Cardio-oncology最新文献

Background: Variants in cardiomyopathy genes have been identified in patients with cancer therapy-related cardiac dysfunction (CTRCD), suggesting a genetic predisposition for the development of CTRCD. The diagnostic yield of genetic testing in a CTRCD population compared to a cardiomyopathy patient cohort is not yet known and information on which genes should be assessed in this population is lacking.

Methods: We retrospectively included 46 cancer patients with a history of anthracycline induced CTRCD (defined as a decrease in left ventricular ejection fraction (LVEF) to < 50% and a ≥ 10% reduction from baseline by echocardiography). Genetic testing was performed for 59 established cardiomyopathy genes. Only variants of uncertain significance and (likely) pathogenic variants were included. Diagnostic yield of genetic testing was compared with a matched cohort of patients with dilated cardiomyopathy (DCM, n = 46) and a matched cohort of patients without cardiac disease (n = 111).

Results: Average LVEF at time of CTRCD diagnosis was 30.1 ± 11.0%. Patients were 52.9 ± 14.6 years old at time of diagnosis and 30 (65.2%) were female. Most patients were treated for breast cancer or lymphoma, with a median doxorubicin equivalent dose of 300 mg/m² [112.5-540.0]. A genetic variant, either pathogenic, likely pathogenic or of uncertain significance, was identified in 29/46 (63.0%) of patients with CTRCD, which is similar to the DCM cohort (34/46, 73.9%, p = 0.262), but significantly higher than in the negative control cohort (47/111, 39.6%, p = 0.018). Variants in TTN were the most prevalent in the CTRCD cohort (43% of all variants). All (likely) pathogenic variants identified in the CTRCD cohort were truncating variants in TTN. There were no significant differences in severity of CTRCD and in recovery rate in variant-harbouring individuals versus non-variant harbouring individuals.

Conclusions: In this case-control study, cancer patients with anthracycline-induced CTRCD have an increased burden of genetic variants in cardiomyopathy genes, similar to a DCM cohort. If validated in larger prospective studies, integration of genetic data in risk prediction models for CTRCD may guide cancer treatment. Moreover, genetic results have important clinical impact, both for the patient in the setting of precision medicine, as for the family members that will receive genetic counselling.

Aims: Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy.

Methods: Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion. The study endpoints were i) incidence of cancer therapy-related cardiac dysfunction (CTRCD), CTRCD were also balanced for any grade CRS, but CTRCD occurred of Cardiology Guidelines on Cardio-Oncology (decrements of left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and/or elevations of cardiac biomarkers (high sensitivity troponin I, natriuretic peptides) and ii), correlations of echocardiographic metrics with inflammatory biomarkers.

Results: Incidence of CTRCD was high at 7 days (59,3%), particularly in subjects with CRS. The integrated definition of CTRCD allowed the identification of the majority of cases (50%). Moreover, early LVEF and GLS decrements were inversely correlated with fibrinogen and interleukin-2 receptor levels (p always ≤ 0.01).

Conclusions: There is a high incidence of early CTRCD in patients treated with CAR-T cells, and a link between CTRCD and inflammation can be demonstrated. Dedicated patient monitoring protocols are advised.

Background: Cardiovascular (CV) disease is a leading cause of death in breast cancer (BC) patients due to the increased age and treatments. While individual β-blockers have been investigated to manage CV complications, various β-blockers have not been compared for their effects on CV death in this population. We aimed to compare CV mortality in older BC patients taking one of the commonly used β-blockers.

Methods: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) - Medicare data (2010-2015). Patients of age 66 years or older at BC diagnosis receiving metoprolol, atenolol, or carvedilol monotherapy were included. The competing risk regression model was used to determine the risk of CV mortality in the three β-blocker groups. The multivariable model was adjusted for demographic and clinical covariates. The adjusted hazard ratio (HR) and 95% confidence intervals (CI) were reported for the risk of CV mortality.

Results: The study cohort included 6,540 patients of which 55% were metoprolol users, 30% were atenolol users, and 15% were carvedilol users. Metoprolol was associated with a 37% reduced risk of CV mortality (P = 0.03) compared to carvedilol after adjusting for the covariates (HR = 0.63; 95% CI 0.41-0.96). No significant difference in the risk of CV mortality between atenolol and carvedilol users was observed (HR = 0.74; 95% CI 0.44-1.22).

Conclusions: Our findings suggest that metoprolol is associated with a reduced risk of CV mortality in BC patients. Future studies are needed to confirm these findings and understand the mechanism of action.

Background: Contemporary radiotherapy for the treatment of lung cancer is effective in targeting tumor tissue while limiting heart exposure, yet cardiac toxicity still occurs, often becoming clinically apparent years later. Cardiorespiratory fitness (CRF) is an independent predictor of cardiovascular, cancer-related, and overall mortality and may serve as a sensitive measure of subclinical cardiac toxicity following anti-cancer treatments. Prior work has demonstrated a significant relationship between reduced CRF and impaired left-ventricular (LV) diastolic reserve in cancer survivors following thoracic radiotherapy. The purpose of this study was to assess early longitudinal changes in CRF and cardiac function in patients with lung cancer following radiotherapy.

Methods: Ten patients (69 [61-76] years, 70% female) with lung cancer without known cardiovascular disease scheduled to receive radiotherapy involving a clinically-relevant heart dose (≥ 5 Gy to > 10% of heart volume) were evaluated prior to and following treatment. Changes in CRF (peak oxygen consumption [VO_2peak], oxygen uptake efficiency slope [OUES]), cardiac function (LV ejection fraction [LVEF], rest and exercise diastolic function [diastolic functional reserve index (DFRI)]), cardiac biomarkers (N-terminal pro-brain natriuretic peptide [NT-proBNP], high-sensitivity C-reactive protein [hsCRP]), and health-related quality of life (HRQOL; Functional Assessment of Cancer Therapy-General-7 [FACT-G7]) were measured.

Results: The VO_2peak was reduced at baseline (1.245 [0.882-1.605] L·min^- 1; 70 [62-86] %-predicted) and significantly declined (1.095 [0.810-1.448] L·min^- 1, P = 0.047; 62 [56-76] %-predicted, P = 0.005) at 6.0 [3.0-6.0] months post-radiotherapy. Similarly, a significant decline in the OUES was observed (1.63 [1.27-1.88] to 1.57 [1.12-1.75], P = 0.032). Systolic cardiac function was normal at baseline and did not change following radiotherapy (LVEF; 62 [56-65]% to 66 [57-68]%, P = 0.475). The DFRI significantly declined following radiotherapy (34.9 [22.7-41.6] vs. 12.8 [3.1-35.9]). The hsCRP increased significantly from 4.4 [1.4-5.8] to 6.1 [3.7-20.7] g/L, P = 0.047 with a trend towards higher levels of NT-proBNP (65 [49-125] to 121 [88-191] pg/mL, P = 0.110). Health-related quality of life significantly decreased (FACT-G7; 21.5 [18.8-25] to 15.5 [11.5-20]; P = 0.021) post-radiotherapy.

Conclusions: Patients with lung cancer receiving radiotherapy with a clinically-significant heart dose experience reductions in CRF (VO_2peak, OUES) as early as six months following treatment with concurrent reductions in diastolic reserve (DFRI), HRQOL, and increases in cardiac biomarkers (NT-proBNP, hsCRP).

Long-term anti-HER2 therapy in metastatic HER2 + cancers is increasing, but data about the incidence and risk factors for developing late Cancer therapy-related cardiac dysfunction (CTRCD) are missing. We conducted a single-centre, retrospective analysis of a cohort of late anti-HER2 related cardiac dysfunction referred to our Cardio-Oncology service. We include seventeen patients with metastatic disease who developed CTRCD after at least five years of continuous anti-HER2 therapy. Events occurred after a median time of 6.5 years (IQR 5.3-9.0) on anti-HER2 therapy. The lowest (median) LVEF and GLS were 49% (IQR 45-55) and - 15.4% (IQR - 14.9 - -16.3) respectively. All our patients continued or restarted, after a brief interruption, their anti-HER2 therapy. Most (16/17) were started on heart failure medical therapy and normalized their left ventricular ejection fraction at a follow-up. Our study has demonstrated that CTRCD can occur after many years of stability on anti-HER2 therapy and reinforces the importance of continuing cardiovascular surveillance in this population.

Background: Cancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed.

Methods: The study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline ± trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Asymptomatic CTRCD is defined as: severe if new LVEF reduction to < 40%, moderate if new LVEF reduction by ≥ 10 percentage points to an LVEF of 40-49% or new LVEF reduction by, 10 percentage points to an LVEF of 40- 49% and either new relative decline in GLS by .15% from baseline or new rise in cardiac biomarkers and mild if LVEF ≥ 50% and new relative decline in GLS by .15% from baseline and/or new rise in cardiac biomarkers. Symptomatic CTRCD is defined as: very severe if HF requiring inotropic support, mechanical circulatory support, or consideration of transplantation, severe if required hospitalization, moderate if required outpatient intensification of diuretic and HF therapy and mild if there are mild HF symptoms and no intensification of therapy required according to the latest ESC cardio oncology guidelines. The Lower reference value set for RV S' was less than 10cm/s to define RV systolic dysfunction according to ASE guidelines.

Results: CTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value < -15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC = 0.947, sensitivity = 91.67%, specificity = 90%).

Conclusion: Chemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV & RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD.

Background: Due to advancements in methods of cancer treatment, the population of people living with and beyond cancer is dramatically growing. The number of cancer survivors developing cardiovascular diseases and heart failure is also rising, due in part to the cardiotoxic nature of many cancer treatments. Guidelines are being increasingly released, emphasising the need for interdisciplinary action to address this gap in survivorship care. However, the extent to which interventions exist, incorporating the recommendations of cardio-oncology research, remains undetermined.

Objective: The aim of this scoping review is to assess the nature, extent and remit of existing cancer care interventions and their integration of cardio-oncology principles.

Methods: The review was conducted in accordance with the PRISMA Extension for Scoping Reviews Guidelines. Databases were independently searched for articles from 2010 to 2022, by two members of the research team. Data were charted and synthesised using the following criteria: (a) the focus of the intervention (b) the medium of delivery (c) the duration (d) the modalities included in the interventions (e) the research articles associated with each intervention (f) the type of studies conducted (g) key measures used (h) outcomes reported.

Results: Interventions encompassed six key modalities: Psychological Support, Physical Activity, Nutrition, Patient Education, Lifestyle and Caregiver Support. The focus, medium of delivery and duration of interventions varied significantly. While a considerable number of study protocols and pilot studies exist documenting HSMIs, only 25% appear to have progressed beyond this stage of development. Of those that have, the present review did not identify any 'feasible' interventions that covered each of the six modalities, while being generalisable to all cancer survivors and incorporating the recommendations from cardio-oncology research.

Conclusion: Despite the substantial volume of research and evidence from the field of cardio-oncology, the findings of this scoping review suggest that the recommendations from guidelines have yet to be successfully translated from theory to practice. There is an opportunity, if not necessity, for cardiac rehabilitation to expand to meet the needs of those living with and beyond cancer.

Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow suppression, are well recognized. However, coronary vasospasm represents a less commonly recognized but significant complication of fluoropyrimidine-based therapies such as capecitabine. Proposed mechanisms for this adverse effect complication include direct endothelium-independent vasoconstriction, activation of protein kinase C, and activation of the cyclooxygenase pathway. In this report, we present a case of capecitabine-induced coronary vasospasm leading to progressive, focal ST-elevations, myocardial ischemia, and subsequently polymorphic ventricular tachycardia. These events were captured on telemetry, in a male in his early 40s, diagnosed with stage IIIB sigmoid colon cancer. Notably, the patient had no pre-existing coronary artery disease or other cardiovascular risk factors. Upon diagnosis, the patient was initiated on a calcium channel blocker, verapamil, to mitigate further coronary vasospasm events. After thorough discussions that prioritized the patient's input and values, an implantable cardioverter-defibrillator was placed subcutaneously. Following discharge, the patient restarted capecitabine therapy along with verapamil prophylaxis and did not experience any subsequent shocks from his ICD as assessed during his outpatient follow-up visits. This case emphasizes the need to involve patients in decision-making processes, especially when managing unexpected and serious complications, to ensure treatments align with their quality of life and personal preferences.

Background: Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiving cardiotoxic chemotherapy.

Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, Cochrane, Clinical Trials.gov, and MedRxiv through July 17th, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI).

Prospero id: CRD42023460902.

Results: We included thirteen RCTs with a total of 952 patients. Exercise significantly increased VO₂ peak (MD: 1.95 with 95% CI [0.59, 3.32], P = 0.005). However, there was no significant effect regarding left ventricular ejection fraction, global longitudinal strain, cardiac output, stroke volume, left ventricular end-diastolic volume, left ventricular end-systolic volume, E/A ratio, resting heart rate, peak heart rate, resting systolic blood pressure, and resting diastolic blood pressure. Also, there was no significant difference regarding any adverse events (AEs) (RR: 4.44 with 95% CI [0.47, 41.56], P = 0.19), AEs leading to withdrawal (RR: 2.87 with 95% CI [0.79, 10.43], P = 0.11), serious AEs (RR: 3.00 with 95% CI [0.14, 65.90], P = 0.49), or all-cause mortality (RR: 0.25 with 95% CI [0.03, 2.22], P = 0.21).

Conclusion: Exercise is associated with increased VO₂ peak in cancer patients receiving cardiotoxic chemotherapy. However, there was no significant difference between exercise and usual care regarding the echocardiographic and safety outcomes.