR amyloidosis 1
   • Grade 2-3 myocardial uptake suggests ATTR amyloidosis 1

3. Tissue diagnosis:

   • Endomyocardial biopsy with Congo red staining and immunohistochemistry remains the gold standard 1
   • Abdominal fat aspiration biopsy is more sensitive than minor salivary gland biopsy for detecting subclinical amyloidosis in RA patients 3

4. If ATTR amyloidosis is confirmed:

   • Genetic testing with TTR gene sequencing to differentiate hereditary variant from wild-type ATTR 1

Treatment Implications

• Tocilizumab (IL-6 receptor antibody) has shown promise in treating cardiac AA amyloidosis in RA, with documented regression of LV hypertrophy and improvement in systolic function 5
• Methotrexate and other disease-modifying antirheumatic drugs may reduce the risk of amyloidosis in RA patients 3
• For ATTR cardiac amyloidosis, specific treatments like tafamidis may be indicated regardless of RA status 4
• Etanercept and infliximab should be avoided in patients with established heart failure 1

Important Considerations

• Cardiac amyloidosis may be underdiagnosed in RA due to overlap of symptoms with other cardiac manifestations of RA
• The diagnosis of cardiac amyloidosis in RA requires a high index of suspicion, particularly when cardiac symptoms are disproportionate to disease activity
• Proper identification of the amyloid protein type is crucial as treatment strategies differ significantly between AA and ATTR amyloidosis 4
• Screening for subclinical amyloidosis should be considered in high-risk RA patients, particularly those with long-standing disease and extraarticular manifestations 3