Transthyretin amyloid cardiomyopathy (ATTR-CM) is an increasingly diagnosed disease, affecting up to 10% of elderly patients with heart failure and preserved left ventricular ejection fraction. While several staging systems have been established to predict mortality in ATTR-CM patients, little is known about determinants of functional status in this heterogenous population.

We analysed 70 patients with ATTR-CM in a monocentric, retrospective study. Diagnosis was made based on endomyocardial biopsy, scintigraphy, and haematological tests in accordance with current guidelines. All patients underwent comprehensive cardiac evaluation as part of routine clinical care, including clinical, echocardiographic, and hemodynamic assessment. Functional status was evaluated by assessing NYHA functional class. Mean age was 77±1 years, 89% of patients were of male gender. The population was highly symptomatic, with 39% of patients presenting with NYHA class III or IV. Hereditary ATTR-CM was identified in 7% of patients. NYHA functional class III or IV was associated with lower glomerular filtration rate (53±3 vs. 64±3 mL/min/1.73m², p=0.008), reduced right ventricular systolic function (tricuspid annular plane systolic excursion 16±1 vs. 19±1 mm, p=0.001), increased left ventricular end diastolic pressure (21±2 vs. 15±2 mmHg, p=0.043), and elevated serum NTproBNP level (7227±1548 vs. 2868±465 pg/mL, p=0.002). Established disease staging systems HeiRisk score, Mayo stage, and National Amyloidosis Center stage each predicted NYHA functional class in univariate analysis (p=0.015, 0.006 and 0.010, respectively), while being inferior to NTproBNP (p<0.0001). In multivariate analysis, tissue Doppler-derived E/E’ remained the only independent predictor of worse NYHA functional status (0.039, 95% CI 0.001-0.0076, p=0.045).

Echocardiographic tissue Doppler-derived E/E’ is a strong predictor of functional status in ATTR-CM, outperforming established disease biomarkers and staging systems. Thus, echocardiographic evaluation of diastolic function might be helpful in guiding therapy for ATTR-CM, warranting further investigation.