Association of Tension-Adjusted Myocardial Work and Its Temporal Indices with LGE-Defined Myocardial Injury in Acute Myocarditis: A Proof-of-Concept Study

Background: Cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) is an important marker of myocardial injury in acute myocarditis (AM). Although echocardiographic myocardial work (MWI) provides a non-invasive assessment of left ventricular (LV) mechanics, conventional MWI does not account for ventricular geometry or temporal distribution of myocardial work. These factors may provide additional physiological information relevant to myocardial injury. Objective: To investigate the association of conventional and geometry- and timing-informed myocardial work measures with LGE-defined injury in AM in a preliminary proof-of-concept study. Methods: In this retrospective, single-center study, 41 patients with AM underwent echocardiography and CMR within ±10 days. Conventional segmental MWI was derived from pressure-strain loops. Tension-adjusted myocardial work (TAMW) incorporated ventricular geometry using CMR-derived ventricular volume and wall volume into the myocardial work estimation. Front Loading Index (FLI) and Back Loading Index (BLI) quantified the relative contribution of constructive work during the initial and final 20% of the ejection phase, respectively. Associations between myocardial work indicators and segmental LGE were assessed using Spearman correlation and linear mixed-effects (LME) models with patient-specific random intercepts. Multiple comparisons were addressed using Holm correction. Additional analyses examined segmental localization, within- and between-patient variability, patient-specific slopes and the influence of extreme observations. Results: Spearman correlations between LGE and MWI (ρ = −0.09, p = 0.01) and TAMW (ρ = −0.06, p = 0.08) were weak. In LME analysis, greater LGE was associated with lower MWI (β = −2.57, 95% CI −4.71 to −0.42, Holm-adjusted p = 0.038) and lower TAMW (β = −11.09, 95% CI −21.24 to −0.94, Holm-adjusted p = 0.038). Exploratory model comparison using LGE as the common outcome showed comparable model support for standardized MWI and TAMW (AIC = 6264.7 and 6265.7 respectively; ΔAIC = 0.97). FLI was not significantly associated with LGE in the LME analysis (β = −0.00021, 95% CI: −0.000558 to 0.000147, Holm-adjusted p = 0.253), whereas BLI showed a significant positive association with LGE (β = 0.000127, 95% CI: 0.000065 to 0.000190, Holm-adjusted p < 0.001) The BLI association was not maintained after accounting for segmental localization. Conclusions: In this preliminary proof-of-concept, MWI and TAMW showed weak inverse associations with segmental LGE in the primary analysis, while BLI demonstrated an exploratory positive association with LGE and FLI was not independently associated with LGE. These findings demonstrate the feasibility of incorporating ventricular geometry and temporal distribution into myocardial work assessment but do not establish superiority or incremental value over conventional MWI. Further prospective studies are required to determine the reproducibility, physiological significance, and clinical utility of these additional dimensions.