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

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

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

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

Radiation therapy in the thoracic region: Radio-induced cardiovascular disease, cardiac delineation and sparing, cardiac dose constraints, and cardiac implantable electronic devices

Cancer Radiother. 2023 Aug 28:S1278-3218(23)00138-5. doi: 10.1016/j.canrad.2023.06.027. Online ahead of print.

ABSTRACT

Radiation therapy in the thoracic region may deliver incidental ionizing radiation to the surrounding healthy structures, including the heart. Radio-induced heart toxicity has long been a concern in breast cancer and Hodgkin's lymphoma and was deemed a long-term event. However, recent data highlight the need to limit the dose to the heart in less favorable thoracic cancers too, such as lung and esophageal cancers in which incidental irradiation led to increased mortality. This article will summarize available cardiac dose constraints in various clinical settings and the types of radio-induced cardiovascular diseases encountered as well as delineation of cardiac subheadings and management of cardiac devices. Although still not completely deciphered, heart dose constraints remain intensively investigated and the mean dose to the heart is no longer the only dosimetric parameter to consider since the left anterior descending artery as well as the left ventricle should also be part of dosimetry constraints.

PMID:37648559 | DOI:10.1016/j.canrad.2023.06.027

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PubMed articles on: Cardio-Oncology

Cell membrane-camouflaged bufalin targets NOD2 and overcomes multidrug resistance in pancreatic cancer

Drug Resist Updat. 2023 Aug 21;71:101005. doi: 10.1016/j.drup.2023.101005. Online ahead of print.

ABSTRACT

AIMS: Multidrug resistance in pancreatic cancer poses a significant challenge in clinical treatment. Bufalin (BA), a compound found in secretions from the glands of toads, may help overcome this problem. However, severe cardiotoxicity thus far has hindered its clinical application. Hence, the present study aimed to develop a cell membrane-camouflaged and BA-loaded polylactic-co-glycolic acid nanoparticle (CBAP) and assess its potential to counter chemoresistance in pancreatic cancer.

METHODS: The toxicity of CBAP was evaluated by electrocardiogram, body weight, distress score, and nesting behavior of mice. In addition, the anticarcinoma activity and underlying mechanism were investigated both in vitro and in vivo.

RESULTS: CBAP significantly mitigated BA-mediated acute cardiotoxicity and enhanced the sensitivity of pancreatic cancer to several clinical drugs, such as gemcitabine, 5-fluorouracil, and FOLFIRINOX. Mechanistically, CBAP directly bound to nucleotide-binding and oligomerization domain containing protein 2 (NOD2) and inhibited the expression of nuclear factor kappa-light-chain-enhancer of activated B cells. This inhibits the expression of ATP-binding cassette transporters, which are responsible for chemoresistance in cancer cells.

CONCLUSIONS: Our findings indicate that CBAP directly inhibits NOD2. Combining CBAP with standard-of-care chemotherapeutics represents a safe and efficient strategy for the treatment of pancreatic cancer.

PMID:37647746 | DOI:10.1016/j.drup.2023.101005

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PubMed articles on: Cardio-Oncology

Role of echocardiography in patients treated with immune checkpoints inhibitors

J Echocardiogr. 2023 Aug 30. doi: 10.1007/s12574-023-00621-z. Online ahead of print.