2. THYROID AND CVS
Case 1
• A 25 year old female presented with SOB cl
II-III .
– Pulse 70/min,
– BP- 100/60.
– Echo-large pericardial effusion , no tamponade.
– TSH- 33 mIU/mL.
Recovered with thyroid correction
Mild PE, BP-130/80.
3. THYROID AND CVS
Case 2
• 65 year old presented with palpitaions and
NYHA class 4 breathlessness.
– ECG- AF with FVR.
– ECHO global hypokinesia , EF40%
– TSH<0.01.
• Stabilised and sinus rhythm was restored
with antithyroid medications.
4. THYROID AND CVS
OVERVEIW
• Introduction
• Hemodynamics
• Hypothyroid and heart
• Hyperthyroid and heart
• Subclinical hypothyroid and
hyperthyroid
• Amiodarone and heart.
5. THYROID AND CVS
INTRODUCTION
• In ontogeny, the thyroid and heart anlage
migrate together.
• Thyroid gland and the heart share a close
relationship that arises in embryology.
7. THYROID AND CVS
CARDIOVASCULAR HEMODYNAMICS
• Thyroid hormone effects on the heart and
peripheral vasculature include
– decreased SVR and
– increased resting heart rate,
– Increase in left ventricular contractility, and
– blood volume
9. CARDIAC CONTRACTION
SERCA PHOSPHOLAMBAN
SYSTEM
SERCA
Reuptake of calcium in early diastole
Phosphorylation of Phospholamban
relaxation of LV
inhibits SERCA
Contraction of LV
inhibits
T3
Cytosolic Calcium
increase -- contraction
decrease-- relaxation
Ca++
Ca++
11. THYROID AND CVS
• Herat rate
• The pacemaker-related genes, are
transcriptionally regulated by thyroid
hormone.
• Stimulation of -adrenergic receptors
accelerates diastolic depolarization and
increases heart rate.
12. THYROID AND CVS
• Basal metabolic rate
• Thyroid hormone increases BMR in almost
every tissue and organ system in the body.
• This increased metabolic demands lead to
changes in cardiac output, SVR, and blood
pressure.
13. THYROID AND CVS
• Blood pressure
• Hyperthyroidism:
– Arterial stiffness is increased
– Typically causes systolic blood pressure to rise
– A widened pulse pressure
• Hypothyroidism:
– Endothelial dysfunction and impaired VSM
relaxation lead to increased SVR.
– lead to diastolic hypertension in 30% of
patients.
14. THYROID AND CVS
• Cardiac output
• Increased
• In hyperthyroidism, cardiac output 50% to 300%
higher than in normal individuals.
• In hypothyroidism, decrease by 30% to 50%.
• Restoration of normal cardiovascular
hemodynamics can occur with treatment.
15. THYROID AND CVS
• Pulmonary Hypertension
• Primarily in hyper thyroidism
• The increase in cardiac output without the
concomitant decline in pulmonary vascular
resistance observed in the systemic circulation.
• Some evidence exists that autoimmune disease
may play a role in both hypothyroid- and
hyperthyroid-linked cases of primary
pulmonary hypertension.
19. THYROID AND CVS
HYPOTHYROIDISM
• Major cardiovascular changes
– decrease in cardiac output
– decrease in cardiac contractility
– reduction in heart rate
– increase in peripheral vascular resistance.
• Others
– Hypercholesterolemia ,
– diastolic hypertension,
– carotid intimal media thickness
20. THYROID AND CVS
• CLINICAL MANIFESTATIONS —
• Exertional dyspnea and exercise intolerance -due
to skeletal muscle dysfunction.
• Cardiac dysfunction with poor contractility,
dilatation
• Edema, often nonpitting
21. THYROID AND CVS
Rhythm
• Bradycardia
• Low QRS voltage
• Widespread T-wave inversions (usually without ST
deviation)
• QT prolongation-rarely Torsedes
• First degree AV block
• Interventricular conduction delay
22. THYROID AND CVS
• Mechanism
• Myxoedematous deposits within the
myocardium.
• Decreased activity of the sympathetic
nervous system.
• Effects on the myocardium of reduced
levels of thyroxine (i.e. reduced
inotropy/chronotropy)
23. THYROID AND CVS
Bradycardia (30 bpm) with
Low QRS voltages (esp. in the limb leads). and
widespread T-wave inversions.
MYXOEDEMA
25. THYROID AND CVS
PERICARDIAL EFFUSION
•Pericardial effusions, in approximately 25% of patients
and may be quite large.
•Increased systemic capillary permeability and
disturbances in electrolyte metabolism.
• characterized by a high protein and cholesterol content.
26. THYROID AND CVS
• Lipid abnormalities and others:
– Marked increase LDL and apo B-
• cholesterol 7-hydroxylase is negatively regulated by
T3(decreased cholesterol catabolism)
– High Homocysteine
– High Creatine kinase — The isoenzyme
distribution is almost completely MM,indicating
skeletal muscle, not myocardial.
27. THYROID AND CVS
• Accelerated coronary artery disease .
– Hypercholesterolemia
– Diastolic hypertension, and
– Elevated homocysteine levels
– Elevated C-reactive protein and
– Endothelial dysfunction
• Patients with angina pectoris probably have
less symptoms as they are less active and
peripheral oxygen demands decrease.
28. TREATMENT
• In older patients or those
with a history of angina,
begin therapy with a low
dose of T4, as an
example 12.5 or 25 mcg
daily, because of the
possibility of inducing
an arrhythmia or an
exacerbation of angina.
• If revascularization is
indicated better to start
T4 after the procedure.
30. THYROID AND CVS
HYPERTHYROIDISM
• Increases in
– heart rate
– cardiac contractility,
– systolic and mean pulmonary artery pressure,
– cardiac output, diastolic relaxation, and
– myocardial oxygen consumption
• Reductions in
– systemic vascular resistance and
– diastolic pressure
31. THYROID AND CVS
• Tachycardia, at rest, during sleep, and exaggerated
during exercise.
• Palpitations – tachy/forceful cardiac contractility
• Hyperdynamic precordium.
• Systolic hypertension with widened pulse pressure
• Exertional dyspnea, which is due to respiratory
and skeletal muscle weakness
Clinical features
32. THYROID AND CVS
• Means–Lerman scratch
• Uncommon heart murmur which occurs in
patients with hyperthyroidism.
• It is a mid-systolic scratching sound best heard
over the second left intercostal space at the end of
expiration.
• Results from the rubbing of
the pericardium against the pleura in the context
of hyperdynamic circulation and tachycardia,
• Mimic the sound of a pericardial rub.
33. THYROID AND CVS
ANGINA PECTORIS
• Increase in cardiac oxygen consumption, due
either to a
– direct effect of triiodothyronine (T3) on cardiac
muscle or to an
– increase in peripheral oxygen demand.
• Prinzmetal angina
– In the young patient with normal coronary
anatomy, this may be due to coronary
vasospasm .
34. THYROID AND CVS
RHYTHM
• Atrial tissue is very sensitive to the effects
of thyroid hormone .
• More
– APCs,
– non-sustained SVT,
– VPCs,
• Reduced heart rate variability
35. THYROID AND CVS
RHYTHM
ATRIAL FIBRILLATION
• 2% and 20%.
• Associated with
– Male sex,
– increasing age , >60yrs.
– coronary heart disease.
– heart failure.
– valvular heart disease .
• subclinical hyperthyroidism -- same relative risk
37. THYROID AND CVS
• Treatment of AF-
– BB- beta1-selective or nonselective agent to
control the ventricular response
– Digoxin- better avoid decreased sensitivity to this
drug
– CCB- may lead to hypotension.
• Anticoagulation is controversial.
– Increased vitamin K metabolism leading to an
increase in sensitivity to warfarin anticoagulation.
– Advancing age is the main risk factor
– Asprin is effective safe alternative.
39. THYROID AND CVS
HEART FAILURE
• High output failure- not used these days
• Factors responsible
– Exaggerated sinus tachycardia or
– atrial fibrillation (rate-related)
– Mitral valve prolapse (MVP)– MR
• Increased prevalence in Graves’ and
Hashimoto’s diseases .
• Treated with BB and I 131.
40. THYROID AND CVS
PULMONARY HYPERTENSION
• PH has been reported with increasing frequency in
patients with overt hyperthyroidism.
• Pulmonary artery pressures average twice normal
values (10 mmHg) and may be as high as 30 to 50
mmHg.
• These changes reverse with treatment of the
hyperthyroidism .
41. THYROID AND CVS
MOYAMOYA DISEASE
• Characterized by anatomic occlusion of the terminal
portions of internal carotid arteries.
• In these patients, treatment of the hyperthyroidism can
prevent further cerebral ischemic symptoms.
• This reinforces the importance of routine thyroid function
tests (to include TSH) in patients who present with cardiac
and cerebral vascular ischemic symptoms
» Im SH, Oh CW, Kwon OK, Kim JE, Han DH. Moyamoya disease associated
with Graves disease: , J Neurosurg. 2005;102:1013–1017
43. THYROID AND CVS
SUBCLINICAL HYPOTHYROIDISM
• On TSH screening, the magnitude of
subclinical thyroid disease may exceed that
of overt disease by threefold to fourfold.
45. THYROID AND CVS
• Patients with subclinical hypothyroidism have
– prolonged isovolumic relaxation times,
– systolic contractile function does not change .
• Replacement with T4 at a mean dose of 68 μg/day
(range, 50 to 100 μg/day)
– restored isovolumic relaxation times to normal,
– systemic vascular resistance declined and
– systolic function improved significantly
46. THYROID AND CVS
• Study from the U.K. General Practitioners
data base showed that treatment of TSH levels
between 5 and 10 mIU/mL lowered the
incidence of ischemic heart disease events and
cardiovascular mortality in patients younger
than 70 years.
47. THYROID AND CVS
SUBCLINICAL HYPERTHYROIDISM
• Serum TSH level is low (<0.1 mIU/mL) and T4
and T3 levels are normal.
• The prevalence of atrial fibrillation after 10 years
was 28% Vs 11% with a relative risk of 3.1.
48. THYROID AND CVS
• Therapy can be individualized with regard to three
specific groups.
• The first group
– excessive thyroid medication, needs reduction of dose.
• The second group
– Previous diagnosis of thyroid cancer who are receiving
T4 to suppress TSH.
– younger patients -- beta blockers can useful
– In older patients, lowering the T4 dosage .
49. THYROID AND CVS
• The third group
– Endogenous thyroid gland overactivity,
including Graves disease or nodular goiter.
– Older patients are at risk for AF
– Methimazole 5 to 10 mg/day
– Consideration should be given to the use of
radioiodine for definitive therapy.
51. THYROID AND CVS
AMIODARONE AND THYROID FUNCTION
• Thyroid dysfunction in 60% of pts treated .
• Why
– Amiodarone is an iodine-rich (30% iodine
content by weight)
– structural similarity to levothyroxine
• Either
– hypothyroidism (5% to 25% of treated
patients) or
– hyperthyroidism (2% to 10% of treated
patients) in iodine-deficient areas.
52. THYROID AND CVS
AMIODARONE INDUCED
HYPOTHYROIDISM(AIH)
100mg amiodarone 3mg
iodine.
Risk factors
Preexistent thyroid disease.
Hashimoto’s thyroiditis.
Inhibition of 5 -deiodinase activity
Inhibits T4 to T3
The average iodine content in diet is about
0.3 mg/day.
Directly inhibit thyroid gland function
54. THYROID AND CVS
AMIODARONE-INDUCED
THYROTOXICOSIS (AIT)
• Less common but perhaps more challenging.
• 2% to 10% and vary directly with duration .
• Onset was often sudden, during chronic treatment,
or up to 1 year after stopping therapy.
55. THYROID AND CVS
• 2 forms of AIT exist.
• Type 1 hyperthyroidism
– with preexistent thyroid disease and goiter.
– more often in regions where iodine intake is low.
• Type 2 hyperthyroidism is caused by an
– inflammatory process that causes increased release of
thyroid hormones from a previously normal thyroid
gland.
• Sometimes Difficult to distinguish between them.
56. THYROID AND CVS
• TREATMENT OF TYPE I AIT:
• Thionamides — may be slow response and large
doses may be required.
• Surgery — Patients who are refractory to
antithyroid drug therapy should be treated by
thyroidectomy.
• Radioiodine ablation - is usually not an option
due to low radioiodine uptake in these patients as
they are iodine excess in body.
57. THYROID AND CVS
• Caution:
• Amiodarone appears to ameliorate
hyperthyroidism by blocking T4 to T3 conversion,
beta-adrenergic receptors, and possibly T3
receptors.
• Amiodarone should not be discontinued until
hyperthyroid symptoms are well controlled since
worsening of hyperthyroid symptoms due to
increased T3 levels.
58. THYROID AND CVS
• TREATMENT OF TYPE II AIT
• Glucocorticoids —
• Patients with type II hyperthyroidism respond well
to moderately large doses of corticosteroids
(eg, prednisone 40 to 60 mg/day) even if
the amiodarone is continued.
59. THYROID AND CVS
Whether to continue amiodarone……
• Since the t1/2 is about 100 days, there is no
immediate benefit on stopping amiodarone.
• Continue for life-threatening ventricular
arrhythmias.
• If not for life-threatening ventricular arrhythmias
discontinue if alternative can be used.
60. THYROID AND CVS
• Treatment if mechanism
unknown /“Mixed”form:
• combinationof prednisone (40 mg/day) and m
ethimazole (40 mg/day) is prudent initial therapy.
– A rapid response suggests type II
hyperthyroidism; the methimazole can then be
tapered or stopped and,
– A poor response initially argues for type I
hyperthyroidism. If so, steroids can be tapered.
62. THYROID AND CVS
Changes in Thyroid Hormone Metabolism
That Accompany Cardiac Disease
Decrease in serum T3.
63. THYROID AND CVS
• Low serum T3 level strongly predicts all-cause and
cardiovascular mortality.
• In ACS Serum T3 levels fall by about 20% and
reach a nadir after approximately 96 hours.
• Up to 30% of patients with heart failure have a low
serum T3 level.
• In view of the deleterious effects of hypothyroidism
on the myocardium, T3 replacement may provide
benefit.
64. THYROID AND CVS
When to check
Thyroid Function Testing
• Unexplained AF
• Unexplained CHF
• Pericardial effusion
• Diastolic hypertension
• On amiodarone every 3 months.
• Hyperlipidemia
• Critically ill patients.
65. THYROID AND CVS
When the Thyroid Speaks…the
Heart Listens”
MA Sussman.,Circ. Res 2001
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