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Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma 预防乳腺癌和淋巴癌患者的心脏损伤
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1016/j.jaccao.2024.07.010
David Austin MBChB, MD , Rebecca H. Maier MSc , Nasima Akhter PhD , Mohammad Sayari MSc , Emmanuel Ogundimu PhD , Jamie M. Maddox MBChB , Sharareh Vahabi MBChB, MD , Alison C. Humphreys MBBcH, MD , Janine Graham MBChB , Helen Oxenham MBChB, MD , Sophie Haney MBBS , Nicola Cresti MD, PhD , Mark Verrill MB, BChir , Wendy Osborne MBBS , Kathryn L. Wright MBChB , Rebecca Goranova MBBS , James R. Bailey MBBS, PhD , Nagesh Kalakonda MBBS, PhD , Mac Macheta MBChB , Mari F. Kilner MBChB , Chris Plummer BM, BCh, PhD

Background

Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.

Objectives

The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.

Methods

This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m2 doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.

Results

Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.

Conclusions

Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574)
背景心脏毒性是接受蒽环类化疗的癌症幸存者所担心的问题。依那普利被认为具有减轻癌症患者心脏毒性的潜力。目的 PROACT(预防乳腺癌和淋巴瘤患者心脏损伤)临床试验评估了依那普利在预防乳腺癌或非霍奇金淋巴瘤高剂量蒽环类化疗患者心脏毒性(表现为心肌损伤和心功能损害)方面的效果。方法这项前瞻性、多中心、开放标签、随机对照试验采用了观察者盲法终点的优效设计。共有 111 名参与者计划接受 6 个周期的化疗,计划剂量≥300 毫克/平方米多柔比星当量,他们被随机分配接受依那普利(滴定至每天 20 毫克)或不含依那普利的标准治疗。结果 在化疗期间和化疗后1个月,依那普利组54名患者中有42名(77.8%)观察到心肌损伤,而标准治疗组54名患者中有45名(83.3%)观察到心肌损伤(OR:0.65;95% CI:0.23-1.78)。在服用依那普利的 53 名患者中,有 25 人(47.2%)通过心肌肌钙蛋白 I(26.2 ng/L)检测到损伤,而在服用标准疗法的 53 名患者中,有 24 人(45.3%)通过心肌肌钙蛋白 I 检测到损伤(OR:1.10;95% CI:0.50-2.38)。在使用依那普利的 47 名患者中,有 10 人(21.3%)的左室整体纵向应变较基线相对下降超过 15%,而在使用标准护理的 41 名患者中,有 9 人(21.9%)的左室整体纵向应变较基线相对下降超过 15%(OR:0.95;95% CI:0.33-2.74)。服用依那普利的 49 例患者中,有 2 例(4.1%)患者的左心室射血分数绝对值下降了 10%至 50%,而接受标准护理的患者中没有出现这种情况。结论在化疗期间的标准护理中加入依那普利并不能预防接受高剂量蒽环类化疗患者的心脏毒性。(PROACT:我们能预防乳腺癌和淋巴瘤患者化疗相关的心脏损伤吗?)
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引用次数: 0
Multicohort Epigenome-Wide Association Study of All-Cause Cardiovascular Disease and Cancer Incidence 全因心血管疾病和癌症发病率的多队列表观基因组关联研究
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1016/j.jaccao.2024.07.014
Arce Domingo-Relloso PhD , Angela L. Riffo-Campos PhD , Naisi Zhao DrPH , Guillermo Ayala PhD , Karin Haack PhD , Carlos Manterola MD, PhD , Dorothy A. Rhoades MD, MPH , Jason G. Umans MD, PhD , M Daniele Fallin PhD , Miguel Herreros-Martinez MS , Marina Pollan MD, PhD , Eric Boerwinkle PhD , Elizabeth A. Platz ScD, MPH , Miranda R. Jones PhD , Jan Bressler PhD , Roby Joehanes PhD , Calen P. Ryan PhD , Juan R. Gonzalez PhD , Daniel Levy MD , Daniel W. Belsky PhD , Maria Tellez-Plaza MD, PhD

Background

Emerging evidence reveals a complex relationship between cardiovascular disease (CVD) and cancer, which share common risk factors and biological pathways.

Objectives

The aim of this study was to evaluate common epigenetic signatures for CVD and cancer incidence in 3 ethnically diverse cohorts: Native Americans from the SHS (Strong Heart Study), European Americans from the FHS (Framingham Heart Study), and European Americans and African Americans from the ARIC (Atherosclerosis Risk In Communities) study.

Methods

A 2-stage strategy was used that included first conducting untargeted epigenome-wide association studies for each cohort and then running targeted models in the union set of identified differentially methylated positions (DMPs). We also explored potential molecular pathways by conducting a bioinformatics analysis.

Results

Common DMPs were identified across all populations. In a subsequent meta-analysis, 3 and 1 of those DMPs were statistically significant for CVD only and both cancer and CVD, respectively. No meta-analyzed DMPs were statistically significant for cancer only. The enrichment analysis pointed to interconnected biological pathways involved in cancer and CVD. In the DrugBank database, elements related to 1-carbon metabolism and cancer and CVD medications were identified as potential drugs for target gene products. In an additional analysis restricted to the 950 SHS participants who developed incident CVD, the C index for incident cancer increased from 0.618 (95% CI: 0.570-0.672) to 0.971 (95% CI: 0.963-0.978) when adjusting the models for the combined cancer and CVD DMPs identified in the other cohorts.

Conclusions

These results point to molecular pathways and potential treatments for precision prevention of CVD and cancer. Screening based on common epigenetic signatures of incident CVD and cancer may help identify patients with newly diagnosed CVD at increased cancer risk.
背景越来越多的证据揭示了心血管疾病(CVD)和癌症之间的复杂关系,它们有着共同的风险因素和生物学途径:方法采用两阶段策略,包括首先对每个队列进行非靶向的全表观基因组关联研究,然后在已识别的差异甲基化位置(DMPs)联合集中运行靶向模型。我们还通过生物信息学分析探索了潜在的分子通路。在随后的荟萃分析中,分别有 3 个和 1 个 DMPs 仅对心血管疾病和癌症与心血管疾病有统计学意义。没有任何荟萃分析的 DMPs 只对癌症有统计学意义。富集分析表明,癌症和心血管疾病涉及相互关联的生物通路。在 DrugBank 数据库中,与 1 碳代谢以及癌症和心血管疾病药物有关的元素被确定为目标基因产品的潜在药物。在一项仅限于发生心血管疾病的 950 名 SHS 参与者的额外分析中,当根据其他队列中发现的癌症和心血管疾病联合 DMPs 调整模型时,发生癌症的 C 指数从 0.618(95% CI:0.570-0.672)上升到 0.971(95% CI:0.963-0.978)。根据心血管疾病和癌症发病的共同表观遗传特征进行筛查可能有助于识别癌症风险增加的新诊断心血管疾病患者。
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引用次数: 0
Autonomic Dysfunction Among Adult Survivors of Childhood Cancer in the St. Jude Lifetime Cohort Study 圣裘德终生队列研究中儿童癌症成年幸存者的自主神经功能障碍
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1016/j.jaccao.2024.08.005
John D. Groarke MBBCh, MPH , Kirsten K. Ness PT, PhD , Rikeenkumar Dhaduk , Juan C. Plana MD , Jean Bernard Durand MD , Russell V. Luepker MD, MS , Vijaya M. Joshi MD , Matthew Ehrhardt MD , Daniel A. Mulrooney MD , Stephanie B. Dixon MD , Anju Nohria MD , Daniel M. Green MD , Rebecca M. Howell PhD , Deo Kumar Srivastava PhD , John L. Jefferies MD, MPH , Leslie L. Robison PhD , Melissa M. Hudson MD , Gregory T. Armstrong MD, MSCE

Background

The burden and functional significance of autonomic dysfunction among survivors of childhood cancer is unknown.

Objectives

We evaluated the prevalence, risk factors, and functional relevance of autonomic dysfunction in survivors.

Methods

We conducted a cross-sectional prospective evaluation of 1,041 adult survivors of childhood cancer treated with anthracyclines (31.1%), chest-directed radiation (13.5%), both (19.5%), or neither (35.9%), and 286 community control subjects enrolled in the SJLIFE (St Jude Lifetime Cohort Study). Four measures of autonomic dysfunction were evaluated: elevated resting heart rate, decreased heart rate reserve, decreased systolic blood pressure response to exercise, and delayed heart rate recovery. Logistic regression tested associations with impaired cardiorespiratory fitness (peak Vo2 < 80% predicted).

Results

Survivors (50.7% female) were 9.0 ± 5.8 years at cancer diagnosis and 35.5 ± 8.9 years at evaluation. Prevalence (survivors vs control subjects) of elevated resting heart rate (17.9% vs 7.0%), decreased heart rate reserve (21.7% vs 9.1%), decreased systolic blood pressure response to exercise (25.3% vs 12.6%), and delayed heart rate recovery (24.3% vs 10.6%) was more than 2-fold higher among survivors (P < 0.001 for all). Carboplatin (adjusted OR: 2.50; 95% CI: 1.42-4.40; P = 0.001), chest-directed radiation therapy (adjusted OR: 2.06; 95% CI: 1.52-2.75; P < 0.001), and cranial radiation (adjusted OR: 1.49; 95% CI: 1.08-2.05; P = 0.015) were associated with an increased likelihood of having ≥2 measures of autonomic dysfunction. Survivors with ≥2 measures of autonomic dysfunction were at increased risk for impaired cardiorespiratory fitness (adjusted OR: 2.71; 95% CI: 1.82-4.02; P < 0.001).

Conclusions

Survivors of childhood cancer manifest a higher prevalence of autonomic dysfunction associated with impaired cardiorespiratory fitness.
背景儿童癌症幸存者自主神经功能障碍的负担和功能意义尚不清楚。目的我们评估了幸存者自主神经功能障碍的患病率、风险因素和功能意义。方法我们对 1,041 名接受过蒽环类药物治疗(31.1%)、胸部放射治疗(13.5%)、两种治疗均接受(19.5%)或两种治疗均未接受(35.9%)的儿童癌症成年幸存者,以及加入 SJLIFE(圣裘德终生队列研究)的 286 名社区对照受试者进行了横断面前瞻性评估。研究人员评估了自律神经功能失调的四项指标:静息心率升高、心率储备下降、收缩压对运动的反应减弱以及心率恢复延迟。结果幸存者(50.7% 为女性)确诊癌症时的年龄为 9.0 ± 5.8 岁,评估时的年龄为 35.5 ± 8.9 岁。幸存者与对照组相比,静息心率升高(17.9% 对 7.0%)、心率储备降低(21.7% 对 9.1%)、收缩压对运动的反应降低(25.3% 对 12.6%)和心率恢复延迟(24.3% 对 10.6%)的发生率高出 2 倍多(P 均为 0.001)。卡铂(调整后 OR:2.50;95% CI:1.42-4.40;P = 0.001)、胸部定向放疗(调整后 OR:2.06;95% CI:1.52-2.75;P <;0.001)和颅脑放疗(调整后 OR:1.49;95% CI:1.08-2.05;P = 0.015)与自主神经功能障碍≥2 项指标的可能性增加有关。结论儿童癌症幸存者出现与心肺功能受损相关的自主神经功能障碍的几率较高。
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引用次数: 0
Genomics for Improving Heart Failure Risk Assessment in Cancer Patients 基因组学用于改进癌症患者心衰风险评估
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1016/j.jaccao.2024.06.001
Sonia Shah PhD
{"title":"Genomics for Improving Heart Failure Risk Assessment in Cancer Patients","authors":"Sonia Shah PhD","doi":"10.1016/j.jaccao.2024.06.001","DOIUrl":"10.1016/j.jaccao.2024.06.001","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 5","pages":"Pages 728-730"},"PeriodicalIF":12.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142437698","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}
引用次数: 0
Cardiac Dysfunction in Children and Young Adults Treated With MEK Inhibitors 接受 MEK 抑制剂治疗的儿童和青少年的心功能障碍
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-10-01 DOI: 10.1016/j.jaccao.2024.07.004
Jonathan D. Bender MD, MS , Natasha Pillay-Smiley DO , Garick D. Hill MD, MS , Peter de Blank MD, MSCE , Trent R. Hummel MD , Brian D. Weiss MD , Ashish Kumar MD, PhD , Huaiyu Zang PhD , Nicholas J. Ollberding PhD , Thomas D. Ryan MD, PhD
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引用次数: 0
Cancer Therapy and Exercise Intolerance: The Heart Is But a Part 癌症治疗与运动不耐受:心脏只是一部分
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-08-01 DOI: 10.1016/j.jaccao.2024.04.006

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond the heart. The authors provide a framework using the oxygen pathway to understand the impact of cancer treatment on peak oxygen uptake, a marker of integrative cardiopulmonary function and CVD risk. Peripheral toxicities and the impact on oxygen transport are discussed. Consideration for the broad effects of cancer therapies will improve the prediction and identification of cancer survivors at risk for CVD, functional disability, and premature mortality and those who would benefit from therapeutic intervention, ultimately improving patient outcomes.

癌症疗法不断发展,成功改善了许多癌症患者的生存状况并减少了疾病进展。癌症治疗效果的改善也暴露出一些相互竞争的合并症,其中一些可能会因癌症疗法而恶化。许多早期癌症患者致残和致死的主要原因是心血管疾病(CVD),这通常归因于癌症治疗对心脏的直接或间接损伤。在这篇综述中,作者提出,与传统和新型癌症疗法相关的毒性应考虑到心脏以外的因素。作者利用氧途径提供了一个框架,以了解癌症治疗对摄氧量峰值的影响,摄氧量峰值是综合心肺功能和心血管疾病风险的标志。作者还讨论了外周毒性及其对氧运输的影响。考虑到癌症疗法的广泛影响,将能更好地预测和识别有心血管疾病、功能障碍和过早死亡风险的癌症幸存者,以及那些将从治疗干预中获益的人,最终改善患者的预后。
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引用次数: 0
Echocardiography-Guided Radiofrequency Ablation for Cardiac Tumors 超声心动图引导下的心脏肿瘤射频消融术
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-08-01 DOI: 10.1016/j.jaccao.2024.03.008
Junzhe Huang MS , Changhui Lei MBBS , David H. Hsi MD , Minjuan Zheng MD, PhD , Hui Ma MBBS , Shengjun Ta MBBS , Rui Hu MS , Chao Han MD, PhD , Wenxia Li MBBS , Jing Li MBBS , Dong Qu MBBS , Fangqi Ruan PhD , Jing Wang MD, PhD , Bo Wang MBBS , Xueli Zhao MBBS , Jiao Liu PhD , Lina Zhao MD, PhD , Zhe Wang MD, PhD , Jian Yang MD, PhD , Liwen Liu MD, PhD

Background

Patients with cardiac tumors may present challenges for surgical resection due to poor clinical condition. Echocardiography-guided transapical radiofrequency ablation for cardiac tumors (TARFACT) potentially offers a less invasive palliative therapy option.

Objectives

This study aimed to evaluate the safety and efficacy of TARFACT.

Methods

Five patients with cardiac tumors (mucinous liposarcoma, myocardial hypertrophy with inflammatory cell infiltration mass, fibrous tissue tumor hyperplasia, myocardial clear cell sarcoma, and cardiac rhabdomyoma) were included. All patients underwent TARFACT and were assessed with electrocardiogram, echocardiographic imaging, biochemical analysis, and pathological confirmation.

Results

The median follow-up for all patients was 9 (range 4-12) months. Three surviving patients were alive at their last follow-up (9, 12, and 12 months, respectively), whereas 2 patients with late-stage tumors survived 6 months and 13 months after TARFACT, respectively. After TARFACT, all patients showed significant reductions in tumor size: the mean length decreased from 6.7 ± 2.0 cm to 4.7 ± 1.8 cm (P = 0.007); and the mean width decreased from 5.0 ± 2.1 cm to 2.5 ± 0.7 cm (P = 0.041). NYHA functional class also improved: median (IQR) decreased from 3.0 (1.5) to 2.0 (1.0) (P = 0.038), Peak E-wave on echocardiography showed a mean increase from 64.4 ± 15.7 cm/s to 76.6 ± 18.6 cm/s (P = 0.008), and NT-pro BNP levels had a median (IQR) reduction from 115.7 (252.1) pg/mL to 55.0 (121.6) pg/mL (P = 0.043).

Conclusions

TARFACT is a novel palliative treatment option for cardiac tumors, reducing accessible tumors and improving clinical symptoms in a preliminary group of patients. (Cardiac Tumors Interventional [Radio Frequency/Laser Ablation] Therapy [CTIH]; NCT02815553)

背景心脏肿瘤患者由于临床状况不佳,手术切除可能面临挑战。本研究旨在评估 TARFACT 的安全性和有效性。方法纳入五例心脏肿瘤患者(粘液性脂肪肉瘤、心肌肥大伴炎性细胞浸润肿块、纤维组织瘤增生、心肌透明细胞肉瘤和心脏横纹肌瘤)。结果所有患者的中位随访时间为 9 个月(4-12 个月)。三名存活患者在最后一次随访时(分别为 9 个月、12 个月和 12 个月)仍然存活,两名晚期肿瘤患者分别在 TARFACT 术后 6 个月和 13 个月存活。TARFACT 术后,所有患者的肿瘤大小均显著缩小:平均长度从 6.7 ± 2.0 厘米降至 4.7 ± 1.8 厘米(P = 0.007);平均宽度从 5.0 ± 2.1 厘米降至 2.5 ± 0.7 厘米(P = 0.041)。NYHA 功能分级也有所改善:中位数(IQR)从 3.0 (1.5) 降至 2.0 (1.0) (P = 0.038),超声心动图显示的峰值 E 波平均速度从 64.4 ± 15.7 cm/s 升至 76.6 ± 18.6 cm/s (P = 0.008),NT-pro BNP 水平的中位数(IQR)从 115.结论TARFACT是一种新型的心脏肿瘤姑息治疗方案,可减少可触及的肿瘤,并初步改善一组患者的临床症状。(心脏肿瘤介入[射频/激光消融]疗法[CTIH];NCT02815553)
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引用次数: 0
Deep Inspiration Breath Hold for Cardiac Sparing 深吸气屏气,以达到心脏疏导的目的
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-08-01 DOI: 10.1016/j.jaccao.2024.06.003
Fleure Gallant MDCM , Reshma Jagsi MD, DPhil
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引用次数: 0
Association of Cardiac Substructure Radiation Dose With Arrhythmia 心脏亚结构辐射剂量与心律失常的关系
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-08-01 DOI: 10.1016/j.jaccao.2024.07.007
Gerard Walls MB, BCH, PhD , Alan McWilliam PhD
{"title":"Association of Cardiac Substructure Radiation Dose With Arrhythmia","authors":"Gerard Walls MB, BCH, PhD ,&nbsp;Alan McWilliam PhD","doi":"10.1016/j.jaccao.2024.07.007","DOIUrl":"10.1016/j.jaccao.2024.07.007","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"6 4","pages":"Pages 557-559"},"PeriodicalIF":12.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266608732400228X/pdfft?md5=729fcb153664ea069b35258ac41dc29e&pid=1-s2.0-S266608732400228X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142011401","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}
引用次数: 0
Probing the Anthracycline-Induced Myocardial Injury 探究蒽环类药物诱发的心肌损伤
IF 12 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Pub Date : 2024-08-01 DOI: 10.1016/j.jaccao.2024.04.008
Claudius Statescu MD, Manel El Blidi-Rahmani MD
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引用次数: 0
期刊
Jacc: Cardiooncology
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