{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T06:31:55Z","timestamp":1747204315476,"version":"3.40.5"},"posted":{"date-parts":[[2022,9,13]]},"group-title":"In Review","reference-count":21,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T00:00:00Z","timestamp":1663027200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2022,9,7]]},"abstract":"<title>Abstract<\/title>\n        <p>Purpose\n Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of T4 into T3 is thought to decrease the availability of T3 and contribute to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (TH) are associated with clinical status and outcomes.\nMethods\n We evaluated 79 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modelling to study the associations of TH and FT3\/FT4 ratio with clinical and echocardiographic parameters, and survival analysis to evaluate associations with the composite of urgent HF visit, HF hospitalization or cardiovascular death, over a median follow-up of 2.8 years.\nResults\n The mean age was 73.5 years and 47% were men. The mean FT3\/FT4 ratio was 2.63 (SD 0.43). Subjects with lower FT3\/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3\/FT4 ratio was associated with higher body fat (\u03b2=-5.60kg per FT3\/FT4 unit, p\u2009=\u20090.034), higher pulmonary arterial systolic pressure (PASP) (\u03b2=-10.26mmHg, p\u2009=\u20090.002) and lower left ventricular ejection fraction (LVEF) (\u03b2\u2009=\u20093.60%, p\u2009=\u20090.008). Lower FT3\/FT4 ratio was associated with higher risk for the composite HF outcome (HR\u2009=\u20092.50, 95%CI 1.04\u20135.88, per 1-unit decrease in FT3\/FT4, p\u2009=\u20090.041).\nConclusions\n In patients with HFpEF, lower FT3\/FT4 ratio was associated with higher body fat, higher PASP and lower LVEF. Lower FT3\/FT4 predicted a higher risk of urgent HF visit, HF hospitalization or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion may be associated with HFpEF progression.<\/p>","DOI":"10.21203\/rs.3.rs-2042487\/v1","type":"posted-content","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T20:48:45Z","timestamp":1663102125000},"source":"Crossref","is-referenced-by-count":0,"title":["Clinical and pathophysiologic insights of FT3\/FT4 ratio in patients with Heart Failure with Preserved Ejection Fraction: data from the NETDiamond cohort"],"prefix":"10.21203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4111-3787","authenticated-orcid":false,"given":"Ana Rita","family":"Leite","sequence":"first","affiliation":[{"name":"Cardiovascular R&D Center - UniC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Jo\u00e3o S\u00e9rgio","family":"Neves","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Ang\u00e9lico-Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Francisco","family":"Vasques-N\u00f3voa","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Francisca A.","family":"Saraiva","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"In\u00eas Beatriz","family":"Pinho","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Ana Cristina","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Marta","family":"Borges-Canha","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Madalena","family":"von Hafe","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Catarina","family":"Vale","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Andr\u00e9 P.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Jos\u00e9 Paulo","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Centro Hospitalar Universit\u00e1rio S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Pedro","family":"von Hafe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Jorge","family":"Almeida","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Centro Hospitalar Universit\u00e1rio de S\u00e3o Jo\u00e3o, Porto, Portugal"}]},{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal"}]},{"given":"Adelino","family":"Leite-Moreira","sequence":"additional","affiliation":[{"name":"Cardiovascular R&D Center - UnIC@RISE, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Portugal"}]}],"member":"297","reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1089\/thy.2018.0416","article-title":"Thyroid and Cardiovascular Disease: Research Agenda for Enhancing Knowledge, Prevention, and Treatment","volume":"29","author":"Cappola AR","year":"2019","unstructured":"A.R. Cappola, A.S. Desai, M. Medici, L.S. Cooper, D. Egan, G. Sopko, G.I. Fishman, S. Goldman, D.S. Cooper, S. Mora, P.J. Kudenchuk, A.N. Hollenberg, C.L. McDonald, P.W. Ladenson, Thyroid and Cardiovascular Disease: Research Agenda for Enhancing Knowledge, Prevention, and Treatment. Thyroid. 29, 760\u2013777 (2019). https:\/\/doi.org\/10.1089\/thy.2018.0416","journal-title":"Thyroid."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1172\/JCI107825","article-title":"Thyroid hormone action: in vitro characterization of solubilized nuclear receptors from rat liver and cultured GH1 cells","volume":"54","author":"Samuels HH","year":"1974","unstructured":"H.H. Samuels, J.S. Tsai, J. Casanova, F. Stanley, Thyroid hormone action: in vitro characterization of solubilized nuclear receptors from rat liver and cultured GH1 cells. J. Clin. Invest. 54, 853\u2013865 (1974). https:\/\/doi.org\/10.1172\/JCI107825","journal-title":"J. Clin. Invest."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2571","DOI":"10.1172\/JCI29812","article-title":"Deiodinases: implications of the local control of thyroid hormone action","volume":"116","author":"Bianco AC","year":"2006","unstructured":"A.C. Bianco, B.W. Kim, Deiodinases: implications of the local control of thyroid hormone action. J. Clin. Invest. 116, 2571 (2006). https:\/\/doi.org\/10.1172\/JCI29812","journal-title":"J. Clin. Invest."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s10557-019-06870-4","article-title":"The Role of Thyroid Hormones in Heart Failure","volume":"33","author":"Vale C","year":"2019","unstructured":"C. Vale, J.S. Neves, M. von Hafe, M. Borges-Canha, A. Leite-Moreira, The Role of Thyroid Hormones in Heart Failure. Cardiovasc. Drugs Ther. 33, 179\u2013188 (2019). https:\/\/doi.org\/10.1007\/s10557-019-06870-4","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s12020-019-02050-4","article-title":"Novel uses of thyroid hormones in cardiovascular conditions","volume":"66","author":"Razvi S","year":"2019","unstructured":"S. Razvi, Novel uses of thyroid hormones in cardiovascular conditions. Endocrine. 66, 115\u2013123 (2019). https:\/\/doi.org\/10.1007\/s12020-019-02050-4","journal-title":"Endocrine."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1016\/j.hfc.2019.02.008","article-title":"The Management of Thyroid Abnormalities in Chronic Heart Failure. Hear","volume":"15","author":"Biondi B","year":"2019","unstructured":"B. Biondi, The Management of Thyroid Abnormalities in Chronic Heart Failure. Hear. Fail. Clin. 15, 393\u2013398 (2019). https:\/\/doi.org\/10.1016\/j.hfc.2019.02.008","journal-title":"Fail. Clin."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1172\/JCI44678","article-title":"IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells","volume":"121","author":"Wajner SM","year":"2011","unstructured":"S.M. Wajner, I.M. Goemann, A.L. Bueno, P.R. Larsen, A.L. Maia, IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. J. Clin. Invest. 121, 1834\u20131845 (2011). https:\/\/doi.org\/10.1172\/JCI44678","journal-title":"J. Clin. Invest."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1530\/JOE-10-0481","article-title":"Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease","volume":"209","author":"Maia AL","year":"2011","unstructured":"A.L. Maia, I.M. Goemann, E.L. Meyer, S.M. Wajner, Deiodinases: the balance of thyroid hormone: type 1 iodothyronine deiodinase in human physiology and disease. J. Endocrinol. 209, 283\u2013297 (2011). https:\/\/doi.org\/10.1530\/JOE-10-0481","journal-title":"J. Endocrinol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/j.numecd.2020.10.011","article-title":"Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease","volume":"31","author":"Yuan D","year":"2021","unstructured":"D. Yuan, C. Zhang, S. Jia, Y. Liu, L. Jiang, L. Xu, Y. Zhang, J. Xu, B. Xu, R. Hui, R. Gao, Z. Gao, L. Song, J. Yuan, Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr. Metab. Cardiovasc. Dis. 31, 579\u2013586 (2021). https:\/\/doi.org\/10.1016\/j.numecd.2020.10.011","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.ejheart.2004.04.016","article-title":"Relation between free triiodothyronine\/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy","volume":"7","author":"Kozdag G","year":"2005","unstructured":"G. Kozdag, D. Ural, A. Vural, A. Agacdiken, G. Kahraman, T. Sahin, E. Ural, B. Komsuoglu, Relation between free triiodothyronine\/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur. J. Heart Fail. 7, 113\u2013118 (2005). https:\/\/doi.org\/10.1016\/j.ejheart.2004.04.016","journal-title":"Eur. J. Heart Fail."},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1177\/2042018820958331","article-title":"Thyroid hormones and modulation of diastolic function: a promising target for heart failure with preserved ejection fraction","author":"Neves JS","year":"2020","unstructured":"J.S. Neves, C. Vale, M. von Hafe, M. Borges-Canha, A.R. Leite, J. Almeida-Coelho, A. Louren\u00e7o, I. Falc\u00e3o-Pires, D. Carvalho, A. Leite-Moreira, Thyroid hormones and modulation of diastolic function: a promising target for heart failure with preserved ejection fraction, http:\/\/journals.sagepub.com\/doi\/10.1177\/2042018820958331, (2020)"},{"year":"2021","author":"McDonagh TA","key":"ref12","unstructured":"T.A. McDonagh, M. Metra, M. Adamo, R.S. Gardner, A. Baumbach, M. B\u00f6hm, H. Burri, J. Butler, J. Celutkiene, O. Chioncel, J.G.F. Cleland, A.J.S. Coats, M.G. Crespo-Leiro, D. Farmakis, M. Gilard, S. Heymans: 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure, https:\/\/academic.oup.com\/eurheartj\/article\/42\/36\/3599\/6358045, (2021)"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1007\/S10741-016-9554-7\/FIGURES\/2","article-title":"Thyroid hormones and cardiac remodeling","volume":"21","author":"Cokkinos DV","year":"2016","unstructured":"D.V. Cokkinos, S. Chryssanthopoulos, Thyroid hormones and cardiac remodeling. Heart Fail. Rev. 21, 365\u2013372 (2016). https:\/\/doi.org\/10.1007\/S10741-016-9554-7\/FIGURES\/2","journal-title":"Heart Fail. Rev."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.amjcard.2012.02.068","article-title":"Association of serum triiodothyronine with B-type natriuretic peptide and severe left ventricular diastolic dysfunction in heart failure with preserved ejection fraction","volume":"110","author":"Selvaraj S","year":"2012","unstructured":"S. Selvaraj, I. Klein, S. Danzi, N. Akhter, R.O. Bonow, S.J. Shah, Association of serum triiodothyronine with B-type natriuretic peptide and severe left ventricular diastolic dysfunction in heart failure with preserved ejection fraction. Am. J. Cardiol. 110, 234\u2013239 (2012). https:\/\/doi.org\/10.1016\/j.amjcard.2012.02.068","journal-title":"Am. J. Cardiol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1111\/NYAS.12374","article-title":"Thyroid hormone signaling in energy homeostasis and energy metabolism","volume":"1311","author":"Mcaninch EA","year":"2014","unstructured":"E.A. Mcaninch, A.C. Bianco, Thyroid hormone signaling in energy homeostasis and energy metabolism. Ann. N Y Acad. Sci. 1311, 77\u201387 (2014). https:\/\/doi.org\/10.1111\/NYAS.12374","journal-title":"Ann. N Y Acad. Sci."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1161\/CIRCEP.113.000502","article-title":"Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats","volume":"6","author":"Zhang Y","year":"2013","unstructured":"Y. Zhang, E.I. Dedkov, D. Teplitsky, N.Y. Weltman, C.J. Pol, V. Rajagopalan, B. Lee, M. Gerdes, A.: Both hypothyroidism and hyperthyroidism increase atrial fibrillation inducibility in rats. Circ. Arrhythmia Electrophysiol. 6, 952\u2013959 (2013). https:\/\/doi.org\/10.1161\/CIRCEP.113.000502","journal-title":"Circ. Arrhythmia Electrophysiol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1119","DOI":"10.1016\/J.JACC.2008.11.051","article-title":"Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study","volume":"53","author":"Lam CSP","year":"2009","unstructured":"C.S.P. Lam, V.L. Roger, R.J. Rodeheffer, B.A. Borlaug, F.T. Enders, M.M. Redfield, Pulmonary hypertension in heart failure with preserved ejection fraction: a community-based study. J. Am. Coll. Cardiol. 53, 1119\u20131126 (2009). https:\/\/doi.org\/10.1016\/J.JACC.2008.11.051","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"e005266","DOI":"10.1161\/CIRCHEARTFAILURE.118.005266","article-title":"Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes","volume":"11","author":"Kannan L","year":"2018","unstructured":"L. Kannan, P.A. Shaw, M.P. Morley, J. Brandimarto, J.C. Fang, N.K. Sweitzer, T.P. Cappola, A.R. Cappola, Thyroid Dysfunction in Heart Failure and Cardiovascular Outcomes. Circ. Hear. Fail. 11, e005266 (2018). https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.118.005266","journal-title":"Circ. Hear. Fail."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/0735-1097(90)90462-X","article-title":"Altered thyroid hormone metabolism in advanced heart failure","volume":"16","author":"Hamilton MA","year":"1990","unstructured":"M.A. Hamilton, L.W. Stevenson, M. Luu, J.A. Walden, Altered thyroid hormone metabolism in advanced heart failure. J. Am. Coll. Cardiol. 16, 91\u201395 (1990). https:\/\/doi.org\/https:\/\/doi.org\/10.1016\/0735-1097(90)90462-X","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"888","DOI":"10.3389\/fcvm.2022.859608","article-title":"Value of FT3\/FT4 Ratio in Prognosis of Patients With Heart Failure: A Propensity-Matched Study","volume":"9","author":"Wang C","year":"2022","unstructured":"C. Wang, S. Han, Y. Li, F. Tong, Z. Li, Z. Sun, Value of FT3\/FT4 Ratio in Prognosis of Patients With Heart Failure: A Propensity-Matched Study. Front. Cardiovasc. Med. 9, 888 (2022). https:\/\/doi.org\/10.3389\/fcvm.2022.859608","journal-title":"Front. Cardiovasc. Med."},{"key":"ref21","unstructured":"Statements & Declarations"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2042487\/v1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2042487\/v1.html","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T21:03:43Z","timestamp":1664571823000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.researchsquare.com\/article\/rs-2042487\/v1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,13]]},"references-count":21,"URL":"https:\/\/doi.org\/10.21203\/rs.3.rs-2042487\/v1","relation":{},"subject":[],"published":{"date-parts":[[2022,9,13]]},"subtype":"preprint"}}