Abstract

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Background: The association between overt hypothyroidism (HT) and coronary heart disease is well known. Even subclinical hypothyroidism independently increases the relative risk of coronary artery disease and myocardial infarction and reduces coronary flow reserve.

Methods and results: A patient with severe HP and typical angina on exersion is presented having multiple epicardial coronary artery disease on CT-assisted coronary arteriography and decreased and heterogeneous myocardial perfusion on contrast echocardiography secondary to both macro and  microvascular coronary artery disease

Conclusions: Hypothyroidism is an important clinical situation and a risk factor to be considered for coronary artery involvement.

Background

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Hypothyroidism is an important risk factor for coronary artery disease and heart failure. Thyroid function determines independently the extent and severity of coronary artery disease and leads to increased number of major cardiovascular events and  decreased survival (1,2,3) . Even subclinical hypothyroidism independently increases the  relative risk of coronary artery disease and myocardial infarction and reduces coronary flow reserve  in the absence of epicardial coronary artery disease.(4). The evolving new techniques for coronary artery stenosis visualization and myocardial perfusion disturbances-CT-assisted  coronary arteriography and contrast-enhanced echocardiography could be used as  non-invasive tests for coronary artery status  elucidation in patients with hypothyroidism.

Methods and results

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A patient of  61 was admitted to the Department of Medicine after being treated for psychomotor agitation at  Outpatient Psychiatry Department with signs and symptoms of severe hypothyroidism-cold and dry skin, facial puffiness, yellow discoloration of the skin, , hoarse voice, hearing deficit, slow slurred speech and   chest pain on mild exertion. BP was 160/100, HR-65 bpm, non- specific ST-T changes were evident on  ECG and  CPK-MB and troponin were normal.  Thyroid stimulating hormone was elevated 85 mU/ml, so was  cholesterol-8,9 mmol/l. Echocardiography showed normal LV volumes with preserved systolic and segmental motion and EF-54%, abnormal relaxation on diastolic transmitral flow, preserved myocardial velocities on TDI and  mild pericardial effusion. Patient refused catheter-based selective coronary arteriography, so  CT - assisted coronary angiography was performed.

A standard procedure with  application of Levovist  on CT Dual Source Siemens Definition Machine with test bolus and calculated amount  of contrast was used. Reconstructed images were evaluated and coronary artery stenosis were measured using incorporated software.

Contrast echocardiography was performed as well this time for evaluation of  myocardial perfusion using echo contrast agent  SonoVue (Bracco). This second-generation ultrasound contrast agent of  sulfur hexafluorid- containing microbubbles surrounded by a phospholipid shell and mean size and concentration of microbubbles of 2.5 μm and respectively 1 to 5·10⁸·ml⁻¹. The procedure included reconstitution of 2.5 mg of the agent with  normal saline to the final solution of 5 ml with infusion of reconstituted agent followed by  10 ml saline flash. Acoustic power and compression were maximized and gain settings were optimized at the onset of study and held constant throughout. Mechanical index was set at 1.6 for flash images and 0.1 for real-time images and contrast images were acquired in apical 4-chamber. Myocardial perfusion was judged qualitatively after the splash of high mechanical index for destruction of bubbles and the ensuing replenishment of myocardial tissue.

Results: Three-vessel  proximal coronary artery disease was found with diffuse involvement of coronary arteries. (Fig.1)

Contrast echocardiography has shown hyperechogenic myocardium especially of the septum with decreased systole-diastolic changes in myocardial echogenecityton non-contrast phase and non-homogeneous hypoperfusion of the apical and lateral segments of contrast echocardiography reflecting both increased fibrosis of myocardium and the presence of both  macro and microvascular involvement of the myocardium (Fig 2).

The patients has refused on multiple occasion to undergo any kind of interventional procedure be it percutaneous coronary intervention or aorto - coronary bypass surgery operation

Disscussion

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It is well known that hypothyroidism is a risk factor for earlier and accelerated epicardial coronary atherosclerosis and reduced coronary artery flow reserve. In patients with clinically manifested   coronary artery disease hypothyroidism is found more often  and  all-cause mortality and cardiovascular moratality are increased. Reduced coronary artery flow reserve a hallmark of microvascular disease of the coronary arteries is found even in patients with subclinical HT (1,2,3,4)

Evidence from magnetic resonance imaging studies of subclinical hypothyroidism show significantly decreased cardiac preload and an increased afterload with a consequent reduction in stroke volume and cardiac output was found.  Diffuse hypo-opacification of myocardium was mentioned and replacement therapy fully normalized the hemodynamic alterations. (5)

In some patients with severe hypothyroidism thyroxine replacement therapy precipitates or aggravates angina pectoris, whereas in other patients angina pectoris is ameliorated or even disappears. The reason for this paradox is unknown. It has been attributed either to reversible endocrine cardiomyopathy in the form of asymmetric septal hypertrophy (ASH) (9) or reversible anatomical narrowing of the coronary arteries. The results of a recent investigation, in which myocardial performance was surveyed by radionuclide ventriculography throughout early thyroxine replacement therapy in severe hypothyroidism, were compatible with the presence of reversible coronary dysfunction rather than of ASH.

Exercise and redistribution tomographic myocardial thallium-201 imaging (SPECT) was performed before thyroxine replacement therapy and repeated after 10 days and again after 2 months during therapy. In patients without coronary artery disease substantial regional perfusion defects were demonstrated after exercise that were normalized at rest or  after thyroxine therapy. With restoration of euthyroidism, exercise and redistribution SPECT became  normal in every patient. Determination of exact confidence limits reveals that the proportional incidence of myocardial perfusion defects in hypothyroidism, indicating myocardial ischemia, will at least be 22% with 95% probability. Despite the relatively low specificity of SPECT it seems pertinent to conclude that impaired myocardial perfusion as assessed by SPECT probably is due to reversible coronary dysfunction inherent to the hypothyroid state, and that this is not an infrequent manifestation of severe hypothyroidism.(6)    

To study myocardial perfusion in primary hypothyroidism accompanied by cardiac pain patients were examined by using resting and stress 201Tl myocardial scintigraphy. At rest all the patients showed impaired myocardial perfusion. A decrease in 201Tl accumulation, which corresponded to the areas of impaired perfusion, was observed in 54% of segments. A severe impairment of myocardial 201Tl washout was recorded in all the patients. With exercise additional transient myocardial perfusion was found. (7)   

Myocardial oxidative metabolism was measured by positron emission tomography with [11C] acetate in patients with hypothyroidism as well and cine magnetic resonance imaging was applied to determine left ventricular geometry. Compared to hormone replacement state, systemic vascular resistance and  left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and stroke work index were significantly lower. Despite an additional reduction of oxidative metabolism, the wall motion index was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility.

Estimates of cardiac work show that it is more  severely suppressed than estimates of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease. Thus, noninvasive estimates of cardiac efficiency suggest that myocardial performance is less efficient in hypothyroidism(8).

Echocardiographic videodensity textural characteristics were also studied and was shown to be  increased in overt and subclinical hypothyroidism due to increased tissue fibrosis and possible interstitial edema with accompanying decreased diastolic-systolic variation in videodensity. In recent papers a significant correlation among systo-diastolic changes detected by Color Doppler myocardial imaging and integrated backscatter with serum TSH levels were found. The cyclic variation index at the septum, the PWDTI S-peak wave and the systolic strain of septum were inversely related to the serum TSH levels.(10,11,12,13)

Conclusions

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New echocardiographic techniques allow early detection of ultrastructural and regional functional systolic and diastolic abnormalities. Myocardial tissue characterization is important diagnostic clue in manifest hypothyroidism and contemporary techniques are evolving for evaluation of myocardial perfusion in hypothyroid patients

References

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Source(s) of Funding

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No special funding

Competing Interests

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No conflict of interests

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