Jacc: Cardiooncology最新文献

英文中文

Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy. 双特异性t细胞介入治疗相关的心血管不良事件。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-03-09 DOI: 10.1016/j.jaccao.2026.01.005

Osnat Itzhaki Ben Zadok, Shai Shimony, Shannon Miller, David Stein, Shahrier Hossain, Giada Bianchi, Anju Nohria

Background: Although some cancer immunotherapies have been linked to increased cardiovascular risk, data on T-cell engager (TCE) therapy-associated cardiovascular complications remain limited.

Objectives: This study sought to characterize the incidence and factors associated with cardiovascular events (CVEs) and mortality during TCE therapy.

Methods: We conducted a dual-center retrospective study of patients with cancer treated with TCEs between 2016 and 2024. The cumulative incidence of on-treatment CVEs (heart failure, arrhythmias, myocardial infarction, stroke) and cardiovascular mortality was evaluated using Fine-Gray competing-risks models incorporating time-dependent grade ≥2 cytokine-release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS). Factors associated with all-cause mortality were assessed using Cox models including CVEs as a time-dependent covariate.

Results: Among 567 patients (median age 67 years [Q1-Q3: 57-75]; 46.0% female), 25.9% had preexisting cardiovascular disease. The most common malignancies were multiple myeloma (40.9%) and acute lymphoblastic leukemia (35.6%). The restricted mean follow-up was 248 days (range: 0-973), during which 65 CVEs occurred (cumulative incidence 10.4%; 95% CI: 8.1-13.1), most commonly new left ventricular dysfunction (2.3%) and new-onset atrial fibrillation (2.1%). Cardiovascular mortality was rare (2 cases, 0.4%). Coronary artery disease was the only baseline variable independently associated with CVEs, whereas development of grade ≥2 CRS and/or ICANS was associated with a significant time-dependent increase in CVE risk. CVEs were significantly associated with higher all-cause mortality, independent of baseline clinical factors and TCE agent.

Conclusions: TCE therapy demonstrates a favorable cardiovascular safety profile overall, yet cardiovascular complications during therapy are associated with markedly increased mortality risk. Patients with preexisting coronary artery disease and those who develop high-grade CRS and/or ICANS represent high-risk groups that may benefit from intensified cardiovascular assessment and monitoring.

背景：尽管一些癌症免疫疗法与心血管风险增加有关，但关于t细胞接合剂（TCE）治疗相关心血管并发症的数据仍然有限。目的：本研究旨在描述TCE治疗期间心血管事件（CVEs）和死亡率的发生率和相关因素。方法：我们对2016年至2024年接受TCEs治疗的癌症患者进行了双中心回顾性研究。使用Fine-Gray竞争风险模型，结合时间依赖性≥2级细胞因子释放综合征（CRS）和/或免疫效应细胞相关神经毒性综合征（ICANS），评估治疗期间cve（心力衰竭、心律失常、心肌梗死、中风）和心血管死亡率的累积发生率。使用Cox模型评估与全因死亡率相关的因素，包括cve作为时间相关协变量。结果：567例患者（中位年龄67岁[Q1-Q3: 57-75]； 46.0%为女性）中，25.9%既往存在心血管疾病。最常见的恶性肿瘤是多发性骨髓瘤（40.9%）和急性淋巴细胞白血病（35.6%）。受限平均随访248天（范围：0 ~ 973天），期间发生65例cve（累计发生率10.4%;95% CI: 8.1 ~ 13.1），最常见的是新发左室功能障碍（2.3%）和新发房颤（2.1%）。心血管疾病死亡罕见（2例，0.4%）。冠状动脉疾病是唯一与CVE独立相关的基线变量，而≥2级CRS和/或ICANS的发展与CVE风险的显著时间依赖性增加相关。cve与较高的全因死亡率显著相关，独立于基线临床因素和TCE药物。结论：TCE治疗总体上显示出良好的心血管安全性，但治疗期间的心血管并发症与显著增加的死亡风险相关。既往存在冠状动脉疾病的患者和发生高级别CRS和/或ICANS的患者是可能从加强心血管评估和监测中获益的高危人群。

{"title":"Cardiovascular Adverse Events Associated With Bispecific T-Cell Engager Therapy.","authors":"Osnat Itzhaki Ben Zadok, Shai Shimony, Shannon Miller, David Stein, Shahrier Hossain, Giada Bianchi, Anju Nohria","doi":"10.1016/j.jaccao.2026.01.005","DOIUrl":"https://doi.org/10.1016/j.jaccao.2026.01.005","url":null,"abstract":"<p><strong>Background: </strong>Although some cancer immunotherapies have been linked to increased cardiovascular risk, data on T-cell engager (TCE) therapy-associated cardiovascular complications remain limited.</p><p><strong>Objectives: </strong>This study sought to characterize the incidence and factors associated with cardiovascular events (CVEs) and mortality during TCE therapy.</p><p><strong>Methods: </strong>We conducted a dual-center retrospective study of patients with cancer treated with TCEs between 2016 and 2024. The cumulative incidence of on-treatment CVEs (heart failure, arrhythmias, myocardial infarction, stroke) and cardiovascular mortality was evaluated using Fine-Gray competing-risks models incorporating time-dependent grade ≥2 cytokine-release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS). Factors associated with all-cause mortality were assessed using Cox models including CVEs as a time-dependent covariate.</p><p><strong>Results: </strong>Among 567 patients (median age 67 years [Q1-Q3: 57-75]; 46.0% female), 25.9% had preexisting cardiovascular disease. The most common malignancies were multiple myeloma (40.9%) and acute lymphoblastic leukemia (35.6%). The restricted mean follow-up was 248 days (range: 0-973), during which 65 CVEs occurred (cumulative incidence 10.4%; 95% CI: 8.1-13.1), most commonly new left ventricular dysfunction (2.3%) and new-onset atrial fibrillation (2.1%). Cardiovascular mortality was rare (2 cases, 0.4%). Coronary artery disease was the only baseline variable independently associated with CVEs, whereas development of grade ≥2 CRS and/or ICANS was associated with a significant time-dependent increase in CVE risk. CVEs were significantly associated with higher all-cause mortality, independent of baseline clinical factors and TCE agent.</p><p><strong>Conclusions: </strong>TCE therapy demonstrates a favorable cardiovascular safety profile overall, yet cardiovascular complications during therapy are associated with markedly increased mortality risk. Patients with preexisting coronary artery disease and those who develop high-grade CRS and/or ICANS represent high-risk groups that may benefit from intensified cardiovascular assessment and monitoring.</p>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147470007","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}

引用次数: 0

Carvedilol for Prevention of Chemotherapy-Induced Cardiotoxicity: Final Results of the CECCY Trial. 卡维地洛预防化疗引起的心脏毒性：CECCY试验的最终结果。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-25 DOI: 10.1016/j.jaccao.2025.12.009

Silvia Moreira Ayub-Ferreira, Mônica Samuel Avila, Mauro Rogerio de Barros Wanderley, Fatima das Dores Cruz, Sara Michelly Gonçalves Brandão, Vagner Oliveira Carvalho Rigaud, Cecilia Beatriz Bittencourt Viana Cruz, Guilherme Veiga Guimaraes, Marcio Sommer Bittencourt, Edimar Alcides Bocchi

引用次数: 0

Full Issue PDF 完整版PDF

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/S2666-0873(26)00027-X

引用次数: 0

Proactive Surveillance for ICI Cardiotoxicity ICI心脏毒性的主动监测：进展和下一个前沿。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2025.09.008

Artur Dziewierz MD, PhD , Łukasz Wiśniowski MD, PhD

引用次数: 0

Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers 甲状腺素V142I变异携带者的系统表现和死亡风险：一百万退伍军人项目分析。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2025.12.006

Konstantinos Sideris MD , Tyler J. Nelson BS , Lina Brinker MD , Anthony Gao BS , Catherine Tcheandjieu PhD, DVM , Christos P. Kyriakopoulos MD , Dan Berlowitz MD , Leland Hull MD, MPH , Jeffrey P. Ferraro PhD , Fatai Y. Agiri BS , Kathryn M. Pridgen MA , Steven Roblin PhD , Jacob Joseph MD , Scott M. Damrauer MD , Kyong-Mi Chang MD , Craig C. Teerlink PhD , Josef Stehlik MD, MPH , Spencer Carter MD , Julie A. Lynch PhD, RN, MBA

Background

The most common pathogenic transthyretin variant underlying variant transthyretin amyloidosis in the United States is c.424G>A, p.Val142Ile (V142I). In affected individuals, disease manifests predominantly as heart failure (HF) and cardiomyopathy (CM), with atrial fibrillation (AF) or atrial flutter (AFL), carpal tunnel syndrome (CTS), spinal stenosis (SS), and neuropathy also common.

Objectives

The aim of this study was to investigate the association of TTR V142I carrier status with these established outcomes.

Methods

A retrospective cohort study was conducted among individuals of African ancestry enrolled in the MVP (Million Veteran Program). Participants with at least 1 V142I allele were matched to control subjects on the basis of race, sex, and birth year. Outcomes included HF or CM, AF or AFL, CTS, SS, neuropathy, all-cause mortality, cardiovascular mortality, and HF-related hospitalization. Cumulative incidence and multivariable Cox proportional hazards regression models were used to compare V142I carriers with control subjects.

Results

The final study cohort included 2,658 V142I carriers and 13,459 matched control subjects. After multivariable adjustment, V142I carriers had significantly higher risks for HF or CM (HR: 1.20; 95% CI: 1.10-1.31), AF or AFL (HR: 1.26; 95% CI: 1.13-1.40), CTS (HR: 1.43; 95% CI: 1.30-1.57), SS (HR: 1.17; 95% CI: 1.07-1.28), and neuropathy (HR: 1.24; 95% CI: 1.13-1.36) compared with control subjects. A higher risk for HF or CM was observed among V142I carriers than matched control subjects with the following amyloidosis-related red-flag symptoms: AF or AFL (HR: 1.26; 95% CI: 1.03-1.52), CTS (HR: 1.40; 95% CI: 1.20-1.64), SS (HR: 1.26; 95% CI: 1.06-1.49), and neuropathy (HR: 1.28; 95% CI: 1.11-1.48). V142I carriers also had a significantly higher risk for all-cause mortality (HR: 1.12; 95% CI: 1.01-1.25), cardiovascular mortality (HR: 1.37; 95% CI: 1.14-1.65), and HF-related hospitalization (HR: 1.25; 95% CI: 1.07-1.45).

Conclusions

These findings highlight the systemic manifestations of variant transthyretin amyloidosis associated with the TTR V142I variant and underscore the need for increased awareness and earlier diagnostic efforts in high-risk populations.

背景：在美国最常见的致病性转甲状腺素变异是c.424G b> A, p.Val142Ile （V142I）。在受影响的个体中，疾病主要表现为心力衰竭（HF）和心肌病（CM），伴有心房颤动（AF）或心房颤振（AFL），腕管综合征（CTS），椎管狭窄（SS）和神经病变也很常见。目的：本研究的目的是调查TTR V142I携带者状态与这些既定结果的关系。方法：一项回顾性队列研究对参加MVP（百万退伍军人计划）的非洲裔个体进行了研究。至少有1个V142I等位基因的参与者根据种族、性别和出生年份与对照组进行匹配。结果包括HF或CM、AF或AFL、CTS、SS、神经病变、全因死亡率、心血管死亡率和HF相关住院。采用累积发生率和多变量Cox比例风险回归模型对V142I携带者与对照组进行比较。结果：最终的研究队列包括2658名V142I携带者和13459名匹配的对照受试者。多变量调整后，与对照组相比，V142I携带者发生HF或CM （HR: 1.20; 95% CI: 1.10-1.31）、AF或AFL （HR: 1.26; 95% CI: 1.13-1.40）、CTS （HR: 1.43; 95% CI: 1.30-1.57）、SS （HR: 1.17; 95% CI: 1.07-1.28）和神经病变（HR: 1.24; 95% CI: 1.13-1.36）的风险明显更高。V142I携带者发生HF或CM的风险高于具有以下淀粉样变相关危险症状的对照组：AF或AFL （HR: 1.26; 95% CI: 1.03-1.52）、CTS （HR: 1.40; 95% CI: 1.20-1.64）、SS （HR: 1.26; 95% CI: 1.06-1.49）和神经病变（HR: 1.28; 95% CI: 1.11-1.48）。V142I携带者的全因死亡率（HR: 1.12; 95% CI: 1.01-1.25）、心血管死亡率（HR: 1.37; 95% CI: 1.14-1.65）和hf相关住院（HR: 1.25; 95% CI: 1.07-1.45）的风险也显著较高。结论：这些发现强调了与TTR V142I变异相关的变异型转甲状腺蛋白淀粉样变的系统性表现，并强调了在高危人群中提高认识和早期诊断的必要性。

{"title":"Systemic Manifestations and Mortality Risk in Transthyretin V142I Variant Carriers","authors":"Konstantinos Sideris MD , Tyler J. Nelson BS , Lina Brinker MD , Anthony Gao BS , Catherine Tcheandjieu PhD, DVM , Christos P. Kyriakopoulos MD , Dan Berlowitz MD , Leland Hull MD, MPH , Jeffrey P. Ferraro PhD , Fatai Y. Agiri BS , Kathryn M. Pridgen MA , Steven Roblin PhD , Jacob Joseph MD , Scott M. Damrauer MD , Kyong-Mi Chang MD , Craig C. Teerlink PhD , Josef Stehlik MD, MPH , Spencer Carter MD , Julie A. Lynch PhD, RN, MBA","doi":"10.1016/j.jaccao.2025.12.006","DOIUrl":"10.1016/j.jaccao.2025.12.006","url":null,"abstract":"<div><h3>Background</h3><div>The most common pathogenic transthyretin variant underlying variant transthyretin amyloidosis in the United States is c.424G>A, p.Val142Ile (V142I). In affected individuals, disease manifests predominantly as heart failure (HF) and cardiomyopathy (CM), with atrial fibrillation (AF) or atrial flutter (AFL), carpal tunnel syndrome (CTS), spinal stenosis (SS), and neuropathy also common.</div></div><div><h3>Objectives</h3><div>The aim of this study was to investigate the association of <em>TTR</em> V142I carrier status with these established outcomes.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted among individuals of African ancestry enrolled in the MVP (Million Veteran Program). Participants with at least 1 V142I allele were matched to control subjects on the basis of race, sex, and birth year. Outcomes included HF or CM, AF or AFL, CTS, SS, neuropathy, all-cause mortality, cardiovascular mortality, and HF-related hospitalization. Cumulative incidence and multivariable Cox proportional hazards regression models were used to compare V142I carriers with control subjects.</div></div><div><h3>Results</h3><div>The final study cohort included 2,658 V142I carriers and 13,459 matched control subjects. After multivariable adjustment, V142I carriers had significantly higher risks for HF or CM (HR: 1.20; 95% CI: 1.10-1.31), AF or AFL (HR: 1.26; 95% CI: 1.13-1.40), CTS (HR: 1.43; 95% CI: 1.30-1.57), SS (HR: 1.17; 95% CI: 1.07-1.28), and neuropathy (HR: 1.24; 95% CI: 1.13-1.36) compared with control subjects. A higher risk for HF or CM was observed among V142I carriers than matched control subjects with the following amyloidosis-related red-flag symptoms: AF or AFL (HR: 1.26; 95% CI: 1.03-1.52), CTS (HR: 1.40; 95% CI: 1.20-1.64), SS (HR: 1.26; 95% CI: 1.06-1.49), and neuropathy (HR: 1.28; 95% CI: 1.11-1.48). V142I carriers also had a significantly higher risk for all-cause mortality (HR: 1.12; 95% CI: 1.01-1.25), cardiovascular mortality (HR: 1.37; 95% CI: 1.14-1.65), and HF-related hospitalization (HR: 1.25; 95% CI: 1.07-1.45).</div></div><div><h3>Conclusions</h3><div>These findings highlight the systemic manifestations of variant transthyretin amyloidosis associated with the <em>TTR</em> V142I variant and underscore the need for increased awareness and earlier diagnostic efforts in high-risk populations.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"8 1","pages":"Pages 31-44"},"PeriodicalIF":12.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221510","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}

引用次数: 0

Refining Free Light Chain Ratio in Systemic Amyloidosis 改善系统性淀粉样变性的游离轻链比率。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2025.09.007

Zhiwen Zhang MD, Quan Guo MD, Yang Gao MD, Muwei Li PhD, Cao Ma MD

引用次数: 0

CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity CRISPR/Cas9筛选提示RARA和SPNS1参与阿霉素心脏毒性

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2026.01.003

Chris McDermott-Roe PhD , Wenjian Lv PhD , Yeng Shao BSN , Atsushi Hoshino MD, PhD , Zoltan Arany MD, PhD , Kiran Musunuru MD, PhD

Background

Doxorubicin (DOX) causes cardiotoxicity and heart failure in a significant fraction of patients, but the molecular etiology is poorly understood.

Objectives

We adopted a functional genomics-based approach to probe the genetic basis for DOX-induced cardiotoxicity in an exhaustive and agnostic manner.

Methods

Genome-wide and targeted CRISPR/Cas9 screens were performed in immortalized cardiomyocytes and induced pluripotent stem cell–derived cardiomyocytes to identify genetic modifiers of DOX-induced cardiotoxicity.

Results

Our first screen revealed that loss of the Retinoic Acid Receptor Alpha gene (RARA) increased DOX-induced cell death. Conversely, pharmacological activation of RARA protein with tamibarotene reduced DOX-induced toxicity. RNA-Seq analysis showed that whereas DOX broadly suppressed expression of metabolic and mitochondrial genes, tamibarotene mitigated this effect. In a second screen, we interrogated processes involved in DOX uptake, transport, and efflux. Loss of lysosome homeostasis, exemplified by SPNS lysolipid transporter 1 (SPNS1) deficiency, led to DOX hyperaccumulation, suppression of autophagy, increased DNA damage, and increased cell death. In contrast, ribosome loss-of-function and nutrient deprivation significantly reduced DOX accumulation and toxicity.

Conclusions

Our study identified numerous drug–gene interactions that illuminate mechanisms underlying DOX-induced cardiotoxicity and provide a technical framework for future functional genomics screens to nominate therapeutic targets and genetic biomarkers.

背景：阿霉素（DOX）在很大一部分患者中引起心脏毒性和心力衰竭，但其分子病因尚不清楚。目的：我们采用基于功能基因组学的方法，以详尽和不可知的方式探索dox诱导心脏毒性的遗传基础。方法：对永生化心肌细胞和诱导多能干细胞衍生的心肌细胞进行全基因组和靶向CRISPR/Cas9筛选，鉴定dox诱导心脏毒性的遗传修饰因子。结果：我们的第一次筛选显示，视黄酸受体α基因（RARA）的缺失增加了dox诱导的细胞死亡。相反，用他米巴罗汀激活RARA蛋白可以减少dox诱导的毒性。RNA-Seq分析显示，DOX广泛抑制代谢和线粒体基因的表达，而tamibarotene则减轻了这种作用。在第二个筛选中，我们询问了涉及DOX摄取、运输和外排的过程。溶酶体体内平衡的丧失，如SPNS溶脂转运蛋白1 （SPNS1）缺乏，导致DOX过度积累、自噬抑制、DNA损伤增加和细胞死亡增加。相反，核糖体功能丧失和营养剥夺显著降低DOX积累和毒性。结论：我们的研究确定了许多药物-基因相互作用，阐明了dox诱导心脏毒性的机制，并为未来的功能基因组筛选提供了技术框架，以指定治疗靶点和遗传生物标志物。

{"title":"CRISPR/Cas9 Screens Implicate RARA and SPNS1 in Doxorubicin Cardiotoxicity","authors":"Chris McDermott-Roe PhD , Wenjian Lv PhD , Yeng Shao BSN , Atsushi Hoshino MD, PhD , Zoltan Arany MD, PhD , Kiran Musunuru MD, PhD","doi":"10.1016/j.jaccao.2026.01.003","DOIUrl":"10.1016/j.jaccao.2026.01.003","url":null,"abstract":"<div><h3>Background</h3><div>Doxorubicin (DOX) causes cardiotoxicity and heart failure in a significant fraction of patients, but the molecular etiology is poorly understood.</div></div><div><h3>Objectives</h3><div>We adopted a functional genomics-based approach to probe the genetic basis for DOX-induced cardiotoxicity in an exhaustive and agnostic manner.</div></div><div><h3>Methods</h3><div>Genome-wide and targeted CRISPR/Cas9 screens were performed in immortalized cardiomyocytes and induced pluripotent stem cell–derived cardiomyocytes to identify genetic modifiers of DOX-induced cardiotoxicity.</div></div><div><h3>Results</h3><div>Our first screen revealed that loss of the Retinoic Acid Receptor Alpha gene (<em>RARA</em>) increased DOX-induced cell death. Conversely, pharmacological activation of RARA protein with tamibarotene reduced DOX-induced toxicity. RNA-Seq analysis showed that whereas DOX broadly suppressed expression of metabolic and mitochondrial genes, tamibarotene mitigated this effect. In a second screen, we interrogated processes involved in DOX uptake, transport, and efflux. Loss of lysosome homeostasis, exemplified by SPNS lysolipid transporter 1 (<em>SPNS1</em>) deficiency, led to DOX hyperaccumulation, suppression of autophagy, increased DNA damage, and increased cell death. In contrast, ribosome loss-of-function and nutrient deprivation significantly reduced DOX accumulation and toxicity.</div></div><div><h3>Conclusions</h3><div>Our study identified numerous drug–gene interactions that illuminate mechanisms underlying DOX-induced cardiotoxicity and provide a technical framework for future functional genomics screens to nominate therapeutic targets and genetic biomarkers.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"8 1","pages":"Pages 48-61"},"PeriodicalIF":12.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221281","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}

引用次数: 0

Atrial Fibrillation After Stem Cell Transplantation 干细胞移植后心房颤动：系统性易感性的前哨。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2026.01.002

Salim S. Hayek MD , Mary Riwes DO

引用次数: 0

Refining the Role of Epigenetic Age Acceleration in Cardiotoxicity Research 细化表观遗传年龄加速在心脏毒性研究中的作用。

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2025.09.006

Junzhi Cao MD, Wenjie Han MD, Yuan Liu MD

引用次数: 0

Polygenic Risk for Cardiometabolic and Cardiovascular Disease in a Multiethnic Cohort of Breast Cancer Survivors 乳腺癌幸存者多种族队列中心脏代谢和心血管疾病的多基因风险

IF 12.8 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Jacc: Cardiooncology

Pub Date : 2026-02-01 Epub Date: 2026-02-17 DOI: 10.1016/j.jaccao.2025.10.004

Peter N. Fiorica BA , Alexa Zimbalist MS , Haiyang Sheng PhD , Cecile A. Laurent MS , Janise M. Roh MSW, MPH , Valerie S. Lee MHS , Isaac J. Ergas PhD , Jennifer Delmerico MPH , Qianqian Zhu PhD , Richard K. Cheng MD, MSc , Eileen Rillamas-Sun MPH, PhD , Carlos Iribarren MD, MPH, PhD , Jamal S. Rana MD, PhD , Mai Nguyen-Huynh MD, MAS , Dawn L. Hershman MD, MS , Christine B. Ambrosone PhD , Lawrence H. Kushi ScD , Heather Greenlee MPH, ND, PhD , Marilyn L. Kwan PhD , Song Yao MD, PhD

Background

Because of cancer treatment–related cardiotoxicities, women with histories of breast cancer are at increased risk for cardiovascular disease (CVD). Many polygenic scores (PGS) have been developed for predicting risk for CVD-related conditions in the general population, but their performance in breast cancer patients remains largely unexplored.

Objectives

The aim of this study was to examine the performance of PGS for CVD-related traits to predict incident cardiometabolic disorder (CMD) and CVD in women with histories of breast cancer.

Methods

In a prospective multiethnic cohort of 3,620 breast cancer survivors, 27 PGS for CVD-related traits were we computed, and their associations with 12 incident CMD and CVD events were examined. The performance of these PGS was compared relative to clinical covariates–only models and by cardiotoxic cancer treatment.

Results

Twenty-three significant associations were identified after Bonferroni correction between PGS and CMD or CVD events in breast cancer patients. Although the model performance of PGS and multi-PGS added to or combined with clinical models for CMD and CVD risk prediction was numerically greater, these were not statistically significant. For some outcomes, PGS performed worse among patients who received cardiotoxic cancer treatments.

Conclusions

Although there may be potential value of PGS in predicting the risk for CMD and CVD events in women with histories of breast cancer, current PGS performance is limited. This work highlights the need to develop de novo PGS in breast cancer patients and to include ancestrally diverse patient populations.

背景：由于癌症治疗相关的心脏毒性，有乳腺癌病史的女性患心血管疾病（CVD）的风险增加。许多多基因评分（PGS）已被开发用于预测普通人群心血管疾病相关疾病的风险，但其在乳腺癌患者中的表现仍未得到充分研究。目的：本研究的目的是检查PGS对CVD相关特征的表现，以预测有乳腺癌病史的女性心血管代谢障碍（CMD）和CVD的发生。方法：在一个包含3620名乳腺癌幸存者的前瞻性多种族队列中，我们计算了27个CVD相关特征的PGS，并检查了它们与12例CMD和CVD事件的关联。这些PGS的性能相对于临床仅协变量模型和心脏毒性癌症治疗进行了比较。结果：经Bonferroni校正后，在乳腺癌患者的PGS和CMD或CVD事件之间发现了23个显著关联。虽然PGS和多PGS加入或结合临床模型预测CMD和CVD风险的模型性能在数值上更大，但这些没有统计学意义。对于某些结果，PGS在接受心脏毒性癌症治疗的患者中表现更差。结论：尽管PGS在预测有乳腺癌病史的女性发生CMD和CVD事件的风险方面可能具有潜在价值，但目前PGS的表现有限。这项工作强调需要在乳腺癌患者中开发新的PGS，并包括不同祖先的患者群体。

{"title":"Polygenic Risk for Cardiometabolic and Cardiovascular Disease in a Multiethnic Cohort of Breast Cancer Survivors","authors":"Peter N. Fiorica BA , Alexa Zimbalist MS , Haiyang Sheng PhD , Cecile A. Laurent MS , Janise M. Roh MSW, MPH , Valerie S. Lee MHS , Isaac J. Ergas PhD , Jennifer Delmerico MPH , Qianqian Zhu PhD , Richard K. Cheng MD, MSc , Eileen Rillamas-Sun MPH, PhD , Carlos Iribarren MD, MPH, PhD , Jamal S. Rana MD, PhD , Mai Nguyen-Huynh MD, MAS , Dawn L. Hershman MD, MS , Christine B. Ambrosone PhD , Lawrence H. Kushi ScD , Heather Greenlee MPH, ND, PhD , Marilyn L. Kwan PhD , Song Yao MD, PhD","doi":"10.1016/j.jaccao.2025.10.004","DOIUrl":"10.1016/j.jaccao.2025.10.004","url":null,"abstract":"<div><h3>Background</h3><div>Because of cancer treatment–related cardiotoxicities, women with histories of breast cancer are at increased risk for cardiovascular disease (CVD). Many polygenic scores (PGS) have been developed for predicting risk for CVD-related conditions in the general population, but their performance in breast cancer patients remains largely unexplored.</div></div><div><h3>Objectives</h3><div>The aim of this study was to examine the performance of PGS for CVD-related traits to predict incident cardiometabolic disorder (CMD) and CVD in women with histories of breast cancer.</div></div><div><h3>Methods</h3><div>In a prospective multiethnic cohort of 3,620 breast cancer survivors, 27 PGS for CVD-related traits were we computed, and their associations with 12 incident CMD and CVD events were examined. The performance of these PGS was compared relative to clinical covariates–only models and by cardiotoxic cancer treatment.</div></div><div><h3>Results</h3><div>Twenty-three significant associations were identified after Bonferroni correction between PGS and CMD or CVD events in breast cancer patients. Although the model performance of PGS and multi-PGS added to or combined with clinical models for CMD and CVD risk prediction was numerically greater, these were not statistically significant. For some outcomes, PGS performed worse among patients who received cardiotoxic cancer treatments.</div></div><div><h3>Conclusions</h3><div>Although there may be potential value of PGS in predicting the risk for CMD and CVD events in women with histories of breast cancer, current PGS performance is limited. This work highlights the need to develop de novo PGS in breast cancer patients and to include ancestrally diverse patient populations.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"8 1","pages":"Pages 65-76"},"PeriodicalIF":12.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146221270","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}

引用次数: 0

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Jacc: Cardiooncology

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀