Malak El-Rayes MD , Mohamed Adam MSc , Jiming Fang PhD , Xuesong Wang MSc , Irene Jeong MSc , Peter C. Austin PhD , Andrew C.T. Ha MD , Michael G. Fradley MD , Thomas A. Boyle MD , Eitan Amir MB ChB, PhD , Paaladinesh Thavendiranathan MD, MSc , Husam Abdel-Qadir MD, PhD
{"title":"The Association of Malignancy With Stroke and Bleeding in Atrial Fibrillation","authors":"Malak El-Rayes MD , Mohamed Adam MSc , Jiming Fang PhD , Xuesong Wang MSc , Irene Jeong MSc , Peter C. Austin PhD , Andrew C.T. Ha MD , Michael G. Fradley MD , Thomas A. Boyle MD , Eitan Amir MB ChB, PhD , Paaladinesh Thavendiranathan MD, MSc , Husam Abdel-Qadir MD, PhD","doi":"10.1016/j.jaccao.2024.10.014","DOIUrl":"10.1016/j.jaccao.2024.10.014","url":null,"abstract":"<div><h3>Background</h3><div>It is undetermined if malignancy independently increases stroke risk in atrial fibrillation (AF).</div></div><div><h3>Objectives</h3><div>This study sought to determine the association of malignancy with stroke and bleeding in AF.</div></div><div><h3>Methods</h3><div>Population-based cohort study using administrative datasets of people aged ≥66 years with newly diagnosed AF. People diagnosed with malignancy within 5 years before AF diagnosis were matched to cancer-free control subjects on age, sex, AF diagnosis details, CHA<sub>2</sub>DS<sub>2</sub>-VASc score, and ATRIA bleeding score. Outcomes included hospitalizations for stroke and hospitalization/emergency visits for bleeding. Cause-specific regression was used to determine the HR for malignancy after adjusting for time-varying anticoagulation status. Analyses were repeated for specific subgroups of cancer patients (with matched control subjects).</div></div><div><h3>Results</h3><div>Among 199,710 AF patients, 24,991 (12.5%) people had prior malignancy. Malignancy was associated with more inpatient diagnoses of AF (vs outpatient) and less anticoagulation. We matched 43,802 people with AF (21,901 with malignancy, mean age 78.1 years; 59.5% male). After adjusting for anticoagulation status, malignancy had a similar hazard of stroke (HR: 1.01; 95% CI: 0.88-1.15) but higher hazard of bleeding (HR: 1.45; 95% CI: 1.37-1.53) compared with cancer-free control subjects in the matched sample. Analyses of cancer subgroups with comparison to matched control subjects mostly showed consistent results, except for: 1) increased hazard of stroke in lung cancer; and 2) lack of increased bleeding hazard in breast cancer and lymphoma.</div></div><div><h3>Conclusions</h3><div>People with AF and malignancy generally had similar hazards of stroke but higher hazards of bleeding compared with cancer-free control subjects, suggesting that malignancy should not lower the threshold for anticoagulation in AF.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 157-167"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437060","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}
Sara H. Johansen MSc , Torbjørn Wisløff PhD , Elisabeth Edvardsen PhD , Sofie T. Kollerud MSc , Johanne S.S. Jensen MSc , Ginika Agwu BAc , Konstantina Matsoukas MLIS , Jessica M. Scott PhD , Tormod S. Nilsen PhD
{"title":"Effects of Systemic Anticancer Treatment on Cardiorespiratory Fitness","authors":"Sara H. Johansen MSc , Torbjørn Wisløff PhD , Elisabeth Edvardsen PhD , Sofie T. Kollerud MSc , Johanne S.S. Jensen MSc , Ginika Agwu BAc , Konstantina Matsoukas MLIS , Jessica M. Scott PhD , Tormod S. Nilsen PhD","doi":"10.1016/j.jaccao.2024.11.004","DOIUrl":"10.1016/j.jaccao.2024.11.004","url":null,"abstract":"<div><h3>Background</h3><div>Poor cardiorespiratory fitness (CRF) is associated with a higher symptom burden and an increased prevalence of long-term treatment–related cardiovascular disease risk factors in cancer survivors. However, the magnitude of systemic therapy–related CRF impairment remains unclear.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate the effects of systemic anticancer treatment on CRF and identify physiological determinants underpinning CRF impairment.</div></div><div><h3>Methods</h3><div>A systematic literature search was performed in PubMed, Embase, CINAHL, SPORTDiscus, and the Cochrane Library. The primary endpoint was the change in CRF, measured by peak oxygen consumption (V<span>o</span><sub>2peak</sub>), from before to after systemic treatment. Secondary endpoints included post-treatment differences in V<span>o</span><sub>2peak</sub> between cancer survivors and noncancer control subjects, along with physiological determinants of V<span>o</span><sub>2peak</sub>. Two meta-regressions were conducted to examine the association between CRF and cardiac output and arteriovenous oxygen difference.</div></div><div><h3>Results</h3><div>A total of 44 studies were included, comprising 27 prospective trials (61%; n = 1,234 cancer survivors, median age 52.4 years) and 17 cross-sectional studies (39%; n = 1,372 cancer survivors, median age 54.0 years; n = 1,923 noncancer control subjects, median age 56.0 years). Systemic anticancer treatment was associated with a significant decrease in V<span>o</span><sub>2peak</sub> (weighted mean difference −2.13 mL·kg<sup>−1</sup>·min<sup>−1</sup>; 95% CI: −2.76 to −1.50 mL·kg<sup>−1</sup>·min<sup>−1</sup>). No significant differences were observed between patient subgroups (esophagogastric, breast, and colon or rectal cancers). At a median follow-up of 2 years (range: 6 weeks to 12 years) post-therapy, cancer survivors had a significantly lower V<span>o</span><sub>2peak</sub> (weighted mean difference −6.39 mL·kg<sup>−1</sup>·min<sup>−1</sup>; 95% CI: −7.60 to −5.18 mL·kg<sup>−1</sup>·min<sup>−1</sup>) compared with noncancer control subjects. Reduced arteriovenous oxygen difference was associated with lower V<span>o</span><sub>2peak</sub> (β = 2.55; 95% CI: 2.05-3.06; <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Systemic anticancer treatment leads to substantial and sustained impairments in CRF.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 96-106"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437052","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}
Vencel Juhasz MD , Thiago Quinaglia MD, PhD , Zsofia D. Drobni MD, PhD , Julius C. Heemelaar MD , Donna S. Neuberg ScD , Yuchi Han MD , Bonnie Ky MD, MSCE , Raymond Y. Kwong MD, MPH , James L. Januzzi MD , Aarti Asnani MD , Robert A. Redd MS , Negareh Mousavi MD , Michael Jerosch-Herold PhD , Marielle Scherrer-Crosbie MD, PhD , Tomas G. Neilan MD, MPH
{"title":"Atorvastatin and Myocardial Extracellular Volume Expansion During Anthracycline-Based Chemotherapy","authors":"Vencel Juhasz MD , Thiago Quinaglia MD, PhD , Zsofia D. Drobni MD, PhD , Julius C. Heemelaar MD , Donna S. Neuberg ScD , Yuchi Han MD , Bonnie Ky MD, MSCE , Raymond Y. Kwong MD, MPH , James L. Januzzi MD , Aarti Asnani MD , Robert A. Redd MS , Negareh Mousavi MD , Michael Jerosch-Herold PhD , Marielle Scherrer-Crosbie MD, PhD , Tomas G. Neilan MD, MPH","doi":"10.1016/j.jaccao.2024.11.008","DOIUrl":"10.1016/j.jaccao.2024.11.008","url":null,"abstract":"<div><h3>Background</h3><div>In the STOP-CA (Statins to Prevent the Cardiotoxicity From Anthracyclines) trial, atorvastatin preserved the left ventricular ejection fraction among patients with lymphoma treated with anthracyclines. The protective mechanisms are currently unclear.</div></div><div><h3>Objectives</h3><div>The aim of this study was to test the effect of atorvastatin on the anthracycline-associated increase in myocardial extracellular volume (ECV) using cardiac magnetic resonance imaging (MRI).</div></div><div><h3>Methods</h3><div>Cardiac MRI with mapping was performed at baseline and at 12-month follow-up. ECV was calculated, and the primary endpoint was a ≥3% increase. Increases of ≥1 SD in native T1 and T2 times and ECV were secondary endpoints.</div></div><div><h3>Results</h3><div>The subgroup included 171 participants with paired cardiac MRI scans, and 127 had contrast scans of appropriate quality (median age 52 years, 47% women). The proportion of participants with ≥3% increases in ECV was lower in the atorvastatin compared with the placebo group (8% vs 29%; <em>P</em> = 0.002; OR: 0.20; 95% CI: 0.06 to 0.59). A ≥3% increase in ECV was associated with an 8.4% decrease in left ventricular ejection fraction at follow-up (95% CI: −6.31 to −10.38; <em>P</em> < 0.001). The proportion of participants with ≥1-SD increases in T1 and T2 times was statistically similar between groups at 12 months. At 24 months, there were fewer heart failure events among those without ≥3% increases in ECV (8% vs 24%; <em>P</em> = 0.054), though not statistically significantly.</div></div><div><h3>Conclusions</h3><div>Compared with placebo, atorvastatin limited ECV expansion among participants with lymphoma undergoing anthracycline chemotherapy. This study is the first to provide mechanistic insight into statins’ cardioprotective effects with anthracyclines. (Statins to Prevent the Cardiotoxicity From Anthracyclines [STOP-CA]; <span><span>NCT02943590</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 125-137"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437056","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}
{"title":"Unveiling the Mechanisms of Anthracycline Cardiotoxicity","authors":"Giselle C. Meléndez MD , Angelica M. Riojas PhD","doi":"10.1016/j.jaccao.2025.01.006","DOIUrl":"10.1016/j.jaccao.2025.01.006","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 138-140"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437057","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}
{"title":"Impaired Cardiorespiratory Fitness in Cancer Survivors","authors":"Kate A. Bolam PhD, Erin J. Howden PhD","doi":"10.1016/j.jaccao.2025.01.002","DOIUrl":"10.1016/j.jaccao.2025.01.002","url":null,"abstract":"","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 107-109"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437053","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}
Danielle Medina-Hernández MSc , Laura Cádiz PhD , Annalaura Mastrangelo PhD , Andrea Moreno-Arciniegas MD , Miguel Fernández Tocino MSc , Alejandro A. Cueto Becerra MSc , Anabel Díaz-Guerra Priego MSc , Warren A. Skoza MD , María Isabel Higuero-Verdejo DVM , Gonzalo Javier López-Martín Tech , Claudia Pérez-Martínez PhD , Antonio de Molina-Iracheta DVM , María Caballero-Valderrama MD, PhD , Javier Sánchez-González PhD , David Sancho PhD , Valentin Fuster MD, PhD , Carlos Galán-Arriola DVM, PhD , Borja Ibáñez MD, PhD
{"title":"SGLT2i Therapy Prevents Anthracycline-Induced Cardiotoxicity in a Large Animal Model by Preserving Myocardial Energetics","authors":"Danielle Medina-Hernández MSc , Laura Cádiz PhD , Annalaura Mastrangelo PhD , Andrea Moreno-Arciniegas MD , Miguel Fernández Tocino MSc , Alejandro A. Cueto Becerra MSc , Anabel Díaz-Guerra Priego MSc , Warren A. Skoza MD , María Isabel Higuero-Verdejo DVM , Gonzalo Javier López-Martín Tech , Claudia Pérez-Martínez PhD , Antonio de Molina-Iracheta DVM , María Caballero-Valderrama MD, PhD , Javier Sánchez-González PhD , David Sancho PhD , Valentin Fuster MD, PhD , Carlos Galán-Arriola DVM, PhD , Borja Ibáñez MD, PhD","doi":"10.1016/j.jaccao.2024.12.004","DOIUrl":"10.1016/j.jaccao.2024.12.004","url":null,"abstract":"<div><h3>Background</h3><div>Anthracycline-induced cardiotoxicity (AIC) is characterized by a disruption in myocardial metabolism.</div></div><div><h3>Objectives</h3><div>The authors used a large animal model to test sodium-glucose cotransporter inhibitor therapy to prevent AIC.</div></div><div><h3>Methods</h3><div>Female large white pigs (n = 36) were used to identify the most translational AIC regimen: 6 triweekly intravenous doxorubicin injections (1.8 mg/kg each). Another group of 32 pigs were randomized (1:1:2) to doxorubicin plus empagliflozin 20 mg, doxorubicin plus empagliflozin 10 mg, or doxorubicin control. Pigs were serially examined using multiparametric cardiac magnetic resonance and magnetic resonance spectroscopy. At the end of the 21-week follow-up period, blood samples were obtained to measure myocardial metabolic substrate extraction, and the left ventricle was harvested and processed for analysis using metabolomics, transmission electron microscopy, mitochondrial respirometry, and histopathology.</div></div><div><h3>Results</h3><div>Final left ventricular ejection fraction (LVEF), the prespecified primary outcome, was significantly higher in pigs receiving 20 mg empagliflozin than in the doxorubicin control group (median 57.5% [Q1-Q3: 55.5%-60.3%] vs 47.0% [Q1-Q3: 40.8%-47.8%]; <em>P</em> = 0.027). Final LVEF in pigs receiving 10 mg empagliflozin was 51% (Q1-Q3: 46.5%-55.5%; <em>P</em> = 0.020 vs 20 mg empagliflozin). The incidence of AIC events was 0%, 50%, and 72% in the empagliflozin 20 mg, empagliflozin 10 mg, and doxorubicin control groups, respectively. Empagliflozin 20 mg treatment resulted in enhanced ketone body consumption by the myocardium, preserved magnetic resonance spectroscopy–measured cardiac energetics, and improved mitochondrial structure and function on transmission electron microscopy and respirometry. These changes were more modest with the 10-mg empagliflozin dose.</div></div><div><h3>Conclusions</h3><div>Sodium-glucose cotransporter-2 inhibitor therapy with empagliflozin exerts a dose-dependent cardioprotective effect against AIC. The improved LVEF was accompanied by enhanced ketone body consumption, improved cardiac energetics, and preserved mitochondrial structure and function.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 171-184"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437048","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}
Cornelia Englisch MD , Stephan Nopp MD, MSc , Florian Moik MD, PhD , Daniel Steiner MD , Angelika M. Starzer MD , Monika Fritzer-Szekeres MD , Matthias Preusser MD , Anna S. Berghoff MD, PhD , Ingrid Pabinger MD , Cihan Ay MD
{"title":"Growth Differentiation Factor-15 Predicts Major Bleeding in Cancer Patients","authors":"Cornelia Englisch MD , Stephan Nopp MD, MSc , Florian Moik MD, PhD , Daniel Steiner MD , Angelika M. Starzer MD , Monika Fritzer-Szekeres MD , Matthias Preusser MD , Anna S. Berghoff MD, PhD , Ingrid Pabinger MD , Cihan Ay MD","doi":"10.1016/j.jaccao.2024.11.007","DOIUrl":"10.1016/j.jaccao.2024.11.007","url":null,"abstract":"<div><h3>Background</h3><div>The hemostatic system is tightly interconnected with cancer. Research has focused predominantly on thrombotic complications, but less is known about bleeding and bleeding risk prediction. Growth differentiation factor (GDF)-15 has previously emerged as a prognostic biomarker for bleeding.</div></div><div><h3>Objectives</h3><div>The aim of this study was to investigate the association and predictive ability of GDF-15 for bleeding risk in patients with cancer.</div></div><div><h3>Methods</h3><div>The CAT-BLED (Vienna Cancer, Thrombosis, and Bleeding) study is a prospective, observational cohort study including cancer patients initiating systemic anticancer therapies. Patients were followed for up to 2 years for thrombotic and bleeding events. The primary outcome was major bleeding. GDF-15 was measured at inclusion and at 3 and 6 months of follow-up.</div></div><div><h3>Results</h3><div>A total of 779 patients (48% women, median age 62 years, 15% on therapeutic anticoagulation) were included. During a median follow-up period of 18 months, 79 patients (10.1%) experienced major bleeding (12-month cumulative incidence 8.8%; 95% CI: 6.7-10.9). Higher GDF-15 levels were independently associated with increased major bleeding risk (adjusted subdistribution HR per doubling: 1.29; 95% CI: 1.04-1.59), and patients with levels greater than the cohort median (1,864 ng/L) had a significantly higher 12-month cumulative incidence (13.1% vs 4.6%; <em>P</em> < 0.001). This association remained robust in follow-up measurements at 3 and 6 months. GDF-15 showed moderate to good discrimination for predicting 6-month major bleeding risk (C statistic = 0.69; 95% CI: 0.60-0.77). GDF-15 was not associated with venous thromboembolism but was strongly associated with mortality (adjusted HR: 1.37; 95% CI: 1.25-1.50).</div></div><div><h3>Conclusions</h3><div>GDF-15 levels predict major bleeding risk in cancer patients and are not associated with venous thromboembolism, making GDF-15 a particularly promising biomarker for bleeding risk prediction.</div></div>","PeriodicalId":48499,"journal":{"name":"Jacc: Cardiooncology","volume":"7 2","pages":"Pages 141-152"},"PeriodicalIF":12.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437047","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}