Longitudinal changes in amyloid burden as measured by extracellular volume (ECV) on cardiac MRI for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM)
M O'Neill-Dee, T Bergamaschi, H Jeong, A Parulkar, K Brown, G Lee, S Dorbala, S Cuddy, K Bersell, R Falk, R Kwong, D Sosnovik, C M Stultz, H K GagginAbstract
Background
Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive infiltrative cardiomyopathy associated with substantial morbidity and mortality. Tafamidis, a TTR stabilizer, was the only approved disease-modifying medication from 2019 until 2024. The extent to which myocardial amyloid burden continues to evolve during treatment with tafamidis remains unclear. Extracellular volume (ECV) on cardiac magnetic resonance (CMR) was used as a quantitative surrogate of myocardial amyloid burden, as it reflects extracellular expansion and has been validated as a marker of amyloid burden.
Purpose
To characterize longitudinal changes in amyloid burden in ATTR-CM patients receiving tafamidis and aggressive guideline-directed medical therapy (GDMT) for heart failure.
Methods
This retrospective longitudinal cohort (2014-2025, one patient on tafamidis prior to 2019) included ATTR-CM patients from two tertiary centers treated with tafamidis who underwent ≥1 clinically-performed CMR. ECV was measured at the mid to basal septum. Progression of amyloid burden was defined as an absolute increase in ECV ≥5%, and regression was defined as an absolute decrease in ECV ≥5% from baseline to follow up at 1, 2 or 3 years. All comparisons were performed with a Wilcoxon signed rank test. Due to small numbers, year 2 and 3 were combined in paired comparisons. If more than one CMR was performed in the same year, then the average ECV was used to determine progression or regression.
Results
Among 384 patients (median age 78.5 years, 91.3% male, median NT-proBNP 1835 pg/mL, eGFR 55 mL/min/1.73m²) who received tafamidis and had CMR, baseline ECV was available in 200 patients with 224 CMR’s , with follow-up in 64 patients with 74 CMR’s at 1 year, 49 patients with 54 CMR’s at 2 years, and 15 patients with 30 CMR’s at 3 years. Not all patients had both 1 and 2-3 year CMR. Mean ECV increased by 3.17% at 1 year (p=0.002) and by 7.21% at 2–3 years (p<0.001). Women and NAC stage 2/3 patients appeared to increase their ECV over time more than men and NAC stage 1 patients. Progression occurred in 33.9% of patients at 1 year and 34.7% of patients at 2–3 years. Regression occurred in 11.9% of patients at 1 year and 8.2% of patients at 2-3 years.
Conclusion
In a contemporary ATTR-CM cohort treated with tafamidis and GDMT, a significant proportion of patients had progression of amyloid burden over time. Further evaluation is needed to better understand progression patterns by sex and NAC staging.Table ATable B