Authors: Jalyn Martin, Justin Joy, Brian Tran, Matthew Brown, Susie Sennhauser, Matthew Gold, Daniel Gold, Kunal Bhatt
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disease caused by myocardial deposition of misfolded transthyretin (TTR) fibrils, resulting in heart failure. TTR stabilizers, including tafamidis and acoramidis, reduce mortality and hospitalization by preventing tetramer dissociation. However, there is no standardized biomarker to assess treatment response. Clinical follow-up commonly incorporates serum prealbumin, N-terminal pro-B-type natriuretic peptide (NT-proBNP), imaging, and hospitalization rates. Prior studies suggest that lower baseline prealbumin and early post-treatment increases are associated with clinical outcomes, but its prognostic utility in real-world populations remains unclear.
Methods: This was a retrospective chart review of adults diagnosed with ATTR-CM who received TTR stabilizer therapy (i.e. tafamidis, tafamidis meglumine, or acoramidis) at the Emory Advanced Heart Failure Clinic between November 1, 2019, to December 1, 2025. Patients were included in this study if they had both baseline and follow-up (≥ 3 months) prealbumin levels. Ineligible patients were those with previous TTR stabilizer or TTR silencer use, on dual stabilizers, on a concurrent TTR silencer (patisiran, vutrisiran, inotersen, or eplontersen), or enrolled in an active ATTR-CM clinical trial. The primary outcome was the absolute change in prealbumin levels following TTR stabilizer therapy. Secondary outcomes included the association between absolute change in prealbumin and all-cause hospitalization and all-cause mortality (time to event analysis), as well as the absolute change in NT-proBNP following TTR stabilizer initiation. Descriptive statistics, paired t-test, logistical regression, and Cox proportional hazard regression were used to summarize the data.
Results:
Of 222 patients screened, 150 were excluded, primarily due to missing follow-up prealbumin measurements. A total 72 patients were included in the analysis, all treated with tafamidis. Prealbumin rose significantly after TTR stabilizer initiation, with a mean paired increase of 8.99 mg/dL (95% CI 7.40 to 10.59; p<0.001). The composite outcome of hospitalization and death occurred in 47 (65.3%) patients, with 14 deaths and 47 hospitalizations.
After adjustment for age, sex, and race, each 5 mg/dL higher follow-up prealbumin was associated with a lower risk of hospitalization (HR 0.41; 95% CI 0.21 to 0.78; p=0.007) and the composite outcome (HR 0.37; 95% CI 0.20 to 0.69; p=0.002). No significant association was observed for mortality alone with either follow-up prealbumin or change in prealbumin. Mean absolute change in NT-proBNP was 165.7 pg/mL.
Conclusions: Higher prealbumin after TTR stabilizer initiation was associated with a reduced risk of all-cause hospitalizations and composite events. Baseline prealbumin in prealbumin predicted subsequent cardiac-related hospitalizations and all-cause mortality in an exploratory analysis. Further research in larger cohorts with longer follow-up is needed to validate these findings and further identify predictors of response to TTR stabilizer therapy.
