Predictors of major adverse cardiovascular events in patients with wild-type transthyretin amyloid cardiomyopathy: insights from a regional hospital experience

Abstract Introduction Transthyretin cardiac amyloidosis (ATTR-CA) results from the deposition of amyloid fibrils in the myocardium, leading to restrictive cardiomyopathy and reduced myocardial contractile reserve. This progressive process often results in symptomatic chronic heart failure (HF) and, eventually, death. Objectives Identify predictors of extended major adverse cardiovascular events (MACE) in patients (pts) with ATTR-CA followed at a Cardiomyopathy Clinic (CC) in a regional hospital in Portugal. Methods Retrospective single-center study of pts diagnosed with wild-type ATTR-CA per ESC algorithm from 2018 to 2024. Clinical, echocardiographic, electrocardiographic and analytical data were collected at the time of diagnosis (table 1). The occurrence of extended MACE, defined as cardiovascular (CV) mortality, myocardial infarction, stroke and HF hospitalizations, was assessed 18 months after diagnosis. Pts who suffered MACE (group 1) were compared with those who did not (group 2). Results 45 pts were included (80±6 yrs, 91% male), of whom 20 (44%) had MACE (group 1). Group 1 pts more frequently had atrial fibrillation (AF) (95 vs 48%, p0.001), chronic kidney disease (CKD) (80 vs 44%, p=0.014) and chronic obstructive pulmonary disease (COPD) (40 vs 12%, p=0.041). After multivariate logistic regression of these 3 comorbidities, only AF (OR 24.83, CI 95% 2.31-266.46, p=0.008) and CKD (OR 7.55, CI 95% 1.51-37.66, p=0.014) remained independent predictors of MACE. Regarding echocardiographic variables, group 1 pts demonstrated lower left atrial (LA) reservoir strain (LASr) 5.5 (IQR 3) vs 7.0% (IQR 8); p=0.039 and LA contractile strain (LASct) 0.0 (IQR 2) vs -3.0% (IQR 6); p=0.026. Additionally, group 1 more often had atrioventricular block (40 vs 4%, p=0.012) and showed significantly higher NT-proBNP levels (5655±3006 vs 4030±2927 pg/mL, p=0.028). ROC analysis identified cut-offs for predicting MACE in ATTR-CA pts: creatinine ≥1.25 mg/dl (AUC 0.764, sensitivity (S) 85%, specificity (E) 64%), NT-proBNP ≥3220 pg/ml (AUC 0.705, S 90%, E 52%), and LASct ≥-2.5% (AUC 0.675, S 80%, E 52%). The primary driver of 18-month MACE was HF hospitalizations (86%), followed by CV mortality (14%). Conclusions In this ATTR-CA population, pts with extended MACE had lower LASr and LASct values and higher NT-proBNP levels at diagnosis. Assessing these parameters may help predict adverse outcomes. Additionally, AF and CKD were identified as independent risk factors for MACE.