{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T03:54:00Z","timestamp":1777521240532,"version":"3.51.4"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":665,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010447","name":"Deutsches Zentrum f\u00fcr Herz-Kreislauf-Forschung\u2013German Centre for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1118"],"award-info":[{"award-number":["CRC 1118"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1550"],"award-info":[{"award-number":["CRC 1550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1118"],"award-info":[{"award-number":["CRC 1118"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 1550"],"award-info":[{"award-number":["CRC 1550"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>First, we retrospectively analysed patient data of n = 265 TTS cases (85.7% female, mean age 71.1 \u00b1 14.1 years) with documented initial plasma glucose from the Department of Cardiology of the University Hospital Heidelberg in Germany (May 2011 to May 2021). Median split of the study population according to glucose levels (\u2264123 mg\/dL vs. &amp;gt;123 mg\/dL) yielded significantly elevated mean heart rate (80.75 \u00b1 18.96 vs. 90.01 \u00b1 22.19 b.p.m., P &amp;lt; 0.001), left ventricular end-diastolic pressure (LVEDP, 18.51 \u00b1 8.35 vs. 23.09 \u00b1 7.97 mmHg, P &amp;lt; 0.001), C-reactive protein (26.14 \u00b1 43.30 vs. 46.4 \u00b1 68.6 mg\/L, P = 0.006), leukocyte count (10.12 \u00b1 4.29 vs. 15.05 \u00b1 9.83\/nL, P &amp;lt; 0.001), peak high-sensitive Troponin T (hs-TnT, 515.44 \u00b1 672.15 vs. 711.40 \u00b1 736.37 pg\/mL, P = 0.005), reduced left ventricular ejection fraction (EF, 34.92 \u00b1 8.94 vs. 31.35 \u00b1 8.06%, P &amp;lt; 0.001), and elevated intrahospital mortality (2.3% vs. 12.1%, P = 0.002) in the high-glucose group (Student's t-test, Mann\u2013Whitney U test, or chi-squared test). Linear regression indicated a significant association of glucose with HR (P &amp;lt; 0.001), LVEDP (P = 0.014), hs-TnT kinetics from admission to the next day (P &amp;lt; 0.001), hs-TnT the day after admission (P &amp;lt; 0.001), as well as peak hsTnT (P &amp;lt; 0.001). Logistic regression revealed significant association of glucose with a composite intrahospital outcome including catecholamine use, respiratory support, and resuscitation [OR 1.010 (1.004\u20131.015), P = 0.001]. To further investigate the potential role of glucose in TTS pathophysiology experimentally, we utilized an in vivo murine model of epinephrine (EPI)-driven reversible AHF. For this, male mice underwent therapeutic injection of insulin (INS, 1 IU\/kg) or\/and glucose (GLU, 0.5 g\/kg) after EPI (2.5 mg\/kg), both of which markedly improved mean EF (EPI 34.3% vs. EPI + INS + GLU 43.7%, P = 0.025) and significantly blunted mean hs-TnT (EPI 14 393 pg\/mL vs. EPI + INS 6864 pg\/mL at 24 h, P = 0.039). Particularly, insulin additionally ameliorated myocardial pro-inflammatory gene expression, suggesting an anti-inflammatory effect of acute insulin therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated initial plasma glucose was associated with adverse outcome-relevant parameters in TTS and may present a surrogate parameter of heightened catecholaminergic drive. In mice, insulin- and glucose injection both improved EPI-induced AHF and myocardial damage, indicating insulin resistance rather than detrimental effects of hyperglycaemia itself as the underlying cause. Future studies will investigate the role of HbA1c as a risk stratifier and of insulin-based therapy in TTS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14623","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T21:04:47Z","timestamp":1703106287000},"page":"1515-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Insulin Resistance in Takotsubo Syndrome"],"prefix":"10.1093","volume":"11","author":[{"given":"Bastian","family":"Bruns","sequence":"first","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"Institute of Experimental Cardiology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maximilian","family":"Joos","sequence":"additional","affiliation":[{"name":"Institute of Experimental Cardiology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nesrin","family":"Elsous","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jobst-Hendrik","family":"Schultz","sequence":"additional","affiliation":[{"name":"Department of General Internal Medicine and Psychosomatics, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Pneumology, Heidelberg University Hospital , Heidelberg ,","place":["Germany"]},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site , Heidelberg\/Mannheim 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