BACKGROUND The end-systolic pressure-volume relation (ESPVR) provides a useful measure of contractile function. However, the need to acquire multiple cardiac cycles at varying loads limits its applicability. We therefore developed and tested a novel single-beat estimation method that is based on normalized human time-varying elastance curves [EN(tN)]. RESULTS Pressure-volume (PV) data were measured by conductance catheter in 87 patients with normal or myopathic hearts. Time-varying elastance curves were generated from 72 PV loops (52 patients) and normalized both by amplitude and time to peak amplitude. The resulting EN(tN) curves were remarkably consistent despite variations in underlying cardiac disease, contractility, loading, and heart rate, with minimal interloop variance during the first 25% to 35% of contraction. On the basis of this finding and assuming ESPVR linearity and constant volume-intercept, ESPVRs were estimated from one beat with the use of PV data measured at normalized time (tN) and end systole (tmax) to predict intercept: Vo(SB) = [EN(tN) x P(tmax) x V(tN)-P(tN)x V(tmax)]/[EN(tN) x P(tmax)-P(tN)] and slope Emax(SB) = Pes/[Ves-Vo(SB)]. Single-beat estimates were highly correlated with measured ESPVR values obtained by standard multiple-beat analysis (including data from 35 additional patients). Emax(SB) accurately reflected acute inotropic change and was influenced little by loading. The new estimation method also predicted measured ESPVRs better than prior techniques and was applicable to noninvasive analysis. CONCLUSIONS ESPVRs can be reliably estimated in humans from single cardiac cycles by a new method that has a potential for noninvasive application.