Abstract
Atrial fibrillation (A-fib) is the most common cardiac arrhythmia which is associated with an increased risk of mortality secondary to stroke and coronary artery disease. Intravenous glucocorticoid therapy (such as dexamethasone and hydrocortisone) is frequently used peri-operatively in patients undergoing cardiac surgery to prevent A-fib. Dexamethasone is also frequently used in patients with single or bilateral vestibular schwannomas (VS), to reduce tumor swelling both before and after radiation treatment. We describe a case of A-fib in a 50 year-old female patient with neurofibromatosis type 2 (NF-2), who was prescribed dexamethasone for post-radiation tumor edema.
1
Case
CM was diagnosed with NF-2 in 1987 at the age of 25 years when she presented with tinnitus, hearing loss and vertigo. Diagnostic imaging revealed bilateral vestibular schwannomas (VS). She underwent left VS resection in 2001. In 2009 tumor growth was noted and she had stereotactic radiation therapy (SRT); 3125 cGy in five fractions over 1 week with 10 beams, to the left base of skull lesion. Post-SRT she received a 2-week course of oral (PO) dexamethasone 2 mg three times per day (t.i.d.). Although the left VS has remained stable the right VS showed steady enlargement and she underwent SRT of the right VS (5000 cGy in 25 fractions) to control tumor growth in July 2012.
During treatment of the right VS she experienced facial numbness and fullness in the head which responded well initially to a 2-week course of oral dexamethasone 2 mg t.i.d. She presented again in October with occipital headaches and right-sided facial numbness. A CT scan was performed which revealed further tumor enlargement as well as pontine and middle cerebellar peduncle compression (see Fig. 1 ). Oral dexamethasone 2 mg t.i.d was restarted on October 7, 2012 and titrated up to 4 mg b.i.d. over 1 week as symptoms progressively worsened. Patient presented to the local hospital about 10 days later with generalized weakness, diaphoresis and palpitations. An electrocardiogram revealed paroxysmal atrial fibrillation with a ventricular rate of 133 beats per minute (see Fig. 2 ).
In the hospital she received two 2.5 mg doses of intravenous metoprolol over a 3 hour period followed by 25 mg metoprolol orally (PO) and within 12 hours she reverted to normal sinus rhythm (see Fig. 3 ). Cardiology assessment was unremarkable with normal high sensitivity Troponin T assay ( < 14 ng/L) and a normal transthoracic echocardiogram which showed no structural abnormality. She was weaned off dexamethasone over the next 4 weeks. She remained in sinus rhythm. Metoprolol was discontinued at the 3 month follow-up assessment by cardiology.
2
Discussion
Dexamethasone is frequently prescribed before surgery or with SRT to manage edema and brainstem tumor compression and high dose therapy over long term can lead to the development of iatrogenic Cushing’s syndrome. Although A-fib is of the commonest arrhythmia, affecting more than 250,000 Canadians, our patient did not have the usual risk factors such as: advanced age, diabetes, high blood pressure, or underlying cardiovascular disease. In a nested case-control study high dose steroid ( > 7.5 mg prednisone equivalents) use for 1 month or less was associated with new onset arrhythmia. In this study by Van der Hooft et al. all patients who received a prescription for corticosteroids within 1 month of diagnosis of new-onset A-fib were identified. They conclude that some of these patients (4 out of 43) had never received a high-dose corticosteroid prescription before and these patients were also at higher risk of developing A-fib compared to the general population. The study by Van der Hooft et al. however does provide some evidence in the literature that short-term high-dose corticosteroid use may be associated with a higher risk of A-fib (albeit in four patients). It is interesting that many of the patients in this study had asthma and COPD (disorders that could also be associated with higher risk of A-fib), but some patients, like our patient, were receiving steroids for disorders not typically associated with A-fib.
In contrast, meta-analysis of randomized double blind trials has shown demonstrable prophylactic efficacy of dexamethasone in reducing post-operative A-fib in patients undergoing cardiac surgery. It seems that the protective effect of steroids in patients undergoing cardiac surgery may have to do with attenuating the systemic inflammatory response and reducing myocardial inflammation, and this may be how A-fib is prevented in this population. One would be very cautious about generalizing these conclusions to patients who have not undergone cardiac surgery. Results are conflicting with other investigators reporting little or no biological effect in single prospective, randomized, double-blind, placebo-controlled trials.
Dexamethasone is a selective glucocorticoid receptor agonist with reportedly minimal mineralocorticoid receptor (MR) activation. Both glucocorticoid and mineralocorticoid receptors are found in human atria. Atrial fibrillation and myocardial infarction are commonly associated with MR activation with MR inhibition providing cardiovascular protection . In experimental animal models MR antagonism alters atrial ionic channels affecting atrial electrophysiology exerting its cardioprotective effect. High doses of dexamethasone aggravated infarct area and apoptotic index in a rat model of myocardial infarction, effects that were blocked by the MR antagonist spironolactone . Increased local expression in human atrial tissue of MR and 11beta-hydroxysteroid dehydrogenase type 2, which is responsible for the inactivation of glucocorticoids, occurs in patients with chronic persistent AF (> 6 mo) relative to patients that had no history of AF and normal sinus rhythm. In other case reports of atrial fibrillation due to corticosteroids there was a relationship between a transient increase in serum potassium and the development of atrial fibrillation. CM had a serum K + level of 5 mmol/L (upper level of normal) at the time of presentation to the emergency department. Serum potassium levels decreased to 4.6 mmol/L when A-fib resolved and with the return of normal sinus rhythm. The cardioprotective effects of dexamethasone are tempered by the finding that high doses of glucocorticosteroids can have mineralocorticosteroid effects. Mineralocorticoid receptor activity may not be dose specific as it has been demonstrated that the deleterious effects of glucocorticoids in primary neonatal rat cardiac myocyte cultures result from their ability to activate MR under stress conditions . Stress sensitization to the effects of dexamethasone may explain CM’s new onset A-fib in light of the fact that she did have corticosteroid treatment in the past (at the same dose) without previously developing A-fib.
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