Longitudinal Electrocardiographic Findings in ATTR Amyloidosis: A Single-Center Study

BACKGROUND: Amyloidosis is an infiltrative disease characterized by the extracellular accumulation of amyloid fibrils originating from protein misfolding. When the heart is involved, it is defined as cardiac amyloidosis (CA). Transthyretin cardiac amyloidosis (ATTR-CA), which includes both wild-type (ATTRwt-CA) and hereditary (ATTRv-CA) forms, is one of the most common causes of CA. The electrocardiogram (ECG) is a cheap, widely available tool that can aid the identification, diagnosis, and prognostic assessment of ATTR-CA. AIM OF THE STUDY: Studies evaluating temporal electrocardiographic changes in transthyretin cardiac amyloidosis are scarce. Therefore, this study aims to investigate electrocardiographic changes in patients with ATTR-CA over time and to evaluate their prognostic value. MATERIALS AND METHODS: This was a single-center, observational, retrospective study conducted on adult patients (>18 years) followed in the outpatient clinic for Cardiac Amyloidosis at the University Hospital of Padua from January 2020 to March 2026. Patients with a definitive diagnosis of ATTR-CA and a 12-lead ECG available at diagnosis and at 12 months of follow-up were included. Patients with paced ECG rhythm were excluded. Clinical-anamnestic characteristics, medical history, laboratory parameters, electrocardiographic and echocardiographic data, and outcome data were collected. The primary endpoint was the composite of hospitalization for heart failure and all-cause death. RESULTS: Among 92 patients with ATTR-CA, incident or progressed intraventricular block (IVB) occurrence was observed in 20 patients (22%) at 12-month ECG. These individuals had significantly higher baseline National Amyloidosis Center (NAC) stage II/III prevalence (47% vs. 22%, p=0.032), longer QRS duration (121 vs. 104 msec, p=0.043), lower left-ventricular ejection fraction (LVEF) (47% vs. 56%, p=0.009), and lower tricuspid annular plane systolic excursion (TAPSE) (15 vs. 19 mm, p=0.022) compared to those with stable IV conduction. After a median follow-up of 16 months (IQR 9 – 24), 24% (n=22) patients met the primary composite endpoint. 12-month incident/progressed IVB was associated with the primary endpoint occurrence after 12-months evaluation at univariable (HR 2.64, 95% CI 1.04–6.54, p=0.036) and at multivariable analysis (HR 2.64, 95% CI 1.04–6.70, p=0.041), together with 12-month NAC stage worsening (HR 12.85, 95% CI 5.05–32.70, p<0.001). Their contemporary presence was associated with the highest incidence of the primary endpoint (log-rank p < 0.0001). CONCLUSIONS: In patients with ATTR-CA, incident or progressed IVB at 12-month ECG evaluation is a common finding that appears to preferentially occur in individuals with advanced disease at diagnosis and exhibited a potential role as disease progression marker. These findings suggest that periodic ECG assessment may complement established prognostic tools in ATTR-CA, and that integrating conduction system changes with established disease progression markers could refine risk stratification.