The Relationship of Common Cardiac Issues and Thyroid Disease

ABSTRACT

Common medical disorders such as hypertension (HTN), dyslipidemia, coronary artery disease (CAD), heart failure, atrial fibrillation and pericardial disease are often associated with thyroid dysfunction.[1] Indeed, thyroid dysfunction can cause or promote all of these cardiovascular risk factors and diseases directly or indirectly. Moreover, thyroid dysfunction varies in severity, speed of onset, course and complications so that the patient may present at various times in the natural history of these cardiovascular diseases. In understanding the intimate relationship of all these clinical problems, the physician will want to maintain a high index of suspicion for thyroid dysfunction when heart disorders are present and for heart disorders when overt or subclinical thyroid dysfunction is present. A brief paradigm can simplify this conundrum: if the patient has heart problems, think of thyroid dysfunction; if the patient has thyroid dysfunction, think of heart problems. The most common examples follow[2]:

1. Atrial fibrillation, check thyroid function[3]
2. Coronary disease, check thyroid function
3. Hypertension, check thyroid function[4],[5],[6]
4. Heart failure, check thyroid function
5. Pericardial disease, check thyroid function[7],[8],[9]
6. Thyrotoxicosis, check for arrhythmias, heart failure or congestive state
7. Hypothyroidism, check for coronary artery risk factors and disease
8. Thyroid dysfunction, check the blood pressure

PATIENT CASE ILLUSTRATION

A 65 year old woman with long-standing hypertension presents with increasing dyspnea on exertion. Examination reveals a blood pressure (BP) of 170/80, signs of congestive heart failure, and atrial fibrillation with an uncontrolled ventricular response. A Doppler echocardiogram demonstrates global hypokinesia, left ventricular hypertrophy and a left ventricular ejection fraction of 25%. The heart failure improves with furosemide, beta blockers, aldactone, ACE inhibition and oral anticoagulants. However, the ventricular rate remains at 100 BPM. Later, thyroid function tests (TFTs) reveal a high T4 and low TSH, consistent with overt hyperthyroidism. Repeat neck palpation reveals a single thyroid nodule which is “hot” on scanning. Adding propylthiouracil, the ventricular rate gradually becomes controlled. Once the patient is euthyroid and a transesophageal echocardiogram (TEE) is negative for thrombi, the patient has cardioversion and remains in sinus rhythm. Her ejection fraction (EF) increases to 55% and global hypokinesis resolves.

CHALLENGES

Should the TFT’s have been done at presentation?

Approximately 1% of adults with new onset atrial fibrillation have hyperthyroidism. This number is high enough to warrant TFTs being done on anyone with atrial fibrillation including those with an apparent alternate cause, such as recent chest or mediastinal surgery, a history of hypertension with an enlarged left atrium, mitral valve disease, coronary disease or the sick sinus syndrome.

In this case it is especially important to identify the hyperthyroidism since the patient is in heart failure and has global hypokinesia, which may be a manifestation of tachycardia-mediated cardiomyopathy with heart failure. Her excellent response to becoming euthyroid with sinus rhythm supports that tachycardia was a significant precipitating cause of the heart failure. Other thyroid related considerations are the loss of atrial kick with onset of atrial fibrillation, diminished diastolic flow time across the mitral valve, increased afterload due to systolic hypertension which can be caused by hyperthyroidism, and thyroid-mediated systolic and diastolic dysfunction.

The treatment of hyperthyroidism related atrial fibrillation follows the recommended guidelines for atrial fibrillation in general; rate control, anticoagulation[10] and return to sinus rhythm. Prompt rate control is usually achieved by the use of beta blockers, although nonhydropyridine calcium blockers and/or digitalis are also used instead or in addition. Direct treatment of the hyperthyroidism[11] also helps control the ventricular response. Anticoagulation[12] can be achieved in nonvalvular atrial fibrillation with aspirin, warfarin or the new novel anticoagulants[13] such as the direct thrombin antagonist dabigatran or factor Xa inhibitor rivaroxaban—guided by the CHADS2 score or CHA2DS2-VASc score. Cardioversion as a rule should be deferred until the patient is rendered euthyroid.

Should the cardioversion have been done immediately?

The prevailing opinion is to defer cardioversion until the patient is euthyroid since persistent hyperthyroidism makes cardioversion less successful and the atrial fibrillation more likely to recur. Amiodarone can be used despite its heavy load of iodine. Recent adverse cardiovascular experiences with dronederone for chronic atrial fibrillation suggest that we await further studies to clarify its use with paroxysmal atrial fibrillation while it appears contraindicated for sustained atrial fibrillation (The PALLAS study). The disadvantages appear to outweigh the advantage of its not containing iodine.

Is it likely that this patient had “high output failure”?

In Arthur C. Guyton’s classic book Circulatory Physiology: Cardiac output and its regulation published in 1963 by W. B. Saunders Company, Philadelphia[14], the great physiologist emphasized that normally it is not the heart that determines cardiac output but rather the peripheral vasculature. In dilating arterioles, thyroid hormone reduces afterload and increases cardiac output. This in turn augments venous return. If cardiac function is not impaired, the heart will pump the blood that returns to it and the increased cardiac output will persist. In time the altered circulation results in salt and water retention and later a congestive state. The combination of high cardiac output and congestion is called “high output failure” although high output congestive state seems a more accurate term.

That this is not the case with this patient is demonstrated by her Doppler echocardiogram, showing impaired cardiac function and reduced cardiac output. With the high output congestive state of hyperthyroidism, the Doppler echocardiogram would be expected to show ventricular hyperkinesis and increased left ventricular ejection fraction and cardiac output. Distinguishing between frank heart failure and “high output failure” is an important aspect of the evaluation of hyperthyroid patients who appear to be in heart failure. Furthermore, all patients with heart disease, arrhythmias, and/or heart failure should have TFTs. The opposite is also true. All patients with thyroid dysfunction should be checked for heart disease, arrhythmias, and/or heart failure.

Unlike this patient with Plummer’s disease, the most common cause of hyperthyroidism is Graves’ disease. Fortunately, the Thyretain™ TSI Reporter Bioassay for Graves’ disease became available in 2009. There are important differences in the management of this form of autoimmune thyroiditis, making the Thyretain™ TSI Reporter Bioassay an important addition to our diagnostic armamentarium.

What is the relationship between thyroid dysfunction and hypertension?

Since blood pressure is dependent on cardiac output (Q̇) and peripheral vascular resistance (PVR), any changes in Q̇ or PVR can result in a change in blood pressure. For example, in hypothyroidism the associated arteriolar vasoconstriction increases PVR and elevates diastolic blood pressure. While in hyperthyroidism arteriolar vasodilatation lowers PVR and would be expected to lower blood pressure. However, there is an important concept called counterregulation. If blood pressure falls, homeostatic mechanisms are activated to prevent the fall, resulting in an increase in heart rate and Renin-Angiotensin-Aldosterone- System (RAAS) activation with retention of salt and water. The resultant increase in blood volume and cardiac output raises systolic blood pressure. Thus, while hypothyroidism causes diastolic hypertension, hyperthyroidism causes systolic hypertension while lowering diastolic blood pressure. The wide pulse pressure contributes to the findings of a hyperdynamic circulation.

Approximately, one quarter of the population is hypertensive. While correcting the thyroid dysfunction would be expected to restore normal blood pressure in most people, those with antecedent or coexistent alternate causes for hypertension would likely still remain hypertensive. In the absence of evidence based studies, the pathophysiology of hypertension in hyperthyroidism would be expected to respond to beta blockers and diuretics. However in hypothyroidism, beta blockers would be less likely to be effective since most such agents have unopposed alpha stimulation to cause more vasoconstriction and beta blockers could augment any associated bradycardia. Beta blockers with alpha blocking capability or other vasodilating agents would more likely be helpful while correcting the thyroid dysfunction.

How are hypothyroidism and coronary disease related?

Hypothyroidism may cause or accelerate atherosclerosis and myocardial ischemia in several ways.[15] By raising blood pressure and causing dyslipidemia, hypothyroidism would increase myocardial oxygen demand while atherogenesis could cause decreased coronary blood flow. Vascular endothelial dysfunction would prevent flow- mediated vasodilatation while left ventricular systolic and diastolic dysfunction would increase wall stress, called load. Since the prime determinants of myocardial oxygen demand are heart rate, systolic blood pressure, preload and afterload, any augmentation of these would increase oxygen demand.

When hypothyroidism occurs in a patient with known or suspected coronary disease, there is an obligatory concern that increased myocardial oxygen demand caused by thyroid hormone might precipitate myocardial ischemia or infarction. For this reason, the caveat to pick lower doses of thyroid replacement and go slow in increasing the dose is logical. In time if hypothyroid mediated diastolic hypertension resolves, treatment of the hypothyroidism should have a favorable effect on ischemia.

Also important is distinguishing stable ischemia from an acute coronary syndrome. While the former requires caution in starting and accelerating thyroid replacement therapy, the later requires consideration of coronary angiography and perhaps an intervention before starting thyroid hormone replacement. Thyroid function tests should be drawn before administering iodine containing contrast. In hypothyroid patients with known or suspected coronary disease the starting dose of thyroid hormone (T4) should be 12.5 to 25 mcg daily.

Does hypothyroidism cause pericarditis, pericardial effusion or both?

While hypothyroidism occasionally causes frank pericarditis, pericardial effusion is more common and relates to salt and water retention. Such a complication needs to be identified to distinguish the cause of an increased cardiac silhouette on chest x-ray: heart failure, pericardial effusion and/or cardiac tamponade. The source of the fluid is from the myocardium and visceral pericardium and possibly related to changes in the lymphatic circulation of the heart. Although pericardial tamponade is a clinical diagnosis based on the patient’s neck veins, pulsus paradoxicus, and/or electrical alternans on the EKG, an echocardiogram is a key test in documenting the effusion and diastolic collapse of the right heart chambers.

Does subclinical hypothyroidism or hyperthyroidism carry similar risks and relationships?

With subclinical thyroid dysfunction,[16] the thyroid hormone level remains normal while the TSH is abnormally elevated (hypothyroidism)[17],[18],[19] or depressed (hyperthyroidism).[20] Overall the cardiovascular risks are similar though less frequent. Thus, overt hyperthyroidism carries a higher risk of atrial fibrillation than subclinical hyperthyroidism. Even high normal thyroid hormone levels have some increased risk of atrial fibrillation. While there is controversy about whether to treat asymptomatic subclinical disease, the growing frequency of such disorders with age and the ease of getting a TSH level provide ample support for routine testing. If there is subclinical thyroid dysfunction, the patient should have their thyroid function monitored more often, perhaps twice a year, or if symptoms emerge. If there is coexistent disease that may be thyroid mediated, such as atrial fibrillation, thyroid treatment merits consideration.

CONCLUSION

Thyroid dysfunction can emulate a plethora of medical problems and involve virtually every organ system. Moreover, thyroid dysfunction varies in severity, speed of onset, course and complications so that the patient can present at almost any time in the natural history of the disease. Thyroid dysfunction is often a quiet stalker, can be a mimic, and can both obscure co-morbidities or be obscured by them. The composite makes for an authentic challenge for the primary care doctor especially with the common time constraints.

---

References

1. Klein I. Chapter 86: Endocrine disorders and cardiovascular disease. In Braunwald’s Heart Disease. Bonow RO, Mann DL, Zipes DP, and Libby P—editors. Ninth Edition, volume 2. Elsevier (Saunders). 2012. pp 1833-1841.
2. Ladenson PW. Recognition and management of cardiovascular disease related to thyroid dysfunction. Am J Med. 1990 Jun;88(6):638-41.
3. Traube E, Coplan NL. Embolic risk in atrial fibrillation that arises from hyperthyroidism. Texas Heart Institute J 2011;38(3):225-8.
4. Klein M, Pascal V, et al. Heart and thyroid [article in French]. Ann Endocrinol (Paris). 1995;56(5):473-86.
5. Völzke H, Alte D, et al. The association between subclinical hyperthyroidism and blood pressure in a population- based study. J Hypertes. 2006 Oct;24(10):1947-53.
6. Prisant LM, Gujral JS, et al. Hyperthyroidism: a secondary cause of isolated systolic hypertension. J Clin Hypertens(Greenwhich). 2006 aug;8(8):596-9.
7. Ovadia S, Lysyy L, et al. Pericardial effusion as an expression of thyrotoxicosis. Tex Heart Inst J. 2007;34(1):88-90.
8. Patil VC, Patil HV, et al. Cardiac tamponade in a patient with primary hypothyroidism. Indian J Endocrinol Metab. 2011 July;15(Suppl2):S144-S146.
9. Alexander, JS. Pericardial effusion of "Gold Paint" appearance due to presence of cholesterin. Brit. Med. J. 1919; 2: 463.
10. Peterson P and Hansen JM. Stroke in thyrotoxicosis with atrial fibrillation. Stroke. 1988;19:15-18
11. Franklyn JA and Boelaert K. Thyrotoxicosis. Lancet 2012;379:1155-66.
12. Wann LS, Curtis AB, January CT, et al. 2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline): A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2011;57:223-242.
13. De Caterina R, Husted S, Wallentin L, et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC working group on thrombosis—task force on anticoagulation in heart disease position paper. J Am Coll Cardiol. 2012;59:1413-1425.
14. Arthur C. Guyton’s Circulatory Physiology: Cardiac output and its regulation. W. B. Saunders Company, Philadelphia 1963
15. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid. 2000 Aug;10(8):665-79.
16. Cooper DS and Biondi B. Subclinical thyroid disease. Lancet 2012;379: 1142-54.
17. Kahaly GJ. Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid. 2000 Aug;10(8):665-79.
18. Niafar M, Toufan M, et al. Subclinical hypothyroidism effects on cardiac function. Pak J Biol Sci. 2009 Aug 1;12(15):1056-62
19. Alibaz OF, Yurdakul S, et al. Evaluation of the effect of L:thyroxin therapy on endothelial functions in patients with subclinical hypothyroidism. Endocrine. 2011 Oct;40(2):280-4.
20. Völzke H, Alte D, et al. The association between subclinical hyperthyroidism and blood pressure in a population- based study. J Hypertes. 2006 Oct;24(10):1947-53.