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

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.