JOURNAL ARTICLE

Noninvasive risk stratification of patients with transthyretin amyloidosis

Arnt V Kristen, Katrin Scherer, Sebastian Buss, Fabian aus dem Siepen, Sabine Haufe, Ralf Bauer, Katrin Hinderhofer, Evangelos Giannitsis, Stefan Hardt, Uwe Haberkorn, Hugo A Katus, Henning Steen
JACC. Cardiovascular Imaging 2014, 7 (5): 502-10
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OBJECTIVES: We sought to evaluate noninvasive parameters by electrocardiography, echocardiography, technetium-99m-3,3-diphosphono-1,2-propanodicarboxylic acid ((99m)Tc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR).

BACKGROUND: ATTR may present with highly variable symptoms, including polyneuropathy and cardiomyopathy, the latter being associated with a poor outcome. However, data on noninvasive risk stratification of ATTR are limited.

METHODS: A total of 70 patients with ATTR were evaluated by echocardiography, cardiac biomarkers, and (99m)Tc-DPD scintigraphy. Cardiac magnetic resonance was performed in 30 patients. Echocardiographic findings and plasma levels of biomarkers were correlated with results of quantitative analysis of scintigraphy using a region-of-interest technique (whole-body as well as heart tracer retention). Receiver-operating characteristic (ROC) analysis was performed to calculate a cutoff value of (99m)Tc-DPD scintigraphy for heart retention for the diagnosis of cardiac amyloid involvement with the highest sensitivity and specificity. Univariate and multivariate analyses were performed in patients with cardiac involvement (n = 60) to determine noninvasive predictors of all-cause mortality.

RESULTS: Scintigraphy findings correlated with morphological (interventricular septum thickness, left ventricular hypertrophy index) as well as functional (mitral annular systolic velocity, mitral/tricuspid annular plane systolic excursion) findings, cardiac biomarkers, renal function, and late gadolinium enhancement. The ROC-derived cutoff for the detection of cardiac amyloidosis by scintigraphic heart tracer retention was 4.8%. Univariate Cox regression revealed N-terminal pro-B-type natriuretic peptide, troponin T, mitral annular plane systolic excursion, and left ventricular hypertrophy index as predictors of all-cause mortality. However, on multivariate analysis, troponin T remained the only independent predictor of survival. The ROC-derived cutoff value of troponin T predicting all-cause mortality with the highest sensitivity (80.0%) and specificity (68.7%) was 0.0375 ng/l.

CONCLUSIONS: Quantitative analysis of tracer retention is capable of characterizing the severity of cardiac involvement in ATTR. By multivariate analysis, troponin T remained the only independent predictor of survival.

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