Patients
A total of 149 patients were retrospectively enrolled, and 152 cases of [99mTc]Tc-DPD images were analyzed because three patients underwent imaging study twice. The characteristics of 149 patients are summarized in Table 1. Among the 152 images, 18 showed positive findings with visual grades ³ 1. EMB was performed in 27 patients for whom the definitive diagnosis of CA or an exclusion was of a clinical interest; 13 were diagnosed with CA and 14 were normal. Correlations between [99mTc]Tc-DPD image findings and clinical characteristics were analyzed in 142 patients, with excluding 7 patients who were finally confirmed as ischemic cardiomyopathy. Echocardiography was performed in 124, of which SUVmax was available in 59 cases. The median time interval from [99mTc]Tc-DPD imaging was 8.5 days (range 0–344 days). Cardiac MRI was performed in 30, of which 20 cases had ECV and SUVmax measurements. The median time interval between [99mTc]Tc-DPD imaging and MRI was 3.5 days (range 0–339 days).
Planar Image Indexes: Inter-observer Agreement and Correlation with Visual Grade
Inter-observer agreement between the two independent readers was excellent for both visual grades, DS (k = 0.95, 95% CI 0.89–1.00) and PS (k = 0.96, 95% CI 0.91–1.00) (Supplementary Table 1). Quantitative indexes on planar image also showed high ICC between the two readers (0.918 for H/WB and 0.901 for H/CL, Supplementary Table 2). On the Bland-Altman plot, mean ± 1.96 SD values of the differences were 0.01 ± 0.02 and –0.39 ± 1.47 for H/WB and H/CL, respectively (Supplementary Fig. 1).
H/WB and H/CL showed high correlations with visual grades. There were significant differences in H/WB and H/CL between grades 0 and 1, and between 1 and 2, for both DS and PS (P < 0.001 for both, Table 2). However, H/WB and H/CL were significantly different between grades 2 and 3 only for DS, but not for PS (Fig. 1). According to these results, DS was adopted as the visual grading system in the further analyses.
SPECT/CT Indexes: Inter-observer Agreement and Correlation with Visual Grade
All SPECT/CT indexes showed high ICC between the two readers (0.958–1.000, Supplementary Table 2), which were higher than those of the planar indexes. Among them, SUVmax showed the highest ICC. When the agreement was analyzed in each visual grade group, SUVmax showed perfect agreement between the two readers in DS 2 and 3, despite a small difference in DS 1 (Figure 2a). Other indexes also showed high ICCs between the two readers, although they were slightly lower than that of SUVmax (Supplementary Table 2). In particular, C-index in DS 3 showed a significant difference between the two readers (P = 0.020, Supplementary Fig. 2d). On Bland-Altman plot, mean ± 1.96 SD values of the differences were 0.01 ± 0.25, 0.12 ± 0.36, –87 ± 213, and 0.50 ± 1.34, for SUVmax, SUVmean, TMU, and C-index, respectively (Supplementary Fig. 1).
SPECT/CT indexes showed associations with DS (Table 2), and SUVmax was significantly different between DS grades 1 and 2, and between 2 and 3, whereas other indexes were not (Fig. 3). SUVmax, SUVmean, and TMU showed excellent correlations with H/WB and H/CL (r = 0.898–0.974), whereas C-index showed a relatively lower correlation (r = 0.696 and 0.799) (Supplementary Fig. 2). In the ROC curve analyses in terms of SUVmax and DS, 2.14, 3.76, and 7.77 were selected as the optimal cutoff values for differentiating DS 0 vs. 1, 1 vs. 2, and 2 vs. 3, respectively (Fig. 4).
Relation of Quantitative Indexes to Pathologic Diagnosis and Clinical Features
In 27 patients who underwent EMB, H/WB, H/CL, and SUVmax were significantly different between patients diagnosed with normal, AL, and ATTR (Fig. 5). All the indexes were significantly higher in ATTR than normal and AL.
In 59 cases whose echocardiography and SUVmax data were available, E/A and E/e’ did not show significant correlation with DS, although there was a weak positive correlation between SUVmax and E/A (r = 0.268, P = 0.087) (Supplementary Fig.3). In 20 cases whose cardiac MRI and SUVmax data were available, ECV was significantly different between DS 0 and 3 (P = 0.015) (Supplementary Fig. 4a), and ECV showed a significant correlation with SUVmax (r = 0.772, P < 0.001) (Supplementary Fig. 4b).