Pyvovar S. M., Rudyk Yu. S., Lozyk T. V., Galchinska V. Yu., Chenchik T. O.

THE EFFECT OF BETA-BLOCKERS ON A COURSE OF CHRONIC HEART FAILURE IN PATIENTS WITH A NONTOXIC GOITER


About the author:

Pyvovar S. M., Rudyk Yu. S., Lozyk T. V., Galchinska V. Yu., Chenchik T. O.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

The major cause of mortality in many countries is cardiovascular pathology. Heart failure (HF) is the final stage of the cardio-vascular continuum. Recent years, interest in the study of comorbidity in HF has increased significantly. This is due to the fact that the concomitant pathology not only affects the severity of the HF course, but also can determine the variability of the response to prescribed treatment. Non-toxic goiter (NTG) is one of the most common thyroid pathology in our country. At NTG in some patients changes in thyroid function are detected. Subclinical and clinical hypothyroidism are often observed. Thyrotoxicosis may develop over the years due to the "autonomization" of thyroid nodules. Earlier, we reported that patients with NTG have a high incidence of the low T3 syndrome (LT3S) in HF. β-blockers (β-AB) reduce mortality (up to 30%) in HF. In addition, this group of drugs did not show a significant effect on survival in decompensated patients. It is also known that β-AB lead to blockade of deiodinases, which leads to a decrease in T4 to T3 conversion, that is why they are prescribed to patients with hyperthyroidism. It can be assumed that the use of β-AB in HF in patients with NTG requires more detailed study. Objective: to study the effect of the use of β-blockers (β-AB) in patients with NTG on the course of HF. Object and research methods. 381 patients with HF on a background of post-infarction cardiosclerosis were included. In 218 (57.2 %) patients were diagnosed with NTG. Levels of TSG, T3f and T4f were evaluated. Echocardioscopy and ultrasound examination of the thyroid gland were performed. The course of HF was studied for 2 years. Results. Patients with HF without NTG who received bisoprolol at dose over 5 mg had a significant reduction in the risk of re-hospitalization (RH) (odds ratio (OR) = 0.174 (0.057-0.530), p = 0.002) and combined endpoint (CE) (OR = 0.403 (0.180-0.905), p = 0.025), comparing to patients who received β-AB at a dose lower or equal 5 mg as a result of intolerance or low compliance. It was not possible to detect a decrease in the risk of a non-sensitive course of HF with increasing dose of β-AB in the group of patients with NTG. Patients with NTG have a higher incidence of low T3 syndrome (LT3S), compared to patients without NTG (39.4 % vs. 9.8 %, respectively, at p = 0.0001). Prescribing β-AB in patients with NTG but without LT3S leads to a decrease in the risk of RH due to HF decompensation (OR = 0.399 (0.173-0.925), p = 0.029) and CE (OR = 0.419 (0.188-0.935), p = 0.031). Prescription of β-AB at a dose over 5 mg in patients with NTG without LT3S leads to a further reduction in the risk of RH (OR = 0.123 (0.035-0.431), p = 0.0001) and CE (OR = 0.224 (0.086-0.587), p = 0.001). Conclusions. The use of β-AB in patients with NTG has no dose-dependent effect on the course of HF. A probable cause of this is the high incidence of LT3S among patients in this population. The use of β-AB in patients with NTG without LT3S leads to a significant reduction in RH frequency and the risk of CE developing within 2 years.

Tags:

heart failure, non-toxic goiter, low T3 syndrome, β-blockers, thyrotropic hormone, triiodothyronine, thyroxine.

Bibliography:

  1. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2016. The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Heart Journal. 2016;8:2129-200. DOI: 10.1093/eurheartj/ehw128
  2. Tokmachev RYe, Mukhortova MS, Budnevskiy AV, Tokmachev YeV, Ovsyannikov YeS. Komorbidnost' khronicheskoy serdechnoy nedostatochnosti i khronicheskoy obstruktivnoy bolezni legkikh: osobennosti patogeneza, kliniki i diagnostiki. Kardiovaskulyarnaya terapiya i profilaktika. 2018;17(6):62-8. [in Russian].
  3. Yuzvenko TYu. Osoblyvosti perebihu tsukrovoho diabetu 2-ho typu u poyednanni z hipotyreozom. Mizhnarodnyy endokrynolohichnyy zhurnal. 2015;8(72):73-7. DOI:10.22141/2224-0721.8.72.2015.72341 [in Ukrainian].
  4. Berghout A, Wiersinga WM, Smits NJ, Touber JL. Interrelationships between age, thyroid volume, thyroid nodularity, and thyroid function in patients with sporadic non toxic goiter. Am J Med. 1990;89:602-8.
  5. Pyvovar SM, Rudyk YuS, Lozyk TV, Galchinska VYu, Chenchik TO. Osoblyvosti vyznachennya syndromu «nyz’koho tryyodtyroninu» pry sertseviy nedostatnosti ta yoho vplyv na perebih zakhvoryuvannya. Zaporozhye medical journal. 2019;4(21):437-43. [in Ukrainian].
  6. Hjalmarson A, Goldstein S, Fagerberg B, Wedel H, Waagstein F, Kjekshus J, et al. MERIT-HF Study Group. Effects of controlled-release metoprolol on total mortality, hospitalizations, and wellbeing in patients with heart failure: the Metoprolol CR/XL Randomized Intervention Trial in congestive Heart Failure (MERIT-HF). JAMA. 2000;283:1295-302.
  7. Tagami T, Yambe Y, Tanaka T, Tanaka T, Ogo A, Yoshizumi H, et al. Short-term effects of β-adrenergic antagonists and methimazole in new-onset thyrotoxicosis caused by Graves' disease. Intern Med. 2012;51(17):2285-90. Epub 2012 Sep 1.
  8. Voronkov LH, Amosova KM, Bahriy AE, Dziak GV, Diadik OI, Zarinov OI, ta in. Rekomendatsiyi Asotsiatsiyi kardiolohiv Ukrayiny z diahnostyky, likuvannya ta profilaktyky khronichnoyi sertsevoyi nedostatnosti u doroslykh. Kyyiv; 2009. s. 4-22. [in Ukrainian].
  9. Pyvovar SM, Rudyk YuS. Syndrom nyzʹkoho tryyodtyroninu ta zastosuvannya b-adrenoblokatoriv pry sertseviy nedostatnosti. «Novitni tendentsiyi v diahnostytsi ta likuvanni vnutrishnikh khvorob»: materialy naukovo-praktychnoyi konferentsiyi z mizhnarodnoyu uchastyu, prysvyachenoyi 100-richchyu vid dnya narodzhennya akademika L. T. Maloyi, 15-16 zhovtnya 2019 r. Za red. Bilovola OM. ta in. Kharkiv; 2019. s. 170-1. [in Ukrainian].
  10. Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al. Trends in heart failure incidence and survival in a community based population. JAMA. 2004 Jul 21;292(3):344-50. DOI: 10.1001/ jama. 292.3.344
  11. Ma ST, Zhao W, Liu B, Jia RY, Zhao CJ, Cui LQ. Association between β1 adrenergic receptor gene Arg389Gly polymorphism and risk of heart failure: a meta-analysis. Genet Mol Res. 2015;14:5922-9. DOI: 10.4238/2015. June.1.9.
  12. Charib TGH. Thyroid incidentalomas: management approaches to non palpable nodules discovered incidentally on thyroid imaging. Ann Int Med. 1997;126:226-31.
  13.  Turchina SI, Nachetova TA. Distireoz kak faktor riska formirovaniya vtorichnoy amenorei u devushek, prozhivayushchikh v usloviyakh slabogo yododefitsita. Health of woman. 2017;8(124):16-20. DOI: 10.15574 HW.2017.124.16 [in Russiаn].
  14. Krohn K, Führer D, Bayer Y, Eszlinger M, Brauer V, Neumann S, et al. Molecular Pathogenesis of Euthyroid and Toxic Multinodular Goiter. Endocr Rev. June. 2005;26(4):504-24. DOI: 10.1210 er.2004 0005
  15. Moreno JC, Visser TJ. Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):91-8. DOI: 10.1016 j.mce.2010.03.010
  16. Kim B, Carvalho-Bianco SD, Larsen PR. Thyroid hormone and adrenergic signaling in the heart. Arq Bras Endocrinol Metab. 2004;48(1):171-5.
  17. Silva JE. Thyroid hormone control of thermogenesis and energy balance. Thyroid. 1995;5:481-92.
  18. Naga Prasad SV, Nienaber J, Rockman HA. Beta-adrenergic axis and heart disease. Trends Genet. 2001;17:44-9.
  19. Larsen PR, Larsen FT, Zavacki AM. Role of the Iodothyronine Deiodinases in the Physiology and Pathophysiology of Thyroid Hormone Action. Eur Thyroid J. 2012;1:232-42. DOI: 10.1159/00034392212
  20. De Groot LJ. Non-thyroidal illness syndrome is a manifestation of hypothalamic-pituitary dysfunction, and in view of current evidence, should be treated with appropriate replacement therapies. Crit Care Clin. 2006 Jan;22(1):57-86. DOI: 10.1016/j.ccc.2005.10.001
  21. Tomohiro Hayashi, Takuya Hasegawa, Hideaki Kanzaki, Akira Funada, Makoto Amaki, Hiroyuki Takahama, et al. Subclinical hypothyroidism is an independent predictor of adverse cardiovascular outcomes in patients with acute decompensated heart failure. ESC Heart Fail. 2016 Sep;3(3):168-76. DOI: 10.1002/ehf2.12084
  22. Danzi S, Klein I. Thyroid disease and the cardiovascular system. Endocrinol Metab Clin North Am. 2014;43:517-28. DOI: 10.1089/ 105072502760143836
  23. Dobre D, van Veldhuisen DJ, Goulder MA, Krum H, Willenheimer R. Clinical effects of initial 6 months monotherapy with bisoprolol versus enalapril in the treatment of patients with mild to moderate chronic heart failure. Data from the CIBIS III Trial. Cardiovasc. Drugs. Ther. 2008;22:399-405.
  24. Torp-Pedersen C, Metra M, Charlesworth A, Spark P, Lukas MA, Poole-Wilson PA, et al. COMET Investigators. Effects of metoprolol and carvedilol on pre-existing and new onset diabetes in patients with chronic heart failure: data from the Carvedilol Or Metoprolol European Trial (COMET). Heart. 2007;93(8):968-73.
  25. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. Update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J. Am. Coll. Cardiol. 2009;53(15):1343-82.
  26. Wiersinga WM, Touber JL. The influence of beta-adrenoreceptor blocking agents on plasma thyroxine and triiodothyronine. J Clin Endocrinol Metab. 1977;45(2):293-8.
  27. Perrild H, Hansen JM, Skovsted L, Christensen LK. Different effects of propranolol, alprenolol, sotalol, atenolol and metoprolol on serum T3 and serum rT3 in hyperthyroidism. Clin Endocrinol (Oxf). 1983;18(2):139-42.
  28. Jahagirdar VR, Strouhal P, Holder G, Gama R, Singh BM. Thyrotoxicosis factitia masquerading as recurrent Graves’ disease: endogenous antibody immunoassay interference, a pitfall for the unwary. Ann Clin Biochem. 2008;45:325-7.
  29. Fugazzola L, Persani L, Mannavola D, Reschini E, Vannucchi G, Weber G, et al. Recombinant human TSH testing is a valuable tool for differential diagnosis of congenital hypothyroidism during L-thyroxine replacement. Clin Endocrinol (Oxford). 2003;59:230-6.
  30. Rubio IG, Silva MN, Knobel M, Romão R, Possato R, Gebrin E, et al. Peripheral blood levels of thyroglobulin Mrna and serum thyroglobulin concentrations after radioiodine ablation of multinodular goiter with or without pre-treatment with recombinant human thyrotropin. J Endocrinol Invest. 2007;30:535-40.
  31. Chopra IJ, Teco GN, Nguyen AH, Solomon DH. In search of an inhibitor of thyroid hormone binding to serum proteins in nonthyroid illnesses. J Clin Endocrinol Metab. 1979;49:63-9.
  32. Christian Trummer, Verena Schwetz, Felix Aberer, Marlene Pandis, Elisabeth Lerchbaum, Stefan Pilz. Rapid Changes of Thyroid Function in a Young Woman with Autoimmune Thyroid Disease. Med Princ Pract. 2019 Jul;28(4):397-400. DOI: 10.1159/000499754
  33. Nattel S, Rangno RE, Van Loon G. Mechanism of propranolol withdrawal phenomena. Circulation. 1979 Jun;59(6):1158-64.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 4 Part 1 (153), 2019 year, 142-148 pages, index UDK 616.12-008.46-085.22:616.441-006.5

DOI: