{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:59:00Z","timestamp":1787587140618,"version":"build-2736575974"},"reference-count":23,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Reports"],"abstract":"<jats:p>Background: Cardiac rhabdomyomas (CRs) are the most common cardiac tumors in newborns. Approximately 80\u201390% of cases are associated with tuberous sclerosis complex (TSC). In selective cases, Everolimus has resulted in a remarkable tumoral regression effect in children with TS. The optimal dosage for neonates is still unknown. Case presentation: We describe the use of Everolimus in a neonate with multiple biventricular CRs, causing subaortic obstruction, in which a low-dose treatment (0.1 mg\/die), in an effort to maintain serum trough levels of 3\u20137 ng\/mL, was successfully used off-label, without adverse effects. Conclusions: We showed that a low-dose Everolimus regimen may be an effective and safe treatment for CR regression in TS neonates, when the minimum therapeutic range was maintained.<\/jats:p>","DOI":"10.3390\/pediatric13010015","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T01:26:33Z","timestamp":1614561993000},"page":"104-112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Efficacy of Everolimus Low-Dose Treatment for Cardiac Rhabdomyomas in Neonatal Tuberous Sclerosis: Case Report and Literature Review"],"prefix":"10.3390","volume":"13","author":[{"given":"Luisa Federica","family":"Nespoli","sequence":"first","affiliation":[{"name":"Pediatric Cardiology Unit, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Albani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Corti","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Unit, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigina","family":"Spaccini","sequence":"additional","affiliation":[{"name":"Clinical Genetics Unit, Department of Obstetrics and Gynecology, \u201cV. Buzzi\u201d Children\u2019s Hospital, University of Milano, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Alfei","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Unit, \u201cV. Buzzi\u201d Children\u2019s Hospital, Milano, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Daniele","sequence":"additional","affiliation":[{"name":"Neonatal Pathology and Neonatal Intensive Care Unit, \u201cV. Buzzi\u201d Children\u2019s Hospital, University of Milano, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2795-9874","authenticated-orcid":false,"given":"Gian Vincenzo","family":"Zuccotti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"},{"name":"Department of Biomedical and Clinical Science \u201cL. Sacco\u201d, University of Milano, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Lista","sequence":"additional","affiliation":[{"name":"Neonatal Pathology and Neonatal Intensive Care Unit, \u201cV. Buzzi\u201d Children\u2019s Hospital, University of Milano, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-5974","authenticated-orcid":false,"given":"Valeria","family":"Calcaterra","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"},{"name":"Pediatric and Adolescent Unit, Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Savina","family":"Mannarino","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Unit, \u201cVittore Buzzi\u201d Children\u2019s Hospital, 20154 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/iju.13390","article-title":"Tuberous Sclerosis Complex Board of Osaka University Hospital. Tuberous sclerosis complex: Recent advances in manifestations and therapy","volume":"24","author":"Uemura","year":"2017","journal-title":"Int. J. Urol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1590\/abd1806-4841.20186972","article-title":"Tuberous sclerosis complex: Review based on new diagnostic criteria","volume":"93","author":"Portocarrero","year":"2018","journal-title":"Bras Dermatol."},{"key":"ref_3","first-page":"264-e1","article-title":"Cardiac Rhabdomyomas in Tuberous sclerosis complex","volume":"192","author":"Mantilla","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"319","DOI":"10.17219\/acem\/62121","article-title":"Cardiac tumors in children: A 20-year review of clinical presentation, diagnostics and treatment","volume":"26","author":"Kwiatkowska","year":"2017","journal-title":"Adv. Clin. Exp. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1007\/s00246-016-1528-y","article-title":"Accelerated Cardiac Rhabdomyoma regression with Everolimus in infants with tuberous sclerosis complex","volume":"38","author":"Aw","year":"2017","journal-title":"Pediatr. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13023-017-0596-2","article-title":"mTOR inhibitors in the pharmacologic management of tuberous sclerosis complex and their potential role in other rare neurodevelopmental disorders","volume":"12","author":"Franz","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s40272-019-00337-7","article-title":"Off-label use of Sirolimus and Everolimus in a Pediatric Center: A case series and review of the literature","volume":"21","author":"Bevacqua","year":"2019","journal-title":"Paediatr. Drugs"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","article-title":"Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference","volume":"49","author":"Northrup","year":"2013","journal-title":"Pediatr. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e001493","DOI":"10.1161\/JAHA.114.001493","article-title":"Cardiovascular manifestations of tuberous sclerosis complex and summary of the revised diagnostic criteria and surveillance and management recommendations from the International Tuberous Sclerosis Consensus Group","volume":"3","author":"Hinton","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Garg, A., Gorla, S.R., Kardon, R.E., and Swaminathan, S. (2019). Rapid Involution of Large Cardiac Rhabdomyomas With Everolimus Therapy. World J. Pediatr. Congenit Heart Surg., 2150135118822711.","DOI":"10.1177\/2150135118822711"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.pediatrneurol.2015.01.004","article-title":"Use of mTOR inhibitor everolimus in three neonates for treatment of tumors associated with tuberous sclerosis complex","volume":"52","author":"Goyer","year":"2015","journal-title":"Pediatr. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"45","DOI":"10.4103\/apc.APC_79_18","article-title":"Symptomatic improvement using everolimus in infants with cardiac rhabdomyoma","volume":"12","author":"Dhulipudi","year":"2019","journal-title":"Ann. Pediatr. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e213","DOI":"10.1055\/s-0039-1692198","article-title":"Effect and Complications of Everolimus Use for Giant Cardiac Rhabdomyomas with Neonatal Tuberous Sclerosis","volume":"9","author":"Shibata","year":"2019","journal-title":"AJP Rep."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1017\/S1047951118000598","article-title":"Giant left ventricular rhabdomyoma treated successfully with everolimus: Case report and review of literature","volume":"28","year":"2018","journal-title":"Cardiol. Young"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1007\/s00246-017-1688-4","article-title":"Regression of Neonatal Cardiac Rhabdomyoma in Two Months Through Low-Dose Everolimus Therapy: A Report of Three Cases","volume":"38","author":"Chang","year":"2017","journal-title":"Pediatr. Cardiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1017\/S1047951116000421","article-title":"Everolimus-induced near-resolution of giant cardiac rhabdomyomas and large renal angiomyolipoma in a newborn with tuberous sclerosis complex","volume":"26","author":"Colaneri","year":"2016","journal-title":"Cardiol. Young"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"bcr2015212946","DOI":"10.1136\/bcr-2015-212946","article-title":"Rapid resolution of cardiac rhabdomyomas following everolimus therapy","volume":"2015","author":"Choudhry","year":"2015","journal-title":"BMJ Case Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1111\/echo.13015","article-title":"Oral Everolimus for Treatment of a Giant Left Ventricular Rhabdomyoma in a Neonate-Rapid Tumor Regression Documented by Real Time 3D Echocardiography","volume":"32","author":"Wagner","year":"2015","journal-title":"Echocardiography"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1093\/tropej\/fmu056","article-title":"Regression of symptomatic multiple cardiac rhabdomyomas associated with tuberous sclerosis complex in a newborn receiving everolimus","volume":"61","author":"Beken","year":"2015","journal-title":"J. Trop. Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1017\/S1047951114002261","article-title":"Everolimus treatment of a newborn with rhabdomyoma causing severe arrhythmia","volume":"25","author":"Atik","year":"2015","journal-title":"Cardiol. Young"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1335","DOI":"10.1542\/peds.2010-2910","article-title":"Regression of a cardiac rhabdomyoma in apatient receiving everolimus","volume":"127","author":"Tiberio","year":"2011","journal-title":"Pediatrics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jpeds.2017.06.076","article-title":"Everolimus for the Treatment of Tuberous Sclerosis Complex-Related Cardiac Rhabdomyomas in Pediatric Patients","volume":"190","author":"Dahdah","year":"2017","journal-title":"J. Pediatr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/ped.12816","article-title":"Regression of massive cardiac rhabdomyoma on everolimus therapy","volume":"58","author":"Hoshal","year":"2016","journal-title":"Pediatr. Int."}],"container-title":["Pediatric Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2036-7503\/13\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:30:43Z","timestamp":1760160643000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2036-7503\/13\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":23,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["pediatric13010015"],"URL":"https:\/\/doi.org\/10.3390\/pediatric13010015","relation":{},"ISSN":["2036-7503"],"issn-type":[{"value":"2036-7503","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]}}}