Overtture study: disease burden at diagnosis in ATTR amyloidosis patients with cardiac impairment in Spain

Abstract Background/Introduction Transthyretin (ATTR) amyloidosis is a debilitating condition, characterized by the accumulation of transthyretin amyloid fibrils in various organs and tissues. This condition encompasses a spectrum of phenotypes, including cardiomyopathy (ATTR-CM), polyneuropathy (ATTR-PN), or mixed presentations (both ATTR-CM and ATTR-PN symptoms), each contributing to significant morbidity and mortality. Despite advancements in diagnostic tools and therapeutic options, there remain critical gaps in understanding the patient journey, particularly the delays experienced from symptom onset to diagnosis, and their consequences. Purpose The OverTTuRe study aims to provide comprehensive insights into the pre- and post-diagnosis journey of patients across all ATTR phenotypes. Specifically, this communication focuses on the baseline data and the pre-diagnostic journey (e.g. time to diagnosis, manifestations, healthcare resources) of the Spanish cohort of patients with cardiac involvement (ATTR-CM and mixed phenotypes). Methods Observational, retrospective chart review in 11 Spanish hospitals. 213 ATTR-CM and 150 ATTR mixed-phenotype patients diagnosed from 2009 onwards were included (Figure 1). ATTR phenotype at diagnosis was assigned by the participating investigators. Mean age at diagnosis was 77.4 years (SD=10.9), 23.4% were female. 97.0% had a late onset (defined as age at diagnosis ≥50). The predominant genotype was ATTR wild-type (69.7%), especially among ATTR-CM patients (91.9%). For patients with hereditary ATTR amyloidosis (30.3%), the most frequent variants were late-onset Val50Met (53.1%) and Val142Ile (16.7%). From the first clinical manifestation associated with ATTR amyloidosis until diagnosis, the median time was 19.4 months (IQR 3.6-82.6). At the time of diagnosis, 16.1% of patients were classified as NYHA III-IV, and 51.1% were in NAC stages 2-3. Median NT-proBNP was 2,379 pg/mL (IQR 1,100-5,006) with 57.3% having 2,000 pg/ml and 40.9% 3,000 pg/mL. Cardiomyopathy, heart failure, and atrial fibrillation were the most common conditions at diagnosis; however, a wide range of extra-cardiac symptoms (including autonomic nervous system) were also observed, particularly among patients with mixed phenotypes. Healthcare resource utilisation (HCRU) in the 12 months prior to diagnosis was notable, with a mean (SD) of 2.4 (4.3) visits to specialists and 31.1% of patients having at least one hospitalisation, both due to ATTR amyloidosis (as assessed retrospectively). Baseline data are summarized in Table 1. Conclusions Our findings highlight the remarkable disease burden affecting patients with ATTR-CM and ATTR-mixed amyloidosis at the time of diagnosis, which coincides with their prolonged and challenging diagnostic journey. These insights may help to establish improved recommendations for diagnostic pathways and, given the presence of multiple comorbidities, promote a comprehensive, proactive and multidisciplinary approach.Figure 1-Study Flowchart Table 1-Baseline characteristics (at dx)