Comparative performance of ^99mTc-pyrophosphate vs. ^99mTc-hydroxymethylene diphosphonate for cardiac amyloid...

Cardiac amyloid radionuclide imaging (CARI) with ^99mTc-pyrophosphate (PYP) enables the noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Recent PYP shortages have necessitated substitution with ^99mTc-hydroxymethylene diphosphonate (HMDP), yet direct comparative data are limited. We aimed to compare scan interpretation, ATTR-CM prevalence, and myocardial-to-blood pool discrimination between PYP and HMDP in real-world clinical practice.

We retrospectively analyzed 992 consecutive patients who underwent SPECT/CT for suspected ATTR-CM at a single referral center between October 2022 and January 2025. PYP was used except during two shortage periods (December 2023 to February 2024 and October 2024 to January 2025), when HMDP was substituted. Scan interpretation and final ATTR-CM diagnoses were recorded. The myocardial-to-blood-pool radiotracer uptake ratio (3D Score) was measured as a surrogate for contrast resolution.

Of 992 unique patients (median age 76, 27% female), 816 received PYP and 176 (18%) received HMDP. Baseline clinical, echocardiographic, and biomarker characteristics were similar between groups. Rates of positive scans (PYP: 26%, HMDP: 25%; P = 0.95) and final ATTR-CM diagnoses (28% vs 26%; P = 0.59) were comparable. Among patients with positive scans (n = 256), HMDP yielded significantly higher 3D Scores (2.0 [1.7-2.5] vs 1.4 [1.2-1.7], P < 0.001), suggesting enhanced myocardial-to-blood pool contrast resolution.

In a large cohort with similar clinical profiles, HMDP provided equivalent diagnostic yield and superior myocardial-to-blood-pool discrimination compared to PYP. These findings support HMDP as a good alternative during PYP shortages, with potential advantages in contrast resolution.