Arrhythmia

Management
in Thyroid
Heart Disease
HENDARTO ARIF BUDIMAN, dr
BUDI BAKTIJASA DHARMADJATI dr, Sp.JP(K)FIHA

Department of Cardiology and Vascular Medicine

Faculty of Medicine, Universitas Airlangga, Dr. Soetomo General Hospital,
Surabaya
Contents
01 Introduction

02 Discussion
• Pathophysiology of Arrhythmia
• Clinical Presentation
• Physiology of Thyroid Hormone
• Thyroid Effect in Cardiac Myocyte
• Thyroid Dysfunction in Arrhythmia
• Arrhythmia Treatment in Thyroid Dysfunction

03 Summary
INTRODUCTION
 Cardiac dysrhythmia (or arrhythmia) is a disturbance in the rate of
cardiac muscle contractions, or any variation from the normal
rhythm or rate of heart beat: abnormal regular and irregular
rhythms as well as loss of rhythm (BMJ, 2021)

Thyroid disease estimated affect 9% to 15% of the adult female

population and a smaller percentage of adult men. Excess and
deficiency of thyroid hormones can induce or worsen
cardiovascular disorders, including atrial and ventricular
arrhythmias, atherosclerotic vascular disease, dyslipidemia, and
heart failure, thus contributing to a higher risk of morbidity and
premature death.

The therapeutic approach to arrhythmia conditions is a challenge

for a clinician to prevent the worsening of the condition and
mortality due to thyroid disease.

• Overview of dysrhythmias (cardiac)- Summary of relevant conditions | BMJ Best Practice. (n.d.). Retrieved September 11,
2021, from https://bestpractice.bmj.com/topics/en-gb/837
• Cappola, A. R., Desai, A. S., Medici, M., Cooper, L. S., Egan, D., Sopko, G., Fishman, G. I., Goldman, S., Cooper, D. S.,
Mora, S., Kudenchuk, P. J., Hollenberg, A. N., McDonald, C. L., & Ladenson, P. W. (2019). Thyroid and Cardiovascular
Disease. Circulation, 139(25), 2892–2909. https://doi.org/10.1161/CIRCULATIONAHA.118.036859.
• Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000;
160: 526–530.
DISCUSSION
 Pathophysiology of Arrhythmia
Arrhythmia: heart rhythm disturbances in the heart that manifest in irregularities
and/or abnormalities of fast rhythms (tachycardia) or slow abnormalities
(bradycardia).

Mechanism of Arrhythmia:
1. Abnormal automaticity.
2. Triggered activity refers to pacemaker activity that is dependent on
after depolarizations from a prior impulse or series of impulses.
3. Impuls conduction disturbances / Reentry

Tse, G. (2015). Mechanisms of cardiac arrhythmias. https://doi.org/10.1016/j.joa.2015.11.003.

Klein I. Chapter 81: Endocrine disorders and cardiovascular disease. In: Braunwald’s Heart Dis- ease. 10th edition.
Philadelphia, Pennsylvania: Elsevier, 2014:1793–808. 12.
 Clinical Presentation of Arrhythmia
Symptoms:
Heart palpitations, syncope, pre-syncope or shortness of breath.
The onset mode of an episode :type of arrhythmia and the selection of appropriate therapy.
Patients should be asked : frequency and duration of episodes, severity of symptoms.

Physical Examinations:
Heart rate, blood pressure ,quality of the patient's pain.
Variations in the intensity of the first heart sound and systolic blood pressure .

Supporting examinations: Conventional ECG, momentary ECG or 12 lead ECG. If needed: bed monitoring ECG,
Holter monitor, Exercise ECG, Esophageal ECG and Intracardial ECG.

Laboratory examinations such as thyroid hormone, echocardiography, CXR, precipitation factors..

Opie LH. Drugs for the Heart. 8th ed. Saunders; 2013. 273-325 hal.
Mann DL, Zopes DP, Libby P, Bonow RO. Braunwald;s Heart Disease: A Textbook of Cardiovascular Medicine. 10 ed. Saunders, 2014. 748-
797 hal.
 • Physiology of Thyroid Hormone
• Thyroid function is regulated by the hypothalamic-
pituitary-thyroid axis via a classic endocrine feedback loop
mechanism.
• The 2 main iodinated THs are T4 and triiodothyronine
(T3). Both have biological effects; T3 is considered the
active and more potent hormone.
• The normal negative feedback regulation of thyroid
function is disrupted by illness, including conditions such
as acute myocardial infarction (AMI) or heart failure (HF),
and is characterized by a reduction in serum TH without a
concomitant rise in circulating TSH levels.

• Larsen PR. Thyroid-pituitary interaction: feed- back regulation of thyrotropin secretion by thyroid
hormones. N Engl J Med 1982;306:23–32
• Razvi, S., Jabbar, A., Pingitore, A., Danzi, S., Biondi, B., Klein, I., Peeters, R., Zaman, A., & Iervasi,
G. (2018). Thyroid Hormones and Cardiovascular Function and Diseases. Journal of the American
College of Cardiology, 71(16), 1781–1796. https://doi.org/10.1016/j.jacc.2018.02.045.
 Thyroid Effect in Cardiac Myocyte

T3 has both genomic and nongenomic effects

on the cardiac myocyte.
• Genomic effects are mediated by the
transport of plasma T3 into the cardiac
myocyte and direct binding to the TR
• It regulates transcription of specific cardiac
genes. Positively regulated genes are
transcribed and negatively regulated genes
are repressed in the presence of T3.
• Nongenomic mechanisms include direct
modulation of membrane ion channels
Razvi, S., Jabbar, A., Pingitore, A., Danzi, S., Biondi, B., Klein, I., Peeters, R., Zaman, A., & Iervasi, G. (2018).
Thyroid Hormones and Cardiovascular Function and Diseases. Journal of the American College of Cardiology,
71(16), 1781–1796. https://doi.org/10.1016/j.jacc.2018.02.045.
Klein I, Danzi S (2007) Thyroid disease and the heart. Circulation 116(15):1725–1735).
 Hyperthyroid in Arrhythmia
1. Atrial Arrythmia

Thyroid hormone had the following effects on arrhythmogenesis

• Decreased APD (action potential duration)
• Increased spontaneous activity in pulmonary vein cardiomyocytes
• Increased occurrence of delayed after-depolarizations in
pulmonary vein beating and non-beating cardiomyocytes
• Increased after-depolarizations in beating cardiomyocytes

• Hyperthyroidism has been associated with atrial tachyarrhythmia

and with sustained AF occurring in 20–30% of patients even after
return to the euthyroid state.

• The risk of AF or flutter in hyperthyroidism: higher in men than in women.

• Risk of AF in hyperthyroidism increased with increasing age during the age
range of 20– 89 years.
• Epstein FH, Klein I, Ojamaa K (2001) Thyroid hor- mone and the cardiovascular system. N Engl J Med 344(7):501–509.
• Frost L, Vestergaard P, Mosekilde L. Hyper- thyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch
Intern Med 2004; 164:1675–8.
• Klein I, Danzi S (2007) Thyroid disease and the heart. Circulation 116(15):1725–1735)
• Reddy, V., Taha, W., Kundumadam, S., & Khan, M. (2017). Atrial fibrillation and hyperthyroidism: A literature review. Indian
Heart Journal, 69(4), 545–550. https://doi.org/10.1016/j.ihj.2017.07.004
 Hyperthyroid in Arrhythmia
1. Atrial Arrythmia

• RR of AF in subjects with low serum thyrotropin (normal free T3,T4) compared

to normal :5.2.
• Low serum thyrotropin is associated with >5 fold higher likelihood for AF with
subclinical hyperthyroidism

• Framingham Heart Study: low thyrotropin (<0.1 mU/L) had 28% incidence of
AF, compared with 11% in normal subjects. RR for development of AF was
3.1

• Left atrial (LA) mechanical and electromechanical function in subclinical

thyroid disorders is impaired and TSH is an independent determinant of inter-
atrial delay. It may be related to the increased incidence of arrhythmias.

• N J, Francis J (2005) Atrial fibrillation and hyperthy- roidism. Indian Pacing Electrophysiol J 5(4):305– 311
• Ozturk S, Dikbas O, Baltacı D et al (2012) Evaulation of atrial conduction abnormalities and left atrial mechanical functions
in patients with subclinical thyroid disorders. Endokrynol Pol 63(4):286–293
 Hyperthyroid in Arrhythmia

2. Ventricular Arrythmia
• Rare in hyperthyroid patients
• QT prolongation is described in Graves disease with
thyrotoxicosis
• Few cases of isolated VF without structural heart disease and
electrolyte imbalance in hyperthyroidism have been reported.

Bradyarrhythmia, AV block and sick sinus syndrome (SSS), is a

rare finding in hyperthyroid patients; One study reported that only
3% of cases of AV blocks with pacemaker implantation were
caused by primary hyperthyroidism.

• Kulairi Z, Deol N, Tolly R, Manocha R, Naseer M. QT prolongation due to Graves’ disease. Case Rep Cardiol 2017;2017:1.
• Kobayashi H, Haketa A, Abe M, Tahira K, Hatanaka Y, Tanaka S et al. Unusual manifestation of Graves’ disease: ventricular
fibrillation. Eur Thyroid J 2015;4: 207–12
• Ozcan KS, Osmonov D, Erdinler I, Altay S, Yildirim E, Turkkan C et al. Atrioventricular block in patients with thyroid
dysfunction: prognosis after treatment with hormone supplementation or antithyroid medication. J Cardiol 2012;60:327–32.
 Hypothyroid in Arrhythmia
• Hypothyroidism is accompanied by ventricular arrhythmias and
conduction disturbances.
• A typical ECG in hypothyroidism shows bradycardia, a low voltage of
the QRS complexes, elongation of the PQ and flattening or inverting of
the T waves.

One case-control study of 152 hypothyroid and 152 euthyroid patients,

revealed higher prevalence of VT (P=0.04) and ventricular arrhythmias
(P=0.007) in hypothyroid patients120 and Torsades de Pointes with
prolongation of QT interval and bradycardia.

It is advised to consider hypothyroidism in differential diagnosis of

polymorphic VT.

There are case reports on advanced AV block of 2nd and 3rd degree
reversed by thyroid replacement therapy and temporary pacemaker
implantation in overt and subclinical hypothyroidism
• Chojnowski K, Bielec A, Czarkowski M et al (2007) Repeated ventricular. Cardiol J 14(2):198–201
• Kannan L, Kotus-Bart J, Amanullah A. Prevalence of cardiac arrhythmias in hypothyroid and euthyroid patients. Horm
Metab Res 2017;49:430–3
• Ellis CR, Murray KT. When an ICD is not the answer.. . Hypothyroidism- induced cardiomyopathy and torsades de pointes.
J Cardiovasc Electrophysiol 2008;19:1105–
• Kandan SR, Saha M. Severe primary hypothyroidism presenting with torsades de pointes. BMJ Case Rep
2012;2012:bcr1220115306. doi: 10.1136/bcr. 12.2011.5306.
 Thyroid Dysfunction Induced by Amiodarone
• Amiodaron is the most commonly used antiarrhythmic drug worldwide.
• It is effective in the treatment of supraventricular and ventricular
tachyarrhythmia.
• Benefit of being tolerated in both patients with normal and impaired LV systolic
function.

Amiodarone-induced thyroid dysfunction manifests as amiodarone-induced

hyperthyroidism with two distinctive types:
• type 1, which develops in presence of underlying thyroid disease with excessive
hormone production in response to iodide load associated with amiodarone leading
to true hyperthyroidism.
• type 2, destructive thyroiditis that develops due to direct toxic effects if iodine
associated with amiodarone.

• Chojnowski K, Bielec A, Czarkowski M et al (2007) Repeated ventricular. Cardiol J 14(2):198–201

• Kannan L, Kotus-Bart J, Amanullah A. Prevalence of cardiac arrhythmias in hypothyroid and euthyroid patients. Horm
Metab Res 2017;49:430–3
• Ellis CR, Murray KT. When an ICD is not the answer.. . Hypothyroidism- induced cardiomyopathy and torsades de pointes.
J Cardiovasc Electrophysiol 2008;19:1105–
• Kandan SR, Saha M. Severe primary hypothyroidism presenting with torsades de pointes. BMJ Case Rep
2012;2012:bcr1220115306. doi: 10.1136/bcr. 12.2011.5306.
 Management of Arrhythmia in Thyroid Dysfunction

• Antithyroid treatment and attainment of euthyroid state should be the first

line in management of AF in the setting of hyperthyroidism,

• For rate control of AF and as an adjunct to antithyroid therapy, non-selective

beta-blockers like propranolol may be used,

• Beta-Adrenergic Blockade Propranolol (20–40 mg every 6 h) or longer

acting beta blockers (i.e., atenolol/bisoprolol), are useful to control
adrenergic symptoms such as palpitations and tremor, especially in the
early stages before ATD take effect.

• Successful treatment of hyperthyroidism with either radioiodine or thioureas

is associated with a reversion to sinus rhythm in the majority of patients.

Gorenek, B., Boriani, G., Dan, G. A., Fauchier, L., Fenelon, G., Huang, H., Kudaiberdieva, G., Lip, G. Y. H.,
Mahajan, R., Potpara, T., Ramirez, J. D., Vos, M. A., Marin, F., Blomstrom-Lundqvist, C., Rinaldi, A., Bongiorni,
M. G., Sciaraffia, E., Nielsen, J. C., Lewalter, T., … Fuenmayor, A. (2018). European Heart Rhythm
Association (EHRA) position paper on arrhythmia management and device therapies in endocrine disorders,
endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS).
Europace, 20(6), 895–896. https://doi.org/10.1093/europace/euy051.
 Management of Arrhythmia in Thyroid Dysfunction

• Recommendation of cardioversion in patients with persistent AF after

establishment of euthyroid state, and in case of recurrent AF when the
patient is euthyroid, ablation should be considered.

• After chemically euthyroid, electrical or pharmacological cardioversion

should be attempted.
• Elective cardioversion for those patients where AF persists is highly
effective and sinus rhythm maintenance rates are greater than 50% over 10
years.

Bepridil is a very beneficial medicine for patients with hyperthyroidism-induced

AF; however, it should be used with caution, and frequent or continuous
electrocardiogram (ECG) monitoring is necessary to avoid serious side effects

• Gorenek, B., Boriani, G., Dan, G. A., Fauchier, L., Fenelon, G., Huang, H., Kudaiberdieva, G., Lip, G. Y. H., Mahajan, R., Potpara, T., Ramirez, J. D., Vos, M. A., Marin, F., Blomstrom-
Lundqvist, C., Rinaldi, A., Bongiorni, M. G., Sciaraffia, E., Nielsen, J. C., Lewalter, T., … Fuenmayor, A. (2018). European Heart Rhythm Association (EHRA) position paper on
arrhythmia management and device therapies in endocrine disorders, endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS).
Europace, 20(6), 895–896. https://doi.org/10.1093/europace/euy051.
• Marrakchi, S., Kanoun, F., Idriss, S., Kammoun, I., & Kachboura, S. (2014). Arrhythmia and thyroid dysfunction. Herz 2014 40:2, 40(2), 101–109. https://doi.org/10.1007/S00059-014-
4123-0.
 Management of Arrhythmia in Thyroid Dysfunction

The VT/VF, accompanying hypothyroidism requires correction with thyroid

hormones, DC shock in urgent cases, correction of electrolyte balance, and
bradycardia if QT prolongation and Torsades de Pointes arrhythmia. If
arrhythmia is sustained or recurs, the implantation of ICD could be considered.

Rarely, in patients with implanted pacemakers and ICDs, overt or

subclinical hypothyroidism due to functional changes in tissue might increase
pacing threshold or create exit block in atrial and ventricular pacing leads that
usually are reversible by correction of thyroid status.

• Anticoagulation of patients with hyperthyroidism and AF is controversial.

• Hyperthyroidism does not independently confer higher risk for
stroke/systemic embolic events as compared to non-hyperthyroid
patients,and annual risk of stroke in hyperthyroid patients with AF is lower
than in non-hyperthyroid patients.
• Warfarin reduced the risk of ischaemic stroke in non-self-limiting AF patients
with hyperthyroidism and CHA2DS2VASc Stroke score>_1.

• Gorenek, B., Boriani, G., Dan, G. A., Fauchier, L., Fenelon, G., Huang, H., Kudaiberdieva, G., Lip, G. Y. H., Mahajan, R., Potpara, T., Ramirez, J. D., Vos, M. A., Marin, F., Blomstrom-
Lundqvist, C., Rinaldi, A., Bongiorni, M. G., Sciaraffia, E., Nielsen, J. C., Lewalter, T., … Fuenmayor, A. (2018). European Heart Rhythm Association (EHRA) position paper on
arrhythmia management and device therapies in endocrine disorders, endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS).
Europace, 20(6), 895–896. https://doi.org/10.1093/europace/euy051.
• Marrakchi, S., Kanoun, F., Idriss, S., Kammoun, I., & Kachboura, S. (2014). Arrhythmia and thyroid dysfunction. Herz 2014 40:2, 40(2), 101–109. https://doi.org/10.1007/S00059-014-
4123-0.
 Management of Amiodarone induced Thyroid Dysfunction

• Gorenek, B., Boriani, G., Dan, G. A., Fauchier, L., Fenelon, G., Huang, H., Kudaiberdieva, G., Lip, G. Y. H., Mahajan, R., Potpara, T., Ramirez, J. D., Vos, M. A., Marin, F., Blomstrom-
Lundqvist, C., Rinaldi, A., Bongiorni, M. G., Sciaraffia, E., Nielsen, J. C., Lewalter, T., … Fuenmayor, A. (2018). European Heart Rhythm Association (EHRA) position paper on
arrhythmia management and device therapies in endocrine disorders, endorsed by Asia Pacific Heart Rhythm Society (APHRS) and Latin American Heart Rhythm Society (LAHRS).
Europace, 20(6), 895–896. https://doi.org/10.1093/europace/euy051.
SUMMARY
 SUMMARY
• Thyroid hormones are able to trigger arrhythmias in mostly at the atrial level.
• The incidence of cardiac arrhythmias is in relation to an altered thyroid status.
• Hypothyroidism is mostly associated with reduced likelihood of cardiac arrhythmias unlike
hyperthyroidism which increases the risk especially for the atrial and lower in ventricular
arrhythmias.
• The main management of arrhythmia therapy is to achieve euthyroid conditions, so the use
of anti-thyroid is preferred in addition to the use of anti-arrhythmic drugs.
THANK YOU