Structural and functional echocardiographic characterisation and prognostic determinants in real-world transthyretin amyloid cardiomyopathy patients on standard of care
E Pedio, S Martano, A Carla', F Sturda', G Colonna, S MaraziaAbstract
Introduction
Transthyretin amyloid cardiomyopathy (ATTR-CM) is increasingly recognised as a significant cause of heart failure, particularly in elderly populations. Disease-modifying therapies, notably tafamidis, have altered the clinical landscape, yet real-world data on echocardiographic evolution and prognostic markers under standard of care remain limited.
Purpose
To characterise the structural and functional echocardiographic profile and identify clinical and imaging predictors of adverse outcomes in a contemporary cohort of ATTR-CM patients managed with standard of care therapy.
Methods
We retrospectively analysed 163 consecutive patients diagnosed with ATTR-CM at a single centre (Lecce, Italy) between January 2020 and October 2025. Diagnosis was established non-invasively by echocardiography, bone-avid tracer scintigraphy (Perugini grade >=2) and exclusion of monoclonal gammopathy. All patients underwent TTR gene sequencing. Comprehensive echocardiography including speckle-tracking global longitudinal strain (GLS) was performed at baseline, 6 and 12 months. The primary composite endpoint was all-cause mortality or heart failure hospitalisation. Cox proportional hazards regression was used to identify prognostic predictors.
Results
Median age was 77 years (IQR 67-83); 73.6% were male. Wild-type ATTR accounted for 62% and variant forms for 38% (Phe84Leu 52.2%, Val142Ile 34.3%). Most patients were in NYHA class II (53.4%) or III (23.3%). Baseline echocardiography showed concentric wall thickening (interventricular septum 16 mm), preserved ejection fraction (EF 54%) and impaired GLS (-14.7%). Over 12 months, echocardiographic parameters remained stable (EF 54%, GLS -14.6%), with improvement in TAPSE/PASP ratio (0.7 to 0.9 mm/mmHg) and reduced prevalence of advanced diastolic dysfunction (54% to 17.8%). On Cox regression, significant predictors of the composite endpoint included age (HR 1.064, p=0.001), NYHA class (HR 5.059, p<0.001), Perugini score (HR 1.826, p=0.003), atrial fibrillation (HR 2.238, p=0.013), eGFR (HR 0.972, p=0.002), troponin I (HR 1.008, p=0.011), interventricular septal thickness (HR 1.180, p<0.001), EF (HR 0.941, p<0.001), GLS (HR 1.148, p<0.001), E/e' (HR 1.087, p=0.004) and TAPSE/PASP ratio (HR 0.140, p<0.001).
Conclusions
In this real-world ATTR-CM cohort, standard of care therapy was associated with echocardiographic stability over 12 months. Both clinical variables (NYHA class, renal function, atrial fibrillation) and advanced echocardiographic parameters (GLS, E/e', TAPSE/PASP ratio) emerged as strong independent predictors of adverse outcomes, supporting a multiparametric approach to risk stratification in contemporary ATTR-CM management.