Temporal Shifts in Diagnostic Testing for Cardiac Amyloidosis Across U.S. Health Systems

Temporal Shifts in Diagnostic Testing for Cardiac Amyloidosis Across U.S. Health Systems | 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 Temporal Shifts in Diagnostic Testing for Cardiac Amyloidosis Across U.S. Health Systems Issam Motairek, Bryan Abadie, Andrew Higgins, Pavan Bhat, Andres Carmona Rubio, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8799253/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Purpose: To evaluate temporal trends in diagnostic testing for cardiac transthyretin amyloidosis (ATTR-CM) across U.S. health systems in the contemporary era. Methods: We conducted a retrospective, descriptive analysis using the TriNetX U.S. Collaborative Network, identifying patients diagnosed with wild-type or hereditary ATTR-CM between January 2017 and November 2025. ATTR-specific ICD-10 codes were combined with evidence of cardiac involvement, and patients with light-chain amyloidosis or plasma cell dyscrasias were excluded. Diagnostic testing, including technetium-99m (Tc-99m) bone scintigraphy, cardiac magnetic resonance imaging (CMR), and biopsy, was assessed within an extended diagnostic ascertainment window spanning 24 months before and 12 months after diagnosis. Results: The number of patients diagnosed with ATTR-CM increased markedly over time. Use of Tc-99m scintigraphy and CMR rose substantially in absolute terms, while biopsy utilization declined steadily. Dual-modality imaging increased modestly, and invasive histologic confirmation became progressively less common, indicating a shift toward imaging-based diagnosis. Conclusion: Between 2017 and 2025, diagnostic evaluation of ATTR-CM shifted decisively toward noninvasive imaging, with declining reliance on biopsy. Although imaging volume increased, proportional adoption did not keep pace with expanding case identification, underscoring the need for broader implementation of guideline-recommended diagnostic pathways. Cardiac amyloidosis transthyretin amyloidosis technetium-99m pyrophosphate scintigraphy nuclear cardiology diagnostic trends noninvasive imaging Figures Figure 1 Main Cardiac amyloidosis has evolved from a rare cause of restrictive cardiomyopathy to a key focus in heart failure practice. The widespread adoption of technetium-99m (Tc-99m)–based bone scintigraphy has enabled accurate, noninvasive identification of transthyretin cardiac amyloidosis (ATTR-CA). 1 The recently published 2024 American Society of Nuclear Cardiology (ASNC) Cardiac Amyloid Radionuclide Imaging (CARI) quality metrics emphasize its role as a first-line diagnostic tool in suspected ATTR-CM. 2 We performed a retrospective, descriptive analysis using the TriNetX U.S. Collaborative Network to evaluate temporal trends in diagnostic testing among patients with cardiac ATTR-CM between January 2017 and November 2025. TriNetX aggregates de-identified electronic health record data across multiple U.S. health systems. Patients were identified using ICD-10 codes specific to wild-type or hereditary transthyretin amyloidosis (E85.82, E85.2) together with evidence of cardiac involvement, defined by concurrent codes for cardiomyopathy or heart failure (I43, I42.5, I42.9, or I50.x). To minimize diagnostic misclassification, patients with light-chain amyloidosis or plasma cell dyscrasias (E85.81, C90.x, C88.x, D47.2, D47.9) were excluded. The index date was defined as the first qualifying ATTR diagnosis code. Because ATTR-CM codes are frequently assigned after confirmatory testing, entered following care at outside institutions, or applied provisionally prior to subtype confirmation, we used an extended diagnostic ascertainment window spanning 24 months prior to and 12 months following the index date. This approach was designed to reflect real-world diagnostic workflows and capture testing performed during evaluation as well as testing that preceded formal coding within the health system. Diagnostic modalities included Tc-99m pyrophosphate scintigraphy, cardiac magnetic resonance imaging (CMR), and biopsy. Temporal trends were evaluated by year of diagnosis and reported as absolute counts and proportions. This study was From 2017 to 2025, the annual number of patients diagnosed with cardiac ATTR increased from 59 to 2,221 across 17 to 46 contributing U.S. health systems; the overall cohort had a mean age of 77 years, was 81% male, included 70% White, 22% Black, 2% Asian, and 2% Hispanic patients, and exhibited a high burden of comorbid conditions including atrial fibrillation (53%), chronic kidney disease (38%), hypertension (68%), chronic ischemic heart disease (49%), diabetes mellitus (28%), and obesity (26%). Use of Tc-99m scintigraphy increased from 19 patients in 2017 to 468 in 2024 and 420 in 2025. As a proportion of diagnosed patients, Tc-99m use rose from 32.2% in 2017 to a peak of 41.5% in 2019, followed by a decline to 18.9% in 2025. Cardiac MRI use increased in absolute terms from 10 patients in 2017 to 341 in 2024 and 354 in 2025, while proportional use remained relatively stable at approximately 16–19%, suggesting growth consistent with broader increases in CMR availability rather than disproportionate adoption specific to ATTR diagnosis. Dual-modality imaging increased from 10 patients in 2017 to 129 in 2024 and 110 in 2025 (Figure 1). In contrast, biopsy use declined steadily over time, from 11 patients (18.6%) in 2017 to 155 (7.1%) in 2024 and 124 (5.6%) in 2025, while combined scintigraphy and biopsy remained uncommon. Collectively, these findings indicate a sustained shift away from invasive histologic confirmation toward noninvasive imaging-based evaluation of cardiac ATTR-CM. This analysis demonstrates a major transformation in the diagnostic approach to cardiac ATTR-CM. Gillmore et al. established the specificity of bone-avid scintigraphy when monoclonal protein disorders are excluded. 3 The ATTR-ACT trial later confirmed tafamidis as the first disease-modifying therapy, accelerating recognition and screening. 4 ASNC CARI guidelines now endorse imaging-based diagnosis, reducing reliance on biopsy. 2 Our findings align with claims-based Medicare analyses showing increased scintigraphy use and declining biopsy rates. 5 Extending these observations through 2025, our analysis demonstrates that although absolute imaging utilization continues to increase, proportional adoption has not kept pace with rapidly expanding case identification, highlighting persistent dissemination gaps. This analysis has limitations. TriNetX data are de-identified and do not permit confirmation of imaging results, biopsy site, or diagnostic intent. Diagnostic pathways such as non-cardiac biopsy with cardiac involvement inferred by imaging may not be fully captured. Imaging or biopsy performed outside participating institutions or prior to network entry may also be underrepresented, and coding practices may vary across health systems. Despite these constraints, the consistency of observed trends across a growing number of institutions supports a genuine nationwide shift in diagnostic practice. Between 2017 and 2025, diagnostic evaluation of cardiac ATTR-CM shifted decisively toward noninvasive imaging, with substantial growth in Tc-99m scintigraphy and CMR accompanied by declining biopsy use. Continued efforts are needed to ensure consistent implementation of guideline-recommended diagnostic pathways as disease recognition expands. Declarations Competing Interests The authors have no relevant financial or non-financial interests to disclose. Ethics Approval This study used de-identified data from the TriNetX Research Network and was therefore exempt from institutional review board approval. Human Ethics and Consent to Participate Human Ethics and Consent to Participate declarations: not applicable. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contributions I.M. and W.A.J. contributed to the study conception and design. Data extraction and analysis were performed by I.M. The first draft of the manuscript was written by I.M., B.A., and W.A.J. Manuscript revision and critical intellectual input were provided by B.A., A.H., P.B., A.C.R., M.H., W.A.J., and ourselves. All authors read and approved the final manuscript. Data Availability The data that support the findings of this study are available from the TriNetX Research Network. Restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. Data are available from the corresponding author upon reasonable request and with permission of TriNetX. References Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR et al (2022) 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. JACC 79:e263–e421 Hage FG, Bourque JM, Pandey S, Shah NR, Soman P, Abbott BG, Abidov A, Aggarwal NR, AlJaroudi W, Bhambhvani PG et al American Society of Nuclear Cardiology quality metrics for cardiac amyloid radionuclide imaging. Journal of Nuclear Cardiology [Internet]. 2024 [cited 2025 Oct 29];40. Available from: https://www.journalofnuclearcardiology.org/article/S1071-3581(24)00723-2/fulltext Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M et al (2016) Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation 133:2404–2412 Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T et al (2018) Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 379:1007–1016 Bourque JM, Schepart A, Bhambri R, Castaño A, O’Brien A, Chen Y, Prasad S, Roy A, Grodin JL (2022) Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population. Am J Cardiol 167:98–103 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 16 Mar, 2026 Reviewers invited by journal 10 Feb, 2026 Editor assigned by journal 09 Feb, 2026 First submitted to journal 08 Feb, 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. 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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-8799253","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":589083106,"identity":"4ebb9fde-2a67-4311-96bd-df4e846330ba","order_by":0,"name":"Issam Motairek","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAr0lEQVRIiWNgGAWjYLCCBAYJOQYGxgfEqmcGazEGMgxI0AIEiQ1Ea9Ft7z/44eEei/T+9sMMDB/31BLWYnbmMLNEwjOJ3BlnkhkYZzw7ToSWG8kMEgkHJHI3SPAfYOY5cIwoLcw/gFrSDSSYGYjWwgayJQGqpYYov5hZALUYgvxycMaBA0RoOd74+OaPA3Xy/O2HGR98OFBHWAsKAFpxmEQtQECqLaNgFIyCUTASAAC/IDmRINfH0AAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3294-8659","institution":"Cleveland Clinic","correspondingAuthor":true,"prefix":"","firstName":"Issam","middleName":"","lastName":"Motairek","suffix":""},{"id":589083107,"identity":"49952e64-6d4a-4863-aaa9-fbe37184585e","order_by":1,"name":"Bryan Abadie","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Bryan","middleName":"","lastName":"Abadie","suffix":""},{"id":589083109,"identity":"cbea2a3c-e143-4c41-9972-e6661389b263","order_by":2,"name":"Andrew Higgins","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Andrew","middleName":"","lastName":"Higgins","suffix":""},{"id":589083110,"identity":"652447b1-cd9b-4dd8-8b36-999dcbe2a285","order_by":3,"name":"Pavan Bhat","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Pavan","middleName":"","lastName":"Bhat","suffix":""},{"id":589083112,"identity":"1d213157-c436-4fd2-821c-767c16269ffd","order_by":4,"name":"Andres Carmona Rubio","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Andres","middleName":"Carmona","lastName":"Rubio","suffix":""},{"id":589083114,"identity":"3cc13c75-5d77-4d52-b379-fc940853c452","order_by":5,"name":"Mazen Hanna","email":"","orcid":"","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Mazen","middleName":"","lastName":"Hanna","suffix":""},{"id":589083116,"identity":"c02c64e1-5a1a-4a98-ae3b-e04d7e202404","order_by":6,"name":"Wael Jaber","email":"","orcid":"https://orcid.org/0000-0001-5642-2112","institution":"Cleveland Clinic","correspondingAuthor":false,"prefix":"","firstName":"Wael","middleName":"","lastName":"Jaber","suffix":""}],"badges":[],"createdAt":"2026-02-05 16:18:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8799253/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8799253/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102790851,"identity":"f235b404-eb70-41de-bf8c-12cd823ed60f","added_by":"auto","created_at":"2026-02-16 17:13:40","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":147645,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTemporal Trends in Diagnostic Testing for Cardiac Transthyretin Amyloidosis (2017–2025)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eA.\u003c/strong\u003e Proportion of patients with cardiac ATTR undergoing Tc-99m pyrophosphate scintigraphy, cardiac magnetic resonance imaging, both modalities, or biopsy within an ascertainment window spanning 24 months prior to and 12 months following diagnosis.\u003cbr\u003e\n \u003cstrong\u003eB.\u003c/strong\u003e Annual number of patients undergoing each diagnostic modality.\u003cbr\u003e\nAcross U.S. health systems, absolute use of noninvasive imaging increased substantially over time, while biopsy use declined, highlighting a sustained shift toward imaging-based diagnosis. Data for 2025 represent a partial year of observation.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8799253/v1/c4b89912fbe68d801b262735.png"},{"id":102790852,"identity":"afaca5de-4f6f-4c71-a532-cf15ba697e5a","added_by":"auto","created_at":"2026-02-16 17:13:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":456703,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8799253/v1/f09c81c6-6e20-40d2-ac4a-5938933b260a.pdf"}],"financialInterests":"","formattedTitle":"Temporal Shifts in Diagnostic Testing for Cardiac Amyloidosis Across U.S. Health Systems","fulltext":[{"header":"Main","content":"\u003cp\u003eCardiac amyloidosis has evolved from a rare cause of restrictive cardiomyopathy to a key focus in heart failure practice. The widespread adoption of technetium-99m (Tc-99m)–based bone scintigraphy has enabled accurate, noninvasive identification of transthyretin cardiac amyloidosis (ATTR-CA).\u003csup\u003e1\u003c/sup\u003e The recently published 2024 American Society of Nuclear Cardiology (ASNC) \u003cem\u003eCardiac Amyloid Radionuclide Imaging (CARI)\u003c/em\u003e quality metrics emphasize its role as a first-line diagnostic tool in suspected ATTR-CM.\u003csup\u003e2\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe performed a retrospective, descriptive analysis using the TriNetX U.S. Collaborative Network to evaluate temporal trends in diagnostic testing among patients with cardiac ATTR-CM between January 2017 and November 2025. TriNetX aggregates de-identified electronic health record data across multiple U.S. health systems. Patients were identified using ICD-10 codes specific to wild-type or hereditary transthyretin amyloidosis (E85.82, E85.2) together with evidence of cardiac involvement, defined by concurrent codes for cardiomyopathy or heart failure (I43, I42.5, I42.9, or I50.x). To minimize diagnostic misclassification, patients with light-chain amyloidosis or plasma cell dyscrasias (E85.81, C90.x, C88.x, D47.2, D47.9) were excluded.\u003c/p\u003e\n\u003cp\u003eThe index date was defined as the first qualifying ATTR diagnosis code. Because ATTR-CM codes are frequently assigned after confirmatory testing, entered following care at outside institutions, or applied provisionally prior to subtype confirmation, we used an extended diagnostic ascertainment window spanning 24 months prior to and 12 months following the index date. This approach was designed to reflect real-world diagnostic workflows and capture testing performed during evaluation as well as testing that preceded formal coding within the health system. Diagnostic modalities included Tc-99m pyrophosphate scintigraphy, cardiac magnetic resonance imaging (CMR), and biopsy. Temporal trends were evaluated by year of diagnosis and reported as absolute counts and proportions. This study was\u003c/p\u003e\n\u003cp\u003eFrom 2017 to 2025, the annual number of patients diagnosed with cardiac ATTR increased from 59 to 2,221 across 17 to 46 contributing U.S. health systems; the overall cohort had a mean age of 77 years, was 81% male, included 70% White, 22% Black, 2% Asian, and 2% Hispanic patients, and exhibited a high burden of comorbid conditions including atrial fibrillation (53%), chronic kidney disease (38%), hypertension (68%), chronic ischemic heart disease (49%), diabetes mellitus (28%), and obesity (26%). Use of Tc-99m scintigraphy increased from 19 patients in 2017 to 468 in 2024 and 420 in 2025. As a proportion of diagnosed patients, Tc-99m use rose from 32.2% in 2017 to a peak of 41.5% in 2019, followed by a decline to 18.9% in 2025. Cardiac MRI use increased in absolute terms from 10 patients in 2017 to 341 in 2024 and 354 in 2025, while proportional use remained relatively stable at approximately 16–19%, suggesting growth consistent with broader increases in CMR availability rather than disproportionate adoption specific to ATTR diagnosis. Dual-modality imaging increased from 10 patients in 2017 to 129 in 2024 and 110 in 2025 (Figure 1).\u003c/p\u003e\n\u003cp\u003eIn contrast, biopsy use declined steadily over time, from 11 patients (18.6%) in 2017 to 155 (7.1%) in 2024 and 124 (5.6%) in 2025, while combined scintigraphy and biopsy remained uncommon. Collectively, these findings indicate a sustained shift away from invasive histologic confirmation toward noninvasive imaging-based evaluation of cardiac ATTR-CM.\u003c/p\u003e\n\u003cp\u003eThis analysis demonstrates a major transformation in the diagnostic approach to cardiac ATTR-CM. Gillmore et al. established the specificity of bone-avid scintigraphy when monoclonal protein disorders are excluded.\u003csup\u003e3\u003c/sup\u003e The ATTR-ACT trial later confirmed tafamidis as the first disease-modifying therapy, accelerating recognition and screening.\u003csup\u003e4\u003c/sup\u003e ASNC CARI guidelines now endorse imaging-based diagnosis, reducing reliance on biopsy.\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eOur findings align with claims-based Medicare analyses showing increased scintigraphy use and declining biopsy rates.\u003csup\u003e5\u003c/sup\u003e Extending these observations through 2025, our analysis demonstrates that although absolute imaging utilization continues to increase, proportional adoption has not kept pace with rapidly expanding case identification, highlighting persistent dissemination gaps.\u003c/p\u003e\n\u003cp\u003eThis analysis has limitations. TriNetX data are de-identified and do not permit confirmation of imaging results, biopsy site, or diagnostic intent. Diagnostic pathways such as non-cardiac biopsy with cardiac involvement inferred by imaging may not be fully captured. Imaging or biopsy performed outside participating institutions or prior to network entry may also be underrepresented, and coding practices may vary across health systems. Despite these constraints, the consistency of observed trends across a growing number of institutions supports a genuine nationwide shift in diagnostic practice.\u003c/p\u003e\n\u003cp\u003eBetween 2017 and 2025, diagnostic evaluation of cardiac ATTR-CM shifted decisively toward noninvasive imaging, with substantial growth in Tc-99m scintigraphy and CMR accompanied by declining biopsy use. Continued efforts are needed to ensure consistent implementation of guideline-recommended diagnostic pathways as disease recognition expands.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eCompeting Interests\u003c/h2\u003e \u003cp\u003eThe authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eEthics Approval\u003c/h2\u003e \u003cp\u003eThis study used de-identified data from the TriNetX Research Network and was therefore exempt from institutional review board approval.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eHuman Ethics and Consent to Participate\u003c/h2\u003e \u003cp\u003eHuman Ethics and Consent to Participate declarations: not applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contributions\u003c/h2\u003e \u003cp\u003eI.M. and W.A.J. contributed to the study conception and design. Data extraction and analysis were performed by I.M. The first draft of the manuscript was written by I.M., B.A., and W.A.J. Manuscript revision and critical intellectual input were provided by B.A., A.H., P.B., A.C.R., M.H., W.A.J., and ourselves. All authors read and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e \u003cp\u003eThe data that support the findings of this study are available from the TriNetX Research Network. Restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. Data are available from the corresponding author upon reasonable request and with permission of TriNetX.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHeidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR et al (2022) 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure. JACC 79:e263\u0026ndash;e421\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHage FG, Bourque JM, Pandey S, Shah NR, Soman P, Abbott BG, Abidov A, Aggarwal NR, AlJaroudi W, Bhambhvani PG et al American Society of Nuclear Cardiology quality metrics for cardiac amyloid radionuclide imaging. \u003cem\u003eJournal of Nuclear Cardiology\u003c/em\u003e [Internet]. 2024 [cited 2025 Oct 29];40. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.journalofnuclearcardiology.org/article/S1071-3581(24)00723-2/fulltext\u003c/span\u003e\u003cspan address=\"https://www.journalofnuclearcardiology.org/article/S1071-3581(24)00723-2/fulltext\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M et al (2016) Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation 133:2404\u0026ndash;2412\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, Kristen AV, Grogan M, Witteles R, Damy T et al (2018) Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. N Engl J Med 379:1007\u0026ndash;1016\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBourque JM, Schepart A, Bhambri R, Casta\u0026ntilde;o A, O\u0026rsquo;Brien A, Chen Y, Prasad S, Roy A, Grodin JL (2022) Temporal Trends in Diagnostic Testing Patterns for Wild-Type Transthyretin Amyloid Cardiomyopathy in the Medicare Fee-for-Service Population. Am J Cardiol 167:98\u0026ndash;103\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-hybrid-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejhi","sideBox":"Learn more about [European Journal of Hybrid Imaging](http://ejhi.springeropen.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejhi/default.aspx","title":"European Journal of Hybrid Imaging","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Cardiac amyloidosis, transthyretin amyloidosis, technetium-99m pyrophosphate, scintigraphy, nuclear cardiology, diagnostic trends, noninvasive imaging","lastPublishedDoi":"10.21203/rs.3.rs-8799253/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8799253/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u003cbr\u003e\nTo evaluate temporal trends in diagnostic testing for cardiac transthyretin amyloidosis (ATTR-CM) across U.S. health systems in the contemporary era.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003cbr\u003e\nWe conducted a retrospective, descriptive analysis using the TriNetX U.S. Collaborative Network, identifying patients diagnosed with wild-type or hereditary ATTR-CM between January 2017 and November 2025. ATTR-specific ICD-10 codes were combined with evidence of cardiac involvement, and patients with light-chain amyloidosis or plasma cell dyscrasias were excluded. Diagnostic testing, including technetium-99m (Tc-99m) bone scintigraphy, cardiac magnetic resonance imaging (CMR), and biopsy, was assessed within an extended diagnostic ascertainment window spanning 24 months before and 12 months after diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003cbr\u003e\nThe number of patients diagnosed with ATTR-CM increased markedly over time. Use of Tc-99m scintigraphy and CMR rose substantially in absolute terms, while biopsy utilization declined steadily. Dual-modality imaging increased modestly, and invasive histologic confirmation became progressively less common, indicating a shift toward imaging-based diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e\u003cbr\u003e\nBetween 2017 and 2025, diagnostic evaluation of ATTR-CM shifted decisively toward noninvasive imaging, with declining reliance on biopsy. Although imaging volume increased, proportional adoption did not keep pace with expanding case identification, underscoring the need for broader implementation of guideline-recommended diagnostic pathways.\u003c/p\u003e","manuscriptTitle":"Temporal Shifts in Diagnostic Testing for Cardiac Amyloidosis Across U.S. Health Systems","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-16 17:13:35","doi":"10.21203/rs.3.rs-8799253/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-03-16T07:33:40+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-10T15:35:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-10T04:40:35+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Hybrid Imaging","date":"2026-02-08T23:42:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-hybrid-imaging","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejhi","sideBox":"Learn more about [European Journal of Hybrid Imaging](http://ejhi.springeropen.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ejhi/default.aspx","title":"European Journal of Hybrid Imaging","twitterHandle":"@officialEANM","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5711085d-9fa1-4207-a30d-020614069dca","owner":[],"postedDate":"February 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T17:13:35+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-16 17:13:35","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8799253","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8799253","identity":"rs-8799253","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}