Cardio-oncology最新文献

Aims: Cancer therapy-related cardiac dysfunction (CTRCD) is a dreaded complication of anthracycline therapy. CTRCD most frequently appears in patients with cardiovascular risk factors (CVR) or known cardiovascular disease. However, limited data exist on incidence and course of anthracycline-induced CTRCD in patients without preexisting risk factors. We therefore aimed to longitudinally investigate a cohort of young women on anthracycline treatment due to breast cancer without cardiovascular risk factors or known cardiovascular disease (NCT03940625).

Methods and results: We enrolled 59 women with primary breast cancer and scheduled anthracycline-based therapy, but without CVR or preexisting cardiovascular disease. We conducted a longitudinal assessment before, immediately and 12 months after cancer therapy with general laboratory, electrocardiograms, echocardiography and cardiovascular magnetic resonance (CMR), including myocardial relaxometry with T1, T2 and extracellular volume mapping. Every single patient experienced a drop in CMR-measured left ventricular ejection fraction (LVEF) of 6 ± 3% immediately after cancer therapy. According to the novel definition 32 patients (54.2%) developed CTRCD after 12 months defined by reduction in LVEF, global longitudinal strain (GLS) and/or biomarkers elevation, two of them were symptomatic. Global myocardial T2 relaxation times as well as myocardial mass increased coincidently with a decline in wall-thickening. While T2 values and myocardial mass normalized after 12 months, LVEF and GLS remained impaired.

Conclusion: In every single patient anthracyclines induce a decline of myocardial contractility, even among patients without pre-existing risk factors for CTRCD. Our data suggest to thoroughly evaluate whether this may lead to an increased risk of future cardiovascular events.

Background: The therapeutic landscape of chronic myeloid leukaemia (CML) has been transformed by tyrosine kinase inhibitors (TKI). Nilotinib, showed higher rates of major molecular response than imatinib, however associated with higher cardiovascular (CV) toxicity. We sought to describe the CV events associated with nilotinib in a real-world population and assess the predictive value of the HFA-ICOS risk score.

Methods: The HFA-ICOS baseline risk was calculated for patients with CML treated with nilotinib beween 2006 and 2021. The primary end point was the incidence of all CV events. The secondary end point was the incidence of ischaemic events. Survival analysis evaluated the risk (hazard ratio [HR]) of events stratified by baseline risk category, whilst on nilotinib therapy.

Results: Two hundred and twenty-nine eligible patients were included. The incidence of CV events was 20.9% (95% CI: 15.7-26.2%) following a median duration of treatment of 34.4 months. The secondary end point occurred in 12.7% (95% CI: 8.4-16.9%) of the population. Patients with higher HFA-ICOS baseline score had higher rates of CV events (low: 11.2%, medium: 28.2% [HR: 2.51, 95% CI: 1.17-5.66], high/very high: 32.4% [HR: 3.57, 95% CI: 1.77-7.20]) and ischaemic events (low: 5.20%, medium: 17.9% [HR: 2.19, 95% CI: 0.97-4.96], high/very high: 21.6% [HR: 3.9, 95% CI: 1.91-7.89]). In patients who did not have a CV event, the median total dose at last follow up or cessation of nilotinib therapy was lower when compared to the total daily median dose of nilotinib in patients who had a CV event (450 mg vs. 600 mg, p = 0.0074).

Conclusions: The HFA-ICOS risk stratification tool is an efficient discriminator at low, medium and high/very high risk of developing cardiovascular events, with an overall positive trend towards increasing cardiotoxicity rates with rising risk catergories. This study provides evidence to support the use of this predictive tool in nilotinib treated patients.

Background: Cardiac troponin is commonly raised in patients presenting with malignancy. The prognostic significance of raised troponin in these patients is unclear.

Objectives: We sought to investigate the relation between troponin and mortality in a large, well characterised cohort of patients with a routinely measured troponin and a primary diagnosis of malignancy.

Methods: We used the National Institute for Health Research (NIHR) Health Informatics Collaborative data of 5571 patients, who had troponin levels measured at 5 UK cardiac centres between 2010 and 2017 and had a primary diagnosis of malignancy. Patients were classified into solid tumour or haematological malignancy subgroups. Peak troponin levels were standardised as a multiple of each laboratory's 99th -percentile upper limit of normal (xULN).

Results: 4649 patients were diagnosed with solid tumours and 922 patients with haematological malignancies. Raised troponin was an independent predictor of mortality in all patients (Troponin > 10 vs. <1 adjusted HR 2.01, 95% CI 1.73 to 2.34), in solid tumours (HR 1.84, 95% CI 1.55 to 2.19), and in haematological malignancy (HR 2.72, 95% CI 1.99 to 3.72). There was a significant trend in increasing mortality risk across troponin categories in all three subgroups (p < 0.001).

Conclusion: Raised troponin level is associated with increased mortality in patients with a primary diagnosis of malignancy regardless of cancer subtype. Mortality risk is stable for patients with a troponin level below the ULN but increases as troponin level increases above the ULN in the absence of acute coronary syndrome.

Background: Doxorubicin (DXR) is an effective chemotherapeutic agent. DOX-induced cardiomyopathy (DICM), a major limitation of DXR, is a complication with limited treatment options. We previously reported that Red Ginseng (steamed and dried the root of Panax Ginseng cultivated for over six years; RGin) is beneficial for the treatment of DICM. However, the mechanism underlying the action of RGin remains unclear. In this study, we investigated the mechanism of action underlying the efficacy of RGin in the treatment of DICM.

Methods: Four-week-old DBA/2 mice were divided into: vehicle, DXR, RGin, and DXR + RGin (n = 10/group). Mice were treated with DXR (4 mg/kg, once a week, accumulated 20 mg/kg, i.p.) or RGin (0.5 g/kg, three times a week, i.p.). To evaluate efficacy, the survival rate and left ventricular ejection fraction (LVEF) were measured as a measure of cardiac function, and cardiomyocytes were subjected to Masson trichrome staining. To investigate the mechanism of action, western blotting was performed to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1, transferrin receptor (TfR), and other related proteins. Data were analyzed using the Easy R software. Between-group comparisons were performed using one-way analysis of variance and analyzed using a post-hoc Tukey test. Survival rates were estimated using the Kaplan-Meier method and compared using the log-rank test. P < 0.05 was considered statistically significant in all analyses.

Results: RGin treatment prolongs survival and protects against reduced LVEF. In the DXR group, Nrf2 was not activated and cell death was accelerated. Furthermore, there was an increase in the TfR levels, suggesting abnormal iron metabolism. However, the DXR + RGin group showed activation of the Nrf2 pathway and suppression of myocardial cell death. Furthermore, there was no increase in TfR expression, suggesting that there were no abnormalities in iron metabolism. Therefore, the mechanism of action of RGin in DICM involves an increase in antioxidant activity and inhibition of cell death through activation of the Nrf2 pathway.

Conclusion: RGin is a useful therapeutic candidate for DICM. Its efficacy is supported by the activation of the Nrf2 pathway, which enhances antioxidant activity and inhibits cell death.

Background: The anthracycline doxorubicin (DOX) is a highly effective anticancer agent, especially in breast cancer and lymphoma. However, DOX can cause cancer therapy-related cardiovascular toxicity (CTR-CVT) in patients during treatment and in survivors. Current diagnostic criteria for CTR-CVT focus mainly on left ventricular systolic dysfunction, but a certain level of damage is required before it can be detected. As diastolic dysfunction often precedes systolic dysfunction, the current study aimed to identify functional and molecular markers of DOX-induced CTR-CVT with a focus on diastolic dysfunction.

Methods: Male C57BL/6J mice were treated with saline or DOX (4 mg/kg, weekly i.p. injection) for 2 and 6 weeks (respectively cumulative dose of 8 and 24 mg/kg) (n = 8 per group at each time point). Cardiovascular function was longitudinally investigated using echocardiography and invasive left ventricular pressure measurements. Subsequently, at both timepoints, myocardial tissue was obtained for proteomics (liquid-chromatography with mass-spectrometry). A cohort of patients with CTR-CVT was used to complement the pre-clinical findings.

Results: DOX-induced a reduction in left ventricular ejection fraction from 72 ± 2% to 55 ± 1% after 2 weeks (cumulative 8 mg/kg DOX). Diastolic dysfunction was demonstrated as prolonged relaxation (increased tau) and heart failure was evident from pulmonary edema after 6 weeks (cumulative 24 mg/kg DOX). Myocardial proteomic analysis revealed an increased expression of 12 proteins at week 6, with notable upregulation of SERPINA3N in the DOX-treated animals. The human ortholog SERPINA3 has previously been suggested as a marker in CTR-CVT. Upregulation of SERPINA3N was confirmed by western blot, immunohistochemistry, and qPCR in murine hearts. Thereby, SERPINA3N was most abundant in the endothelial cells. In patients, circulating SERPINA3 was increased in plasma of CTR-CVT patients but not in cardiac biopsies.

Conclusion: We showed that mice develop heart failure with impaired systolic and diastolic function as result of DOX treatment. Additionally, we could identify increased SERPINA3 levels in the mice as well as patients with DOX-induced CVT and demonstrated expression of SERPINA3 in the heart itself, suggesting that SERPINA3 could serve as a novel biomarker.

Background: The effects of exercise in patients with breast cancer (BC), has shown some profit, but consistency and magnitude of benefit remains unclear. We aimed to conduct a meta-analysis to assess the benefits of varying types of exercises in patients with BC.

Methods: Literature search was conducted across five electronic databases (MEDLINE, Web of Science, Scopus, Google Scholar and Cochrane) from 1st January 2000 through 19th January 2024. Randomized controlled trials (RCTs) assessing the impact of different types of exercise on outcomes related to fitness and quality of life (QOL) in patients with BC were considered for inclusion. Outcomes of interest included cardiorespiratory fitness (CRF), health-related quality of life (HRQOL), muscle strength, fatigue and physical function. Evaluations were reported as mean differences (MDs) with 95% confidence intervals (CIs) and pooled using random effects model. A p value < 0.05 was considered significant.

Results: Thirty-one relevant articles were included in the final analysis. Exercise intervention did not significantly improved the CRF in patients with BC when compared with control according to treadmill ergometer scale (MD: 4.96; 95%Cl [-2.79, 12.70]; P = 0.21), however exercise significantly improved CRF according to cycle ergometer scales (MD 2.07; 95% Cl [1.03, 3.11]; P = 0.0001). Physical function was significantly improved as well in exercise group reported by 6-MWT scale (MD 80.72; 95% Cl [55.67, 105.77]; P < 0.00001). However, exercise did not significantly improve muscle strength assessed using the hand grip dynamometer (MD 0.55; 95% CI [-1.61, 2.71]; P = 0.62), and fatigue assessed using the MFI-20 (MD -0.09; 95% CI [-5.92, 5.74]; P = 0.98) and Revised Piper scales (MD -0.26; 95% CI [-1.06, 0.55] P = 0.53). Interestingly, exercise was found to improve HRQOL when assessed using the FACT-B scale (MD 8.57; 95% CI [4.53, 12.61]; P < 0.0001) but no significant improvements were noted with the EORTIC QLQ-C30 scale (MD 1.98; 95% CI [-1.43, 5.40]; P = 0.25).

Conclusion: Overall exercise significantly improves the HRQOL, CRF and physical function in patients with BC. HRQOL was improved with all exercise types but the effects on CRF vary with cycle versus treadmill ergometer. Exercise failed to improve fatigue-related symptoms and muscle strength. Large RCTs are required to evaluate the effects of exercise in patients with BC in more detail.

Background: The use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer may precipitate cardiotoxic events. We aimed to perform a meta-analysis to evaluate the cardiotoxicity associated with ICIs in patients with lung cancer.

Methods: A literature search was conducted across four electronic databases (Cochrane CENTRAL, MEDLINE, OVID EMBASE and Google Scholar) from inception through 31st May 2023. Randomized controlled trials (RCTs) assessing the impact of ICIs on cardiac outcomes in lung cancer patients were considered for inclusion. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled and analysis was performed using a random-effects model. The Grading of Recommendations Assessment, Development and Evaluation approach was followed to assess confidence in the estimates of effect (i.e., the quality of evidence).

Results: A total of 30 studies including 16,331 patients, were included in the analysis. Pooled results showed that single ICI (RR: 2.15; 95% CI: 1.13-4.12; p = 0.02; I2 = 0%) or a combination of single ICI plus chemotherapy (RR: 1.38 [1.05-1.82]; p = 0.02) significantly increased the risk of cardiac adverse events when compared with chemotherapy alone. No significant difference was noted when a dual ICI (RR: 0.48 [0.13-1.80]; p = 0.27) was compared with single ICI. In addition, there was no significant association between the use of ICIs and incidence of cardiac failure (RR: 1.11 [0.48-2.58]; p = 0.80), or arrhythmia (RR: 1.87; [0.69-5.08]; p = 0.22).

Conclusion: Compared with chemotherapy alone, use of a single ICI or a combination of single ICI plus chemotherapy significantly increased the risk of cardiotoxicity. However, employing dual immunotherapy did not result in a significant increase in the risk of cardiotoxicity when compared to the use of a single ICI.

The landscape of cancer survivorship is increasingly populated by individuals facing a spectrum of cardiometabolic risks, attributed to both their oncological history and treatment regimens. This manuscript synthesizes findings from various studies, highlighting the prevalence of traditional risk factors-hypertension, dyslipidemia, diabetes-as well as emergent concerns like obesity and metabolic syndrome among survivors. The impact of demographic variables, specific cancer types, and treatment modalities on cardiometabolic health is explored. Through a lens of multidisciplinary management and future research directives, we advocate for an integrative approach to cardiometabolic health in cancer survivors, aiming to ensure their victory over cancer extends into long-term well-being.

Purpose: Immune checkpoint inhibitors (ICIs)-associated myocarditis was a rare yet severe complication observed in individuals undergoing immunotherapy. This study investigated the immune status and characteristics of patients diagnosed with ICIs- associated myocarditis.

Methods: A total of seven patients diagnosed with ICIs-associated myocarditis were included in the study, while five tumor patients without myocarditis were recruited as reference controls. Additionally, 30 healthy individuals were recruited as blank controls. Biochemical indices, electrocardiogram, and echocardiography measurements were obtained both prior to and following the occurrence of myocarditis. High-throughput sequencing of T cell receptor (TCR) was employed to assess the diversity and distribution characteristics of TCR CDR3 length, as well as the diversity of variable (V) and joining (J) genes of T lymphocytes in peripheral blood.

Results: In the seven patients with ICIs-associated myocarditis, Troponin T (TNT) levels exhibited a significant increase following myocarditis, while other parameters such as brain natriuretic peptide (BNP), QTc interval, and left ventricular ejection fraction (LVEF) did not show any significant differences. Through sequencing, it was observed that the diversity and uniformity of CDR3 in the ICIs-associated myocarditis patients were significantly diminished. Additionally, the distribution of CDR3 nucleotides deviated from normality, and variations in the utilization of V and J gene segments.

Conclusion: The reconstitution of the TCR immune repertoire may play a pivotal role in the recognition of antigens in patients with ICIs-associated myocarditis.

Background: To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma.

Methods: Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change.

Results: Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047).

Conclusions: These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet.

Trial registration: DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.