Apolipoprotein A-IV Cardiac Amyloidosis as a Diagnostic Pitfall: Beyond the Non-Invasive Algorithm

Figures

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  Figure 1. Electrocardiogram The electrocardiogram showed sinus rhythm with a slightly prolonged PR interval (210 milliseconds) and low voltage relative to the severity of left ventricular hypertrophy on echocardiography.

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  Figure 2. Echocardiography Echocardiography showed concentric left ventricular hypertrophy without relevant valvular disease (parasternal long-axis view) (A). Interventricular septum of 17 mm and inferolateral wall of 12 mm, resulting in an increased relative wall thickness of 0.63 and an indexed left ventricular mass of 123 g/m2 (apical 4-chamber view) (B). Diastolic dysfunction was present with an E/A ratio of 0.8, medial e' of 3.7 cm/s, and an elevated E/e' ratio of 18.9 (C). Strain imaging showed reduced systolic longitudinal strain (−5.2%) with apical sparing (D).

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  Figure 3. Cardiac Magnetic Resonance Cine imaging (4-chamber view [A] and short-axis view [D]) showed concentric left ventricular hypertrophy with a maximum wall thickness of 24 mm (asterisk in panel D) and mild pericardial effusion. Late gadolinium enhancement images in the 4-chamber and basal short-axis views are shown in panels B and E, respectively, demonstrating diffuse enhancement throughout the left ventricle (open arrows), with partial transmural involvement. Native T1 mapping (mid-ventricular short axis) showed clearly elevated values, especially in the septum (septal native T1: 1,277 milliseconds; normal value: <1,020 milliseconds) (asterisk in panel C). There were also elevated T2 values (septal T2 value: 67 milliseconds; normal value: <56 milliseconds) (asterisk in panel F).

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  Figure 4. Bone Scintigraphy Planar imaging (A) and single-photon emission computed tomography (B) did not show any cardiac uptake (Perugini grade 0) on technetium-labeled bone scintigraphy.

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  Figure 5. Fat Pad Biopsy and Immunohistochemistry (A) Fat pad biopsy and subsequent histochemistry revealed evident Congo red staining. Immunohistochemistry was negative for amyloid A (B), transthyretin (TTR) (C), kappa light chains (D), and lambda light chains (E).

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  Figure 6. Cardiac Biopsy and Congo Red Histochemistry (A-C) Cardiac biopsy confirmed amyloid presence by Congo red staining.

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  Visual Summary. Diagnostic Blind Spot A pathognomonic imaging phenotype for cardiac amyloidosis with negative noninvasive screening, leading to the definitive diagnosis of apolipoprotein A–IV amyloidosis via mass spectrometry. AL = light chain; ECV = extracellular volume; ATTR = transthyretin amyloidosis; LGE = late gadolinium enhancement.