Patterns of treatment and genetic testing in transthyretin amyloid cardiomyopathy: a real-world, multinational survey

Background/Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is caused by transthyretin (TTR) deposition in the myocardium, classed as hereditary (vATTR-CM) in the presence of TTR gene variants, or wild type (wtATTR-CM) with nonmutated TTR deposition. Genetic testing is key for the early intervention of vATTR-CM, with disease-modifying therapies (DMTs) such as TTR stabilisers, to slow progression and increase survival. However, real world data describing patterns of treatment and genetic testing for ATTR-CM patients are limited. Purpose To describe treatment and genetic testing patterns in a multinational sample of ATTR-CM patients. Methods Secondary analyses were conducted using data from the Adelphi ATTR Disease Specific Programme™, a cross-sectional survey, with retrospective data collection, of physicians in Europe (France, Germany, Italy, Spain, and the United Kingdom), the United States, and Japan. Physicians reported demographics, New York Heart Association (NYHA) classification, treatment history and genetic testing for up to 10 consecutively consulting patients. Patients with a confirmed genetic variant were considered hereditary, and those with no variant were considered wild type. Missing data were not imputed. Results Overall, 181 physicians provided data for 858 patients (Europe n=542, US n=204, Japan n=112). Mean (standard deviation; SD) age was 71.1 (12.6) years, and 70.3% were male. In total, 19.0% of patients had NYHA I, 61.4% had II, 17.6% had III and 2.0% had IV. Overall, 73.4% of patients were prescribed a drug treatment at the time of survey, with 67.9% of all patients prescribed a DMT (table 1). Genetic testing status is summarised in Figure 1. Overall, 68.4% of patients had received genetic testing. Of the tested patients with known results (n=407), 54.1% were wild type and 45.9% were hereditary. Among hereditary patients (n=187), the most common variants were Val30met (29.4%), Val122Ile (19.3%) and Thr60Ala (8.6%). Conclusion Despite physicians reporting most patients as being NYHA class II or higher, around one-third of patients were not prescribed DMTs. A similar proportion had not undergone genetic testing. This suggests some patients are not receiving standard-of-care, or treatment tailored to variant prognosis, potentially leading to sub-optimal management and health outcomes.Table 1.Treatment status at survey Figure 1.Genetic testing status