Abstract

Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99mTc-DPD tracer uptake in ATTR.Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [TTR] variant carriers) with 99mTc-DPD and TTE were selected; 99mTc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed.Results: Forty ATTR patients (wild-type n = 17; hereditary ATTR and TTR variant carriers n = 23; median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99mTc-DPD tracer uptake included LV average wall thickness (r = 0.837), LV indexed mass (LVMI; r = 0.802), RV wall thickness (r = 0.610), average e' (r = −0.830), E/e' ratio (r = 0.786), LV global longitudinal strain (GLS; r = 0.714) and RV GLS (r = 0.632; p < 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness; area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS; AUC of 0.86 and 0.88, respectively) parameters.Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99mTc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.

Highlights

  • Systemic amyloidosis is a multiorgan disease resulting from extracellular deposition of insoluble amyloid fibrils, formed from aggregated, misfolded proteins [1, 2]

  • transthoracic echocardiography (TTE) and 99mTc-DPD scintigraphy were performed with a median time of 7 days between scans; 88% of patients had scans within 4 months of each other

  • The salient findings from this study are the demonstration of robust correlation of left ventricle (LV) and right ventricle (RV) structural and functional echocardiographic parameters with 99mTc-DPD tracer uptake analysis, using 99mTc-DPD SPECT-CT as a quantitative measure of ATTR deposition in myocardial tissue

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Summary

Introduction

Systemic amyloidosis is a multiorgan disease resulting from extracellular deposition of insoluble amyloid fibrils, formed from aggregated, misfolded proteins [1, 2]. Cardiac amyloidosis is predominantly caused by light chain amyloid (AL) and transthyretin amyloidosis [ATTR] [2]; other amyloid subtypes are less prevalent and rarely demonstrate cardiac involvement [2]. Technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy emerged as an important diagnostic modality with strong tracer avidity for the transthyretin protein, with high sensitivity and specificity [10, 11, 14, 15]. Most cardiac amyloidosis studies using 99mTc-DPD scintigraphy employed qualitative visual grading or semi-quantitative grading with heart-to-body ratios [15, 16]. Few studies employed quantitative 99mTc-DPD tracer uptake analysis, and little is known about tracer uptake correlation with specific structural and functional cardiac changes [16, 17]

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