The use of 99mTc-PYP SPECT/CT in monitoring therapeutic changes of eplontersen in patients with hereditary transthyretin cardiomyopathy

Abstract Objective Hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) is a progressive and fatal disease. Emerging data suggests the potential role of technetium-99m (99mTc)-pyrophosphate (PYP) scintigraphy to monitor the efficacy of ATTR-CM treatment. We aimed to determine whether eplontersen treatment alters the quantitative uptake of 99mTc-PYP in patients with ATTR-CM. Methods We analyzed a prospective cohort of hATTR-CM patients receiving eplontersen (45 mg/4 weeks). Patients with hATTR-CM who had not received eplontersen, inotersen, tafamidis or patisiran were identified retrospectively as the control group. 99mTc-PYP single-photon emission computed tomography/computed tomography (SPECT/CT) was performed at baseline and at 1 to 2 years later. Volumetric heart to lung (H/L) ratio was measured. Results Thirteen hATTR-CM patients were enrolled, of whom six received eplontersen and the other seven patients were enrolled as the control group. The median follow-up time was 544 days. A significant decrease in volumetric H/L ratio (3.774 ± 0.474 to 2.979 ± 0.354, p = 0.028) after eplontersen treatment was noted in the eplontersen group, while there was no significant change (4.141 ± 0.557 to 3.915 ± 0.3864, p = 0.237) in the control group. Comparing the two groups, the patients who received eplontersen showed a significantly greater decrease in volumetric H/L ratio compared to the control group (-20.7% ± 7.8% vs -3.4% ± 8.1%, p = 0.007). Conclusion 99mTc-PYP uptake measured by volumetric H/L ratio significantly decreased after eplontersen treatment in patients with hATTR-CM. Our results suggest the effectiveness of eplontersen in patients with hATTR-CM and the role of 99mTc-PYP SPECT/CT to monitor the efficacy of eplontersen treatment.Workflow of volumetric H/L ratioChanges in volumetric H/L ratio