Cardio-oncologyPub Date : 2024-02-09DOI: 10.1186/s40959-024-00206-4
Yvonne Koop, Femke Atsma, Marilot C T Batenburg, Hanneke Meijer, Femke van der Leij, Roxanne Gal, Sanne G M van Velzen, Ivana Išgum, Hester Vermeulen, Angela H E M Maas, Saloua El Messaoudi, Helena M Verkooijen
{"title":"Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost.","authors":"Yvonne Koop, Femke Atsma, Marilot C T Batenburg, Hanneke Meijer, Femke van der Leij, Roxanne Gal, Sanne G M van Velzen, Ivana Išgum, Hester Vermeulen, Angela H E M Maas, Saloua El Messaoudi, Helena M Verkooijen","doi":"10.1186/s40959-024-00206-4","DOIUrl":"10.1186/s40959-024-00206-4","url":null,"abstract":"<p><strong>Background: </strong>Thoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed.</p><p><strong>Objective: </strong>We aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age.</p><p><strong>Methods: </strong>We identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis.</p><p><strong>Results: </strong>1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2-22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2-1.02) for 75-year old patients.</p><p><strong>Conclusion: </strong>In patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10854185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139711733","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}
Cardio-oncologyPub Date : 2024-02-07DOI: 10.1186/s40959-024-00201-9
Arsalan Hamid, Gregg C Fonarow, Javed Butler, Michael E Hall
{"title":"How do breast cancer clinical trials approach cardiovascular safety: targeted or generalized?","authors":"Arsalan Hamid, Gregg C Fonarow, Javed Butler, Michael E Hall","doi":"10.1186/s40959-024-00201-9","DOIUrl":"10.1186/s40959-024-00201-9","url":null,"abstract":"<p><strong>Background: </strong>Different breast cancer pharmacotherapy agents cause different forms of cardiovascular toxicity. We aim to assess if breast cancer pharmacotherapy trials approach cardiovascular safety in a targeted or generalized manner when administering different agents.</p><p><strong>Methods: </strong>We searched Embase and Medline for phase 2 and 3 breast cancer pharmacotherapy trials. We examined exclusion criterion for cardiovascular conditions and cardiovascular safety assessment through cardiovascular imaging, electrocardiogram, troponin, or natriuretic peptides. Fisher's exact test was utilized to compare reporting.</p><p><strong>Results: </strong>Fifty breast cancer clinical trials were included in this study. Trials administering microtubule inhibitors were most likely to exclude patients with any CV condition compared with trials administering other agents (93.5% vs. 68.4%; p < 0.05), particularly coronary artery disease (77.4% vs. 36.8%; p < 0.01) but reported performing an electrocardiogram in 13 (41.9%) trials. Trials administering anti-HER 2 agents excluded all patients with at least one CV condition, particularly patients with heart failure (100.0% vs. 62.9%) and were more likely to perform echocardiograms (80.0% vs. 22.9%, p < 0.001) compared with other agents. Other agents excluded participants in a generalized manner and do not frequently perform targeted safety assessments.</p><p><strong>Conclusions: </strong>Only trials administering microtubule inhibitors or anti-HER 2 therapy exclude patients with cardiovascular disease in a targeted approach. However, anti-HER 2 therapy trials are the only breast cancer clinical trials that perform targeted safety assessments. Breast cancer clinical trials need to develop a targeted approach to cardiovascular safety assessments to permit inclusion of high-risk participants and generate clinical trial data generalizable to patients with cardiovascular disease undergoing cancer therapy.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10848621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139697037","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}
Cardio-oncologyPub Date : 2024-01-15DOI: 10.1186/s40959-023-00191-0
Jian Chu, Lillian Tung, Issam Atallah, Changli Wei, Melody Cobleigh, Ruta Rao, Steven B Feinstein, Lydia Usha, Kathrin Banach, Jochen Reiser, Tochukwu M Okwuosa
{"title":"Soluble urokinase plasminogen activator receptor and cardiotoxicity in doxorubicin-treated breast cancer patients: a prospective exploratory study.","authors":"Jian Chu, Lillian Tung, Issam Atallah, Changli Wei, Melody Cobleigh, Ruta Rao, Steven B Feinstein, Lydia Usha, Kathrin Banach, Jochen Reiser, Tochukwu M Okwuosa","doi":"10.1186/s40959-023-00191-0","DOIUrl":"10.1186/s40959-023-00191-0","url":null,"abstract":"<p><strong>Background: </strong>Soluble urokinase plasminogen activator receptor is an inflammatory biomarker that may prognosticate cardiovascular outcomes. We sought to determine the associations between soluble urokinase plasminogen activator receptor and established markers of cardiotoxicity in breast cancer patients receiving doxorubicin.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of women with newly diagnosed breast cancer receiving standard-dose doxorubicin (240 mg/m<sup>2</sup>) at Rush University Medical Center and Rush Oak Park Hospital (Chicago, IL) between January 2017 and May 2019. Left ventricular ejection fraction, global longitudinal strain, and cardiac biomarkers (N-terminal prohormone B-type natriuretic peptide, troponin-I, and high-sensitivity C-reactive protein) were measured at baseline and at intervals up to 12-month follow-up after end of treatment. The associations between soluble urokinase plasminogen activator receptor and these endpoints were evaluated using multivariable mixed effects linear regression.</p><p><strong>Results: </strong>Our study included 37 women (mean age 47.0 ± 9.3 years, 60% white) with a median baseline soluble urokinase plasminogen activator receptor level of 2.83 ng/dL. No participant developed cardiomyopathy based on serial echocardiography by one-year follow-up. The median percent change in left ventricular strain was -4.3% at 6-month follow-up and absolute changes in cardiac biomarkers were clinically insignificant. There were no significant associations between soluble urokinase plasminogen activator receptor and these markers of cardiotoxicity (all p > 0.05).</p><p><strong>Conclusions: </strong>In this breast cancer cohort, doxorubicin treatment was associated with a very low risk for cardiotoxicity. Across this narrow range of clinical endpoints, soluble urokinase plasminogen activator receptor was not associated with markers of subclinical cardiotoxicity. Further studies are needed to clarify the prognostic utility of soluble urokinase plasminogen activator receptor in doxorubicin-associated cardiomyopathy and should include a larger cohort of leukemia and lymphoma patients who receive higher doses of doxorubicin.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139471909","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}
Cardio-oncologyPub Date : 2024-01-11DOI: 10.1186/s40959-023-00199-6
Moran Gvili Perelman, Rafael Y Brzezinski, Barliz Waissengrin, Yasmin Leshem, Or Bainhoren, Tammi Arbel Rubinstein, Maxim Perelman, Zach Rozenbaum, Ofer Havakuk, Yan Topilsky, Shmuel Banai, Ido Wolf, Michal Laufer-Perl
{"title":"Sodium-glucose co-transporter-2 inhibitors in patients treated with immune checkpoint inhibitors.","authors":"Moran Gvili Perelman, Rafael Y Brzezinski, Barliz Waissengrin, Yasmin Leshem, Or Bainhoren, Tammi Arbel Rubinstein, Maxim Perelman, Zach Rozenbaum, Ofer Havakuk, Yan Topilsky, Shmuel Banai, Ido Wolf, Michal Laufer-Perl","doi":"10.1186/s40959-023-00199-6","DOIUrl":"10.1186/s40959-023-00199-6","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) have revolutionized the prognosis of cancer. Diabetes mellitus (DM) has been shown to have a negative effect on patients treated with ICIs. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are effective antidiabetic therapies associated with reduced all-cause mortality and cardiovascular (CV) outcomes.</p><p><strong>Objective: </strong>To evaluate the prognostic value of SGLT2i on all-cause mortality and cardiotoxicity among patients treated with ICIs.</p><p><strong>Methods: </strong>We performed a retrospective analysis of patients diagnosed with cancer and type 2 DM (DM2) and treated with ICIs at our center. Patients were divided into two groups according to baseline treatment with or without SGLT2i. The primary endpoint was all-cause mortality and the secondary endpoint was MACE, including myocarditis, acute coronary syndrome, heart failure, and arrhythmia.</p><p><strong>Results: </strong>The cohort included 119 patients, with 24 (20%) patients assigned to the SGLT2i group. Both groups exhibited a comparable prevalence of cardiac risk factors, although the SGLT2i group displayed a higher incidence of ischemic heart disease. Over a median follow-up of 28 months, 61 (51%) patients died, with a significantly lower all-cause mortality rate in the SGLT2i group (21% vs. 59%, p = 0.002). While there were no significant differences in MACE, we observed zero cases of myocarditis and atrial fibrillation in the SGLT2i, compared to 2 and 6 cases in the non-SGLT2i group.</p><p><strong>Conclusions: </strong>SGLT2i therapy was associated with a lower all-cause mortality rate in patients diagnosed with cancer and DM2 and treated with ICIs. Further studies are needed to understand the mechanism and evaluate its benefit on cardiotoxicity.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10782769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139428468","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}
Cardio-oncologyPub Date : 2024-01-02DOI: 10.1186/s40959-023-00196-9
Sinal Patel, Francisco X Franco, Malcolm McDonald, Carlos Rivera, Bernardo Perez-Villa, Patrick Collier, Rohit Moudgil, Neha Gupta, Diego B Sadler
{"title":"Use of computed tomography coronary calcium score for prediction of cardiovascular events in cancer patients: a retrospective cohort analysis.","authors":"Sinal Patel, Francisco X Franco, Malcolm McDonald, Carlos Rivera, Bernardo Perez-Villa, Patrick Collier, Rohit Moudgil, Neha Gupta, Diego B Sadler","doi":"10.1186/s40959-023-00196-9","DOIUrl":"10.1186/s40959-023-00196-9","url":null,"abstract":"<p><strong>Background: </strong>CT- coronary calcium score, is one of the most studied and widely available modalities in cardiovascular medicine. Coronary artery calcium score (CACS) is an established predictor of coronary artery disease. The 'standard of care' diagnostic modality to measure CACS is ECG-gated Cardiac Multi-Detector Computed Tomography. There is convincing evidence of a strong association between CACS and major cardiovascular (CV) events in asymptomatic individuals. Cancer patients (C) may have a higher risk for CV disease than non-cancer patients (NC) related not only to cancer treatments but also to shared biological factors and pathways. Thus, identifying tools for early detection of CV disease in this population is of utmost importance.</p><p><strong>Methods: </strong>A retrospective cohort analysis was performed with patients from Cleveland Clinic Florida and Ohio who had CACS from 2017 to 2021. Patients who had cancer diagnosis prior to CACS were matched to NC for age and sex. CV events after their index CACS events were compared between C and NC, and matched control and propensity analysis were conducted.</p><p><strong>Results: </strong>Ten thousand seven hundred forty-two patients had CACS; 703 cancer patients had CACS and were eligible. Extensive CACS (> 400) were significantly higher in cancer, 94 (13.37%) vs non-cancer patients, 76 (10.83%), P = 0.011. Furthermore, after propensity matched analysis, CACS > 400 was 14.8% in C vs 9.6% in NC, P = < 0.05. CV events were similar in both cohorts (p = NS), despite less CV risk factors in cancer patients (P = < 0.05). For the combined moderate (101-400) & extensive (> 400) CACS, the prevalence of stroke and peripheral arterial disease, a marker of systemic atherosclerosis, was significantly higher in patients with cancer (P < 0.01).</p><p><strong>Conclusions: </strong>Despite having fewer CV risk factors in our study, similar CACS in cancer patients are suggestive of a higher prevalence of CV disease independent of traditional risk factors. High CACS and the overall prevalence of vascular events were more frequent in patients with cancer. Higher prevalence of peripheral arterial disease and cerebrovascular accident further suggests the increased atherosclerotic burden in C.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10759457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086056","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}
Cardio-oncologyPub Date : 2023-12-15DOI: 10.1186/s40959-023-00198-7
Julia Matzenbacher Dos Santos, Aby Joiakim, David A Putt, Marielle Scherrer-Crosbie, Hyesook Kim
{"title":"14,15-Dihydroxyeicosatrienoic acid, a soluble epoxide hydrolase metabolite in blood, is a predictor of anthracycline-induced cardiotoxicity - a hypothesis generating study.","authors":"Julia Matzenbacher Dos Santos, Aby Joiakim, David A Putt, Marielle Scherrer-Crosbie, Hyesook Kim","doi":"10.1186/s40959-023-00198-7","DOIUrl":"https://doi.org/10.1186/s40959-023-00198-7","url":null,"abstract":"<p><strong>Background: </strong>Early identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a chemotherapeutic agent, have increased cardiac expression of 14,15-dihydroxyeicosatrienoic acid (14,15-DHET), a bioactive lipid implicated in hypertension and coronary artery disease. However, the utility of 14,15-DHET as plasma biomarkers was not defined. The aim of this study is to investigate if levels of 14,15-DHET are an early blood biomarker to predict the subsequent occurrence of cardiotoxicity in cancer patients after chemotherapy.</p><p><strong>Methods: </strong>H9c2 rat cardiomyocytes were treated with DOX (1 μM) for 2 h and levels of 14,15-DHET in cell media was quantified at 2, 6 or 24 h in media after DOX treatment. Similarly, female Sprague-Dawley rats were treated with DOX for two weeks and levels of 14,15-DHET was assessed in plasma at 48 h and 2 weeks after DOX treatment. Changes in brain natriuretic peptide (BNP) mRNA, an early cardiac hypertrophy process, were determined in the H9c2 cells and rat cardiac tissue. Results were confirmed in human subjects by assessment of levels of 14,15-DHET in plasma of breast cancer patients before and after DOX treatment and left ventricular ejection fraction (LVEF), a clinical marker of cardiotoxicity.</p><p><strong>Results: </strong>Levels of 14,15-DHET in cell media and rat plasma increased ~ 3-fold and was accompanied with increase in BNP mRNA in H9c2 cells and rat cardiac tissue after DOX treatment. In matched plasma samples from breast cancer patients, levels of 14,15-DHET were increased in patients that developed cardiotoxicity at 3 months before occurrence of LVEF decrease.</p><p><strong>Conclusions: </strong>Together, these results indicate that levels of 14,15-DHET are elevated prior to major changes in cardiac structure and function after exposure to anthracyclines. Increased levels of 14,15-DHET in plasma may be an important clinical biomarker for early detection of anthracycline-induced cardiotoxicity in cancer patients.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722875/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138797339","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}
Cardio-oncologyPub Date : 2023-12-06DOI: 10.1186/s40959-022-00152-z
Juan Del Cid Fratti, Vijayasree Paleru, Madhuri Bajaj, Chetan Bhardwaj
{"title":"The toxic tango: TKI and TCI cardiotoxicities.","authors":"Juan Del Cid Fratti, Vijayasree Paleru, Madhuri Bajaj, Chetan Bhardwaj","doi":"10.1186/s40959-022-00152-z","DOIUrl":"10.1186/s40959-022-00152-z","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICI) and Tyrosine kinase inhibitors (TKI) are effective for several types of cancers, but they can have several cardiotoxicity sides effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that were successfully treated with high-dose steroids and PCI.</p><p><strong>Case presentation: </strong>Seventy-two year-old man patient treated with on pembrolizumab 200 mg IV every 3 weeks and Axitinib 5 mg PO q12h for the past 5 months complained of acute shortness of breath, altered mental status, and chronic diarrhea. Coronary angiography demonstrated a thrombotic lesion in the right coronary artery (RCA) that was treated successfully with percutaneous coronary intervention (PCI). Despite PCI he continued to complain of shortness of breath further workup with Cardiac MRI (CMR) was obtained showed an ejection fraction of 38%, small pericardial effusion, and delayed gadolinium enhancement (DGE) in the inferior wall suggestive of myocarditis. An empirical trial of high-dose steroids improved all patient symptoms and ejection fraction; therefore, the chemotherapy regimen was changed.</p><p><strong>Conclusion: </strong>This case report highlights the potential vasculogenic effects of Axitinib and immune-related myocarditis of pembrolizumab. Cardiologists and oncologists should be vigilant for the cardiotoxic effects of Axitinib and pembrolizumab.</p>","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138497943","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}
Cardio-oncologyPub Date : 2023-12-01DOI: 10.1186/s40959-023-00197-8
Amir Askarinejad, A. Alizadehasl, Amir Ghaffari Jolfayi, Sara Adimi
{"title":"Hypertension in Cardio-Oncology Clinic: an update on etiology, assessment, and management","authors":"Amir Askarinejad, A. Alizadehasl, Amir Ghaffari Jolfayi, Sara Adimi","doi":"10.1186/s40959-023-00197-8","DOIUrl":"https://doi.org/10.1186/s40959-023-00197-8","url":null,"abstract":"","PeriodicalId":9804,"journal":{"name":"Cardio-oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138623309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}