{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T14:23:48Z","timestamp":1740147828352,"version":"3.37.3"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T00:00:00Z","timestamp":1665619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012330","name":"Okayama University","doi-asserted-by":"publisher","award":["RECTOR"],"award-info":[{"award-number":["RECTOR"]}],"id":[{"id":"10.13039\/501100012330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["453989101","453989101","507803309"],"award-info":[{"award-number":["453989101","453989101","507803309"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K19450"],"award-info":[{"award-number":["21K19450"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Universit\u00e4tsklinikum W\u00fcrzburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Curr Cardiol Rep"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Purpose of Review<\/jats:title>\n                <jats:p>Statins are routinely applied in patients with coronary artery disease, as they allow significantly to\u00a0reduce blood cholesterol levels. Although those drugs are endorsed by current guidelines and prescribed routinely, a substantial portion of patients are still statin-intolerant and image-piloted strategies may then be helpful to identify patients that need further intensified treatment, e.g., to initiate treatment with proprotein convertase subtilisin \/\u00a0kexin type 9 inhibitors (PCSK9i). In addition, it has also been advocated that statins exhibit nonlipid, cardio-protective effects including improved cardiac nerve integrity, blood flow, and anti-inflammatory effects in congestive heart failure (HF) patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Recent Findings<\/jats:title>\n                <jats:p>In subjects after myocardial infarction treated with statins, <jats:sup>123I<\/jats:sup>I-metaiodobenzylguanidine (MIBG) scintigraphy has already revealed enhanced cardiac nerve function relative to patients without statins. In addition, all of those aforementioned statin-targeted pathways in HF can be visualized and monitored using dedicated cardiac radiotracers, e.g., <jats:sup>123<\/jats:sup>I-MIBG or <jats:sup>18<\/jats:sup>F-AF78 (for cardiac nerve function), <jats:sup>18<\/jats:sup>F-flurpiridaz (to determine coronary flow) or <jats:sup>68<\/jats:sup>Ga-PentixaFor (to detect inflammation).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Summary<\/jats:title>\n                <jats:p>Statins exhibit various cardio-beneficial effects, including improvement of cardiac nerve function, blood flow, and reduction of inflammation, which can all be imaged using dedicated nuclear cardiac radiotracers. This may allow for in vivo monitoring of statin-induced cardioprotection beyond lipid profiling in HF patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11886-022-01792-4","type":"journal-article","created":{"date-parts":[[2022,10,13]],"date-time":"2022-10-13T09:04:18Z","timestamp":1665651858000},"page":"1849-1853","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Effects of Lipid Lowering Medications on Myocardial Blood Flow, Inflammation, and Sympathetic Nerve Activity Using Nuclear Techniques"],"prefix":"10.1007","volume":"24","author":[{"given":"Takahiro","family":"Higuchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sebastian E.","family":"Serfling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven P.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3372-6046","authenticated-orcid":false,"given":"Rudolf A.","family":"Werner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,13]]},"reference":[{"key":"1792_CR1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1038\/s41569-018-0098-5","volume":"15","author":"BB Adhyaru","year":"2018","unstructured":"Adhyaru BB, Jacobson TA. Safety and efficacy of statin therapy. Nat Rev Cardiol. 2018;15:757\u201369.","journal-title":"Nat Rev Cardiol"},{"key":"1792_CR2","doi-asserted-by":"crossref","unstructured":"Cholesterol Treatment Trialists C, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670\u201381.","DOI":"10.1016\/S0140-6736(10)61350-5"},{"key":"1792_CR3","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1161\/CIRCULATIONAHA.105.552174","volume":"112","author":"L Gao","year":"2005","unstructured":"Gao L, Wang W, Li YL, et al. Simvastatin therapy normalizes sympathetic neural control in experimental heart failure: roles of angiotensin II type 1 receptors and NAD(P)H oxidase. Circulation. 2005;112:1763\u201370.","journal-title":"Circulation"},{"key":"1792_CR4","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1007\/s12471-016-0883-x","volume":"25","author":"L Cerit","year":"2017","unstructured":"Cerit L, Duygu H, Gulsen K, Gunsel A. Effect of statins on coronary blood flow after percutaneous coronary intervention in patients with stable coronary artery disease. Neth Heart J. 2017;25:258\u201363.","journal-title":"Neth Heart J"},{"key":"1792_CR5","unstructured":"Statins associated with improved heart structure and function. 2017.\u00a0\u00a0https:\/\/www.escardioorg\/The-ESC\/Press-Office\/Press-releases\/Statins-associated-with-improved-heart-structure-and-function, last Assessed 2 Aug\u00a02022."},{"key":"1792_CR6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1023\/A:1022103222857","volume":"8","author":"S von Haehling","year":"2003","unstructured":"von Haehling S, Anker SD, Bassenge E. Statins and the role of nitric oxide in chronic heart failure. Heart Fail Rev. 2003;8:99\u2013106.","journal-title":"Heart Fail Rev"},{"key":"1792_CR7","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1056\/NEJMoa042378","volume":"352","author":"PM Ridker","year":"2005","unstructured":"Ridker PM, Cannon CP, Morrow D, et al. C-reactive protein levels and outcomes after statin therapy. N Engl J Med. 2005;352:20\u20138.","journal-title":"N Engl J Med"},{"key":"1792_CR8","doi-asserted-by":"publisher","first-page":"3599","DOI":"10.1093\/eurheartj\/ehab368","volume":"42","author":"TA McDonagh","year":"2021","unstructured":"McDonagh TA, Metra M, Adamo M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;42:3599\u2013726.","journal-title":"Eur Heart J"},{"key":"1792_CR9","doi-asserted-by":"publisher","first-page":"951","DOI":"10.2967\/jnumed.119.240440","volume":"61","author":"RA Werner","year":"2020","unstructured":"Werner RA, Thackeray JT, Diekmann J, Weiberg D, Bauersachs J, Bengel FM. The changing face of nuclear cardiology: guiding cardiovascular care toward molecular medicine. J Nucl Med. 2020;61:951\u201361.","journal-title":"J Nucl Med"},{"key":"1792_CR10","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/s11883-009-0003-0","volume":"11","author":"JG Robinson","year":"2009","unstructured":"Robinson JG. Is a statin as part of a polypill the answer? Curr Atheroscler Rep. 2009;11:15\u201322.","journal-title":"Curr Atheroscler Rep"},{"key":"1792_CR11","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10557-018-6775-0","volume":"32","author":"TN Harrison","year":"2018","unstructured":"Harrison TN, Hsu JY, Rosenson RS, et al. Unmet patient need in statin intolerance: the clinical characteristics and management. Cardiovasc Drugs Ther. 2018;32:29\u201336.","journal-title":"Cardiovasc Drugs Ther"},{"key":"1792_CR12","doi-asserted-by":"publisher","first-page":"3140","DOI":"10.1210\/jc.2015-1520","volume":"100","author":"H Bays","year":"2015","unstructured":"Bays H, Gaudet D, Weiss R, et al. Alirocumab as add-on to atorvastatin versus other lipid treatment strategies: ODYSSEY OPTIONS I randomized trial. J Clin Endocrinol Metab. 2015;100:3140\u20138.","journal-title":"J Clin Endocrinol Metab"},{"key":"1792_CR13","doi-asserted-by":"publisher","first-page":"1458","DOI":"10.1007\/s12350-019-01883-w","volume":"28","author":"RA Werner","year":"2021","unstructured":"Werner RA, Thackeray JT, Bengel FM. Does lipid-lowering medication improve cardiac sympathetic nerve integrity? J Nucl Cardiol. 2021;28:1458\u201360.","journal-title":"J Nucl Cardiol"},{"key":"1792_CR14","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1016\/j.jacc.2010.01.014","volume":"55","author":"AF Jacobson","year":"2010","unstructured":"Jacobson AF, Senior R, Cerqueira MD, et al. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study. J Am Coll Cardiol. 2010;55:2212\u201321.","journal-title":"J Am Coll Cardiol."},{"key":"1792_CR15","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1007\/s12350-019-01857-y","volume":"28","author":"S Takahashi","year":"2021","unstructured":"Takahashi S, Kasama S, Toyama T, et al. Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol. J Nucl Cardiol. 2021;28:1449\u201357.","journal-title":"J Nucl Cardiol"},{"key":"1792_CR16","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s40336-018-0289-4","volume":"6","author":"RA Werner","year":"2018","unstructured":"Werner RA, Chen X, Hirano M, et al. SPECT vs. PET in cardiac innervation imaging: clash of the titans. Clin Transl Imaging. 2018;6:293\u2013303.","journal-title":"Clin Transl Imaging."},{"key":"1792_CR17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.tcm.2019.02.007","volume":"30","author":"RA Werner","year":"2020","unstructured":"Werner RA, Chen X, Rowe SP, Lapa C, Javadi MS, Higuchi T. Recent paradigm shifts in molecular cardiac imaging-establishing precision cardiology through novel (18)F-labeled PET radiotracers. Trends Cardiovasc Med. 2020;30:11\u20139.","journal-title":"Trends Cardiovasc Med"},{"key":"1792_CR18","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1007\/s11307-019-01407-5","volume":"22","author":"X Chen","year":"2020","unstructured":"Chen X, Fritz A, Werner RA, et al. Initial Evaluation of AF78: a Rationally designed fluorine-18-labelled PET radiotracer targeting norepinephrine transporter. Mol Imaging Biol. 2020;22:602\u201311.","journal-title":"Mol Imaging Biol"},{"key":"1792_CR19","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/j.jcmg.2020.09.026","volume":"14","author":"JGE Zelt","year":"2021","unstructured":"\u2022\u2022 Zelt JGE, Britt D, Mair BA, et al. Regional distribution of fluorine-18-flubrobenguane and carbon-11-hydroxyephedrine for cardiac PET imaging of sympathetic innervation. JACC Cardiovasc Imaging. 2021;14:1425\u201336. This study showed that the 18F-labeled cardiac innervation radiotracer provides equivalent information on cardiac denervation when compared to its established 11C-labeled equivalent. 18F-labeled radiotracers, however, have the advantage of distribution to remote PET\/CT facilities due their longer half-life.","journal-title":"JACC Cardiovasc Imaging"},{"key":"1792_CR20","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.2967\/jnumed.115.158493","volume":"56","author":"RA Werner","year":"2015","unstructured":"Werner RA, Rischpler C, Onthank D, et al. Retention kinetics of the 18F-labeled sympathetic nerve PET tracer LMI1195: comparison with 11C-hydroxyephedrine and 123I-MIBG. J Nucl Med. 2015;56:1429\u201333.","journal-title":"J Nucl Med"},{"key":"1792_CR21","doi-asserted-by":"publisher","first-page":"3849","DOI":"10.1161\/01.CIR.0000150540.54220.C4","volume":"110","author":"A Daugherty","year":"2004","unstructured":"Daugherty A, Rateri DL, Lu H, Inagami T, Cassis LA. Hypercholesterolemia stimulates angiotensin peptide synthesis and contributes to atherosclerosis through the AT1A receptor. Circulation. 2004;110:3849\u201357.","journal-title":"Circulation"},{"key":"1792_CR22","first-page":"182","volume":"48","author":"V Dilsizian","year":"2007","unstructured":"Dilsizian V, Eckelman WC, Loredo ML, Jagoda EM, Shirani J. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. J Nucl Med. 2007;48:182\u20137.","journal-title":"J Nucl Med"},{"key":"1792_CR23","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1016\/j.jacc.2012.09.023","volume":"60","author":"K Fukushima","year":"2012","unstructured":"Fukushima K, Bravo PE, Higuchi T, et al. Molecular hybrid positron emission tomography\/computed tomography imaging of cardiac angiotensin II type 1 receptors. J Am Coll Cardiol. 2012;60:2527\u201334.","journal-title":"J Am Coll Cardiol"},{"key":"1792_CR24","doi-asserted-by":"publisher","first-page":"10460","DOI":"10.1021\/acsomega.8b01885","volume":"3","author":"X Chen","year":"2018","unstructured":"Chen X, Hirano M, Werner RA, Decker M, Higuchi T. Novel (18)F-labeled PET imaging agent FV45 targeting the renin-angiotensin system. ACS Omega. 2018;3:10460\u201370.","journal-title":"ACS Omega"},{"key":"1792_CR25","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1016\/j.jacc.2009.07.005","volume":"54","author":"C Briguori","year":"2009","unstructured":"Briguori C, Visconti G, Focaccio A, et al. Novel approaches for preventing or limiting events (Naples) II trial: impact of a single high loading dose of atorvastatin on periprocedural myocardial infarction. J Am Coll Cardiol. 2009;54:2157\u201363.","journal-title":"J Am Coll Cardiol"},{"key":"1792_CR26","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1016\/j.jacc.2012.11.022","volume":"61","author":"DS Berman","year":"2013","unstructured":"Berman DS, Maddahi J, Tamarappoo BK, et al. Phase II safety and clinical comparison with single-photon emission computed tomography myocardial perfusion imaging for detection of coronary artery disease: flurpiridaz F 18 positron emission tomography. J Am Coll Cardiol. 2013;61:469\u201377.","journal-title":"J Am Coll Cardiol"},{"key":"1792_CR27","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/s10554-018-1469-z","volume":"35","author":"RA Werner","year":"2019","unstructured":"Werner RA, Chen X, Rowe SP, Lapa C, Javadi MS, Higuchi T. Moving into the next era of PET myocardial perfusion imaging: introduction of novel (18)F-labeled tracers. Int J Cardiovasc Imaging. 2019;35:569\u201377.","journal-title":"Int J Cardiovasc Imaging"},{"key":"1792_CR28","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1016\/j.jcmg.2012.10.006","volume":"5","author":"V Dilsizian","year":"2012","unstructured":"Dilsizian V, Taillefer R. Journey in evolution of nuclear cardiology: will there be another quantum leap with the F-18-labeled myocardial perfusion tracers? JACC Cardiovasc Imaging. 2012;5:1269\u201384.","journal-title":"JACC Cardiovasc Imaging"},{"key":"1792_CR29","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1161\/01.CIR.100.3.230","volume":"100","author":"PM Ridker","year":"1999","unstructured":"Ridker PM, Rifai N, Pfeffer MA, Sacks F, Braunwald E. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation. 1999;100:230\u20135.","journal-title":"Circulation."},{"key":"1792_CR30","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1056\/NEJMoa0807646","volume":"359","author":"PM Ridker","year":"2008","unstructured":"Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195\u2013207.","journal-title":"N Engl J Med"},{"key":"1792_CR31","doi-asserted-by":"publisher","first-page":"164","DOI":"10.2967\/jnmt.109.062950","volume":"37","author":"J Ducharme","year":"2009","unstructured":"Ducharme J, Goertzen AL, Patterson J, Demeter S. Practical aspects of 18F-FDG PET when receiving 18F-FDG from a distant supplier. J Nucl Med Technol. 2009;37:164\u20139.","journal-title":"J Nucl Med Technol"},{"key":"1792_CR32","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1007\/s12350-016-0522-3","volume":"23","author":"V Dilsizian","year":"2016","unstructured":"Dilsizian V, Bacharach SL, Beanlands RS, et al. ASNC imaging guidelines\/SNMMI procedure standard for positron emission tomography (PET) nuclear cardiology procedures. J Nucl Cardiol. 2016;23:1187\u2013226.","journal-title":"J Nucl Cardiol"},{"key":"1792_CR33","doi-asserted-by":"publisher","first-page":"372","DOI":"10.1016\/j.jcmg.2021.08.013","volume":"15","author":"RA Werner","year":"2022","unstructured":"\u2022 Werner RA, Koenig T, Diekmann J, et al. CXCR4-targeted imaging of post-infarct myocardial tissue inflammation: prognostic value after reperfused myocardial infarction. JACC Cardiovasc Imaging. 2022;15:372\u20134. Findings from this study showed that a local non-invasive molecular imaging read-out of the inflammation in the infarcted area may have better predictive potential to identify high-risk patients prone to later major cardiovascular events than other established clinical parameters right after myocardial infarction.","journal-title":"JACC Cardiovasc Imaging"},{"key":"1792_CR34","doi-asserted-by":"crossref","unstructured":"Buck AK, Serfling SE, Lindner T, et al. CXCR4-targeted theranostics in oncology. Eur J Nucl Med Mol Imaging. 2022.","DOI":"10.1007\/s00259-022-05849-y"}],"container-title":["Current Cardiology Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11886-022-01792-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11886-022-01792-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11886-022-01792-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T10:17:49Z","timestamp":1670926669000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11886-022-01792-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,13]]},"references-count":34,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["1792"],"URL":"https:\/\/doi.org\/10.1007\/s11886-022-01792-4","relation":{},"ISSN":["1523-3782","1534-3170"],"issn-type":[{"type":"print","value":"1523-3782"},{"type":"electronic","value":"1534-3170"}],"subject":[],"published":{"date-parts":[[2022,10,13]]},"assertion":[{"value":"30 September 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2022","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with Ethical Standards"}},{"value":"The present study did not involve human or animal subjects.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval and Consent to Participate"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}}]}}