Pub Date : 2025-02-01DOI: 10.1016/j.jaccao.2024.09.014
Marc P. Bonaca MD, MPH , Ninian N. Lang MBChB, PhD , Alice Chen MD , Laleh Amiri-Kordestani MD , Leslie Lipka MD, PhD , Michal Zwiewka MD , Colette Strnadova PhD , Sigrid Klaar MD, PhD , Susan Dent MD , Tijana Krnjeta Janicijevic PharmD, PhD , Joerg Herrmann MD , Ana Barac MD, PhD , Rudolf A. de Boer MD , Anita Deswal MD, MBBS, MPH , Morten Schou MD , Tomas G. Neilan MD, MPH , Peter van der Meer MD , Javid Moslehi MD , Lavanya Kondapalli MD , Bonnie Ky MD, MSCE , Mark C. Petrie MD
The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required. However, implications include increased costs and slower development. The Cardiovascular Safety Research Consortium facilitated stakeholder discussions with representation from academia, industry, and regulators. A think tank was assembled with the aim of providing recommendations for improved collection and reporting of cardiovascular safety signals in oncology trials. Two working groups were formed. The first focuses on incorporation of consensus definitions of cardiovascular disease into the Common Terminology Criteria for Adverse Events used in oncology trial reporting. The second group considers methods for ascertainment and adjudication of cardiovascular events in cancer trials. The overarching aim of this primer is to improve understanding of the potential cardiovascular toxicities of cancer therapies.
{"title":"Cardiovascular Safety in Oncology Clinical Trials","authors":"Marc P. Bonaca MD, MPH , Ninian N. Lang MBChB, PhD , Alice Chen MD , Laleh Amiri-Kordestani MD , Leslie Lipka MD, PhD , Michal Zwiewka MD , Colette Strnadova PhD , Sigrid Klaar MD, PhD , Susan Dent MD , Tijana Krnjeta Janicijevic PharmD, PhD , Joerg Herrmann MD , Ana Barac MD, PhD , Rudolf A. de Boer MD , Anita Deswal MD, MBBS, MPH , Morten Schou MD , Tomas G. Neilan MD, MPH , Peter van der Meer MD , Javid Moslehi MD , Lavanya Kondapalli MD , Bonnie Ky MD, MSCE , Mark C. Petrie MD","doi":"10.1016/j.jaccao.2024.09.014","DOIUrl":"10.1016/j.jaccao.2024.09.014","url":null,"abstract":"<div><div>The development of novel treatments has improved cancer outcomes but may result in cardiovascular toxicities. Traditional approaches to clinical trial safety evaluation have limitations in their ability to detect signals of cardiovascular risk. Mechanisms to increase power and specificity to clarify cardiovascular safety are required. However, implications include increased costs and slower development. The Cardiovascular Safety Research Consortium facilitated stakeholder discussions with representation from academia, industry, and regulators. A think tank was assembled with the aim of providing recommendations for improved collection and reporting of cardiovascular safety signals in oncology trials. Two working groups were formed. The first focuses on incorporation of consensus definitions of cardiovascular disease into the Common Terminology Criteria for Adverse Events used in oncology trial reporting. The second group considers methods for ascertainment and adjudication of cardiovascular events in cancer trials. The overarching aim of this primer is to improve understanding of the potential cardiovascular toxicities of cancer therapies.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 83-95"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jaccao.2024.11.009
Beina Hui MD, Weibin Hu MD, Yongkai Lu PhD
{"title":"Navigating the Uncharted","authors":"Beina Hui MD, Weibin Hu MD, Yongkai Lu PhD","doi":"10.1016/j.jaccao.2024.11.009","DOIUrl":"10.1016/j.jaccao.2024.11.009","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Page 188"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jaccao.2024.10.012
Shuang Yang MS , Xiwei Lou MS , Mustafa M. Ahmed MD , Stephen E. Kimmel MD , Karen C. Daily DO , Thomas J. George MD , Carl J. Pepine MD , Jiang Bian PhD , Dejana Braithwaite PhD, MSc , Dongyu Zhang PhD , Yi Guo PhD
Background
Prior research suggests that breast cancer patients with a high burden of frailty may face an increased risk of cardiotoxicity.
Objectives
This study sought to examine the association between frailty and cardiotoxicity rates in female breast cancer patients receiving adjuvant therapy after surgery.
Methods
We analyzed data from the OneFlorida+ clinical research network, focusing on breast cancer patients treated with adjuvant chemotherapy and targeted therapy from 2012 to 2022. Cardiovascular rates during adjuvant treatments were calculated based on pre-existing frailty, measured using the cumulative deficit frailty index (electronic health record frailty index). We employed multivariable Gray’s method to examine the association between frailty with cardiotoxicity.
Results
The final cohort included 2,050 patients (mean age 50.6 years), with 415 (20.2%) experiencing nonfatal adverse cardiovascular events after adjuvant therapy. The incidence of adverse cardiovascular events was 17.8% in robust, 23.2% in prefrail, and 29.4% in frail patients. In multivariable analysis, prefrail (adjusted subdistribution HR [sHR]: 1.35; 95% CI: 1.06-1.71; P = 0.015) and frail (adjusted sHR: 1.70; 95% CI: 1.11-2.61; P = 0.015) patients had a higher likelihood of experiencing adverse cardiovascular events compared with robust patients. Among non-Hispanic White and Black patients, prefrail (adjusted sHR: 1.48; 95% CI: 1.04-2.11; P = 0.031; and adjusted sHR: 1.59; 95% CI: 1.06-2.37; P = 0.024, respectively) and frail (adjusted sHR: 1.96; 95% CI: 1.10-3.50; P = 0.022; and adjusted sHR: 2.13; 95% CI: 1.11-4.10; P = 0.023, respectively) patients were more likely to experience adverse cardiovascular events compared with robust patients. No significant differences were observed in other racial/ethnic groups.
Conclusions
These findings highlight the need for close monitoring of cardiotoxicity in frail breast cancer patients undergoing adjuvant treatments to improve cardiovascular risk management.
{"title":"Impact of Pre-Existing Frailty on Cardiotoxicity Among Breast Cancer Patients Receiving Adjuvant Therapy","authors":"Shuang Yang MS , Xiwei Lou MS , Mustafa M. Ahmed MD , Stephen E. Kimmel MD , Karen C. Daily DO , Thomas J. George MD , Carl J. Pepine MD , Jiang Bian PhD , Dejana Braithwaite PhD, MSc , Dongyu Zhang PhD , Yi Guo PhD","doi":"10.1016/j.jaccao.2024.10.012","DOIUrl":"10.1016/j.jaccao.2024.10.012","url":null,"abstract":"<div><h3>Background</h3><div>Prior research suggests that breast cancer patients with a high burden of frailty may face an increased risk of cardiotoxicity.</div></div><div><h3>Objectives</h3><div>This study sought to examine the association between frailty and cardiotoxicity rates in female breast cancer patients receiving adjuvant therapy after surgery.</div></div><div><h3>Methods</h3><div>We analyzed data from the OneFlorida+ clinical research network, focusing on breast cancer patients treated with adjuvant chemotherapy and targeted therapy from 2012 to 2022. Cardiovascular rates during adjuvant treatments were calculated based on pre-existing frailty, measured using the cumulative deficit frailty index (electronic health record frailty index). We employed multivariable Gray’s method to examine the association between frailty with cardiotoxicity.</div></div><div><h3>Results</h3><div>The final cohort included 2,050 patients (mean age 50.6 years), with 415 (20.2%) experiencing nonfatal adverse cardiovascular events after adjuvant therapy. The incidence of adverse cardiovascular events was 17.8% in robust, 23.2% in prefrail, and 29.4% in frail patients. In multivariable analysis, prefrail (adjusted subdistribution HR [sHR]: 1.35; 95% CI: 1.06-1.71; <em>P</em> = 0.015) and frail (adjusted sHR: 1.70; 95% CI: 1.11-2.61; <em>P</em> = 0.015) patients had a higher likelihood of experiencing adverse cardiovascular events compared with robust patients. Among non-Hispanic White and Black patients, prefrail (adjusted sHR: 1.48; 95% CI: 1.04-2.11; <em>P</em> = 0.031; and adjusted sHR: 1.59; 95% CI: 1.06-2.37; <em>P</em> = 0.024, respectively) and frail (adjusted sHR: 1.96; 95% CI: 1.10-3.50; <em>P</em> = 0.022; and adjusted sHR: 2.13; 95% CI: 1.11-4.10; <em>P</em> = 0.023, respectively) patients were more likely to experience adverse cardiovascular events compared with robust patients. No significant differences were observed in other racial/ethnic groups.</div></div><div><h3>Conclusions</h3><div>These findings highlight the need for close monitoring of cardiotoxicity in frail breast cancer patients undergoing adjuvant treatments to improve cardiovascular risk management.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 110-121"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jaccao.2024.11.005
Jan M. Leerink MD, PhD , Elizabeth A.M. Feijen PhD
{"title":"Novel Potential Blood Biomarkers for Detection of Anthracycline-Related Cardiomyopathy in Childhood Cancer Survivors","authors":"Jan M. Leerink MD, PhD , Elizabeth A.M. Feijen PhD","doi":"10.1016/j.jaccao.2024.11.005","DOIUrl":"10.1016/j.jaccao.2024.11.005","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 68-69"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jaccao.2024.10.006
June-Wha Rhee MD , Raju Pillai MD , Sitong Chen MPH , Alysia Bosworth BA , Artem Oganesyan MD , Liezl Atencio MD , Kendall Freeman BS , Caitlyn Estrada BS , Tati Guzman BS , Kara Lukas BS , Kelly Peng BS , Brianna Sigala BS , Aleksi Lukuridze BS , Lanie Lindenfeld MA , Faizi Jamal MD , Pradeep Natarajan MD , Smita Bhatia MD, MPH , Alex F. Herrera MD , Matthew G. Mei MD , Ryotaro Nakamura MD , Saro H. Armenian DO, MPH
Background
Patients with lymphoma are at high risk for developing heart failure (HF) after autologous hematopoietic cell transplantation (HCT). More accurate risk determination pre-HCT may facilitate screening and prevention of HF.
Objectives
The aim of this study was to examine the association between clonal hematopoiesis of indeterminate potential (CHIP) and the risk for HF after HCT for lymphoma.
Methods
This was a retrospective cohort study of 861 patients who underwent autologous HCT for lymphoma between 2010 and 2016 at City of Hope Comprehensive Cancer Center. Targeted DNA sequencing was performed to determine the presence of CHIP (variant allele frequency ≥ 2%). The primary outcome of interest was the 5-year cumulative incidence of de novo HF. Other outcomes of interest included overall and cause-specific mortality.
Results
Overall, 186 patients (21.7% of the cohort) had at least 1 CHIP variant, and 59 (6.9%) had ≥2 variants. DNMT3A, PPM1D, and TET2 were the most frequently mutated genes. The 5-year incidence of HF was significantly higher in patients with CHIP compared with those without CHIP (13.8% vs 4.7%; P < 0.001; sub-distribution hazard ratio [sHR]: 2.48; 95% CI: 1.32-4.68); the HF incidence increased by variant allele frequency: 0-2% (4.7%), 2-10% (11.7%), and >10% (18.5%), P < 0.001. Patients with CHIP had significantly worse overall survival after HCT, compared with those without (63.4% vs 80.3%; P < 0.001), due primarily to the higher risk for nonrelapse mortality (subdistribution HR: 5.37; 95% CI: 2.34-12.35).
Conclusions
CHIP was highly prevalent and associated with risk for HF and nonrelapse mortality after HCT. These findings highlight the role of CHIP as a novel biomarker and potential target for intervention to improve outcomes after autologous HCT.
{"title":"Clonal Hematopoiesis and Risk of Heart Failure After Autologous Hematopoietic Cell Transplantation for Lymphoma","authors":"June-Wha Rhee MD , Raju Pillai MD , Sitong Chen MPH , Alysia Bosworth BA , Artem Oganesyan MD , Liezl Atencio MD , Kendall Freeman BS , Caitlyn Estrada BS , Tati Guzman BS , Kara Lukas BS , Kelly Peng BS , Brianna Sigala BS , Aleksi Lukuridze BS , Lanie Lindenfeld MA , Faizi Jamal MD , Pradeep Natarajan MD , Smita Bhatia MD, MPH , Alex F. Herrera MD , Matthew G. Mei MD , Ryotaro Nakamura MD , Saro H. Armenian DO, MPH","doi":"10.1016/j.jaccao.2024.10.006","DOIUrl":"10.1016/j.jaccao.2024.10.006","url":null,"abstract":"<div><h3>Background</h3><div>Patients with lymphoma are at high risk for developing heart failure (HF) after autologous hematopoietic cell transplantation (HCT). More accurate risk determination pre-HCT may facilitate screening and prevention of HF.</div></div><div><h3>Objectives</h3><div>The aim of this study was to examine the association between clonal hematopoiesis of indeterminate potential (CHIP) and the risk for HF after HCT for lymphoma.</div></div><div><h3>Methods</h3><div>This was a retrospective cohort study of 861 patients who underwent autologous HCT for lymphoma between 2010 and 2016 at City of Hope Comprehensive Cancer Center. Targeted DNA sequencing was performed to determine the presence of CHIP (variant allele frequency ≥ 2%). The primary outcome of interest was the 5-year cumulative incidence of de novo HF. Other outcomes of interest included overall and cause-specific mortality.</div></div><div><h3>Results</h3><div>Overall, 186 patients (21.7% of the cohort) had at least 1 CHIP variant, and 59 (6.9%) had ≥2 variants. <em>DNMT3A</em>, <em>PPM1D</em>, and <em>TET2</em> were the most frequently mutated genes. The 5-year incidence of HF was significantly higher in patients with CHIP compared with those without CHIP (13.8% vs 4.7%; <em>P</em> < 0.001; sub-distribution hazard ratio [sHR]: 2.48; 95% CI: 1.32-4.68); the HF incidence increased by variant allele frequency: 0-2% (4.7%), 2-10% (11.7%), and >10% (18.5%), <em>P</em> < 0.001. Patients with CHIP had significantly worse overall survival after HCT, compared with those without (63.4% vs 80.3%; <em>P</em> < 0.001), due primarily to the higher risk for nonrelapse mortality (subdistribution HR: 5.37; 95% CI: 2.34-12.35).</div></div><div><h3>Conclusions</h3><div>CHIP was highly prevalent and associated with risk for HF and nonrelapse mortality after HCT. These findings highlight the role of CHIP as a novel biomarker and potential target for intervention to improve outcomes after autologous HCT.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 20-33"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-01DOI: 10.1016/j.jaccao.2024.12.002
Itamar Braga Dias MSc, Alexander H. Maass MD, PhD
{"title":"Dantrolene as a Potential Strategy to Prevent Doxorubicin-Induced Cardiotoxicity","authors":"Itamar Braga Dias MSc, Alexander H. Maass MD, PhD","doi":"10.1016/j.jaccao.2024.12.002","DOIUrl":"10.1016/j.jaccao.2024.12.002","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 1","pages":"Pages 53-55"},"PeriodicalIF":12.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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