Hyperthyroidism precipitating cardiac arrest in a patient with Brugada pattern

Abstract

A 38-year-old man previously healthy suffered an out-of-hospital cardiac arrest; he was resuscitated successfully and admitted to the intensive care unit. His initial ECG suggested a Brugada pattern; other laboratory tests revealed low potassium level, low Thyroid Stimulating Hormone (TSH) and high FT4. He was started on carbimazole for hyperthyroidism, along with other supportive care. A comprehensive cardiac evaluation was done, including ajmaline and flecainide tests, results were inconclusive. An implantable cardioverter defibrillator device (ICD) was inserted to prevent such catastrophic events in the future. After discharge and on follow-up, our patient was doing well. His thyroid function test (TFT) was normal; moreover, a follow-up ICD interrogation did not record any arrhythmias. This case report highlighted asymptomatic hyperthyroidism as a precipitant for Brugada pattern resulting in sudden cardiac arrest.

Background

Sudden cardiac arrest (SCA) is generally defined as death due to cardiac causes occurring within 1 hour of the onset of symptoms; cardiovascular disease is the most common cause of natural death in developed nations.¹ Although SCA in the general population often occurs in individuals without a known cardiac history, structural abnormalities can be identified in the majority.² One of the rare causes of SCA is Brugada syndrome (BrS).

BrS is an uncommon condition with an estimated prevalence of 5/10 000. It is deemed to be contributed to 4% of all sudden deaths and around 20% of sudden deaths in patients with no structural heart disease due to ventricular arrhythmias, especially during sleep.^{3 4} BrS is typically inherited in an autosomal dominant fashion with variable penetrance; nearly 30% carry a pathogenic mutation in the SCN5A gene, which encodes subunits of a cardiac sodium channel, about 5% have been identified as pathogenic mutations in several other genes, and around 60% of mutations still not well recognised yet.^5–7

Numerous factors may contribute to BrS ’s electrocardiographic and clinical manifestations, including mutations in the cardiac sodium channel SCN genes, right ventricular abnormalities, autonomic tone and fever.^8–13 Because of this related channelopathy, particular substance as cocaine, certain psychotropic drugs and gasoline vapours may also trigger Brugada presentation.^14–17

Thyroid hormones have a vital role in cardiac physiology and haemodynamic functions. They mediated their role by binding T3 to nuclear receptors, which subsequently regulate the expression of genes coding for cardiac proteins.^{18 19} Cardiac arrhythmias are a well-known manifestation of hyperthyroidism often present as sinus tachycardia, supraventricular tachycardia, atrial fibrillation, ventricular tachycardia and in rare situations as ventricular fibrillation (V FIB) leading to cardiac arrest.²⁰ There has been a limited number of reports outlining the relationship between hyperthyroidism and BrS inducing SCA. Therefore, our case worth highlighting such association.

Case presentation

A 39-year-old man with no prior medical illness and no recent symptoms was found at night unresponsive by his wife. She called the emergency medical service (EMS) and commenced basic life support.

EMS team arrived 10 min later, the initial rhythm was V FIB, and return of spontaneous circulation (ROSC) was achieved after one shock and 2 min of cardiopulmonary resuscitation. First ECG post-ROSC was highly suggestive of type 1 Brugada (figure 1); the patient was not febrile nor hypothermic. He was admitted to the critical care unit for postcardiac arrest care.

Figure 1.

The first ECG postcardiac arrest; demonstrates coved ST-segment elevation >2 mm in V2 followed by a negative T wave. aVR, augmented Vector Right; aVL, augmented Vector Left; aVF, augmented Vector Foot.

He is working as a nurse with no medical history and was not on any medications. He had no recent symptoms of heat intolerance, diarrhoea, weight loss, muscle weakness, dizziness or palpitations. His family history was notable for sudden death in his aunt who died during her sleep in her forties with no clear diagnosis.

Investigations

Laboratory studies showed normal full blood counts, however, the metabolic panel demonstrated mild hypokalaemia K=3.3 mmol/L (ref:3.5–5.1) and lowTSH=0.01 mIU/L (ref: 0.03–4.20) and high FT4=48 pmol/L (ref: 11.6–21.9). The other electrolytes were within normal range.

The ECG on admission was strongly suggestive of type 1 Brugada (figure 1). Initial echocardiography showed an Ejection Fraction (EF) of 35% with global hypokinesia. The repeated echocardiography 1 week later showed normal global systolic left ventricular (LV) function (EF 52 %). The postcardiac arrest evaluation, including CT Pulmonary angiogram and CT coronary angiogram, was normal.

Several ECGs during hospitalisation did not show evidence of Brugada pattern (figure 2). After reviewing by the cardiology team, ajmaline and flecainide challenging tests were performed, and the results were inconclusive; ajmaline challenging test was done in a closely monitored setting by injection 60 mg of ajmaline over 5 min; he was kept on telemetry for more than 30 min after drug injection with serial ECGs every 3–5 min; after reviewing, there was no significant change in baseline ECG. On the day after, flecainide 400 mg tablet was given; as injection form was not available, he was closely observed in a monitored bed with 12 leads ECG every 3–5 min for 30 min; he was then kept on telemetry for 6 hours with frequent ECGs every 30 min with no significant changes detected. As he could not afford it, genetic studies were not done. None of his family was involved in the investigation as all first-degree family members live in their home country.

Figure 2.

His ECG during ICU stay. ICU, intensive care unit.

Treatment

During his stay in the critical care unit, he received postcardiac arrest supportive care. This care included fluid therapy, vasopressor and ventilatory support. He achieved ventilatory weaning 3 days later. Carbimazole 30 mg started on day one. For secondary prevention in this SCA survivor, an implantable cardioverter defibrillator device (ICD) was implanted.

Outcome and follow-up

He was discharged home 2 weeks after admission with an ICD and hyperthyroidism treatment. Follow-up on the interval of 3 and 6 months following discharge; he was asymptomatic, his thyroid functions were normal, along with no arrhythmia noted on ICD interrogation.

Discussion

Ventricular arrhythmias, usually as consequences of coronary artery diseases, are an important cause of SCA and responsible for about 80% of these cases.^{21 22} In addition to 10%–15% occur in patients with cardiomyopathies of other causes such as hypertrophic cardiomyopathy, dilated cardiomyopathies, arrhythmogenic right ventricular dysplasia and myocardial infiltrative diseases (sarcoid, amyloidosis).^{22 23} Other 5% including less common causes such as metabolic disorders, drug toxicity, genetic diseases such as long QT syndrome and BrS.^{24 25}

Cardiac manifestations of hyperthyroidism are well known.²⁶ Arrhythmias due to hyperthyroidism often manifest themselves as sinus tachycardia, supraventricular tachycardias, atrial fibrillation or ventricular tachycardia.²⁴ In contrast to V FIB, which is rarely linked to hyperthyroidism.²⁷

On thorough literature review, most of the patients who had SCA due to hyperthyroidism were in thyroid storm, and this was mainly caused by gravies disease,^27–29 whether they have underlying heart disease or not.^27–30 Brugada ECG pattern rarely reported in such cases; Korte et al³¹ described a case of an 18-year-old man presenting with an SCA due to primary VF in the presence of thyroid storm. With subsequent workup revealed BrS type 1.³¹ Additionally, Tsai et al³² reported a case of BrS in association with thyrotoxic periodic paralysis.

To the best of our knowledge, this is the first case of asymptomatic hyperthyroidism presenting as SCA with transient Brugada ECG pattern. In the reported case, the TSH receptor antibody-negative hyperthyroidism diagnosis was based on the findings of high T4, T3, low TSH and negative antibodies. He did not fulfil the criteria for thyroid storm. He did not have any known cardiac or other medical disease and was on no medications. Postresuscitation ECG showed BrS type 1 pattern. However, this pattern was transient and did not persist on subsequent ECGs.

Ajmaline and flecainide tests were inconclusive in our patient, however, this can be due to the incorrect procedural use of the mentioned tests or their sensitivity.³³ Of note, the non-availability of the intravenous form of Na channel blocker in many cardiac catheterisation laboratories, as in our case, oral flecainide was used as an alternative in the challenging test since it was proven to be safe and valuable to unmask BrS in small studies.^34–36 However, no systematic analysis of such data could conclude its sensitivity or compare it to the Intravenous form, as yet.^{35 36}

Treatment for patients diagnosed with BrS has mainly targeted SCA prevention and the termination of any ventricular arrhythmias with ICD insertion, which is indicated for patients with BrS who have experienced SCA,4 6 37 38 similar to our patient. However, despite its role in preventing SCA, ICD has its risks and complications, that is, why using it as a prophylaxis measure is still challenging and ranging from highly recommended for a patient with a history of syncope and documented ventricular arrhythmia to not indicated in an asymptomatic patient with no family history of SCA.4 6 39 40 All first-degree relatives of patients with BrS should be screened with a clinical history and 12-lead ECG, in addition to genetic testing, if the proband has an identified genetic mutation.⁴⁰

Our patient likely had SCA caused by BrS, which is in turn, induced by asymptomatic hyperthyroidism. However, this seems the most plausible explanation for the patient presentation considering the patient’s family history of SCA, and no arrhythmias were detected after correction of Thyroid function. Nevertheless, we acknowledge the two conditions might be separate since there is a possibility that SCA could also be due to a BrS itself or hyperthyroidism with BrS like ECG, despite being rare, but V FIB secondary to hyperthyroidism in patients with normal heart was reported in the literature.²⁷ Additionally, repolarisation changes are known to postcardiac arrest, and these changes can be transit or non-specific, which can be due to multiple factors, including but not limited to pulmonary embolism, electrolytes abnormalities or hypothermia.⁴¹ As BrS-like ECG can occasionally appear post electrical cardioversion,⁴² this is seemingly worthy of consideration in our patient.

There are no available reports of the prevalence nor outcomes of BrS in the context of hyperthyroidism, while supportive care, TFTs correction and preventive ICD insertion remain a life-saving approach as in our case.

Patient’s perspective.

It was very hard experience to me and my wife, and I hope this piece of work would help other people to avoid what happened to me.

Learning points.

• Asymptomatic biochemical hyperthyroidism could precipitate sudden cardiac arrest from arrhythmia.

• Transient Brugada ECG pattern may be seen in a patient with hyperthyroidism and may precipitate serious arrhythmia with catastrophic outcomes.

• Evaluating thyroid status in patient with asymptomatic Brugada pattern, which may avoid fatal consequences, and thyroid function tests should be part of the initial work-up of patients with sudden cardiac arrest.

• Other causes of Brugada syndrome (BrS)-like ECG needs to be acknowledged, especially in postcardiac arrest patients.

• Early cardiopulmonary resuscitation, defibrillation, prompt hyperthyroidism treatment may lead to good functional outcome in patients with sudden cardiac death precipitated by underlying hyperthyroidism.

• First-degree relatives of patients with BrS should be screened with a clinical history and ECG, along with genetic testing, if the proband has an identified genetic mutation.