Cardio-oncology最新文献

Immune checkpoint inhibitor (ICI) therapy is a rapidly expanding pillar of cancer treatment, but it carries the risk of immune-related adverse events. Among the most fatal is ICI-related myocarditis (ICIRM). Cardiac magnetic resonance (CMR) imaging is the non-invasive current gold standard for diagnosis, with significant disparities regarding availability and utilisation. The vast majority of ICIRM cases are reported in high-income countries (HICs), reflecting not only patterns of ICI use, but also a profound diagnostic gap in low- and middle-income countries (LMICs). LMICs face barriers to CMR access, including a stark deficit of MRI scanners, with approximately 1 scanner per million people in LMICs versus 26 per million people in HICs, prohibitive costs, and a critical shortage of trained radiologists and cardiologists. The inequity means that as ICI therapy becomes increasingly accessible worldwide, patients in resource-limited settings will be at a high-risk of undiagnosed and untreated ICIRM. Our paper issues a call to address this critical healthcare disparity. To improve CMR access for ICIRM diagnosis in LMICs, a multi-pronged strategy is imperative - Governmental support and policy change to prioritise infrastructure investment and integrate CMR into national health strategies; targeted educational programmes, such as the SWiM and 'train the trainer' initiatives, to build local expertise in CMR acquisition and interpretation; adoption of technological innovations, including cost-effective rapid CMR protocols and artificial intelligence (AI) tools that can reduce scan times.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) is a variant of autonomic dysfunction (AD) defined by an increase in heart rate (HR) ≥ 30 bpm within 10 minutes (min) of a change from the supine to an upright position, in the absence of orthostatic hypotension. Many studies suggest that AD is common in active cancer patients and is associated with variable symptoms and decreased survival. Based on this evidence, we hypothesized that POTS can be associated with active cancer and might contribute to some of these patients' symptoms and survival.

Methods: Consecutive 220 active cancer patients aged 19-59 were enrolled. They were asked to lay flat for 5-10 min then to stand for 10 min without support. Total of 5 blood pressure (BP) and HR readings were taken (immediately before standing up then immediately after, and at 3, 6, and 10 min while standing). All patient's symptoms were recorded.

Results: 213 patients were included. Age was 48 ± 8, 76% were females,18% had metastasis and 43% were on chemotherapy. 55% reported symptoms of AD, with symptoms associated with standing were reported in 28%. Baseline HR was 76 ± 13 bpm, and systolic BP was 129 ± 20. Upon standing, HR increased by 10 ± 3 bpm and systolic BP dropped by 1.3 ± 0.4. Immediately after standing, 47 (22%) Patients developed symptoms.18 patients (8.5%) met the criteria for POTS, where HR increased by 37 ± 5 with an increase in systolic BP by -1.6 ± 6. Patients with POTS had higher HR upon standing (p = 0.000), HR at 3 min (p = 0.005), HR at 6 min (p = 0.002), and HR at 10 min (p = 0.000). In contrast, baseline HR and BP showed no significant difference between patients with and without POTS (p = 0.74 and 0.11). After 16.9 ± 5.5 months, there was no statistical deterrence in all-cause mortality between POTS and non-POTS patients.

Conclusion: POTS and orthostatic intolerance are prevalent in active cancer, where onset of symptoms started after cancer diagnosis in many patients. These patients have a significant association with higher HR upon standing and overall prognosis comparable to that of patients without POTS.

Background: SARS-CoV-2 non-structural protein 6 (NSP6) in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Its reported role in immune evasion, viral replication and egress from the cells as well as its gain of function mutations occurring independently in various variants underscores its importance.

Methods: Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of regulated host proteins interacting with reported SARS-CoV-2 NSP6 interacting proteins - SIGMAR1, ATP13A3, ATP5MG, and ATP6AP1. Tissue-specific protein interactomes and hub genes in these interactomes were found, and drugs targeting them were sought out.

Results: Key hub genes in the brain were CCND1, CDK2, CCNA1, CDC6, CDKN1B, SKP1, CCNB1, etc., whereas in the heart were RAB7A, ATP6V0D1, LAMP2, TGFB1, CANX, LGALS3, etc. Lung hub genes were ATP6V0A1, ATP6V0A2, ATP6V0D1, ATP6V1D, ATP6V1B1, ATP6V1E1, TGFB1, EGF, TGFBR2, and LGALS3. Hub gene associated pathways in the brain were iron uptake and transport, G1/S transition, and small cell Lung cancer. Differentiation of dendritic cells and reduction of intraphagosomal pH to 5 - were prominent pathways in lung. In heart, phagosome associated pathways, and regulation of intracellular were prominent. Key therapeutic targets identified in the brain are CDK2, targeted by acetaminophen and raltitrexed; CCNE1 by palbociclib; and CCND1 by palbociclib, acetaminophen, lapatinib, doxorubicin, and methotrexate. In the heart, TGFB1 and APP are targeted by inositol, while LGALS3, upregulated after COVID-19 can be targeted by non-approved drugs (Belapectin, Olitigaltin, Lactose anhydrous, Davanat). In the lungs, TGFB1 and TGFBR2 are targeted by irinotecan, and EGF by cetuximab.

Conclusions: This study highlights probable hub genes, drugs targeting them, and associated pathways perturbed by SARS-CoV-2 NSP6. Galectin3 (LGALS3) upregulated in both heart and brain after COVID-19 infection is reported to be influencing all the ten hallmarks of cancer. Our bioinformatics and systems study hints probable effect of COVID-19 infection in cancer incidence and warrants in-depth studies for present scenario of long and recurrent COVID-19.

Background: Despite advances in radiotherapeutic techniques, radiation-induced cardiovascular diseases (CVD) remain a leading but often underrecognized cause of morbidity and mortality in cancer survivors. Radiation exposure can trigger a broad spectrum of cardiotoxic effects yet clinical awareness and strategies for managing these long-term complications remain limited. Among emerging indicators of vascular dysfunction, measures of vascular flexibility offer key biomarkers for assessing vascular compliance and cardiovascular risk.

Methods: The present study hence investigated age- and dose-dependent effects of local irradiation on vascular function of the murine Arteria saphena in C57BL/6 wild-type and atherosclerosis-prone apolipoprotein E-knockout (ApoE^-/-) mice, a well established model for human CVD. Pathological effects of irradiation on vascular function of the A. saphena were assessed using in vivo Optical Coherence Tomography. Vascular flexibility in terms of arterial diameters and speed of diameter changes during vasoconstriction and vasodilation were recorded one day and 3, 6, 9, 12, or 18 months following irradiation with single doses of 2, 5, 8, 10, 16 Gy.

Results: Baseline arterial diameters declined with age in both strains, with earlier onset in ApoE^-/- mice. Significant interactions with radiation dose indicate greater radiation sensitivity in ApoE^-/- mice and additive effects of radiation and aging in both strains. Vasoconstriction halved arterial diameters in wild-type and more so in ApoE^-/- mice, reflecting an enhanced vasoconstrictive response that diminished after 16 Gy. Contractility was found to be age-dependent, peaking between 6 and 12 months post-irradiation, while time to half-maximal constriction remained unchanged across conditions. Maximal vasodilation ranged from 1.2 to 2 × baseline, initially higher in ApoE^-/- mice but declining earlier with age than in wildtype mice. ApoE^-/- mice exhibited more sustained vasodilation, which progressively slowed with age and higher radiation doses in both strains.

Conclusion: Both mouse strains exhibited marked age-related vascular changes, with ApoE^-/- mice showing greater radiation sensitivity. The combined effects of aging and radiation were most prominent in reduced arterial diameters at baseline and after vasoconstriction, along with slower vasodilation reflecting elevated vascular resistance linked to hypertension. Early blood pressure management is therefore essential to reduce the risk of radiation-induced CVD.

Background: Children, adolescents, and young adults with cancer (referred to as CAYAs) are at risk of long-term health complications, with cardiovascular disease (CVD) being a major concern. In addition, sociodemographic characteristics and traditional cardiovascular risk factors may also contribute to disparities in outcomes compared with those of the general population. The aim of this study was to investigate the timing, patterns, and combinations of CVDs, as well as associated morbidity, mortality, and sociodemographic factors, in CAYAs with CVD compared with matched controls with CVD.

Methods: A register-based cohort study consisting of all Swedish cancer patients under 25 years old and during a 63-year observation time was used. CAYAs and controls with CVD (n = 58,981) were included and compared in terms of the timing and combinations of CVD, and mortality.

Results: The median age at first CVD was 41.8 years in CAYAs and 49.6 years in controls (p < 0.0001), with male CAYAs being the youngest at 25.0 years. During a median follow-up of 34.6 years, most CAYAs (65.2%) developed one CVD, while two or three coexisting CVDs occurred in 20.2% and 8.2%, respectively. Mostly hypertension in combination with cerebrovascular disease, ischemic heart disease and arrhythmias. More than three CVDs were more common in CAYAs than in controls (6.4% vs. 5.9%). A total of 21.8% of the CAYAs died, and the risk of all-cause mortality after the first CVD was 2.43-fold greater (hazard ratio (HR) 95% confidence interval (CI) 2.31-2.54, p < 0.0001), and for cardiovascular mortality, the risk was 2.17-fold greater (HR 95% CI 2.02-2.33, p < 0.0001) than that of the controls. In CAYAs with CVD, older age, male sex, and living in the central part of Sweden were associated with higher mortality, whereas higher education and marriage were protective (p < 0.0001).

Conclusions: Compared with controls CAYAs develop advanced CVD and combinations of multiple CVDs earlier in life, and they have a greater risk of all-cause and cardiovascular mortality. Factors associated with increased mortality risk include male sex and geographic variation, whereas marriage and higher education appear to be protective.

Background: Anthracyclines can cause dose-dependent cardiotoxicity that may be irreversible. To minimize cardiotoxic effects, substituting doxorubicin for liposomal doxorubicin (LD) has been explored as a cardioprotective strategy.

Objectives: To describe randomized clinical trials (RCTs) comparing the efficacy and safety of LD with other anthracycline-based regimens.

Methods: We conducted a systematic review and meta-analysis of RCTs comparing LD with other anthracycline-based regimens, using data from Medline, Embase, Emcare, the Cochrane Central Register, and LILACS.

Results: Twelve studies including 3027 patients with breast cancer (6), multiple myeloma (2), lymphoma (2), sarcoma (1), and acute lymphocytic leukemia (1) were included. Most participants (86%) were women with breast cancer. Nine studies compared LD with conventional doxorubicin and three with epirubicin. Overall, the risk of bias was classified as "some concerns". Follow-up ranged from 24-72 months - the median follow-up time among the studies was 37 months. There was a reduction in heart failure (HF) incidence in the LD group compared to the control (RR 0.32, 95%CI 0.18-0.55). A significant decrease in left ventricular ejection fraction (LVEF), as defined by each study´s criteria, was less frequent in the LD group compared to other anthracycline-based therapies (RR 0.39, 95%CI 0.30-0.51). All-cause mortality (RR 0.98, 95%CI 0.90-1.07) and tumor response (RR 0.99, 95%CI 0.93-1.05) did not differ between the groups.

Conclusions: LD use was associated with a decrease in the occurrence of HF compared to other anthracycline-based therapies, with no worse cancer outcomes. A significant decrease in LVEF was also less frequent in the LD group; however, no difference was found in cardiovascular mortality.

Background: Treatment of breast cancer by chemotherapy or radiotherapy exposes the patient to the risk of cardiotoxicity, which can be assessed pre-therapeutically using scores such as the Heart Failure Association and International Cardio-Oncology Society (HFA-ICOS) score. We aimed to evaluate the risk of cardiotoxicity using the HFA-ICOS score in a group of Cameroonian women before treatment of breast cancer by chemotherapy and/or radiotherapy.

Methods: We conducted a cross-sectional analytic study using retrospective data collected from the Cardiology and Oncology departments at Yaounde Central Hospital and the Internal Medicine department at Yaounde General Hospital over an eight-year period, from 2017 to 2024, with a focus on the nine months from November 2023 to June 2024. Inclusion criteria consisted of patients with histologically confirmed breast cancer treated with chemotherapy and/or radiotherapy. We performed a multivariate analysis to determine the factors associated with moderate and high risk of cardiotoxicity, with a significance threshold of p ≤ 0.05.

Results: Of the 130 patients recruited, the median age was 46.5 years (interquartile range, IQR, 36.75-58.00), with extremes of 21 and 76 years. Comorbidities mainly were overweight/obesity in 92 (70.7%) cases and arterial hypertension in 32 (24.6%) cases. Invasive ductal carcinoma was the main histological type, accounting for 126 (96.9%) cases, and triple-negative carcinoma was the most frequent molecular subtype, comprising 55 (42.3%) cases. Treatment consisted of exclusive chemotherapy in 96 (73.8%) cases and radiotherapy associated with chemotherapy in 27 (20.8%) cases. Based on the HFA-ICOS score, the cardiotoxicity risk was low in 93 (71.5%) patients. The independent factors associated with the risk of moderate to severe cardiotoxicity were age ≥ 60 years (adjusted OR: 5.97; 95% CI 1.73-20.60; adjusted p = 0.005), obesity (adjusted OR: 5.81; 95% CI 1.78-18.91; p = 0.003) and hypertension (adjusted OR: 27.10; 95% CI 7.51-97.76; p < 0.001). Exclusive chemotherapy was a protective factor (adjusted OR: 0.24; 95% CI 0.07-0.81; adjusted p = 0.021).

Conclusion: Women with breast cancer in Cameroon tend to be relatively young and present a low risk of cardiotoxicity before starting anti-cancer treatment.