Multimodal Diagnosis of Cardiac Amyloidosis: Integrating Imaging, Histochemistry, and Proteomics of Precise Typing.

Amyloidosis is a group of disorders caused by extracellular deposition of insoluble fibrillar proteins, leading to progressive organ dysfunction. Cardiac amyloidosis is clinically significant, as myocardial infiltration results in restrictive cardiomyopathy, arrhythmias, and heart failure. The main subtypes are light-chain (AL) and transthyretin (ATTR) amyloidosis, while AA and isolated atrial amyloidosis (IAA) are less common. Accurate subtype identification is crucial for management and prognosis. Diagnosis requires a multimodal approach combining imaging and tissue-based techniques. Echocardiography is usually first-line, showing increased wall thickness, biatrial enlargement, and apical sparing. Cardiac magnetic resonance (CMR) provides superior tissue characterization through late gadolinium enhancement and elevated extracellular volume. Nuclear scintigraphy with 99mTc-labeled tracers enables non-invasive ATTR detection, while amyloid-specific PET tracers show potential for early diagnosis. Histochemical confirmation remains essential. Congo Red staining with apple-green birefringence under polarized light is the diagnostic gold standard, supported by Thioflavin T, PAS, and Alcian Blue stains. Immunohistochemistry and mass spectrometry aid amyloid typing, while electron microscopy provides ultrastructural confirmation. Integrating imaging, histochemical, immunohistochemical, and proteomic techniques enhances early recognition and precise classification, improving therapeutic strategies and patient outcomes.