Low myocardial extracellular volume is associated with increased QRS voltages and false positives in ECG-based left ventricular hypertrophy classification in elite athletes

Abstract Background Increased QRS voltages in athletes’ ECGs are attributed to electrophysiological cellular adaptations, complicating the detection of left ventricular hypertrophy (LVH). Conversely, higher extracellular volume (ECV), indicative of diffuse fibrosis, reduces QRS voltages – so-called ‘relative voltage deficiency’– and can mask true LVH on ECG. Purpose To investigate sex-specific associations between QRS voltages and myocardial ECV and assess the impact of ECV on false-positive and negative ECG-LVH detection in elite athletes. Methods We conducted a cross-sectional, sex-specific, contrast-enhanced CMR study in healthy, elite athletes with normal ECGs and no complete right bundle branch blocks. Myocardial ECV (%) was measured from pre- and post-contrast T1 mapping. LVH on CMR was defined as an indexed LVM 75 g/m² (men) or 59 g/m² (women). Primary analyses evaluated correlations between ECV, LVM, and summed 12-lead ECG voltages (including voltage/LVM to assess independence), as well as Sokolow-Lyon and Cornell voltages. Secondary multivariable logistic regression examined the association of ECV on false-positive and false-negative ECG-LVH rates using Sokolow-Lyon (≥3.5 mV) and sex-specific Cornell (≥2.8 mV in men; ≥2.3 mV in women) criteria for CMR-LVH. Results In 162 elite athletes (median age 25 years, 44% female, 45% endurance, 96% Caucasian), 23% met Sokolow-Lyon criteria, 6% met Cornell criteria, and 17% had LVH on CMR. The median myocardial ECV was 23% (range 19–31%), which was lower in male compared to female athletes (22% Q1-Q3: 21–23% vs 25% 23–26%; p0.001). In both sexes, summed 12-lead voltages were inversely correlated with ECV (ρ=–0.36 to –0.37; p=0.001), independent of LVM (voltage/LVM: ρ=–0.33; p=0.004). Only in female athletes did 12-lead voltages correlate with LVM (ρ=0.37; p=0.001). Logistic regression confirmed that lower ECV was associated with an increased likelihood of false-positive Sokolow-Lyon (OR: 0.64 per 1% ECV increment; p=0.011), independent of body mass index (OR: 0.77 per kg/m²; p=0.039) male sex (OR: 2.7; p=0.123) and age (OR: 0.93 per year; p=0.075; AUROC 0.82). Higher ECV conferred greater odds of a false-negative (OR 3.98 per %; p=0.041), though this was limited by small LVH-positive sample size. In Cornell-based models, lower ECV was not statistically significantly associated with increased false-positive rate (OR 0.59; p=0.059). Conclusion In elite athletes, lower ECV ("denser" myocardium) is associated with increased QRS voltages and higher false-positive ECG-LVH rate, particularly for Sokolow-Lyon, while higher ECV may dampen voltages and can mask true LVH on the ECG. Although sex-specific criteria partly mitigate ECV-related effects, these findings demonstrate inherent limitations of voltage-based LVH criteria in athletes. Unexpectedly low QRS voltages in athletes with otherwise high LVM may imply increased ECV, though further research is warranted.Figure:Likelihood of False Pos SL rate Table:Population characteristics