Cardio-oncology最新文献

Purpose: The purpose of this systematic review and meta-analysis is to explore the utilization of cardioprotective medications in patients treated with RT and assess their impact on cardiovascular and cerebrovascular events.

Materials/methods: A literature search of PubMed, Embase and Scopus was performed in March 2025. Studies of adult patients treated with RT to the head and neck or thoracic regions which investigated the effects of cardioprotective medications (defined as anti-hypertensives, lipid-lowering therapies or anti-thrombotic medications) on the incidence of cardiovascular or cerebrovascular events were eligible for inclusion. Studies that reported the proportion of patients treated with RT who were utilizing cardioprotective medications as recommended by CVD guidelines were also included. Meta-analysis was performed using R with a random effects model.

Results: There were 10 retrospective studies which were eligible for inclusion. Five of the ten studies included patients with head and neck cancer only, whilst two studies included patients with lung cancer and one study included patients with breast cancer alone. Meta-analysis of three studies suggested that patients treated with RT who received statin therapy had a reduced risk of cerebrovascular events (stroke or transient ischemic attack), with a relative risk of 0.74 (95% CI 0.60-0.90). There was no difference in major adverse cardiac events (MACE) for patients treated with RT to the head and neck or thoracic regions who received statin therapy compared to those who did not (relative risk 0.99, 95% CI 0.67 to 1.46, n = 5 studies). A meta-analysis of four studies suggested that 59% (95% CI 35% to 80%) of patients treated with RT not on statin therapy had indications for commencement of these medications.

Conclusion: Current evidence exploring the impact of cardioprotective medications on CVD risk in patients treated with RT is heterogenous and limited to retrospective non-randomized studies. A considerable proportion of patients undergoing RT are not being prescribed cardioprotective medications as suggested by existing CVD guidelines.

Introduction: Anthracycline-induced cardiotoxicity (AIC) is a serious complication of chemotherapy, and there is a need for cost-effective biomarkers to enable risk stratification. Serum neprilysin (sNEP) has been investigated as a biomarker in various cardiovascular conditions, but its role in AIC has not been evaluated.

Methods: Twelve-week-old Sprague-Dawley rats received intraperitoneal doxorubicin (DOX) either as a single 20 mg/kg dose (acute model, n = 8), four weekly doses of 5 mg/kg (chronic model, n = 11), or saline (controls, n = 8 for each model). Echocardiography was performed at baseline and on the final study day. Blood and left ventricular (LV) tissue were collected within 24 h (acute model) or one week (chronic model) after the last injection. NEP protein and mRNA expression were measured in LV tissue, and sNEP concentrations were determined in serum.

Results: In the chronic AIC model, LV NEP protein expression was significantly reduced compared with controls (982.56 ± 90.57 vs. 1132.86 ± 132.30 ng/L, p < 0.05). In the acute model, sNEP levels showed a strong positive correlation with the severity of LV cardiomyocyte vacuolization (rs = 0.81, p < 0.05). In the chronic model, sNEP levels were strongly and negatively correlated with cardiac output (r = - 0.91, p < 0.05).

Conclusions: Chronic DOX exposure reduces LV NEP protein expression. Elevated serum sNEP is associated with greater early cardiomyocyte injury, while in chronic AIC, it correlates with a more severe decline in cardiac output. These findings suggest sNEP may be a potential biomarker for AIC.

In cardio-oncology, the gap between mechanistic studies and pharmacological trials impedes the delineation of effective cardioprotective strategies. The angiotensin-receptor/neprilysin inhibitor (ARNI) have shown beneficial effects in patients with heart failure with reduced ejection fraction, but failed to show significant benefit in cardio-oncology. In a preclinical model, soluble neprilysin levels (sNEP) tracked anthracycline-induced myocardial damage and systolic dysfunction and sNEP levels may predict benefits of ARNI. The neutral results of clinical trials testing sacubitril/valsartan in this setting underscore the challenge of bridging pre-clinical knowledge to patients' management and call for clinical trials in precision medicine approaches in which biomarkers (i.e. sNEP) may guide treatment (i.e. ARNI).

Cardiovascular disease is the prevailing cause of death among cancer survivors. Remarkable increase in cardiac disease burden in this group is likely due to the effects of cancer itself and, especially, cardiotoxic cancer treatments. Of the cardiotoxic cancer treatments, anthracyclines are notoriously known for causing vascular damage and severe cardiovascular complications. A defining feature of cardiac damage by doxorubicin (Dox), a prototypical anthracycline, is that it typically progresses after completion of chemotherapy. As the nature of delayed deterioration is not understood, we focused in this study on the events that occur upon completion of chemotherapy. We adopted the Dox treatment/washout model to examine its lasting effects on endothelial cells. Our ChIP sequencing, transcriptomic, reporter plasmid, and Smad2/3 phosphorylation experiments demonstrated enhanced activity of the canonical TGF-β and activin pathways during Dox washout. Another notable feature was sustained mesenchymal reprogramming with significant upregulation of transcripts characteristic of fibroblastic and smooth muscle lineages, both in endothelial cultures and cardiac microvascular endothelial cells in vivo. We utilized a selective ALK4/5/7 receptor kinase inhibitor, SB431542 (SB), to probe the role of the canonical TGF-β/activin pathways in endothelial-to-mesenchymal reprogramming by Dox. When present during Dox washout, SB blocked increased expression of both mesenchymal transcripts and protein markers, and prevented cytoskeletal changes and fibronectin production by the treated endothelial cells. Cytoskeletal rearrangements led to increased endothelial monolayer permeability that was abolished by SB treatment. Thus, increased production of ALK4/5 receptor ligands, TGF-β2 and activin, and heightened Smad2/3 activation response to these ligands during Dox washout leads to sustained mesenchymal reprogramming of endothelial cells and compromised endothelial barrier function.