Validation of Pressure-Strain Loops for Non-Invasive Assessment of Ventriculo-Arterial Coupling

Background and ObjectivesLeft ventricular pressure-strain loop (LV-PSL) analysis provides noninvasive myocardial work indices that may reflect ventricular-arterial (VA) coupling, but their behavior under controlled physiologic stressors is incompletely defined. We aimed to characterize directional changes in LV-PSL, derived indices during standardized interventions predominantly affecting preload, afterload, or contractility in healthy adults. MethodsIn this prospective, within-subject repeated-measures study, 61 healthy volunteers underwent interventions designed to elicit domain-specific hemodynamic perturbations. Group 1 (n=31) performed isotonic exercise (contractility-dominant). Group 2 (n=30) performed isometric handgrip (afterload-increasing) and passive leg raising (PLR; preload augmentation with concurrent afterload change). LV-PSL indices were assessed at baseline and during each intervention. Six co-primary endpoints were prespecified: Global Work Index (GWI), peak systolic strain, strain range, systolic strain rate (SSR), arterial elastance (Ea), and end-systolic pressure (ESP). Within-subject changes were analyzed using paired tests with multiplicity adjustment and determined effect sizes. Reproducibility was evaluated using intraclass correlation coefficients (ICC). ResultsLV-PSL responses were directionally consistent with established pressure-volume physiology. Isotonic exercise produced large increases in contractility-sensitive indices, including GWI (dz=1.03), peak systolic strain (dz=0.88), strain range (dz=1.10), SSR (dz=1.29), and ESP (r=1.26), all adjusted p<0.001, while Ea remained unchanged. In contrast, isometric handgrip and PLR elicited afterload-dominant responses, with significant increases in ESP (dz=1.11 and 1.21, respectively; adjusted p<0.001) and Ea (dz=0.79 and 0.77; adjusted p[&le;]0.001), without significant changes in GWI or strain-derived indices after adjustment. Intraobserver reproducibility was good-to-excellent (ICC 0.86-0.90), and interobserver reproducibility was moderate-to-good (ICC 0.72-0.87). ConclusionsIn healthy adults, LV-PSL indices demonstrate good reproducibility and appropriate sensitivity to hemodynamic perturbations. Exercise elicited contractility-dominant responses, whereas handgrip and PLR induced afterload-dominant changes. These physiologically coherent response patterns support LV-PSL as a practical non-invasive surrogate for invasive pressure-volume assessment. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/26347879v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@113c652org.highwire.dtl.DTLVardef@1413e5aorg.highwire.dtl.DTLVardef@64b898org.highwire.dtl.DTLVardef@930462_HPS_FORMAT_FIGEXP M_FIG Central Illustration - Validation of Non-Invasive Pressure-Strain Loops for Assessing Ventriculo-Arterial Coupling The study evaluated left ventricle pressure-strain loop (LV-PSL) derived indices during three hemodynamic interventions in healthy volunteers: Group 1 - exercise (contractility-dominant), Group 2 - isometric handgrip (afterload-dominant), and passive leg raising (preload/afterload modulation). Center heatmap shows effect sizes (Cohens dz or rank-biserial r) for six co-primary PSL endpoints. Color intensity indicates effect magnitude (red = positive, blue = negative); asterisks denote significance after Holm-Bonferroni correction (**p[&le;]0.001). Exercise produced robust responses in 5/6 parameters, while handgrip and passive leg raising showed intervention-specific patterns, particularly for afterload indices. PSL methodology demonstrates high reproducibility and physiological sensitivity for non-invasive ventriculo-arterial coupling assessment. Abbreviations: LV-PSL, Left ventricle pressure-strain loop; PLR, passive leg raising; VA, ventriculo-arterial C_FIG