Diffuse Myocardial Fibrosis Reduces Electrocardiographic Voltage Measures of Left Ventricular Hypertrophy Independent of Left Ventricular Mass

Abstract

Background Myocardial fibrosis quantified by myocardial extracellular volume fraction ( ECV ) and left ventricular mass (LVM) index ( LVMI ) measured by cardiovascular magnetic resonance might represent independent and opposing contributors to ECG voltage measures of left ventricular hypertrophy ( LVH ). Diffuse myocardial fibrosis can occur in LVH and interfere with ECG voltage measures. This phenomenon could explain the decreased sensitivity of LVH detectable by ECG , a fundamental diagnostic tool in cardiology. Methods and Results We identified 77 patients (median age, 53 [interquartile range, 26–60] years; 49% female) referred for contrast‐enhanced cardiovascular magnetic resonance with ECV measures and 12‐lead ECG . Exclusion criteria included clinical confounders that might influence ECG measures of LVH . We evaluated ECG voltage‐based LVH measures, including Sokolow‐Lyon index, Cornell voltage, 12‐lead voltage, and the vectorcardiogram spatial QRS voltage, with respect to LVMI and ECV . ECV and LVMI were not correlated ( R 2 =0.02; P =0.25). For all voltage‐related parameters, higher LVMI resulted in greater voltage ( r =0.33–0.49; P <0.05 for all), whereas increased ECV resulted in lower voltage ( r =−0.32 to −0.57; P <0.05 for all). When accounting for body fat, LV end‐diastolic volume, and mass‐to‐volume ratio, both LVMI (β=0.58, P =0.03) and ECV (β=−0.46, P <0.001) were independent predictors of QRS voltage (multivariate adjusted R 2 =0.39; P <0.001). Conclusions Myocardial mass and diffuse myocardial fibrosis have independent and opposing effects upon ECG voltage measures of LVH . Diffuse myocardial fibrosis quantified by ECV can obscure the ECG manifestations of increased LVM . This provides mechanistic insight, which can explain the limited sensitivity of the ECG for detecting increased LVM .