Prevalence of transthyretin amyloid cardiomyopathy in patients with left ventricular hypertrophy: the RETTRACE Study

Abstract Introduction Amyloid transthyretin amyloid cardiomyopathy (ATTR-CM) is a rare, systemic, life-threatening disease, characterized by both cardiac and extra-cardiac symptoms and signs. Its diagnosis remains challenging, however it is increasingly being pursued due to the availability of non-invasive diagnostic means, namely bone scintigraphy. Data regarding the prevalence of ATTR-CM in Greece are scarce. Purpose We aimed to study the prevalence and characteristics of ATTR-CM, both wild-type (ATTRwt-CM) and hereditary (ATTRv-CM), in patients with left ventricular hypertrophy (LVH) of undetermined etiology in Greece. Methods RETTRACE is an on-going, low- risk, prospective, multicenter, nationwide descriptive study, in 14 major outpatient Cardiology centers throughout Greece. Its primary endpoint is the prevalence of ATTR-CM in adults ≥ 50 years, with: a) Heart Failure with preserved Ejection Fraction (HFpEF) or Heart Failure with mildly reduced Ejection Fraction (HFmrEF) and a left ventricular wall thickness (LVWT) of ≥12mm, or b) a LVWT ≥14 mm of unknown etiology. Secondary endpoints include the prevalence of ATTRv-CM, the description of clinical characteristics of ATTR-CM patients, and their quality of life, as evaluated with the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the EuroQol-5-Dimensions Questionnaire (EQ-5D-3L). Patients were screened and managed according to local clinical practice. Screening for light chain (AL) amyloidosis was done by immunofixation electrophoresis (serum and urine) and serum free light-chain (sFLC) assay, while biopsy was performed at the investigator’s discretion. TTR genotyping was done centrally. Results The RETTRACE interim analysis (data-cut-off: May 31st, 2023), includes 153 patients (men: 52,9%), with a mean (SD) age of 77 (10.3) years. Basic demographics are shown in Table 1. Amongst patients who had bone scintigraphy results available, 71 (51.4%) were grade 0 according to the Perugini score. Furthermore, 62 tests of grades 1-3 were assessed by two independent reviewers and their final consensus was used to estimate the primary endpoint. In total, 24 out of 134 eligible patients were deemed to have ATTR-CM (17.9%), per applied criteria. Two of them carried mutations (Val114Ala and Ala101Thr respectively). As compared to non-ATTR-CM patients, those with ATTR-CM were older (mean age of 82.9 vs 76.0 years, p=0.004), less frequently hypertensive (54.2% vs 78.2%, p=0.021) and had more frequently undergone carpal tunnel surgery (29.2% vs 10.0%, p=0.021). Moreover, they had a poorer quality of life by MLHFQ (median 19.5 vs 40.0, p=0.05), while no significant differences were found in the EQ-5D-3L questionnaire. Conclusions ATTR-CM has a significant prevalence in a Greek population of adults ≥ 50 years with LVH of undetermined etiology. RETTRACE study results will provide valuable information for this underdiagnosed, life-threatening condition.