5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Graves' disease–induced complete heart block and asystole

      case-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Key Teaching Points • Though the most common cardiovascular effects of hyperthyroidism are sinus tachycardia, atrial fibrillation, and atrial or ventricular premature complexes, complete atrioventricular (AV) block can occur, but it remains a rare occurrence. • Identifying underlying thyroid dysfunction in patients presenting with AV block is critical, as treating the underlying thyroid dysfunction can help remove the stimulus triggering the arrhythmias. In addition, medications used to treat hyperthyroidism include beta blockers, which can be detrimental in patients with AV block. • There is no consensus on the management of patients with thyrotoxicosis and AV block, and further studies need to be performed to understand the natural progression and optimal timing and duration of device-based therapy. Introduction Complete heart block or third-degree atrioventricular (AV) block is a disease of the cardiac conduction system that results in lack of electrical conduction from atria to the ventricles. It is more common in the older patient and it is most often owing to age-related degeneration and fibrosis of the conduction system. 1 Hypothyroidism is a known, but rather uncommon, cause of AV block, particularly in young and middle-aged adults. 1 Hyperthyroidism is an extremely rare cause and has been described in only a few case reports, most commonly in association with acute inflammatory states, infections, or medications such as digoxin.2, 3, 4 We present a case of a young male patient with symptomatic complete heart block and asystole in the setting of newly diagnosed Graves' disease. Case report A 41-year-old man with no significant past medical history presented with syncope. The patient described loss of consciousness without preceding chest pain, dyspnea, or palpitations. Prior to this episode, the patient noted a several-day history of subjective fevers and a nonproductive cough, but denied a history of tick bites, rashes, or arthralgia. Upon arrival to the hospital, he was hypertensive but vital signs and physical examination were otherwise unremarkable. Electrocardiogram showed sinus tachycardia with a complete heart block and an accelerated junctional rhythm (Figure 1). Initial laboratory evaluation revealed a normal complete blood count and electrolytes (potassium 4.5 mmol/L, total calcium 9.3 mg/dL [normal range 8.9–10.1 mg/dL], phosphorus 2.6 mg/dL [normal range 2.5–4.5 mg/dL], and magnesium 1.9 mg/dL [normal range 1.7–2.3 mg/dL]). Inflammatory markers were mildly elevated, with a C-reactive protein of 48.9 mg/L and erythrocyte sedimentation rate of 33 mm/h. Lyme serology was negative. Of note, he had a severely depressed thyroid-stimulating hormone (TSH) (<0.01 mIU/L) and an elevated free thyroxine level (T4) of 4 ng/dL (reference range 0.9–1.7 ng/dL), which was confirmed on repeat testing. Figure 1 Electrocardiogram acquired from the patient on presentation, which shows complete dissociation of atrial and ventricular activity consistent with third-degree atrioventricular block. Echocardiography revealed a structurally normal heart with left ventricular ejection fraction of 59%. Computed tomography angiography of the chest was negative for pulmonary embolism and dissection. Cardiac magnetic resonance imaging (MRI) demonstrated no evidence of myocarditis or infiltrative disease. While hospitalized, he sustained recurrent syncope in the context of 10- and 13-second periods of complete heart block without an escape rhythm. Further evaluation revealed a positive thyroid receptor antibody with a level of 2.41 IU/L (normal <1.75 IU/L), highly suggestive of Graves' disease in the setting of elevated T4 and suppressed TSH. He was treated with methimazole. Given his long periods of recurrent asystole with syncope, temporary pacing wires were placed on initial presentation. The patient required minimal V pacing, with rhythms mostly consistent with sinus tachycardia and an accelerated junctional rhythm. However, given his initial presentation with syncope and prolonged pauses, a permanent dual-chamber pacemaker was ultimately placed. At 5 months' follow-up, thyroid hormone levels normalized and he was clinically euthyroid on methimazole (Figure 2). He had no recurrent syncope or pre-syncope. Holter monitoring and device interrogations showed normal sinus rhythm with atrial pacing and 1 brief period of AV sequential pacing. Figure 2 Change in thyroid hormone levels with therapy. A: Change in free T4 (in ng/dL), and B: change in total T3 (in ng/dL), following initiation of methimazole (day 4 of hospitalization). Both indices were elevated on presentation and normalized with methimazole therapy. Discussion Thyroid hormones, mainly mediated through the actions of tri-iodothyronine (T3), have adrenergic, chronotropic, and inotropic effects on the heart. 5 Indeed, many of the known clinical effects of hyperthyroidism, such as tachycardia, sweating, and palpitations, mimic a state of catecholamine excess. However, measured plasma levels of catecholamines tend to be normal to low in hyperthyroidism, 6 suggesting that a state of heightened adrenergic sensitivity exists. 7 However, evidence for this has been conflicting, and β-adrenergic receptor knockout mouse studies have shown similar cardiovascular effects from exposure to thyroid hormone compared to those with intact receptors. 8 T3 results in transcriptional modulation of several components central to enhancing contractile function, including alpha-myosin heavy chains, sarcoplasmic reticulum proteins, calcium-activated ATPase (Ca2+-ATPase), phospholamban (a protein that regulates calcium ion uptake into the sarcoplasmic reticulum), the Na+-K+-ATPase pump, and voltage-gated potassium channels. Furthermore, thyroid hormones, themselves, decrease systemic vascular resistance. 9 These effects combined result in an overall increased heart rate and cardiac output and widened pulse pressure (Figure 3). 5 Figure 3 Schematic outlining the cardiovascular effects of thyroid hormone (mainly mediated through T3). Thyroid hormone results in an increase in the transcription of molecules central to contractile function, such as α-myosin heavy chain and sarcoplasmic reticulum Ca2+-ATPase, which results in a positive inotropic effect. It also results in an increase in adrenergic response through increased transcription of β1-adrenergic receptors and guanine-nucleotide regulatory proteins, resulting in a positive chronotropic effect. The hormones also have peripheral vascular effects resulting in decreased systemic vascular resistance, which results in increased blood volume as a response through increased renal sodium reabsorption. All these effects combined result in an increase in cardiac output. 5 It is not surprising, therefore, that the most common cardiovascular effects of hyperthyroidism are sinus tachycardia and atrial fibrillation. 5 Though the mechanisms of tachyarrhythmias in hyperthyroidism are therefore quite clear (increasing the rate of systolic depolarization and diastolic repolarization, decreasing the action potential duration and the refractory period of the atrial myocardium and AV node 10 ), the mechanism of hyperthyroidism-related bradyarrhythmias and AV block is less well understood. Furthermore, previous cases of thyrotoxicosis causing complete heart block that were reported in the literature were associated with other coexisting factors, such as acute infection 3 or coadministration of cardiac medications. 2 Nevertheless, our case highlights that this presentation, which is different from the classic atrial fibrillation arrhythmia associated with hyperthyroidism, in the absence of other acute precipitating factors supports the postulation that thyroid hormone can act directly on the AV node. Although the patient's cardiac MRI did not demonstrate any obvious signs of inflammation at any point within the myocardium, one case report describing a similar presentation—which is the only published case report to include an autopsy, to our knowledge—demonstrated interstitial inflammation of the AV node, the His bundle, and its branches. 11 Throughout the course of his hospitalization, various rhythms were noted, which included sinus tachycardia, an accelerated junctional rhythm, and complete heart block. The presence of these rhythms in the setting of thyrotoxicosis and in the absence of structural heart disease is peculiar. An accelerated junctional rhythm arises when the rate of an AV junctional pacemaker exceeds that of the sinus node. Although no studies have been done to specifically evaluate the underlying pathophysiology of this arrhythmia in states of thyrotoxicosis, it is well known that the AV node is under autonomic regulation. Furthermore, calcium dynamics have been shown to play a key role in AV node automaticity. 12 As previously mentioned, T3 plays a key role in regulation of molecules involved in calcium flux, including sarcoplasmic reticulum proteins and calcium ATPase. Additional mechanistic studies are required to further elucidate the intricacies of this arrhythmia in this clinical setting. However, an important clinical entity to consider is thyrotoxic periodic paralysis, which is a condition that can occur in patients with hyperthyroidism, characterized by abrupt onset of paralysis and hypokalemia, and can result in AV block, ventricular fibrillation, and asystole. This condition can occur in any patient but is most commonly seen in men of Asian descent. Common precipitants of this condition include exercise and a carbohydrate-rich meal. Although the condition classically results in hypokalemia, normokalemic patients have been described. 13 Though the data regarding the degree of reversibility in patients with AV block who have their hyperthyroidism treated are lacking, perhaps owing to the rarity of this presentation, it has been shown that in patients with thyrotoxicosis and atrial fibrillation with no underlying valvular heart disease, 62% of patients spontaneously reverted to sinus rhythm within 1 year after commencing treatment of their thyrotoxicosis, and typically within 8–10 weeks after achieving a euthyroid state. 14 The other important point to consider is that medications that are often used to treat hyperthyroidism include beta blockers, which can be detrimental in patients with AV block. There are scant data and no guidelines to guide the management of patients with thyrotoxicosis who present with high-grade AV block. Our patient presented with third-degree AV block along with symptomatic periods of asystole. Current guidelines recommend permanent pacing for patients with third-degree heart block. 15 The guidelines also, however, stress that potentially reversible causes such as medications, ischemia/infarction, electrolyte abnormalities, and Lyme disease should ideally not be treated with permanent pacing. 15 There is no specific mention of advanced AV block in the specific setting of thyroid dysfunction. 15 There is no clear indication as to how long pacing is required or at what point explanting the pacemaker could be safely considered. One study, by Ozcan and colleagues, 4 followed 21 patients with AV block associated with hyperthyroidism, of whom 20 patients (95.2%) underwent pacemaker implantation. Nine patients had normalization of their TSH with therapy, but 8 of those patients had persistent or recurrent AV block. Meanwhile, 12 patients had persistently low TSH levels despite therapy and all of those patients had persistent AV block during the initial hospital follow-up period (21 days), and 10 of the 12 patients had persistent AV block and were therefore pacemaker dependent on extended follow-up. It is important to note that the time to resolution of the AV block after starting medical therapy was more than 21 days, and therefore, prolonged temporary pacing is often not a reasonable option, which makes implantation of a permanent pacemaker a plausible option despite this being a “transient risk factor.” Although this study was limited by a small sample size and a short duration of follow-up, it highlights that AV dysfunction does persist in a substantial proportion of patients despite treatment of their underlying thyroid dysfunction, in contrast to the high degree of reversibility of atrial fibrillation once the underlying hyperthyroidism is treated. Conclusion We present a case of symptomatic complete heart block and asystole in the setting of newly diagnosed Graves' disease. Although hyperthyroidism is a known but rare cause of advanced AV block, there are insufficient data on optimal management of these patients, especially regarding device implantation. Further studies are required to better understand the degree of reversibility of AV block in this setting and the optimal timing and duration of cardiac pacing.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          Management of atrial fibrillation in the post-thyrotoxic state.

          This study was designed to investigate the appropriate timing for cardioversion in patients with chronic atrial fibrillation who had been rendered euthyroid from a thyrotoxic state. We carried out a retrospective study of 163 patients with thyrotoxic atrial fibrillation, with a mean follow-up of 34 months. With control of thyroid function alone, 101 patients had spontaneous reversion of atrial fibrillation to sinus rhythm and 62 patients had persistent atrial fibrillation. In those with spontaneous reversion, the longest duration of atrial fibrillation prior to the euthyroid state was 13 months. In those with persistent fibrillation, the shortest duration of atrial fibrillation prior to the euthyroid state was eight months. Almost three-quarters of those with spontaneous reversion had conversion to sinus rhythm within three weeks of becoming euthyroid. No spontaneous reversion occurred if atrial fibrillation was still present after the patients had been in a euthyroid state for four months. This study suggests that spontaneous reversion of atrial fibrillation to sinus rhythm is highly unlikely if the duration of atrial fibrillation before the euthyroid state is achieved exceeds 13 months, or if it is still present after the patient has been in a euthyroid state for four months, Cardioversion should be performed at about the 16th week after the euthyroid state is achieved.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            A review on advanced atrioventricular block in young or middle-aged adults.

            Complete atrioventricular block is a relatively uncommon arrhythmia that is nonetheless increasingly seen in elderly people of developed countries, due to the increase in life expectancy. Congenital and degenerative etiologies are the most commonly seen among young and old patients, respectively. However, scientific literature is surprisingly scarce regarding the etiology of complete atrioventricular block in the asymptomatic otherwise healthy young and middle-aged adult population. Coronary artery disease, autoimmune disorders such as systemic lupus erythematosus or rheumatoid arthritis, history of acute or chronic infectious or hypersensitivity myocarditis, infiltrative processes, hypothyroidism, congenital cardiopathies such as left ventricular noncompaction or Ebstein anomaly, lamin A/C mutations, and pathologic hypervagotony and idiopathic degenerative scleroatrophy of the atrioventricular junctional specialized tissue (Lenegre-Lev disease) are among the most frequent etiologies of complete atrioventricular block in young or middle-aged adults. To our knowledge, no comprehensive review on the specificities of the investigation warranted in this age group has ever been developed, nor have the implications of particular diagnoses on treatment modalities been appropriately addressed. We aim at reviewing the most frequent differential diagnoses of advanced atrioventricular block in otherwise healthy asymptomatic or mildly symptomatic young or middle-aged adults and their impact on therapeutic options. Additionally, we suggest a diagnostic algorithm that may be helpful in this group of patients.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The effect of altered thyroid state on atrial intracellular potentials.

              1. A group of rabbits was made hypothyroid by thyroidectomy, and another group was injected daily with L-thyroxine. After an appropriate interval respective alterations in thyroid state were confirmed by measurement of heart weight and of plasma iodine, and the animals' atria were isolated for recording.2. Measurements were made of atrial contractions, conduction velocity, spontaneous heart rate and maximum driven frequency, and action potentials were recorded with intracellular micro-electrodes.3. The resting potential and action potential heights were not affected by differences of thyroid state.4. Atrial arrhythmias are common in hyperthyroidism, rare in myxoedema. The possibility that hypothyroidism might reduce the rate of rise of the action potential, as do anti-arrhythmic drugs, and hyperthyroidism increase it, was investigated. Although the rate of rise was slower in hypothyroid atria at some driving frequencies, this could not alone account for an anti-arrhythmic effect, because at frequencies near the spontaneous heart rate the rate of rise of the action potential was not reduced.5. The duration of the repolarization phase of the action potential was greatly prolonged in atria from thyroidectomized rabbits, and was shortened in hyperthyroid atria. These changes could account for a reduced probability of arrhythmias in hypothyroidism, and the converse in hyperthyroidism.
                Bookmark

                Author and article information

                Contributors
                Journal
                HeartRhythm Case Rep
                HeartRhythm Case Rep
                HeartRhythm Case Reports
                Elsevier
                2214-0271
                29 December 2017
                March 2018
                29 December 2017
                : 4
                : 3
                : 105-108
                Affiliations
                []Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota
                []Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
                []Department of Endocrinology, Mayo Clinic, Rochester, Minnesota
                Author notes
                [] Address reprint requests and correspondence: Dr Peter A. Noseworthy, Department of Cardiovascular Diseases, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905. noseworthy.peter@ 123456mayo.edu
                Article
                S2214-0271(17)30212-9
                10.1016/j.hrcr.2017.12.001
                5918183
                3f3c8621-15df-4739-8604-ad3552f8a0ef
                © 2017 Heart Rhythm Society. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Categories
                Case Report

                atrioventricular block,graves disease,thyrotoxicosis,permanent pacemaker,asystole

                Comments

                Comment on this article