Unveiling transthyretin cardiac amyloidosis and its predictors among elderly patients with severe aortic stenosis undergoing transcatheter aortic valve replacement

Abstract

Aims: Transthyretin cardiac amyloidosis (ATTR-CA) has been reported in patients with aortic stenosis (AS) but its prevalence and phenotype are not known. We examine elderly patients with severe symptomatic AS undergoing transcatheter aortic valve replacement (TAVR) and determine the prevalence and phenotype of ATTR-CA non-invasively.

Methods and results: We performed technetium-99m pyrophosphate (99mTc-PYP) cardiac scintigraphy prospectively on patients who underwent TAVR, to screen for ATTR-CA. Transthoracic echocardiography and speckle-strain imaging were performed. We assessed the association of several parameters with ATTR-CA using multivariable logistic regression and constructed receiver operating curves to evaluate the best predictors of ATTR-CA. Among 151 patients (mean age 84 ± 6 years, 68% men), 16% (n = 24) screened positive for ATTR-CA with 99mTc-PYP scintigraphy. Compared with patients without ATTR-CA, ATTR-CA patients had a thicker interventricular septum (1.3 vs. 1.1 cm, P = 0.007), higher left ventricular (LV) mass index (130 vs. 98 g/m2, P = 0.002), and lower stroke volume index (30 vs. 36 mL/m2, P = 0.009). ATTR-CA patients had advanced diastolic dysfunction with higher E/A ratio (2.3 vs. 0.9, P = 0.001) and lower deceleration time (176 vs. 257 ms, P < 0.0001); impairment in systolic function with lower ejection fraction (48% vs. 56%, P = 0.011), myocardial contraction fraction (26 vs. 41, P < 0.0001), and average of lateral and septal mitral annular tissue Doppler S' (4.0 vs. 6.6 cm/s, P < 0.0001). While ATTR-CA patients had more impaired global longitudinal strain (-12 vs. -16%, P = 0.007), relative apical longitudinal strain was the same regardless of ATTR-CA diagnosis (0.98 vs. 0.98, P = 0.991). Average S' best predicted ATTR-CA in multivariable logistic regression (odds ratio 16.67 per 1 cm/s decrease with AUC 0.96, 95% confidence interval 0.90-0.99, P = 0.002) with a value ≤6 conferring 100% sensitivity for predicting a positive 99mTc-PYP amyloid scan.

Conclusions: Transthyretin cardiac amyloidosis is prevalent in 16% of patients with severe calcific AS undergoing TAVR and is associated with a severe AS phenotype of low-flow low-gradient with mildly reduced ejection fraction. Average tissue Doppler mitral annular S' of < 6 cm/s may be a sensitive measure that should prompt a confirmatory 99mTc-PYP scan and subsequent testing for ATTR-CA. Prospective assessment of outcomes after TAVR is needed in patients with and without ATTR-CA.

Keywords: Aortic stenosis; Low-flow low-gradient; Strain; TAVR; Transthyretin cardiac amyloidosis.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1

Predictors of ATTR-CA in elderly patients undergoing transcatheter aortic valve replacement. Quantitative assessment of technetium-99m pyrophosphate myocardial uptake (A) is shown in a patient with (bottom) and without ATTR-CA (top) with corresponding H/CL ratio. ROC curves for predictors of ATTR-CA (B). DT, deceleration time; H/CL, heart-to-contralateral ratio; MCF, myocardial contraction fraction; VMR, voltage-mass ratio; ATTR-CA, transthyretin cardiac amyloidosis.

Figure 2

Left ventricular geometry among patients undergoing transcatheter aortic valve replacement with and without ATTR-CA. P-value comparing patients with ATTR-CA vs. no ATTR-CA. ATTR-CA, transthyretin cardiac amyloidosis.

Figure 3

Speckle-strain imaging in elderly patients with severe symptomatic AS with and without ATTR-CA. Bullseye plots demonstrate relative apical sparing is the same whether amyloid is present or not. AS, aortic stenosis; ATTR-CA, transthyretin cardiac amyloidosis.

Figure 4

Prevalence and phenotype of ATTR-CA among patients undergoing transcatheter aortic valve replacement at our institution. ATTR-CA, transthyretin cardiac amyloidosis.