Background: Cancer patients' vulnerability to QT prolongation contradicts certain anti-cancer drug usage. Until now, the QT prolongation's impact on CV mortality in cancer patients remains unclear, potentially biasing therapeutic decisions.
Methods: This retrospective observational cohort included adult cancer patients with an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n = 59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry.
Results: The AUC of QTcB (90 days: 0.70, 1 year: 0.68) for predicting CV mortality was better than QTcFri and QTcFra (90 days: 0.63 and 0.50, 1 year: 0.65 and 0.56). Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P = 0.02) and one year (1.006, P < 0.01). Compared to those with QTcB < 500ms, the patients with QTcB ≥ 500ms were older and had more comorbidities and mortalities within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality. In the patients already with QTcB ≥ 500ms, the patients receiving the unexpected uses of QT-prolonging drugs were not associated with higher one-year CV mortality than those without (P = 0.14).
Conclusions: Rather than a prolonged QT interval per se, comorbidities contributed to CV mortality and irreversible outcomes in cancer patients.
{"title":"Association between QT prolongation and cardiovascular mortality in cancer patients.","authors":"Cheng-Han Chan, Chih-Min Liu, Pei-Fen Chen, Li-Lien Liao, I-Chien Wu, Yu-Feng Hu","doi":"10.1186/s40959-024-00271-9","DOIUrl":"https://doi.org/10.1186/s40959-024-00271-9","url":null,"abstract":"<p><strong>Background: </strong>Cancer patients' vulnerability to QT prolongation contradicts certain anti-cancer drug usage. Until now, the QT prolongation's impact on CV mortality in cancer patients remains unclear, potentially biasing therapeutic decisions.</p><p><strong>Methods: </strong>This retrospective observational cohort included adult cancer patients with an electrocardiogram (ECG) performed in a tertiary hospital in Taiwan. The first performed ECGs after cancer diagnosis (n = 59,568) were analyzed. The corrected QT intervals by Bazett (QTcB), Fridericia (QTcFri), and Framingham (QTcFra) formulae were used to predict the 90-day and one-year CV mortality according to the Taiwan death registry.</p><p><strong>Results: </strong>The AUC of QTcB (90 days: 0.70, 1 year: 0.68) for predicting CV mortality was better than QTcFri and QTcFra (90 days: 0.63 and 0.50, 1 year: 0.65 and 0.56). Using the restricted cubic spline regression model adjusted by age and comorbidities, QTcB increased a significant but trivial risk of CV mortality at 90 days (hazard ratio, 1.007, P = 0.02) and one year (1.006, P < 0.01). Compared to those with QTcB < 500ms, the patients with QTcB ≥ 500ms were older and had more comorbidities and mortalities within one year. The incidence of sudden death and ventricular arrhythmias was only 0.2%. After adjusting for comorbidities, QTcB was neither associated with 90-day nor one-year CV mortality. In the patients already with QTcB ≥ 500ms, the patients receiving the unexpected uses of QT-prolonging drugs were not associated with higher one-year CV mortality than those without (P = 0.14).</p><p><strong>Conclusions: </strong>Rather than a prolonged QT interval per se, comorbidities contributed to CV mortality and irreversible outcomes in cancer patients.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"69"},"PeriodicalIF":3.2,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459176","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 : 2024-10-12DOI: 10.1186/s40959-024-00272-8
Anna Vaynrub, Leila Mishalani, Jayant Raikhelkar, Katherine D Crew
Background: While trastuzumab has been shown to improve disease-free and overall survival in patients with HER2-positive breast cancer, it may also cause trastuzumab-induced cardiotoxicity (TIC). Although racial and ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites (NHW), limited data exists on TIC incidence in diverse multi-ethnic populations. Our objective was to assess racial and ethnic differences in TIC and left ventricular ejection fraction (LVEF) recovery among patients with HER2-positive breast cancer.
Methods: We conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007 and 2022 who had received adjuvant trastuzumab. We analyzed associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the primary outcomes of TIC and LVEF recovery, using multivariable logistic regression models. TIC was defined as > 10% decrease in LVEF to an overall LVEF < 50%; LVEF recovery as a return to a LVEF > 50%.
Results: Among 496 evaluable patients, median age was 53 years (IQR: 45.0-62.0) with 36.6% NHW, 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Other. Fifty-three (10.6%) patients developed TIC, half of whom experienced LVEF recovery. Compared to NHW, NHB had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4%, respectively), however, race/ethnicity was not a significant predictor of TIC after adjusting for confounders. Increasing age, lower baseline LVEF, anthracycline use, and presence of hypertension or coronary artery disease were significantly associated with TIC in multivariable analysis.
Conclusions: TIC was more common among NHB compared to NHW, however, Black race was not consistently associated with TIC after adjustment for CVD risk factors. This suggests that CVD comorbidities (e.g., hypertension) that more frequently affect racial and ethnic minorities and are modifiable may explain differences in TIC incidence and recovery.
{"title":"Predictors of trastuzumab-induced cardiotoxicity among racially and ethnically diverse patients with HER2-positive breast cancer.","authors":"Anna Vaynrub, Leila Mishalani, Jayant Raikhelkar, Katherine D Crew","doi":"10.1186/s40959-024-00272-8","DOIUrl":"https://doi.org/10.1186/s40959-024-00272-8","url":null,"abstract":"<p><strong>Background: </strong>While trastuzumab has been shown to improve disease-free and overall survival in patients with HER2-positive breast cancer, it may also cause trastuzumab-induced cardiotoxicity (TIC). Although racial and ethnic minorities are at higher risk for cardiovascular disease (CVD) compared to non-Hispanic Whites (NHW), limited data exists on TIC incidence in diverse multi-ethnic populations. Our objective was to assess racial and ethnic differences in TIC and left ventricular ejection fraction (LVEF) recovery among patients with HER2-positive breast cancer.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study including patients diagnosed with stage I-III HER2-positive breast cancer between 2007 and 2022 who had received adjuvant trastuzumab. We analyzed associations between sociodemographic factors, tumor characteristics, treatment regimens, and CVD risk factors with the primary outcomes of TIC and LVEF recovery, using multivariable logistic regression models. TIC was defined as > 10% decrease in LVEF to an overall LVEF < 50%; LVEF recovery as a return to a LVEF > 50%.</p><p><strong>Results: </strong>Among 496 evaluable patients, median age was 53 years (IQR: 45.0-62.0) with 36.6% NHW, 15.8% non-Hispanic Black (NHB), 27.8% Hispanic, and 19.8% Other. Fifty-three (10.6%) patients developed TIC, half of whom experienced LVEF recovery. Compared to NHW, NHB had a higher rate of TIC (9.3% vs. 17.7%, respectively) and lower rate of LVEF recovery (70.6% vs. 21.4%, respectively), however, race/ethnicity was not a significant predictor of TIC after adjusting for confounders. Increasing age, lower baseline LVEF, anthracycline use, and presence of hypertension or coronary artery disease were significantly associated with TIC in multivariable analysis.</p><p><strong>Conclusions: </strong>TIC was more common among NHB compared to NHW, however, Black race was not consistently associated with TIC after adjustment for CVD risk factors. This suggests that CVD comorbidities (e.g., hypertension) that more frequently affect racial and ethnic minorities and are modifiable may explain differences in TIC incidence and recovery.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"68"},"PeriodicalIF":3.2,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11470559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459179","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 : 2024-10-11DOI: 10.1186/s40959-024-00267-5
Cheng Hwee Soh, Thomas H Marwick
Background: Cancer survivors have an increased risk of incident heart failure (HF) attributable to shared risk factors and cancer treatment-induced cardiac dysfunction. Selection for HF screening depends on risk assessment, but the optimal means of assessing risk is undefined. We undertook a comparison of HF risk calculators among survivors.
Methods: In this study from the UK Biobank, cancer and HF diagnoses were determined based on the International Classification of Diseases (ICD)-10 code and non-cancer participants were included as controls. Participants' risk of incident HF was determined using the Heart Failure Association-International Cardio-oncology Society (HFA-ICOS), the Atherosclerosis Risk in Communities (ARIC-HF) and the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF). The predictive performances of each were compared using the area under the curve (AUC).
Results: After propensity matching with age and sex, 9,232 survivors from breast cancer or lymphoma (mean age 59.9 years, 87.8% female), and 23,800 survivors from other cancer types (mean age 59.1 years, 85.8% female) were included in the analysis. The discriminative value for HFA-ICOS (AUC 0.753 [95%CI: 0.739-0.766]) and ARIC-HF (0.757 [95%CI: 0.744-0.770]) were similar, and superior to PCP-HF (0.717 [95%CI: 0.702-0.732]). The overall performance for each risk score was better among participants in other cancer types than those with breast cancer and lymphoma.
Conclusions: HFA-ICOS and ARIC-HF outperformed the PCP-HF among cancer- and non-cancer cohort, although all showed modest discrimination for incident HF to be applied to clinical practice. A cancer-specific HF prediction tool could facilitate HF prevention among survivors.
{"title":"Comparison of heart failure risk assessment tools among cancer survivors.","authors":"Cheng Hwee Soh, Thomas H Marwick","doi":"10.1186/s40959-024-00267-5","DOIUrl":"10.1186/s40959-024-00267-5","url":null,"abstract":"<p><strong>Background: </strong>Cancer survivors have an increased risk of incident heart failure (HF) attributable to shared risk factors and cancer treatment-induced cardiac dysfunction. Selection for HF screening depends on risk assessment, but the optimal means of assessing risk is undefined. We undertook a comparison of HF risk calculators among survivors.</p><p><strong>Methods: </strong>In this study from the UK Biobank, cancer and HF diagnoses were determined based on the International Classification of Diseases (ICD)-10 code and non-cancer participants were included as controls. Participants' risk of incident HF was determined using the Heart Failure Association-International Cardio-oncology Society (HFA-ICOS), the Atherosclerosis Risk in Communities (ARIC-HF) and the Pooled Cohort Equations to Prevent Heart Failure (PCP-HF). The predictive performances of each were compared using the area under the curve (AUC).</p><p><strong>Results: </strong>After propensity matching with age and sex, 9,232 survivors from breast cancer or lymphoma (mean age 59.9 years, 87.8% female), and 23,800 survivors from other cancer types (mean age 59.1 years, 85.8% female) were included in the analysis. The discriminative value for HFA-ICOS (AUC 0.753 [95%CI: 0.739-0.766]) and ARIC-HF (0.757 [95%CI: 0.744-0.770]) were similar, and superior to PCP-HF (0.717 [95%CI: 0.702-0.732]). The overall performance for each risk score was better among participants in other cancer types than those with breast cancer and lymphoma.</p><p><strong>Conclusions: </strong>HFA-ICOS and ARIC-HF outperformed the PCP-HF among cancer- and non-cancer cohort, although all showed modest discrimination for incident HF to be applied to clinical practice. A cancer-specific HF prediction tool could facilitate HF prevention among survivors.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"67"},"PeriodicalIF":3.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142406184","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 : 2024-10-09DOI: 10.1186/s40959-024-00268-4
Lindsay A Edwards, Christina Yang, Surbhi Sharma, Zih-Hua Chen, Lahari Gorantla, Sanika A Joshi, Nicolas J Longhi, Nahom Worku, Jamie S Yang, Brandy Martinez Di Pietro, Saro Armenian, Aarti Bhat, William Border, Sujatha Buddhe, Nancy Blythe, Kayla Stratton, Kasey J Leger, Wendy M Leisenring, Lillian R Meacham, Paul C Nathan, Shanti Narasimhan, Ritu Sachdeva, Karim Sadak, Eric J Chow, Patrick M Boyle
Background: Despite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers.
Methods: We designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test.
Results: The dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn't develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models.
Conclusions: This methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy.
{"title":"Building a machine learning-assisted echocardiography prediction tool for children at risk for cancer therapy-related cardiomyopathy.","authors":"Lindsay A Edwards, Christina Yang, Surbhi Sharma, Zih-Hua Chen, Lahari Gorantla, Sanika A Joshi, Nicolas J Longhi, Nahom Worku, Jamie S Yang, Brandy Martinez Di Pietro, Saro Armenian, Aarti Bhat, William Border, Sujatha Buddhe, Nancy Blythe, Kayla Stratton, Kasey J Leger, Wendy M Leisenring, Lillian R Meacham, Paul C Nathan, Shanti Narasimhan, Ritu Sachdeva, Karim Sadak, Eric J Chow, Patrick M Boyle","doi":"10.1186/s40959-024-00268-4","DOIUrl":"10.1186/s40959-024-00268-4","url":null,"abstract":"<p><strong>Background: </strong>Despite routine echocardiographic surveillance for childhood cancer survivors, the ability to predict cardiomyopathy risk in individual patients is limited. We explored the feasibility and optimal processes for machine learning-enhanced cardiomyopathy prediction in survivors using serial echocardiograms from five centers.</p><p><strong>Methods: </strong>We designed a series of deep convolutional neural networks (DCNNs) for prediction of cardiomyopathy (shortening fraction ≤ 28% or ejection fraction ≤ 50% on two occasions) for at-risk survivors ≥ 1-year post initial cancer therapy. We built DCNNs with four subsets of echocardiographic data differing in timing relative to case (survivor who developed cardiomyopathy) index diagnosis and two input formats (montages) with differing image selections. We used holdout subsets in a 10-fold cross-validation framework and standard metrics to assess model performance (e.g., F1-score, area under the precision-recall curve [AUPRC]). Performance of the input formats was compared using a combined 5 × 2 cross-validation F-test.</p><p><strong>Results: </strong>The dataset included 542 pairs of montages: 171 montage pairs from 45 cases at time of cardiomyopathy diagnosis or pre-diagnosis and 371 pairs from 70 at-risk survivors who didn't develop cardiomyopathy during follow-up (non-case). The DCNN trained to distinguish between non-case and time of cardiomyopathy diagnosis or pre-diagnosis case montages achieved an AUROC of 0.89 ± 0.02, AUPRC 0.83 ± 0.03, and F1-score: 0.76 ± 0.04. When limited to smaller subsets of case data (e.g., ≥ 1 or 2 years pre-diagnosis), performance worsened. Model input format did not impact performance accuracy across models.</p><p><strong>Conclusions: </strong>This methodology is a promising first step toward development of a DCNN capable of accurately differentiating pre-diagnosis versus non-case echocardiograms to predict survivors more likely to develop cardiomyopathy.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"66"},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388385","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 : 2024-10-04DOI: 10.1186/s40959-024-00270-w
Dustin N Krüger, Matthias Bosman, Emeline M Van Craenenbroeck, Guido R Y De Meyer, Constantijn Franssen, Pieter-Jan Guns
Background: Doxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients. However, the effect of DEXRA on vascular dysfunction during DOX treatment has not been documented. Therefore, here we investigated whether DEXRA protects against DOX-induced arterial stiffness, endothelial dysfunction, and SERPINA3N upregulation in tissue and plasma from mice.
Methods: Male C57BL6/J mice were treated with DOX (4 mg/kg), DEXRA (40 mg/kg), a combination (DEXRA + DOX), or VEHICLE (0.9% NaCl) weekly i.p. for 6 weeks (n = 8 per group). Cardiovascular function was measured in vivo by ultrasound imaging at baseline, weeks 2 and 6. Vascular reactivity was analyzed ex vivo in the thoracic aorta at week 6 and molecular analysis was performed.
Results: DEXRA prevented left ventricular ejection fraction decline by DOX (DEXRA + DOX: 62 ± 2% vs DOX: 51 ± 2%). Moreover, DEXRA prevented the increase in pulse wave velocity by DOX (DEXRA + DOX: 2.1 ± 0.2 m/s vs DOX: 4.5 ± 0.3 m/s) and preserved endothelium-dependent relaxation (DEXRA + DOX: 82 ± 3% vs DOX: 62 ± 3%). In contrast to DOX-treated mice, SERPINA3N did not increase in the DEXRA + DOX group.
Conclusion: Our results not only confirm the cardioprotective effects of DEXRA against DOX-induced cardiotoxicity but also add preservation of vascular endothelial cell function as an important mechanism. Moreover, the study demonstrates the potential of SERPINA3N as a biomarker for monitoring cardiovascular complications of DOX in high-risk patients.
{"title":"Dexrazoxane prevents vascular toxicity in doxorubicin-treated mice.","authors":"Dustin N Krüger, Matthias Bosman, Emeline M Van Craenenbroeck, Guido R Y De Meyer, Constantijn Franssen, Pieter-Jan Guns","doi":"10.1186/s40959-024-00270-w","DOIUrl":"10.1186/s40959-024-00270-w","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX) is used for breast cancer and lymphoma, but can cause cardiotoxicity, arterial stiffness, and endothelial dysfunction. We recently reported SERPINA3N as biomarker of cardiovascular toxicity in patients and mice. Dexrazoxane (DEXRA) is an FDA-approved drug that prevents DOX-induced cardiac toxicity in high-risk patients. However, the effect of DEXRA on vascular dysfunction during DOX treatment has not been documented. Therefore, here we investigated whether DEXRA protects against DOX-induced arterial stiffness, endothelial dysfunction, and SERPINA3N upregulation in tissue and plasma from mice.</p><p><strong>Methods: </strong>Male C57BL6/J mice were treated with DOX (4 mg/kg), DEXRA (40 mg/kg), a combination (DEXRA + DOX), or VEHICLE (0.9% NaCl) weekly i.p. for 6 weeks (n = 8 per group). Cardiovascular function was measured in vivo by ultrasound imaging at baseline, weeks 2 and 6. Vascular reactivity was analyzed ex vivo in the thoracic aorta at week 6 and molecular analysis was performed.</p><p><strong>Results: </strong>DEXRA prevented left ventricular ejection fraction decline by DOX (DEXRA + DOX: 62 ± 2% vs DOX: 51 ± 2%). Moreover, DEXRA prevented the increase in pulse wave velocity by DOX (DEXRA + DOX: 2.1 ± 0.2 m/s vs DOX: 4.5 ± 0.3 m/s) and preserved endothelium-dependent relaxation (DEXRA + DOX: 82 ± 3% vs DOX: 62 ± 3%). In contrast to DOX-treated mice, SERPINA3N did not increase in the DEXRA + DOX group.</p><p><strong>Conclusion: </strong>Our results not only confirm the cardioprotective effects of DEXRA against DOX-induced cardiotoxicity but also add preservation of vascular endothelial cell function as an important mechanism. Moreover, the study demonstrates the potential of SERPINA3N as a biomarker for monitoring cardiovascular complications of DOX in high-risk patients.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"65"},"PeriodicalIF":3.2,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451066/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375207","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 : 2024-09-28DOI: 10.1186/s40959-024-00266-6
Anna Borowiec, Patrycja Ozdowska, Magdalena Rosinska, Agnieszka Maria Zebrowska, Agnieszka Jagiello-Gruszfeld, Sławomir Jasek, Joanna Waniewska, Beata Kotowicz, Hanna Kosela-Paterczyk, Elzbieta Lampka, Katarzyna Pogoda, Andrzej Cieszanowski, Zbigniew Nowecki, Jan Walewski
Background: The presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. Current guidelines of the European Society of Cardiology (ESC) for cardio-oncology do not recommend the use of the CAC score to determine the status of risk in cancer patients. The aim of this study is to evaluate the presence and burden of CAC on cardiac tomography and the distribution of the cardiovascular toxicity risk factors in patients with moderate and high baseline risk of cancer therapy-related cardiovascular toxicity.
Methods: The study prospectively included cancer patients, diagnosed and qualified for systemic treatment with anthracycline chemotherapy. Clinical data and blood samples were collected from all patients. Additionally, the echocardiography and coronary computed tomography (CCTA) with the calculation of the coronary artery calcium (CAC) score were performed.
Results: A total of 80 patients (mean age 60.5 years, 75 female) were included in the study. The majority of patients (62, 77.5%) had breast cancer, 11 (13.8%) were diagnosed with sarcoma, and 7 (8.8%) with lymphoma. There were 42 (52.5%) patients classified as having moderate (MR) and 38 (47.5%) as having high risk (HR) of cancer therapy-related cardiovascular toxicity according to current ESC guidelines. In comparison with moderate risk, high risk patients were older and more likely to have hypertension, hyperlipidaemia and chronic kidney disease. The mean coronary artery calcium score was significantly higher in the HR group (150.4 vs. 24.8; p = 0.000). Furthermore, cardiac biomarkers were also higher in high-risk patients (p = 0.000). In echocardiographic parameters global longitudinal strain (GLS) was lower (p = 0.012), and diastolic dysfunction was more common in the HR group. However, the left ventricle ejection fraction (LVEF) was similar in the MR and HR groups.
Conclusions: In patients at high and moderate risk for cancer therapy-related cardiovascular toxicity, cardiovascular toxicity risk factors were common and more prevalent in the high-risk group. The coronary artery calcium score was also significantly higher in the high-risk group. Assessing the presence and burden of coronary artery calcium is an attractive option to assess additional cardiovascular risk in cancer patients.
{"title":"Coronary artery calcium score and other risk factors in patients at moderate and high risk of cancer therapy-related cardiovascular toxicity.","authors":"Anna Borowiec, Patrycja Ozdowska, Magdalena Rosinska, Agnieszka Maria Zebrowska, Agnieszka Jagiello-Gruszfeld, Sławomir Jasek, Joanna Waniewska, Beata Kotowicz, Hanna Kosela-Paterczyk, Elzbieta Lampka, Katarzyna Pogoda, Andrzej Cieszanowski, Zbigniew Nowecki, Jan Walewski","doi":"10.1186/s40959-024-00266-6","DOIUrl":"https://doi.org/10.1186/s40959-024-00266-6","url":null,"abstract":"<p><strong>Background: </strong>The presence and burden of coronary artery calcium (CAC) is a strong predictor of cardiovascular events. Current guidelines of the European Society of Cardiology (ESC) for cardio-oncology do not recommend the use of the CAC score to determine the status of risk in cancer patients. The aim of this study is to evaluate the presence and burden of CAC on cardiac tomography and the distribution of the cardiovascular toxicity risk factors in patients with moderate and high baseline risk of cancer therapy-related cardiovascular toxicity.</p><p><strong>Methods: </strong>The study prospectively included cancer patients, diagnosed and qualified for systemic treatment with anthracycline chemotherapy. Clinical data and blood samples were collected from all patients. Additionally, the echocardiography and coronary computed tomography (CCTA) with the calculation of the coronary artery calcium (CAC) score were performed.</p><p><strong>Results: </strong>A total of 80 patients (mean age 60.5 years, 75 female) were included in the study. The majority of patients (62, 77.5%) had breast cancer, 11 (13.8%) were diagnosed with sarcoma, and 7 (8.8%) with lymphoma. There were 42 (52.5%) patients classified as having moderate (MR) and 38 (47.5%) as having high risk (HR) of cancer therapy-related cardiovascular toxicity according to current ESC guidelines. In comparison with moderate risk, high risk patients were older and more likely to have hypertension, hyperlipidaemia and chronic kidney disease. The mean coronary artery calcium score was significantly higher in the HR group (150.4 vs. 24.8; p = 0.000). Furthermore, cardiac biomarkers were also higher in high-risk patients (p = 0.000). In echocardiographic parameters global longitudinal strain (GLS) was lower (p = 0.012), and diastolic dysfunction was more common in the HR group. However, the left ventricle ejection fraction (LVEF) was similar in the MR and HR groups.</p><p><strong>Conclusions: </strong>In patients at high and moderate risk for cancer therapy-related cardiovascular toxicity, cardiovascular toxicity risk factors were common and more prevalent in the high-risk group. The coronary artery calcium score was also significantly higher in the high-risk group. Assessing the presence and burden of coronary artery calcium is an attractive option to assess additional cardiovascular risk in cancer patients.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"64"},"PeriodicalIF":3.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342488","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 : 2024-09-28DOI: 10.1186/s40959-024-00259-5
Michelle Bloom, Jose A Alvarez-Cardona, Sarju Ganatra, Ana Barac, Iskra Pusic, Daniel Lenihan, Susan Dent
Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.
癌症患者的心力衰竭(HF)与高发病率和高死亡率有关。癌症治疗的成功使癌症幸存者人数呈指数级增长,然而,心血管疾病(CVD)目前已成为癌症确诊 5 年后限制生命的主要疾病 [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897,2019]。预防和早期发现心血管疾病,包括心肌病(CM)和高血压至关重要。欧洲心脏病学会(ESC)发布了心脏病肿瘤学(CO)指南[Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022],详细介绍了癌症治疗过程中和治疗结束后的心血管(CV)风险分层、预防、监测、诊断和治疗。在此,我们利用一个病例来总结ESC指南中与高血压临床医生相关的内容,重点是癌症患者的风险分层、早期检测、CM和高血压的预防以及指南指导的药物治疗的作用。
{"title":"How to utilize current guidelines to manage patients with cancer at high risk for heart failure.","authors":"Michelle Bloom, Jose A Alvarez-Cardona, Sarju Ganatra, Ana Barac, Iskra Pusic, Daniel Lenihan, Susan Dent","doi":"10.1186/s40959-024-00259-5","DOIUrl":"https://doi.org/10.1186/s40959-024-00259-5","url":null,"abstract":"<p><p>Heart failure (HF) in patients with cancer is associated with high morbidity and mortality. The success of cancer therapy has resulted in an exponential rise in the population of cancer survivors, however cardiovascular disease (CVD) is now a major life limiting condition more than 5 years after cancer diagnosis [Sturgeon, Deng, Bluethmann, et al 40(48):3889-3897, 2019]. Prevention and early detection of CVD, including cardiomyopathy (CM) and HF is of paramount importance. The European Society of Cardiology (ESC) published guidelines on Cardio-Oncology (CO) [Lyon, López-Fernández, Couch, et al 43(41):4229-4361, 2022] detailing cardiovascular (CV) risk stratification, prevention, monitoring, diagnosis, and treatment throughout the course and following completion of cancer therapy. Here we utilize a case to summarize aspects of the ESC guideline relevant to HF clinicians, with a focus on risk stratification, early detection, prevention of CM and HF, and the role for guideline directed medical therapy in patients with cancer.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"63"},"PeriodicalIF":3.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342503","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 : 2024-09-14DOI: 10.1186/s40959-024-00261-x
Jeff Kolbus, Mopelola T Adeola, Janelle M Tipton, Caitlin E D Luebcke
Background: Preliminary research reveals that many nurses feel inadequate and possess limited knowledge when it comes to managing cardiotoxicity, underscoring the necessity for educational programs to enhance nursing skills in this area.
Methods: The aim of the study was to assess the impact of an educational intervention on nurses perceived self-efficacy in recognizing patients exhibiting symptoms of cancer treatment-related cardiotoxicity. The study was set in a 16-bed cardiac critical care unit (CCU) within a 462-bed hospital. The sample group was comprised of registered nurses (RNs) working on or floating to the CCU. The study used a within-subjects design. Participants completed a pre-education survey, attended one of six 30-minute education interventions, and completed a post-education survey. The outcome variables were 7 self-confidence questions from the Nursing Self-Efficacy Scale for Managing Cancer Treatment-Related Cardiotoxicity (NSS-CTC) on a 5-point Likert scale and one yes or no self-efficacy question. Descriptive statistics and paired T-tests were applied to analyze pre- and post-education surveys.
Results: The pre-and post-education comparative analysis for each of the 7 NSS-CTC self-confidence questions was statistically significant with test statistics ranging from t = 3.43 to t = 8.69 and p-values ranging from 0.0021 to less than 0.0001. All 26 RNs answered "yes" in their ability to detect symptoms of cancer therapy-related cardiotoxicity after the education.
Conclusions: The lack of education for cardiac nurses against the backdrop of increasing cardiotoxicity in cancer patients showcases the essential need for cardiac nurse early symptom recognition education.
{"title":"Enhancing nurse competence in early recognition of cardiotoxicity.","authors":"Jeff Kolbus, Mopelola T Adeola, Janelle M Tipton, Caitlin E D Luebcke","doi":"10.1186/s40959-024-00261-x","DOIUrl":"https://doi.org/10.1186/s40959-024-00261-x","url":null,"abstract":"<p><strong>Background: </strong>Preliminary research reveals that many nurses feel inadequate and possess limited knowledge when it comes to managing cardiotoxicity, underscoring the necessity for educational programs to enhance nursing skills in this area.</p><p><strong>Methods: </strong>The aim of the study was to assess the impact of an educational intervention on nurses perceived self-efficacy in recognizing patients exhibiting symptoms of cancer treatment-related cardiotoxicity. The study was set in a 16-bed cardiac critical care unit (CCU) within a 462-bed hospital. The sample group was comprised of registered nurses (RNs) working on or floating to the CCU. The study used a within-subjects design. Participants completed a pre-education survey, attended one of six 30-minute education interventions, and completed a post-education survey. The outcome variables were 7 self-confidence questions from the Nursing Self-Efficacy Scale for Managing Cancer Treatment-Related Cardiotoxicity (NSS-CTC) on a 5-point Likert scale and one yes or no self-efficacy question. Descriptive statistics and paired T-tests were applied to analyze pre- and post-education surveys.</p><p><strong>Results: </strong>The pre-and post-education comparative analysis for each of the 7 NSS-CTC self-confidence questions was statistically significant with test statistics ranging from t = 3.43 to t = 8.69 and p-values ranging from 0.0021 to less than 0.0001. All 26 RNs answered \"yes\" in their ability to detect symptoms of cancer therapy-related cardiotoxicity after the education.</p><p><strong>Conclusions: </strong>The lack of education for cardiac nurses against the backdrop of increasing cardiotoxicity in cancer patients showcases the essential need for cardiac nurse early symptom recognition education.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"62"},"PeriodicalIF":3.2,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11401397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280961","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 : 2024-09-12DOI: 10.1186/s40959-024-00265-7
Farah Yasmin, Abdul Moeed, Muhammad Tanveer Alam, Vikash Virwani, Yumna Khabir, Asim Shaikh, Apurva V Vyas, M Chadi Alraies
Clinical outcomes for TAVR in cancer survivors with prior chest radiation therapy (C-XRT) who develop symptomatic aortic-valve stenosis are not adequately assessed in major clinical trials leading to conflicting results. Hence, we conducted this meta-analysis to evaluate the, safety, efficacy, and mortality outcomes of cancer survivors with prior C-XRT undergoing TAVR. MEDLINE and Scopus were searched up to March 2024. Observational studies and randomized controlled trials comparing severe aortic stenosis patients with and without prior C-XRT undergoing TAVR with at least one outcome of interest were shortlisted. Data were analyzed using random-effects model to derive weighted mean differences, and risk ratios with 95% confidence intervals. Six studies with 6,191 patients (278 C-XRT and 5,913 no-C-XRT) were included. All-cause mortality at 30-day (RR 1.63, p = 0.12) and 1-year interval (RR 1.59, p = 0.08) showed no significant differences with prior C-XRT versus no-C-XRT. Worsening CHF was the only post-procedural safety outcome significantly higher in patients with prior C-XRT (RR 1.98, p = 0.0004) versus no- C-XRT. The efficacy end-points i.e., improvement in LVEF (MD 1.24; -0.50, 2.98), and aortic valve gradient (MD -0.63; -1.32, 0.05) were not significantly different. TAVR has similar all-cause mortality, efficacy and safety (except CHF worsening) among cancer survivors with and without a prior history of C-XRT.
{"title":"Outcomes after transcatheter aortic valve replacement in cancer survivors with prior chest radiation therapy: an updated systematic review and meta-analysis.","authors":"Farah Yasmin, Abdul Moeed, Muhammad Tanveer Alam, Vikash Virwani, Yumna Khabir, Asim Shaikh, Apurva V Vyas, M Chadi Alraies","doi":"10.1186/s40959-024-00265-7","DOIUrl":"https://doi.org/10.1186/s40959-024-00265-7","url":null,"abstract":"<p><p>Clinical outcomes for TAVR in cancer survivors with prior chest radiation therapy (C-XRT) who develop symptomatic aortic-valve stenosis are not adequately assessed in major clinical trials leading to conflicting results. Hence, we conducted this meta-analysis to evaluate the, safety, efficacy, and mortality outcomes of cancer survivors with prior C-XRT undergoing TAVR. MEDLINE and Scopus were searched up to March 2024. Observational studies and randomized controlled trials comparing severe aortic stenosis patients with and without prior C-XRT undergoing TAVR with at least one outcome of interest were shortlisted. Data were analyzed using random-effects model to derive weighted mean differences, and risk ratios with 95% confidence intervals. Six studies with 6,191 patients (278 C-XRT and 5,913 no-C-XRT) were included. All-cause mortality at 30-day (RR 1.63, p = 0.12) and 1-year interval (RR 1.59, p = 0.08) showed no significant differences with prior C-XRT versus no-C-XRT. Worsening CHF was the only post-procedural safety outcome significantly higher in patients with prior C-XRT (RR 1.98, p = 0.0004) versus no- C-XRT. The efficacy end-points i.e., improvement in LVEF (MD 1.24; -0.50, 2.98), and aortic valve gradient (MD -0.63; -1.32, 0.05) were not significantly different. TAVR has similar all-cause mortality, efficacy and safety (except CHF worsening) among cancer survivors with and without a prior history of C-XRT.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"61"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280962","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 : 2024-09-12DOI: 10.1186/s40959-024-00262-w
Netanel Golan, Rafael Y Brzezinski, Moaad Slieman, Shafik Khoury, Ofer Havakuk, Yan Topilsky, Shmuel Banai, Michal Laufer-Perl
Background: Cancer therapy is considered to cause accelerated ischemia. Ankle-Brachial Index (ABI) measurement is an inexpensive, simple, available test for the early diagnosis of peripheral artery disease (PAD); however, it is not performed routinely. We aimed to evaluate the role of routine ABI measurement for the diagnosis of PAD among patients diagnosed with cancer and whether it correlates with left ventricular (LV) dysfunction.
Methods: A retrospective, single-center study including patients diagnosed with cancer at Tel Aviv Sourasky Medical Center. The cohort included patients performing routine ABI and LV global longitudinal strain (GLS) echocardiography. The primary endpoint was the prevalence of PAD and whether it correlates with LV dysfunction, defined by LV GLS absolute value < 19%. The secondary composite endpoint evaluated the association between reduced ABI to LV dysfunction and all-cause mortality.
Results: Among 226 patients, PAD was diagnosed in 14 patients (6%). We revealed a positive correlation between ABI and LV GLS (r = 0.22, p < 0.01) with a reduced mean ABI score among patients with reduced LV GLS. A reduced mean ABI was observed among the positive composite endpoint group; however, it was not statistically significant (p = 0.35).
Conclusions: We report, for the first time to our knowledge, the routine use of ABI testing among patients diagnosed with cancer. ABI showed a significant correlation to LV GLS, implying a potential tool in the early diagnosis of atherosclerosis and cardiotoxicity. Considering its low cost and availability, future prospective trials are needed to integrate its role in routine assessment.
背景:癌症治疗被认为会加速缺血。踝肱指数(ABI)测量是一种廉价、简单、可用于早期诊断外周动脉疾病(PAD)的检测方法;然而,它并不是常规检测方法。我们旨在评估常规 ABI 测量在诊断癌症患者 PAD 中的作用,以及它是否与左心室(LV)功能障碍相关:这是一项回顾性单中心研究,研究对象包括特拉维夫苏拉斯基医疗中心的癌症患者。研究对象包括进行常规 ABI 和左心室整体纵向应变 (GLS) 超声心动图检查的患者。主要终点是PAD的患病率以及它是否与左心室功能障碍(以左心室GLS绝对值定义)相关:在 226 名患者中,14 名患者(6%)被确诊为 PAD。我们发现 ABI 与 LV GLS 之间存在正相关(r = 0.22,p 结论:ABI 与 LV GLS 之间存在正相关:据我们所知,我们首次报告了在癌症患者中常规使用 ABI 检测的情况。ABI 与左心室 GLS 呈明显相关性,这意味着它是早期诊断动脉粥样硬化和心脏毒性的潜在工具。考虑到 ABI 的低成本和可用性,未来需要进行前瞻性试验,将其纳入常规评估中。
{"title":"Routine Ankle-Brachial Index (ABI) measurement: a window into atherosclerosis and early left ventricular dysfunction in patients diagnosed with cancer.","authors":"Netanel Golan, Rafael Y Brzezinski, Moaad Slieman, Shafik Khoury, Ofer Havakuk, Yan Topilsky, Shmuel Banai, Michal Laufer-Perl","doi":"10.1186/s40959-024-00262-w","DOIUrl":"https://doi.org/10.1186/s40959-024-00262-w","url":null,"abstract":"<p><strong>Background: </strong>Cancer therapy is considered to cause accelerated ischemia. Ankle-Brachial Index (ABI) measurement is an inexpensive, simple, available test for the early diagnosis of peripheral artery disease (PAD); however, it is not performed routinely. We aimed to evaluate the role of routine ABI measurement for the diagnosis of PAD among patients diagnosed with cancer and whether it correlates with left ventricular (LV) dysfunction.</p><p><strong>Methods: </strong>A retrospective, single-center study including patients diagnosed with cancer at Tel Aviv Sourasky Medical Center. The cohort included patients performing routine ABI and LV global longitudinal strain (GLS) echocardiography. The primary endpoint was the prevalence of PAD and whether it correlates with LV dysfunction, defined by LV GLS absolute value < 19%. The secondary composite endpoint evaluated the association between reduced ABI to LV dysfunction and all-cause mortality.</p><p><strong>Results: </strong>Among 226 patients, PAD was diagnosed in 14 patients (6%). We revealed a positive correlation between ABI and LV GLS (r = 0.22, p < 0.01) with a reduced mean ABI score among patients with reduced LV GLS. A reduced mean ABI was observed among the positive composite endpoint group; however, it was not statistically significant (p = 0.35).</p><p><strong>Conclusions: </strong>We report, for the first time to our knowledge, the routine use of ABI testing among patients diagnosed with cancer. ABI showed a significant correlation to LV GLS, implying a potential tool in the early diagnosis of atherosclerosis and cardiotoxicity. Considering its low cost and availability, future prospective trials are needed to integrate its role in routine assessment.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"60"},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11391668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280975","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}