Mapper-based topological subtyping of early diuretic response in ICU patients with acute heart failure: a retrospective cohort study with external validation in eICU-CRD

Mapper-based topological subtyping of early diuretic response in ICU patients with acute heart failure: a retrospective cohort study with external validation in eICU-CRD | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Mapper-based topological subtyping of early diuretic response in ICU patients with acute heart failure: a retrospective cohort study with external validation in eICU-CRD Jiacheng Tian This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9012160/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: Fixed-threshold definitions of diuretic resistance may miss heterogeneous and time-varying response patterns in ICU acute heart failure (AHF). We aimed to identify stable and interpretable subtypes of early loop-diuretic response using a Mapper-based topological framework with external validation. Methods: In MIMIC-IV v3.1, we included adult ICU stays with an AHF diagnosis and first intravenous loop diuretic within 24 h of ICU admission (t0). t0-anchored features captured furosemideequivalent exposure, cumulative urine output and diuretic efficiency index (DEI) over 2 h/6 h/12 h, and hemodynamic/renal context. Mapper graphs were built with two-stage parameter search and evaluated by bootstrap co-membership Jaccard similarity (200 iterations; 80% resampling). Branch labels were assessed for incremental prognostic value for in-hospital mortality using Cox and logistic regression, and for AKI within 48 h (KDIGO creatinine proxy) as a mechanistic endpoint. We performed external validation in eICU-CRD v2.0 using a harmonized pipeline. Results: The cohort comprised 2,373 ICU stays. The optimal Mapper yielded 58 nodes and 393 edges (coverage 1.000) with high stability (mean Jaccard 0.924±0.038; stability score 0.944). Four major branches (A–D) showed marked mortality differences (log-rank p = 1.659 × 10−19). After adjustment, branches C and D had higher mortality risk than A and improved discrimination (AUC 0.712 to 0.737). AKI48h also differed across branches (p = 2.137 × 10−7). In eICU-CRD v2.0, the external validation recapitulated a comparable topology and major-branch structure with a consistent mortality-risk gradient (log-rank p = 5.441 × 10−4). Conclusion: t0-anchored Mapper subphenotyping provides a stable and interpretable representation of diuretic-response heterogeneity in ICU AHF with independent prognostic and mechanistic relevance. acute heart failure diuretic resistance urine output topological data analysis Mapper MIMIC-IV Full Text Additional Declarations No competing interests reported. Supplementary Files supplement.pdf Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9012160","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":602186302,"identity":"810aa3b9-c560-4dd9-8051-40322971c3e5","order_by":0,"name":"Jiacheng Tian","email":"data:image/png;base64,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","orcid":"","institution":"","correspondingAuthor":true,"prefix":"","firstName":"Jiacheng","middleName":"","lastName":"Tian","suffix":""}],"badges":[],"createdAt":"2026-03-02 16:10:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9012160/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9012160/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104780686,"identity":"04d9a753-6e74-4682-ae49-07acba8b316b","added_by":"auto","created_at":"2026-03-17 07:53:37","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":417216,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9012160/v1_covered_65364867-1648-489f-a638-28b379182847.pdf"},{"id":104338498,"identity":"9b9a6ca7-0fb0-471a-bc33-069193145932","added_by":"auto","created_at":"2026-03-10 16:20:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":475515,"visible":true,"origin":"","legend":"","description":"","filename":"supplement.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9012160/v1/5e718adc7e2f5acf401309b3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Mapper-based topological subtyping of early diuretic response in ICU patients with acute heart failure: a retrospective cohort study with external validation in eICU-CRD","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute heart failure, diuretic resistance, urine output, topological data analysis, Mapper, MIMIC-IV","lastPublishedDoi":"10.21203/rs.3.rs-9012160/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9012160/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose: \u003c/strong\u003eFixed-threshold definitions of diuretic resistance may miss heterogeneous and time-varying response patterns in ICU acute heart failure (AHF). We aimed to identify stable and interpretable subtypes of early loop-diuretic response using a Mapper-based topological framework with external validation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In MIMIC-IV v3.1, we included adult ICU stays with an AHF diagnosis and first intravenous loop diuretic within 24 h of ICU admission (t0). t0-anchored features captured furosemideequivalent exposure, cumulative urine output and diuretic efficiency index (DEI) over 2 h/6 h/12 h, and hemodynamic/renal context. Mapper graphs were built with two-stage parameter search and evaluated by bootstrap co-membership Jaccard similarity (200 iterations; 80% resampling). Branch labels were assessed for incremental prognostic value for in-hospital mortality using Cox and logistic regression, and for AKI within 48 h (KDIGO creatinine proxy) as a mechanistic endpoint. 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