Pub Date : 2025-10-01DOI: 10.1016/j.jaccao.2025.05.012
Rachele Cagnazzo BS , Mario Stabile MD , Gabriele Zoppoli MD, PhD , Rudolf A. De Boer MD, PhD , Wouter C. Meijers MD, PhD , Peter van Der Meer MD, PhD , Pietro Ameri MD, PhD
{"title":"Mismatch Between Preclinical Cardio-Oncology and Clinical Oncology Research","authors":"Rachele Cagnazzo BS , Mario Stabile MD , Gabriele Zoppoli MD, PhD , Rudolf A. De Boer MD, PhD , Wouter C. Meijers MD, PhD , Peter van Der Meer MD, PhD , Pietro Ameri MD, PhD","doi":"10.1016/j.jaccao.2025.05.012","DOIUrl":"10.1016/j.jaccao.2025.05.012","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 770-773"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jaccao.2025.08.003
Jacqueline B. Vo PhD, RN, MPH , Carolyn Brandt MPH , Kekoa Taparra MD, PhD, MPH , Cody Ramin PhD , Amy Berrington de González DPhil , Gretchen L. Gierach PhD, MPH , Wayne R. Lawrence DrPH , Jongeun Rhee ScD, MS , Meredith S. Shiels PhD , Lene H.S. Veiga PhD , Paloma R. Mitra BA , Jaimie Z. Shing PhD, MPH , Stella S. Yi PhD
{"title":"Disparities in Heart Disease Mortality Among Asian American and Pacific Islander Breast Cancer Survivors, 2000 to 2019","authors":"Jacqueline B. Vo PhD, RN, MPH , Carolyn Brandt MPH , Kekoa Taparra MD, PhD, MPH , Cody Ramin PhD , Amy Berrington de González DPhil , Gretchen L. Gierach PhD, MPH , Wayne R. Lawrence DrPH , Jongeun Rhee ScD, MS , Meredith S. Shiels PhD , Lene H.S. Veiga PhD , Paloma R. Mitra BA , Jaimie Z. Shing PhD, MPH , Stella S. Yi PhD","doi":"10.1016/j.jaccao.2025.08.003","DOIUrl":"10.1016/j.jaccao.2025.08.003","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 767-769"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jaccao.2025.07.010
Yi Li MA , Jiantao Ma PhD
{"title":"DNA Methylation–Based Epigenetic Clocks and Cardiovascular Disease","authors":"Yi Li MA , Jiantao Ma PhD","doi":"10.1016/j.jaccao.2025.07.010","DOIUrl":"10.1016/j.jaccao.2025.07.010","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 705-707"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jaccao.2025.07.012
Paolo Milani MD, PhD , Giuseppe Damiano Sanna MD, PhD , Claudia Bellofiore MD , Mario Nuvolone MD, PhD , Marco Basset MD, PhD , Roberta Mussinelli MD, PhD , Giulia Mazzini BS , Martina Nanci MD , Martina Ciardo MD , Serena Caminito BS , Matin Ghazi Esfahani MS , Mohammadjavad Sadrzadeh MS , Alessandro Fogliani MD , Francesca Benigna MD , Gianluigi Guida MD , Francesco Salinaro MD, PhD , Tiziana Bosoni BS , Alessandra Barassi MD , Andrea Foli MD , Riccardo Albertini MD , Giovanni Palladini MD, PhD
Background
Detection of monoclonal components (MCs) using serum and urine immunofixation (IFE) and free light chain measurement is a critical early step in diagnosing cardiac amyloidosis. Patients with MCs are referred for biopsy-based diagnostic work-up. New reference ranges for the free light chain ratio (FLCR), adjusted for age and estimated glomerular filtration rate, have been proposed.
Objectives
The aim of this study was to compare the diagnostic performance of the new vs the conventional FLCR in patients with light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis.
Methods
The analysis included 1,705 patients with AL amyloidosis and 675 with ATTRwt amyloidosis.
Results
In the AL cohort, 44 patients (3%) had negative results on serum and urine IFE at diagnosis. Among these, 13 patients had normal conventional FLCRs and 15 had normal new FLCRs, with no significant difference in diagnostic sensitivity (70.4% [95% CI: 55.8%-82.5%] vs 65.9% [95% CI: 50.0%-79.5%]; P = 0.82). Overall diagnostic sensitivity for MC detection was similar between the new and conventional FLCRs (99.2% vs 99.1%). Among patients with ATTRwt amyloidosis and negative serum and urine IFE results, 156 (26.5%) had abnormal FLCRs using the conventional cutoff, compared with only 12 (2%) using the new FLCR. At hematologic response assessment in AL amyloidosis, concordance in the definition of complete response between the 2 FLCR methods was 94.9% (95% CI: 93.4%-95.9%).
Conclusions
The new FLCR demonstrates equivalent diagnostic sensitivity in AL amyloidosis and can be integrated into complete response criteria. In patients with suspected ATTRwt amyloidosis, it significantly reduces the proportion of FLCR-only abnormalities, thereby limiting the need for biopsy confirmation.
背景：利用血清和尿液免疫固定（IFE）和游离轻链检测单克隆成分（MCs）是诊断心脏淀粉样变性的关键早期步骤。MCs患者被转诊进行基于活检的诊断检查。自由轻链比（FLCR）的新参考范围，根据年龄和估计的肾小球滤过率进行了调整。目的：本研究的目的是比较新型与传统FLCR在轻链（AL）淀粉样变性和野生型甲状腺转蛋白（ATTRwt）淀粉样变性患者中的诊断性能。方法：对1705例AL型淀粉样变患者和675例attrt型淀粉样变患者进行分析。结果：在AL队列中，44例（3%）患者在诊断时血清和尿液IFE结果为阴性。其中，13例患者常规flcr正常，15例患者新flcr正常，诊断敏感性无显著差异（70.4% [95% CI: 55.8% ~ 82.5%] vs 65.9% [95% CI: 50.0% ~ 79.5%]; P = 0.82）。新型和传统FLCRs对MC检测的总体诊断敏感性相似（99.2% vs 99.1%）。在患有ATTRwt淀粉样变性且血清和尿液IFE结果阴性的患者中，156例（26.5%）使用传统的截止值有异常的FLCR，而使用新的FLCR只有12例（2%）。在AL淀粉样变性的血液学反应评估中，两种FLCR方法在完全缓解定义上的一致性为94.9% （95% CI: 93.4%-95.9%）。结论：新的FLCR对AL淀粉样变性具有相当的诊断敏感性，可纳入完全缓解标准。在疑似ATTRwt淀粉样变的患者中，它显著降低了仅flcr异常的比例，从而限制了活检确认的需要。
{"title":"Diagnostic Performance of the New Free Light Chain Ratio in Systemic Amyloidosis","authors":"Paolo Milani MD, PhD , Giuseppe Damiano Sanna MD, PhD , Claudia Bellofiore MD , Mario Nuvolone MD, PhD , Marco Basset MD, PhD , Roberta Mussinelli MD, PhD , Giulia Mazzini BS , Martina Nanci MD , Martina Ciardo MD , Serena Caminito BS , Matin Ghazi Esfahani MS , Mohammadjavad Sadrzadeh MS , Alessandro Fogliani MD , Francesca Benigna MD , Gianluigi Guida MD , Francesco Salinaro MD, PhD , Tiziana Bosoni BS , Alessandra Barassi MD , Andrea Foli MD , Riccardo Albertini MD , Giovanni Palladini MD, PhD","doi":"10.1016/j.jaccao.2025.07.012","DOIUrl":"10.1016/j.jaccao.2025.07.012","url":null,"abstract":"<div><h3>Background</h3><div>Detection of monoclonal components (MCs) using serum and urine immunofixation (IFE) and free light chain measurement is a critical early step in diagnosing cardiac amyloidosis. Patients with MCs are referred for biopsy-based diagnostic work-up. New reference ranges for the free light chain ratio (FLCR), adjusted for age and estimated glomerular filtration rate, have been proposed.</div></div><div><h3>Objectives</h3><div>The aim of this study was to compare the diagnostic performance of the new vs the conventional FLCR in patients with light chain (AL) amyloidosis and wild-type transthyretin (ATTRwt) amyloidosis.</div></div><div><h3>Methods</h3><div>The analysis included 1,705 patients with AL amyloidosis and 675 with ATTRwt amyloidosis.</div></div><div><h3>Results</h3><div>In the AL cohort, 44 patients (3%) had negative results on serum and urine IFE at diagnosis. Among these, 13 patients had normal conventional FLCRs and 15 had normal new FLCRs, with no significant difference in diagnostic sensitivity (70.4% [95% CI: 55.8%-82.5%] vs 65.9% [95% CI: 50.0%-79.5%]; <em>P</em> = 0.82). Overall diagnostic sensitivity for MC detection was similar between the new and conventional FLCRs (99.2% vs 99.1%). Among patients with ATTRwt amyloidosis and negative serum and urine IFE results, 156 (26.5%) had abnormal FLCRs using the conventional cutoff, compared with only 12 (2%) using the new FLCR. At hematologic response assessment in AL amyloidosis, concordance in the definition of complete response between the 2 FLCR methods was 94.9% (95% CI: 93.4%-95.9%).</div></div><div><h3>Conclusions</h3><div>The new FLCR demonstrates equivalent diagnostic sensitivity in AL amyloidosis and can be integrated into complete response criteria. In patients with suspected ATTRwt amyloidosis, it significantly reduces the proportion of FLCR-only abnormalities, thereby limiting the need for biopsy confirmation.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 751-759"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-01DOI: 10.1016/j.jaccao.2025.06.001
Xiaoxi Meng PhD , Tiffany Eulalio PhD , Yoonji Kim PhD , John Easton PhD , Heather L. Mulder BSc , Emily Walker BSc , Geoffrey Neale PhD , Nan Song PhD , Kyla Shelton MPH , Rebecca M. Howell PhD , Mengqi Xing MR , Sedigheh Mirzaei PhD , Deo Kumar Srivastava PhD , Bonnie Ky MD , Stephanie B. Dixon MD , Melissa M. Hudson MD , Kirsten K. Ness PhD , Gregory T. Armstrong MD , Zhaoming Wang PhD
Background
Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.
Objectives
The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.
Methods
This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region–specific radiotherapy (RT) and chemotherapeutic agents such as anthracyclines and corticosteroids, were abstracted from medical records. Outcomes included 3 CMRFs (abnormal glucose metabolism, hypertension, and obesity) and 2 cardiovascular diseases (cardiomyopathy and myocardial infarction). Mediation analysis was conducted to quantify the extent to which EAA mediated the association between each treatment exposure and each clinical outcome.
Results
EAA partially mediated the associations between abdominal RT and abnormal glucose metabolism (DunedinPACE 35.4%, GrimAge2 16.2%), between abdominal RT (DunedinPACE 25.9%) or anthracyclines (DunedinPACE 12.5%) and hypertension, and between corticosteroids and obesity (DunedinPACE 8.6%). EAA also mediated the associations between heart RT and cardiomyopathy (PCPhenoAge 30.3%, DunedinPACE 19.9%, GrimAge2 14.4%) and myocardial infarction (PCPhenoAge 24.1%, DunedinPACE 15.5%, GrimAge2 13.2%), and anthracyclines and cardiomyopathy (GrimAge2 6.0%, PCPhenoAge 5.2%, DunedinPACE 3.9%).
Conclusions
EAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases. These findings provide insight into biological aging as a potential mechanistic pathway and support the development of interventions targeting accelerated aging to mitigate long-term treatment-related toxicities and reduce premature mortality in this high-risk population.
{"title":"Epigenetic Age Acceleration Mediates Treatment Effects on Cardiometabolic and Cardiovascular Risk in Childhood Cancer Survivors","authors":"Xiaoxi Meng PhD , Tiffany Eulalio PhD , Yoonji Kim PhD , John Easton PhD , Heather L. Mulder BSc , Emily Walker BSc , Geoffrey Neale PhD , Nan Song PhD , Kyla Shelton MPH , Rebecca M. Howell PhD , Mengqi Xing MR , Sedigheh Mirzaei PhD , Deo Kumar Srivastava PhD , Bonnie Ky MD , Stephanie B. Dixon MD , Melissa M. Hudson MD , Kirsten K. Ness PhD , Gregory T. Armstrong MD , Zhaoming Wang PhD","doi":"10.1016/j.jaccao.2025.06.001","DOIUrl":"10.1016/j.jaccao.2025.06.001","url":null,"abstract":"<div><h3>Background</h3><div>Childhood cancer survivors are at increased risk for epigenetic age acceleration (EAA) and subsequent morbidities, including cardiometabolic risk factors (CMRFs) and cardiovascular diseases, because of prior genotoxic treatments.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate the mediating role of EAA in the relationship between cancer treatment exposures and risk for CMRFs and cardiovascular diseases.</div></div><div><h3>Methods</h3><div>This study included 2,939 5-year survivors from SJLIFE (St. Jude Lifetime Cohort) who underwent DNA methylation profiling using peripheral blood mononuclear cells. EAA was calculated using 3 established epigenetic clocks: DunedinPACE, PCPhenoAge, and GrimAge2. Treatment data, including body region–specific radiotherapy (RT) and chemotherapeutic agents such as anthracyclines and corticosteroids, were abstracted from medical records. Outcomes included 3 CMRFs (abnormal glucose metabolism, hypertension, and obesity) and 2 cardiovascular diseases (cardiomyopathy and myocardial infarction). Mediation analysis was conducted to quantify the extent to which EAA mediated the association between each treatment exposure and each clinical outcome.</div></div><div><h3>Results</h3><div>EAA partially mediated the associations between abdominal RT and abnormal glucose metabolism (DunedinPACE 35.4%, GrimAge2 16.2%), between abdominal RT (DunedinPACE 25.9%) or anthracyclines (DunedinPACE 12.5%) and hypertension, and between corticosteroids and obesity (DunedinPACE 8.6%). EAA also mediated the associations between heart RT and cardiomyopathy (PCPhenoAge 30.3%, DunedinPACE 19.9%, GrimAge2 14.4%) and myocardial infarction (PCPhenoAge 24.1%, DunedinPACE 15.5%, GrimAge2 13.2%), and anthracyclines and cardiomyopathy (GrimAge2 6.0%, PCPhenoAge 5.2%, DunedinPACE 3.9%).</div></div><div><h3>Conclusions</h3><div>EAA accounted for a substantial proportion of the association between cancer treatment exposures and risk for CMRFs and cardiovascular diseases. These findings provide insight into biological aging as a potential mechanistic pathway and support the development of interventions targeting accelerated aging to mitigate long-term treatment-related toxicities and reduce premature mortality in this high-risk population.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 6","pages":"Pages 691-704"},"PeriodicalIF":12.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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