{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:46:06Z","timestamp":1794008766834,"version":"4.8.0"},"reference-count":28,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,6,1]]},"abstract":"\n Importance<\/jats:title>\n Adverse myocardial remodeling and fibrosis contribute to heart failure progression and are thought to be driven by activated fibroblasts. Noninvasive assessment of myocardial fibroblast activation may improve phenotyping and risk stratification in heart failure.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate myocardial fibroblast activation in patients with heart failure with reduced ejection fraction using gallium 68\u2013labeled fibroblast activation protein inhibitor 46 ([\n 68<\/jats:sup>\n Ga]FAPI-46) positron emission tomography (PET) and magnetic resonance imaging (MRI).\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This was a prospective case-control study including patients with heart failure with reduced ejection fraction, patients with prior myocardial infarction without heart failure, and healthy volunteers. A subset of patients with heart failure underwent repeat imaging after more than 6 months. Data analysis was conducted from January 2024 to January 2025.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n All participants underwent [\n 68<\/jats:sup>\n Ga]FAPI-46 PET\/MRI.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n Myocardial fibroblast activation quantified using maximum standardized uptake values (SUVmax) of [\n 68<\/jats:sup>\n Ga]FAPI-46.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 81 participants were included (mean [SD] age, 66.2 [9.7] years; 22 [27%] female): 42 with heart failure (21 with heart failure due to ischemic cardiomyopathy from a previous myocardial infarction and 21 with a nonischemic etiology; mean [SD] left ventricular ejection fraction, 41% [9%]), 20 with a prior myocardial infarction but preserved left ventricular systolic function, and 19 healthy volunteers. No myocardial fibroblast activation was observed in healthy volunteers. All patients with heart failure demonstrated increased myocardial [\n 68<\/jats:sup>\n Ga]FAPI-46 uptake compared with healthy volunteers (mean [SD] SUVmax, 2.7 [1.5] vs 1.5 [0.3];\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). Uptake was highest in patients with ischemic cardiomyopathy, localizing to regions of established myocardial infarction (mean [SD] SUVmax, 3.2 [1.1]). Patients with nonischemic cardiomyopathy exhibited a different pattern of diffuse, lower-intensity uptake (mean [SD] SUVmax, 2.3 [0.5]), with the highest signal in the basal septum irrespective of late gadolinium enhancement. Patients with ischemic cardiomyopathy had higher uptake than patients with prior myocardial infarction without heart failure (n\u2009=\u200920) despite no major difference in infarct size (mean [SD] SUVmax, 3.2 [1.1] vs 2.5 [0.3];\n P<\/jats:italic>\n \u2009=\u2009.03). Among patients with heart failure who underwent repeat imaging, higher baseline [\n 68<\/jats:sup>\n Ga]FAPI-46 uptake was associated with less improvement in ejection fraction with optimal medical therapy over time (\n r<\/jats:italic>\n \u2009=\u2009\u22120.52;\n P<\/jats:italic>\n \u2009=\u2009.02).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n In this case-control study, patients with heart failure demonstrated persistent myocardial fibroblast activation with distinct spatial patterns according to cardiomyopathy etiology. Noninvasive imaging of fibroblast activation may provide mechanistic insights, aid risk stratification, and support the development of targeted antifibrotic therapies in heart failure.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2026.0661","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T15:30:35Z","timestamp":1776267035000},"page":"515","source":"Crossref","is-referenced-by-count":5,"title":["Myocardial Fibroblast Activation in Ischemic and Nonischemic Cardiomyopathy"],"prefix":"10.1001","volume":"11","author":[{"given":"Shruti S.","family":"Joshi","sequence":"first","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"Barton","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krithika","family":"Loganath","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil J.","family":"Craig","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menaka","family":"Mahendran","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Whittington","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tariq","family":"Ramtoola","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle C.","family":"Williams","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin J. R.","family":"van Beek","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"},{"name":"Edinburgh Heart Centre, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Baker","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Fletcher","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Clark","sequence":"additional","affiliation":[{"name":"British Heart Foundation Centre of Research Excellence, University of Edinburgh, Edinburgh, United 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