Regional left atrial voltage analysis using automated anatomical segmentation in left ventricular cardiomyopathy patients undergoing catheter ablation for atrial arrhythmias

Background Diffuse interstitial fibrosis is a key arrhythmogenic substrate for atrial arrhythmias (AAs) but may be under-detected by commonly used bipolar voltage thresholds in electroanatomical mapping (EAM). In ventricular EAM of LV cardiomyopathy (LV-CM) patients, the distribution and type of fibrosis may differ according to genotype. There, lower averaged unipolar voltage (UV) has been shown to reflect less viable myocardium and to relate to interstitial fibrosis. Whether this translates to atrial fibrosis in LV-CM patients is unknown. Purpose To develop and evaluate an automated workflow for LA segmentation according to the EHRA 2025 regionalization definitions1 and to compare regional unipolar voltage patterns across LV-CM genotypes. Methods High density EAM data of LV-CM patients undergoing CA for atrial fibrillation (AF) or non CTI-dependent atrial tachycardia (AT) between 2016-2024 and four control patients without structural heart disease undergoing CA for paroxysmal AF (PAF) or focal AT were included. A postprocessing pipeline was developed to perform automated LA segmentation of anatomical shells from different EAM systems according to recent EHRA consensus recommendations using an open-source tool2 (Figure 1). Individual mapping points obtained in sinus rhythm or during pacing from the coronary sinus were merged with segmented anatomical shells to enable anatomical region-specific unipolar voltage analysis. Results Fifty-four LV-CM patients (age 57 ±13 years, 80% male, LV-EF 47% ±11%, LAVI 45±16ml/m2, GLS -14%±5%; Genetics: LMNA n=8; TTN n=6; gene elusive and other LP/PV genotypes n=40) were included yielding 69,389 mapping points. Four control patients (age 46±13 years, all with normal LV-EF, LAVI 27±3ml/m2) provided 16,768 points. Automated segmentation succeeded in all cases. Median unipolar voltage was lower in LV-CM than in controls (1.55 mV, IQR [0.8–2.88] vs. 3.11 mV, IQR [1.94–4.87]; p<0.001) and was reduced across all anatomical segments. In genotype-specific sub analysis, LMNA (1.48 mV, IQR [0.72–2.43]) and the group containing gene-elusive and remaining LP/PV patients (1.48mV, IQR [0.79-2.74) showed the lowest voltages, whereas TTN was more preserved (2.17 mV, IQR [1.13–3.21]); all groups vs. controls p<0.001). Comparing the segmental distribution of UVs between the different groups, patterns appeared similar with a general lowering of UVs in the LV-CM groups compared to the controls (Figure 2). Conclusion Automated LA segmentation according to the 2025 EHRA definition enables systematic regional unipolar voltage analysis. LV-CM patients undergoing AF or atypical flutter ablation globally reduced atrial unipolar voltages, with pronounced genotype-specific differences. This approach supports unipolar mapping as an additional substrate biomarker beyond bipolar voltage thresholds and may provide novel methodology for prognostic assessment in AF care.