Progressive electrocardiographic remodeling despite Tafamidis therapy in transthyretin amyloid cardiomyopathy (ATTR-CM)

Scritto il 29/08/2026
da Lilou Escorbiac

J Electrocardiol. 2026 Aug 25;99:154440. doi: 10.1016/j.jelectrocard.2026.154440. Online ahead of print.

ABSTRACT

BACKGROUND: Electrocardiographic (ECG) abnormalities are a hallmark of transthyretin amyloid cardiomyopathy (ATTR-CM), yet longitudinal ECG changes under disease-modifying therapy remain poorly characterized.

METHODS: In this retrospective multicenter study, 140 patients with confirmed ATTR-CM receiving tafamidis underwent serial 12‑lead ECG assessment at baseline and after one year. ECG parameters were analyzed in relation to biomarker-based disease stage, clinical progression, and all-cause mortality. Longitudinal ECG changes were evaluated using Wilcoxon signed rank and McNemar tests. Survival analyses were conducted using Kaplan-Meier estimates and univariable Cox regression.

RESULTS: At baseline, PR interval, QRS duration, and QTc were significantly associated with advanced disease stage, whereas QRS voltage and heart rate were not. During follow-up, patients showed clinical progression with worsening functional status despite stable biomarker-based disease stage. Serial ECG assessment demonstrated ongoing electrical remodeling with significant QRS prolongation (109 vs. 114 ms, p < 0.001), increasing conduction disturbances, and a doubling of pacemaker stimulation. These changes occurred independently of disease stage and were confirmed in patients without pacemaker-stimulated rhythm. Longitudinal changes in QRS voltage were inconsistent and depended on the analytic approach. Baseline QRS duration ≥120 ms and markedly prolonged PR interval (>220 ms) were associated with adverse outcome, whereas longitudinal ECG changes were not independently associated with mortality.

CONCLUSIONS: In ATTR-CM, baseline conduction abnormalities - but not longitudinal ECG changes - were associated with adverse outcomes. Despite tafamidis therapy, ECG abnormalities continued to progress, predominantly reflecting ongoing conduction system involvement independent of biomarker-based disease stage, suggesting that serial ECG assessment may complement disease monitoring rather than risk stratification.

PMID:42667731 | DOI:10.1016/j.jelectrocard.2026.154440