Pub Date : 2024-12-19DOI: 10.1186/s40959-024-00285-3
Michael H Udin, Sunitha Shyam Sunder, Sarmila Nepali, Sharma Kattel, Amr Abdelradi, Scott T Doyle, Ciprian N Ionita, Qian Liu, Umesh C Sharma, Saraswati Pokharel
Background: Cancer patients are known to be associated with increased risk of cardiovascular disease. However, no studies have examined the differential impact of hematologic malignancies (HMs) and solid tumors (STs) on cardiac morphology at the tissue level.
Objective: We aimed to examine histopathological features alongside cardiovascular biomarkers in patients with HMs and STs who underwent post-mortem evaluation.
Methods: We analyzed cardiac changes in 198 patients with HMs and 164 patients with solid tumors STs. We compared demographics, echocardiogram data, exposure to various antineoplastic agents, and post-mortem findings. Additionally, cardiac histological validation was conducted on post-mortem cardiac specimens to examine cardiac tissue morphology, focusing on cardiomyocyte nuclear density, collagen content, and collagen fiber orientation.
Results: HM patients displayed significantly disordered collagen fiber alignment (0.71 vs 0.83, P = 0.027), and reduced cardiomyocyte nuclear density (56 vs 72, P = 0.002) compared to ST patients. Similarly, hemoglobin level was decreased (6.71 vs 8.06, P < 0.001) in HM patients compared to ST patients. HM patients also showed elevated B-type natriuretic peptide levels (2,275 vs 867, P < 0.001), without significant differences in creatine-kinase MB and cardiac troponin levels. Multivariate analysis identified increased right ventricular thickness, low diastolic blood pressure, and high cardiac troponin levels as risk factors for cardiac death in HM patients.
Conclusions: This study demonstrates that HM patients have fewer cardiomyocyte nuclei and poorly aligned collagen, with serum biomarker evidence of increased cardiac dysfunction. This supports the necessity for specialized cardiac care for these patients.
背景:已知癌症患者与心血管疾病的风险增加有关。然而,没有研究在组织水平上检查血液恶性肿瘤(HMs)和实体肿瘤(STs)对心脏形态的不同影响。目的:我们的目的是检查HMs和STs患者死后评估的组织病理学特征和心血管生物标志物。方法:我们分析了198例HMs患者和164例实体瘤性STs患者的心脏变化。我们比较了人口统计学、超声心动图数据、暴露于各种抗肿瘤药物和死后发现。此外,对死后心脏标本进行心脏组织学验证,以检查心脏组织形态学,重点关注心肌细胞核密度、胶原含量和胶原纤维取向。结果:与ST患者相比,HM患者表现出明显的胶原纤维排列紊乱(0.71 vs 0.83, P = 0.027),心肌细胞核密度降低(56 vs 72, P = 0.002)。同样,血红蛋白水平降低(6.71 vs 8.06, P)。结论:本研究表明HM患者心肌细胞核减少,胶原排列不良,血清生物标志物表明心功能障碍增加。这支持了对这些患者进行专门心脏护理的必要性。
{"title":"Differential cardiac impacts of hematological malignancies and solid tumors: a histopathological and biomarker study.","authors":"Michael H Udin, Sunitha Shyam Sunder, Sarmila Nepali, Sharma Kattel, Amr Abdelradi, Scott T Doyle, Ciprian N Ionita, Qian Liu, Umesh C Sharma, Saraswati Pokharel","doi":"10.1186/s40959-024-00285-3","DOIUrl":"10.1186/s40959-024-00285-3","url":null,"abstract":"<p><strong>Background: </strong>Cancer patients are known to be associated with increased risk of cardiovascular disease. However, no studies have examined the differential impact of hematologic malignancies (HMs) and solid tumors (STs) on cardiac morphology at the tissue level.</p><p><strong>Objective: </strong>We aimed to examine histopathological features alongside cardiovascular biomarkers in patients with HMs and STs who underwent post-mortem evaluation.</p><p><strong>Methods: </strong>We analyzed cardiac changes in 198 patients with HMs and 164 patients with solid tumors STs. We compared demographics, echocardiogram data, exposure to various antineoplastic agents, and post-mortem findings. Additionally, cardiac histological validation was conducted on post-mortem cardiac specimens to examine cardiac tissue morphology, focusing on cardiomyocyte nuclear density, collagen content, and collagen fiber orientation.</p><p><strong>Results: </strong>HM patients displayed significantly disordered collagen fiber alignment (0.71 vs 0.83, P = 0.027), and reduced cardiomyocyte nuclear density (56 vs 72, P = 0.002) compared to ST patients. Similarly, hemoglobin level was decreased (6.71 vs 8.06, P < 0.001) in HM patients compared to ST patients. HM patients also showed elevated B-type natriuretic peptide levels (2,275 vs 867, P < 0.001), without significant differences in creatine-kinase MB and cardiac troponin levels. Multivariate analysis identified increased right ventricular thickness, low diastolic blood pressure, and high cardiac troponin levels as risk factors for cardiac death in HM patients.</p><p><strong>Conclusions: </strong>This study demonstrates that HM patients have fewer cardiomyocyte nuclei and poorly aligned collagen, with serum biomarker evidence of increased cardiac dysfunction. This supports the necessity for specialized cardiac care for these patients.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"90"},"PeriodicalIF":3.2,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11657889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853163","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 : 2024-12-18DOI: 10.1186/s40959-024-00292-4
John Lee, Sean Tan, Satish Ramkumar
Despite advanced in targeted cancer therapies, anthracyclines remain essential in treating various malignancies, albeit with risks of cancer therapy-related cardiac dysfunction (CTRCD). Out of the myriad of mitigation strategies for CTRCD, statins are an attractive preventive therapy for anthracycline associated CTRCD given their widespread availability, cheap costs and added benefit of atherosclerotic cardiovascular disease (ASCVD) risk reduction. Recent trials of PREVENT, SPARE-HF, and STOP-CA investigated atorvastatin's efficacy in preventing CTRCD, with mixed outcomes. While STOP-CA showed a significant reduction in CTRCD rates (22% vs. 8% in placebo), PREVENT and SPARE-HF found no statistical differences between statin and placebo groups. The trials faced challenges such as selection bias, exclusion of patients with comorbidities, and reliance on imaging-derived outcomes, which may not reflect clinically meaningful benefits. This calls for improved trial designs that prioritize diverse patient recruitment, longer follow-ups, and clinically relevant endpoints to enhance the translational impact of findings. Addressing these challenges collaboratively between oncology and cardiology will be crucial for optimizing patient outcomes in this vulnerable population. Future studies should emphasize both immediate cardioprotective effects and long-term cardiovascular benefits of statins, especially in the context of atherosclerotic cardiovascular disease in cancer survivors.
{"title":"Challenges in the implementation of cardio-oncology trials: lessons learnt from investigating statins in the prevention of anthracycline cardiotoxicity.","authors":"John Lee, Sean Tan, Satish Ramkumar","doi":"10.1186/s40959-024-00292-4","DOIUrl":"10.1186/s40959-024-00292-4","url":null,"abstract":"<p><p>Despite advanced in targeted cancer therapies, anthracyclines remain essential in treating various malignancies, albeit with risks of cancer therapy-related cardiac dysfunction (CTRCD). Out of the myriad of mitigation strategies for CTRCD, statins are an attractive preventive therapy for anthracycline associated CTRCD given their widespread availability, cheap costs and added benefit of atherosclerotic cardiovascular disease (ASCVD) risk reduction. Recent trials of PREVENT, SPARE-HF, and STOP-CA investigated atorvastatin's efficacy in preventing CTRCD, with mixed outcomes. While STOP-CA showed a significant reduction in CTRCD rates (22% vs. 8% in placebo), PREVENT and SPARE-HF found no statistical differences between statin and placebo groups. The trials faced challenges such as selection bias, exclusion of patients with comorbidities, and reliance on imaging-derived outcomes, which may not reflect clinically meaningful benefits. This calls for improved trial designs that prioritize diverse patient recruitment, longer follow-ups, and clinically relevant endpoints to enhance the translational impact of findings. Addressing these challenges collaboratively between oncology and cardiology will be crucial for optimizing patient outcomes in this vulnerable population. Future studies should emphasize both immediate cardioprotective effects and long-term cardiovascular benefits of statins, especially in the context of atherosclerotic cardiovascular disease in cancer survivors.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"88"},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11653537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853160","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 : 2024-12-05DOI: 10.1186/s40959-024-00278-2
Antonia Beitzen-Heineke, David R Wise, Jeffrey S Berger
Androgen deprivation therapy (ADT), a key element of prostate cancer treatment, is associated with increased risk for cardiovascular morbidity and mortality. The underlying mechanisms include adverse metabolic alterations, but further mechanisms are likely. Animal studies suggest increased progression of atherosclerosis in androgen deprived conditions. Based on in vitro studies, lack of androgens may modulate immune cells including monocytes, macrophages, and T-cells towards a pro-inflammatory phenotype and pro-atherogenic function. As a novel aspect, this review summarizes existing data on the effect of androgens and androgen deprivation on platelet activity, which play a major role in inflammation and in the initiation and progression of atherosclerotic lesions. Testosterone modulates platelet aggregation responses which are affected by dose level, source of androgen, and age. Data on the effects of ADT on platelet activity and aggregation are limited and conflicting, as both increased and decreased aggregation responses during ADT have been reported. Gaps in knowledge about the mechanisms leading to increased cardiovascular risk during ADT remain and further research is warranted. Improved understanding of pathogenic pathways linking ADT to cardiovascular risk may help identify clinically useful diagnostic and prognostic biomarkers, and accelerate finding novel therapeutic targets, and thus optimize prostate cancer treatment outcomes.
{"title":"Thrombo-inflammation linking androgen suppression with cardiovascular risk in patients with prostate cancer.","authors":"Antonia Beitzen-Heineke, David R Wise, Jeffrey S Berger","doi":"10.1186/s40959-024-00278-2","DOIUrl":"10.1186/s40959-024-00278-2","url":null,"abstract":"<p><p>Androgen deprivation therapy (ADT), a key element of prostate cancer treatment, is associated with increased risk for cardiovascular morbidity and mortality. The underlying mechanisms include adverse metabolic alterations, but further mechanisms are likely. Animal studies suggest increased progression of atherosclerosis in androgen deprived conditions. Based on in vitro studies, lack of androgens may modulate immune cells including monocytes, macrophages, and T-cells towards a pro-inflammatory phenotype and pro-atherogenic function. As a novel aspect, this review summarizes existing data on the effect of androgens and androgen deprivation on platelet activity, which play a major role in inflammation and in the initiation and progression of atherosclerotic lesions. Testosterone modulates platelet aggregation responses which are affected by dose level, source of androgen, and age. Data on the effects of ADT on platelet activity and aggregation are limited and conflicting, as both increased and decreased aggregation responses during ADT have been reported. Gaps in knowledge about the mechanisms leading to increased cardiovascular risk during ADT remain and further research is warranted. Improved understanding of pathogenic pathways linking ADT to cardiovascular risk may help identify clinically useful diagnostic and prognostic biomarkers, and accelerate finding novel therapeutic targets, and thus optimize prostate cancer treatment outcomes.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"87"},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784252","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 : 2024-12-03DOI: 10.1186/s40959-024-00293-3
Golnaz Kheradkhah, Mohammad Sheibani, Tina Kianfar, Zahra Toreyhi, Yaser Azizi
Chemotherapy is one of the routine treatment for preventing rapid growth of the tumor cells. However, chemotherapeutic agents, especially doxorubicin cause damages to the normal cells especially cardiomyocytes. Cardiotoxicity induced by chemotherapeutic drugs lead to the myocardial cell injury and finally causes left ventricular dysfunction. It seems that there were some differences in the severity of cardiovascular side effects of drugs used in the treatment of cancers. Sex hormones in male and female play crucial roles in cardiovascular development and physiological function of the heart and blood vessels. Gender differences and sex-specific hormones influence various aspects of cardiovascular health, including ventricular function, mitochondrial autophagy, and the development of abdominal aortic aneurysms. The most important gender related hormones are LH, FSH, testosterone, estrogen, progesterone, prolactin and oxytocin. They exert very important cardiovascular effects via different signaling mechanisms. Sex related hormones are also important in the cardiovascular side effects of chemotherapeutic agents, so that chronic cardiotoxicity induced by anthracyclines is more common in women. During different stages of life (before, during, and after sexual life), the levels of these hormones will be changed. This alterations can affect cardiovascular function during physiological conditions and pathological process. Because of the importance of the sex related hormones in the cardiac function, in this review we tried to comprehensively elucidate the role of these physiological hormones in cardiotoxicity induced by chemotherapeutic agents with emphasizing their signaling mechanisms.
{"title":"A comprehensive review on the effects of sex hormones on chemotherapy-induced cardiotoxicity: are they lucrative or unprofitable?","authors":"Golnaz Kheradkhah, Mohammad Sheibani, Tina Kianfar, Zahra Toreyhi, Yaser Azizi","doi":"10.1186/s40959-024-00293-3","DOIUrl":"10.1186/s40959-024-00293-3","url":null,"abstract":"<p><p>Chemotherapy is one of the routine treatment for preventing rapid growth of the tumor cells. However, chemotherapeutic agents, especially doxorubicin cause damages to the normal cells especially cardiomyocytes. Cardiotoxicity induced by chemotherapeutic drugs lead to the myocardial cell injury and finally causes left ventricular dysfunction. It seems that there were some differences in the severity of cardiovascular side effects of drugs used in the treatment of cancers. Sex hormones in male and female play crucial roles in cardiovascular development and physiological function of the heart and blood vessels. Gender differences and sex-specific hormones influence various aspects of cardiovascular health, including ventricular function, mitochondrial autophagy, and the development of abdominal aortic aneurysms. The most important gender related hormones are LH, FSH, testosterone, estrogen, progesterone, prolactin and oxytocin. They exert very important cardiovascular effects via different signaling mechanisms. Sex related hormones are also important in the cardiovascular side effects of chemotherapeutic agents, so that chronic cardiotoxicity induced by anthracyclines is more common in women. During different stages of life (before, during, and after sexual life), the levels of these hormones will be changed. This alterations can affect cardiovascular function during physiological conditions and pathological process. Because of the importance of the sex related hormones in the cardiac function, in this review we tried to comprehensively elucidate the role of these physiological hormones in cardiotoxicity induced by chemotherapeutic agents with emphasizing their signaling mechanisms.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"86"},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766715","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 : 2024-11-27DOI: 10.1186/s40959-024-00291-5
Fei Fei Gong, Eli Grunblatt, Woo Bin Voss, Vibhav Rangarajan, Sasan Raissi, Kimberly Chow, Lua Jafari, Nikita P Patel, Inga Vaitenas, Milica Marion, Haydee Ramirez, Manyun Zhao, Adin-Christian Andrei, Abigail S Baldridge, Gillian Murtagh, Kameswari Maganti, Vera H Rigolin, Nausheen Akhter
Background: Global longitudinal strain (GLS) has been used to identify patients at risk for cancer-therapy related cardiac dysfunction (CTRCD). However, there is limited data on the effectiveness of initiating cardioprotective therapy based on a strain-guided strategy in early stage HER2+ breast cancer patients. This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer patients on non-anthracycline based regimens.
Methods: Study participants were prospectively assigned to one of four arms. Patients with normal LVEF and GLS remained in Arm A. Patients whose GLS decreased by > 15% from baseline or to < -15% during follow up were randomized 1:1 to prophylactic carvedilol (Arm B) or no therapy (Arm C). Patients who developed CTRCD were assigned to Arm D. The primary endpoint was GLS stability. The secondary endpoints were development of CTRCD and rate of anti-HER2 treatment interruption.
Results: Among 110 patients who completed follow up, 84 were assigned to Arm A, 10 each were randomized to Arms B or C, and 6 were assigned to Arm D. At the end of the study period, there were no significant differences in GLS stability, development of CTRCD, or number of cancer therapy cycles completed between patients who did and did not receive cardioprotective therapy.
Conclusions: In this prospective randomized GLS-guided study of prophylactic carvedilol in early stage HER2+ breast cancer patients on non-anthracycline regimens, there were no significant difference between groups in GLS stability, CTRCD or trastuzumab cycles held. These findings may identify a low-risk group of patients who may be considered for less intensive cardiac surveillance.
Trial registration: https://clinicaltrials.gov/study/NCT02993198 . Start date: 4/2015. This trial included patients who were retrospectively registered.
背景:全球纵向应变(GLS)已被用于识别癌症治疗相关心功能障碍(CTRCD)的高危患者。然而,基于应变指导策略对早期 HER2+ 乳腺癌患者启动心脏保护治疗的有效性数据有限。这项随机临床试验评估了基于应变指导策略的卡维地洛治疗是否能预防接受非蒽环类药物治疗的HER2+乳腺癌患者发生CTRCD:研究参与者被前瞻性地分配到四组中的一组。随访期间GLS从基线下降>15%或降至<-15%的患者按1:1随机分配至预防性卡维地洛(B组)或不治疗(C组)。出现 CTRCD 的患者被分配到 D 组。次要终点是出现 CTRCD 和抗 HER2 治疗中断率:在完成随访的 110 名患者中,84 人被分配到 A 组,10 人被随机分配到 B 组或 C 组,6 人被分配到 D 组。在研究期结束时,接受和未接受心脏保护疗法的患者在 GLS 稳定性、CTRCD 发生率或完成癌症治疗周期数方面没有显著差异:在这项前瞻性随机GLS指导研究中,对使用非蒽环类疗法的早期HER2+乳腺癌患者进行预防性卡维地洛治疗后,各组间在GLS稳定性、CTRCD或曲妥珠单抗治疗周期方面没有明显差异。这些发现可能会确定一组低风险患者,可考虑对其进行强度较低的心脏监测。试验注册:https://clinicaltrials.gov/study/NCT02993198 。开始日期:2015 年 4 月。该试验包括回顾性登记的患者。
{"title":"A strain-guided trial of cardioprotection in early-stage breast cancer patients on anti-HER2 therapy (PROTECT HER2).","authors":"Fei Fei Gong, Eli Grunblatt, Woo Bin Voss, Vibhav Rangarajan, Sasan Raissi, Kimberly Chow, Lua Jafari, Nikita P Patel, Inga Vaitenas, Milica Marion, Haydee Ramirez, Manyun Zhao, Adin-Christian Andrei, Abigail S Baldridge, Gillian Murtagh, Kameswari Maganti, Vera H Rigolin, Nausheen Akhter","doi":"10.1186/s40959-024-00291-5","DOIUrl":"10.1186/s40959-024-00291-5","url":null,"abstract":"<p><strong>Background: </strong>Global longitudinal strain (GLS) has been used to identify patients at risk for cancer-therapy related cardiac dysfunction (CTRCD). However, there is limited data on the effectiveness of initiating cardioprotective therapy based on a strain-guided strategy in early stage HER2+ breast cancer patients. This randomized clinical trial assessed if treatment with carvedilol based on a strain-guided strategy can prevent development of CTRCD in HER2+ breast cancer patients on non-anthracycline based regimens.</p><p><strong>Methods: </strong>Study participants were prospectively assigned to one of four arms. Patients with normal LVEF and GLS remained in Arm A. Patients whose GLS decreased by > 15% from baseline or to < -15% during follow up were randomized 1:1 to prophylactic carvedilol (Arm B) or no therapy (Arm C). Patients who developed CTRCD were assigned to Arm D. The primary endpoint was GLS stability. The secondary endpoints were development of CTRCD and rate of anti-HER2 treatment interruption.</p><p><strong>Results: </strong>Among 110 patients who completed follow up, 84 were assigned to Arm A, 10 each were randomized to Arms B or C, and 6 were assigned to Arm D. At the end of the study period, there were no significant differences in GLS stability, development of CTRCD, or number of cancer therapy cycles completed between patients who did and did not receive cardioprotective therapy.</p><p><strong>Conclusions: </strong>In this prospective randomized GLS-guided study of prophylactic carvedilol in early stage HER2+ breast cancer patients on non-anthracycline regimens, there were no significant difference between groups in GLS stability, CTRCD or trastuzumab cycles held. These findings may identify a low-risk group of patients who may be considered for less intensive cardiac surveillance.</p><p><strong>Trial registration: </strong>https://clinicaltrials.gov/study/NCT02993198 . Start date: 4/2015. This trial included patients who were retrospectively registered.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"85"},"PeriodicalIF":3.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738477","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 : 2024-11-26DOI: 10.1186/s40959-024-00289-z
Rachel Jaber Chehayeb, Jaiveer Singh, Carlos Matute-Martinez, Nathan W Chen, Ana Ferrigno Guajardo, Derrick Lin, Ritujith Jayakrishnan, Anthos Christofides, Etienne Leveille, Yunju Im, Giulia Biancon, Jennifer VanOudenhove, Eiman Ibrahim, Anastasias Ardasheva, Alokkumar Jha, John Hwa, Stephanie Halene, Jennifer M Kwan
Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of cardiomyopathy in patients with solid malignancies. CHIP has also been shown to increase T cell activation in heart failure patients. It is unclear whether CHIP can affect the risk of immune checkpoint inhibitor (ICI) myocarditis in patients with cancer treated with immunotherapy.
Methods: We enrolled patients with solid tumors in a prospective study, determined CHIP status at time of enrollment through blood whole exome sequencing, and assessed incidence of ICI myocarditis from time of enrollment through December 1st, 2023. We performed a competing risk cox regression to evaluate the role of CHIP in ICI myocarditis, accounting for patient demographics, cardiac comorbidities, cardiotoxic cancer therapy, and dual ICI use in our covariates. We also generated cumulative incidence curves using subdistribution hazards to evaluate development of ICI myocarditis stratified by CHIP vs no CHIP. Chart review was performed to evaluate patient co-morbidities, lab values, imaging findings and outcomes.
Results: Among the 88 patients receiving ICI therapy, average age was 67 ± 14 years, of which 50% harbored CHIP variants. Among all comorbidities, including diabetes, heart failure and obstructive coronary artery disease, only coronary artery calcifications were significantly increased in patients with CHIP. There were no statistically significant differences in cancer therapy or cardiovascular drugs between patients with and without CHIP. Among examined outcomes, patients with CHIP had a statistically higher rate of ICI myocarditis (overall: 57%, CHIP: 73% (32/44), no CHIP: 41% (18/44), p = 0.003) and death (CHIP: 60%, no CHIP 31%, p = 0.011). In a multivariate competing risk analysis, CHIP status doubled the risk of developing ICI myocarditis, similar to the risk of dual ICI use (CHIP status HR 2.74, 95% CI: 1.44-5.22, p = 0.002 vs dual ICI use HR 2.39, 95% CI: 1.11-5.14, p = 0.026).
Conclusions: This study is the first to show that CHIP independently increases risk of ICI myocarditis, with implications for risk stratification of patients prior to ICI initiation and frequency of cardiac monitoring.
{"title":"Clonal hematopoiesis of indeterminate potential is associated with increased risk of immune checkpoint inhibitor myocarditis in a prospective study of a cardio-oncology cohort.","authors":"Rachel Jaber Chehayeb, Jaiveer Singh, Carlos Matute-Martinez, Nathan W Chen, Ana Ferrigno Guajardo, Derrick Lin, Ritujith Jayakrishnan, Anthos Christofides, Etienne Leveille, Yunju Im, Giulia Biancon, Jennifer VanOudenhove, Eiman Ibrahim, Anastasias Ardasheva, Alokkumar Jha, John Hwa, Stephanie Halene, Jennifer M Kwan","doi":"10.1186/s40959-024-00289-z","DOIUrl":"10.1186/s40959-024-00289-z","url":null,"abstract":"<p><strong>Background: </strong>Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to increase all-cause mortality and risk of cardiomyopathy in patients with solid malignancies. CHIP has also been shown to increase T cell activation in heart failure patients. It is unclear whether CHIP can affect the risk of immune checkpoint inhibitor (ICI) myocarditis in patients with cancer treated with immunotherapy.</p><p><strong>Methods: </strong>We enrolled patients with solid tumors in a prospective study, determined CHIP status at time of enrollment through blood whole exome sequencing, and assessed incidence of ICI myocarditis from time of enrollment through December 1st, 2023. We performed a competing risk cox regression to evaluate the role of CHIP in ICI myocarditis, accounting for patient demographics, cardiac comorbidities, cardiotoxic cancer therapy, and dual ICI use in our covariates. We also generated cumulative incidence curves using subdistribution hazards to evaluate development of ICI myocarditis stratified by CHIP vs no CHIP. Chart review was performed to evaluate patient co-morbidities, lab values, imaging findings and outcomes.</p><p><strong>Results: </strong>Among the 88 patients receiving ICI therapy, average age was 67 ± 14 years, of which 50% harbored CHIP variants. Among all comorbidities, including diabetes, heart failure and obstructive coronary artery disease, only coronary artery calcifications were significantly increased in patients with CHIP. There were no statistically significant differences in cancer therapy or cardiovascular drugs between patients with and without CHIP. Among examined outcomes, patients with CHIP had a statistically higher rate of ICI myocarditis (overall: 57%, CHIP: 73% (32/44), no CHIP: 41% (18/44), p = 0.003) and death (CHIP: 60%, no CHIP 31%, p = 0.011). In a multivariate competing risk analysis, CHIP status doubled the risk of developing ICI myocarditis, similar to the risk of dual ICI use (CHIP status HR 2.74, 95% CI: 1.44-5.22, p = 0.002 vs dual ICI use HR 2.39, 95% CI: 1.11-5.14, p = 0.026).</p><p><strong>Conclusions: </strong>This study is the first to show that CHIP independently increases risk of ICI myocarditis, with implications for risk stratification of patients prior to ICI initiation and frequency of cardiac monitoring.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"84"},"PeriodicalIF":3.2,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715343","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 : 2024-11-25DOI: 10.1186/s40959-024-00287-1
Maciej Wiewiora, Hanna Wiewiora, Ewa Chmielik, Michal Jarzab, Michael Grynkiewicz, Marcin Kubeczko
Background: Budd-Chiari syndrome is a rare and severe vascular liver disease. We presented patient with fulminant liver failure secondary to leiomyosarcoma of the IVC and thrombosis.
Case presentation: A 44-year-old female presented with fulminant liver failure secondary to inferior vena cava (IVC) thrombosis. Contrast-enhanced computed tomography subsequently revealed a thrombus within the IVC, extending cranially to the right atrium and caudally to the renal veins. The patient's condition, characterized by early comatose symptoms, necessitated surgical intervention. Under extracorporeal circulation, a right atriotomy with thrombus lesion removal and descending thrombectomy of the IVC was performed. Hepatic congestion resolved after the thrombus was removed. A pathological examination of the excised thrombus revealed the presence of high-grade leiomyosarcoma.
Conclusions: In cases where a thrombus extends from the IVC to the right atrium, urgent surgical intervention with extracorporeal circulation should be considered.
{"title":"Sternotomy and extracorporal circulation for fulminant Budd-Chiari syndrome due to leiomyosarcoma of the inferior vena cava.","authors":"Maciej Wiewiora, Hanna Wiewiora, Ewa Chmielik, Michal Jarzab, Michael Grynkiewicz, Marcin Kubeczko","doi":"10.1186/s40959-024-00287-1","DOIUrl":"10.1186/s40959-024-00287-1","url":null,"abstract":"<p><strong>Background: </strong>Budd-Chiari syndrome is a rare and severe vascular liver disease. We presented patient with fulminant liver failure secondary to leiomyosarcoma of the IVC and thrombosis.</p><p><strong>Case presentation: </strong>A 44-year-old female presented with fulminant liver failure secondary to inferior vena cava (IVC) thrombosis. Contrast-enhanced computed tomography subsequently revealed a thrombus within the IVC, extending cranially to the right atrium and caudally to the renal veins. The patient's condition, characterized by early comatose symptoms, necessitated surgical intervention. Under extracorporeal circulation, a right atriotomy with thrombus lesion removal and descending thrombectomy of the IVC was performed. Hepatic congestion resolved after the thrombus was removed. A pathological examination of the excised thrombus revealed the presence of high-grade leiomyosarcoma.</p><p><strong>Conclusions: </strong>In cases where a thrombus extends from the IVC to the right atrium, urgent surgical intervention with extracorporeal circulation should be considered.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"83"},"PeriodicalIF":3.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709172","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}
The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis. Here, we present four cases of ICI-related fulminant myocarditis (FM). Three of the four cases resulted in fatal outcomes despite aggressive treatment with mechanical circulatory support and immunosuppressive therapy with corticosteroids. Given the poor prognosis of ICI-FM, the establishment of rapid and adequate therapeutic interventions on the basis of clinical and pathological evaluation is imperative.
{"title":"Clinical and pathological characteristics of immune checkpoint inhibitor-related fulminant myocarditis.","authors":"Ryo Izumi, Toru Hashimoto, Hiroshi Kisanuki, Kei Ikuta, Wataru Otsuru, Soshun Asakawa, Shoei Yamamoto, Kayo Misumi, Takeo Fujino, Keisuke Shinohara, Shouji Matsushima, Kazuya Hosokawa, Shunsuke Katsuki, Taro Mori, Mikiko Hashisako, Yuki Tateishi, Takeshi Iwasaki, Yoshinao Oda, Shintaro Kinugawa, Kohtaro Abe","doi":"10.1186/s40959-024-00288-0","DOIUrl":"10.1186/s40959-024-00288-0","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis. Here, we present four cases of ICI-related fulminant myocarditis (FM). Three of the four cases resulted in fatal outcomes despite aggressive treatment with mechanical circulatory support and immunosuppressive therapy with corticosteroids. Given the poor prognosis of ICI-FM, the establishment of rapid and adequate therapeutic interventions on the basis of clinical and pathological evaluation is imperative.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"82"},"PeriodicalIF":3.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142686115","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 : 2024-11-14DOI: 10.1186/s40959-024-00277-3
Markus B Heckmann, Jan P Münster, Daniel Finke, Hauke Hund, Fabian Schunn, Jürgen Debus, Christine Mages, Norbert Frey, Ann-Kathrin Rahm, Lorenz H Lehmann
Background: Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy.
Methods and results: A retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up.
Conclusion: Thoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation.
{"title":"Cardiac arrhythmias during and after thoracic irradiation for malignancies.","authors":"Markus B Heckmann, Jan P Münster, Daniel Finke, Hauke Hund, Fabian Schunn, Jürgen Debus, Christine Mages, Norbert Frey, Ann-Kathrin Rahm, Lorenz H Lehmann","doi":"10.1186/s40959-024-00277-3","DOIUrl":"10.1186/s40959-024-00277-3","url":null,"abstract":"<p><strong>Background: </strong>Cardiac arrhythmia has been reported as a significant complication of thoracic radiotherapy. Both bradyarrhythmias and tachyarrhythmias have been reported, highlighting the arrhythmia-modulating potential of radiation in certain oncologic therapies. This study aimed to analyse the arrhythmic burden in patients with cardiac implantable electrical devices (CIEDs) undergoing thoracic irradiation, examining both immediate effects of radiotherapy and long-term sequelae post-therapy.</p><p><strong>Methods and results: </strong>A retrospective cohort study was conducted involving patients with CIEDs who received thoracic radiotherapy between January 2012 and December 2022. Two distinct analyses were performed involving (1) daily CIED follow-ups during radiotherapy and (2) long-term arrhythmic outcomes post-therapy. For long-term outcomes, Patients were matched in a 1:2 ratio with non-irradiated controls based on age, sex, cardiovascular risk factors, cardiac disease, and beta-blocker use. Statistical analyses included negative binomial regression and propensity score matching. A total of 186 patients underwent daily CIED monitoring during radiotherapy, with 79 receiving thoracic irradiation. Thoracic irradiation was negatively associated with atrial arrhythmia (OR 0.11 [0.02;0.70, 95% CI], adjusted p = 0.0498) and there was a tendency towards less ventricular events (OR 0.14 [0.02;1.41, 95% CI], adjusted p = 0.3572) during radiotherapy in a univariate regression analysis. This association was not significant in the multivariate (OR 0.44 [0.10;1.80, 95%-CI], p = 0.16) model including a history of atrial fibrillation, diabetes and beta-blocker use. Coronary artery disease was associated with an increase in atrial and ventricular arrhythmia. For the long-term analysis, 122 patients were followed up after thoracic (N = 33) and non-thoracic radiation (N = 89) and compared to 244 matched controls drawn from approximately 10.000 CIED-patients. There was no significant increase in arrhythmic events compared to controls over a median follow-up of 6.6 months. A previous history of ventricular or atrial arrhythmic events was the strongest predictor for events during the follow-up.</p><p><strong>Conclusion: </strong>Thoracic radiotherapy can be safely administered in patients with CIEDs. However, patients with a history of arrhythmia are more prone to arrhythmic events during and after radiation. These findings highlight the need for personalized arrhythmia management strategies and further research to understand the mechanisms underlying the antiarrhythmic effects of thoracic radiation.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"81"},"PeriodicalIF":3.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615401","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 : 2024-11-12DOI: 10.1186/s40959-024-00283-5
Matthew Lui, Noah Kim, Raja Zaghlol, Pouya Joolharzadeh, Elena Deych, Clifford Robinson, Shahed Badiyan, Pamela K Woodard, Joshua D Mitchell
Background: Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients.
Objectives: This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC.
Methods: Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. Demographics, comorbidities, and radiation treatment characteristics were gathered, and CAC groups were assessed for the incidence of MACE after initiation of radiation therapy.
Results: Out of 137 patients, 39 patients had no CAC, and 98 patients had any CAC (38 with mild CAC, 34 with moderate CAC, and 26 with severe CAC). There was 1 MACE event in the no CAC group and 11 in patients with any CAC. The presence of CAC was associated with increased MACE compared to no CAC (p = 0.034). Semiquantitative CAC analysis correlated with formal CAC scoring.
Conclusion: There is a significantly lower incidence of MACE in patients with no CAC on planning CT compared to patients with higher burdens of CAC. CAC burden is an important risk factor for adverse cardiovascular events in patients with NSCLC undergoing thoracic radiation. Semiquantitative CAC scoring may be a useful proxy when formal CAC scoring is unavailable.
{"title":"Coronary artery calcium on lung cancer radiation planning CT aids cardiovascular risk assessment.","authors":"Matthew Lui, Noah Kim, Raja Zaghlol, Pouya Joolharzadeh, Elena Deych, Clifford Robinson, Shahed Badiyan, Pamela K Woodard, Joshua D Mitchell","doi":"10.1186/s40959-024-00283-5","DOIUrl":"10.1186/s40959-024-00283-5","url":null,"abstract":"<p><strong>Background: </strong>Patients with non-small cell lung cancer (NSCLC) undergoing thoracic radiation are at high cardiovascular risk. Semiquantitative assessment of coronary artery calcification (CAC) on baseline planning non-gated chest computed tomography (CT) scans may help further risk stratify patients.</p><p><strong>Objectives: </strong>This study aimed to characterize the association between CAC and major adverse cardiovascular events (MACE; myocardial infarction or stroke) and assess the utility of semiquantitative assessment of CAC.</p><p><strong>Methods: </strong>Patients with NSCLC with non-contrast planning chest CT scans were evaluated for CAC. Planning scans were visually graded using the CAC-DRS method, stratifying patients into no, mild, moderate, and severe CAC groups. Demographics, comorbidities, and radiation treatment characteristics were gathered, and CAC groups were assessed for the incidence of MACE after initiation of radiation therapy.</p><p><strong>Results: </strong>Out of 137 patients, 39 patients had no CAC, and 98 patients had any CAC (38 with mild CAC, 34 with moderate CAC, and 26 with severe CAC). There was 1 MACE event in the no CAC group and 11 in patients with any CAC. The presence of CAC was associated with increased MACE compared to no CAC (p = 0.034). Semiquantitative CAC analysis correlated with formal CAC scoring.</p><p><strong>Conclusion: </strong>There is a significantly lower incidence of MACE in patients with no CAC on planning CT compared to patients with higher burdens of CAC. CAC burden is an important risk factor for adverse cardiovascular events in patients with NSCLC undergoing thoracic radiation. Semiquantitative CAC scoring may be a useful proxy when formal CAC scoring is unavailable.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":"10 1","pages":"80"},"PeriodicalIF":3.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11556125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615408","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}