Electrical progression despite tafamidis in transthyretin cardiac amyloidosis

Introduction

Tafamidis improves survival in transthyretin cardiac amyloidosis (ATTR-CM); however, detailed real-world data describing its longitudinal effects on clinical status, cardiac structure, and electrical remodeling remain limited. A better understanding of disease progression under tafamidis in routine clinical practice is needed.

Purpose

To characterize 12-month changes in functional status, biomarkers, electrocardiographic parameters, and echocardiographic structure and function in patients with ATTR-CM treated with tafamidis.

Methods

We conducted a retrospective observational study including patients with ATTR-CM treated with tafamidis. NYHA functional class, NT-proBNP, electrocardiographic parameters (PR interval, QRS duration, QRS voltage pattern, and new-onset atrial fibrillation), and echocardiographic variables (wall thickness, left ventricular ejection fraction [LVEF], global longitudinal strain [GLS], diastolic indices, and left atrial volume index) were assessed at treatment initiation and after 12 months.

Results

Forty-five patients initiated tafamidis therapy (median age 83 years; 80% male). Hypertension (88.9%) and atrial fibrillation (AF) (60%) were common at baseline, and 22.2% had prior pacemaker implantation. Baseline assessment showed mild functional limitation, elevated NT-proBNP levels, prolonged QRS duration, and typical echocardiographic features of ATTR-CM.

Over 12 months, NYHA class remained stable (median Δ 0.0 [–1.0 to 0.0], p=0.491), although 35.7% improved by at least one functional class. NT-proBNP levels demonstrated marked inter-individual variability without a consistent trend (median Δ +376 pg/mL [−1332 to +750], p=0.807).

Electrocardiographically, PR interval remained unchanged (median Δ +4 ms [−38 to +19], p=0.866), whereas QRS duration increased significantly (Δ +7 ms [3.5 to 17.8], p<0.001).

Notably, new-onset AF developed in 32% of patients without AF at baseline.

Echocardiographic parameters remained largely stable, including LVEF (Δ −2.0% [−7.0 to +3.0], p=0.363), septal thickness (Δ 0.0 mm [−1.0 to 0.5], p=0.518), posterior wall thickness (Δ +1.0 mm [−2.77 to +1.85], p=0.916), LV mass index (Δ +2.7 g/m² [−40.6 to 19.4], p=0.893), GLS (Δ +2.6% [−2.16 to +9.60], p=0.500), E/e′ (Δ +3 [−5.75 to +5], p=0.713), and left atrial volume index (Δ +3 mL/m² [−1.5 to 13.5], p=0.195).

Conclusion

In real-world ATTR-CM, tafamidis therapy is associated with stabilization of functional status, biomarkers, and cardiac structure over 12 months. However, electrical disease progression persists, as evidenced by significant QRS widening and frequent new-onset atrial fibrillation. These findings highlight ongoing electrophysiological vulnerability despite disease-modifying therapy and support the need for systematic ECG surveillance and validation in larger cohorts.Baseline characteristicsFor image description, please refer to the figure legend and surrounding text.Twelve-months changesFor image description, please refer to the figure legend and surrounding text.