High Rate of Systolic Heart Failure in Patients with Hereditary Transthyretin Cardiac Amyloid

Purpose Hereditary Transthyretin Cardiac Amyloidosis (hATTR- CM) is an infiltrative cardiomyopathy that is usually associated with significant ventricular hypertrophy and restrictive diastolic dysfunction. Recent studies have demonstrated that patients with the V122Ile hATTR-CM variant present with worse functional status at diagnosis compared to wild-type and other hereditary variants. Therefore, we sought to assess the prevalence of systolic heart failure and associated clinical characteristics at the time of diagnosis of V122Ile hATTR-CM patients in our single, tertiary care center. Methods 69 patients were diagnosed with V122Ile hATTR-CM between 2013 - 2020 by genetic testing in combination with technetium pyrophosphate scanning or endomyocardial biopsy. Demographic and diagnostic data were collected by retrospective chart review and patients with systolic heart failure, defined as EF ≤ 40%, were identified. All data is reported as mean ± standard error or percentage of whole. Results Among our cohort of 69 patients with V122Ile hATTR-CM, 46 (67%) were found to have systolic heart failure with a LVEF of 26% ± 10.1, IVS thickness of 17.4 mm ± 4.1, and LV Mass Index was 166.2 g/m2 ± 61.2. Troponin I and BNP biomarkers averaged 0.26 ± 0.61 and 885 ± 561, respectively. The most prominent extra-cardiac manifestations among the systolic heart failure group were bilateral carpal tunnel syndrome in 25 (54%) patients, lumbar stenosis in 11 (24%), and polyneuropathy in 9 (20%). A significant delay in diagnosis was seen with an average time of 19 months from time of presentation to ATTR diagnosis. Average survival time after diagnosis was 2.5 ± 1.8 years and 6 (16%) patients underwent successful orthotopic heart transplant. 33% of patients with systolic heart failure were found to have primary prevention ICDs. Conclusion In a cohort of 69 V122Ile hATTR-CM patients, 67% were found to have systolic heart failure at the time of initial diagnosis. A significant delay was noted in time to diagnosis, which is consistent with the existing literature. Despite the delay in diagnosis and depressed LVEF at presentation, average survival remained > 2 years. Delayed diagnosis remains a critical problem for hATTR-CM patients.