Early symptoms and medical history of patients with transthyretin amyloidosis cardiomyopathy: Results from the multi-country OverTTuRe study

Abstract Background/Introduction Transthyretin amyloidosis is a progressive and life-threatening condition causing multisystem dysfunction, notably in the heart (ATTR-CM) and peripheral nerves (ATTR-PN), with many patients exhibiting symptoms of both. It can result from hereditary mutations (ATTRv) or an age-related process in wild-type (ATTRwt). The condition is significantly underdiagnosed and an underrecognised cause of heart failure. Real-world data on ATTR-CM, including patient characteristics, from different countries and populations are limited. Purpose The aim of this study was to describe demographics, clinical characteristics and medical history of patients identified as having ATTR-CM across different regions, healthcare systems and populations with different genetic compositions to support earlier recognition and treatment. Methods OverTTuRe is a multi-country study generating real-world evidence on adult symptomatic patients with ATTR amyloidosis. The study population included patients diagnosed with ATTR amyloidosis in several national registries (Sweden, Germany, Canada) or through retrospective chart reviews (Spain and China). Here we present data recorded in the Swedish Transthyretin amyloidosis registry (SveaTTR) from 2000 to October 2024 and patients diagnosed with ATTR amyloidosis from 2009 to 2023 sampled through a chart review at 11 hospitals in Spain. Analyses of data from other countries are ongoing and will also be presented. Patients were assigned to the cardiac phenotype of the disease based on their symptoms and manifestations at baseline (Sweden), or as judged by the investigator (Spain). Results In total, 640 patients were included; 277 from Sweden and 363 from Spain. Besides cardiac manifestations, 61 (22%) patients in Sweden had neuropathic symptoms at the time of disease onset and were classified as having ATTR amyloidosis with mixed phenotype. The corresponding proportion in Spain based on medical records was as high as 41% (n=150). Baseline patient characteristics are presented in the table. Patients with a mixed phenotype were generally younger, more likely female, having a genetic mutation, with peripheral neuropathy being the most common non-cardiac manifestation at diagnosis. The Swedish population of patients with ATTR amyloidosis was in comparison to the Spanish population younger, having fewer chronic conditions, and with ATTR-CM more often being hereditary. The discrepancies between mean and median time from first manifestation to diagnosis of ATTR amyloidosis indicate that some patients suffer from a severe delay, particularly in Spain. Conclusions These findings demonstrate the high degree of neuropathic manifestations across the spectrum of ATTR amyloidosis with cardiomyopathy phenotype, with peripheral neuropathy being the most common. The observed delay in diagnosis of ATTR amyloidosis indicates the need for an increased awareness and earlier clinical suspicion given the poor prognosis if untreated.