Pub Date : 2024-09-07DOI: 10.1186/s40959-024-00264-8
Jian-Rong Peng, Jason Chia-Hsun Hsieh, Chih-Hao Chang, Chi Chuang, Yu-Ching Wang, Tzu-Yang Chen, Hung-Chi Su, Hsin-Fu Lee
Background: Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer therapy. This study examines the cardiovascular risks of ICIs compared to non-ICI therapies.
Methods: Utilizing the Chang Gung Research Database (CGRD) of Taiwan, this retrospective study analyzed 188,225 cancer patients, with 1,737 undergoing ICI treatment from January 1, 2008, to June 30, 2021. Through 1:1 propensity score matching (PSM), we compared specific outcomes between patients treated with ICIs and those who were not. The analysis also accounted for the competing risk of mortality in assessing the results after PSM. The observation period spanned from this index date to whichever came first: the date of the specific outcomes, the last follow-up recorded, or the end date of the study on June 30, 2022.
Results: The study found no significant increase in the risk of cardiac death, non-fatal myocardial infarction, heart failure hospitalization, deep vein thrombosis, or pulmonary embolism in patients treated with ICIs as compared to those receiving non-ICI therapy. Interestingly, ICI treatment was linked to a lower risk of non-fatal stroke (0.27% per year vs. 0.46% per year; subdistribution hazard ratio = 0.59; 95% confidence interval = 0.35-0.98; P = 0.0430). Furthermore, subgroup analysis revealed that the ICI group had a decreased risk of cardiac death in patients with cancers other than head and neck cancer, and a reduced risk of stroke among diabetic patients.
Conclusions: ICIs do not significantly elevate the risk of cardiovascular events in cancer patients and may lower the stroke risk, underscoring the need for additional prospective studies to clarify these findings.
{"title":"Cardiovascular and venous thromboembolism risks in cancer patients treated with immune checkpoint inhibitors compared to non-users- a multi-center retrospective study.","authors":"Jian-Rong Peng, Jason Chia-Hsun Hsieh, Chih-Hao Chang, Chi Chuang, Yu-Ching Wang, Tzu-Yang Chen, Hung-Chi Su, Hsin-Fu Lee","doi":"10.1186/s40959-024-00264-8","DOIUrl":"10.1186/s40959-024-00264-8","url":null,"abstract":"<p><strong>Background: </strong>Immune Checkpoint Inhibitors (ICIs) have revolutionized cancer therapy. This study examines the cardiovascular risks of ICIs compared to non-ICI therapies.</p><p><strong>Methods: </strong>Utilizing the Chang Gung Research Database (CGRD) of Taiwan, this retrospective study analyzed 188,225 cancer patients, with 1,737 undergoing ICI treatment from January 1, 2008, to June 30, 2021. Through 1:1 propensity score matching (PSM), we compared specific outcomes between patients treated with ICIs and those who were not. The analysis also accounted for the competing risk of mortality in assessing the results after PSM. The observation period spanned from this index date to whichever came first: the date of the specific outcomes, the last follow-up recorded, or the end date of the study on June 30, 2022.</p><p><strong>Results: </strong>The study found no significant increase in the risk of cardiac death, non-fatal myocardial infarction, heart failure hospitalization, deep vein thrombosis, or pulmonary embolism in patients treated with ICIs as compared to those receiving non-ICI therapy. Interestingly, ICI treatment was linked to a lower risk of non-fatal stroke (0.27% per year vs. 0.46% per year; subdistribution hazard ratio = 0.59; 95% confidence interval = 0.35-0.98; P = 0.0430). Furthermore, subgroup analysis revealed that the ICI group had a decreased risk of cardiac death in patients with cancers other than head and neck cancer, and a reduced risk of stroke among diabetic patients.</p><p><strong>Conclusions: </strong>ICIs do not significantly elevate the risk of cardiovascular events in cancer patients and may lower the stroke risk, underscoring the need for additional prospective studies to clarify these findings.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"59"},"PeriodicalIF":3.2,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-05DOI: 10.1186/s40959-024-00260-y
Andrés J Daniele, Vanesa Gregorietti, Diego Costa, Teresa López-Fernández
<p><strong>Background: </strong>Anthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10-15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatment METHODS: The EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.</p><p><strong>Results: </strong>During the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04-0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.</p><p><strong>Conclusion: </strong>Empagliflozin is
{"title":"Use of EMPAgliflozin in the prevention of CARDiotoxicity: the EMPACARD - PILOT trial.","authors":"Andrés J Daniele, Vanesa Gregorietti, Diego Costa, Teresa López-Fernández","doi":"10.1186/s40959-024-00260-y","DOIUrl":"10.1186/s40959-024-00260-y","url":null,"abstract":"<p><strong>Background: </strong>Anthracycline-based chemotherapy represents a cornerstone treatment for a number of common cancers, including breast cancer, lymphoma, and sarcoma. However, anthracycline-induced cardiotoxicity remains a significant concern, often presenting as a decline in cardiac function which can ultimately lead to heart failure (HF) or asymptomatic left ventricular dysfunction, in up to 10-15% of patients.Sodium-glucose transport protein 2 inhibitor (SGLT2i) therapies have been demonstrated to reduce the incidence of HF in high-risk non-cancer patients. Preliminary retrospective data suggest their role in mitigating the incidence of HF during or after anthracycline treatment METHODS: The EMPACARD-PILOT trial was a prospective case‒control study involving breast cancer patients scheduled to undergo anthracycline-based chemotherapy in a 4-cycle protocol of 60 mg/m2 doxorubicin. We used the HFA/ICOS risk score to identify patients at high or very high risk of cardiotoxicity. Patients with diabetes mellitus or stable heart failure with preserved ejection fraction (HFpEF) were prescribed empagliflozin (10 mg per day), starting seven days before the administration of anthracyclines and continuing for a period of six months. Those not meeting these criteria served as controls. The primary endpoint was cancer therapy-related cardiac dysfunction (CTRCD) incidence. CTRCD was defined as either a decrease in left ventricular ejection fraction (LVEF) of at least 10% to a final value below 50% or a reduction in global longitudinal strain (GLS) of at least 15% from baseline at any point during the study. The secondary endpoints included mortality and hospitalization due to cardiovascular causes or clinical heart failure. Exploratory endpoints included increases in serum troponin and NT-proBNP levels and a decrease in the glomerular filtration rate (GFR). The safety endpoints tracked includedketoacidosis, hypoglycemia, sepsis, neutropenic fever, and urinary tract infections.</p><p><strong>Results: </strong>During the enrollment period, 785 breast cancer patients were analysed. Of these, 107 met the inclusion criteria, and 76 subsequently provided informed consent. The study was conducted with comparable adherence rates of 81.5% in both the empagliflozin group (n = 38) and the control group (n = 38). The follow-up data from 62 patients revealed a significant reduction in the primary outcome within 6 months for the empagliflozin group compared with the control group (6.5% vs. 35.5%, p = 0.005), with a relative risk of 0.18 (95% CI: 0.04-0.75). Compared with the control treatment, treatment with empagliflozin also significantly preserved the ejection fraction at 6 months follow-up (56.8% ± 5.8% vs. 53.7% ± 6.7, p = 0.029). However, there were no significant differences between the groups in terms of NT-proBNP, cTnI, clinical heart failure, GFR, or mortality/hospitalization due to heart failure.</p><p><strong>Conclusion: </strong>Empagliflozin is","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"58"},"PeriodicalIF":3.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-04DOI: 10.1186/s40959-024-00258-6
Karini Merolillo, Maria Inês González Solari, Tayani Palma Cohen, Andreas Lutz, Patricia de Carvalho, Fabio Cañellas, Diogo Rech, Otávio de Carvalho, Alice Zelmanowicz, Alexandre Machado Lehnen, Nance Nardi, Natalia Motta Leguisamo
Background: Doxorubicin (DOX) has been widely used in the treatment of breast cancer, but it is directly associated with late-onset cardiovascular disease (CVD). Whether anthropometric, food intake or other risk factors together with DOX-based chemotherapy can increase the risk of developing cardiotoxicity remains uncertain. We examined the association between anthropometric variables with doxorubicin-induced cardiotoxicity in women with breast cancer.
Methods: Twenty-six women (53.7 ± 9.6 y) undergoing DOX-based chemotherapy (408.3 ± 66.7 mg/m2) participated in the study. We collected data on body composition (bioimpedance), dietary intake (24 h) and cardiac function (echocardiographic assessment of left ventricular ejection fraction, LVEF). All measurements were taken at baseline, one month of treatment completion and one-year follow-up after start of treatment. DOX-induced cardiotoxicity was defined as ≥ 10% absolute decrease in LVEF. Thus, the participants were then grouped as DOX-induced (DIC) or non-DOX-induced (non-DIC) cardiotoxicity. Data are shown as mean ± SD (standard deviation). We performed comparisons between the two groups using Student's t-test for independent samples or Generalized Estimating Equations (groups + 3 evaluation time points) with Bonferroni post-hoc test. Lastly, the correlations were analyzed using Pearson correlation; p < 0.05 for all tests.
Results: At baseline the participants' body mass index (BMI) was 29.9 ± 7.9 kg/m2 and LVEF was 67.4 ± 6.2%. Seven of them (26.9%) developed therapy-induced cardiotoxicity (ΔLVEF - 3.2 ± 2.6%; p < 0.001). Postmenopausal status and family history of CVD were more prevalent in the DIC group than non-DIC group. We found no consistent BMI changes in the groups over time. Interestingly, the non-DIC group showed a small increase in visceral fat at treatment completion and increased waist circumference at one-year follow-up compared to baseline. These same changes were not seen in the DIC group. We also observed a pattern of correlation of some anthropometric variables with LVEF: the more unfavorable the body composition the more pronounced the LVEF decrease at one-year follow-up, though not associated with cardiotoxicity.
Conclusions: Our study did not provide sufficient evidence to support that anthropometric variables, food intake or other risk factors increase the risk of developing cardiotoxicity. However, there are apparent trends that need to be further investigated in larger samples.
{"title":"Association of anthropometric variables with therapy-induced cardiotoxicity in women with breast cancer: a pilot study for a randomized clinical trial.","authors":"Karini Merolillo, Maria Inês González Solari, Tayani Palma Cohen, Andreas Lutz, Patricia de Carvalho, Fabio Cañellas, Diogo Rech, Otávio de Carvalho, Alice Zelmanowicz, Alexandre Machado Lehnen, Nance Nardi, Natalia Motta Leguisamo","doi":"10.1186/s40959-024-00258-6","DOIUrl":"https://doi.org/10.1186/s40959-024-00258-6","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) has been widely used in the treatment of breast cancer, but it is directly associated with late-onset cardiovascular disease (CVD). Whether anthropometric, food intake or other risk factors together with DOX-based chemotherapy can increase the risk of developing cardiotoxicity remains uncertain. We examined the association between anthropometric variables with doxorubicin-induced cardiotoxicity in women with breast cancer.</p><p><strong>Methods: </strong>Twenty-six women (53.7 ± 9.6 y) undergoing DOX-based chemotherapy (408.3 ± 66.7 mg/m<sup>2</sup>) participated in the study. We collected data on body composition (bioimpedance), dietary intake (24 h) and cardiac function (echocardiographic assessment of left ventricular ejection fraction, LVEF). All measurements were taken at baseline, one month of treatment completion and one-year follow-up after start of treatment. DOX-induced cardiotoxicity was defined as ≥ 10% absolute decrease in LVEF. Thus, the participants were then grouped as DOX-induced (DIC) or non-DOX-induced (non-DIC) cardiotoxicity. Data are shown as mean ± SD (standard deviation). We performed comparisons between the two groups using Student's t-test for independent samples or Generalized Estimating Equations (groups + 3 evaluation time points) with Bonferroni post-hoc test. Lastly, the correlations were analyzed using Pearson correlation; p < 0.05 for all tests.</p><p><strong>Results: </strong>At baseline the participants' body mass index (BMI) was 29.9 ± 7.9 kg/m<sup>2</sup> and LVEF was 67.4 ± 6.2%. Seven of them (26.9%) developed therapy-induced cardiotoxicity (ΔLVEF - 3.2 ± 2.6%; p < 0.001). Postmenopausal status and family history of CVD were more prevalent in the DIC group than non-DIC group. We found no consistent BMI changes in the groups over time. Interestingly, the non-DIC group showed a small increase in visceral fat at treatment completion and increased waist circumference at one-year follow-up compared to baseline. These same changes were not seen in the DIC group. We also observed a pattern of correlation of some anthropometric variables with LVEF: the more unfavorable the body composition the more pronounced the LVEF decrease at one-year follow-up, though not associated with cardiotoxicity.</p><p><strong>Conclusions: </strong>Our study did not provide sufficient evidence to support that anthropometric variables, food intake or other risk factors increase the risk of developing cardiotoxicity. However, there are apparent trends that need to be further investigated in larger samples.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"57"},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction).
Methods: Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG).
Results: GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort.
Conclusion: GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.
{"title":"Hypothesis paper: GDF15 demonstrated promising potential in Cancer diagnosis and correlated with cardiac biomarkers.","authors":"Xiaohe Hao, Zhenyu Zhang, Jing Kong, Rufei Ma, Cuiping Mao, Xun Peng, Kun Ru, Lisheng Liu, Chuanxi Zhao, Xinkai Mo, Meijuan Cai, Xiangguo Yu, Qinghai Lin","doi":"10.1186/s40959-024-00263-9","DOIUrl":"10.1186/s40959-024-00263-9","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular toxicity represents a significant adverse consequence of cancer therapies, yet there remains a paucity of effective biomarkers for its timely monitoring and diagnosis. To give a first evidence able to elucidate the role of Growth Differentiation Factor 15 (GDF15) in the context of cancer diagnosis and its specific association with cardiac indicators in cancer patients, thereby testing its potential in predicting the risk of CTRCD (cancer therapy related cardiac dysfunction).</p><p><strong>Methods: </strong>Analysis of differentially expressed genes (DEGs), including GDF15, was performed by utilizing data from the public repositories of the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). Cardiomyopathy is the most common heart disease and its main clinical manifestations, such as heart failure and arrhythmia, are similar to those of CTRCD. Examination of GDF15 expression was conducted in various normal and cancerous tissues or sera, using available database and serum samples. The study further explored the correlation between GDF15 expression and the combined detection of cardiac troponin-T (c-TnT) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), assessing the combined diagnostic utility of these markers in predicting risk of CTRCD through longitudinal electrocardiograms (ECG).</p><p><strong>Results: </strong>GDF15 emerged as a significant DEG in both cancer and cardiomyopathy disease models, demonstrating good diagnostic efficacy across multiple cancer types compared to healthy controls. GDF15 levels in cancer patients correlated with the established cardiac biomarkers c-TnT and NT-proBNP. Moreover, higher GDF15 levels correlated with an increased risk of ECG changes in the cancer cohort.</p><p><strong>Conclusion: </strong>GDF15 demonstrated promising diagnostic potential in cancer identification; higher GDF15, combined with elevated cardiac markers, may play a role in the monitoring and prediction of CTRCD risk.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"56"},"PeriodicalIF":3.2,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1186/s40959-024-00256-8
Nicole Felix, Alleh Nogueira, Pedro E P Carvalho, Thomaz Alexandre Costa, Lucas Tramujas, Giuliano Generoso, Stephanie Feldman, Philippe Garot, Maria do Carmo Andrade Duarte de Farias
Background: Patients with active cancer and aortic stenosis may be under-referred for valve interventions due to concerns over a prohibitive risk. However, whether active cancer impacts outcomes after transcatheter aortic valve replacement (TAVR) remains unknown.
Methods: We searched PubMed, Embase, and Cochrane Library in December 2023 for studies comparing the post-TAVR outcomes of patients with versus without active cancer. We pooled odds ratios (OR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) applying a random-effects model. Statistical analyses were performed in R version 4.3.2.
Results: We included nine observational studies analyzing 133,906 patients, of whom 9,792 (7.3%) had active cancer. Compared with patients without cancer, patients with active cancer had higher short- (OR 1.33; 95% CI 1.15-1.55; p < 0.001) and long-term mortality (OR 2.29; 95% CI 1.80-2.91; p < 0.001) rates, not driven by cardiovascular mortality (OR 1.30; 95% CI 0.70-2.40; p = 0.40), and higher major bleeding rates (OR 1.66; 95% CI 1.15-2.42; p = 0.008). The higher mortality rate was sustained in an adjusted analysis (aHR 1.77; 95% CI 1.34-2.35; p < 0.001). There was no significant difference in cardiac, renal, and cerebral complications at a follow-up ranging from 180 days to 10 years.
Conclusion: Patients with active cancer undergoing TAVR had higher non-cardiovascular mortality and bleeding rates, with comparable incidences of other complications. This highlights the need for a shared decision and appropriate patient selection considering cancer type, staging, bleeding risk, and optimal timing for intervention.
{"title":"Outcomes of patients with active cancer after transcatheter aortic valve replacement: an updated meta-analysis.","authors":"Nicole Felix, Alleh Nogueira, Pedro E P Carvalho, Thomaz Alexandre Costa, Lucas Tramujas, Giuliano Generoso, Stephanie Feldman, Philippe Garot, Maria do Carmo Andrade Duarte de Farias","doi":"10.1186/s40959-024-00256-8","DOIUrl":"https://doi.org/10.1186/s40959-024-00256-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with active cancer and aortic stenosis may be under-referred for valve interventions due to concerns over a prohibitive risk. However, whether active cancer impacts outcomes after transcatheter aortic valve replacement (TAVR) remains unknown.</p><p><strong>Methods: </strong>We searched PubMed, Embase, and Cochrane Library in December 2023 for studies comparing the post-TAVR outcomes of patients with versus without active cancer. We pooled odds ratios (OR) and adjusted hazard ratios (aHR) with 95% confidence intervals (CI) applying a random-effects model. Statistical analyses were performed in R version 4.3.2.</p><p><strong>Results: </strong>We included nine observational studies analyzing 133,906 patients, of whom 9,792 (7.3%) had active cancer. Compared with patients without cancer, patients with active cancer had higher short- (OR 1.33; 95% CI 1.15-1.55; p < 0.001) and long-term mortality (OR 2.29; 95% CI 1.80-2.91; p < 0.001) rates, not driven by cardiovascular mortality (OR 1.30; 95% CI 0.70-2.40; p = 0.40), and higher major bleeding rates (OR 1.66; 95% CI 1.15-2.42; p = 0.008). The higher mortality rate was sustained in an adjusted analysis (aHR 1.77; 95% CI 1.34-2.35; p < 0.001). There was no significant difference in cardiac, renal, and cerebral complications at a follow-up ranging from 180 days to 10 years.</p><p><strong>Conclusion: </strong>Patients with active cancer undergoing TAVR had higher non-cardiovascular mortality and bleeding rates, with comparable incidences of other complications. This highlights the need for a shared decision and appropriate patient selection considering cancer type, staging, bleeding risk, and optimal timing for intervention.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"55"},"PeriodicalIF":3.2,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11386488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-26DOI: 10.1186/s40959-024-00255-9
M K Honaryar, M Locquet, R Allodji, G Jimenez, B Pinel, O Lairez, L Panh, J Camilleri, D Broggio, J Ferrières, F De Vathaire, S Jacob
Background: Radiation therapy (RT) for breast cancer (BC) can result in subtle cardiac dysfunction that can occur early after treatment. In 2022, the European Society of Cardiology (ESC) published the first guidelines in cardio-oncology with a harmonized definition of cancer therapy-related cardiac dysfunction (CTRCD). The aim of this study was to evaluate CTRCD occurrence over 24 months of follow-up after RT in BC patients and to analyze the association with cardiac radiation exposure.
Methods: The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40-75 years, with conventional and 2D Speckle tracking echocardiography performed before RT, 6 and 24 months after RT. Based on ESC cardio-oncology guidelines, CTRCD and corresponding severity were defined with left ventricle ejection fraction and global longitudinal strain decrease, occurring at 6 or 24 months after RT. Dosimetry for whole heart, left ventricle (LV) and left coronary artery (left anterior descending and circumflex arteries (CX)) was considered to evaluate the association with CTRCD, based on logistic regressions (Odds Ratio - OR and 95% confidence interval - 95%CI). Youden index based on receiver operating characteristic curve analysis was used to identify the optimal threshold of dose-volume parameters for predicting CTRCD.
Results: The study included 72 BC patients with a mean age of 58 ± 8.2 years. A total of 32 (44%) patients developed CTRCD during follow-up: 20 (28%) mild CTRCD, 7 (9%) moderate CTRCD, and 5 (7%) severe CTRCD. Cardiac radiation doses were generally higher among patients with CTRCD rather than non-CTRCD. Dose-response relationships were significant for mean CX dose (OR = 2.48, 95%CI (1.12-5.51), p = 0.02) and marginally significant for V2 of LV (OR = 1.03 95%CI (1.00-1.06), p = 0.05). V2 of LV ≥ 36% and mean CX dose ≥ 1.40 Gy thresholds were determined to be optimal for predicting CTRCD.
Conclusion: For BC patients treated with RT without chemotherapy, CTRCD can be observed in an important proportion of the population over 24 months after treatment. Left ventricle and circumflex coronary artery exposure were found to be associated with CTRCD and could be used for the prediction of such cardiotoxicity. Further research remains needed to confirm these results.
{"title":"Cancer therapy-related cardiac dysfunction after radiation therapy for breast cancer: results from the BACCARAT cohort study.","authors":"M K Honaryar, M Locquet, R Allodji, G Jimenez, B Pinel, O Lairez, L Panh, J Camilleri, D Broggio, J Ferrières, F De Vathaire, S Jacob","doi":"10.1186/s40959-024-00255-9","DOIUrl":"10.1186/s40959-024-00255-9","url":null,"abstract":"<p><strong>Background: </strong>Radiation therapy (RT) for breast cancer (BC) can result in subtle cardiac dysfunction that can occur early after treatment. In 2022, the European Society of Cardiology (ESC) published the first guidelines in cardio-oncology with a harmonized definition of cancer therapy-related cardiac dysfunction (CTRCD). The aim of this study was to evaluate CTRCD occurrence over 24 months of follow-up after RT in BC patients and to analyze the association with cardiac radiation exposure.</p><p><strong>Methods: </strong>The prospective monocentric BACCARAT study included BC patients treated with RT without chemotherapy, aged 40-75 years, with conventional and 2D Speckle tracking echocardiography performed before RT, 6 and 24 months after RT. Based on ESC cardio-oncology guidelines, CTRCD and corresponding severity were defined with left ventricle ejection fraction and global longitudinal strain decrease, occurring at 6 or 24 months after RT. Dosimetry for whole heart, left ventricle (LV) and left coronary artery (left anterior descending and circumflex arteries (CX)) was considered to evaluate the association with CTRCD, based on logistic regressions (Odds Ratio - OR and 95% confidence interval - 95%CI). Youden index based on receiver operating characteristic curve analysis was used to identify the optimal threshold of dose-volume parameters for predicting CTRCD.</p><p><strong>Results: </strong>The study included 72 BC patients with a mean age of 58 ± 8.2 years. A total of 32 (44%) patients developed CTRCD during follow-up: 20 (28%) mild CTRCD, 7 (9%) moderate CTRCD, and 5 (7%) severe CTRCD. Cardiac radiation doses were generally higher among patients with CTRCD rather than non-CTRCD. Dose-response relationships were significant for mean CX dose (OR = 2.48, 95%CI (1.12-5.51), p = 0.02) and marginally significant for V2 of LV (OR = 1.03 95%CI (1.00-1.06), p = 0.05). V2 of LV ≥ 36% and mean CX dose ≥ 1.40 Gy thresholds were determined to be optimal for predicting CTRCD.</p><p><strong>Conclusion: </strong>For BC patients treated with RT without chemotherapy, CTRCD can be observed in an important proportion of the population over 24 months after treatment. Left ventricle and circumflex coronary artery exposure were found to be associated with CTRCD and could be used for the prediction of such cardiotoxicity. Further research remains needed to confirm these results.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier- NCT02605512.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"54"},"PeriodicalIF":3.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11345963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-22DOI: 10.1186/s40959-024-00250-0
Jieli Tong, Nikolaos Vogiatzakis, Maria Sol Andres, Isabelle Senechal, Ahmed Badr, Sivatharshini Ramalingam, Stuart D Rosen, Alexander R Lyon, Muhummad Sohaib Nazir
Background: Immune checkpoint inhibitor (ICI) myocarditis is an uncommon but potentially fatal complication of immunotherapy. Cardiac imaging is essential to make timely diagnoses as there are critical downstream implications for patients.
Objective: To determine the agreement of cardiac magnetic resonance (CMR) and 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in patients with suspected ICI myocarditis.
Methods: Patients with suspected ICI myocarditis, who underwent CMR and 18 F-FDG-PET imaging at a single cardio-oncology service from 2017 to 2023, were enrolled. CMR was performed according to recommended guidelines for assessment of myocarditis. 18 F-FDG-PET imaging was performed following 18 h carbohydrate-free fast. Imaging was analysed by independent reviewers to determine the presence or absence of ICI myocarditis.
Results: Twelve patients (mean age 60 ± 15 years old, 7 [58%] male) underwent both CMR and 18 F-FDG-PET imaging. Three (25%) met the 2018 Lake Louise Criteria for CMR diagnosis of myocarditis; 4 (33%) had evidence of myocardial inflammation as determined by 18 F-FDG-PET. Amongst those with positive 18 F-FDG-PET, mean standard uptake value (SUV) was 3.5 ± 1.7. There was agreement between CMR and PET in 7 cases (CMR and PET positive (n = 1), CMR and PET negative (n = 6)) and discordance in 5 cases (CMR positive and PET negative (n = 2), CMR negative and PET positive (n = 3)).
Conclusion: Both CMR and PET provide complementary clinical information in diagnostic of ICI myocarditis. CMR informs on myocardial oedema, whilst 18 F-FDG-PET provides information on glucose metabolism reflecting monocyte and lymphocytic activity. Future studies should investigate the role of hybrid PET-CMR for the timely diagnosis of ICI myocarditis.
{"title":"Complementary use of cardiac magnetic resonance and 18 F-FDG positron emission tomography imaging in suspected immune checkpoint inhibitor myocarditis.","authors":"Jieli Tong, Nikolaos Vogiatzakis, Maria Sol Andres, Isabelle Senechal, Ahmed Badr, Sivatharshini Ramalingam, Stuart D Rosen, Alexander R Lyon, Muhummad Sohaib Nazir","doi":"10.1186/s40959-024-00250-0","DOIUrl":"10.1186/s40959-024-00250-0","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitor (ICI) myocarditis is an uncommon but potentially fatal complication of immunotherapy. Cardiac imaging is essential to make timely diagnoses as there are critical downstream implications for patients.</p><p><strong>Objective: </strong>To determine the agreement of cardiac magnetic resonance (CMR) and 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in patients with suspected ICI myocarditis.</p><p><strong>Methods: </strong>Patients with suspected ICI myocarditis, who underwent CMR and 18 F-FDG-PET imaging at a single cardio-oncology service from 2017 to 2023, were enrolled. CMR was performed according to recommended guidelines for assessment of myocarditis. 18 F-FDG-PET imaging was performed following 18 h carbohydrate-free fast. Imaging was analysed by independent reviewers to determine the presence or absence of ICI myocarditis.</p><p><strong>Results: </strong>Twelve patients (mean age 60 ± 15 years old, 7 [58%] male) underwent both CMR and 18 F-FDG-PET imaging. Three (25%) met the 2018 Lake Louise Criteria for CMR diagnosis of myocarditis; 4 (33%) had evidence of myocardial inflammation as determined by 18 F-FDG-PET. Amongst those with positive 18 F-FDG-PET, mean standard uptake value (SUV) was 3.5 ± 1.7. There was agreement between CMR and PET in 7 cases (CMR and PET positive (n = 1), CMR and PET negative (n = 6)) and discordance in 5 cases (CMR positive and PET negative (n = 2), CMR negative and PET positive (n = 3)).</p><p><strong>Conclusion: </strong>Both CMR and PET provide complementary clinical information in diagnostic of ICI myocarditis. CMR informs on myocardial oedema, whilst 18 F-FDG-PET provides information on glucose metabolism reflecting monocyte and lymphocytic activity. Future studies should investigate the role of hybrid PET-CMR for the timely diagnosis of ICI myocarditis.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"53"},"PeriodicalIF":3.2,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-20DOI: 10.1186/s40959-024-00252-y
Saba Maleki, Zahra Esmaeili, Niloofar Seighali, Arman Shafiee, Sara Montazeri Namin, Mohammad Amin Tofighi Zavareh, Sima Shamshiri Khamene, Izat Mohammadkhawajah, Michael Nanna, Azin Alizadeh-Asl, Jennifer M Kwan, Kaveh Hosseini
Purpose: Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy.
Methods: We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study.
Results: The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade ≥ 2 (RR 2.36, 95% CI 1.86-2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%-3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated.
Conclusions: CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy.
{"title":"Cardiac adverse events after Chimeric Antigen Receptor (CAR) T cell therapies: an updated systematic review and meta-analysis.","authors":"Saba Maleki, Zahra Esmaeili, Niloofar Seighali, Arman Shafiee, Sara Montazeri Namin, Mohammad Amin Tofighi Zavareh, Sima Shamshiri Khamene, Izat Mohammadkhawajah, Michael Nanna, Azin Alizadeh-Asl, Jennifer M Kwan, Kaveh Hosseini","doi":"10.1186/s40959-024-00252-y","DOIUrl":"10.1186/s40959-024-00252-y","url":null,"abstract":"<p><strong>Purpose: </strong>Chimeric antigen receptor (CAR) T-cell therapy is a new revolutionary method for treating refractory or relapsed hematologic malignancies, CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and cardiotoxicity. We directed a systematic review and meta-analysis to determine the incidence and predictors of cardiovascular events (CVE) with CAR T-cell therapy.</p><p><strong>Methods: </strong>We investigated PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies reporting cardiovascular outcomes in CAR-T cell recipients. The study protocol was listed in the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42023478602). Twenty-three studies were included in this study.</p><p><strong>Results: </strong>The pooled incidence of CVE was 54% for arrhythmias, 30% for heart failure, 20% for cardiomyopathy, 10% for acute coronary syndrome, and 7% for cardiac arrest. Patients with CVE had a higher incidence of cytokine release syndrome grade ≥ 2 (RR 2.36, 95% CI 1.86-2.99). The incidence of cardiac mortality in our meta-analysis was 2% (95% CI: 1%-3%). Left ventricular ejection fraction decline was greater in the CVE group (-9.4% versus -1.5%, p < 0.001). Cardiac biomarkers like BNP, CRP, creatinine, and ferritin were also elevated.</p><p><strong>Conclusions: </strong>CAR T-cell therapy commonly leads to cardiotoxicity, mediated by cytokine release syndrome. Vigilant monitoring and tailored treatments are crucial to mitigate these effects. Importantly, there's no significant difference in cardiac mortality between groups, suggesting insights for optimizing preventive interventions and reducing risks after CAR T-cell therapy.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"52"},"PeriodicalIF":3.2,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-13DOI: 10.1186/s40959-024-00254-w
Arif Albulushi, Aisha Al Balushi, Muhhamed Shahzad, Ismail Al Bulushi, Hatim Al Lawati
The landscape of cancer survivorship is increasingly populated by individuals facing a spectrum of cardiometabolic risks, attributed to both their oncological history and treatment regimens. This manuscript synthesizes findings from various studies, highlighting the prevalence of traditional risk factors-hypertension, dyslipidemia, diabetes-as well as emergent concerns like obesity and metabolic syndrome among survivors. The impact of demographic variables, specific cancer types, and treatment modalities on cardiometabolic health is explored. Through a lens of multidisciplinary management and future research directives, we advocate for an integrative approach to cardiometabolic health in cancer survivors, aiming to ensure their victory over cancer extends into long-term well-being. Furthermore, we discuss the outcome implications of these cardiometabolic risk factors on cardiovascular disease development, future cardiovascular events, and overall survival, supported by studies showing improved outcomes through exercise and risk factor control.
{"title":"Navigating the crossroads: cardiometabolic risks in cancer survivorship - a comprehensive review.","authors":"Arif Albulushi, Aisha Al Balushi, Muhhamed Shahzad, Ismail Al Bulushi, Hatim Al Lawati","doi":"10.1186/s40959-024-00254-w","DOIUrl":"10.1186/s40959-024-00254-w","url":null,"abstract":"<p><p>The landscape of cancer survivorship is increasingly populated by individuals facing a spectrum of cardiometabolic risks, attributed to both their oncological history and treatment regimens. This manuscript synthesizes findings from various studies, highlighting the prevalence of traditional risk factors-hypertension, dyslipidemia, diabetes-as well as emergent concerns like obesity and metabolic syndrome among survivors. The impact of demographic variables, specific cancer types, and treatment modalities on cardiometabolic health is explored. Through a lens of multidisciplinary management and future research directives, we advocate for an integrative approach to cardiometabolic health in cancer survivors, aiming to ensure their victory over cancer extends into long-term well-being. Furthermore, we discuss the outcome implications of these cardiometabolic risk factors on cardiovascular disease development, future cardiovascular events, and overall survival, supported by studies showing improved outcomes through exercise and risk factor control.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"51"},"PeriodicalIF":3.2,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11321223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-09DOI: 10.1186/s40959-024-00253-x
Steve Kong, Sanjana Nagraj, Dennis L Cooper, Kevin J Ferrick, Lili Zhang
Background: Fludarabine is a chemotherapeutic agent with lymphodepleting effects that is increasingly used as part of a conditioning regimen prior to allogeneic stem cell transplantation. Fludarabine is generally considered a relatively safe medication with only rare cases of cardiotoxic side effects.
Case presentation: Here, we present a case of a 30-year-old woman who was undergoing conditioning for a haploidentical cell transplantation for treatment of Fanconi anemia with a 5-day course of daily fludarabine infusion. After her second fludarabine infusion, she was noted to have ectopic atrial bradycardia that resolved with supportive therapy and completion of fludarabine infusion.
Conclusion: We report the first case of ectopic atrial bradycardia associated with fludarabine. Although rare and transient, clinicians should recognize this rare cardiotoxic side effect of fludarabine.
{"title":"A case report of fludarabine associated ectopic atrial bradycardia and literature review of fludarabine induced bradycardia.","authors":"Steve Kong, Sanjana Nagraj, Dennis L Cooper, Kevin J Ferrick, Lili Zhang","doi":"10.1186/s40959-024-00253-x","DOIUrl":"10.1186/s40959-024-00253-x","url":null,"abstract":"<p><strong>Background: </strong>Fludarabine is a chemotherapeutic agent with lymphodepleting effects that is increasingly used as part of a conditioning regimen prior to allogeneic stem cell transplantation. Fludarabine is generally considered a relatively safe medication with only rare cases of cardiotoxic side effects.</p><p><strong>Case presentation: </strong>Here, we present a case of a 30-year-old woman who was undergoing conditioning for a haploidentical cell transplantation for treatment of Fanconi anemia with a 5-day course of daily fludarabine infusion. After her second fludarabine infusion, she was noted to have ectopic atrial bradycardia that resolved with supportive therapy and completion of fludarabine infusion.</p><p><strong>Conclusion: </strong>We report the first case of ectopic atrial bradycardia associated with fludarabine. Although rare and transient, clinicians should recognize this rare cardiotoxic side effect of fludarabine.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"50"},"PeriodicalIF":3.2,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11312176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}