Improving strategies for the diagnosis of cardiac amyloidosis

Abstract

Amyloidosis refers to a group of rare but potentially fatal, protein misfolding diseases. The heart is frequently involved in the most common types, that is, immunoglobulin light chain and transthyretin amyloidosis and is the single most important predictor of patient outcomes. A major limitation in improving patient outcomes, in addition to developing novel therapeutics, is the late diagnosis of the disease. Once suspected, an organ for biopsy should be targeted and the amyloid type should be identified by mass spectrometry. An endomyocardial biopsy should be offered if cardiac involvement is in doubt. Echocardiography, MRI and nuclear imaging can provide valuable diagnostic and prognostic information and can secure the diagnosis if amyloid has been identified in an extracardiac tissue.

Keywords:

• amyloidosis
• heart failure
• heart failure with preserved ejection fraction
• immunoglobulin free light chains
• infiltrative cardiomyopathies
• transthyretin

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Amyloidoses are a highly heterogeneous group of rare diseases caused by deposition of misfolded proteins in various organs. The heart is commonly affected in many cases and is a major determinant of patient outcomes.

• The two most common amyloidoses affecting the heart are immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis.

• The disease presents with very non-specific signs and symptoms and a high index of suspicion should be maintained. A major ‘bottleneck’ in improving patient outcomes is late diagnosis, during which precious organ function is lost.

• Once suspected, the first step in diagnosis includes testing of cardiac biomarkers and targeting an organ for biopsy. Fat pad and/or a bone marrow biopsy are easily obtainable and can have a high yield in identifying Congo red amyloid deposits.

• If in doubt, an endomyocardial biopsy should always be pursued.

• Amyloid typing by mass spectrometry is the gold standard for identifying the amyloidogenic protein.

• Modern echocardiography has increased the sensitivity and specificity for identifying early cardiac involvement and is an essential part of the diagnostic work-up.

• More advanced imaging (MRI and nuclear based) should be considered on a case-by-case basis, but is usually not necessary to diagnose the disease. The incremental prognostic value that these methods have over echocardiography and cardiac biomarkers is also unclear.

Notes