Methodist Journal


Adult Congenital Heart Update

Vol 15, Issue 2 (2019)



The Growing Number of Adults Surviving with Congenital Heart Disease

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Drs. MacGillivray and Lin Take the Lead in Adult Congenital Heart Disease

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Advanced Cardiac Imaging for Complex Adult Congenital Heart Diseases

149 Fontan Conversions

Anomalous Aortic Origin of a Coronary Artery

Pulmonary Valve Replacement for Tetralogy of Fallot

Management of the Adult with Arterial Switch

Ebstein’s Anomaly

Heart Transplantation in Adults with Congenital Heart Disease

Cholesterol: Can’t Live With It, Can’t Live Without It


Simultaneous Transfemoral Mitral and Tricuspid Valve in Ring Implantation: First Case Report with Edwards Sapien 3 Valve

Uneventful Follow-Up 2 Years after Endovascular Treatment of a High Flow Iatrogenic Aortocaval Fistula Causing Pulmonary Hypertension and Right Heart Failure

Device-Related Thrombus: A Reason for Concern?

Retained Coronary Balloon Requiring Emergent Open Surgical Retrieval: An Uncommon Complication Requiring Individualized Management Strategies


Do I Look Fat in This? Multimodality Imaging Findings of a Cardiac Lipoma



The Kidney in Congenital Cyanotic Heart Disease


Talking Statins with Antonio Gotto


Lipids and Renal Disease


Addressing the Feedback Loop Between Depression, Diabetes, and Cardiovascular Disease


Letter to the Editor in Response to “Cardiac Autonomic Neuropathy in Diabetes Mellitus”

Vol 13, Issue 4 (2017)

Article Full Text


Hypothyroidism and the Heart: Much More Than Meets the Eye

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Article Citation:

Sharma AK, Shah S, Ganatra S, Chaudhry GM. Hypothyroidism and the Heart: Much More Than Meets the Eye. Methodist DeBakey Cardiovasc J. 2017;13(4):261-262.

doi: 14797/mdcj-13-4-261

hypothyroidism ,   subclinical hypothyroidism ,   thyroxine ,   thyroid-stimulating hormone

The pleiotropic effects of thyroid hormone are essential from the embryonic state for the optimal development, maturation, and functioning of cardiac tissue. In addition, thyroid hormone (TH) has been shown to play a critical reparative role in the setting of myocardial injury.1 Hypothyroidism is associated with hyperlipidemia, an increased risk of coronary artery disease, and left ventricular systolic and diastolic dysfunction.1 In issue 13.2 of this journal, Udovcic et al. presented a clinically relevant and concise review titled “Hypothyroidism and the Heart.”2 Even so, several key aspects of the interaction between TH and heart disease deserve attention—specifically, the complex biological mechanisms underlying the role of TH in the development of heart failure.

Abnormal thyroid function can affect cardiac metabolism, structure, function, and response to therapy. In a hypothyroid state, cardiac tissue shows poor substrate utilization (glucose, lactate, and free fatty acids) by mitochondria. Hypothyroidism stimulates fibroblasts and promotes myocardial fibrosis and, eventually, cardiac dysfunction.3 In adult rats, long-standing hypothyroidism has been shown to cause loss of coronary arterioles and a maladaptive change in myocyte shape that eventually lead to the development of heart failure.4 Alterations in TH receptor homeostasis are shown to regulate regression of the damaged myocardium to the fetal phenotype. Thyroid hormone treatment may preferentially rebuild the injured myocardium by reactivating developmental gene programming and fetal phenotype, leading to cell dedifferentiation and creating a permissive state for regeneration.5

Cross-sectional studies have demonstrated low levels of T3 in about 30% of patients with heart failure, and the decrease in serum T3 is proportional to the severity of the condition as assessed by New York Heart Association classification.6 With negligible deiodinase activity, the cardiac myocytes are particularly vulnerable and depend on plasma T3.7 Low free T3 levels have been associated with larger heart chambers and worse left ventricular systolic function. Hypothyroidism can also lead to malfunction of cardiac rhythm management devices by increasing pacing thresholds, resulting in loss of capture that can be corrected by hormonal repletion.9,10 Among patients receiving cardiac resynchronization therapy (CRT), those with hypothyroidism had significantly higher all-cause mortality and heart failure hospitalizations compared to patients with euthyroid status, thus blunting the impact of this otherwise proven intervention.11 Interestingly, the beneficial effect of CRT on thyroid function was documented in a small study in which CRT recipients had improvements in free T3 levels and free T3/free T4 ratio, regardless of reverse cardiac remodeling.12

With negligible cardiac myocyte deiodinase activity as well as impaired peripheral conversion of T4 to T3, it appears reasonable to treat with T3 instead of T4 in the setting of congestive heart failure and post-ischemic myocardium. Currently, direct assessment of tissue TH level is not possible and is extrapolated from plasma hormone levels. Thyroid stimulating hormone (TSH) may not be the best laboratory test in this setting since, in many nonthyroidal conditions, free T3 levels have been found to be low with normal TSH and free T4 levels—a fact that may hold significance in cardiovascular ailments. A biomarker reflecting intracardiac TH signaling or functional status may help formulate a therapeutic approach. It is also noteworthy that preclinical studies have documented T3 to be well tolerated without any significant arrhythmias, myocardial ischemia, or hemodynamic instability.13 An animal model of chronic cardiac unloading demonstrated that treatment with physiological doses of T3 restored the expression of Ca++ cycling and handling proteins and contractile function of cardiac myocytes.14

Treatment with TH may be a potential strategy to protect post-ischemic damaged myocardium from pathological growth and remodeling, with beneficial changes in myocyte shape, microcirculation, and collagen. An ongoing study—ThiRST (Thyroid Hormone Replacement therapy in ST elevation myocardial infarction-European Community ITC-STREP FP7 PONTE Research Project)—aims to investigate the safety and feasibility of TH replacement in patients with ST elevation myocardial infarction and to determine effects on post-ischemic remodeling, left ventricular function, and clinical outcomes (cardiac and noncardiac death, coronary revascularization, hospitalization).

At this point, more studies are needed to explore the full therapeutic potential of thyroid hormones, specifically T3, for treatment of cardiac myocyte injury in a post-ischemic state and heart failure. In addition, thyroid function may have a role in the optimal functioning of devices such as pacemakers and CRT. It is indeed intriguing to hypothesize that a low T3 state in cardiac tissue, with its regulation of many structural and functional genes, is part of a vicious pathophysiological pathway that sustains cardiac remodeling and leads to an increase in mortality.



1. Gerdes AM, Iervasi G. Thyroid replacement therapy and heart failure. Circulation. 2010 Jul 27;122(4):385-93.

2. Udovcic M, Pena RH, Patham B, Tabatabai L, Kansara A. Hypothyroidism and the heart. Methodist Debakey Cardiovasc J. 2017 Apr-Jun;13(2):55-9.

3. Chen WJ, Lin KH, Lee YS. Molecular characterization of myocardial fibrosis during hypothyroidism: evidence for negative regulation of the pro-alpha1(I) collagen gene expression by thyroid hormone receptor. Mol Cell Endocrinol. 2000 Apr 1;162(1-2):45-55.

4. Tang YD, Kuzman JA, Said S, Anderson BE, Wang X, Gerdes AM. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction. Circulation. 2005 Nov 15;112(20):3122-30.

5. Lee YK, Ng KM, Chan YC, et al. Triiodothyronine promotes cardiac differentiation and maturation of embryonic stem cells via the classical genomic pathway. Mol Endocrinol. 2010 Sep;24(9):1728-36.

6. Hamilton MA, Stevenson LW, Luu M, Walden JA. Altered thyroid hormone metabolism in advanced heart failure. J Am Coll Cardiol. 1990 Jul;16(1):91-5.

7. Katzeff HL, Powell SR, Ojamaa K. Alterations in cardiac contractility and gene expression during low T3 syndrome:prevention with T3. Am J Physiology. 1997;271:E951-E956.

8. Kozdag G, Ural D, Vural A, et al. Relation between free triiodothyronine/free thyroxine ratio, echocardiographic parameters and mortality in dilated cardiomyopathy. Eur J Heart Fail. 2005 Jan;7(1):113-8.

9. Patton KK, Levy M, Viswanathan M. Atrial lead dysfunction: an unusual feature of hypothyroidism. Pacing Clin Electrophysiol. 2008;31:1650-2.

10. Esposito F, Liguori V, Maresca G, et al. Subclinical hypothyroidism: a reversible cause of complete loss of ventricular lead capture. Circ Arrhythmia Electrophysiol. 2014 Feb;7:182-4.

11. Sharma AK, Vegh E, Orencole M, et al. Association of hypothyroidism with adverse events in patients with heart failure receiving cardiac resynchronization therapy. Am J Cardiol. 2015 May 1;115(9):1249-53.

12. Celikyurt U, Agacdiken A, Geyik B, Kozdag G, Vural A, Ural D. Effect of Cardiac Resynchronization Therapy on Thyroid Function. Clin Cardiol. 2011 Nov;34(11):703-5.

13. Pingitore A, Galli E, Barison A, et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab. 2008 Apr;93(4):1351-8.

14. Ito K, Kagaya Y, Shimokawa H. Thyroid hormone and chronically unloaded hearts. Vascul Pharmacol. 2010;52:138-41.

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