Multi-imaging characterisation of cardiac phenotype in different types of amyloidosis

Abstract

Abstract Background Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of myocardial tracer uptake across different types of amyloidosis is yet to be defined. Purpose We sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis using extensive characterisation comprising of biomarkers, echocardiographic and cardiac magnetic resonance (CMR) imaging. Methods A total of 296 patients (117 immunoglobulin light-chain [AL] amyloidosis, 165 transthyretin [ATTR] amyloidosis, 7 apolipoprotein-A1-amyloidosis [AApoAI],and 7 apolipoprotein-A4-amyloidosis [AApoA4]) underwent deep characterisation of their cardiac phenotype. Results AL-amyloidosis patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no evidence of CA to characteristic features of CA, while AL-amyloidosis patients with grade 1–3 always produced characteristic CMR features. In ATTR-amyloidosis the CA burden strongly correlated with myocardial tracer uptake (correlation between bone scintigraphy cardiac uptake and CMR derived extracellular volume: R=0.88, 95% CI [0.84–0.91], P<0.001), except in patients with the Ser77Tyr variant. AApoAI-amyloidosis presented with grade 0–1 myocardial tracer uptake, and unique features of disproportionate right sided involvement such as disproportionate right ventricular (RV) and right atrial uptake on bone scintigraphy, RV free wall thickening, and tricuspid valve thickening and dysfunction. Within our cohort, AApoAIV-amyloidosis always presented with grade 0 myocardial tracer uptake, and characteristic features of CA on CMR. All AL-amyloidosis patients with grade 1 myocardial tracer uptake had characteristic CMR features of CA (n=48, 100%), while only ATTR-amyloidosis grade 1 patients with the Ser77Tyr variant had characteristic features of CA on CMR (n=5, 11.4%). Following the exclusion of Ser77Tyr and AApoAI, a CMR showing characteristic features of CA or an extracellular volume >0.40 in a patient with grade 1 myocardial tracer uptake had a sensitivity and specificity of 100% for diagnosing AL-amyloidosis. Conclusion Deep characterisation of the cardiac phenotype in different types of amyloidosis, across a range of bone scintigraphy cardiac uptake grades has identified clear differences between each amyloidosis type. The distinctive characteristics in each cohort has allowed the development of a diagnostic pathway to help define the diagnostic differentials and the clinical phenotype in each individual patient, following comprehensive assessment with bone scintigraphy and CMR. Funding Acknowledgement Type of funding sources: None.