Evaluating diagnostic scoring systems for early detection of transthyretin amyloidosis in patients with HFpEF and left ventricular hypertrophy

Abstract Background Transthyretin amyloidosis (ATTR) is a progressive, underdiagnosed condition linked to heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early detection is crucial, as therapies like Tafamidis improve survival and reduce hospitalizations. However, ATTR diagnosis is challenging due to overlapping features with hypertrophic cardiomyopathy (HCM) and Anderson-Fabry disease. Recently, scoring systems such as T-Amylo and ATTR-CM have been developed to enhance detection by integrating clinical, imaging, and biochemical parameters. These tools aim to refine diagnosis, guide further investigations, and enable timely treatment. Purpose This study evaluated the diagnostic value of T-Amylo and ATTR-CM scores in HFpEF patients with LVH. By comparing these scores with noninvasive diagnostic methods—echocardiography, cardiac magnetic resonance (CMR), and technetium-99m scintigraphy—the goal was to assess their effectiveness in identifying ATTR and improving decision-making. Methods This retrospective study included 81 patients (49 males, 32 females; mean age: 71.8 ± 12.7 years) referred between 2019 and 2024 for HFpEF with LVH. All underwent clinical history, blood tests (biomarkers), electrocardiography, echocardiography, CMR, and technetium-99m scintigraphy. Genetic testing was performed where indicated. Key red-flag symptoms (bilateral carpal tunnel syndrome, peripheral neuropathy) were recorded to refine ATTR suspicion. Sensitivity, specificity, and receiver operating characteristic (ROC) curves were analyzed using SPSS software. Results Among 81 patients, 28 (34.6%) were diagnosed with ATTR, while 53 (65.4%) had other LVH etiologies (HCM 28.4%, severe aortic stenosis 30.9%, Fabry disease 6.2%). T-Amylo Score: Sensitivity 75%, specificity 83.3%, AUC 66.7%—effective for ruling out ATTR in low-risk patients. ATTR-CM Score: Sensitivity 35.7%, specificity 97.4%, AUC 74.1%—most effective for confirming ATTR in high-risk cases. ATTR patients showed significantly more extracardiac manifestations (carpal tunnel syndrome, neuropathy). Echocardiographic findings included reduced global longitudinal strain (GLS) with apical sparing and increased right ventricular size. Technetium-99m scintigraphy confirmed ATTR in 64.3% of diagnosed cases, reinforcing its diagnostic role. Conclusions The T-Amylo and ATTR-CM scores provide complementary benefits for ATTR diagnosis in HFpEF patients with LVH. T-Amylo, with moderate sensitivity and specificity, is ideal for ruling out ATTR, while ATTR-CM, with high specificity, is more useful for confirming the disease in high-risk cases. Integrating these scores into clinical workflows can streamline diagnostics and accelerate treatment initiation. Further validation in larger, diverse cohorts is necessary to optimize their clinical utility and enhance patient outcomes.Fig.1 Study flow chart Fig. 2 ROC curves of the scores