Abstract
BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CM) is an increasingly recognized cause of heart failure (HF) in older adults. Several therapies for ATTR-CM are now available, with more currently in development. As such, there is an increasing need for methods to assess response to therapy. We evaluated the associations between serial 99m-technetium pyrophosphate ((99m)Tc-PYP) deep learning measurements with changes in other imaging parameters and clinical outcomes. METHODS: We included patients with a diagnosis of ATTR-CM and at least two (99m)Tc-PYP studies followed through the Amyloidosis Program of Calgary. Patients underwent laboratory testing, echocardiography, and cardiovascular magnetic resonance unless contraindications were present. (99m)Tc-PYP images were quantified using our previously developed deep learning methodology including assessment of cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). RESULTS: In total, 85 patients were included, with a median population age of 79 years (interquartile range [IQR]: 72 - 84) and 76 (89%) male patients. In patients on therapy, there was a reduction in VOI (median: 100 to 51, P < 0.001), CPA (median: 165 to 81, P < 0.001), native T1 (median: 1400 to 1387, P = 0.005), and extracellular volume (median: 50 to 49, P = 0.035) during a median time of 369 days (IQR: 365-516) between scans. There was a modest correlation between change in CPA and change in native T1 (ρ = 0.376, P = 0.009). After adjusting for age, treatment, and CPA at follow-up, an increase in CPA during follow-up was also associated with an increased risk (adjusted hazard ratio: 2.31 per standard deviation increase, 95% confidence interval: 1.28-4.17, P = 0.005). CONCLUSIONS: Serial (99m)Tc-PYP quantitation has modest correlations with other measures of disease burden including native T1. Changes in these measures were associated with risk of cardiovascular death or HF hospitalization, suggesting that the serial measurements may be clinically meaningful surrogate endpoints.