ABSTRACT

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeataleaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitroand in vivomodels. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitronor in vivotoxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.

PMID:37654604 | PMC:PMC10466431 | DOI:10.3389/fphar.2023.1223933

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PubMed articles on: Cardio-Oncology

Baseline Troponin Level and Cardiac Toxicity in HER2-positive Early Breast Cancer Patients Receiving Trastuzumab

In Vivo. 2023 Sep-Oct;37(5):2139-2146. doi: 10.21873/invivo.13311.

ABSTRACT

BACKGROUND/AIM: There is controversy around the use of high-sensitive troponin T (hs-TnT) as an early biomarker of cardiac toxicity in patients with breast cancer on trastuzumab (T).

PATIENTS AND METHODS: Patients receiving adjuvant or neo-adjuvant T for early HER2-positive breast cancer were prospectively included. Transthoracic echocardiograms and matched hs-TnT before T and at 3, 6, and 9 months were performed on all patients. Congestive heart failure, cardiac death, a decline in left ventricular ejection fraction (LVEF) of more than 10% from baseline even if it is still within the normal range, or a drop in LVEF below 55% were all considered signs of cardiac toxicity.

RESULTS: In total, 24 patients (median age: 57; range=39-79 years) were enrolled. Anthracyclines were administered to all patients but three as part of neo/adjuvant treatment before T. Cardiovascular toxicity was observed in 3 out of 24 (12.5%) patients: two non-symptomatic LVEF declines (8.3%) and one heart failure episode (4.2%). In the entire population, the mean baseline hs-TnT level was 10.1±8.8 pg/ml, and after 3, 6, and 12 months, no appreciable change was observed. Patients with cardiac toxicity had mean hs-TnT levels higher than those without (18.3±12.3 vs. 8.2±7.2 pg/ml; p=0.049). A definite trend was evident in the chi-square test (chi2=3.52; p=0.06).

CONCLUSION: In anthracycline-exposed patients with early breast cancer, hs-TnT may be able to identify those at risk of developing cardiac toxicity during neo/adjuvant T treatment.

PMID:37652487 | DOI:10.21873/invivo.13311

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PubMed articles on: Cardio-Oncology

A framework for assessing the impact of cardiac and respiratory motion for STereotactic Arrhythmia Radioablation (STAR) using a digital phantom with a 17-segment model - A STOPSTORM.eu consortium study

Int J Radiat Oncol Biol Phys. 2023 Aug 29:S0360-3016(23)07853-7. doi: 10.1016/j.ijrobp.2023.08.059. Online ahead of print.

ABSTRACT

The optimal motion management strategy for patients receiving stereotactic arrhythmia radioablation (STAR) for the treatment of ventricular tachycardia (VT) is not fully known. We developed a framework using a digital phantom to simulate cardiorespiratory motion in combination with different motion management strategies to gain insight into the impact of cardiorespiratory motion on STAR. The 4D XCAT phantom was expanded with the 17-segment left ventricular (LV) model which allowed placement of STAR targets in standardized ventricular regions. Cardiac- and respiratory-binned 4D-CT scans were simulated for free-breathing, reduced free-breathing, respiratory-gating, and breath-hold scenarios. Respiratory motion of the heart was set to population-averaged values of VT patients: 6, 2, and 1 mm in the Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction was adjusted by reducing LV ejection fraction to 35%. Target displacement was evaluated for all segments using envelopes encompassing the cardiorespiratory motion. Envelopes incorporating only the diastole plus respiratory motion were created to simulate the scenario where cardiac motion is not fully captured on 4D-respiratory CT scans used for radiotherapy planning. The average volume of the 17 segments was 6 cm3 (1-9 cm3). Cardiac contraction-relaxation resulted in maximum segment (centroid) motion of 4, 6, and 3.5 mm in Superior-Inferior, Posterior-Anterior, and Left-Right direction, respectively. Cardiac contraction-relaxation resulted in a motion envelope increase of 49% (24-79%) compared to individual segment volumes, whereas envelopes increased by 126% (79-167%) if also respiratory motion was considered. Envelopes incorporating only the diastole and respiration motion covered on average 68-75% of the motion envelope. The developed LV-segmental XCAT framework showed that free-wall regions display the most cardiorespiratory displacement. Our framework supports the optimization of STAR by evaluating the impact of (cardio)respiratory motion and motion management strategies for VT patients.

PMID:37652302 | DOI:10.1016/j.ijrobp.2023.08.059

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PubMed articles on: Cardio-Oncology

Circulating microRNAs and cytokines as prognostic biomarkers for doxorubicin-induced cardiac injury and for evaluating the effectiveness of an exercise intervention

Clin Cancer Res. 2023 Aug 31. doi: 10.1158/1078-0432.CCR-23-1055. Online ahead of print.

ABSTRACT

PURPOSE: To define a set of biomarkers that can be used to identify patients at high risk of developing late DOX-induced cardiac morbidity with the goal of focused monitoring and early interventions.

EXPERIMENTAL DESIGN: Mice received phosphate buffered saline or DOX 2.5 mg/kg 2x/week for 2 weeks. Blood samples were obtained before and after therapy for quantification of miRNAs (6 and 24 h), cytokines (24 h), and troponin (24 h, 4 and 6weeks). Cardiac function was evaluated using echocardiography before and 24 h after therapy. To assess the effectiveness of exercise intervention in preventing DOX-induced cardiotoxicity blood samples were collected from mice treated with DOX or DOX + exercise. Plasma samples from 13 DOX-treated sarcoma patients were also evaluated before and 24 h after therapy.

RESULTS: Elevations in in plasma miRNA-1, miRNA-499 and IL-1α, IL-1β, and IL-6 were seen in DOX-treated in mice with decreased ejection fraction and fractional shortening 24 h after DOX therapy. Troponin levels were not elevated until 4 weeks after therapy. In mice treated with exercise during Dox there was no elevation in these biomarkers and no change in cardiac function. Elevations in these biomarkers were seen in 12 of 13 sarcoma patients treated with Dox.

CONCLUSIONS: These findings define a potential set of biomarkers to identify and predict patients at risk for developing acute and late cardiovascular diseases with the goal of focused monitoring and early intervention. Further studies are needed to confirm the predictive value of these biomarkers in late cardiotoxicity.

PMID:37651264 | DOI:10.1158/1078-0432.CCR-23-1055

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PubMed articles on: Cardio-Oncology

Case Report: Replacement of PD-1 inhibitors with PD-L1 inhibitors in the treatment of squamous non-small-cell lung carcinoma

Front Immunol. 2023 Aug 15;14:1243980. doi: 10.3389/fimmu.2023.1243980. eCollection 2023.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitor (ICI)-associated cardiotoxicity is a relatively uncommon immune-related adverse effects (irAEs) with a high mortality rate. There are few recommendations for the replacement of different immune checkpoint inhibitors in domestic and international reports.

CASE PRESENTATION: We report a case of a patient with squamous non-small cell lung carcinoma (squamous NSCLC) who developed cardiotoxicity after being treated with a programmed death-1 (PD-1) inhibitor and then changed to a PD-L1 inhibitor to continue the treatment. A significant benefit was observed after four cycles of immunotherapy, and no further cardiotoxicity occurred after the treatment was started.

CONCLUSION: This case demonstrates that myocardial damage induced by tislelizumab (PD-1 inhibitor) can be improved after switching to sugemalimab (PD-L1 inhibitor) and that antitumor immunotherapy is effective. This result may have important implications for optimizing immunotherapy management regimens in cancer patients.

PMID:37649479 | PMC:PMC10465174 | DOI:10.3389/fimmu.2023.1243980

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PubMed articles on: Cardio-Oncology

Hospitalization for acute heart failure during non-working hours impacts on long-term mortality: the REPORT-HF registry

ESC Heart Fail. 2023 Aug 30. doi: 10.1002/ehf2.14506. Online ahead of print.

ABSTRACT

AIMS: Hospital admission during nighttime and off hours may affect the outcome of patients with various cardiovascular conditions due to suboptimal resources and personnel availability, but data for acute heart failure remain controversial. Therefore, we studied outcomes of acute heart failure patients according to their time of admission from the global International Registry to assess medical practice with lOngitudinal obseRvation for Treatment of Heart Failure.

METHODS AND RESULTS: Overall, 18 553 acute heart failure patients were divided according to time of admission into 'morning' (7:00-14:59), 'evening' (15:00-22:59), and 'night' (23:00-06:59) shift groups. Patients were also dichotomized to admission during 'working hours' (9:00-16:59 during standard working days) and 'non-working hours' (any other time). Clinical characteristics, treatments, and outcomes were compared across groups. The hospital length of stay was longer for morning (odds ratio: 1.08; 95% confidence interval: 1.06-1.10, P < 0.001) and evening shift (odds ratio: 1.10; 95% confidence interval: 1.07-1.12, P < 0.001) as compared with night shift. The length of stay was also longer for working vs. non-working hours (odds ratio: 1.03; 95% confidence interval: 1.02-1.05, P < 0.001). There were no significant differences in in-hospital mortality among the groups. Admission during working hours, compared with non-working hours, was associated with significantly lower mortality at 1 year (hazard ratio: 0.88; 95% confidence interval: 0.80-0.96, P = 0.003).

CONCLUSIONS: Acute heart failure patients admitted during the night shift and non-working hours had shorter length of stay but similar in-hospital mortality. However, patients admitted during non-working hours were at a higher risk for 1 year mortality. These findings may have implications for the health policies and heart failure trials.

PMID:37649316 | DOI:10.1002/ehf2.14506

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PubMed articles on: Cardio-Oncology

Risk of Incident Heart Failure Among Young Adult Cancer Survivors

JACC CardioOncol. 2023 May 16;5(4):539-541. doi: 10.1016/j.jaccao.2023.03.009. eCollection 2023 Aug.

NO ABSTRACT

PMID:37614576 | PMC:PMC10443104 | DOI:10.1016/j.jaccao.2023.03.009

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PubMed articles on: Cardio-Oncology

Cardiovascular Risk Factor Disparities in Adult Survivors of Childhood Cancer Compared With the General Population

JACC CardioOncol. 2023 Apr 11;5(4):489-500. doi: 10.1016/j.jaccao.2023.01.011. eCollection 2023 Aug.

ABSTRACT

BACKGROUND: It is unknown whether a history of childhood cancer modifies the established disparities in cardiovascular risk factors (CVRFs) observed in the general population.

OBJECTIVES: We sought to determine if disparities in CVRFs by race/ethnicity are similar among childhood cancer survivors compared with the general population.

METHODS: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort with a longitudinal follow-up of 24,084 5-year survivors diagnosed between 1970 and 1999. Multivariable piecewise exponential regression estimated incidence rate ratios (IRRs) for hypertension, hyperlipidemia, diabetes, obesity, and ≥2 CVRFs by race/ethnicity. The CCSS sibling cohort and the National Health and Nutrition Examination Survey cohort were used to compare the sociodemographic-adjusted IRRs for same-race/same-ethnicity disparities.

RESULTS: Non-Hispanic Black (NHB) (n = 1,092) and Hispanic (n = 1,405) survivors compared with non-Hispanic White (NHW) (n = 13,960) survivors reported a higher cumulative incidence of diabetes (8.4%, 9.7%, and 5.1%, respectively); obesity (47.2%, 48.9%, and 30.2%, respectively); multiple CVRFs (17.7%, 16.6%, and 12.3%, respectively); and, for NHB survivors, hypertension (19.5%, 13.6%, and 14.3%, respectively) by 40 years of age (P 0.001). Controlling for sociodemographic and treatment factors compared with NHW survivors, IRRs for NHB were increased for hypertension (IRR: 1.4; 95% CI: 1.1-1.8), obesity (IRR: 1.7; 95% CI: 1.4-2.1), and multiple CVRFs (IRR: 1.6; 95% CI: 1.2-2.1). IRRs for Hispanic survivors were increased for diabetes (IRR: 1.8; 95% CI: 1.2-2.6) and obesity (IRR: 1.4; 95% CI: 1.2-1.7). The pattern of IRRs for CVRF differences was similar among CCSS sibling and National Health and Nutrition Examination Survey cohorts.

CONCLUSIONS: The higher burden of CVRFs among NHB and Hispanic survivors compared with NHW survivors was similar to the general population. The promotion of cardiovascular health equity is critical in this high-risk population.

PMID:37614575 | PMC:PMC10443116 | DOI:10.1016/j.jaccao.2023.01.011

C

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PubMed articles on: Cancer & VTE/PE

Incidence of Pulmonary and Respiratory Conditions in Gaucher Disease from 2000 to 2020: A Multi-institutional Cohort Study

In Vivo. 2023 Sep-Oct;37(5):2276-2283. doi: 10.21873/invivo.13330.

ABSTRACT

BACKGROUND/AIM: Gaucher disease (GD) is a rare lysosomal storage disorder that can involve the lungs and pulmonary vasculature. The long-term effects of GD on respiratory health remain unclear due to limited data on the natural history of this disease. We analyzed electronic health records for 11,004 patients with GD over 10-20 years to determine the incidence of pulmonary hypertension (PH), lung disease, and other respiratory comorbidities and better understand disease course to guide management.

PATIENTS AND METHODS: We conducted a retrospective cohort study using the TriNetX research database of 130 million international patients. The incidence of primary/secondary PH, pulmonary heart disease, interstitial/obstructive/restrictive lung disease, pulmonary hemorrhage, and pulmonary embolism was assessed in patients with GD from 2000-2020.

RESULTS: Incidence rates of all conditions assessed increased from 10 to 20 years of follow-up. Excess risk of PH, lung disease, and pulmonary hemorrhage was significantly higher in GD patients after 20 versus 10 years.

CONCLUSION: Extended follow-up in GD is associated with substantially higher risks of PH, lung disease and other respiratory comorbidities, highlighting the need for close monitoring and early intervention to mitigate long-term pulmonary decline. Improved understanding of mechanisms driving respiratory deterioration can support the development of novel treatments to optimize outcomes in this population at high risk of pulmonary morbidity and mortality.

PMID:37652520 | DOI:10.21873/invivo.13330

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PubMed articles on: Cancer & VTE/PE

Epidemiology and clinical patterns of Lung Abscesses in ICU: A French multicenter retrospective study

Chest. 2023 Aug 29:S0012-3692(23)05371-0. doi: 10.1016/j.chest.2023.08.020. Online ahead of print.

ABSTRACT

BACKGROUND: Data are scarce regarding epidemiology and management of critically ill patients with lung abscesses.

RESEARCH QUESTION: What are the clinical and microbiological characteristics of critically ill patients with lung abscesses, how are they managed in the ICUs, and what are the risk factors of in-ICU mortality?

STUDY DESIGN AND METHODS: Retrospective observational multicenter study, based on ICD-10 codes, between 2015 and 2022 in France. In-ICU mortality-associated factors were determined by multivariate logistic regression.

RESULTS: We analyzed 171 ICU patients with pulmonary abscesses. 78% were male with a mean age of 56.5 ± 16.4 years. 20.4% were excessive alcohol users, 25.2% had a chronic lung disease (14% COPD), and 20.5% had a history of cancer. Overall, 40.9% were immunocompromised and 38% qualified for nosocomial infection. Presenting symptoms included fatigue or weight loss in 62%, fever (50.3%) and dyspnea (47.4%). Hemoptysis was reported in 21.7%. A polymicrobial infection was present in 35.6%. The most frequent pathogens were Enterobacteriaceae in 31%, S. aureus in 22% and Pseudomonas aeruginosa in 19.3%. 10.5% were fungal infections. Several clusters of clinico-radiological patterns were associated with specific microbiological documentation and could guide empiric antibiotic regimen. 11.7% had percutaneous abscess drainage; surgery was performed in 12.7%, and 12% required bronchial-artery embolization for hemoptysis. In-ICU mortality was 21.5%, and age [OR: 1.05 (1.02-1.91), P=0.007], RRT during ICU stay [OR: 3.56 (1.24-10.57), P=0.019], and fungal infection [OR: 9.12 (2.69-34.5), P=0.0006] were independent predictors of mortality after multivariate logistic regression, while drainage or surgery were not.

INTERPRETATION: Pulmonary abscesses in the ICU are a rare but severe disease often resulting from a polymicrobial infection with a high proportion of Enterobacteriaceae, S. aureus, and P. aeruginosa. Percutaneous drainage, surgery or arterial embolization was required in more than a third of cases. Further prospective studies focusing on first-line antimicrobial therapy and source control procedure are warranted to improve and standardize patient management.

PMID:37652296 | DOI:10.1016/j.chest.2023.08.020

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PubMed articles on: Cancer & VTE/PE

The unfolded protein response links ER stress to cancer-associated thrombosis

JCI Insight. 2023 Aug 31:e170148. doi: 10.1172/jci.insight.170148. Online ahead of print.