{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:10:00Z","timestamp":1790327400404,"version":"4.1.0"},"reference-count":28,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["P3-0019"],"award-info":[{"award-number":["P3-0019"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P3-0019"],"award-info":[{"award-number":["P3-0019"]}],"id":[{"id":"https:\/\/ror.org\/059bp8k51","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>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 \u00b110 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 (\u03c1 = \u22120.09, p = 0.01) and TAMW (\u03c1 = \u22120.06, p = 0.08) were weak. In LME analysis, greater LGE was associated with lower MWI (\u03b2 = \u22122.57, 95% CI \u22124.71 to \u22120.42, Holm-adjusted p = 0.038) and lower TAMW (\u03b2 = \u221211.09, 95% CI \u221221.24 to \u22120.94, 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; \u0394AIC = 0.97). FLI was not significantly associated with LGE in the LME analysis (\u03b2 = \u22120.00021, 95% CI: \u22120.000558 to 0.000147, Holm-adjusted p = 0.253), whereas BLI showed a significant positive association with LGE (\u03b2 = 0.000127, 95% CI: 0.000065 to 0.000190, Holm-adjusted p &lt; 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.<\/jats:p>","DOI":"10.3390\/jcm15197455","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:09:02Z","timestamp":1790323742000},"page":"7455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Tension-Adjusted Myocardial Work and Its Temporal Indices with LGE-Defined Myocardial Injury in Acute Myocarditis: A Proof-of-Concept Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Kanza","family":"Awais","sequence":"first","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6870-2200","authenticated-orcid":false,"given":"Konstantin","family":"Tripunovski","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Tadeja Poropat","family":"Flerin","sequence":"additional","affiliation":[{"name":"Department of Radiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Andreja \u010cerne","family":"\u010cercek","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9085-2308","authenticated-orcid":false,"given":"Borut","family":"Kirn","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1097\/HCO.0000000000000577","article-title":"Imaging the itis","volume":"34","year":"2019","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1007\/s00330-007-0612-3","article-title":"Value of MRI in patients with a clinical suspicion of acute myocarditis","volume":"17","author":"Yelgec","year":"2007","journal-title":"Eur. Radiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Awais, K., Kralj, L., Cercek, A.C., and Kirn, B. (2025). Influence of Natural Variability and Anatomical Misalignment on the Correlation Between Segmental Myocardial Edema and Strain in Acute Myocarditis. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030712"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.mri.2020.08.008","article-title":"Tissue-tracking in the assessment of late gadolinium enhancement in myocarditis and myocardial infarction","volume":"73","author":"Doimo","year":"2020","journal-title":"Magn. Reson. Imaging"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12872-023-03201-2","article-title":"Cardiac magnetic resonance feature tracking myocardial strain analysis in suspected acute myocarditis: Diagnostic value and association with severity of myocardial injury","volume":"23","author":"Gao","year":"2023","journal-title":"BMC Cardiovasc. Disord."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1007\/s10554-017-1115-1","article-title":"Three-dimensional speckle tracking longitudinal strain is related to myocardial fibrosis determined by late-gadolinium enhancement","volume":"33","author":"Spartera","year":"2017","journal-title":"Int. J. Cardiovasc. Imaging"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12947-019-0168-9","article-title":"Global longitudinal strain is a more reproducible measure of left ventricular function than ejection fraction regardless of echocardiographic training","volume":"17","author":"Karlsen","year":"2019","journal-title":"Cardiovasc. Ultrasound"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.echo.2023.07.002","article-title":"State-of-the-Art: Noninvasive Assessment of Left Ventricular Function Through Myocardial Work","volume":"36","author":"Moya","year":"2023","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1093\/eurheartj\/ehs016","article-title":"A novel clinical method for quantification of regional left ventricular pressure\u2013strain loop area: A non-invasive index of myocardial work","volume":"33","author":"Russell","year":"2012","journal-title":"Eur. Heart J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1016\/j.jcmg.2022.07.001","article-title":"Myocardial Work and Work Index","volume":"15","author":"Flachskampf","year":"2022","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1007\/s00246-024-03543-4","article-title":"Impaired Myocardial Work in Children with Hypertrophic Cardiomyopathy and Left Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging","volume":"46","author":"Jacquemyn","year":"2024","journal-title":"Pediatr. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Awais, K., Tripunovski, K., \u010cercek, A.\u010c., Flerin, T.P., and Kirn, B. (2026). Incorporating Ventricular Geometry into the Myocardial Work Index: A Proof-of-Concept Study. Biomedicines, 14.","DOI":"10.3390\/biomedicines14071606"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e190010","DOI":"10.1148\/ryct.2019190010","article-title":"Comparison of Original and 2018 Lake Louise Criteria for Diagnosis of Acute Myocarditis: Results of a Validation Cohort","volume":"1","author":"Luetkens","year":"2019","journal-title":"Radiol. Cardiothorac. Imaging"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"E35","DOI":"10.1161\/HYP.0000000000000087","article-title":"Measurement of Blood Pressure in Humans: A Scientific Statement from the American Heart Association","volume":"73","author":"Muntner","year":"2019","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/s12968-020-00610-6","article-title":"Standardized image interpretation and post-processing in cardiovascular magnetic resonance\u20142020 update","volume":"22","author":"Bluemke","year":"2020","journal-title":"J. Cardiovasc. Magn. Reson."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.anbehav.2008.11.006","article-title":"A simple method for distinguishing within- versus between-subject effects using mixed models","volume":"77","author":"Wright","year":"2009","journal-title":"Anim. Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e011492","DOI":"10.1161\/CIRCIMAGING.120.011492","article-title":"Prognostic Impact of Late Gadolinium Enhancement by Cardiovascular Magnetic Resonance in Myocarditis","volume":"14","author":"Georgiopoulos","year":"2021","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_18","first-page":"1","article-title":"Myocardial Work, an Echocardiographic Measure of Post Myocardial Infarct Scar on Contrast-Enhanced Cardiac Magnetic Resonance","volume":"151","author":"Abou","year":"2021","journal-title":"Am. J. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3762","DOI":"10.21037\/qims-21-1098","article-title":"Relative basal myocardial weakness: Differentiating dermatomyositis and polymyositis with cardiac involvement from viral myocarditis using speckle-tracking echocardiography and quantification of myocardial work","volume":"12","author":"Liu","year":"2022","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0006-3495(91)82201-9","article-title":"Relation between left ventricular cavity pressure and volume and systolic fiber stress and strain in the wall","volume":"59","author":"Arts","year":"1991","journal-title":"Biophys. J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1093\/eurheartj\/eht210","article-title":"Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases","volume":"34","author":"Caforio","year":"2013","journal-title":"Eur. Heart J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"H996","DOI":"10.1152\/ajpheart.00191.2013","article-title":"Assessment of wasted myocardial work: A novel method to quantify energy loss due to uncoordinated left ventricular contractions","volume":"305","author":"Russell","year":"2013","journal-title":"Am. J. Physiol.-Heart Circ. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/ehjci\/jew019","article-title":"Wasted septal work in left ventricular dyssynchrony: A novel principle to predict response to cardiac resynchronization therapy","volume":"17","author":"Vecera","year":"2016","journal-title":"Eur. Heart J.-Cardiovasc. Imaging"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.echo.2017.10.009","article-title":"Value of Myocardial Work Estimation in the Prediction of Response to Cardiac Resynchronization Therapy","volume":"31","author":"Galli","year":"2018","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1093\/ehjci\/jex325","article-title":"Timing of myocardial shortening determines left ventricular regional myocardial work and regional remodelling in hearts with conduction delays","volume":"19","author":"Cvijic","year":"2018","journal-title":"Eur. Heart J.-Cardiovasc. Imaging"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e007224","DOI":"10.1161\/CIRCEP.118.007224","article-title":"Left Ventricular Remodeling Results in Homogenization of Myocardial Work Distribution","volume":"12","author":"Duchenne","year":"2019","journal-title":"Circ. Arrhythm. Electrophysiol."},{"key":"ref_27","first-page":"1898","article-title":"Pathobiology of cardiac dyssynchrony and resynchronization therapy","volume":"20","author":"Verzaal","year":"2018","journal-title":"EP Eur."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/sono.12474","article-title":"Segmental myocardial strain in myocarditis in young adults: Natural variability versus myocarditis signal","volume":"12","author":"Kirn","year":"2024","journal-title":"Sonography"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:33:40Z","timestamp":1790325220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,25]]},"references-count":28,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["jcm15197455"],"URL":"https:\/\/doi.org\/10.3390\/jcm15197455","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,25]]}}}