Noninvasive Risk Stratification of Patients With Transthyretin Amyloidosis

ObjectivesWe sought to evaluate noninvasive parameters by electrocardiography, echocardiography, technetium-99m–3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy, and cardiac magnetic resonance for the prediction of all-cause mortality in patients with cardiac transthyretin amyloidosis (ATTR).BackgroundATTR 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.MethodsA total of 70 patients with ATTR were evaluated by echocardiography, cardiac biomarkers, and 99mTc-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 99mTc-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.ResultsScintigraphy 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.ConclusionsQuantitative 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.