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Background and purpose: Outcomes for cancer patients with steroid-resistant immune checkpoint inhibitor-associated myocarditis (srICIAM) are poor. Intensified immunosuppressive therapies, including tofacitinib, a novel Janus kinase (JAK) inhibitor, may have some therapeutic benefits. However, due to the lack of sufficient clinical data, the effectiveness of such treatments and their impact on cardiovascular outcomes remain unclear. This study aimed to investigate the therapeutic effect of tofacitinib on srICIAM. Methods: This retrospective case-control study included 36 malignant tumor patients who received immune checkpoint inhibitor treatment at Zhongshan Hospital affiliated to Fudan University from July 2019 to May 2022 and developed srICIAM. Patients receiving corticosteroids in combination with tofacitinib were assigned to the tofacitinib group (n=19), while those not treated with tofacitinib were allocated to the control group (n=17). The study compared clinical characteristics, laboratory findings, and imaging results between the two groups. Additionally, follow-up was conducted to monitor the incidence of cardiovascular endpoints in these patients. The research plan was approved by the Ethics Committee of Zhongshan Hospital Affiliated to Fudan University (Approval Number: B2021-275R). This study was conducted in accordance with the ethical guidelines of the Helsinki Declaration. Results: Compared to the control group, and with no significant difference in the cumulative dose and duration of corticosteroids (P

Background and purpose: Adriamycin, also named as doxorubicin, is an effective antineoplastic anthracycline drug used worldwide. However, its cardiotoxicities characterized as dilated cardiomyopathy and congestive heart failure have limited its clinical application. This study aimed to compare the effects of benazepril, atorvastatin, sacubitril/valsartan and carvedilol on the protection of adriamycin-induced cardiomyopathy, which are commonly used as cardioprotective agents for hypertension, hyperlipidemia and cardiomyopathy, and then preliminarily explored the underlying mechanisms. Methods: Adult male C57BL/6 mice were divided into saline, adriamycin, adriamycin+atorvastatin, adriamycin+benazepril, adriamycin+sacubitril/valsartan and adriamycin+carvedilol groups. In addition to the saline group, adriamycin solution (4 mg/kg per week) was injected intraperitoneally for 5 weeks to establish the dox-induced cardiomyopathy model in vivo. Different groups were pretreated with different cardioprotective agents 0.2 mL per day for each mouse by gavage for a total of 6 weeks. The dose was: atorvastatin 10 mg/kg per day, benazepril 10 mg/kg per day, sakubactro/valsartan 60 mg/kg per day (sakubactro 28.8 mg/kg per day, valsartan 31.2 mg/kg per day) and carvedilol 5 mg/kg per day, respectively. Two-dimensional echocardiography, cell apoptosis, fibrosis and inflammation markers were analyzed in these mice. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was used to detect the total mRNA in cardiomyocytes, and Western blot was used to detect the expression levels of Bax and Bcl-2. Among BALB/c mice inoculated with 4T1 breast tumor cells, the tumor volume and mass were studied before and after treatments with different cardioprotective drugs to evaluate the effects of cardioprotective drugs on tumor growth. Results: The data revealed that all these four cardioprotective agents effectively inhibited adriamycin-induced left ventricular dysfunction, ameliorated histopathological damage, suppressed adriamycin-induced cell apoptosis and modulated the expressions of Bcl-2 and Bax proteins. They also attenuated adriamycin-mediated expressions of proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in the myocardium. Furthermore, sacubitril/valsartan not only enormously improved left ventricular ejection fraction (LVEF) (65.1%±3.8%, 63.5%±4.6%, 61.6%±4.1% and 62.1%±5.2%, P

Background and purpose: Immune checkpoint inhibitors (ICIs) have changed the landscape of cancer treatment during the last 10 years. They have significantly extended survival for patients with malignancy. However, immune-related adverse events (irAE) have been reported and attracted attention with widespread use of ICIs. Currently, there is no reliable biomarker to clinically predict the risk of irAE. This study established a risk prediction model of irAE in tumor patients receiving ICIs based on multiple biological indicators. Methods: A total of 91 patients treated in Zhongshan Hospital of Fudan University from October 2018 to December 2020 were included in the study. Patients included in the study were divided into irAE group and control group according to whether they had grade 2 or higher irAE after receiving ICIs. Biological indicators including serum soluble form of suppression of tumorigenicity-2 (sST2), prognostic nutritional index (PNI) and platelet to lymphocyte ratio (PLR) were collected before and after ICIs treatment. Logistic regression model containing these biomarkers was constructed to predict the risk of irAE. Results: A total of 13 patients in the irAE group. Baseline PNI level, baseline PLR level and post-treatment sST2 peak level showed a significant difference between the irAE group and control group (P

Background and purpose: Myocarditis induced by programmed death-1 (PD-1) inhibitors is in urgent need of animal models to explore therapeutic targets. The study aimed to figure out the best modeling method of this typical autoimmune myocarditis in mice. Methods: Thirty 6-week-old healthy male BALB/c mice were numbered and randomly divided into control group, autoimmune myocarditis group (TnⅠgroup) and immune checkpoint inhibitor (ICI)-related myocarditis group (TnⅠ+anti-PD-1 group), 10 in each group. Except for the control group, mice were subcutaneously injected with 0.1 mL complete Freund’s adjuvant containing 0.25 mg of mouse cardiac TnⅠ peptide on day 1 and day 7, respectively. From day 7, TnⅠ+anti-PD-1 group received intraperitoneal injection of PD-1 inhibitor at 5 mg/kg each time, once every 2 d, for a total of 5 times with a cumulative dose of 25 mg/kg. The general state, mortality, cardiac index, echocardiography, myocardial pathology and the levels of creatine kinase (CK) and CK isoenzyme (CK-MB) in serum were observed. Results: Compared with control group, the mass of mice in both TnⅠ and TnⅠ+anti-PD-1 groups decreased significantly on day 21 and day 56 (P0.05), while a significant rise of cardiac index (P

Background and purpose: Adjuvant radiotherapy for breast cancer after early breast-conserving surgery has been recommended by the guidelines. However, the feasibility of hypofractionated radiotherapy with simultaneous integrated boost is not available. In this randomized controlled study, the cardiac dosimetry parameters and cardiac ultrasound indexes of the two radiotherapy plans were compared to evaluate the safety of hypofractionated radiotherapy with simultaneous integrated boost plan in terms of cardiotoxicity. Methods: A total of 40 patients with breast cancer who received breast-conserving surgery were selected in Zhongshan Hospital, Fudan University from March 2017 to March 2018. They were randomly divided into two groups, including 20 patients reveiving hypofractionated radiotherapy with simultaneous integrated boost plan (whole breast 4 005 cGy/15 Fx, tumor bed 4 500 cGy/15 Fx) and 20 patients reveiving conventional fractionation with simultaneous integrated boost plan (whole breast 5 000 cGy/25 Fx, tumor bed 6 000 cGy/25 Fx). The cardiac dosimetric parameters and cardiac ultrasound indexes of the two groups were compared. The dosimetric parameters included the average doses (Dmean) of the whole heart, left ventricle, right ventricle, right ventricular free wall, ventricular septum and left anterior descending (LAD) coronary artery, and the relative volume fraction of each structure irradiated by 5-35 Gy (V5 Gy-V35 Gy). The follow-up indexes of echocardiography included aortic root diameter, left atrial diameter, left ventricular end diastolic diameter, left ventricular end systolic diameter, ventricular septal thickness, left ventricular posterior wall thickness, pulmonary artery systolic pressure, left ventricular ejection fraction, E peak, A peak, E-peak deceleration time (DT), E, A, E/A and S wave peak. In addition, the cosmetic effect on breast after radiotherapy in the two groups was also evaluated. Results: Dmean of the whole heart in the hypofractionated group and the conventional group were (471.86±170.54) and (733.07±79.11) cGy (P0.05); Dmean of left ventricle were (908.64±865.60) vs (946.93±116.13) cGy (P>0.05). Dmean of right ventricle were (590.37±197.99) vs (905.73±180.82) cGy (P0.05). There was no significant difference in cosmetic effect between the two groups (P>0.05). Conclusion: Compared with the conventional fractionation plan, hypofractionated radiotherapy with simultaneous integrated boost significantly reduced the radiation dose of the whole heart and some cardiac substructures, and there were no abnormal cardiac ultrasound indexes during one-year follow-up. The dose fractionation method in this study is safe and feasible. Limiting the whole heart dose alone can not effectively protect LAD, so it is recommended to outline the cardiac substructure and limit the dose alone to better protect the heart.

Background and purpose: The treatment-related cardiovascular disease in patients with breast cancer poses a greater mortality threat than cancer itself. To assist clinical oncologist, we introduced a scale to help clinicians by screening out patients with breast cancer who were at risk of cardiovascular diseases. The breast cancer patients in Zhongshan Hospital, Fudan University were analyzed retrospectively by the scale. Methods: This was a single center, retrospective trial. A total of 760 patients who met the inclusion and exclusion criteria were enrolled in this trial from January 1, 2017 to December 31, 2018. The incidence rate of cardiovascular risk was collected from patients eligible for admission. Secondly, follow-up information for each patient was evaluated by the scale and the clinician. The repeatability, sensitivity, specificity and consistency of the scale were evaluated. Results: The average follow-up duration was (746.55±309.94) d, and the average population age was (56.60±12.62) years. A total of 36 patients developed severe arrhythmias during or after the treatment, 8 patients with emerging myocardial injury and 6 patients with emerging cardiac insufficiency. The follow-up rates of patients with test for NT-proBNP from half a year to one year and more than one year after baseline were 34.31% and 29.62%, while 35.48% and 32.48% for those who took echocardiography. The sensitivity, specificity and overall accuracy of medium-and high-risk patient tests were 0.828, 0.934 and 0.921, respectively. The sensitivity, specificity and overall accuracy of high-risk patient tests were 0.983, 0.986, and 0.986, respectively. The linear consistency with clinical judgment was κ=0.633, P

Objective: To evaluate the accuracy of echocardiography in identifying aortic valve structures and determine the prevalence of bicuspid aortic valves (BAV) in severe aortic stenosis (AS) population to provide useful information for transcatheteraortic valve replacement (TAVR)., Methods: A total of 300 AS patients undergoing surgical aortic valve replacement were included to determine the accuracy of transthoracic echocardiography in indentifying BAV from January 2009 to July 2013. The echocardiographic data of our hospital from 2004 to 2012 was retrospectively reviewed. 1 371 patients with isolated severe native aortic valves stenosis were consecutively enrolled., Results: The aortic valve structures could be defined by transthoracic echocardiography in 75.7% (227/300) patients with severe AS. With BAV diagnosis during operation as gold standard, the accuracy of transthoracic echocardiography in identifying BAV was 89.4% (203/227). Among 1 371 patients with severe AS, the percentage of BAV in patients aged <40 years, aged 40-59 years, aged 60-69 years, aged 70-79 years and aged ≥ 80 years was 60.0% (57/95), 57.5% (262/456), 42.7% (184/431), 43.2% (133/308) and 21.0% (17/81), respectively. Incidence of BAV in patients with degenerative calcific valve was significant higher than in those with rheumatic heart disease (44.3% (552/1 246) vs. 4.0% (3/76), P<0.01). Proportion of combined aortic regurgitation ≥ grade 2 was significantly lower, ascending aortic diameter was larger and left ventricular end-diastolic dimension was smaller in BAV patients compared to severe AS patients with tricuspid valves (all P<0.01), while aortic valve annuals diameter and accompanying cardiovascular diseases between BAV and tricuspid aortic valve groups were similar (all P>0.05)., Conclusions: Transthoracic echocardiography could accurately identify aortic valve structures in about 76% patients. BAV is common in severe AS patients across all ages. These results provide important information for the popularization of TVAR.