Paroxysmal atrial fibrillation after initiation of fingolimod for multiple sclerosis treatment

Abstract

is an oral disease-modifying therapy (DMT) approved for relapsing multiple sclerosis (MS) that acts via modulation of the sphingosine-1phosphate (S1P) receptor. 1 Fingolimod also targets the cardiovascular system, frequently causing reduced heart rate after the first dose. 2 We describe a patient with MS who developed paroxysmal atrial fibrillation (PAF) after initiating fingolimod therapy.Case report. A 42-year-old man with no medical history other than MS presented with a persistently relapsing progressive course. Since other DMTs were discontinued because of adverse effects or lack of effectiveness (figure, A), we started the patient on fingolimod. Routine screening, consisting of an ECG showing a normal sinus rhythm of 62 beats per minute (bpm) and blood tests of serum liver functions and leukocyte count and differentiation, did not point to any contraindications. We prescribed fingolimod (0.5 mg/day) to be administered under cardiac surveillance. Approximately 2.5 hours after the first dose, the patient had 5 short episodes of narrow complex tachycardia within 10 minutes. Each episode lasted 6-15 seconds and consisted of an abruptly increased heart rate to 210 bpm alternating with a sinus rhythm at 75 bpm. Blood pressure remained stable around 130/70 mm Hg. The patient had palpitations, chest pain, paresthesia in his limbs, and a feeling of heat (core temperature 36.8°C) during these episodes and stated he had never experienced these before.Cardiologic examination revealed no abnormalities. ECG and blood tests for electrolytes, kidney function, and measures of infection were normal.The cardiologist diagnosed PAF, sometimes preceded by beats with abnormal QRS morphology (figure, B). This is most likely explained by the Ashman phenomenon; when lower heart rates are suddenly followed by tachycardia, it may take several heart beats before conduction velocity in the His-Purkinje system (HPS) has increased, resulting in transient aberrant intraventricular conduction. 3 A single dose of sotalol 40 mg was prescribed to urgently treat the high heart rate, at the risk of drug interaction with fingolimod.The patient had a few more PAF episodes the night following sotalol but none by the following day. A rechallenge with fingolimod was justifiable because a clinically relevant interactive effect of the low-dose sotalol was considered unlikely after 20 hours, and at this moment a causal relation with fingolimod was uncertain. However, approximately 2.5 hours after the second dose, a short series of PAF recurred during 30 minutes, with identical signs and symptoms as the initial episodes. They started with an episode of 30 seconds at 180 bpm, followed by episodes of 2-10 seconds alternating with a sinus rhythm at 78 bpm. Again at night a single episode occurred and none by the next day.Since arrhythmias reproducibly started 2.5 hours after fingolimod administration, we assumed causality and discontinued treatment.Following discharge, physicians from the cardiology clinic extensively evaluated the patient (including transt...

Assessment of atrial electromechanical delay and echocardiographic parameters in patients with multiple sclerosis

“…13 Although fingolimod is generally known as the cause of bradycardia, it has been reported in the literature that it causes paroxysmal atrial fibrillation. 14 In our study, no statistically significant AEMD was determined between the MS patient groups and the control group using and not using immunomodulators, but the left and right intraatrial EMD values were determined to be longer compared to the control group. There are some observational studies in the literature reporting that the risk of AF was reduced in MS. 15,16 It was considered that this may be due to the frequency of female gender in the MS patient group and/or may be associated with decreased aerobic capacity because of the inactivity in the patients.…”

Electrocardiographic assessments and cardiac events after fingolimod first dose – a comprehensive monitoring study

“…No patient required overnight monitoring due to QT interval prolongation > 500 ms, as warranted by the EU label. Although single reports on spontaneous arrhythmias have been published [11–16], no such events were observed in this large cohort.…”

Ventricular tachycardia on chronic fingolimod treatment for multiple sclerosis

“…That study showed more atrioventicular blocks and bradycardias but no episodes of VT or atrial flutter at first dose and at month 3 2. However, the detection of five short periods of symptomatic paroxysmal atrial fibrillation was recently described in a patient 2.5 h after receiving the first dose of fingolimod, and an increase in ventricular premature complexes in another patient with three syncopes while on treatment, demonstrating the potential arrythmogenic effect of fingolimod 3 4…”