Physiological Characterization of Pressure-Strain Loops Indices as Non-Invasive Surrogates for Ventriculo-Arterial Coupling: A Proof-of-Concept Study

Pressure–strain loop (PSL) analysis integrates myocardial deformation with estimated left-ventricular pressure and may provide a non-invasive approach to assess ventriculo-arterial coupling. However, its physiological behavior under controlled hemodynamic stress has not been systematically evaluated in humans. In this prospective physiologic study, healthy volunteers underwent standardized hemodynamic maneuvers. One cohort performed semi-supine exercise (contractility-dominant), while a second cohort underwent isometric handgrip followed by modified passive leg raising (afterload- and preload-modulating maneuvers). Left-ventricular PSL indices were derived from speckle-tracking echocardiography combined with brachial pressure calibration. Five pre-specified PSL indices reflecting afterload (arterial elastance, end-systolic pressure), contractility (systolic strain rate, peak systolic strain), and myocardial work (global work index) were defined as co-primary endpoints. Within-subject changes were analyzed using paired tests with Holm–Bonferroni correction. Exercise produced large increases in contractility-sensitive indices (Cohen's dz 0.88–1.29, all adjusted p < 0.001), while pressure indices rose selectively with handgrip and modified passive leg raising (Cohen’s dz 0.77–1.21, adjusted p ≤ 0.001). These findings demonstrate that PSL analysis detects physiologically meaningful hemodynamic responses in humans and provides non-invasive indices consistent with established ventricular–arterial coupling dynamics.