OR02 Early Markers Of Diasease Progression In Attr-Cm

Background Transthyretin Amyloid Cardiomyopathy (ATTR-CM) is a serious and progressive disease. Several progression markers have demonstrated prognostic value at 12 months(1,2,3,4,5), yet their usefulness in the early identification of patients with an unfavorable course remains uncertain. Purpose We aimed to evaluate the prognostic value at 6 months of previously reported 12-month ATTR progression markers. Methods A landmark survival analysis was conducted for five established 12-month progression markers of ATTR-CM, assessed at 6 months from the baseline visit in 596 consecutive ATTR-CM patients. The progression markers evaluated were: outpatient loop diuretic dose intensification (ODI; defined as any increase in loop diuretic dose), worsening of NT-proBNP (defined as an increase of >30% and >700 pg/mL), worsening of New York Heart association (NYHA) functional class, worsening of estimated glomerular filtration rate (eGFR; defined as a >20% reduction), and hospitalization for heart failure (HF) within the first 6 months. Only patients with available data at that time point and follow-up information were included in the analysis of each parameter. Results At 6 months, 586 (98.3%) subjects were alive. Among those with data available at 6 months, 189/532 (35.5%) met the ODI criterion, 114/427 (26.7%) met the NT-proBNP criterion, 56/456 (12.3%) met the eGFR criterion, 70/525 (13.3%) showed NYHA worsening, and 47/586 (8%) were hospitalized for HF. Kaplan–Meier analysis demonstrated that only ODI (p=0.018), NT-proBNP (p<0.001), HF hospitalization (p=0.012), and eGFR (p=0.019) were associated with mortality during follow-up. Subsequent Cox analysis showed that ODI (HR: 1.48 [1.06–2.05], p=0.02), NT-proBNP (HR: 2.66 [1.80–3.93], p<0.001), eGFR (HR: 1.74 [1.09–2.78], p=0.02), and HF hospitalization (HR: 4.07 [2.73–6.07], p<0.001) were associated with higher mortality during follow-up. When the four criteria (ODI, NT-proBNP, eGFR, and HF hospitalization) were jointly evaluated alongside other prognostic variables (National amyloid center stage and age) in a multivariable Cox regression model, NT-proBNP (HR: 1.91 [1.29–2.84], p=0.01) and HF hospitalization (HR: 1.98 [1.11–3.52], p=0.02) were the only 12-months progression markers that remained independently associated with mortality at 6 months. Conclusions The evaluation of 12-month prognostic markers in ATTR demonstrated that worsening of NT-proBNP levels and HF hospitalization at 6 months are independent predictors of mortality in patients with ATTR and may serve as early indicators of disease progression.