Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis

Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis | 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 Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis Attila Feher, Nabil Boutagy, Evangelos K. Oikonomou, Stephanie Thorn, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-34522/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Jul, 2021 Read the published version in The Journal of Rheumatology → Version 1 posted You are reading this latest preprint version Abstract Introduction: Cardiovascular (CV) disease including coronary microvascular dysfunction is the leading cause of morbidity and mortality in patients with autoimmune conditions and may be linked with Raynaud phenomenon (RP). Positron emission tomography/computed tomography (PET/CT) has emerged as the noninvasive gold standard for the evaluation of coronary microvascular function. As such, we sought to determine the prevalence of coronary microvascular dysfunction as assessed by PET/CT-derived coronary flow reserve (MFR) in patients with primary and secondary RP evaluated for dyspnea or chest pain. Materials and methods: Patients with a diagnosis of RP in the electronic health record who underwent dynamic rest-stress 82-Rubidium PET/CT from 09/2012-09/2019 for evaluation of chest pain or dyspnea were studied. Heart rate-blood pressure product corrected MFR was calculated (Corridor 4DM, INVIA). Patients were grouped based on their comorbid autoimmune condition, and differences in MFR and clinical predictors of reduced MFR (< 2.0) were compared between patients and healthy controls (n=17, 35% female, age: 35 ± 5 years, BMI 27 ± 4kg/m 2 ). Results: 49 patients with RP (84% female, age: 65 ± 11 years, BMI: 33 ± 11 kg/m 2 ) were studied. Of these, 11 had primary RP, 18 had systemic sclerosis (SSc) and 20 had other autoimmune diagnosis (n=6 systemic lupus erythematosus, n=6 rheumatoid arthritis, n=4 overlap syndrome, n=2 Sjogren’s syndrome, n=2 inflammatory arthritis). Patients with primary RP had MFR comparable to healthy participants. In patients with secondary RP, only those with underlying SSc had significantly reduced MFR compared to healthy participants (p=0.002, 1.62 ± 0.32 vs 2.22 ± 0.44). In multivariable logistic regression, SSc was an independent predictor of reduced MFR. In addition, there was a modest significant correlation between time since autoimmune disease diagnosis and MFR (r= -0.37; 95% CI: -0.61 to -0.09; p=0.01). Inflammatory markers (sedimentation rate: r= -0.19, C-reactive protein: r= -0.31) were not significantly associated with MFR (p>0.05). Conclusions: Our findings suggest that there is reduced PET/CT MFR compared to healthy participants in patients with SSC and secondary RP, and that SSc may be an independent predictor of reduced MFR. Patients with primary RP had MFR values that were comparable to healthy participants. Larger prospective studies are warranted to fully elucidate the prognostic value of MFR in patients with secondary RP. Vascular Medicine Nuclear Medicine & Medical Imaging myocardial flow reserve myocardial blood flow autoimmune disease positron emission tomography prognosis Raynaud phenomenon microvascular cardiac disease cardiovascular disease Figures Figure 1 Figure 2 Figure 3 Figure 4 Full Text Supplementary Files SupplementalFigure.PNG Regional coronary flow reserves in the LAD (left anterior descending), LCx (left circumflex) and RCA (right coronary) arteries. BMI: body mass index, RP: Raynaud phenomenon, CT: computed tomography, PET: positron emission tomography, CI: confidence interval. Cite Share Download PDF Status: Published Journal Publication published 15 Jul, 2021 Read the published version in The Journal of Rheumatology → 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. 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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-34522","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":657109,"identity":"3097c168-0b2b-4898-ba06-c61f4a001275","order_by":0,"name":"Attila Feher","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Attila","middleName":"","lastName":"Feher","suffix":""},{"id":657110,"identity":"921286e2-399f-4e1c-81b8-3e4a666da5e6","order_by":1,"name":"Nabil Boutagy","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nabil","middleName":"","lastName":"Boutagy","suffix":""},{"id":657111,"identity":"d18af191-9a59-4bc0-8743-8b0bbd77f092","order_by":2,"name":"Evangelos K. Oikonomou","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Evangelos","middleName":"K.","lastName":"Oikonomou","suffix":""},{"id":657112,"identity":"fd5dcc40-3cfb-454f-9aa0-0f94837d1d6d","order_by":3,"name":"Stephanie Thorn","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Stephanie","middleName":"","lastName":"Thorn","suffix":""},{"id":657113,"identity":"19e5761f-1980-454b-bc3b-a83004de7cd8","order_by":4,"name":"Yi-Hwa Liu","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yi-Hwa","middleName":"","lastName":"Liu","suffix":""},{"id":657114,"identity":"1eab1e26-ee44-47a1-85fc-52275270ad77","order_by":5,"name":"Edward Miller","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Edward","middleName":"","lastName":"Miller","suffix":""},{"id":657115,"identity":"c3d36b8f-bc51-4053-b711-58f15a0b5cc2","order_by":6,"name":"Albert Sinusas","email":"","orcid":"","institution":"Yale University School of Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Albert","middleName":"","lastName":"Sinusas","suffix":""},{"id":657116,"identity":"91ea1a11-9dfa-4dfd-96f4-e906204decac","order_by":7,"name":"Monique Evangeline Hinchcliff","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYJCCAyDCgJmBAYgseNibDwMFCkBiCURpkeDhOZYGVGqAXwsYgNSAtDDwHMsxwKtFt7334IG3bTYM5uy8Bz8X1EjI8LDxfJP4YWDDwM+eY4BNi9mZcwkH57alMVg28yVLzzgGdBgb7zbJHoM0BsmeN9i13MgxOMzbdpjB4DCPGTNvgwSPvXzvNgkeA6DIDRy2QLT8R2gBOuyZ5B+D/wz2+LUcQNHCJs1jABSRwOWXMwYH55xLBrqEx1iaB+wXNmNrGYNkHokzzwqwajneY/zhTZmdnMH5M4afeWps7HnYmB/efFNhJ8ffnrwBayiDAA8YIQCLBAOaCDYtKID5A17lo2AUjIJRMNIAAAI7VWZYc6QYAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-8652-9890","institution":"Yale School Of Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Monique","middleName":"Evangeline","lastName":"Hinchcliff","suffix":""}],"badges":[],"createdAt":"2020-06-09 16:06:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-34522/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-34522/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.3899/jrheum.210040","type":"published","date":"2021-07-15T21:07:03+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":1303221,"identity":"2f545e78-efd4-4abb-9f64-73360585ef86","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":597547,"visible":true,"origin":"","legend":"Representative relative perfusion images, time activity curves and myocardial blood flow\n(MBF) values obtained at stress (Str) and rest (Rst) for a patient with systemic sclerosis (A) and for a\nhealthy control subject (B). Perfusion imaging showed no perfusion defects, however for the systemic\nsclerosis patient blood flow quantification revealed global reduction in stress myocardial blood flow\nand coronary flow reserve (\u003c2.0) whereas the healthy control subject had normal myocardial blood\nflow values. SA: short axis, HLA: horizontal long axis, VLA: vertical long axis, LV: left ventricle, RV:\nright ventricle, LAD: left anterior descending artery, LCX: left circumflex artery, RCA: right coronary\nartery","description":"","filename":"1.PNG","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/1.PNG"},{"id":1303222,"identity":"6fb43146-1ee2-4f16-9002-1d51db1d4fee","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":26163,"visible":true,"origin":"","legend":"Correlation between coronary flow reserve and time since RP (Raynaud phenomenon)\ndiagnosis (A), sedimentation rate (B) and C-reactive protein levels (C). CI: confidence interval\n","description":"","filename":"2.PNG","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/2.PNG"},{"id":1303223,"identity":"3d4b1f29-d9be-407f-9b46-3f5750bec665","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":33777,"visible":true,"origin":"","legend":"Rest (A) and stress (B) myocardial blood flow (MBF) and coronary flow reserve (MFR, C) in\nhealthy controls, patients with primary Raynaud phenomenon (RP), secondary RP with autoimmune\ndisease (AID) other than systemic sclerosis (SSc) and in patients with SSc.","description":"","filename":"3.PNG","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/3.PNG"},{"id":1303224,"identity":"530cff7e-b245-4294-ae98-0b16229eeae8","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":48372,"visible":true,"origin":"","legend":"Forest plot of odds ratios (OR) of clinical predictors of reduced coronary flow reserve (MFR\n\u003c2.0). BMI: body mass index, RP: Raynaud phenomenon, CT: computed tomography, PET: positron\nemission tomography, CI: confidence interval.","description":"","filename":"4.PNG","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/4.PNG"},{"id":1303227,"identity":"759b5403-6910-4fab-8c83-241ca323ccb7","added_by":"auto","created_at":"2020-06-10 22:35:56","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1147899,"visible":true,"origin":"","legend":"","description":"","filename":"RaynaudManuscriptPETCFR2020JUN08complete.pdf","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1_stamped.pdf"},{"id":1303225,"identity":"322a3a19-373a-4bf8-b6a7-cf8775064f7e","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1119914,"visible":true,"origin":"","legend":"","description":"","filename":"RaynaudManuscriptPETCFR2020JUN08complete.pdf","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/RaynaudManuscriptPETCFR2020JUN08complete.pdf"},{"id":13508952,"identity":"3051008f-add8-485c-bcf0-7662ea6db1d0","added_by":"auto","created_at":"2021-09-16 23:41:35","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":828730,"visible":true,"origin":"","legend":"","description":"","filename":"RaynaudManuscriptPETCFR2020JUN08complete.pdf","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1_covered.pdf"},{"id":1303226,"identity":"f24af0bb-6ed8-47dc-acaf-50579784dc8b","added_by":"auto","created_at":"2020-06-10 22:35:54","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":25632,"visible":true,"origin":"","legend":"Regional coronary flow reserves in the LAD (left anterior descending), LCx\n(left circumflex) and RCA (right coronary) arteries. BMI: body mass index, RP: Raynaud\nphenomenon, CT: computed tomography, PET: positron emission tomography, CI: confidence\ninterval.","description":"","filename":"SupplementalFigure.PNG","url":"https://assets-eu.researchsquare.com/files/rs-34522/v1/SupplementalFigure.PNG"}],"financialInterests":"","formattedTitle":"Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis","fulltext":[{"header":"Full Text","content":"\u003cp\u003eThis preprint is available for \u003ca href='/article/rs-34522/latest.pdf' target='_blank'\u003edownload as a PDF\u003c/a\u003e.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"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":"myocardial flow reserve, myocardial blood flow, autoimmune disease, positron emission tomography, prognosis, Raynaud phenomenon, microvascular cardiac disease, cardiovascular disease","lastPublishedDoi":"10.21203/rs.3.rs-34522/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-34522/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"Introduction: Cardiovascular (CV) disease including coronary microvascular dysfunction is the leading cause of morbidity and mortality in patients with autoimmune conditions and may be linked with Raynaud phenomenon (RP). Positron emission tomography/computed tomography (PET/CT) has emerged as the noninvasive gold standard for the evaluation of coronary microvascular function. As such, we sought to determine the prevalence of coronary microvascular dysfunction as assessed by PET/CT-derived coronary flow reserve (MFR) in patients with primary and secondary RP evaluated for dyspnea or chest pain. \n \nMaterials and methods: Patients with a diagnosis of RP in the electronic health record who underwent dynamic rest-stress 82-Rubidium PET/CT from 09/2012-09/2019 for evaluation of chest pain or dyspnea were studied. Heart rate-blood pressure product corrected MFR was calculated (Corridor 4DM, INVIA). Patients were grouped based on their comorbid autoimmune condition, and differences in MFR and clinical predictors of reduced MFR (\u003c 2.0) were compared between patients and healthy controls (n=17, 35% female, age: 35 ± 5 years, BMI 27 ± 4kg/m 2 ). \n \nResults: 49 patients with RP (84% female, age: 65 ± 11 years, BMI: 33 ± 11 kg/m 2 ) were studied. Of these, 11 had primary RP, 18 had systemic sclerosis (SSc) and 20 had other autoimmune diagnosis (n=6 systemic lupus erythematosus, n=6 rheumatoid arthritis, n=4 overlap syndrome, n=2 Sjogren’s syndrome, n=2 inflammatory arthritis). Patients with primary RP had MFR comparable to healthy participants. In patients with secondary RP, only those with underlying SSc had significantly reduced MFR compared to healthy participants (p=0.002, 1.62 ± 0.32 vs 2.22 ± 0.44). In multivariable logistic regression, SSc was an independent predictor of reduced MFR. In addition, there was a modest significant correlation between time since autoimmune disease diagnosis and MFR (r= -0.37; 95% CI: -0.61 to -0.09; p=0.01). Inflammatory markers (sedimentation rate: r= -0.19, C-reactive protein: r= -0.31) were not significantly associated with MFR (p\u003e0.05).\n \nConclusions: Our findings suggest that there is reduced PET/CT MFR compared to healthy participants in patients with SSC and secondary RP, and that SSc may be an independent predictor of reduced MFR. Patients with primary RP had MFR values that were comparable to healthy participants. Larger prospective studies are warranted to fully elucidate the prognostic value of MFR in patients with secondary RP.","manuscriptTitle":"Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Computed Tomography in Patients with Systemic Sclerosis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2020-06-10 22:35:53","doi":"10.21203/rs.3.rs-34522/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","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}}],"origin":"","ownerIdentity":"3fd0dcd3-e83b-47e7-834b-1e495bff9cfa","owner":[],"postedDate":"June 10th, 2020","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":117684,"name":"Vascular Medicine"},{"id":117685,"name":"Nuclear Medicine \u0026 Medical Imaging"}],"tags":[],"updatedAt":"2021-07-27T21:07:03+00:00","versionOfRecord":{"articleIdentity":"rs-34522","link":"https://doi.org/10.3899/jrheum.210040","journal":{"identity":"the-journal-of-rheumatology","isVorOnly":true,"title":"The Journal of Rheumatology"},"publishedOn":"2021-07-15 21:07:03","publishedOnDateReadable":"July 15th, 2021"},"versionCreatedAt":"2020-06-10 22:35:53","video":"","vorDoi":"10.3899/jrheum.210040","vorDoiUrl":"https://doi.org/10.3899/jrheum.210040","workflowStages":[]},"version":"v1","identity":"rs-34522","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-34522","identity":"rs-34522","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}