Comparison of semi-quantitative amyloid deposition between PYP and HMDP scintigraphy for diagnosing ATTR-cardiac amyloidosis

Introduction: Cardiac amyloidosis (CA) encompasses various types, with transthyretin CA (ATTR-CA) being one of the most prevalent, characterized by the deposition of transthyretin (TTR). Notably, bone scintigraphy has proven valuable for the noninvasive diagnosis of ATTR-CA. Two commonly employed preparations are Tc-99m pyrophosphate (PYP) and Tc-99m hydroxymethylene diphosphonate (HMDP). While PYP involves semiquantitative evaluation through the heart-to-side lung ratio (H/CL) in addition to visual assessment, the utility of H/CL in HMDP remains uncertain. This study aims to assess and compare the significance of the H/CL in HMDP scintigraphy with that in PYP for the diagnosis of ATTR-CA.

Methods: This study incorporated 239 examinations wherein ATTR-CA was suspected, and either HMDP or PYP scintigraphy was conducted, leading to a definitive diagnosis (HMDP: 63scans, ATTR-CA: 55 scans, Non-ATTR-CA: 8 scans; PYP: 176 scans, ATTR-CA: 67 scans, Non-ATTR-CA: 109 scans). The diagnosis of ATTR-CA was established through subendocardial biopsy, biopsy of other organs, and findings from cardiac magnetic resonance imaging and/or echocardiography. Anterior planar images were obtained 3 hours post-administration of either HMDP or PYP. Additionally, 16 out of 63 scans for HMDP and 114 out of 176 scans for PYP were obtained at the 1-hour post-administration. Regions of interest were defined in the heart and contralateral lungs following the guidelines of the American Society of Nuclear Cardiology Practice Points. Subsequently, the H/CL was calculated. The study investigated the relationship between H/CL values in HMDP and PYP scans and their respective diagnostic capabilities for ATTR-CA.

Results: At the 1-hour scan, the mean H/CL of HMDP for ATTR-CA cases was 2.02, notably higher than the value of 1.27 observed for non-ATTR-CA cases (p=0.006). Similarly, the mean H/CL of PYP for ATTR-CA stood at 1.85, significantly surpassing the corresponding value of 1.31 for non-ATTR-CA cases (p<0.001). In ATTR-CA, HMDP was significantly higher than PYP (p=0.037). At the 3-hour scan, the mean H/CL of HMDP for ATTR-CA was 1.94, demonstrating a substantial elevation compared to the value of 1.16 observed for non-ATTR-CA (p<0.001). Similarly, the mean H/CL of PYP for ATTR-CA was 1.80, significantly exceeding the corresponding value of 1.27 for non-ATTR-CA cases (p<0.001). Notably, in cases of ATTR-CA, HMDP exhibited a significantly higher H/CL than PYP (p=0.049). In the subset of cases where both HMDP and PYP scans were performed, a robust correlation for the H/CL was observed through linear regression analysis. In the ROC analysis, HMDP exhibited an Area Under the Curve (AUC) of 0.923, with a sensitivity of 85.5% and specificity of 100%, using an H/CL cutoff of 1.38. In comparison, PYP demonstrated an AUC of 0.948, boasting a sensitivity of 92.5% and specificity of 90.8%. These findings suggest that the diagnostic performance of HMDP, utilizing H/CL, is comparable to that of PYP.

Conclusions: In conclusion, even in HMDP scintigraphy, the incorporation of an appropriate H/CL proves to be valuable in the diagnosis of ATTR-CA.