Vascular dysfunction is associated with symptom severity and quality of life in wild-type transthyretin amyloid cardiomyopathy

Background/Introduction Amyloidosis is characterized by extracellular deposition of misfolded fibrillar proteins, leading to progressive organ dysfunction. In wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM), amyloid deposition predominantly affects the myocardium; however, vascular involvement has also been suggested. Although several previous studies have evaluated vascular function in ATTRwt-CM, the impact of amyloid deposits on vascular function remains incompletely understood. Purpose To characterize vascular function and investigate its association with heart failure symptoms in patients with ATTRwt-CM. Methods We evaluated 43 patients diagnosed with ATTRwt-CM at our hospital between May 2020 and December 2025. Vascular function was assessed using pulse wave analysis, including the ankle–brachial index (ABI), cardio-ankle vascular index (CAVI), and percentage of mean arterial pressure (%MAP). Cardiac function was evaluated by transthoracic echocardiography (TTE), including left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd), and global longitudinal strain (GLS). Laboratory parameters, including hemoglobin levels and biochemical markers, were also analyzed. Symptoms and activities of daily living were assessed using the KCCQ-12 and EQ-5D-5L scores. Results There were 26 patients with NYHA class I-II and 17 with NYHA class III. The mean age was 79.7±6.1 years, and 76.7% were male. The KCCQ-12 and EQ-5D-5L scores were significantly lower in patients with NYHA class III. ABI was significantly lower in NYHA class III (1.08±0.10 vs. 1.16±0.09, p=0.010), whereas %MAP was significantly higher (38.5±4.5% vs. 34.4±4.2%, p=0.005). There were no significant differences in echocardiographic parameters between NYHA class I–II and III. Discriminant analysis demonstrated that higher %MAP, lower ABI, and lower hemoglobin levels were associated with NYHA class III. ABI showed a positive correlation with the KCCQ-12 score (β=0.419, p=0.017). In addition, LVDd was positively correlated with the KCCQ-12 score (β=0.378, p=0.033). In multivariate analysis (analysis of covariance) for KCCQ-12, only ABI remained a significant variable (β=0.474, p=0.005). Conclusion Impaired peripheral vascular function, reflected by lower ABI and higher %MAP, was associated with more severe heart failure symptoms and reduced quality of life in patients with ATTRwt-CM, independent of conventional echocardiographic parameters. These findings suggest that vascular dysfunction may contribute to symptom burden beyond myocardial involvement and may represent an additional therapeutic or prognostic target in ATTRwt-CM.