Physical activity engagement results in a variety of positive health outcomes, including a reduction in cardiovascular disease risk partially due to eccentric remodeling of the heart. The purpose of this investigation was to determine if four replicate lines of High Runner mice that have been selectively bred for voluntary exercise on wheels have a cardiac phenotype that resembles the outcome of eccentric remodeling. Adult females (average age 55 days) from the 4 High Runner and 4 non-selected control lines were anaesthetized via vaporized isoflurane, then echocardiographic images were collected and analyzed for structural and functional differences. High Runner mice in general had lower ejection fractions compared to control mice lines (2-tailed p ​= ​0.023 6) and tended to have thicker walls of the anterior portion of the left ventricle (p ​= ​0.065). However, a subset of the High Runner individuals, termed mini-muscle mice, had greater ejection fraction (p ​= ​0.000 6), fractional shortening percentage (p ​< ​0.000 1), and ventricular mass at dissection (p ​< ​0.002 7 with body mass as a covariate) compared to non-mini muscle mice. Mice from replicate lines bred for high voluntary exercise did not all have inherent positive cardiac functional or structural characteristics, although a genetically unique subset of mini-muscle individuals did have greater functional cardiac characteristics, which in conjunction with their previously described peripheral aerobic enhancements (e.g., increased capillarity) would partially account for their increased V˙ O2max.