Pyridostigmine-induced coronary artery spasm in early-onset myasthenia gravis: a case presentation and review of the literature

Background

Pyridostigmine, an acetylcholinesterase inhibitor used for controlling myasthenia gravis (MG) symptoms, is an uncommon trigger of coronary artery spasm (CAS).1–4 Although the prognosis of CAS is mostly benign, it can cause irreversible myocardial infarction and fatal arrhythmias such as ventricular fibrillation and sinus arrest.5 6 Hence, early recognition and diagnosis, promptly nitrate given, immediate exclusion of acute coronary syndrome (ACS), and identification with the withdrawal of triggers are essential strategies for preventing CAS recurrence and its serious complications. In addition to CAS, MG also influences the patient quality of life, particularly when pyridostigmine, as a symptoms controller, needs to be withdrawn. Alternative agents (eg, corticosteroid, azathioprine, mycophenolate mofetil, etc) should be prescribed at once to prevent an exacerbation of MG.

Case presentation

A woman in her 40s was referred to our hospital due to intermittent chest discomfort accompanied by palpitation and diaphoresis developed 3 days ago. Chest discomfort was characterised as a retrosternal tightness, which radiated to the left scapular region, occurred at rest and spontaneously resolved within 20 min. She was recently diagnosed with seropositive non-thymomatous generalised MG based on fluctuating symptoms of ptosis, diplopia, generalised proximal muscles weakness (Myasthenia Gravis Foundation of America (MGFA) clinical classification: IIA), positive decremental responses of muscle action potentials to repetitive nerve stimulation, an elevated serum antiacetylcholine receptor (AChR) antibody titre of 8 nmol/L (normal, <0.5) and the absence of thymus on CT of the chest. Due to the progression of MG symptoms despite initiation of pyridostigmine with a dose of 120 mg daily, the drug was up titrated to 180 mg daily, which was a few days before the onset of chest pain. She also had well-controlled hypertension treated with amlodipine 5 mg daily and asthma controlled with fluticasone/salmeterol inhaler. She had no history of smoking or illicit drug use. On admission, her vital signs revealed bradycardia with a regular pulse rate of 56 beats per minute and normal blood pressure of 130/60 mm Hg. Other examinations were unremarkable.

Investigations

Twelve-lead ECG demonstrated sinus arrest and junctional escape rhythm with a rate of 60 beats per minute together with a 3 mm ST-segment elevation in limb leads II, III and aVF with a reciprocal ST-segment depression in limb leads I and aVL (figure 1A). According to the presentation and ECG findings, which were highly suspicious for ST-elevation ACS (STE-ACS), the patient was immediately treated with sublingual glycerine nitrate, intravenous heparin, dual antiplatelets including aspirin and ticagrelor and sent to the cardiac catheterisation laboratory without any delay. On the laboratory arrival, however, her chest pain was resolved, and ECG became sinus rhythm with the disappearance of ST-segment elevation (figure 1B). Coronary angiography (CAG) surprisingly showed normal coronary arteries (figure 2A and B). High-sensitivity cardiac troponin T collected at the emergency department was 72 ng/L (normal, <47). Transthoracic echocardiography (TTE) performed after CAG showed normal cardiac size, function and wall motion. Other blood tests were otherwise unremarkable.

Differential diagnosis

Given the history of acute retrosternal chest tightness along with a typical pattern of ST-segment elevation in inferior limb leads and sinus arrest, the first life-threatening condition that needed to be excluded was acute inferior wall STE-ACS from ruptured atheromatous plaque in the proximal right coronary artery (RCA). However, CAG revealed normal coronary arteries, which was suggestive of diseases under the condition named myocardial infarction with non-obstructive coronary arteries; for example, CAS, microvascular dysfunction (MVD), acute myocarditis and stress-induced cardiomyopathy. The most likely diagnosis was CAS according to the chest pain nature that intermittently occurred at rest and transient ST-segment deviation corresponding with the dynamic pain symptom. In spite of no evidence of vasospasm on CAG, this could be explained by the resolution of the symptom and ECG abnormalities before the procedure. Other differential diagnoses were less possible, although could not be totally excluded, due to many reasons; for instance, (1) angina from MVD is typically related to exertion and rarely caused sinus arrest and (2) TTE always demonstrates abnormal wall motion in stress-induced cardiomyopathy and usually in acute myocarditis.

After informing about the risks and benefits, the patient and family agreed and consented to undergo a pyridostigmine rechallenge. Pyridostigmine with a dose of 30 mg was rechallenged under close monitoring in the coronary care unit. The patient developed chest discomfort, and the ECG monitor showed that ST-segment deviation reproduced the previous episode 30 min after the first challenge dose. Again, sublingual glycerine nitrate was immediately given, then her symptom and abnormal ECG findings were rapidly resolved, which strengthened the diagnosis of CAS precipitated by pyridostigmine.

Treatment

Long-acting glycerine mononitrate was prescribed for preventing a recurrent episode of CAS. Pyridostigmine was unavoidably withheld and substituted with immunosuppressive agents including prednisolone 15 mg/day which gradually escalated to 40 mg/day (0.75 mg/kg/day) and azathioprine 50 mg/day which gradually escalated to 100 mg/day (2 mg/kg/day). Prednisolone was planned to taper to the minimum effective dose after symptoms resolve, while azathioprine was planned to continue in minimum effective maintenance dose with monitoring of liver enzymes and complete blood count.

Outcome and follow-up

At a 1-month follow-up visit, the patient reported no recurrent angina episode along with satisfying MG symptoms control, MGFA clinical classification: I (mild weakness of ocular muscle), MGFA postintervention status: minimal manifestation-1 and MGFA MG therapy status: PR and IM (prednisolone and immunosuppression). The patient also agreed to undergo thymectomy, which was scheduled 1 month later.