Successful Outcome of Peripartum Cardiomyopathy in a Myasthenia Gravis Patient

Peripartum cardiomyopathy (PPCM) is a rare cardiac disorder occurring in the peripartum period with mortality rates between 9% and 56%. Its association with myasthenia gravis (MG) has not been previously reported. MG is an autoimmune disease with autoantibodies against the acetylcholine receptor at the neuromuscular junction. First reported in 1901, cardiac disease manifestations in MG include dysrhythmias and myocarditis, particularly in patients with thymoma. There are case reports of malignant thymoma associated with MG, giant cell myocarditis (GCM), and myositis. In this article, we report on a young patient with a history of MG without thymoma, who developed PPCM, and we review the literature about cardiac involvement in MG. A 21-year-old African American female with MG presented with productive cough in her 35th week of pregnancy. She had a history of intubation twice for myasthenic crisis before undergoing thymectomy 6 years ago and has been currently on pyridostigmine therapy. She denied chest pain, dyspnea, diplopia, or dysphagia. The vital signs revealed blood pressure of 139/83 mm Hg, heart rate of 104 beats per minute, temperature of 97.7°F, respiratory rate of 18 breaths per minute, and oxygen saturation of 99% on 2 L oxygen via nasal cannula. Physical examination revealed diminished breath sounds and rales in both lung bases, no jugular venous distention, normal first and second heart sounds, tachycardia, presence of S3, no murmurs, point of maximal apical impulse in the left sixth intercostal space 1 cm lateral to the midclaviclar line, a gravid uterus, and pedal edema. Chest radiography revealed bilateral pleural effusions and infiltrates (Figure 1). She was initially treated for pneumonia with ceftriaxone, azithromycin, pyridostigmine, levalbuterol and atrovent nebulizer treatment, and guaifenesin antitussive. However, after normal vaginal delivery, her dyspnea worsened. Antibiotics were changed to vancomycin and cefepime. Electrocardiography showed sinus tachycardia and T wave inversions in lateral leads (Figure 2). Cardiac enzyme levels were not elevated; however, the brain natriuretic peptide level was 3720 pg/mL. Computerized tomographic angiography of the chest was negative for pulmonary embolism, and echocardiography revealed left ventricular ejection fraction of 15% with severe mitral regurgitation (Figure 3 and Figure 4). A diagnosis of peripartum cardiomyopathy was made, antibiotics were stopped, and heart failure (HF) treatment was initiated. The patient was treated with intravenous furosemide, oral metoprolol, fosinopril, and digoxin and she responded well. The MG remained stable throughout her current pregnancy and hospital course. At 6-month follow-up, she had clinically improved, and echocardiogram revealed significant improvement in left ventricular function (Figure 5 and Figure 6). Chest radiography showing bilateral pleural effusions and infiltrates. Sinus tachycardia and T wave inversions in lateral leads. Echocardiogram at the time of initial presentation showed severe mitral regurgitation. Echocardiogram at the time of initial presentation showed left ventricular ejection fraction of 12%. Echocardiogram 6 months later showed improvement in mitral regurgitation. Echocardiogram 6 months later showed left ventricular ejection fraction of 52%. PPCM in a patient with MG has not been previously reported. PPCM is defined as the development of HF in the last month of pregnancy or within 5 months after delivery, in the absence of a demonstrable cause for cardiac failure or demonstrable heart disease before the last month of pregnancy, and with documented systolic dysfunction.1 The etiology of PPCM is currently unknown, but hypotheses suggest that myocarditis and abnormal immunologic activities in pregnancy such as inflammatory cytokines can cause PPCM.1 MG is an autoimmune disorder in which autoantibodies against the acetylcholine receptor at the neuromuscular junction cause impaired neuromuscular transmission.2 The mean age at onset is 28 years in females and 42 years in males.2 The clinical features include weakness and easy fatigability of skeletal muscles, diplopia, and difficulty in swallowing and articulation.3 Serum antiacetylcholine receptor antibodies are present in 70% to 90% of patients with generalized MG and 50% of patients with ocular MG.3 Seventy-five percent of patients with MG have thymic abnormalities and 10% of them have thymoma, which are mostly benign.2, 3 Thymic hyperplasia is present in 60% to 80% of myasthenic patients.2 Weigert first reported myocardial pathology in MG in 1901.4 Hofstad et al reported a 16% frequency of heart diseases related to MG.4 Cardiac dysrhythmias were the most frequent cardiac clinical signs of MG in this study, and included atrial fibrillation, AV block, paroxysmal tachycardia, and asystole. HF was reported in 3.7% of patients.5 These cardiac findings were more frequent among MG patients with thymoma.4 MG with myocarditis is also often associated with thymoma. The cardiac histopathology associated with MG was first described in 1905 and consists of myofibrillar necrosis, inflammatory changes with edema, hemorrhage, lymphocytic infiltrates, and large histiocytes.6 Case reports have demonstrated the association of GCM with thymoma and MG.7 GCM resulted in HF in 1 patient, and another patient died from cardiac failure after thymoma resection.7, 8 GCM has a clinical course of rapidly progressive HF associated with ventricular arrhythmias.8 MG is also associated with pericarditis.9 Antimyocardium antibodies have been found in patients with thymomas, and antibodies against cardiac conducting tissue have also been demonstrated in MG patients.10 In their study of electrocardiographic findings in 24 MG patients, Buyukozturk et al11 reported that the most common finding was QT prolongation. Other findings included sinus tachycardia, sinus arrhythmias, right bundle-branch block, and nonspecific ST-T wave changes. Another study reported signs of myocardial ischemia as the most frequent pathological finding. Less frequent findings included atrioventricular block, atrial fibrillation, left ventricular strain pattern, atrioventricular junctional rhythm, atrial flutter, and left bundle-branch block.4 Research has found varying effects of pregnancy on MG. According to a study of the outcome of 69 pregnancies in 65 patients, 15% of patients clinically deteriorated during pregnancy, 16% during puerperium, and 17% delivered by cesarean section.12 The majority of pregnancies resulted in term deliveries, but the course of MG in pregnancy is unpredictable.12 Batocchi et al studied 47 MG patients and 64 pregnancies and found that in patients who were receiving therapy, MG symptoms improved in 39%, remained unchanged in 42%, and deteriorated in 19% of patients.13 The described patient had only thymic hyperplasia and not thymoma at the time of thymectomy 6 years ago. She did not develop arrhythmias or myasthenic exacerbation during the current pregnancy and delivered a healthy male child at term by normal vaginal delivery. Since then, her congestive HF symptoms have improved; on her 6-month follow-up visit, echocardiogram revealed significant improvement in left ventricular ejection fraction, as well as severity of mitral regurgitation. To our knowledge, this is the first case of congestive HF in a pregnant patient with MG. Whether autoantibodies associated with MG in the setting of pregnancy can result in congestive HF remains unknown and needs further studies.