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Changes in Thyroid Hormone Metabolism and Gene Expression in the Failing Heart: Therapeutic Implications

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Book cover Thyroid and Heart Failure

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Abstract

Thyroid hormone has profound effects on the heart and cardiovascular system. The cellular and systemic changes that occur with hypothyroidism include blood pressure changes, alterations in lipid metabolism, decreased cardiac contractility, and increased systemic vascular resistance. The resulting increased hypercholesterolemia and diastolic hypertension predispose these patients to atherosclerotic cardiovascular and coronary artery disease. Heart failure is associated with low-T3 syndrome, resulting from alterations in thyroid hormone metabolism. This nonthyroidal illness may cause cardiovascular alterations similar to the changes described for hypothyroidism. New research suggests that T3 treatment of patients with heart failure and low-T3 syndrome improves some of the clinical manifestations of heart failure.

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References

  1. Klein I, Danzi S (2007) Thyroid disease and the heart. Circulation 116:1725–1735

    Article  PubMed  Google Scholar 

  2. Klein I, Ojamaa K (2001) Thyroid hormone and the cardiovascular system. N Engl J Med 344:501–509

    Article  PubMed  CAS  Google Scholar 

  3. Dillmann WH (2002) Cellular action of thyroid hormone on the heart. Thyroid 12:447–452

    Article  PubMed  CAS  Google Scholar 

  4. Kahaly GJ, Dillmann WH (2005) Thyroid hormone action in the heart. Endocrine Rev 26:704–728

    Article  CAS  Google Scholar 

  5. Levey GS, Klein I (1994) Disorders of the thyroid. In: Stein’s Textbook of medicine, 2nd edn. Little Brown, Boston, pp 1383–1396

    Google Scholar 

  6. Crowley WF Jr, Ridgway EC, Bough EW et al (1977) Noninvasive evaluation of cardiac function in hypothyroidism. Response to gradual thyroxine replacement. N Engl J Med 296:1–6

    PubMed  Google Scholar 

  7. Klein I (2008) Endocrine disorders and cardiovascular disease. In: Libby P, Bonow R, Mann D, Zipes D (eds) Braunwald’s Heart disease, 8th edn. Saunders, Philadelphia, pp 2033–2047

    Google Scholar 

  8. Danzi S, Klein I (2006) Treatment of hypertension and thyroid disease. In: Mohler ER, Townsend RR (eds) Advanced therapy in hypertension and vascular disease. BC Decker, Hamilton, Ontario, Canada, pp 354–360

    Google Scholar 

  9. Cappola AR, Ladenson PW (2003) Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab 88:2438–2444

    Article  PubMed  CAS  Google Scholar 

  10. Danzi S, Klein I (2003) Thyroid hormone and blood pressure regulation. Curr Hypertens Rep 5:513–520

    Article  PubMed  Google Scholar 

  11. Biondi B, Palmieri EA, Lombardi G, Fazio S (2002) Effects of thyroid hormone on cardiac function: the relative importance of heart rate, loading conditions, and myocardial contractility in the regulation of cardiac performance in human hyperthyroidism. J Clin Endocrinol Metab 87:968–974

    Article  PubMed  CAS  Google Scholar 

  12. Nakazawa H, Lythall DA, Noh J et al (2000) Is there a place for the late cardioversion of atrial fibrillation? A long-term follow-up study of patients with post-thyrotoxic atrial fibrillation. Eur Heart J 21:327–333

    Article  PubMed  CAS  Google Scholar 

  13. Olsen B, Klein I, Benner R et al (1991) Hyperthyroid myopathy and the response to treatment. Thyroid 1:137–141

    Article  Google Scholar 

  14. Napoli R, Biondi B, Guardasole V et al (2001) Impact of hyperthyroidism and its correction on vascular reactivity in humans. Circulation 104:3076–3080

    Article  PubMed  CAS  Google Scholar 

  15. Prisant LM, Gujral JS, Mulloy AL (2006) Hyperthyroidism: a secondary cause of isolated systolic hypertension. J Clin Hypertens 8:596–599

    Article  Google Scholar 

  16. Palmieri EA, Fazio S, Palmieri V et al (2004) Myocardial contractility and total arterial stiffness in patients with overt hyperthyroidism: acute effects of betal-adrenergic blockade. Eur J Endocrinol 150:757–62.

    Article  PubMed  CAS  Google Scholar 

  17. Asvold BO, Bjoro T, Nilsen T, Vatten LJ (2007) Association between blood pressure and serum TSH concentration within the reference range: a population-based study. J Clin Endocrinol Metab 92:841–5

    Article  PubMed  CAS  Google Scholar 

  18. Marcisz C, Jonderko G, Kucharz EJ (2001) Influence of short-time application of a low sodium diet on blood pressure in patients with hyperthyroidism or hypothyroidism during therapy. Am J Hypertens 14:995–1002

    Article  PubMed  CAS  Google Scholar 

  19. Hoit BD, Khoury SF, Shao Y et al (1997) Effects of thyroid hormone on cardiac b-adrenergic responsiveness in conscious baboons. Circulation 96:592–598

    PubMed  CAS  Google Scholar 

  20. Laragh JH, Sealey JE (2003) Relevance of the plasma renin hormonal control system that regulates blood pressure and sodium balance for correctly treating hypertension and for evaluating ALLHAT. Am J Hypertens 16:407–415

    Article  PubMed  CAS  Google Scholar 

  21. Hak AE, Pols HA, Visser TJ et al (2000) Subclinical hypothyroidism is an independent risk factor for atherosclerosis and myocardial infarction in elderly women: the Rotterdam Study. Ann Intern Med 132:270–278

    PubMed  CAS  Google Scholar 

  22. Razvi S, Ingoe L, Keeka G et al (2007) The beneficial effect of 1-thyroxine on cardiovascular risk factors, endothelial function and quality of life in subclinical hypothyroidism: randomised, crossover trial. J Clin Endocrinol Metab 92:1715–1723

    Article  PubMed  CAS  Google Scholar 

  23. Biondi B, Klein I (2004) Hypothyroidism as a risk factor for cardiovascular disease. Endocrine 24:1–14

    Article  PubMed  CAS  Google Scholar 

  24. Auer J, Scheibner P, Mische T et al (2001) Subclinical hyperthyroidism as a risk factor for atrial fibrillation. Am Heart J 142:838–842

    Article  PubMed  CAS  Google Scholar 

  25. Sawin CT, Geller A, Wolf PA et al (1994) Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 331:1249–1252

    Article  PubMed  CAS  Google Scholar 

  26. Brent G (1994) The molecular basis of thyroid hormone action. N Engl J Med 331:847–853

    Article  PubMed  CAS  Google Scholar 

  27. Lazar MA, Chin WW (1990) Nuclear thyroid hormone receptors. J Clin Invest 86:1777–1782.

    Article  PubMed  CAS  Google Scholar 

  28. Hu X, Lazar MA (2000) Transcriptional repression by nuclear hormone receptors. Trends Endocrinol Metab 11:6–10

    Article  PubMed  CAS  Google Scholar 

  29. Haddad F, Bodell PW, Qin AX et al (2003) Role of antisense RNA in coordinating cardiac myosin heavy chain gene switching. J Biol Chem 278:37132–37138

    Article  PubMed  CAS  Google Scholar 

  30. Danzi S, Klein S, Klein I (2008) Differential regulation of myosin heavy chain genes a and b in the rat atria and ventricles: role of antisense RNA. Thyroid 18:761–768

    Article  PubMed  CAS  Google Scholar 

  31. Wu Y, Koenig RJ (2000) Gene regulation by thyroid hormone. Trends Endocrinol Metab 11:207–211

    Article  PubMed  CAS  Google Scholar 

  32. Davis PJ, Davis FB (2002) Nongenomic actions of thyroid hormone on the heart. Thyroid 12:459–466

    Article  PubMed  CAS  Google Scholar 

  33. Hiroi Y, Kim H-H, Ying H et al (2006) Rapid nongenomic actions of thyroid hormone. Proc Natl Acad Sci USA 103:14104–14109

    Article  PubMed  CAS  Google Scholar 

  34. Bianco AC, Salvatore D, Gereben B et al (2002) Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocrine Rev 23:38–89

    Article  CAS  Google Scholar 

  35. Maia AL, Kim BW, Huang SA et al (2005) Type 2 iodothyronine deiodinase is the major source of plasma T3 in euthyroid humans. J Clin Invest 115:2524–2533

    Article  PubMed  CAS  Google Scholar 

  36. Bianco AC, Larsen PR (2005) Cellular and structural biology of the deiodinases. Thyroid 15:777–786

    Article  PubMed  CAS  Google Scholar 

  37. Katzeff HL, Powell SR, Ojamaa K (1997) Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3. Am J Physiol 273:E951–956

    PubMed  CAS  Google Scholar 

  38. Schmidt-Ott UM, Ascheim DD (2006) Thyroid hormone and heart failure. Curr Heart Fail Rep 3:114–119

    Article  PubMed  CAS  Google Scholar 

  39. Pingitore A, Landi P, Taddei MC et al (2005) Triiodothyronine levels for risk stratification of patients with chronic heart failure. Am J Med 118:132–136

    Article  PubMed  CAS  Google Scholar 

  40. Yu J, Koenig RJ (2006) Induction of type 1 iodothyronine deiodinase to prevent the nonthyroidal illness syndrome in mice. Endocrinology 147:3580–3585

    Article  PubMed  CAS  Google Scholar 

  41. Olivares EL, Marassi MP, Fortunato RS et al (2007) Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats: a time course study. Endocrinology 148:4786–4792

    Article  PubMed  CAS  Google Scholar 

  42. Duntas LH (2002) Thyroid disease and lipids. Thyroid 12:287–293

    Article  PubMed  CAS  Google Scholar 

  43. Thompson GR, Soutar AK, Spengel FA et al (1981) Defects of receptor-mediated low density lipoprotein catabolism in homozygous familial hypercholesterolemia and hypothyroidism in vivo. Proc Natl Acad Sci USA 78:2591

    Article  PubMed  CAS  Google Scholar 

  44. Harjai KJ, Licata AA (2006) Effects of amiodarone on thyroid function. Ann Intern Med 126:63–73

    Google Scholar 

  45. Marvisi M, Zambrelli P, Brianti M et al (2006) Pulmonary hypertension is frequent in hyperthyroidism and normalizes after therapy. Eur J Intern Med 17:267–271

    Article  PubMed  Google Scholar 

  46. Paran Y, Nimrod A, Goldin Y, Justo D (2006) Pulmonary hypertension and predominant right heart failure in thyrotoxicosis. Resuscitation 69:339–341

    Article  PubMed  Google Scholar 

  47. Morkin E, Pennock G, Spooner PH et al (2002) Pilot studies on the use of 3,5-diiodothyropropionic acid, a thyroid hormone analog, in the treatment of congestive heart failure. Cardiology 97:218–225

    Article  PubMed  CAS  Google Scholar 

  48. Henderson KK, Danzi S, Klein I, Samarel A (2009) Physiological replacement of T3 improves left ventricular function in an animal model of myocardial infarction-induced congestive heart failure. Circ Heart Fail (in press)

    Google Scholar 

  49. Ojamaa K, Kenessey A, Shenoy R, Klein I (2000) Thyroid hormone metabolism and cardiac gene expression after acute myocardial infarction in the rat. Am J Physiol 279:E1319–1324

    CAS  Google Scholar 

  50. Thomas TA, Kuzman JA, Anderson BE et al (2005) Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure. Am J Physiol Heart Circ Physiol 288:H2118–2122

    Article  PubMed  CAS  Google Scholar 

  51. Khalife WI, Tang YD, Kuzman JA et al (2005) Treatment of subclinical hypothyroidism reverses ischemia and prevents myocyte loss and progressive LV dysfunction in hamsters with dilated cardiomyopathy. Am J Physiol Heart Circ Physiol 289:H2409–2415

    Article  PubMed  CAS  Google Scholar 

  52. Danzi S, Klein I (2004) Thyroid hormone and the cardiovascular system. Minerva Endocrinol 29:139–150

    PubMed  CAS  Google Scholar 

  53. Morkin E, Pennock GD, Spooner PH et al (2002) Clinical and experimental studies on the use of 3.5-diiodothyropropionic acid, a thyroid hormone analogue, in heart failure Thyroid 12:527–533

    Article  PubMed  CAS  Google Scholar 

  54. Hamilton MA, Stevenson LW, Luu M, Walden JA (1990) Altered thyroid hormone metabolism in advanced heart failure. J Am Coll Cardiol 16:91–95

    Article  PubMed  CAS  Google Scholar 

  55. Klemperer J, Klein I, Gomez M et al (1995) Thyroid hormone treatment after coronary-artery bypass surgery. New Engl J Med 333:1522–1527

    Article  PubMed  CAS  Google Scholar 

  56. Chowdhury D, Parnell VA, Ojamaa K et al (1999) Usefulness of triiodothyronine (T3) treatment after surgery for complex congenital heart disease in infants and children. Am J Cardiol 84:34–36

    Article  Google Scholar 

  57. Pingitore A, Galli E, Barison A et al (2008) 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 93:1351–1358

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Medicine, North Shore University Hospital, Manhasset, NY, USA

    Sara Danzi MD, PhD & Irwin Klein MD

  2. Feinstein Institute for Medical Research, Manhasset, NY, USA

    Sara Danzi MD, PhD & Irwin Klein MD

Authors
  1. Sara Danzi MD, PhD
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  2. Irwin Klein MD
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Editor information

Editors and Affiliations

  1. C.N.R. Clinical Physiology Institute, S. Cataldo Research Campus, Pisa, Italy

    Giorgio Iervasi  & Alessandro Pingitore  & 

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Danzi, S., Klein, I. (2009). Changes in Thyroid Hormone Metabolism and Gene Expression in the Failing Heart: Therapeutic Implications. In: Iervasi, G., Pingitore, A. (eds) Thyroid and Heart Failure. Springer, Milano. https://doi.org/10.1007/978-88-470-1143-4_10

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  • DOI: https://doi.org/10.1007/978-88-470-1143-4_10

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-1142-7

  • Online ISBN: 978-88-470-1143-4

  • eBook Packages: MedicineMedicine (R0)

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