Background
Conduction system disease is a common manifestation of cardiac transthyretin amyloidosis (ATTR-CA). Transthyretin stabilisers and silencers slow disease progression and may prevent arrhythmic complications. The trajectory and prognostic impact of conduction system disease in contemporary cohorts receiving targeted therapy remain unclear.
Objective
To evaluate atrioventricular (AV) and intraventricular conduction disturbances and their association with clinical outcomes in patients with ATTR-CA.
Methods
This ongoing multicenter registry will include patients diagnosed with ATTR-CA after 2020 across 15 European amyloidosis referral centers. The primary endpoint is all-cause mortality. Secondary endpoints are new-onset AV block and new-onset intraventricular conduction delay. Laboratory, echocardiographic, and ECG data at diagnosis and most recent follow-up were collected. Outcomes were censored at 5 years.
Results
338 patients diagnosed with ATTR-CA from 5 European centers were included in this preliminary analysis. The mean age was 79±6 years, and 90% were male. Mean follow-up was 25 months. At diagnosis, 30 patients (8.9%) had a pacemaker in situ for high-grade AV block. NAC stage was 1 in 49% of patients, 2 in 33%, and 3 in 18%. At baseline ECG, 48% were in sinus rhythm (SR), and 44% presented with atrial fibrillation. Among SR patients (n=161), the mean heart rate was 68±11bpm. AV block was observed in 52%, and QRS ≥120ms in 27%.
Patients with AV block had higher NT-proBNP (3214 vs. 2247pg/ml, p=0.02), higher troponin (52 vs. 38pg/ml, p=0.01), and a lower heart rate (66 vs.70bpm, p=0.02). Patients with QRS ≥120ms were more likely to have diabetes (30 vs. 18%, p=0.04) and chronic kidney disease (57 vs. 41%, p=0.02), required higher furosemide doses (51 vs. 36%, p=0.02), and showed higher NT-proBNP (4540 vs. 3105pg/ml, p<0.01) and troponin levels (66 vs. 51pg/ml, p=0.02), greater left ventricular (LV) end-diastolic diameter (46 vs. 44mm, p=0.02), posterior wall thickness (17 vs.15mm, p=0.01), and LV mass index (198 vs. 167g/m², p<0.01), as well as lower LV ejection fraction (48 vs. 52%, p<0.01).
In univariate Cox regression, any degree AV block at diagnosis was associated with all-cause mortality (p=0.03, HR 2.95, 95% CI 1.09–8.0). New onset AV block was observed in 30 patients with no significant predictors in univariate analysis. QRS duration (ms) was associated with increased all-cause mortality (p=0.02, HR 1.01, 95%CI 1.00–1.02). In univariate Cox regression, NAC stage (p=0.03, HR 1.54, 95%CI 1.05–2.26) and low QRS voltage (p=0.03, HR 2.11, 95%CI 1.08–4.1) at baseline predicted new-onset electrical dyssynchrony (QRS ≥130ms). Both remained significant in multivariate analysis (p<0.01, HR 1.69, 95%CI 1.14–2.51; p=0.01, HR 2.35, 95%CI 1.2–4.6).
Conclusion
Conduction system disease is highly prevalent in patients with ATTR-CA and is associated with markers of advanced cardiac involvement. The presence of AV block and QRS prolongation were linked to higher cardiac biomarker levels, more severe structural remodeling, and increased all-cause mortality. NAC stage and low-voltage ECG patterns independently predicted new-onset intraventricular conduction delay. These findings identify conduction abnormalities as key markers of disease severity and poor prognosis in ATTR-CA, emphasizing the need for systematic ECG monitoring and early recognition of patients, who may benefit from closer rhythm surveillance or pacing strategies.
