Functional assessment of the left ventricle is affected by loading conditions. Detection of rejection-mediated myocardial injury in a heterotopic heart transplant model is a challenge for the echocardiographer because the heart is in an unloaded state. We examined the relationship of a novel left ventricular (LV) wall area index (LVWAI) and serum cardiac troponin T (cTnT) levels. The LVWAI, based on prior methods of determining LV mass, was defined as the difference between epicardial and endocardial areas divided by the epicardial area. The biphasic morphometric response of LVWAI reflected changes in the cTnT levels and allowed echocardiographic detection of myocardial injury in hemodynamically unloaded hearts.