Patients in crisis due to myasthenia gravis (MG) exacerbations are by definition ill and unstable. Although many of them may have coexisting illnesses, including cardiac arrhythmias, there are few reports detailing such problems. This may be due to the relative infrequency of such patient admissions and the hyperacuity of their management in a hospitalized setting causing their cardiac issues to be overlooked. Moreover, little is known about cardiac ramifications of MG crisis.
Retrospective chart review of patients within 1 neurologist’s inpatient and outpatient practice was done. Charts were selected based on the coincidence of newly diagnosed AF and MG crisis over a 9-year period. Charts were reviewed to determine factors that may have played a role in the co-occurrence of these 2 diseases.
A 68-year-old male developed 1 year of progressive weakness and ptosis that had worsened in the 6 weeks before his hospital admission. He developed neck drop, diplopia, visual blurring, swallowing difficulty eating requiring taking small bites, exercise fatigue, and weight loss. He also suffered muscle cramping in his neck and in his hands, particularly when tired. He had noticed voice changes when tired.
He was found to have an elevated acetylcholine receptor (AChR) antibody titer of 70.8 nmol/L. He had no cardiac history although he had had palpitations intermittently over the years. During the admission for MG crisis, he received intravenous immunoglobulin (IVIG) 2 g/kg over 5 days and oral prednisone. On day 3 of IVIG treatment, he developed atrial fibrillation (AF) with the rapid ventricular response (RVR), CHADS-VASc Score 1, and required management with digoxin, amiodarone, and rivaroxaban. Cardiac tests including a 2-dimensional and transesophageal echocardiogram (ECHO) and exercise stress tests were negative (no atrial enlargement), as was a computed tomography (CT) scan of the chest for thymoma.
During outpatient follow-up over 6 years, he decreased the dose of prednisone to 4.5 mg daily and continued to take pyridostigmine. He also began rituximab every 6 months with stabilization of his MG. He did not have additional recognized episodes of AF until year 6 of follow-up when had a 15-minute episode of palpitations after forgetting to take metoprolol, although AF was not documented by electrocardiogram.
A 72-year-old male developed a pseudo-internuclear ophthalmoplegia with diplopia due to MG. An AChR antibody was positive (titer not available) due to symptoms being confined (pure ocular). He then developed trouble swallowing and breathing and was admitted for generalized MG crisis. He required intubation, and was treated with prednisone 80 mg daily and IVIG 2.0 g/kg over 5 days and pyridostigmine 60 mg by mouth 3 times daily.
During hospitalization, he developed complications including Klebsiella pneumonia, and a gastrointestinal bleed (not requiring transfusion). CT chest showed no evidence of thymoma. He had no history of coronary or cardiac disease. On hospital day 10, he developed AF with RVR, CHADS-VASc Score 2. Transthoracic ECHO did not show left atrial enlargement. He did not smoke, drink alcohol or use illegal drugs. Other than after being given prednisone in the hospital, he had no history of hypertension or glucose intolerance. He was treated medically and after 2 days of AF converted to sinus rhythm, with normalization of his Forced vital capacity and negative inspiratory force and pseudo-internuclear ophthalmoplegia.
During outpatient follow-up over 6 years, he had no further episodes of AF nor of MG crisis. He reduced the daily dose of prednisone to 5 mg along with pyridostigmine. He no longer required any type of cardiac medication.
A 50-year-old female presented with eyelid closure. On evaluation, she had elevated AChR antibody titers (titers not available). She was admitted for elective thymectomy for thymic hyperplasia seen on CT. She had had palpitations for a year before her thymectomy but had had a negative cardiology evaluation including a treadmill stress test, transthoracic 2-dimensional ECHO, and Holter monitor. She had been treated briefly with β-blockers. She had a 25 pack-year cigarette smoking history but quit smoking 4 weeks preoperatively. Preoperatively she received 3 plasma exchanges.
Postoperatively, she developed AF with RVR, with rates up to 190s. She was treated with aspirin and digoxin and metoprolol. She had intermittent AF for the first year postoperatively, but the AF subsequently disappeared, as did most of the symptoms of MG, except for her continuing to require more naps than usual and having mild ptosis when she was extremely tired. In 7 years of follow-up, she had no additional episodes of AF and was able to come off all medication for MG. She remained on aspirin and metoprolol and had no further cardiac complications.
An 82-year-old male presented to the hospital with slurred speech, neck weakness, and bilateral ptosis. He also had a backward head tilt (peekaboo sign) and had a positive ice test. He did have a remote previously unknown history of a left cerebellar infarct with previously known hypertension, hypothyroidism, and dyslipidemia. AChR binding antibody was positive at 28 nmol/L, and striated muscle antibody was positive at 1:80 dilution. CT chest was negative for thymoma. He initiated pyridostigmine, and oral prednisone at 20 mg daily. His MG improved. He did have continued intermittent ptosis.
Four years after diagnosis of MG, the patient was readmitted for an MG crisis with weakness of his neck and with trouble swallowing. He received 5 days of IVIG, 2 g/kg with substantial improvement. During the hospitalization, he developed AF with RVR and required a diltiazem drip and anticoagulation with apixaban. He reverted to sinus rhythm by the first hospital follow-up. The cardiac evaluation showed a CHADS-VASc 5, ejection fraction of 65% to 69% with no valvular abnormalities, and rapid conversion back to sinus rhythm. He did admit to having had AF 20 years prior but had no records of the prior AF episodes. There was left atrial enlargement seen on transthoracic ECHO.
An 82-year-old female was hospitalized with an MG crisis with symptoms of slurred speech, double vision, trouble swallowing, generalized weakness and pneumonia, and recurrent falls. AChR antibody titer was high at 16.4 nmol/L. She had been diagnosed with MG several months before the MG crisis after presenting with trouble walking, choking, and double vision. CT thorax did not show a thymoma. For the treatment of the crisis, she received IVIG 2 g/kg for 5 days, prednisone 10 mg by mouth daily, pyridostigmine 30 mg by mouth 4 times daily, eventually raised to 60 mg, and mycophenolate mofetil 500 mg by mouth twice daily. She had a history of hypertension and of lacunar infarction, of chronic obstructive pulmonary disease, dyslipidemia, peripheral arterial disease, and recurrent syncope. She had a history of heavy smoking, of 25 pack years.
She was found to have new-onset AF CHADS-VASc 7, with normal ejection fraction when she also had severe MG symptoms. Falls were correlated to the episodes of AF and resolved with treatment of AF. ECHO did show left atrial enlargement.
During 4 years of follow-up, she had no further episodes or complications of AF. She had no further falls and initiated apixaban. Her MG ocular and systemic symptoms remained under good control.
A 68-year-old male presented 8 years after diagnosis of MG. Previously he had presented with slurred speech and diplopia and been diagnosed with a Tensilon test that was strongly positive. Despite a history of childhood Hodgkin’s lymphoma, he was treated with azathioprine and intermittent IVIG as well as prednisone 40 mg, begun when he had a myasthenic flare. Each time the prednisone was reduced below 12.5 mg daily, he had a myasthenic exacerbation. He was maintained also on IVIG 30 g every 2 to 3 weeks, as well as pyridostigmine, and the azathioprine was weaned. He did have chronic ptosis and diplopia of varying levels of severity and mild generalized weakness, as well as a transverse smile. After 7 years of follow-up, during attempted weaning of prednisone to 12.5 mg by another neurologist, he had an MG flare with worsening diplopia and ptosis and difficulty breathing. During the flare, the AChR antibody titer was 70 nmol/L. About 6 weeks after this flare, he developed new AF and required anticoagulation. His MG stabilized on prednisone 15 mg by mouth daily and IVIG 35 g every 2 weeks. During 2 additional years of follow-up, his AF did not recur, nor did he have additional myasthenic flares.
A 61-year-old male with a past medical history of suspected MG, diabetes and hypertension, returned to the hospital a few weeks after discharge for worsening weakness and shortness of breath due to MG crisis. He had not filled his prescriptions for prednisone or Mestinon and thus developed recurrent crisis requiring readmission. On examination, he had an ophthalmoplegia that was nearly complete, although his speech, swallowing, gait, and muscle examination (otherwise) was relatively preserved. Because of diabetes and hypertension, he was unable to increase his prednisone dose significantly. CT chest was negative for thymoma.
Plasmapheresis, 5 treatments over 9 days was administered. The patient improved after the first plasma exchange. On day 4 of plasmapheresis, he developed AF with RVR—CHA2DS2-VASc—2. The rate was in the 120s. Cardiac 2-dimensional ECHO showed a normal ejection fraction and no valvular abnormalities and normal atrial size. He received doses of amiodarone, digoxin and metoprolol that controlled his rhythm within 2 days. The patient was noncompliant with follow-up, and the status of his cardiac and neuromuscular conditions afterwards was not determined.
A 68-year-old male with a variety of severe medical issues, including AF, congestive heart failure, and pneumonia, morbid obesity and sleep apnea, diabetes and gastroesophageal reflux disease, who had had 4 strokes of the right hemisphere, was noted 4 years later to have an AChR antibody level of 15 nmol/L (binding), 56 (blocking), and 37 (modulating). He was profoundly weak and unable to rise from his walker. He was admitted for stabilization of MG and found to be in AF. Prednisone was initiated at a dose of 40 mg by mouth daily along with pyridostigmine. Because of worsening of his respiratory status and further weight gain that exacerbated his medical issues, the prednisone was lowered, after 2 months to 20 mg daily. After several hospitalizations for pneumonia, his MG was considered stable on a consistent smaller dose of steroids, prednisone 10 mg by mouth daily, and pyridostigmine. He was anticoagulated for the paroxysmal AF and had no further episodes of MG crisis nor of AF related strokes during 3 years of follow-up. ECHO showed biatrial dilatation.
Eight patients were identified that had co-occurring MG crisis and new-onset or newly recurring AF when they experienced MG crisis. The majority of the patients had resolution or stability of their AF once the MG crisis or MG activity ended although they remained on AF treatment.
Patients tended to have late-onset MG, to be middle-aged or older (all were over 50 y), to be male (6 of 8 were male), and to be AChR antibody-positive, and to have improvement or remission of their AF once the MG achieved clinical control. None had further Holter monitors, event monitors, or loop recorders to document lack of AF subsequently but most had cardiology follow-up. Three patients had documentation of left atrial enlargement on ECHO (Table 1). None had thymomas although 1 had thymic hyperplasia. Three had previously had strokes, not during MG crisis, caused by a lacune (small vessel disease) in 1 case, and unknown mechanisms in the other 2 but potentially related to the AF.
This series of patients comprises a retrospectively chosen nonconsecutive series of MG patients seen in the office and/or on hospital rounds by a single neurologist over a period of several years due to having a combined problem. Given that significant limitation, the expected population occurrence cannot be determined, nor can the denominator (number of MG crisis patients without AF) be calculated. However, the timing of their AF in the middle of crisis management is notable.
Although medicine used to treat AF, such as quinidine and procainamide, can trigger MG symptoms, none of these patients had such treatment of AF before developing MG crisis (the MG crises occurred first). In addition, cholinomimetic treatments for MG crisis can affect heart rate, but AF is not typically a result of such treatments. We could not identify any prior case series that identified new-onset AF with RVR as a feature of MG crisis.
We propose 2 possible mechanisms. First, the sympathetic tone during severe illness may have stimulated cardiac conduction and caused an arrhythmia. Second, we speculate that there is an effect of the disease and antibodies on the cardiac muscle, but that conclusion would require additional study.