Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study

Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study | 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 Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study Dhruv Rao, Shylah Haldeman, Jeanne Carroll, Rohit Rao This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9261199/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Background Sotatercept, a first-in-class activin signaling inhibitor, has demonstrated disease-modifying efficacy in adults with pulmonary arterial hypertension (PAH). Pediatric data remain limited to ongoing clinical trials. Methods We conducted an IRB-approved, single-center retrospective analysis of pediatric patients with WHO Group 1 or Group 3 PAH treated with off-label sotatercept at Rady Children’s Hospital / UC San Diego. All patients had received maximal background triple therapy yet demonstrated persistent symptoms or adverse hemodynamics. Right heart catheterization was performed before sotatercept initiation and at approximately 24 weeks thereafter. Hemodynamic parameters were analyzed descriptively. Results Seven pediatric patients (median age 14 years; range 4–19) were included. Diagnoses comprised idiopathic PAH, heritable PAH, and PAH associated with congenital heart disease or congenital diaphragmatic hernia. Following sotatercept initiation, the majority of patients demonstrated reductions in pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (mPAP), with heterogeneity in magnitude of response. Pulmonary capillary wedge pressure (PCWP) remained stable in all patients. Conclusions In this small, highly selected pediatric cohort with advanced PAH refractory to triple therapy, off-label sotatercept was associated with favorable hemodynamic trends at 24 weeks. These findings support biologic plausibility suggested by adult randomized trials and underscore the urgent need for prospective pediatric studies. Pediatric pulmonary arterial hypertension Sotatercept Pulmonary vascular resistance Hemodynamics Off-label therapy Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 01 May, 2026 Reviews received at journal 24 Apr, 2026 Reviews received at journal 08 Apr, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers agreed at journal 30 Mar, 2026 Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 30 Mar, 2026 Submission checks completed at journal 30 Mar, 2026 First submitted to journal 29 Mar, 2026 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. 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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-9261199","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":614961785,"identity":"bb99eefa-8849-4d97-9f8f-9c33c09f00a4","order_by":0,"name":"Dhruv Rao","email":"","orcid":"","institution":"University of Arizona","correspondingAuthor":false,"prefix":"","firstName":"Dhruv","middleName":"","lastName":"Rao","suffix":""},{"id":614961787,"identity":"b68403ac-0443-4d3d-9006-0fa3f9390a81","order_by":1,"name":"Shylah Haldeman","email":"","orcid":"","institution":"Rady Children's Hospital-San Diego","correspondingAuthor":false,"prefix":"","firstName":"Shylah","middleName":"","lastName":"Haldeman","suffix":""},{"id":614961789,"identity":"61008263-e1ac-4525-8c15-0ba433fb9a72","order_by":2,"name":"Jeanne Carroll","email":"","orcid":"","institution":"University of California San Diego","correspondingAuthor":false,"prefix":"","firstName":"Jeanne","middleName":"","lastName":"Carroll","suffix":""},{"id":614961790,"identity":"3b7d469f-56b8-446d-84ec-5cbbcbfff38b","order_by":3,"name":"Rohit Rao","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYLCChAoGBgMwIho8OEOqFsaHbaRoMZ99+OGDxHn35M35D29g+LinlrAWmXNpxgaJ24oNd85IK2Cc8ew4YS0SPAxmEonbEhIMbvAYMPMcOEaMFvZvEolzgFrOnyFaCw/QlgaglgM5IC01RGkpNkg4lmC44UZawcEZBw4Q5bCND3/UJMgbnD+88cGHA3WEtaAAoBWHSdQCBKTaMgpGwSgYBSMBAAAafTmuzChv4QAAAABJRU5ErkJggg==","orcid":"","institution":"University of California San Diego","correspondingAuthor":true,"prefix":"","firstName":"Rohit","middleName":"","lastName":"Rao","suffix":""}],"badges":[],"createdAt":"2026-03-29 23:38:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9261199/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9261199/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106093349,"identity":"d99ced79-c2e6-4f04-92e0-805cbd5fa3ac","added_by":"auto","created_at":"2026-04-03 11:36:55","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":542440,"visible":true,"origin":"","legend":"","description":"","filename":"manuscriptv2Sotatercept.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9261199/v1_covered_c253274a-18f8-454e-9b6c-7057ab5f3c31.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pediatric pulmonary arterial hypertension, Sotatercept, Pulmonary vascular resistance, Hemodynamics, Off-label therapy","lastPublishedDoi":"10.21203/rs.3.rs-9261199/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9261199/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eSotatercept, a first-in-class activin signaling inhibitor, has demonstrated disease-modifying efficacy in adults with pulmonary arterial hypertension (PAH). Pediatric data remain limited to ongoing clinical trials.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We conducted an IRB-approved, single-center retrospective analysis of pediatric patients with WHO Group 1 or Group 3 PAH treated with off-label sotatercept at Rady Children\u0026rsquo;s Hospital / UC San Diego. All patients had received maximal background triple therapy yet demonstrated persistent symptoms or adverse hemodynamics. Right heart catheterization was performed before sotatercept initiation and at approximately 24 weeks thereafter. Hemodynamic parameters were analyzed descriptively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eSeven pediatric patients (median age 14 years; range 4\u0026ndash;19) were included. Diagnoses comprised idiopathic PAH, heritable PAH, and PAH associated with congenital heart disease or congenital diaphragmatic hernia. Following sotatercept initiation, the majority of patients demonstrated reductions in pulmonary vascular resistance index (PVRI) and mean pulmonary artery pressure (mPAP), with heterogeneity in magnitude of response. Pulmonary capillary wedge pressure (PCWP) remained stable in all patients.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this small, highly selected pediatric cohort with advanced PAH refractory to triple therapy, off-label sotatercept was associated with favorable hemodynamic trends at 24 weeks. These findings support biologic plausibility suggested by adult randomized trials and underscore the urgent need for prospective pediatric studies.\u003c/p\u003e","manuscriptTitle":"Off-Label Sotatercept Use in Pediatric Pulmonary Arterial Hypertension: A Single-Center Retrospective Hemodynamic Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 22:58:13","doi":"10.21203/rs.3.rs-9261199/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-01T19:30:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-24T18:13:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-09T00:37:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"326671298964082748016585170774498506320","date":"2026-03-30T23:33:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"324790644197541784338343302717823020792","date":"2026-03-30T22:35:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-03-30T22:29:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-30T14:45:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-30T14:45:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2026-03-29T23:27:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"3e1100d7-300b-4dfc-80c8-8e78bd059b67","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-01T19:30:05+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T02:53:13+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 22:58:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9261199","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9261199","identity":"rs-9261199","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}