Although there are several excellent indexes of myocardial contractility, they require accurate measurement of pressure via left ventricular (LV) catheterization. Here we validate a novel noninvasive contractility index that is dependent only on lumen and wall volume of the LV chamber in patients with normal and compromised LV ejection fraction (LVEF). By analysis of the myocardial chamber as a thick-walled sphere, LV contractility index can be expressed as maximum rate of change of pressure-normalized stress (d*/dt max, where * ϭ /P and and P are circumferential stress and pressure, respectively). To validate this parameter, d*/dt max was determined from contrast cine-ventriculography-assessed LV cavity and myocardial volumes and compared with LVEF, dP/dt max, maximum active elastance (Ea,max), and singlebeat end-systolic elastance [E es(SB)] in 30 patients undergoing clinically indicated LV catheterization. Patients with different tertiles of LVEF exhibit statistically significant differences in d*/dt max. There was a significant correlation between d*/dt max and dP/dtmax (d*/ dt max ϭ 0.0075dP/dt max Ϫ 4.70, r ϭ 0.88, P Ͻ 0.01), E a,max (d*/dtmax ϭ 1.20Ea,max ϩ 1.40, r ϭ 0.89, P Ͻ 0.01), and Ees(SB) [d*/dtmax ϭ 1.60Ees(SB) ϩ 1.20, r ϭ 0.88, P Ͻ 0.01]. In 30 additional individuals, we determined sensitivity of the parameter to changes in preload (intravenous saline infusion, n ϭ 10 subjects), afterload (sublingual glyceryl trinitrate, n ϭ 10 subjects), and increased contractility (intravenous dobutamine, n ϭ 10 patients). We confirmed that the index is not dependent on load but is sensitive to changes in contractility. In conclusion, d*/dt max is equivalent to dP/dt max, Ea,max, and Ees(SB) as an index of myocardial contractility and appears to be load independent. In contrast to other measures of contractility, d*/dt max can be assessed with noninvasive cardiac imaging and, thereby, should have more routine clinical applicability. cardiac mechanics; ventricular elastance; ventriculography; wall stress THE QUEST TO DELINEATE and quantify myocardial inotropic function in humans, independent of ventricular loading conditions, is an ongoing preoccupation of researchers and clinicians (15-17, 19, 29, 45-47). In the left ventricle (LV), the peak first time derivative of LV intracavity pressure (dP/dt max ), which is reached just before aortic valve opening, is arguably the most sensitive cardiac index of inotropicity and is the "gold standard" (15, 16). Accurate determination of dP/dt max requires measurement of intraventricular LV pressure by invasive cardiac catheterization. In some individuals with mitral regurgitation, dP/dt max may be approximated from time-resolved mitral regurgitation velocities, which are acquired noninvasively using continuous-wave Doppler echocardiography (1). In general, however, accurate noninvasive assessment of ventricular pressure is very difficult.An additional difficulty with LV dP/dt max is that it is not preload independent (23). Conceivably, the LV pressure-volume relation and e...