{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:37:06Z","timestamp":1788781026252,"version":"build-2803163510"},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Cardiology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to investigate whether a dose\u2013effect relationship exists between the number of microbubbles detected on right heart contrast echocardiography (RHCE) and the clinical severity of migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a cross\u2010sectional study of 190 adult patients diagnosed with migraine who underwent RHCE. Microbubble counts were categorized into four grades per frame (Grades 0\u2013III) based on their appearance in the left atrium within three to six cardiac cycles after right atrial opacification. Migraine severity was assessed using the Migraine Disability Assessment (MIDAS) score and the Headache Impact Test (HIT\u20106). Multivariate linear regression was used to evaluate the association between microbubble grades and migraine severity. The predictive ability of the model was assessed using the residual plots and variance inflation factors. Sensitivity analyses were performed to test the robustness of the findings by adjusting for potential confounders.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A clear dose\u2013response relationship was identified, with patients in higher microbubble\u2010grade groups demonstrating significantly elevated MIDAS and HIT\u20106 scores (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Patients with Grade III microbubbles reported the highest mean MIDAS (18.2\u2009\u00b1\u20096.1) and HIT\u20106 (64.8\u2009\u00b1\u20094.9) scores, compared to those in lower grades (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Regression analyses confirmed that the higher microbubble burden independently predicted migraine severity (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2009=\u20090.46,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Sensitivity analyses yielded consistent findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest a notable dose\u2013effect relationship between RHCE microbubble count and migraine severity. These findings highlight the potential role of right\u2010to\u2010left shunting as a physiological contributor to migraine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/clc.70155","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T08:10:21Z","timestamp":1748851821000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Right Heart Contrast Echocardiography Microbubble Count and Migraine Severity: A Dose\u2013Effect Relationship Study"],"prefix":"10.1002","volume":"48","author":[{"given":"Haijuan","family":"Gu","sequence":"first","affiliation":[{"name":"Department of Ultrasound Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Cardiology Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiesheng","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5842-7570","authenticated-orcid":false,"given":"Jianwei","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Ultrasound Haimen District People's Hospital Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14721"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2020.107528"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01281-z"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417708203"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-024-02760-8"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.972336"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000024"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.727271"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-056937"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6643266"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(91)90705-E"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/15443167221108512"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2022.100992"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12070941"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417738202"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.124.016517"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2022.08.007"},{"issue":"6","key":"e_1_2_11_19_1","first-page":"S20","article-title":"Development and Testing of the Migraine Disability Assessment (MIDAS) Questionnaire to Assess Headache\u2010Related Disability","volume":"56","author":"Stewart W. 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