Cardio-oncology最新文献

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, offering significant survival benefits across diverse malignancies. However, growing evidence suggest an increased occurrence of cardiovascular adverse events (CVAEs) following ICI, which remain poorly characterized in large, real-world populations.

Objectives: To quantify the incidence and spectrum of CVAEs following ICI initiation and identify demographic, clinical, and treatment-related risk factors for CVAE development.

Methods: We conducted a retrospective cohort study using electronic health record data from the OneFlorida + Clinical Research Network. Adult cancer patients (≥ 18 years) with cancer who started FDA-approved ICIs between January 1, 2018, and December 31, 2023, were included. Eligible patients had either ≥ 1 inpatient or ≥ 2 outpatient encounters after. The primary outcome was new-onset CVAE within one year. Kaplan-Meier survival analyses and multivariable Cox regression evaluated associations with risk factors.

Results: Among 9,541 patients initiating ICIs, 2,320 (24.3%) developed a CVAE within one year, with arrhythmia (15.7%), heart failure (5.2%), and stroke (4.1%) being the most common. Cardiometabolic comorbidities (hypertension, hyperlipidemia, diabetes, and obesity) were independently associated with increased CVAE risk. CVAE incidence varied significantly by cancer type, with highest risk observed in breast, liver, and lung cancers compared to melanoma. Triple checkpoint blockade (CTLA-4 + PD-(L)1 + LAG-3) conferred a modest but significant increase in CVAE risk.

Conclusion: CVAEs occurred frequently after ICI initiation, with substantial variation by cancer type, comorbidities, and treatment regimen. These findings highlight the importance of cardiovascular risk assessment and monitoring to optimize outcomes in immuno-oncology.

Background: Recent studies have shown that heart failure (HF) and left ventricular (LV) dysfunction are associated with enhanced tumor growth. However, whether treating LV dysfunction mitigates its impact on cancer progression remains unknown. We hypothesized that HF treatments would attenuate tumor growth in a rodent model of post-myocardial infarction (MI)-induced LV dysfunction, and that different pharmacological agents (carvedilol, enalapril, and empagliflozin) might exert distinct effects on tumor progression.

Methods: MI was induced in female BALB/c mice, leading to LV dysfunction. Mice with LV ejection fraction < 40% two weeks after MI received daily vehicle or one of three HF treatments by gavage. Two weeks later, 2 × 10⁵ 4T1 metastatic breast cancer cells were injected, with a three-week follow-up. The effects of HF treatments on cancer progression were assessed by analyzing: (i) tumor size in vivo over 22 days, (ii) lung metastasis development and (iii) gene expression levels in tumor tissue by RNA sequencing.

Results: Enalapril reversed several MI-induced transcriptomic changes in tumor tissue. Empagliflozin reduced primary tumor growth, while carvedilol reduced metastatic clusters. These effects were absent in control mice without MI, and neither drug directly affected cultured 4T1 cells. Transcriptomic analysis revealed treatment-specific inflammatory pathway regulation. Notably, carvedilol and empagliflozin restored MI-suppressed IFN-γ expression in tumors, accompanied by increased STAT1 expression in 4T1 cells.

Conclusion: Specific HF treatments can mitigate cancer growth in a mouse model of MI-induced LV dysfunction, with outcomes varying by treatment. These benefits occurred only with LV dysfunction, suggesting they result from changes in HF pathophysiology rather than direct drug effects on tumor cells. Restoration of immune signaling may contribute to these effects.

Radiation-induced cardiotoxicity remains a significant concern in breast cancer (BC) patients treated with radiotherapy (RT), with both cardiac radiation exposure and systemic inflammation emerging as key contributors to early cardiovascular complications. This study investigated whether cardiac radiation dose triggers independently or synergistically with systemic inflammation, characterized by C-reactive protein (CRP) elevation to predict coronary artery calcification (CAC) progression in BC survivors. We analyzed 101 chemotherapy-naïve BC women who underwent cardiac CT before and 24 months after RT, with dosimetric analysis of left ventricle (LV) radiation exposure. Sustained CRP elevation was defined as increased CRP at both end of RT and 6 months post-RT. CAC progression was observed in 28 patients (27.7%). Both sustained CRP elevation (OR = 3.42; 95% CI: 1.12-10.5) and mean LV dose (OR = 1.20 per Gy; 95% CI: 1.03-1.40) were independently associated with CAC progression. Although no statistically significant interaction was observed, stratified analyses showed a stronger association between mean LV dose and CAC progression among patients with sustained inflammation (OR = 1.39, 95%CI: 1.07-1.81), whereas this association was weaker and non-significant in patients without systemic inflammation (OR = 1.12, non-significant). The combined model incorporating both predictors showed improved discriminative performance (AUC = 0.733). These findings suggest that systemic inflammation may amplify the effect of cardiac irradiation and that combining inflammatory and dosimetric data improves early prediction of CAC risk. This may help identify high-risk subgroups who could benefit from enhanced cardiovascular monitoring or preventive strategies after BC RT.

Background: Adult survivors of childhood cancers are thought to be at high risk for late-onset cardiovascular complications of prior anti-cancer treatments. While cancer therapy-related cardiac dysfunction (CTRCD) has previously been observed in this population, data are limited regarding the utility of longitudinal echocardiographic monitoring.

Methods: 124 adult survivors of childhood cancer who were previously treated with anthracyclines and/or radiation therapy as children were included in this longitudinal cohort study. Participants were enrolled in Northwestern Medicine's survivorship clinic: Survivors Taking Action and Responsibility (STAR) Program and followed for up to10 years between 2009 and 2022. Serial echocardiography was performed at baseline then at 1, 3, 5, and 7-10 years post-enrollment. Clinical data was collected by chart review. Major adverse cardiovascular events (MACE) and CTRCD were adjudicated according to ACC/AHA MACE criteria and the ESC Cardio-Oncology guidelines respectively.

Results: Over 10 years of follow-up in the STAR Program, 17.7% (22/124) of participants developed MACE, with the highest incidence observed in patients treated with radiation alone. 10.5% (13/124) of patients developed CTRCD by left ventricular ejection fraction (LVEF) criteria while 36.3% (45/124) developed CTRCD by global longitudinal strain (GLS) criteria. New incidence of MACE and CTRCD occurred as late as 7-10 years post-enrollment. Participants who developed CTRCD showed subsequent improvement in both LVEF and GLS by the end of 10 years of follow-up and treatment in the STAR Program.

Conclusions: Survivors of childhood cancer are at high risk for both MACE and CTRCD even many years after initial diagnosis. Patients who received treatment for pediatric cancer, then subsequently enrolled in the STAR Program as adults and received appropriate cardiovascular monitoring and treatment showed improvement in both LVEF and GLS by the end of follow-up, underscoring the importance of a dedicated survivorship clinic for adult survivors of pediatric cancer.

Background: Evidence-based and/or consensus guidance regarding exercise and return-to-play for the adolescent and young adult (AYA) athlete with cardio-oncology concerns is lacking. Many of the recommendations utilized for the diagnosis, surveillance, and management of cancer therapeutic-related cardiotoxicity in children have been extrapolated from adult literature and myocarditis guidelines, the latter of which are primarily concerned with potential for arrhythmias secondary to inflammation and myocardial scarring. In addition, the athlete's heart itself brings about several diagnostic challenges including physiologic changes due to endurance or isometric training. Exercise-induced cardiac remodeling, with enlarged cavity size, lower resting ejection fraction and increased left ventricular wall thickness, depending on the type of exercise, can mimic disease states including both underlying pathologies and the response to cancer therapeutics.

Case presentation: A high school cancer survivor had borderline ejection fraction and abnormal strain indices. He was able to return to competitive sports without complication after clinical evaluation and through a shared decision-making process.

Conclusions: The difficulty in differentiating physiologic from potentially pathologic echocardiographic changes can result in unnecessary disqualification, depriving athletes from social, psychological, and possibly financial benefits. Stress echocardiography indices, such as contractile reserve and mitral E/e' ratio, may inform assessment of systolic and diastolic function, respectively, and may be helpful in risk stratifying and understanding potential performance limitations in AYA athletes with cardio-oncology concerns for exercise and return-to-play. Most recent consensus statements regarding sports participation in the athlete with heart disease focus on a shared decision-making process amongst all stakeholders involved to formulate an informed, safe, and cohesive prescription to enable the athlete to safely re-engage in sports after recovering from a cardiac illness or surgery. Multidisciplinary recommendations emphasize the importance of exercise before, during, and after chemotherapy in an individualized approach to reduce risk factors in oncology patients and improve cardiovascular outcomes. Further research is needed to delineate protocols for the adolescent and young adult cardio-oncology athlete regarding exercise prescriptions and their return-to-play following oncology treatment.

Chemotherapy-induced cardiotoxicity (CIC) is a well-recognized and potentially severe complication of cancer treatment, particularly with anthracyclines and HER2-targeted therapies. As cancer survival improves, long-term cardiovascular outcomes have become increasingly important, yet current preventive strategies-such as dose reduction, dexrazoxane, neurohormonal blockers, and statins-offer only limited protection and are underutilized in routine clinical practice. There is a growing need for novel interventions that are safe, effective, and mechanistically targeted. Dapagliflozin, a SGLT2 inhibitor initially developed for type 2 diabetes, has demonstrated substantial cardioprotective effects in patients with heart failure, regardless of glycemic status. Its mechanisms-including improved cardiac metabolism, mitochondrial preservation, anti-inflammatory and antioxidant effects, and inhibition of fibrosis-align closely with the known pathways of chemotherapy-induced myocardial injury. Preclinical models have shown that dapagliflozin can preserve left ventricular function, reduce biomarker elevation, and prevent structural remodeling in hearts exposed to doxorubicin. Building on this evidence, a randomized, double-blind, placebo-controlled clinical trial (NCT06888505) is currently underway to evaluate dapagliflozin in cancer patients receiving anthracycline-based chemotherapy, with or without trastuzumab. The study incorporates serial biomarker assessments and cardiac function monitoring to assess its preventive potential.Dapagliflozin represents a promising therapeutic candidate in cardio-oncology. Its pleiotropic cardioprotective effects, oral route of administration, and established safety profile make it a strong contender for integration into future preventive strategies aimed at reducing the cardiovascular burden of cancer therapy.

Background: Doxorubicin induced cardiotoxicity in childhood cancer survivors is mediated by mitochondrial dysfunction. The aims of this research are to determine (i) the frequency of mitochondrial DNA (mtDNA) mutations in long-term survivors of childhood acute lymphoblastic leukemia (ALL), and (ii) to determine if co-administration of dexrazoxane reduces the occurrence of mutations.

Methods: Patients previously treated on Dana-Farber Cancer Institute Childhood ALL protocols and at least 4 years from the date of ALL diagnosis were enrolled in this study. MtDNA was isolated from samples of peripheral blood lymphocytes. A vertical denaturing gradient gel electrophoresis method was used for detecting sequence variants in the 22 transfer RNA (tRNA) genes and flanking regions of the human mitochondrial genome. The patients were divided into two cohorts, those with mutations and those without, and compared. The patients and variants were also compared to healthy controls. Mutational status was compared with echocardiographic measurements.

Results: Of the patients who received chemotherapy, there were 51/167 (31%) children who were found to have 61 different sequence variants in mtDNA with 9 patients having more than one variant. There was no association between mutation status and cumulative doxorubicin dose, though patients receiving < 300 mg/m² had fewer mutations of any kind. At a median time of 8.5 years after diagnosis, the number of ALL patients with mtDNA sequence variants was 2.4-fold higher than the number of control children with sequence variants (8 sequence variants in 7/55 or 12.7%). Among patients receiving doxorubicin-based therapies, with (n = 34) or without dexrazoxane (n = 132), there were no statistically significant differences in the patient characteristics or in the frequencies, locations, types, and distribution of mtDNA sequence variants. The mutational status was not associated with echocardiographic changes.

Conclusions: The results of this study indicate that doxorubicin chemotherapy is associated with increases in mtDNA sequence variants in lymphocytes. The role of mtDNA mutations in late-onset cardiomyopathy of doxorubicin, and the potential antimutagenic activity of dexrazoxane, were not established but warrant further investigation.

Background: Right ventricular (RV) dysfunction may arise from several reasons, including pulmonary embolism (PE) or cancer therapy-related cardiotoxicity. PE elevates pulmonary pressures, straining the RV, which can cause dysfunction, while anthracyclines, though primarily recognized for impacting the left ventricle, can also impair the RV. The interplay between these conditions remains poorly understood, particularly the RV's susceptibility to anthracycline cardiotoxicity after recovering from PE-induced strain. This case study highlights a patient who initially had PE-related RV dysfunction; however, data from three medical centers revealed RV recovery after PE, followed by RV failure, with subsequent left ventricular (LV) failure after chemotherapy.

Case presentation: A 41-year-old woman with a history of recurrent sub-massive pulmonary embolism initially treated with embolectomy and tissue plasminogen activator (tPA), was ultimately diagnosed with right pulmonary artery sarcoma. She underwent a pneumonectomy and pulmonary artery reconstruction with plans for chemotherapy and radiation therapy. The patient had RV dilation followed by dysfunction, which resolved on follow-up study after surgery. Subsequently, she received radiation therapy, along with paclitaxel, followed by doxorubicin. During chemotherapy, she developed progressive dyspnea and lower extremity edema. Follow-up transthoracic echocardiography (TTE) demonstrated preserved LV size and function but revealed RV dilation and reduced systolic function. As her LV ejection fraction (LVEF) did not meet the criteria for cardiotoxicity, doxorubicin therapy was continued without modification. Over the next several months, her clinical status worsened, with severe RV dilation, continued lower extremity swelling, and functional decline. She underwent right heart catheterization, which revealed RF volume overload and preserved cardiac output. Subsequent cardiovascular MRI (CMR) revealed biventricular dysfunction. Within eight months of initial RV recovery post-pneumonectomy, she was diagnosed with biventricular failure due to anthracycline-induced cardiotoxicity.

Conclusions: This case highlights the need to expand cardiotoxicity monitoring to include a thorough evaluation of RV function in patients undergoing anthracycline-based therapy. While our patients' RV function recovered after pneumonectomy, the significant decline in RV function within eight months after anthracycline treatment indicates its vulnerability to cardiotoxic stress. Incorporating RV assessments into cardiotoxicity evaluations could allow for earlier detection and intervention, reducing long-term cardiac risks. Current guidelines focus mainly on left ventricular metrics; with our case, we emphasize the need for a more comprehensive approach to cardiac monitoring in these patients.