Case 1
The patient was a 43-year-old male, who had been physically healthy. On August 12, 2015, he underwent mediastinal tumor resection in Guangdong Provincial People’s Hospital. The postoperative pathological diagnosis was “thymoma, type B2”, and the patient received the chemotherapy with cyclophosphamide plus cisplatin. On September 18, 2016, the contrast-enhanced chest CT scan revealed a recurrence of thymoma with left pleural metastasis. On September 23, 2016, a mediastinal mass resection was performed. After the surgery, the patient received chemotherapy with Docetaxel plus Lobaplatin. In July 2018, limb weakness was found in the patient and he was admitted into the hospital. On admission, serum levels of creatine kinase (CK) (6370 U/L), Creatine Kinase-MB Isoenzyme (CK-MB) (97.7 U/L), and troponin T (TNT) (571.8 pg/ml) increased significantly. Left ventricular ejection fraction (LVEF) was 73%, estimated by echocardiography on July 13, 2018. Moreover, biomarkers of vasculitis such as ANCA-nuclear, antinuclear Antibody ANA was positive. Electromyography (EMG) suggested partial myogenic damage. the patient was diagnosed with polymyositis (PM), and the symptom alleviated after treatment of glucocorticoid. Meanwhile, the chest CT indicated the thymoma metastasis to the left thoracic cavity and therefore surgery was performed. Later, multiple CT scans performed in 2019 showed that thymoma was progressing. Accordingly, after the routine examination such as the electrocardiogram (ECG) showing substantially normal, on June 24, 2019, the patients received chemotherapy with pembrolizumab (200mg) plus paclitaxel (300mg).
On July 2, 2019, symptoms of chest tightness, shortness of breath, and limb weakness showed up. The myocardial enzyme tested in the community hospital was elevated. Chest CT scan showed that the pleural metastasis lesion was reduced. The symptoms did not alleviate after the patient was given glucocorticoid (methylprednisolone) and diuretics. Moreover, on July 6, 2019, tracheal intubation and ventilator-assisted ventilation were performed due to dyspnea and respiratory failure. The patient was transferred to Guangdong Provincial Peoples Hospital for intensive care and further treatment on July 7, 2019.
Physical examination on admission: Temperature (T): 36.5 ° C, Pulse (P): 84 beats per min, Respiratory rate (R): 20 times per min, Blood pressure (BP): 122 / 80 mmHg. The patient was conscious. There was no rash on the skin or mucosa. The lungs were clear with no pleural rub. The heart rate (HR) was 80 beats per min with sinus rhythm. No pathological murmur or pericardial friction rubs were detected through auscultation. The limbs were not swollen.
Auxiliary examination:
A. CK: 5806 U/L; CK-MB: 193.5 U/L; peak high sensitive troponin T (HS-TNT): > 10000 pg/ml; peak N terminal pro B type natriuretic peptide (NT-proBNP): 7140 (pg/ml); positive acetylcholine receptor antibody (> 20 nmol / L, normal range < 0.45nmol / L); positive ryanodine receptor calcium release channel receptor antibody (normal range: negative); negative idiopathic inflammatory myopathy panel; negative paraneoplastic syndrome panel.
B. ECG: atrioventricular dissociation, multi-source ventricular escape rhythm, and HR were 60–80 beats per min.
C. Echocardiography: LVEF was 55%.
D. Chest X-ray: infections of lungs on both sides.
E. Muscle biopsy of the right quadriceps: fragmentary specimens, fibrous tissue, fat, and muscle tissue.
F. Myocardial biopsy: Fig. 1.
Diagnosis: 1, acute severe myocarditis, arrhythmia, heart failure, New York Heart Association cardiac function grade IV; 2, suspected acute coronary syndrome; 3, PM; 4, suspected myasthenia gravis; 5, thymic malignant tumor (recurrence)
Intervention: methylprednisolone 80mg/day; immunoglobulin 25g/day; Pyridostigmine Bromide 60mg q6h. Shortness of breath was slightly alleviated after treatment. However, on July 9, 2019, the patient suffered atrioventricular dissociation, ventricular escape beat with the HR of 35–50 beats per min. Temporary pacemaker implantation was performed and coronary angiography showed no occlusion or slow flow (TIMI level 2) of the vessels. Within 24 hours, cardiac arrest, ventricular tachycardia, and ventricular fibrillation showed up repeatedly and all rescue measures proved ineffectual.
Prognosis: death.
Naranjo score2: 2 (Table S1)
Case 2
The patient was a 27-year-old female, who had been physically healthy and denied a history of smoking. On May 12, 2019, a contrast-enhanced chest CT scan revealed a thymic tumor in the anterior superior mediastinum with pleural metastasis. The pleural biopsy indicated thymoma (type B2, stage IV with pleural metastasis. On June 5, 2019, the patient received chemotherapy with albumin-bound Paclitaxel (200mg), carboplatin (740mg) and pembrolizumab (200mg). On June 17, 2019, the patient started to suffer from limb weakness, shortness of breath, right eyelid ptosis, and stress urinary incontinence. The symptoms gradually worsened, and the patient was transferred to the intensive care unit on June 21, 2019.
Physical examination: T: 36.2 ° C, P: 150 beats per min, R: 20 times per min, BP: 124 / 89 mmHg. The patient was conscious. There was no rash on the skin or mucosa. The lungs were clear with no rales or pleural rub. The HR was 134 beats per min with sinus rhythm. No pathological murmur or pericardial friction rubs were detected through auscultation. The limbs were not swollen.
Auxiliary examination:
A. on admission: CK: 10988 U/L; CK-MB: 293.7 U/L; peak HS-TNT: 6558.0 pg/ml; peak NT-proBNP: 4030.0 pg/ml.
B. the ECG showed second-degree atrioventricular blocks: Mobitz type I, intraventricular aberrant conduction. The arrhythmia aggravated ventricular tachycardia later.
C. Echocardiography: LVEF was 41%.
Diagnosis: 1, acute severe myocarditis, arrhythmia, heart failure, New York Heart Association cardiac function grade IV; 2, suspected myasthenia gravis; 3, suspected myositis; 4, thymoma (type B2, stage IV with pleural metastasis).
Intervention: the patient was treated with methylprednisolone 80 mg/day intravenously. The onset of ventricular tachycardia started on the day of admission with the ventricular HR of 200–250 beats per min, accompanied by decreasing blood pressure. Cardioversion helped in converting to sinus rhythm. Continuous renal replacement therapy (CRRT) was initiated on the same day due to anuria. However, the patient suffered from frequent premature ventricular contraction and recurrent ventricular tachycardia. Lidocaine was used as antiarrhythmics and electrolyte disturbance was remedied. The dose of methylprednisolone was increased to 120mg/day. Unfortunately, the patient developed a pulseless ventricular tachycardia on June 23, 2019, and cardiac arrest occurred after cardioversion. All rescue measures proved ineffectual and no return of spontaneous cardiac rhythm.
Prognosis: death.
Naranjo score: 2 (Table S1)
Case 3
The patient was a 52-year-old male, with a medical history of kidney stones and smoked for more than 30 years. In December 2017, mass in the lung was found through an annual health check. On March 27, 2018, the CT scan found a right lung neoplasm with pleural metastasis. The lung biopsy showed thymoma (suspected type B1 or type AB). On April 19, 2018, the therapy of albumin-bound Paclitaxel (200 mg), carboplatin (740 mg), and pembrolizumab (200 mg) were administered. On May 3, 2018, the patient developed fever, soreness, limb weakness, shortness of breath, and left eyelid ptosis. The patient was admitted into the community hospital on May 8, 2018. Tests on myocardial enzymes showed elevated CK (25612 U/L) and CK-MB (969 U/L), positive acetylcholine receptor antibody (5.50 nmol / L, normal range < 0.45nmol / L), positive ryanodine receptor calcium release channel receptor antibody (normal range: negative), and positive connexin antibody (normal range: negative). Chest CT scan showed a mass in the right lung, pneumonia on both sides. Between May 8, 2018, to May 10, 2018, the patient was treated with methylprednisolone 40mg/day intravenously, intravenous immune globulin (IVIG) 35g/day, and anti-infection. On May 10, 2018, the patient developed a complete atrioventricular block with the HR decreasing to 24–28 beats per min. Emergent implantation of the temporary pacemaker was performed. Between May 11, 2018, to May 13, 2018, the dose of methylprednisolone was increased to 500mg/day, combined with IVIG 35g/day). The disease showed no improvement and on May 14, 2018, the patient was transferred to the intensive care unit in Guangdong Provincial People’s Hospital.
Physical examination: T: 36.0 ° C, P: 130 beats per min, R: 25 times per min, BP: 78 / 58 mmHg. The patient was in a coma. There was no rash on the skin or mucosa. The pupils were equal and round with a diameter of 3 mm but no light reflex on both sides. The lungs were rough with moist rales of both lower lungs. No pleural rub was heard. The HR was 130 beats per min with sinus rhythm. No pathological murmur or pericardial friction rubs were detected through auscultation. The limbs were not swollen.
Auxiliary examination:
A. on admission: CK: 7633 U/L, CK-MB: 159.5 U/L. peak HS-TNT: > 10000 pg/ml; peak NT-proBNP: 5696 pg/ml.
B. ECG: complete atrioventricular block.
C. Echocardiography: LVEF was 21%.
Diagnosis: 1. acute severe myocarditis arrhythmia Heart failure, New York Heart Association cardiac function grade IV; 2, myasthenia gravis; 3. Suspected myositis; 4. Thymoma (type B1 or type AB)
Intervention: the patient was treated with methylprednisolone 40 mg/day intravenously, IVIG 35g/day, and anti-infection. Within 24 hours since admission, ventricular escape beat emerged with an HR of approximately 30 beats per min, accompanied by the loss of blood pressure and oxygen saturation. After cardiopulmonary resuscitation, the patients returned to sinus rhythm but no spontaneous circulation. Extra-Corporeal Membrane Oxygenation was implemented. However, the heart function did not improve and was succeeded by multiple organ failure. The family withdrew from treatment on May 15, 2018.
Prognosis: multiple organ dysfunction syndrome and withdrawal of treatment.
Naranjo score: 2 (Table S1)