Patient journey from the appearance of red flags to the diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in Japan: a nationwide retrospective study using a medical claims database

Abstract

Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of common cardiovascular conditions in the elderly, with relatively high rates among patients diagnosed with heart failure (HF) with preserved ejection fraction. In addition to cardiac symptoms such as HF, extracardiac symptoms such as carpal tunnel syndrome (CTS) and lumbar spinal stenosis (LSS) are also red flags for ATTR-CM. Tafamidis is currently the only disease-modifying therapy approved for the treatment of patients with ATTR-CM and is likely to be more effective in the earlier stage. Patients with ATTR-CM often undergo a long and difficult diagnostic journey because of the nonspecificity of clinical manifestations, resulting in delays in establishing the correct diagnosis. Purpose To identify the timing of appearance of comorbidities in patients with ATTR-CM during diagnosis. Methods In this retrospective, non-interventional, observational study using a claims database (dataset period: April 1, 2014–August 31, 2021), adult patients with a diagnosis of ATTR-CM or prescription for tafamidis 80 mg were included. The index date was defined as the first date of recording ATTR-CM diagnosis or the prescription of tafamidis 80 mg, whichever was earlier. The baseline period was defined as the period between the index date and 6 months before the index date. The onset date was defined as the first date of recording diagnosis of the first red-flags that was suspicious for ATTR-CM. Results Of 11,101,578 patients in the database, 246 patients with ATTR-CM met the inclusion criteria. A total of 239 patients were included, of whom 139 had received tafamidis 80 mg. The median (range) age at the index date was 79.0 (46.0–95.0) years, and 79.9% (191/239) were male. The most frequently reported comorbidity defined as onset of ATTR-CM was conduction disorders (88.7%) followed by atrial fibrillation/atrial flutter (50.6%), hypertensive heart disease (19.7%), aortic stenosis (15.9%), and hypertrophic cardiomyopathy (11.7%), with the median (interquartile range [IQR]) time to the index date being 15.5 (5.0–24.5), 14.0 (5.0–22.0), 9.0 (2.0–18.0), 5.0 (2.0–16.0), and 12.0 (6.5–21.5) months, respectively (Fig. 1). LSS (23.9%), neuropathy (13.0%), and CTS (7.5%) were frequently observed as extracardiac symptoms at baseline, and the median (IQR) time from appearance to the index date was 19 (9.0–28.0), 5.0 (1.0–16.0), and 18.0 (14.0–25.0) months, respectively (Fig. 2). Conclusions This study elucidated the time lag between the appearance of cardiac and extracardiac complications of ATTR-CM and its diagnosis in real-world clinical settings. These novel findings highlight the potential for earlier detection of ATTR-CM.