The Impact of Levothyroxine on Cardiac Function in Older Adults With Mild Subclinical Hypothyroidism: A Randomized Clinical Trial - 23/07/20

Doi : 10.1016/j.amjmed.2020.01.018

Baris Gencer, MD ^a,^b, Elisavet Moutzouri, MD, PhD ^c,^d, Manuel R. Blum, MD ^d,^e, Martin Feller, MD, MSc ^c,^d, Tinh-Hai Collet, MD ^f, Cinzia Delgiovane, PhD ^c, Bruno R. da Costa, PhD ^c,^g, Eric Buffle, MD ^h, Pierre Monney, MD ⁱ, Vincent Gabus, MD ⁱ, Hajo Müller, MD ^a, Gerasimos P. Sykiotis, MD, PhD ^f, Patricia Kearney, MD, PhD ^j, Jacobijn Gussekloo, MD, PhD ^k, Rudi Westendorp, MD, PhD ^l, David J. Stott, MB, ChB, MD ^m, Douglas C. Bauer, MD ⁿ, Nicolas Rodondi, MD, MAS ^c,^d,^⁎
^a Service of Cardiology, University Hospitals of Geneva, University of Geneva, Switzerland
^b TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
^c Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
^d Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland
^e Department of Health Research & Policy, Stanford University School of Medicine, Stanford, Calif
^f Service of Endocrinology, Diabetes and Metabolism, Department of Medicine, Lausanne University Hospital, University of Lausanne, Switzerland
^g Applied Health Research Centre (AHRC), Li Ka Shing Knowledge Institute of St. Michael's Hospital, Institute of Health Policy, Management, and Evaluation, University of Toronto, Toronto, Ontario, Canada
^h Department of Cardiology, University of Bern, Bern, Switzerland
ⁱ Service of Cardiology, Department of Heart and Vessels, Lausanne University Hospital, University of Lausanne, Switzerland
^j University College Cork, Cork, Ireland
^k Leiden University Medical Center, Leiden, Netherlands
^l Center for Healthy Aging, University of Copenhagen, Denmark
^m Institute of Cardiovascular and Medical Sciences, University of Glasgow, Scotland, UK
ⁿ University of San Francisco, California, United States

^⁎Requests for reprints should be addressed to Professor Nicolas Rodondi, MD, MAS, Head of Ambulatory Care, Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, 3010 Bern Switzerland.Department of General Internal MedicineInselspitalBern University HospitalUniversity of BernBern3010Switzerland

ABSTRACT

Background

Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function.

Methods

In a randomized, double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants ages ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone [TSH] 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e′ ratio) for diastolic function. Secondary outcomes included e′ lateral/septal, left atrial volume index, and systolic pulmonary artery pressure.

Results

A total of 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n = 96), and it remained elevated at 5.29 mIU/L with placebo (n = 89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs 62.5%, difference = 0.4%, 95% confidence interval −1.8% to 2.5%, P = 0.72) and the E/e′ ratio (10.6 vs 10.1, difference 0.4, 95% confidence interval −0.7 to 1.4, P = 0.47). No differences were found for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, preexisting heart failure, and treatment duration (P value >0.05).

Conclusion

Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism.

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Keywords : Clinical trials, Heart failure, Levothyroxine, Subclinical hypothyroidism, Thyroid

Plan

Thyroid Function Tests

Systolic and Diastolic Cardiac Function

DISCUSSION

CONCLUSION

	Funding: This study was supported grants of the Swiss National Science Foundation to NR (SNSF 320030-150025 and 320030-172676), and investigator-driven grants of the Velux Stiftung (974a, to NR) and of the Swiss Heart Foundation (to NR). The TRUST Trial was supported by a research grant (grant agreement number 278148) from the European Union FP7-HEALTH-2011 program).
	Conflicts of Interest: BG research activities in the TIMI group (Harvard Medical School) supported by grants from the Geneva University Hospitals, Eugenio Litta, and Arthemis Foundations. MRB supported by an intramural personal grant by the Clinical Trials Unit of the Bern University Hospital (grant number 84801053) and by a grant from the Swiss National Science Foundation (P2BEP3_175289). MF supported by an intramural personal grant by the Clinical Trials Unit of the Bern University Hospital (grant number 84801319). T-HC research supported by grants from the Swiss National Science Foundation (PZ00P3-167826). GPS research supported by the Leenaards Foundation (2016 Fellowship for Academic Promotion in Clinical Medicine) and discloses grants and personal fees unrelated to the submitted work from IBSA, Merck, Alfa-Sigma, and Sanofi-Genzyme. Merck KGaA provided study medication as an investigator grant free of any cost or charges. EM, CD, BRdC, EB, PM, VG, HM, PK, JG, RW, DJS, DCB, NR report none. Merck KGaA reviewed the manuscript for medical accuracy before journal submission but played no role in the design, analysis, or reporting of the trial.
	Authorship: All authors had access to the data and a role in writing this manuscript.

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Vol 133 - N° 7

P. 848 - juillet 2020 Retour au numéro

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The Impact of Levothyroxine on Cardiac Function in Older Adults With Mild Subclinical Hypothyroidism: A Randomized Clinical Trial - 23/07/20

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