Predictors of disease burden in patients with untreated transthyretin amyloid cardiomyopathy: post hoc analysis of an international survey study

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive condition that can cause debilitating symptoms.[1] The burden of untreated ATTR-CM was recently evaluated in an international, multicentre, real-world survey study.[2] Identifying predictors of ATTR-CM burden can help improve patients’ therapeutic journey. Purpose To identify predictors of disease burden on patients with ATTR-CM treated with symptomatic but not disease-modifying therapy using data from the recent international real-world survey study. Methods The original study surveyed 208 patients with untreated ATTR-CM recruited from international amyloidosis centres of excellence in 7 countries between July 2021 and August 2022. This post hoc analysis used univariate and multivariate models to evaluate selected survey variables as predictors of patient burden. Variables and outcomes included in the models are described in the figure. Univariate associations were confirmed with a t-test and Pearson correlation coefficient. The full multivariate models included all variables and were then optimised using forward selection and CV Press criteria with 8-fold cross-validation to identify the best predictors. Results The patient population in the original study were generally male (86%) and elderly (median 81 [range: 46 – 90] years), with wild-type ATTR-CM (91% of 155 with genetic testing; median time since diagnosis: 6 months). Of the 199 patients with a recorded NYHA classification, 60% were class II, 22% were class III, 18% were class I, and none were class IV. The investigator reported each neurologic symptom variable (Figure) as a current symptom in 25–41 patients, and gastrointestinal or urinary problems in 36 patients. Out-of-pocket expenses in the prior 3 months were reported by 78 patients. Respective median (IQR) KCCQ-OS, -CS and -TS scores were 67.7 (46.4–84.4; n = 183), 69.0 (49.5–87.5; n = 202), and 75.0 (52.1–91.7; n = 208); HADS-A and HADS-D scores were 5.0 (3.0–8.0; n = 205), and 6.0 (3.0–10.0; n = 204); SF-12 PCS and MCS scores were 36.3 (27.5–43.5; n = 206) and 46.8 (39.4–54.4; n = 206); and PROMIS Fatigue T-score was 50.8 (45.8–57.8; n = 203). In the unadjusted univariate models, NYHA class and the neurologic symptom variable of weakness, especially in the legs, were independently associated with all outcome measures of burden. Closely reflecting the statistically significant predictors in the full multivariate models, older age (continuous or age over 80 years), symptomatic heart failure (NYHA class II or III), female sex, and having weakness, especially in the legs, were among the best predictors of a higher burden in several optimized models (Table). Conclusions In this study of patients with ATTR-CM receiving symptomatic but not disease-modifying therapy, our analysis suggests that older age, female sex, and cardiac or neurologic symptoms are often predictors of higher disease burden.Figure:Variables and outcome measuresTable:Optimised models