Critique on the Fibrillatory Wave Amplitude of ECG Decreases Over Time in Patients With Persistent AF

We read with great interest the article by Li et al. (2026) “The Fibrillatory Wave Amplitude of ECG Decreases Over Time in Patients With Persistent AF,” which provides valuable insight into noninvasive markers of atrial remodeling. In this retrospective cohort of 998 patients, the authors show a significant inverse, nonlinear association between AF duration and both fibrillatory wave amplitude and coarse F-waves in lead V1, with thresholds at 10.184 and 17.238 years. Their large sample, robust modeling, and focus on a simple ECG parameter offer practical utility for estimating AF chronicity, particularly in settings lacking advanced diagnostics. Nonetheless, several limitations warrant consideration. The study by Li et al. offers valuable insight into the relationship between atrial fibrillation (AF) duration and fibrillatory wave amplitude, yet several limitations temper its conclusions. First, AF duration was derived from hospital records, which risks misclassification since AF onset is often silent. This underestimation may distort the nonlinear thresholds identified and weaken the observed inverse association, as highlighted by Steinberg et al. (2014) who showed AF is frequently asymptomatic and undetected. Second, F-wave amplitude was measured manually without reporting interobserver reliability. Manual assessment introduces bias and variability, and given the small effect sizes, even minor measurement error could alter statistical significance. Bollmann et al. (1998) demonstrated that automated spectral analysis improves reproducibility, underscoring the need for objective methods. Third, the study lacks structural validation. Declining F-wave amplitude was interpreted as progressive fibrosis, yet no voltage mapping, LGE-MRI, or histopathology was performed. Without such correlation, the link between amplitude and remodeling remains speculative. Evidence from Marrouche et al. (2014) in the DECAAF study shows that imaging-based fibrosis quantification predicts AF recurrence, highlighting the importance of structural validation. Fourth, medication effects were insufficiently controlled. While amiodarone users were excluded, other agents such as beta-blockers, calcium channel blockers, digoxin, ACE inhibitors, and statins can influence atrial conduction and ECG morphology. Unmeasured pharmacologic confounding may therefore bias results, as shown by Nault et al. (2009) and Saksena et al. (2018) who reported drug effects on atrial activation and fibrillatory wave characteristics. Finally, survival bias is a concern in patients with AF duration exceeding 10 years. These individuals represent survivors who avoided death from stroke or heart failure and were not referred for early ablation, forming a distinct subgroup with potentially milder disease. This selection effect may distort the nonlinear associations observed, echoing Schnabel et al. (2012) caution regarding survival and referral biases in AF cohorts. Future studies should use continuous rhythm monitoring to better define AF onset, integrate biomarkers and LGE-MRI for structural validation, and improve measurement reliability through automated analysis and blinded review. Adjustment for medication effects, subgroup analyses, and prospective longitudinal designs with time-to-event modeling are also needed to strengthen causal inference and reduce bias. In conclusion, while Li et al. provide valuable insight into the potential role of fibrillatory wave amplitude as a noninvasive surrogate of AF chronicity, several methodological and interpretative consideration, including possible duration misclassification, measurement variability, lack of structural validation, pharmacologic confounding, survival bias, limited generalizability, and the cross-sectional design, temper the strength of the causal inferences that can be drawn. Addressing these issues in future prospective, multicenter, and mechanistically integrated studies will be essential to clarify whether F-wave amplitude can be reliably adopted as a surrogate marker of atrial remodeling and AF duration in routine clinical practice. All the authors meet the ICMJE authorship criteria and have made significant and equal contributions to this manuscript. All authors approved the final version and agree to be accountable for all aspects of the work, ensuring the accuracy and integrity of the data and interpretation. The authors have nothing to report. Transparency Statement: The Authors affirm that this manuscript is an honest, accurate, and transparent account of the study being reported, that no important aspects of the study have been omitted, and that any discrepancies from the study as planned (and if relevant, registered) have been explained. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.