Amylo’ExTTRa: exploring extra-cardiac manifestations in patients with ATTR-CM using a French National Health Data System
T Damy, V Algalarrondo, E Donal, O Hanon, J Inamo, A Fravalo, P Hernandez, A Bakdache, A Echaniz-Laguna, O LairezAbstract
Background
Transthyretin (TTR) amyloidosis with cardiomyopathy (ATTR-CM) is a rapidly progressive, debilitating, fatal disease caused by misfolded TTR depositing as amyloid fibrils in cardiac tissue, resulting in progressive heart failure. As amyloid fibrils can deposit in other tissues, patients with ATTR-CM may have extra-cardiac manifestations. These are most commonly musculoskeletal symptoms that can occur prior to cardiac presentation, potentially providing early red flags for diagnosis, while neuropathy impairment is also described. These extra-cardiac manifestations can be associated with frailty and negatively impact patient quality of life (QoL). It is therefore important to assess extra-cardiac manifestations in patients with ATTR-CM to provide a multisystemic approach for patient management and specific treatment selection.
Purpose
To describe the extra-cardiac multisystemic disease burden of patients with ATTR-CM vs matched controls in France.
Methods
This observational study used data from the French National System of Health Data claims database. The prevalence of extra-cardiac clinical manifestations in patients with ATTR-CM (identified by disease-specific treatment) was compared with a control population without ATTR-CM matched by age, sex and region in France (Figure 1).
Results
Overall, data from 8,358 patients with ATTR-CM and 8,358 matched controls were analysed. In this cohort, the mean age in 2023 was 82.7 years and 78% were male. Significantly higher prevalences in patients with ATTR-CM vs matched controls were observed for signs/symptoms of the peripheral nervous system, as shown by increased peripheral neuropathy (+10.0 percentage points difference in prevalence for ATTR-CM vs controls) and orthostatic hypotension (+2.5%); gastrointestinal system with increased constipation (+3.2%), and hospitalisations for malnutrition (+3.0%); musculoskeletal system with increased carpal tunnel surgery (+23.7%), knee/hip surgery (+17.1%) and lumbar spinal stenosis (+6.1%); renal and urinary system with increased severe chronic kidney disease and primary nephrotic syndrome (+1.1%) as well as dysuria or severe urinary infections (+1.9%); ear, nose and throat with increased hearing aid use (+7.6%) and sleep apnoea (+5.9%); and eye with increased cataract surgery (+7.9%). In patients with ATTR-CM, there was also functional capacity impairment with increased use of medical devices for disability (+15.5%) and crutches (+11.8%) vs matched controls, and increased pain medication (+11.5%) and anxiolytic (+2.0%) use (Figure 2).
Conclusion
Clinical manifestations across several organ systems and medications related to QoL impairment were significantly more prevalent in patients with ATTR-CM vs matched controls. Several of these impairments are known to contribute to frailty and decreased QoL. These data confirm the multisystemic nature of ATTR-CM and need for a holistic approach when managing patients with ATTR-CM.