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

Introduction Cardiac amyloidosis due to transthyretin (ATTR-CM) is a systemic, life-threatening disease, which manifests both cardiac and extra-cardiac symptoms and signs. Although its diagnosis remains challenging, it is increasingly recognized due to the availability of non-invasive means, namely cardiac scintigraphy using bone-avid tracers. Data regarding the prevalence of ATTR-CM are scarce. Purpose We aimed to study the prevalence and characteristics of ATTR-CM, both wild (wtATTR-CM) and hereditary (vATTR-CM), in patients with left ventricular hypertrophy (LVH) of undetermined etiology in Greece. Methods RETTRACE is a low- intervention, prospective, multicenter, nationwide, descriptive study, in 14 major 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 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 vATTR-CM, the clinical characteristics of ATTR-CM patients, and their quality of life, using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the EuroQol-5-Dimensions Questionnaire (EQ-5D-3L). Patients were evaluated and managed according to local clinical practice. Bone scintigraphy was performed at each center and scans graded >0 according to the Perugini score, were further evaluated by two independent nuclear physicians. 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 at a central laboratory. Results The RETTRACE final analysis, includes 313 evaluable patients (men: 56.5%), with a mean (SD) age of 76.9 (9.9) years. Basic demographics and clinical characteristics are shown in Table 1. Amongst 294 patients who underwent bone scintigraphy, 177 (60.2%) were rated as grade 0 according to the Perugini score. 92 scans were assessed as grade 2 or 3, by the two independent reviewers, and their consensus combined with negative testing for paraproteinemia was used to estimate the primary endpoint. In total, 47 out of 294 eligible patients (16.0%) were deemed to have ATTR-CM, per applied criteria. Four of them (8.5%) carried mutations (Val114Ala, Ala101Thr, Cys30Arg and Val142Ile). As compared to non-ATTR-CM patients, those with ATTR-CM were older (mean age of 82.2 vs 75.7 years, p<0.001), more frequently exhibited a pseudo-MI pattern on ECG (36.2% vs 17.0%, p=0.005) and had more frequently undergone carpal tunnel surgery (31.9% vs 8.9%, p<0.001). Conclusions ATTR-CM has a significant prevalence in a Greek population of adults ≥ 50 years with LVH of undetermined etiology. RETTRACE study results provide valuable information for patients suffering from this life-threatening disease.