- Case report
- Open Access
Second degree AV block and severely impaired contractility in cardiac myxedema: a case report
© Chatzitomaris et al.; licensee BioMed Central. 2015
- Received: 14 April 2015
- Accepted: 12 May 2015
- Published: 19 May 2015
The heart is a major target organ for thyroid hormone action. Severe overt hypothyroidism can result in diastolic hypertension, lowered cardiac output, impaired left ventricular contractility and diastolic relaxation, pericardial effusion and bradycardia. However, the function of the atrial pacemaker is usually normal and the degree by which the heart rate slows down is often modest. Here we report the case of a 20 year old male Caucasian with severe overt hypothyroidism. He presented with syncopation due to second degree atrioventricular block type Mobitz 2 and heart failure with reduced ejection fraction (38 %). Laboratory testing revealed a severe overt hypothyroidism with markedly elevated TSH (>100 mIU/L) and reduced fT3 and fT4 levels. The condition was caused by hypothyroid Graves’ disease (Graves’ disease with Hashimoto component). Although magnetic resonance imaging of the heart demonstrated decreased cardiac contractility and pericardial effusion, suggesting peri-myocarditis, plasma levels for BNP and troponin I were low. A possible infectious cause was unlikely, since testing for cardiotropic viruses was negative. The patient was treated with intravenous levothyroxine and after peripheral euthyroidism had been achieved, left ventricular ejection fraction returned to normal and pericardial effusion dissolved. Additionally, bradycardiac episodes abated, although intermittent second degree AV block was still occasionally present during the night. In conclusion, overt hypothyroidism may be associated by cardiac myxedema affecting both electrophysiology and contractility, observations that underscore the necessity of thyroid testing in different phenotypes of heart failure.
- Cardiac myxedema
- Thyrocardiac axis
- Hypothyroid Graves’ disease
From a clinical perspective the phenotype of hypothyroidism is modulated by patient’s age , the rate of its onset, and potential comorbidities.
Hypothyroidism is a known risk factor for cardiovascular disease . Atherosclerosis may result from dyslipidemia  and diastolic hypertension , both conditions that may be a consequence of thyroid hormone deficiency. Myocardial dysfunction, both systolic and diastolic, is also associated with hypothyroidism; congestive heart failure may ensue, particularly in individuals with severe thyroid hormone deficiency . Pericardial effusions, though usually small and of little significance, have been identified in up to 50 % of patients with thyroid gland failure [6–9]. Pericardial tamponade is rare but has been reported [10–12]. Hypothyroidism classically has been associated with bradycardia, but the degree, by which the heart rate slows down, is often modest [13, 14]. The function of the atrial pacemaker is normal and atrial ectopy is rare, however premature ventricular beats and occasionally ventricular tachycardia can occur . Hypothyroidism may even be accompanied by the syndrome of torsade de pointes with a long QT interval and ventricular tachycardia, which may resolve with levothyroxine treatment . Disturbances in atrioventricular conduction have been described in myxedema, but seem to be rare. The co-existence of impaired left ventricular contractility, diastolic hypertension, increased systemic vascular resistance, peripheral edema and decreased exercise tolerance suggests that hypothyroidism may result in heart failure. However, hypothyroidism as a sole cause of heart failure has been rarely reported [17–20]. Hypothyroid patients are able to increase their cardiac output and decrease systemic vascular resistance in response to exercise, unlike patients with heart failure [17, 18].
Graves’ disease is a B-cell mediated autoimmune disease induced by the expression of autoantibodies to the thyrotropin (TSH) receptor (TRAbs) as the major pathogenic feature [19–21]. There are two general types of TRAbs, which can each promote a type of autoimmune thyroiditis (AITD): TSIs (also referred to as sTRAbs) that mimic TSH stimulating the thyroid, which results in autoimmune hyperthyroidism, or classical Graves’ disease; and thyroid-blocking antibodies (TBAbs or iTRAbs), which block he binding of TSH to its receptor and can result in B cell-mediated autoimmune hypothyroidism [22–26]. Another type of hypothyroid Graves’ disease may ensue from overlap with T cell-mediated thyroiditis (Graves’ disease with Hashimoto component), where hypothyroidism ensues from destruction of thyroid tissue by cytotoxic T cells. Although overlap syndromes are common in cases of Graves’ disease they rarely lead to hypothyroidism compared with classical Hashimoto’s or Ord’s disease.
Progression of thyroid hormone levels, ejection fraction and cardiac biomarkers after substitution therapy with levothyroxine had been initiated. Reference ranges are reported with units of measurement
Days after admission
Concentrations of thyroid hormones
Echocardiography and MRT
Concentrations of cardiac biomarkers
Pericardial effusion and impaired cardiac contractility are common signs in hypothyroidism, and several cases of cardiac tamponade due to hypothyroidism have been described in the literature [6–12, 27–29]. Both abnormalities have been described to be reversible after achievement of a euthyroid state. In our patient both cardiac contractility and the pericardial effusion normalized or dissolved after 9 days of treatment after euthyroidism was reached. Disturbances in the conduction system of the heart are infrequent in hypothyroidism [30, 31] and, conversely, hypothyroidism is a rare cause of advanced atrioventricular block in young individuals . Affected patients with second and/or third degree AV block in the setting of thyroid dysfunction almost always have to be provided with a permanent pacemaker even after thyroid status has been normalized [13, 14, 33–36]. The reason for this is unclear. However, on a molecular level the clinical phenomena found in hypothyroid-associated cardiac disease may be explained by pleiotropic effects of thyroid hormones on both gene expression and metabolism of myocardial cells. Genomic mechanisms involve T3 binding to TRs, which regulate transcription of specific cardiac genes. Positively regulated are alpha-myosin heavy chain, sarcoplasmic reticulum Ca2+-ATPase, Na+/K+-ATPase, beta1-adrenergic receptor, atrial natriuretic hormone and voltage-gated potassium channels (Kv1.5, Kv4.2, Kv4.3). Negatively regulated are beta-myosin heavy chain, phospholamban, adenylyl cyclase catalytic subunits, thyroid hormone receptor alpha1 and Na+/Ca2+ exchanger. Non-genomic mechanisms include direct modulation of membrane ion channels. Additional extracardiac effects of thyroid hormones on cardiovascular hemodynamics include stimulation of tissue thermogenesis, increase of cardiac output and pulmonary pressure, and decrease of both systemic vascular resistance and diastolic blood pressure with consecutively reduced afterload. Isovolumic relaxation time, as a measure of diastolic function, is increased in subclinical and even more in overt hypothyroidism. Cardiovascular risks associated with hypothyroidism include impaired cardiac contractility and diastolic function, increased systemic vascular resistance, possibly caused by decreased endothelial-derived relaxation factor, and elevated levels of serum cholesterol, C-reactive protein and homocysteine . Abnormal cardiac bioenergetics in hypothyroidism is improved by substitution with levothyroxine .
In addition, regulation of beta-receptor density by thyroid hormones, as described on both genomic and non-genomic levels, could play a key role in this scenario [39, 40]. Fast non-genomic effects may be mediated by microtubule assembly .
Moreover, thyroid hormones have profound effects on myocardial calcium and potassium channels on both RNA and protein level. Hypothyroidism-induced remodelling of K+ channels expression is assumed to be responsible for the blunted response of peak transient outward current (Ito) and sustained current (Isus, a mix of IK, slow and Iss) to changes in membrane potential .
Undiagnosed and/or untreated hypothyroidism may pose a threat of sudden cardiac death, which may be mirrored by myocardial ventricular late potentials in overt hypothyroidism .
Hypothyroidism is a differential diagnosis of suspected peri-myocarditis. This case underscores the clinical relevance of thyrocardiac interaction. Evaluation of thyroid homeostasis should be performed early in the work-up of heart failure and every kind of arrhythmia. Even though electrophysiological scars may outlast myxedema, it may be life-saving to commence substitution therapy with thyroid hormones timely.
Written informed consent was obtained from the patient for the publication of this report and any accompanying images.
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