{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T15:35:44Z","timestamp":1774366544362,"version":"3.50.1"},"reference-count":52,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T00:00:00Z","timestamp":1733097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: The thyroid gland has an important influence on the heart. Long-term exposure to high levels of thyroid hormones may lead to cardiac hypertrophy and dysfunction. The aim of the study was to evaluate the morphological and functional changes in the left ventricle in patients with hyperthyroidism caused by Graves\u2019 disease (GD) in comparison with healthy individuals, as well as to investigate potential differences in these parameters in GD patients in relation to the presence of orbitopathy. Methods: The prospective study included 39 patients with clinical manifestations and laboratory confirmation of GD and 35 healthy controls. All participants underwent a detailed echocardiographic examination. The groups were compared according to demographic characteristics (age and gender), heart rate and echocardiographic characteristics. Results: The patients with hyperthyroidism caused by GD had significantly higher values of left ventricular diameter, left ventricular volume and left ventricular mass compared to the healthy controls. In addition, hyperthyroidism significantly influenced the left ventricular contractility and led to the deterioration of the systolic and diastolic function, as shown together by longitudinal strain, color Doppler and tissue Doppler imaging. However, the patients with GD and orbitopathy showed better left ventricular function than those without orbitopathy. Conclusions: Besides the confirmation of previously known findings, our study indicates possible differences in echocardiographic parameters in GD patients in relation to the presence of orbitopathy. Further investigation with larger samples and meta-analyses of data focused on the evaluation of echocardiographic findings in the context of detailed biochemical and molecular analyses is required to confirm our preliminary results and their clinical significance.<\/jats:p>","DOI":"10.3390\/jcm13237348","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T11:48:56Z","timestamp":1733226536000},"page":"7348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impairment of Left Ventricular Function in Hyperthyroidism Caused by Graves\u2019 Disease: An Echocardiographic Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9841-9458","authenticated-orcid":false,"given":"Ivana","family":"Petrovic Djordjevic","sequence":"first","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5863-6157","authenticated-orcid":false,"given":"Marija","family":"Radomirovic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Petrovic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bojana","family":"Biorac","sequence":"additional","affiliation":[{"name":"Clinic for Digestive Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zvezdana","family":"Jemuovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3758-3719","authenticated-orcid":false,"given":"Milorad","family":"Tesic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2923-4145","authenticated-orcid":false,"given":"Danijela","family":"Trifunovic Zamaklar","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5552-773X","authenticated-orcid":false,"given":"Ivana","family":"Nedeljkovic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Biljana","family":"Nedeljkovic Beleslin","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dragan","family":"Simic","sequence":"additional","affiliation":[{"name":"Clinic for Cardiology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9977-5970","authenticated-orcid":false,"given":"Milos","family":"Zarkovic","sequence":"additional","affiliation":[{"name":"Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bosiljka","family":"Vujisic-Tesic","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ITC49","DOI":"10.7326\/AITC202004070","article-title":"Hyperthyroidism","volume":"172","author":"McDermott","year":"2020","journal-title":"Ann. Intern Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1152\/physrev.00030.2013","article-title":"Thyroid hormone regulation of metabolism","volume":"94","author":"Mullur","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.mcna.2012.01.007","article-title":"Thyroid physiology","volume":"96","author":"Stathatos","year":"2012","journal-title":"Med. Clin. N. Am."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"136","DOI":"10.31083\/j.rcm2304136","article-title":"Cardiac manifestations in hyperthyroidism","volume":"23","author":"Cruz","year":"2022","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1515\/hmbci-2013-0059","article-title":"Thyroid hormones and the heart","volume":"18","year":"2014","journal-title":"Horm. Mol. Biol. Clin. Investig."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41574-019-0218-2","article-title":"Deiodinases and their intricate role in thyroid hormone homeostasis","volume":"15","author":"Luongo","year":"2019","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"60","DOI":"10.14797\/mdcj-13-2-60","article-title":"Hyperthyroidism and the heart","volume":"13","author":"Osuna","year":"2017","journal-title":"Methodist Debakey Cardiovasc. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4235","DOI":"10.1210\/endo.137.10.8828482","article-title":"Uptake of thyroid hormones in neonatal ratcardiac myocytes","volume":"137","author":"Everts","year":"1996","journal-title":"Endocrinology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1056\/NEJM199409293311306","article-title":"The molecular basis of thyroid hormone action","volume":"331","author":"Brent","year":"1994","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1210\/er.2003-0033","article-title":"Thyroid hormone action in the heart","volume":"26","author":"Kahaly","year":"2005","journal-title":"Endocrine Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S1043-2760(00)00263-0","article-title":"Gene regulation by thyroid hormone","volume":"11","author":"Wu","year":"2000","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/S1043-2760(99)00215-5","article-title":"Transcriptional repression by nuclear hormone receptors","volume":"11","author":"Hu","year":"2000","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14104","DOI":"10.1073\/pnas.0601600103","article-title":"Rapid nongenomic actions of thyroid hormone","volume":"103","author":"Hiroi","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrendo.2015.205","article-title":"Nongenomic actions of thyroid hormone","volume":"12","author":"Davis","year":"2016","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1136\/heart.84.4.455","article-title":"Thyroid Disease and the Heart","volume":"84","author":"Toft","year":"2000","journal-title":"Heart"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R76","DOI":"10.1530\/EC-19-0096","article-title":"The impact of thyroid hormone dysfunction on ischemic heart disease","volume":"8","author":"Neves","year":"2019","journal-title":"Endocr. Connect."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"101388","DOI":"10.1016\/j.beem.2020.101388","article-title":"Graves\u2019 disease: Clinical manifestations, immune pathogenesis (cytokines and chemokines) and therapy","volume":"34","author":"Antonelli","year":"2020","journal-title":"Best. Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kulbay, M., Tanya, S.M., Tuli, N., Dahoud, J., Dahoud, A., Alsaleh, F., Arthurs, B., and El-Hadad, C. (2024). A Comprehensive Review of Thyroid Eye Disease Pathogenesis: From Immune Dysregulations to Novel Diagnostic and Therapeutic Approaches. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252111628"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhou, H., Muller, I., Chong, K.K.-L., Ludgate, M., and Fang, S. (2022). Editorial: Mechanisms and Novel Therapies in Graves\u2019 Orbitopathy: Current Update. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.902591"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1136\/heartjnl-2021-319752","article-title":"Incidence, risk factors, natural history and outcomes of heart failure in patients with Graves\u2019 disease","volume":"108","author":"Naser","year":"2022","journal-title":"Heart"},{"key":"ref_21","unstructured":"Fox, T.J., and Anastasopoulou, C. (2024, November 17). Graves Orbitopathy. [Updated 2023 Aug 28], StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK549889\/."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"G43","DOI":"10.1530\/EJE-21-0479","article-title":"The 2021 European Group on Graves\u2019 orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves\u2019 orbitopathy","volume":"185","author":"Bartalena","year":"2021","journal-title":"Eur. J. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/s41574-019-0305-4","article-title":"New insights into the pathogenesis and nonsurgical management of Graves orbitopathy","volume":"16","author":"Taylor","year":"2020","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/j.1365-2265.1996.tb02068.x","article-title":"Cardiomyopathy associated with Graves\u2019 disease","volume":"45","author":"Koshiyama","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1007\/s40618-020-01341-2","article-title":"Putative protective role of autoantibodies against the insulin-like growth factor-1 receptor in Graves\u2019 Disease: Results of a pilot study","volume":"43","author":"Lanzolla","year":"2020","journal-title":"J. Endocrinol. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Macvanin, M., Gluvic, Z., Radovanovic, J., Essack, M., Gao, X., and Isenovic, E.R. (2023). New insights on the cardiovascular effects of IGF-1. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1142644"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, B., Li, Z., and Huang, Y. (2021). Investigating changes in cardiac function and structure of left ventricle by speckle-tracking echocardiography in patients with hyperthyroidism and Graves\u2019 disease. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.695736"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/00015385.2019.1708598","article-title":"Assessment of subclinical left ventricular dysfunction with speckle-tracking echocardiography in hyperthyroid and euthyroid Graves\u2019 disease and its correlation with serum TIMP-1","volume":"76","author":"Duzen","year":"2021","journal-title":"Acta Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s00431-017-3039-0","article-title":"Left ventricular functions in children with newly diagnosed Graves\u2019 disease. A single-center study from Upper Egypt","volume":"177","author":"Metwalley","year":"2018","journal-title":"Eur. J. Pediatr."},{"key":"ref_30","first-page":"226","article-title":"Ventricular functions in patients with Graves\u2019 ophthalmopathy","volume":"22","author":"Yeter","year":"2010","journal-title":"Turkiye Klinikleri J. Cardiovasc. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Li, H., Zeng, R., Liao, Y., Fu, M., Zhang, H., Wang, L., and Li, Y. (2021). Prevalence and risk factors of left ventricular diastolic dysfunction in patients with hyperthyroidism. Front. Endocrinol., 8.","DOI":"10.3389\/fendo.2020.605712"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"944","DOI":"10.5114\/aoms.2013.38685","article-title":"Hyperthyroidism and cardiovascular complications: A narrative review on the basis of pathophysiology","volume":"9","author":"Ertek","year":"2013","journal-title":"Arch. Med. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3","DOI":"10.14797\/mdcvj.197","article-title":"The cardiovascular effects of hyperthyroidism","volume":"6","author":"Nabbout","year":"2010","journal-title":"Methodist DeBakey Cardiovasc. J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"741861","DOI":"10.1100\/2012\/741861","article-title":"Oxidative stress and heart failure in altered thyroid states","volume":"2012","author":"Mishra","year":"2012","journal-title":"Sci. World J."},{"key":"ref_35","first-page":"296","article-title":"Effects of thyroid hormones on the heart","volume":"26","year":"2014","journal-title":"Clin. Investig. Arterioscler."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cpcardiol.2015.04.002","article-title":"Thyroid disease and the heart","volume":"41","author":"Klein","year":"2016","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s11897-008-0026-9","article-title":"Thyrotoxic cardiac disease","volume":"5","author":"Dahl","year":"2008","journal-title":"Curr. Heart Fail Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1016\/j.hlc.2016.10.007","article-title":"Hyperdynamic right heart function in Graves\u2019 hyperthyroidism measured by echocardiography normalises on restoration of euthyroidism","volume":"26","author":"Teasdale","year":"2017","journal-title":"Heart Lung Circ."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1016\/j.bbadis.2017.08.029","article-title":"Insulin-like growth factor-1 signaling in cardiac aging","volume":"1864 Pt B","author":"Lee","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1111\/j.1365-2265.2011.03981.x","article-title":"Hyperthyroidism-induced left ventricular diastolic dysfunction: Implication in hyperthyroidism-related heart failure","volume":"74","author":"Yue","year":"2011","journal-title":"Clin. Endocrinol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.jchf.2013.07.008","article-title":"Thyroid-stimulating hormone and clinical outcomes: The CORONA trial (controlled rosuvastatin multinational study in heart failure)","volume":"2","author":"Perez","year":"2014","journal-title":"JACC Heart Fail"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1136\/hrt.2006.100628","article-title":"Incidence, clinical characteristics and outcome of congestive heart failure as the initial presentation in patients with primary hyperthyroidism","volume":"93","author":"Siu","year":"2007","journal-title":"Heart"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Yang, G., Wang, Y., Ma, A., and Wang, T. (2019). Subclinical thyroid dysfunction is associated with adverse prognosis in heart failure patients with reduced ejection fraction. BMC Cardiovasc. Disord., 19.","DOI":"10.1186\/s12872-019-1055-x"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/s10741-016-9556-5","article-title":"Thyroid hormones and heart failure","volume":"21","author":"Martinez","year":"2016","journal-title":"Heart Fail Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11897-017-0312-5","article-title":"Thyroid Dysfunction and Heart Failure: Mechanisms and Associations","volume":"14","year":"2017","journal-title":"Curr. Heart Fail Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1530\/EJE-12-0627","article-title":"Mechanisms in endocrinology: Heart failure and thyroid dysfunction","volume":"167","author":"Biondi","year":"2012","journal-title":"Eur. J. Endocrinol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1097\/XCE.0000000000000241","article-title":"Speckle tracking echocardiographic assessment of left ventricular longitudinal strain in female patients with subclinical hyperthyroidism","volume":"10","author":"Abdelrazk","year":"2020","journal-title":"Cardiovasc. Endocrinol. Metab."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1002\/jcu.22802","article-title":"Changes in left ventricular function and contractile homogeneity in young adults with newly diagnosed hyperthyroidism due to Graves\u2019 disease","volume":"48","author":"Zhou","year":"2020","journal-title":"J. Clin. Ultrasound"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2248","DOI":"10.21037\/qims-22-534","article-title":"Evaluation of left ventricular myocardial work in patients with hyperthyroidism with different heart rates with noninvasive pressure-strain loop based on two-dimensional speck tracking imaging","volume":"13","author":"Liu","year":"2023","journal-title":"Quant. Imaging Med. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/jcu.23459","article-title":"Four-dimensional speckle tracking echocardiography and fragmented QRS in detection of early left ventricular systolic dysfunction in patients with subclinical hyperthyroidism","volume":"51","author":"Karaca","year":"2023","journal-title":"J. Clin. Ultrasound"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1002\/jcu.23468","article-title":"Early echocardiographic and electrophysiological characteristics of subclinical hyperthyroidism","volume":"51","author":"Kerkhof","year":"2023","journal-title":"J. Clin. Ultrasound"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e86","DOI":"10.1093\/ehjci\/jead046","article-title":"Resting global longitudinal strain and stress echocardiography to detect coronary artery disease burden","volume":"24","author":"Pizzi","year":"2023","journal-title":"Eur. Heart J. Cardiovasc. Imaging"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/23\/7348\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:45:12Z","timestamp":1760114712000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/13\/23\/7348"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,2]]},"references-count":52,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["jcm13237348"],"URL":"https:\/\/doi.org\/10.3390\/jcm13237348","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,2]]}}}