• Received his master degree in 1994 at Shanghai Second Medical University;

• Took his doctor’s degree on Endocrinology at shanghai Jiaotong University school of medicine in 2007;

• From the year 2001 to 2003, He took an advanced study in Baylor College of Medicine , America.

• Headman, Endocrinology and Metabolism section, Institute of Health Sciences, Shanghai Institutes for Biological Sciences since 2004.

• Chief of office, Thyroid disease education project team, Ministry of Health, China since 2009;

• Youth member, Endocrinology society of Chinese Medical Association in 2009.

• Committee member of Chinese thyroid Association in 2010.

Shu Wang, MD, PhDThe archiater of Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, China. Doctoral supervisor.

The Cardiovascular System in Thyrotoxicosis

Dept. of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University, School of Medicine

Shanghai, China

Dr. Shu Wang shuw@sibs.ac.cn

• Thyrotoxicosis has important clinical

consequences for the cardiovascular systems.

• Thyrotoxicosis can increase cardiovascular

morbidity and mortality.

• The cause of cardiovascular signs and symptoms by thyrotoxicosis can easily be neglected.

keep “Thyrotoxicosis” in mind!

• Thyrotoxicosis is the clinical syndrome of hyperthyroidism resulting from excessive quantities of the thyroid hormones.

Case 1 A 63-year-old female patient Chest distress ,palpitation behind fatigue, sweating,weight loss of 1 year Oral glyceryl trinitrate provided no relief PE: heart rate:120 beats per minute; arrhythmia ECG: atrial fibrillation; ST-Tchange Diagnosis:coronary heart disease;atrial fibrillation

Is it an accurate diagnosis ?

★Thyrotoxicosis

Atrial Fibrillation

The causes of atrial fibrillation

InfectionsPulmonary disease

Neurogenic AF

Alcohol Drugs Electric shockSurgery......

Heart

Atrial fibrillationAngina pectoris

SweatingWeight lossheart rate increased

Thyroid funtion ?

FT3>46.08pmol/LFT4 67.5pmol/LTSH ＜ 0.0025μU/LTRAb>40IU/LTGAb 14.51IU/LTPOAb 737.14

thyrotoxicosis induced cardiovascular dysfunction

Thyrotoxicosis induced cardiovascular dysfunction

• The morbidity of thyrotoxicosis induced cardiovascular dysfunction is about 5 ％～ 10 ％ .

• Graves disease is the most common cause of thyrotoxicosis accounting for 60% to 90% of cases.

• Clinical classification: • 1) Hyperthyoidism as an initial cause;• 2) Hyperthyoidism as a worsen factor when patient has

underlying cardiac disease.

Clinical manifestationHypermetabolism syndrome:Weight loss with increased appetiteWarm and sweatingCoarse tremor in extremities,etc.

Cardiac symptoms in an early stage ：Palptations, Exercise intolerance,Dyspnea on exertion, Tachycardia,etc.

Heart complication ：Atrial fibrillation, Cardiomyopathy, Heart failure, Angina pectoris and Myocardial infarction.

The patient presents

SweatingWeight loss

Palpitationschest distress

Atrial fibrillationAngina pectoris

Thyrotoxicosis induced cardiovascular dysfunction

Diagnostic criteria ?

① Atrial Arrhythmias, enlarged heart or ventricular failure②Clinical manifestations and biochemical proof of Hyperthyroidism③After specific treatment ，the above-mentioned can disappear

NYHA(New York Heart Association)

Chinese scholars’ consensus Along with hyperthyroidism ，

One having at least one item of heart abnormality can diagnosed hyperthyroidism heart disease ：①enlarged heart ；② Arrhythmias ；③ congestive heart failure ；④ Angina pectoris and myocardial infarction ；

Meanwhile ， another factors changing heart functions should be excluded

Rarely， young patients with thyrotoxicosis may have chest pain similar in almost all respects to angina pectoris.

Thyrotoxicosis induced cardiovascular dysfunction

What type of thyrotoxicosis induced cardiovascular diseases is the patient ？

Types: Arrhythmia type Heart failure type Cardiomyopathy type

Thyrotoxicosis induced cardiovascular dysfunction

Arrhythmia Type Atrial fibrillation is the most common arrhythmia. The incidence is about 10%~20% hyperthyroidism patients. Heart failure Type Present in 6% of cases. It can be divided into high output failure and

pump failure. Risk factors: Age ＞ 60, long term uncontrolled

hyperthyroidism,underlying heart disease and AF .

Cardiomyopathy Type: (rare) Rate-related cardiomyopathy: Tachycardiainduced cardiomyopathy can

cause heart failure, although LVEF usually normalizes after heart rate or rhythm control.

Dilated cardiomyopathy: Associated with Graves disease might have an auto-immune origin.

Thyrotoxicosis induced cardiovascular dysfunction

In patients with hyperthyroidism ：Morbidity of AF is 8.3%Male sex, increasing age, ischemic heart disease, congestive heart failure, and heart valve disease are associated with an increased risk of AF

Arch Intern Med. 2004;164:1675-1678

Mechanisms

★ The heart is main target organ of Thyroid Hormone.

T3 influence cardiac action by three different routes:

1) T3 exerts a direct effect on cardiac myocytes;

2) T3 may influence the sensitivity of the sympathetic system; 3) T3 leads to periphery hemodynamic changes.

Thyrotoxicosis induced cardiovascular dysfunction

T3 effects on the cardiac myocyte

Genomic nuclear effects:T3 binds to nuclear thyroid hormone receptors (TRs), combined with recruited cofactors.The complex then bind or release specific sequences of DNA , modifying the rate of transcription of specific cardiac genes.

Non-genomic effects:T3 direct modulate the transport of ions (calcium, sodium and potassium) across the plasma membrane, glucose and amino acid transport,mitochondrial function and various intracellular signalling pathways.

Regulated cardiac gene as reported

Interactions between THs and the sympathetic system

Some T3 effects are mediated by an increased activity of the sympathetic system or an increased responsiveness and sensitivity of cardiac tissue to normal sympathomimetic stimuli.

The enhanced sympathetic sensitivity of the hyperthyroid heart may be mediated by an increased number of β-adrenergic receptors.

Haemodynamic changes

SV

R d

ecreases

T3

vascular smooth muscle cells

endothelialcell

nongenomic

genomic

membraneion channels

NO

NO

paracrine manner

vascular

relaxation

T3 relaxs vascular smooth muscle cells though regulation of nitric oxide ( NO), and decreases peripheral resistance.

only 50% of hyperthyroidism patients with congestive heart failure have impaired left ventricular (LV) systolic function . LV diastolic dysfunction may involve in the remaining half.

The patient has been confirmed ， and how to treat it ？

Thyrotoxicosis induced cardiovascular dysfunction

Management and Treatment

• Principle:• ①Recover the thyroid function as soon as

possible.To rapidly reduce the actions of thyroid hormone, ATDs and Radioiodine is recommended;

②Acute treatment of cardiac complications；

• Most patients who get immediate control of hyperthyroidism， can self-recover cardiac disorders gradually.

Thyrotoxicosis induced cardiovascular dysfunction

Therapy of atrial fibrillation

• Control the thyroid function

• About 50% AF in young and new onsets can convert to sinus rhythm after keeping euthyroid for 6~12 months.

• Those AF consisting for more than 4 months after euthyroid ， Drugs and Electroversion can be considered.

• Anticoagulative therapy is recommended in the absence of a specific contraindication, at least until a euthyroid state has been restored and heart failure has been cured.(ACC/AHA)

Therapy of heart failure

• Control the thyroid function;

(The treatment of HF follows its conventional therapy. ）• Expectant treatment: Sedation, oxygen uptaking, sodium

limiting ， etc.• β-blokers is used to stable the heart rate• Digitalis and Diuretic can effectively relieve heart burden

and pulmonary congestion symptoms. However it is hard to restore totally.

• Dosage of Digitalis is greater than usual loading and maintenance dosage maybe needed.

Thyrotoxicosis induced cardiovascular dysfunction

Case 2 A 60-year-old male patient Palpitations, fatigue, weakness, weight loss of 1 month's duration The patient had been taking amiodarone for 2.5 years for

non-sustained ventricular tachycardia episodes. amiodarone had been discontinued for six months PE: heart rate:98 beats per minute

what about thyroid function?

laboratory analysis:FT3 ： 20.08pmol/L FT4 ： 44.5pmol/L TSH ： 0.083U/L

Is it Amiodarone-Induced Thyrotoxicosis?

Amiodarone-Induced Thyrotoxicosis(AIT)

• The incidence of AIT reported in different studies varies

but remains within the range of 5–10% in most studies.• AIT may develop suddenly and early or after many years of

treatment, the usual time period is 2–47 months;• AIT may also develop many months after drug withdrawal.

Iodine deficient individuals render more sensitive to exogenous iodine

Risk factors： female sex, complex cyanotic heart disease, previous Fontan type surgery, and a total daily dose above 200 mg

Why does Amiodarone can Induce Thyrotoxicosis?

Types

★ Some patients exhibit a mixed pattern

• The decision to stop amiodarone in the setting of thyrotoxicosis should be determined on an individual basis in consultation with a cardiologist, based on the presence or absence of effective alternative antiarrhythmic therapy.

Is it need for amiodarone discontinuation?

The need for amiodarone discontinuation is controversial, because :

(1) This drug is frequently the only medication able to control

cardiac arrhythmia, (2) The effects of this fat soluble drug may persist for many

months.(3) Amiodarone may have T3-antagonistic properties and

inhibit T4 to T3 conversion, withdrawal Amiodarone may aggravate cardiac manifestations of thyrotoxicosis.

(4) AIT typically resolves even if amiodarone therapy is continued.

Conclusion: a: Euthyroidism was reached despite continuation of amiodarone in all patients. b: Prednisone remains the preferred treatment of AIT type 2.

Thyrotoxicosis and Pregnancy

• Effects On Cardiovascular hemodynamics are additive

Mother: spontaneous abortion, hyperthyroidism crisis, heart failure, preeclampsia, premature delivery, etc;

Fetus: stillbirth, Growth restriction, goiter, heart failure, etc;

• It is more urgent to control thyroid function and monitor heart function.

There is no evidence of teratogenesis following maternal exposure to beta-blockers in the first trimester.

The risk of IUGR associated with maternal use of beta-blockers exists ， use the smallest effective dose (avoiding large doses) and use is limited to the third trimester.

There is also a theoretical risk of neonatal bradycardia, hypotension and hypoglycaemia if beta-blockers are used up to the time of delivery.

Use β-blocker Cautiously in pregnancy

Take Home Message

• In clinics, the patient's history and thyroid function tests are important. (monitor)

• The first step for treating heart complications is hyperthyroidism control. (treatment)

• It is important to take risk factors into account, such as age, sex, hyperthyroidism type, underlying health problems. (prevention)

Thank you!Thank you!