(VP034) DETERMINANTS OF OUTCOME TO DISEASE-MODIFYING THERAPY FOR TRANSTHYRETIN AMYLOIDOSIS CARDIOMYOPATHY

Background: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an infiltrative process with poor prognosis when left untreated. Despite the approval of tafamidis, a stabilizer therapy, significant knowledge gaps exist regarding its use due to strict eligibility criteria and high costs. Targeting therapy to those experiencing the greatest benefit is complicated because patients are frequently older and have multiple comorbidities. This project determined baseline predictors of all-cause and cardiovascular mortality and hospitalization, as well as the associations of these predictors to therapy in a clinical cohort from an ATTR-CM referral center. An on-treatment cohort of ATTR-CM patients was retrospectively analyzed and compared with untreated patients. It was hypothesized that select baseline variables will be associated with mortality and the need for hospitalization after the initiation of targeted ATTR-CM therapy.

METHODS AND RESULTS: Health records were used to collect baseline parameters associated with all-cause, and cardiovascular mortality and hospitalizations. Baseline and follow-up disease severity parameters across clinical and biochemical domains were assessed. Deaths and hospitalizations were adjudicated as cardiovascular or non-cardiovascular using standardized criteria by trained staff. Associations with all-cause and cardiovascular mortality were assessed with Cox proportional hazards models, with ATTR therapy modeled as a time-varying covariate. A total of 145 patients with ATTR-CM (126, 87% men, 19 women; mean age at diagnosis 79.1±0.7 years) were identified from 2011 to 2021. Eighty (55%) patients were treated with tafamidis. After 2.9±1.8 years of follow-up, there were a total of 58 death events, of which 49 deaths were cardiovascular-related. Patients who received tafamidis were less likely to experience all-cause and cardiovascular mortality (both p< 0.05; Figure 1). The only predictor of cardiovascular hospitalization was baseline eGFR (p < 0.05), whereas various predictors of all-cause and cardiovascular mortality were recognized at baseline across clinical and biochemical domains (Table 1). A significant interaction was also identified, such that higher values of NTproBNP at baseline was associated with less all-cause mortality benefit from ATTR therapy (p < 0.05).

Conclusion: Baseline parameters that indicate determinants of mortality and hospitalization, and influence time to these events, such as NTproBNP and eGFR, are crucial for an improved understanding on how targeted ATTR-CM therapy can alter disease course. This study will help bridge gaps in the optimal management of ATTR-CM patients and ascertain parameters to be used in predicting therapeutic response. Furthermore, healthcare expenditures can also be reduced by identifying those most (and least) likely to derive benefit from this very expensive therapy.