bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of cardiovascular events in patients treated with immune checkpoint inhibitors
Authors: Laenens D , Yu Y , Santens B , Jacobs J , Beuselinck B , Bechter O , Wauters E , Staessen J , Janssens S , Van Aelst L 
Published: October 2022

Abstract

Background
In rare cases, immune checkpoint inhibitors (ICIs) cause immune-mediated myocarditis. However, the true incidence of other major adverse cardiovascular events (MACE) following ICI treatment remains unknown, mainly because late occurring side effects are rarely reported in prospective clinical trials.

Purpose
To identify the incidence and risk factors of MACE in a real-life ICI-treated cancer cohort and to compare the incidence with non-ICI-treated cancer patients and population controls.

Methods
In total, 672 ICI-treated patients were included. The primary endpoint was MACE, a composite of acute coronary syndrome, heart failure, stroke and transient ischemic attack. Secondary outcomes were acute coronary syndrome and heart failure separately. Incidence rates were compared between groups after matching according to age, sex, cardiovascular history and cancer type.

Results
Incidence of MACE was 10.3% during a median time of follow-up of 13 months (IQR 6 to 22). In multivariable analysis, a history of heart failure (hazard ratio (HR): 2.27; 95% confidence interval (CI): 1.03 to 5.04; p=0.043) and valvular heart disease (HR 3.01; 95% CI: 1.05 to 8.66; p=0.041) remained significantly associated with MACE.
Cumulative incidence rates were significantly higher in the matched ICI group (rate at full range of follow-up (rate): 8.51; 95% CI: 6.18 to 11.4) compared with the cancer cohort not exposed to ICI (rate: 5.20; 95% CI: 3.56 to 7.35; p=0.032) and the population controls (rate: 2.55; 95% CI: 2.16 to 2.99; p&lt;0.001) mainly driven by a higher risk of heart failure events (Figure 1).

Conclusions
Cardiovascular events during and after ICI treatment are more common than currently appreciated. Patients at risk are those with a history of cardiovascular disease. Compared with matched cancer and population controls, MACE incidence rates are significantly higher, suggesting a potential harmful effect of ICI treatment besides the underlying risk.

Funding Acknowledgement
Type of funding sources: None.
Baseline left atrial reservoir strain provides independent and incremental prognostic value in predicting chemotherapy related cardiotoxicity
Authors: Yu C , Negishi T , Thavendiranathan P , Pathan F , Penicka M , Cote M A , Massey R J , Miyazaki S , Shirazi M , Santoro C , Vinereanu D , Kosmala W , Thomas L , Marwick T H , Negishi K 
Published: October 2022

Abstract

Background
Currently, few baseline imaging biomarkers can predict chemotherapy induced cardiotoxicity (CTx). The early identification of CTx is critically important as it determines the prospect of LV function recovery (1).

Purpose
We aimed to determine if baseline left atrial (LA) reservoir strain (LAS) is predictive of CTx.

Methods
We performed retrospective analysis of the SUCCOUR study, an international multicentre randomized controlled trial. CTx was defined as an asymptomatic drop of &gt;10% in left ventricular ejection fraction (LVEF) compared to baseline to &lt;55%. LAS analysis was performed using semi-automated speckling tracking of the LA in the four and two chamber views using EchoPAC. Analysis was performed at one year follow up. Cox proportional hazard analysis, c-statistics and Akaike information criterion (AIC) statistical analysis was performed.

Results
After excluding 78 with inadequate images, 229 were included in the analysis. Most participants were female (n=215, 94%), with a mean age of 54±12 years. Median follow up was 1.02 years (IQR 0.98–1.07). A smoking history was the commonest cardiac risk factor (n=68, 30%). Breast cancer was the main cancer type (n=205, 90%). The mean baseline 3D LVEF, LV global longitudinal strain (GLS), LAS, and LA volume index (LAVI) were 61±4%, 20.6±2.5%, 28.6±7.9%, and 28±9ml/m2, respectively. Participants that developed CTx had a lower LAS at baseline compared to those that did not (25.5±7.4% vs 29.0±7.9% respectively; p=0.027). At 1-year follow-up, 29 patients (13%) developed CTx. On univariable Cox proportional hazard analysis, higher baseline LAS was associated with a lower risk of CTx (HR 0.95, 95% CI 0.90–0.99; p=0.026) but other parameters including baseline GLS was not (p=0.17). In nested Cox models (Figure 1), adding LAS significantly improved the model's predictive accuracy for CTx compared to other clinical and imaging parameters. When LAS was added to the same models it showed improvements in the c-statistics and AIC score (Figure 1).

Conclusion
Baseline LAS is an independent and incremental predictor of CTx. LAS could be used for baseline risk stratification in oncology patients who receive potentially cardiotoxic chemotherapy.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): GE Healthcare
Cardiac magnetic resonance relaxometry compared to left ventricular ejection fraction in the identification of anthracycline related cardiac changes: a systematic review and meta-analysis
Authors: Yu C , Pathan S , Jeyaprakash P , Pathan F , Kritharides L , Negishi K 
Published: October 2022

Abstract

Background
Anthracyclines are associated with cancer therapeutics related cardiac dysfunction (CTRCD). The identification of CTRCD currently uses a change in left ventricular ejection fraction (LVEF). Myocardial damage associated with anthracyclines include myocardial inflammation and oedema. This can be assessed using cardiac magnetic resonance (CMR) relaxometry techniques; T1 and T2 mapping and extracellular volume (ECV) fraction.

Purpose
In this meta-analysis, we compared the magnitude of the changes in LVEF and CMR relaxometry techniques wihtin a month of anthracycline therapy completion.

Methods
We performed a structured literature review as per the PRISMA guidelines across three databases (EMBASE, MEDLINE, and SCOPUS) for studies evaluating CMR relaxometry parameter at baseline and soon after completion of anthracycline therapy (3–5 months post baseline). CMR parameters pre and post anthracycline-based chemotherapy were abstracted. A random effects model was used to pool mean difference (MD) in LVEF and ECV given standardisation in imaging acquisition techniques. A random effects model was used to pool standardized mean difference (SMD) in LVEF, T1, T2 and ECV after anthracycline to adjust for variations in imaging techniques and comparison between techniques.

Results
A total of 174 patients were included from seven studies. 91% were female with a mean age of 55.6 years. The pooled MD in LVEF and ECV was −3.15% [95% CI −4.99, −1.31] and 1.61% [0.90, 2.32], respectively. The pooled SMD in LVEF, T1, T2 and ECV was −0.61 [−0.96, −0.25] 0.34 [0.04, 0.63], 0.67 [0.12,1.21], 0.6 [0.31, 0.89], respectively (Table 1).

Conclusions
T2 mapping, ECV and LVEF can identify early myocardial changes better than T1 mapping. These changes suggest there is marked oedema in the myocardial injury from anthracycline therapy. Whilst these findings support the role of CMR relaxometry in identifying CTRCD, further studies are required.

Funding Acknowledgement
Type of funding sources: None.
Increased epicardial adipose tissue volume after anthracycline chemotherapy is associated with a low risk of cardiotoxicity in breast cancer
Authors: Kwon S , Nam B D , Kwon S H , Bang D W 
Published: October 2022

Abstract

Introduction
Chemotherapy-induced cardiotoxicity is a critical issue for patients with breast cancer. Epicardial adipose tissue (EAT) is located between the myocardial surface and the visceral layer of the pericardium. Change of EAT is associated with cardiac dysfunction.

Purpose
Considering that early detection of patients at risk of developing cardiotoxicity during and after anthracycline-based chemotherapy is the most important factor in reducing and reversing cardiac function, there is a need to identify a simple and novel imaging marker that can predict cardiotoxicity at an early stage. Therefore, the objective of the present study was to investigate the relationship between EAT and chemotherapy-induced cardiotoxicity.

Methods
This retrospective study analyzed EAT on chest computed tomography (CT) of patients with early breast cancer using automatic, quantitative measurement software between November 2015 and January 2020. Changes in EAT before and after initiation of chemotherapy were compared according to the type of anticancer drug. Subclinical cardiotoxicity was defined as worsening ≥10% in left ventricular ejection fraction to an absolute value &gt;50% with a lower limit of normal measured with standard echocardiography.

Results
Among 234 patients with breast cancer, 85 were treated with adjuvant anthracycline-based (AC) and 149 were treated with non-anthracycline based (non-AC) chemotherapy. There was a significant increase in EAT volume index (mL/kg/m2) at the end of chemotherapy compared to that at the baseline in the AC group (3.33±1.53 vs. 2.90±1.52, p&lt;0.001), but not in the non-AC group. During the follow-up period, subclinical cardiotoxicity developed in 20 (8.6%) patients in the total population (15.3% in the AC group and 4.8% in the non-AC group). In the multivariable analysis, EAT volume index increment after chemotherapy was associated with a lower risk of subclinical cardiotoxicity in the AC group (Odds ratio: 0.364, 95% CI: 0.136–0.971, p=0.044).

Conclusions
Measurement of EAT during anthracycline-based chemotherapy might help identify subgroups who are vulnerable to chemotherapy-induced cardiotoxicity. Early detection of EAT volume change could enable tailored chemotherapy with cardiotoxicity prevention strategies.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Medical Technology Development Program of the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT).
Cardiac autonomic modulation with donepezil attenuates pyroptosis and mitochondrial dysfunction, leading to improved left ventricular function in trastuzumab-induced cardiotoxicity in rats
Authors: Khuanjing T , Maneechote C , Ongnok B , Prathumsap N , Arinno A , Chunchai T , Arunsak B , Chattipakorn S C , Chattipakorn N 
Published: October 2022

Abstract

Background
Trastuzumab (Trz)-induced cardiotoxicity (TIC) is one of the most common cardiovascular complications of targeted anticancer agents. Cardiac inflammation, cardiac mitochondrial dysfunction, oxidative stress, and cardiac autonomic dysfunction have been identified as potential mechanisms underlying the adverse effects of TIC. Although cardiac inflammation is one of the key mechanisms triggering “pyroptosis”, i.e. a new inflammatory form of programmed cell death, the association between TIC and pyroptosis is still largely unknown. Moreover, the modulation of cardiac autonomic activity using an acetylcholinesterase inhibitor (AChE) has been shown to exert cardioprotection in various heart diseases. However, the role of donepezil (DPZ), an AChE, in treating TIC has never been investigated.

Purpose
We evaluated the cardioprotective effects of DPZ on left ventricular (LV) function, cardiac mitochondrial function, and pyroptosis in rats with TIC. We hypothesised that DPZ reduces mitochondrial dysfunction and pyroptosis, leading to a reduction of LV dysfunction in TIC rats.

Methods
Fifteen male Wistar rats were randomly divided into the control group (n=5, 0.9% normal saline solution, ip) and the Trz group (n=10, 4 mg/kg/day for 7 days, ip). Trz-treated rats were subdivided into the vehicle group (n=5, drinking water, po) and the DPZ group (n=5, 5 mg/kg/day for 7 days, po). At the end of the experiment, echocardiography was performed, and the heart was removed to determine the cardiac mitochondrial function and pyroptosis.

Results
Compared with the control group, %LV ejection fraction (%LVEF) was significantly decreased in the Trz group (Fig. 1A). Trz treatment also markedly increased cardiac mitochondrial reactive oxygen species (ROS) production and mitochondrial depolarisation, as indicated by a lower red/green fluorescence intensity ratio (Fig. 1B and C, respectively). Furthermore, Trz induced pyroptosis by increasing NLR family pyrin domain containing 3 (NLRP3) expression and cleaved Gasdermin D/Gasdermin D ratio, compared to the control group (Fig, 1D–F). Notably, DPZ co-treatment potentially reduced mitochondrial ROS production, mitochondrial depolarisation, and pyroptosis (NLRP3 and cleaved Gasdermin D/Gasdermin D ratio), leading to improved %LVEF (Figure 1).

Conclusion
DPZ alleviated cardiac dysfunction in TIC rats by improving mitochondrial function and reducing pyroptosis. These findings suggested that DZP could be a novel effective pharmacological intervention against TIC.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 1. The National Science and Technology Development Agency Thailand2. The Thailand Research Fund (RGJ)
Effect of serum lipid profile on the risk of breast cancer: systematic review and meta-analysis of 1,717,054 women
Authors: Nouri M , Mohsenpour M A , Katsiki N , Ghobadi S , Jafari A , Faghih S , Banach M , Mazidi M 
Published: October 2022

Abstract

Background
Dyslipidemia has been linked to breast cancer incidence. However, conflicting results exist regarding the associations between lipid components and breast cancer development.

Purpose
The aim of the present meta-analysis was to further investigate the relationships between serum lipid profile and the risk of breast cancer.

Methods
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed to conduct the present systematic review and meta-analysis. Databases such as the PubMed, EMBASE, and Web of Sciences, were searched up to the end of January 2021, using certain MeSH and non-MeSH keywords and their combination to extract related published articles.

Results
Twenty-six prospective studies met the inclusion criteria involving 1,717,054 women, of whom 36,590 were diagnosed with breast cancer during the follow-up. A negative and significant association was found between HDL-C levels and the risk of breast cancer [relative risk (RR): 0.85, 95% CI: 0.72–0.99, I2: 67.6%, p=0.04) (Figure). In contrast, TG (RR: 1.02, 95% CI: 0.91–1.13, I2: 54.2%, p=0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90–1.06, I2: 67.2%, p=0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70–1.30, I2: 83.5%, p=0.78) and LDL-C (RR: 0.93, 95% CI: 0.79–1.09, I2: 0%, p=0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, TC was positively correlated to breast cancer risk (RR: 1.05, 95% CI: 1.01–1.10 and 1.05, 95% CI: 1.01–1.10, respectively), as was TG in studies adjusting for baseline lipids (RR: 0.92, 95% CI: 0.85–0.99) and race (RR: 1.80, 95% CI: 1.22–2.65).

Conclusions
In the present meta-analysis, HDL-C was inversely related to breast cancer risk. In contrast, no significant associations were found for TC (except after adjusting for hormone use and physical activity), TG (except after adjusting for baseline lipids and race), LDL-C and ApoA. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence supporting that low HDL-C is related to an increased risk for this malignancy. Further research is needed to establish the associations between different lipid components and breast cancer risk in certain populations.

Funding Acknowledgement
Type of funding sources: None.
Low-dose anticoagulation for peripheral deep vein thrombosis of the lower extremities in cancer patients
Authors: Nonaka A , Fukuda Y 
Published: October 2022

Abstract

Background
Venous thromboembolism (VTE) is a frequent complication in cancer patients and is often detected as asymptomatic peripheral deep vein thrombosis (DVT). However, guidelines for peripheral DVT have not been established in either general cardiology or onco-cardiology. Furthermore, in cancer patients, it is generally considered difficult to administer standard doses of anticoagulants due to the high risk of bleeding caused by thrombocytopenic tendency during chemotherapy, as well as bleeding lesions such as gastrointestinal and gynecological cancers.
Treatment of peripheral DVT with direct oral anticoagulants (DOACs) may minimize the worsening of bleeding and prevent the transition to proximal DVT.

Objective
The purpose of this study was to investigate the optimal treatment for peripheral DVT in cancer patients.

Methods
242 consecutive patients with peripheral DVT of the lower extremities (excluding complications of pulmonary thromboembolism or proximal DVT) were examined by venous ultrasound from April 2019 to March 2020. 190 patients could be followed up by ultrasound examination, for up to 2 years. The course of the DVT was retrospectively examined. In cases of anticoagulant therapy, standard and low dosage of DOACs were evaluated.

Results
142 patients were treated with anticoagulant (AC) therapy (group AC(+)), 48 patients were without AC therapy (group AC(−)). (4 of the 142 patients were treated with warfarin and the rest with DOACs).
DVT worsened in 8 patients (5.6%) in the AC(+) group and 23 patients (47.9%) in the AC(−) group. DVT worsening was significantly less in the AC(+) group (p&lt;0.0001).
There were no cases of worsening to proximal type in the AC(+) group and 4 cases (17.4%) in the AC(−) group.
Of the 138 patients who used DOACs as AC therapy, 62 used half or less than the standard dose for maintenance (low-dose DOAC group), and 76 used the standard dose as maintenance (standard-dose DOAC group).
In the low-dose DOAC group, DVT worsened in 5 cases, remained unchanged in 7 cases, and improved in 50 cases. In the standard-dose DOAC group, there were 4 cases of worsening DVT, 3 cases of no change, and 69 cases of improvement. There was no significant difference in the DVT treatment effect between the two groups.
There were no thrombus-related deaths.

Conclusion
Peripheral DVT worsens in about half of cancer patients without anticoagulation, and 17% of these worsen to proximal VTE. In addition, low-dose DOACs are found to be as effective as standard-dose DOACs in treating peripheral DVT in cancer patients. Peripheral DVT treatment with low-dose DOACs can reduce the risk of bleeding complications and thrombus-related mortality in cancer patients and should be one of the supportive treatments for the completion of cancer management.

Funding Acknowledgement
Type of funding sources: None.
Cancer as a risk factor for physical dysfunction and poor prognosis in patients with cardiovascular disease
Authors: Miki T , Kamiya K , Hamazaki N , Nozaki K , Ichikawa T , Yamashita M , Uchida S , Noda T , Ueno K , Yamaoka-Tojo M , Maekawa E , Sasaki J , Matsunaga A , Ako J 
Published: October 2022

Abstract

Introduction
The emerging interdisciplinary field of cardio-oncology is of interest to clinicians because a history of cancer or cancer treatment is considered a severe risk factor for cardiovascular disease (CVD). Both cancer and CVD can reduce skeletal muscle mass; together, they can lead to a poorer prognosis. However, it is unclear whether a patient's cancer history can lower physical function and lead to a poor prognosis with the coexistence of cancer history and physical dysfunction in patients with CVD. This study aimed to identify the relationship between cancer history and physical function, as well as the prognostic value of their combination, in patients with CVD.

Methods
We reviewed 3,640 patients with CVD (mean age, 67.9±13.5 years) who underwent physical-function tests (gait speed and 6-min walking distance [6MWD]). We performed multivariate linear regression analysis to assess potential associations between cancer history and physical-function tests in patients with CVD. Additionally, we used the Kaplan–Meier curve and Cox regression analyses to assess survival and prognostic significance for patients divided into four groups according to the presence or absence of cancer history and high or low physical function.

Results
In multivariate linear regression analysis, cancer history was independently associated with lower gait speed and 6MWD (gait speed, P=0.048 and 6MWD, P=0.040). A total of 581 deaths occurred over a median follow-up period of 3.08 years (interquartile range: 1.36–5.27). For all-cause mortality, patients with a history of cancer and reduced physical function were found to have a significantly higher mortality risk even after adjusting for several covariates (gait speed, HR: 1.66, P=0.003 and 6MWD, HR: 1.71, P=0.003).

Conclusion
Cancer history was correlated with physical dysfunction in patients with CVD. Moreover, the coexistence of cancer history and physical dysfunction resulted in poorer prognosis in patients with CVD.

Funding Acknowledgement
Type of funding sources: None.
Five-year cardiovascular outcomes in patients with chronic myeloid leukemia treated with imatinib, dasatinib or nilotinib: data from a large multinational collaborative network
Authors: Belo Nunes R , Da Costa L M A , Bachour P , Cantarelli M J , Neves P D M , Oliveira G B F 
Published: October 2022

Abstract

Background
BCR-ABL tyrosine kinase inhibitors (TKI) have revolutionized the treatment of patients with chronic myeloid leukemia (CML). However, concern has arisen about the cardiac safety profile of these drugs.

Purpose
To compare long-term risks of adverse cardiovascular and cerebrovascular events (ACE), heart failure or left ventricular ejection fraction (LVEF) &lt;50% and venous thromboembolic events (VTE) in patients with CML treated with first-line Bcr-ABL TKIs, using data from a large multinational network.

Methods
Patients aged ≥18 years with chronic myeloid leukemia treated with imatinib or dasatinib or nilotinib and without prior cardiovascular or cerebrovascular disease. We used propensity score matching to balance the cohorts. The 5-year cumulative incidences and hazard ratios were calculated.

Results
We identified 3,722 patients with CML under treatment with Imatinib (n=1,906), Dasatinib (n=1,269) and Nilotinib (n=547). Patients with imatinib compared to dasatinib showed higher risk for ACE (hazard ratio 2,13, 95% IC 1.15–3.94, p=0.016). Patients with imatinib presented lower risk than nilotinib for ACE (hazard ratio 0.50, 95% IC 0.30–0.83, p=0.0074). In relation to heart failure or LVEF &lt;50%, patients with imatinib had higher risk than dasatinib (hazard ratio 9.41, 95% IC 1.22–72.17, p=0.03), but no significant difference was observed between imatinib and nilotinib (hazard ratio 0.48, 95% IC 0,215–1.01, p=0.064). The probability of survival (Kaplan Meier curves) without ACE, heart failure or LVEF &lt;50% and VTE are depicted in the Central Illustration.

Conclusions
In a large cohort of patients with CML, those treated with nilotinib had higher 5-year risk of adverse cardiovascular and cerebrovascular events, while patients with dasatinib showed lower risk than patients with imatinib. The risk of heart failure was higher in patients with imatinib than in patients with dasatinib, but not when compared to nilotinib.

Funding Acknowledgement
Type of funding sources: None.