Objective:To investigate the clinicopathological characteristics and possible pathogenesis of immune checkpoint inhibitor (ICI) induced myocarditis, and to improve understanding of this new type of myocarditis.Methods:Two cases of ICI induced myocarditis with endomyocardial biopsy available for review were selected from the cases with immune-related adverse events treated by ICI in Peking University First Hospital, Beijing, China from 2020 to 2022. The clinical data, histomorphological characteristics, PD-L1 expression of cardiomyocytes, and classification of inflammatory cells in two cases of ICI-induced myocarditis were analyzed. Relevant literature was reviewed.Results:Case 1 was a 64-year-old male diagnosed with gastric signet ring cell carcinoma. Case 2 was a 56-year-old male ad diagnosed with lung squamous cell carcinoma. Both patients developed acute myocarditis during PD-1 inhibitor treatment, and the disease progressed rapidly. Case 2 was more serious than case 1. Endomyocardial biopsy showed definite cardiomyocytic injury and prominent inflammatory infiltration in both cases, which met the full Dallas criteria for myocarditis. The degenerated and necrotic cardiomyocytes accounted for about 10% of the tissues in case 1 and 30% in case 2, respectively. In case 1, the inflammatory cells counted in the densest area were about 150/HPF, comprised of CD20 + cells (about 5/HPF), CD3 + cells (about 60/HPF), CD8 + cells (about 50/HPF) and CD68 + cells (about 70/HPF). In case 2, the inflammatory cells counted in the densest area were about 350/HPF, comprised of CD20 + cells (0/HPF), CD3 + cells (about 100/HPF), CD8 + cells (about 90/HPF) and CD68 + cells (about 200/HPF). In both cases, PD-L1 + cardiomyocytes aggregated in the inflammatory lesions, and the percentage was about 8% and 30% in case 1 and case 2, respectively. Conclusions:ICI-induced myocarditis is frequently acute onset, severe symptoms, and rapid progression. The histological morphology meets the full Dallas criteria for myocarditis. Expression of PD-L1 in cardiomyocytes can be detected in the inflammatory lesions. The inflammatory cells are comprised of CD8 + T lymphocytes and macrophages and the number of macrophages significantly exceeds that of lymphocytes. Combined with the pathological characteristics and the history of ICI treatment, the diagnosis of ICI-induced myocarditis can be made.

Objective:To evaluate the dosimetric properties of intensity-modulated proton therapy (IMPT) plans for simulated treatment planning in patients with ventricular tachycardia (VT) using stereotactic ablative body radiotherapy (SABR), in comparison with the volumetric-modulated arc therapy (VMAT).Methods:A total of 25 gross target volume (GTV) of the apical, anterior, septal, inferior and lateral wall of the left ventricle (LV) were delineated on the CT simulation images of 5 patients with complete data. An additional 5 mm GTV margin was added to the internal target volume (ITV), and an additional 3 mm ITV margin was added to the planning target volume (PTV). VMAT and IMPT plans were designed in each target area. Dose prescription was 25 Gy (RBE) in a single fraction. The dosimetric differences of ITV and organ at risk (OAR) were compared between VMAT and IMPT.Results:The median volume of ITV was 45.40 cm 3(26.72-67.59 cm 3). All plans had adequate target coverage(V 95%Rx≥99%). Compared with the VMAT plans, IMPT reduced the D mean of whole heart, pericardium and non-target cardiac tissues (relative difference) by 44.52%, 44.91% and 60.16%, respectively, which also reduced D 0.03 cm 3 of the left anterior descending artery by 17.58%( P<0.05). After stratified analysis according to the lesion sites, IMPT could still reduce the dose of most OAR. However, the D 0.03 cm 3 of LAD and LCX for the lesions in the anterior wall of LV, the D 0.03 cm 3 of LCX in the inferior wall and D 0.03 cm 3 of LAD in the apical wall did not significantly differ (both P>0.05). Conclusions:Both VMAT and IMPT plans can meet the clinical dosimetric requirements when SABR is simulated in patients with VT. However, IMPT can lower the dose of normal heart tissues, which has the potential benefit of reducing the risk of complications, such as ischemic heart disease, pericarditis/pericardial effusion, etc.

This article presents a case of acute ST-segment elevation myocardial infarction (STEMI) in a pregnant woman caused by coronary artery dissection. The 41-year-old patient had undergone cardiac valve surgery at the age of 1 and had no risk factors such as hypertension, diabetes, smoking, alcohol use, or a family history of coronary artery disease. At 31 +1 weeks of gestation, she experienced sudden chest pain for 4 hours and was emergently referred to Peking University First Hospital on June 1, 2021. Electrocardiogram revealed ST-segment elevation in leads I, aVL, and V 2 to V 6. Biochemical assays showed elevated levels of high-sensitivity cardiac troponin I and creatine kinase-MB. Echocardiography indicated segmental ventricular wall motion abnormalities (apical) and reduced left ventricular function, confirming the diagnosis of acute anterior wall STEMI. The patient promptly underwent emergency coronary angiography and percutaneous coronary intervention and confirmed coronary artery dissection. Postoperative care included antiplatelet, anticoagulation, and supportive treatment. At 34 +3 weeks of gestation, with the condition of acute anterior wall STEMI being relatively stable, a cesarean section was successfully performed. Regular cardiology follow-ups were scheduled postpartum, and cardiac function was normal in two years after discharge.