Multicenter Study of Planar Technetium 99m Pyrophosphate Cardiac Imaging Predicting Survival for Patients With ATTR Cardiac Amyloidosis

IMPORTANCE Transthyretin cardiac amyloidosis (also known as ATTR cardiac amyloidosis) is an increasingly recognized cause of heart failure with preserved ejection fraction. In single-center studies, technetium 99mpyrophosphate (Tc 99m PYP) cardiac imaging noninvasively detects ATTR cardiac amyloidosis, but the accuracy of this technique in a multicenter study and the association of Tc 99mPYPmyocardial uptake with survival are unknown. OBJECTIVE To assess Tc 99mPYP cardiac imaging as a diagnostic tool for ATTR cardiac amyloidosis and its association with survival in a multicenter study. DESIGN, SETTING, AND PARTICIPANTS Retrospective cohort study performed at 3 academic specialty centers for cardiac amyloidosis in the United States in which 229 participants were evaluated for cardiac amyloidosis and also underwent Tc 99mPYP cardiac imaging. The date of analysis and final confirmation from the statistician wasMay 4, 2016. EXPOSURE Tc 99mPYP cardiac imaging for detection of ATTR cardiac amyloidosis. MAIN OUTCOMES AND MEASURES Retention of Tc 99mPYP in the heart was assessed using both a semiquantitative visual score (range, 0 [no uptake] to 3 [uptake greater than bone]) and a quantitative heart to contralateral (H/CL) ratio. The H/CL ratio was calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc 99mPYP imaging. RESULTS Tc 99mPYP imaging of 171 participants (121 with ATTR cardiac amyloidosis and 50 with non-ATTR cardiac amyloidosis [34 with AL amyloidosis and 16 with nonamyloid heart failure with preserved ejection fraction]; 86% male; median [IQR] age, 73 years [65-79 years]) demonstrated 91% sensitivity and 92% specificity for detecting ATTR cardiac amyloidosis with an area under the curve of 0.960 (95% CI, 0.930-0.981). Univariable and multivariable Cox proportional hazards regression analyses among participants with ATTR cardiac amyloidosis showed that an H/CL ratio of 1.6 or greater predicted worse survival (hazard ratio, 3.911 [95% CI, 1.155-13.247]; P =.03 for univariable analysis and 7.913 [95% CI, 1.679-37.296]; P =.01 for multivariable analysis). In Kaplan-Meier analysis over a 5-year follow-up period, survival was significantly worse if the H/CL ratio was 1.6 or greater rather than less than 1.6 (log-rank P =.02). CONCLUSIONS AND RELEVANCE In this multicenter study, Tc 99m PYP cardiac imaging conferred a high level of sensitivity and specificity for differentiation of patients with ATTR cardiac amyloidosis (irrespective of genotype) from patients with AL cardiac amyloidosis and patients with nonamyloid heart failure with preserved ejection fraction. An H/CL ratio of 1.6 or greater was associated with worse survival among patients with ATTR cardiac amyloidosis. Among patients for whom there is a high clinical suspicion of cardiac amyloidosis, Tc 99mPYP may be of diagnostic and prognostic importance.