Contemporary description of cardiac manifestations in ATTR amyloidosis: results from the multi-country OverTTuRe study

Abstract

Abstract Background In transthyretin (ATTR) amyloidosis, amyloid fibrils accumulate in the myocardium, resulting in cardiac manifestations that can ultimately be fatal. The diverse presentation of this condition often results in prolonged diagnostic journeys for patients before they receive a definitive diagnosis of ATTR amyloidosis and treatment. Purpose To delineate the demographic and clinical characteristics of patients diagnosed with ATTR amyloidosis by cardiac manifestations, and to examine the duration from the first recorded cardiac manifestation to diagnosis. Methods OverTTuRe is a multi-country study generating real-world evidence from a cohort of patients identified as having ATTR amyloidosis between 2017-2022. Data were extracted from the US (Optum’s de-identified Clinformatics Data Mart Database) and Japan (Medical Data Vision Database). Additional analyses from European countries are ongoing. Patients aged ≥18 years with a recorded ICD-10 diagnosis code for ATTR amyloidosis (all phenotypes) or record for an ATTR-specific treatment were included. The index date was defined as first recorded date of diagnosis or ATTR-specific treatment. Patients with a diagnostic code or treatment indicative of secondary (AA) amyloidosis or light chain (AL) amyloidosis were excluded. Results 17,720 patients (median age: 75 years; 48.3% males) with ATTR amyloidosis were identified from the US and 4,690 from Japan (median age: 77 years; 57.0% males). Among individuals with 5 years of any available data prior to ATTR amyloidosis diagnosis (US: 9,147 [51.6%]; Japan: 2,600 [55.4%]), the most frequent initial cardiac manifestation ahead of ATTR amyloidosis was heart failure (US: 30.3%; Japan: 42.0%) followed by atrial fibrillation (21.9%) and cardiomyopathy (21.7%) in the US, and angina (21.6%) and atrial fibrillation (18.7%) in Japan. Among patients with 5 years of any available data before diagnosis plus cardiac manifestations, there were higher proportions of males than females and older individuals (Table). Median time from the earliest recording of any cardiac manifestation to the diagnosis of ATTR amyloidosis was 2.4 years (IQR: 0.9, 3.9) in the US and 1.2 years (IQR: 0.1, 3.2) in Japan. Median time to diagnosis increased with age and was similar across sexes in the US, whilst females in Japan had longer median time to diagnosis. Among the cardiac manifestations (heart failure, atrial fibrillation, cardiomyopathy, angina, aortic valve stenosis), 52.5% of patients in Japan had at least 2 manifestations, whilst in the US 59.4% of patients had more than 2 manifestations. Conclusions These findings highlight the prevalence of cardiac manifestations such as heart failure, in patients identified as having ATTR amyloidosis, particularly among men and elderly individuals. The observed delay in diagnosis of ATTR amyloidosis illustrates the importance of increased awareness to support early recognition and treatment to limit adverse clinical outcomes.