Grand Rounds: Thyroid Disease and the Heart

 Commentary by Sarika Modi MD, PGY-2  

Dr. Irwin Klein MD, Professor of Medicine and Cell Biology, of North Shore University Hospital, gave grand rounds on “Thyroid Disease and the Heart” on September 17, 2008.  He began his talk by giving an overview of the broad spectrum of cardiac manifestations seen in hyperthyroidism.  Palpitations are seen in 90% of patients with hyperthyroidism.  Atrial fibrillation is seen in 5-15%, especially in the elderly.  In fact, as Dr Klein pointed out, former president George Bush Senior was diagnosed with Graves’ disease after he was found to be in atrial fibrillation after an episode of shortness of breath while jogging.   Hyperthyroidism in young women can present with angina, but subsequent cardiac catherization will typically reveal normal coronary arteries.  The mechanism of the angina is thought to be vasospasm, similar to Prinzmetal’s angina and migraine headaches.

85% of thyroid hormone produced by the thyroid gland is in the form of T4, but the biologically active form is T3 which arises by peripheral deiodination in the liver and skeletal muscle.  The cardiovascular effects of thyroid hormone include increased heart rate, increased ejection fraction, increased cardiac output (by 150-200%), muscular hypertrophy of the heart, and a fall in systemic vascular resistance.  T3 acts directly on vascular smooth muscle to relax it and decrease systemic vascular resistance.  The kidney senses a decrease in effective arterial volume and activates the renin-angiotensin-aldosterone system, leading to expansion of plasma volume.  The end result is an elevated systolic pressure, a decreased diastolic pressure, with a widened pulse pressure and expanded plasma volume (see Klein NEJM 2001). 

T3 also has a direct effect on transcription in the cardiac myocyte, leading to increased expression of many genes that enhance cardiac contractility, most notably myosin alpha chains and SERCA-2 (a sarcolemmal calcium channel).  In a study of Dr. Klein’s using rat models where an additional “heterotopic” non-functional heart was transplanted into the animal’s circulation in addition to the animal’s own native heart, administration of T4 stimulated left ventricular hypertrophy in the “in-situ” heart, but not in the heterotopic one.  This shows while T3 has direct effects on transcription, the remodeling associated with the heart in hyperthyroidism is dependent on being within a working cardiovascular system. 

Hyperthyroidism also leads to shortened isovolumic relaxation time (the period in cardiac cycle where the ventricular muscle is relaxing prior to filling and where calcium is being actively taken up by the sarcoplasmic reticulum), which in turn leads to increased diastolic flow and a shortened period of isovolumic relaxation  reflecting enhanced diastolic function..  This effect cannot be accounted for simply by the tachycardia seen with hypothyroidism.  Patients with untreated Graves’ disease who were given two weeks of beta blockade to normalize their heart rates continued to have shortened isovolumic relaxation times.  The relaxation time only normalized with anti-thyroid therapy and return to the euthyroid state.  This suggests that there is a direct effect of T3 on the heart through the transcriptional effects described above that is independent of beta-adrenergic tone (See Klein in Braunwald Heart Disease Text 2008).

Dr. Klein then addressed the paradox of hyperthyroidism being a state of elevated cardiac output and hyperdynamic physiology, and patients presenting in heart failure, such as our clinical vignette patient.  In these patients, underlying heart disease should be ruled out.  However, there is also rate-related left ventricular dysfunction, often related to atrial fibrillation, which is often completely reversible once the heart rate is restored to normal.  Hyperthyroidism may also lead to right-sided failure, as increased plasma volume leads to increased flow in the pulmonary vascular beds, leading to pulmonary hypertension and remodeling of the right ventricle in response to higher pressures.

Primary therapy for the hyperthyroidism with cardiovascular complications includes beta blockers (often high doses i.e. propanolol 3-4 times a day) to normalize heart rate and radioactive iodine therapy to return the patient to a euthyroid state.  The speaker also cautioned against the use of intravenous calcium channel blockers in those patients that are otherwise healthy who present with supraventricular tachycardia.  In patients with hyperthyroidism, they can further reduce systemic vascular resistance and can cause patients to go into hypotensive arrest.  The hypotension is responsive to fluids, but it may be worthwhile to consider the diagnosis of hyperthyroidism and check a TSH to exclude thyrotoxicosis prior to the administration of intravenous calcium channel blockers in the setting of supraventricular tachycardias.  Anticoagulation in hyperthyroid patients with atrial fibrillation is not indicated, as most patients will revert to sinus rhythm once their thyroid disease is treated.  It is only indicated for those patients that have another indication for anticoagulation, such as underlying valvular or ischemic heart disease. 

To summarize: 1) Atrial fibrillation from hyperthyroidism is seen most commonly in the elderly and it is not an indication for anticoagulation.  2) T3 directly affects the cardiac myocyte and the vascular smooth muscle cells, leading to increased contractility of the heart, muscle hypertrophy in a working heart, and decreased peripheral vascular resistance.  3) Normalization of the isovolumic relaxation time is a reliable indicator of return to a euthyroid state and is independent of beta-adrenergic blockade.  4) Hyperthyroid related heart failure may be related to underlying heart disease, a rate-dependent left ventricular dysfunction, or right heart failure secondary to pulmonary hypertension.  5) Beta blockade and radioactive iodine therapy are cornerstones for therapy.  Be cautious with IV calcium channel blockers in thyrotoxic patients as they may further decrease systemic vascular resistance and lead to hypotensive arrest.

The Q&A session ended with a brief mention of Dr. Klein’s new research regarding congestive heart failure patients who have been found to have low T3 levels due to impaired peripheral conversion of T4 to T3.  Stay tuned for new evidence suggesting that T3 supplementation in these patients can improve clinical outcomes (See Klein and Danzi J Clin Endo Metab 93, 2008).

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