Incidence and survival of transthyretin amyloid cardiomyopathy from a French nationwide study of in- and out-patient databases

Introduction Transthyretin (TTR) Amyloid Cardiomyopathy (ATTR-CM) is a rare, progressively debilitating, fatal disease with poor prognosis caused by amyloid deposition of fibrils derived from the serum protein TTR in the extracellular matrix of the heart. Due to the absence of treatment before 2018, ATTR-CM was often under-diagnosed and reliable epidemiological data are still needed on this disease. Objective To estimate the annual incidence of ATTR-CM in France between 2011 and 2019, describe characteristics of incident patients and estimate survival using real world data. Method We used the French nationwide exhaustive data (Système national des données de santé database) gathering in- and out-patient claims. As there is no specific ICD-10 marker code for ATTR-CM, ATTR-CM diagnosis required both amyloidosis (identified by E85. ICD-10 code or a tafamidis delivery) and a cardiovascular condition (identified by ICD-10 codes related to either heart failure, arrhythmias, conduction disorders or cardiomyopathies), not necessarily reported at the same visit. Patients with probable AL-form of amyloidosis (identified by the following comorbidities or treatments: chemotherapy, AL-amyloidosis treatments, multiple myeloma, bone marrow transplantation, cerebral amyloid angiopathy) or probable AA-form of amyloidosis (identified by E85.3 ICD-10 code) were excluded. Results Between 2011 and 2019, 8,950 patients with incident ATTR-CM were identified. Incidence rates increased from 0.6/100,000 person-years in 2011 to 3.6/100,000 person-years in 2019, reaching 2,377 new cases in 2019. Sex ratio (M/F) increased from 1.52 in 2011 to 2.23 in 2019. In 2019, median age at diagnosis was 84.0 years (85.5 for women and 83.5 for men). Median survival after diagnosis was 41.9 months (95% CI [39.6, 44.1]). Conclusion This is to our knowledge the first estimate of ATTR-CM incidence on a national scale using comprehensive real-world databases. Nevertheless, the disease was mostly identified by ICD-10 coded diagnosed cases, leading to possible underestimation of the incidence of the disease in France. We observed an increased incidence over the study period, consistent with an improvement in ATTR-CM diagnosis in recent years.