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Wang W, Zhang X, Gao J, Meng X, Wang J, Zhang K, Chen J, Qi J, Shao C, Tang YD. Effects of levothyroxine in subclinical hypothyroidism and heart failure with reduced ejection fraction: An open-label randomized trial. Cell Rep Med 2024; 5:101473. [PMID: 38537636 PMCID: PMC11031377 DOI: 10.1016/j.xcrm.2024.101473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 01/05/2024] [Accepted: 02/21/2024] [Indexed: 04/19/2024]
Abstract
We report a randomized, multicenter, open-label trial (ClinicalTrials.gov: NCT03096613) to investigate the clinical benefits of levothyroxine (L-T4) administration in subclinical hypothyroidism (SCH) patients with heart failure with reduced ejection fraction (HFrEF). Overall, 117 patients were enrolled and received L-T4 plus standard HFrEF treatment (experimental group, N = 57) or standard HFrEF therapy alone (control group, N = 60). The change of 6-min walk test distance in the experimental group was significantly higher than that in the control group at 24 weeks (70.08 ± 85.76 m vs. 27.73 ± 82.00 m, mean difference [95% confidence interval (CI)] 46.90 [12.90, 80.90], p < 0.001). Improvements in New York Heart Association (NYHA) classification (p = 0.033) and thyroid function were significant. Adverse event incidence was similar between groups (risk ratio [95% CI]: 0.942 1.053 (0.424, 2.616); p = 0.628). L-T4 addition to HFrEF treatment improved activity tolerance, NYHA class, and thyroid function within 6 months, suggesting its potential for combined therapy in HFrEF patients with SCH. Future double-blind, placebo-controlled trials should be performed to confirm these results.
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Affiliation(s)
- Wenyao Wang
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Xuan Zhang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jun Gao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Xiangbin Meng
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Jingjia Wang
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Kuo Zhang
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jing Chen
- Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiating Qi
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Chunli Shao
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China
| | - Yi-Da Tang
- Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, China.
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Turić I, Velat I, Bušić Ž, Čulić V. Circulating thyroid hormones and clinical parameters of heart failure in men. Sci Rep 2023; 13:20319. [PMID: 37985786 PMCID: PMC10662258 DOI: 10.1038/s41598-023-47391-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 11/13/2023] [Indexed: 11/22/2023] Open
Abstract
Heart failure (HF) is a multiple hormonal deficiency syndrome which includes alterations in the serum concentration of thyroid hormones (TH). This cross-sectional study enrolled 215 male patients hospitalised for acute HF. Data on cardiovascular risk factors, chronic medications, cardiac function assessed by echocardiography, and clinical parameters of HF were prospectively collected. The independent predictive association of TH with all investigated parameters of the HF severity were assessed. The patient's mean age was 74.4 years, 57.2% had arterial hypertension, 54.0% were consuming alcohol, and 42.3% were diabetics. Multivariate analysis revealed that total triiodothyronine (TT3) was an independent predictor of greater left ventricular ejection fraction (LVEF; β = 0.223, p = 0.008), less progressed left ventricular diastolic dysfunction (LVDD; β = - 0.271, p = 0.001) and lower N-terminal pro-brain natriuretic peptide (NT-proBNP; β = - 0.365, p < 0.001). None of the TH other than TT3 was associated with LVDD or NT-proBNP, whereas free triiodothyronine (β = - 0.197, p = 0.004), free thyroxine (β = - 0.223, p = 0.001) and total thyroxine (β = - 0.140, p = 0.041) were inversely associated with LVEF. The present study suggests that, among TH, serum TT3 level is most closely associated with echocardiographic, laboratory and clinical parameters of the severity of HF in men.
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Affiliation(s)
- Iva Turić
- Department of Cardiology and Angiology, University Hospital Centre Split, 21000, Split, Croatia
| | - Ivan Velat
- Department of Urology, University Hospital Centre Split, Split, Croatia
| | - Željko Bušić
- Department of Neurosurgery, University Hospital Centre Split, Split, Croatia
| | - Viktor Čulić
- Department of Cardiology and Angiology, University Hospital Centre Split, 21000, Split, Croatia.
- University of Split School of Medicine, Split, Croatia.
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Tong X, Shen L, Zhou X, Wang Y, Chang S, Lu S. Comparative Efficacy of Different Drugs for the Treatment of Dilated Cardiomyopathy: A Systematic Review and Network Meta-analysis. Drugs R D 2023; 23:197-210. [PMID: 37556093 PMCID: PMC10439079 DOI: 10.1007/s40268-023-00435-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2023] [Indexed: 08/10/2023] Open
Abstract
BACKGROUND AND OBJECTIVE At present, the therapies of dilated cardiomyopathy concentrated on the symptoms of heart failure and related complications. The study is to evaluate the clinical efficacy of a combination of various conventional and adjuvant drugs in treating dilated cardiomyopathy via network meta-analysis. METHODS The study was reported according to the PRISMA 2020 statement. From inception through 27 June 2022, the PubMed, Embase, Cochrane library, and Web of Science databases were searched for randomized controlled trials on medicines for treating dilated cardiomyopathy. The quality of the included studies was evaluated according to the Cochrane risk of bias assessment. R4.1.3 and Revman5.3 software were used for analysis. RESULTS There were 52 randomized controlled trials in this study, with a total of 25 medications and a sample size of 3048 cases. The network meta-analysis found that carvedilol, verapamil, and trimetazidine were the top three medicines for improving left ventricular ejection fraction (LVEF). Ivabradine, bucindolol, and verapamil were the top 3 drugs for improving left ventricular end-diastolic dimension (LVEDD). Ivabradine, L-thyroxine, and atorvastatin were the top 3 drugs for improving left ventricular end-systolic dimension (LVESD). Trimetazidine, pentoxifylline, and bucindolol were the top 3 drugs for improving the New York Heart Association classification (NYHA) cardiac function score. Ivabradine, carvedilol, and bucindolol were the top 3 drugs for reducing heart rate (HR). CONCLUSION A combination of different medications and conventional therapy may increase the clinical effectiveness of treating dilated cardiomyopathy. Beta-blockers, especially carvedilol, can improve ventricular remodeling, cardiac function, and clinical efficacy in patients with dilated cardiomyopathy (DCM). Hence, they can be used if patients tolerate them. If LVEF and HR do not meet the standard, ivabradine can also be used in combination with other treatments. However, since the quality and number of studies in our research were limited, large sample size, multi-center, and high-quality randomized controlled trials are required to corroborate our findings.
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Affiliation(s)
- Xinyu Tong
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Lijuan Shen
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaomin Zhou
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yudan Wang
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Sheng Chang
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shu Lu
- Wuxi Traditional Chinese Medicine Hospital, Nanjing University of Chinese Medicine, Nanjing, China
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Li ZH, Ni LJ, Liu YQ, Si DY. Rapid progression of heart failure secondary to radioactive iodine treatment of hyperthyroidism: A case report. World J Clin Cases 2023; 11:5316-5321. [PMID: 37621594 PMCID: PMC10445058 DOI: 10.12998/wjcc.v11.i22.5316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/23/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND The deterioration of thyroid health is involved in the progression of heart failure (HF). This is usually a lengthy process, so there are almost no reports on its rapid development. Here we report a case of a young male who rapidly developed hypothyroid cardiomyopathy secondary to radioactive iodine treatment, suggesting that severe HF might occur even after a short period of hypothyroidism. CASE SUMMARY A 26-year-old man was referred to our hospital for HF presenting with dyspnea on exertion and chest discomfort lasting for 1 mo. He received radioactive iodine treatment for hyperthyroidism 1 year ago and had an almost normal echocardiogram 6 mo ago. Admission echocardiogram and cardiac magnetic resonance (CMR) revealed left ventricle (LV) global hypokinesia and severely depressed systolic function. In addition, late gadolinium enhancement indicated no obvious changes in the myocardium. Thyroid function tests showed decreased serum levels of thyroid hormone (TH) and elevated thyroid-stimulating hormone. Based on an exclusionary examination, the patient was diagnosed with hypothyroid cardiomyopathy and was started on replacement therapy. His HF symptoms were completely relieved during the six-month follow-up, and echocardiogram and CMR revealed recovered LV size and ejection fraction. CONCLUSION This report demonstrates that severe fluctuations in TH levels may lead to acute HF, which can completely recover with timely thyroid hormone replacement. In addition, our findings highlight the importance of routinely detecting cardiac function in patients treated with radioactive iodine.
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Affiliation(s)
- Zi-Han Li
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Lu-Jia Ni
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Yuan-Qiao Liu
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Dao-Yuan Si
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
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Li ZH, Ni LJ, Liu YQ, Si DY. Rapid progression of heart failure secondary to radioactive iodine treatment of hyperthyroidism: A case report. World J Clin Cases 2023; 11:5310-5315. [DOI: 10.12998/wjcc.v11.i22.5310] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Revised: 06/23/2023] [Accepted: 07/17/2023] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND The deterioration of thyroid health is involved in the progression of heart failure (HF). This is usually a lengthy process, so there are almost no reports on its rapid development. Here we report a case of a young male who rapidly developed hypothyroid cardiomyopathy secondary to radioactive iodine treatment, suggesting that severe HF might occur even after a short period of hypothyroidism.
CASE SUMMARY A 26-year-old man was referred to our hospital for HF presenting with dyspnea on exertion and chest discomfort lasting for 1 mo. He received radioactive iodine treatment for hyperthyroidism 1 year ago and had an almost normal echocardiogram 6 mo ago. Admission echocardiogram and cardiac magnetic resonance (CMR) revealed left ventricle (LV) global hypokinesia and severely depressed systolic function. In addition, late gadolinium enhancement indicated no obvious changes in the myocardium. Thyroid function tests showed decreased serum levels of thyroid hormone (TH) and elevated thyroid-stimulating hormone. Based on an exclusionary examination, the patient was diagnosed with hypothyroid cardiomyopathy and was started on replacement therapy. His HF symptoms were completely relieved during the six-month follow-up, and echocardiogram and CMR revealed recovered LV size and ejection fraction.
CONCLUSION This report demonstrates that severe fluctuations in TH levels may lead to acute HF, which can completely recover with timely thyroid hormone replacement. In addition, our findings highlight the importance of routinely detecting cardiac function in patients treated with radioactive iodine.
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Affiliation(s)
- Zi-Han Li
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Lu-Jia Ni
- Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Yuan-Qiao Liu
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
| | - Dao-Yuan Si
- Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
- Jilin Provincial Engineering Laboratory for Endothelial Function, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin Province, China
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Karanth J, Vikram S, Mohanty S, Behera V, Ananthakrishnan R, Mahadev N. Short-term electrocardiographic and echocardiographic effects of levothyroxine replacement in adults with newly diagnosed hypothyroidism. JOURNAL OF MARINE MEDICAL SOCIETY 2023. [DOI: 10.4103/jmms.jmms_95_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023] Open
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Chen X, Bao Y, Shi C, Tian L. Effectiveness and Safety of Thyroid Hormone Therapy in Patients with Dilated Cardiomyopathy: A Systematic Review and Meta-analysis of RCTs. Am J Cardiovasc Drugs 2022; 22:647-656. [DOI: 10.1007/s40256-022-00548-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/11/2022] [Indexed: 11/01/2022]
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Zawadzka K, Dziedzic R, Surdacki A, Chyrchel B. Thyroid Hormones-An Underestimated Player in Dilated Cardiomyopathy? J Clin Med 2021; 10:jcm10163618. [PMID: 34441915 PMCID: PMC8397026 DOI: 10.3390/jcm10163618] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 08/03/2021] [Accepted: 08/13/2021] [Indexed: 01/01/2023] Open
Abstract
Dilated cardiomyopathy (DCM) is the most prevalent cardiomyopathy, typified by left ventricular dilation and systolic dysfunction. Many patients with DCM have altered thyroid status, especially lower levels of free triiodothyronine (T3) and elevated levels of thyroid-stimulating hormone. Moreover, growing evidence indicates that even subtle changes in thyroid status (especially low T3) are linked with a worse long-term prognosis and a higher risk of mortality. Notably, recent discoveries have shown that not only local myocardial thyroid hormones (THs) bioavailability could be diminished due to impaired expression of the activating deiodinase, but virtually all genes involved in TH biosynthesis are also expressed in the myocardium of DCM patients. Importantly, some studies have suggested beneficial effects of TH therapy in patients suffering from DCM. Our aim was to discuss new insights into the association between TH status and prognosis in DCM, abnormal expression of genes involved in the myocardial synthesis of TH in DCM, and the potential for TH use in the future treatment of DCM.
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Affiliation(s)
- Karolina Zawadzka
- Students’ Scientific Group at the Second Department of Cardiology, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland; (K.Z.); (R.D.)
| | - Radosław Dziedzic
- Students’ Scientific Group at the Second Department of Cardiology, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland; (K.Z.); (R.D.)
| | - Andrzej Surdacki
- Second Department of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland;
| | - Bernadeta Chyrchel
- Second Department of Cardiology, Faculty of Medicine, Jagiellonian University Medical College, 2 Jakubowskiego Street, 30-688 Cracow, Poland;
- Correspondence: ; Tel.: +48-12-400-2250
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Gerdes AM, Portman MA, Iervasi G, Pingitore A, Cooper DKC, Novitzky D. Ignoring a basic pathophysiological mechanism of heart failure progression will not make it go away. Am J Physiol Heart Circ Physiol 2021; 320:H1919-H1922. [PMID: 33797271 DOI: 10.1152/ajpheart.00105.2021] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
A link between heart failure (HF) and low thyroid hormone (TH) function has been known for over a century. Nonetheless, there is a general belief that TH treatment of patients with HF may not be worth the risk. This is largely based on two clinical trials where heart patients were treated with excessive doses of TH analogs, not actual THs. Further complicating the matter is the fact that normalization of THs in noncardiac patients can often be challenging. This issue is not going away as noted by a steady increase in TH-HF citations in recent years. In this article, we discuss what we know and how we may move the field forward.
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Affiliation(s)
- A Martin Gerdes
- Department of Biomedical Sciences, New York Institute of Technology, College of Osteopathic Medicine, Old Westbury, New York
| | - Michael A Portman
- Department of Cardiology, Children's Hospital and Regional Medical Center, Seattle, Washington
| | - Giorgio Iervasi
- Institute of Clinical Physiology, National Research Council, Pisa, Italy
| | | | - David K C Cooper
- Department of Surgery, University of Alabama at Birmingham, Birmingham, Alabama
| | - Dimitri Novitzky
- Department of Surgery, Tampa Veterans Affairs Medical Center, Tampa, Florida
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