Extracellular volume quantification by dynamic equilibrium cardiac computed tomography in cardiac amyloidosis

Abstract

Background: Cardiac involvement determines outcome in patients with systemic amyloidosis. There is major unmet need for quantification of cardiac amyloid burden, which is currently only met in part through semi-quantitative bone scintigraphy or Cardiovascular Magnetic Resonance (CMR), which measures ECVCMR. Other accessible tests are needed.

Objectives: To develop cardiac computed tomography to diagnose and quantify cardiac amyloidosis by measuring the myocardial Extracellular Volume, ECVCT.

Methods: Twenty-six patients (21 male, 64 ± 14 years) with a biopsy-proven systemic amyloidosis (ATTR n = 18; AL n = 8) were compared with twenty-seven patients (19 male, 68 ± 8 years) with severe aortic stenosis (AS). All patients had undergone echocardiography, bone scintigraphy, NT-pro-BNP measurement and EQ-CMR. Dynamic Equilibrium CT (DynEQ-CT) was performed using a prospectively gated cardiac scan prior to and after (5 and 15 minutes) a standard Iodixanol (1 ml/kg) bolus to measure ECVCT. ECVCT was compared to the reference ECVCMR and conventional amyloid measures: bone scintigraphy and clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area).

Results: ECVCT and ECVCMR results were well correlated (r(2) = 0.85 vs r(2) = 0.74 for 5 and 15 minutes post bolus respectively). ECVCT was higher in amyloidosis than AS (0.54 ± 0.11 vs 0.28 ± 0.04, p<0.001) with no overlap. ECVCT tracked clinical markers of cardiac amyloid severity (NT-pro-BNP, Troponin, LVEF, LV mass, LA and RA area), and bone scintigraphy amyloid burden (p<0.001).

Conclusion: Dynamic Equilibrium CT, a 5 minute contrast-enhanced gated cardiac CT, has potential for non-invasive diagnosis and quantification of cardiac amyloidosis.

Keywords: Amyloidosis; CCT; CMR; Cardiac imaging techniques; Extracellular space.

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1

PseudoEQ Cardiac CT and EQ-CMR Protocols: EQ-CMR was performed either after or at least 24 hours prior to the CT to avoid residual gadolinium causing an increase in measured attenuation. The CMR protocol for amyloidosis is 3.5 × longer than the CT protocol.

Fig. 2

Examples of typical CMR and CT analysis: Top row displays regions of interest (ROIs) in CMR T1 maps images acquired before (A) and after gadolinium contrast (B). Middle and bottom rows show ROIs in gated cardiac CT images acquired pre-contrast (C), 1 minute (D), 5 and 15 minutes post iodine contrast (E + F). ROIs were drawn in the myocardial septum and blood pool.

Fig. 3

Correlation and agreement of ECV derived by CT and CMR: Top row show ECVCMR and ECVCT correlations; the 5 minute CT (A) correlates better than at 15 minutes (B) (r2 = 0.85 vs r2 = 0.74; p<0.001). Bottom row shows Bland-Altman comparisons of the ECV measurement by CMR versus CT at 5 minutes (C) and 15 minutes (D). ECV differences are expressed as a percentage, calculated by subtracting ECVCT from ECVCMR) against mean ECV (solid thick line), with lower (bottom thin line) and upper (top thin line) 95% limits of agreement.

Fig. 4

ECV in patients with definite cardiac amyloidosis: Myocardial ECV by DynEQ-CT at 5 minutes was higher in all patients with definitive cardiac amyloidosis than in patients with severe aortic stenosis (0.54 ± 0.11 vs 0.28 ± 0.04, p < 0.001).

Fig. 5

ECV tracks amyloid burden measured by DPD bone scintigraphy: ECV vs DPD grade in 26 patients with systemic amyloidosis (27 patients with aortic stenosis used as comparator – no evidence of cardiac involvement on myocardial biopsy).