Apolipoprotein A-IV Cardiac Amyloidosis: Beyond ATTR and AL

Cardiac amyloidosis is most commonly caused by transthyretin or immunoglobulin light-chain deposition, and contemporary diagnostic algorithms rely on monoclonal protein assessment and technetium-labeled bone scintigraphy to identify these subtypes. However, rarer forms of amyloid may not be detected by noninvasive testing. We present 2 cases of biopsy-proven apolipoprotein A-IV (ApoA-IV) cardiac amyloidosis illustrating complementary diagnostic pitfalls. The first patient demonstrated classical clinical and multimodality imaging features of cardiac amyloidosis despite negative monoclonal protein studies and pyrophosphate scintigraphy. Endomyocardial biopsy with mass spectrometry confirmed ApoA-IV. The second patient had abnormal serum-free light chains and bone marrow plasma cell involvement suggestive of light-chain amyloidosis, yet cardiac biopsy revealed ApoA-IV, preventing inappropriate chemotherapy. These cases highlight limitations of current nonbiopsy algorithms and emphasize that tissue diagnosis with proteomic typing remains essential when clinical suspicion is high or findings are discordant.