Cardio-oncology最新文献

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.

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.