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Improvement in cancer therapy has led to an increasing number of cancer survivors, some of whom may suffer from the cardiotoxic effects of chemotherapy. Cardiomyopathy can occur years after completion of the chemotherapy and it is important to recognize this early, as complete recovery of cardiac function is possible in some cases. In this article we will review chemotherapy-induced cardiomyopathy and discuss its treatment options. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to identify the clinical implications of myocardial perfusion defects after chemoradiation therapy (CRT) in patients with esophageal and lung cancer.Methods: We retrospectively compared myocardial perfusion imaging (MPI) results before and after CRT in 16 patients with esophageal cancer and 24 patients with lung cancer. New MPI defects in the radiation therapy (RT) fields were considered related to RT. Follow-up to evaluate for cardiac complications and their relation with the results of MPI was performed. Statistical analysis identified predictors of cardiac morbidities.Results: Eleven females and twenty nine males at a mean age of 66.7 years were included. Five patients (31%) with esophageal cancer and seven patients (29%) with lung cancer developed myocardial ischemia in the RT field at mean intervals of 7.0 and 8.4 months after RT. The patients were followed-up for mean intervals of 15 and 23 months in the esophageal and lung cancer groups, respectively. Seven patients in each of the esophageal (44%) and lung (29%) cancer patients (P = 0.5) developed cardiac complications of which one patient with esophageal cancer died of complete heart block. Six out of the fourteen patients (43%) with cardiac complication had new ischemia on MPI after CRT of which only one developed angina. The remaining eight patients with cardiac complications had normal MPI results. MPI result was not a statistically significant predictor of future cardiac complications after CRT. A history of congestive heart failure (CHF) (P = 0.003) or arrhythmia (P = 0.003) is a significant predictor of cardiac morbidity after CRT in univariate analysis but marginal predictors when multivariate analysis was performed (P = 0.06 and 0.06 for CHF and arrhythmia, respectively).Conclusions: Cardiac complications after CRT are more common in esophageal than lung cancer patients but the difference is not statistically significant. MPI abnormalities are frequently seen after CRT but are not predictive of future cardiac complications. A history of arrhythmia or CHF is significantly associated with cardiac complications after CRT. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine if combined intense lifestyle and pharmacologic lipid treatment reduce myocardial perfusion abnormalities and coronary events in comparison to usual-care cholesterol-lowering drugs and whether perfusion changes predict outcomes.Background: Lifestyle and lipid drugs separately benefit patients with coronary artery disease (CAD).Methods: A total of 409 patients with CAD, who underwent myocardial perfusion imaging by dipyridamole positron emission tomography at baseline and after 2.6 years, had quantitative size/severity of perfusion defects measured objectively by automated software with follow-up for five additional years for coronary artery bypass graft, percutaneous coronary intervention, myocardial infarction, or cardiac death. Patients were categorized blindly according to prospective, predefined criteria as "poor" treatment without diet or lipid drugs, or smoking; "moderate" treatment on American Heart Association diet and lipid-lowering drugs or on strict low-fat diet (<10% of calories) without lipid drugs; and "maximal" treatment with diet <10% of calories as fat, regular exercise, and lipid active drugs dosed to target goals of low-density lipoproteins <2.3 mmol/l (90 mg/dl), high-density lipoproteins >1.2 mmol/l (45 mg/dl), and triglycerides <1.1 mmol/l (100 mg/dl).Results: Over five years, coronary events occurred in 6.6%, 20.3%, and 30.6% of patients on maximal, moderate, and poor treatment, respectively (p = 0.001). Size/severity of perfusion abnormalities significantly decreased for patients receiving maximal treatment and increased for patients undergoing moderate and poor treatment (p = 0.003 and 0.0001, respectively). Combined intense lifestyle change plus lipid active drugs and severity/change of perfusion abnormalities independently predicted cardiac events.Conclusions: Intense lifestyle and pharmacologic lipid treatment reduce size/severity of myocardial perfusion abnormalities and cardiac events compared with usual-care cholesterol-lowering drugs. Perfusion changes parallel treatment intensity and predict outcomes. [ABSTRACT FROM AUTHOR]

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression. Anti-inflammatory therapy, therefore, presents a unique dilemma for cancer survivors: while it may decrease cardiovascular risk, it might also promote cancer growth and metastasis by suppressing the immune response. Senescence presents a potentially targetable solution to this challenge; senescence increases the risk of both cancer therapy resistance and vascular disease. Exercise, notably, shows promise in delaying this premature senescence, potentially improving cancer outcomes and lowering vascular disease risk post-treatment. This review focuses on the long-term impact of cancer therapies on vascular health. We underscore the importance of modulating senescence to balance cancer treatment's effectiveness and its vascular impact, and we emphasize investigating the role of exercise-mediated suppression of senescence in improving cancer survivorship., Competing Interests: J.L. Kirkland has a financial interest related to this research, including patents and pending patents covering senolytic drugs and their uses that are held by Mayo Clinic. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with the conflict of interest policies of Mayo Clinic. N.M.J. Hanssen has received honoraria from Boehringer Ingelheim, Bayer, and Novo Nordisk. A. Deswal is a consultant for Bayer. The other authors report no conflicts.

Non-bacterial thrombotic endocarditis (NBTE), formerly recognized as marantic endocarditis, represents a rare cardiovascular pathology intricately linked with hypercoagulable states, notably malignancy and autoimmune disorders. Characterized by the development of sterile vegetations comprised of fibrin and platelets on cardiac valves, NBTE poses a diagnostic challenge due to its resemblance to infective endocarditis. Therapeutic endeavours primarily revolve around addressing the underlying aetiology and instituting anticoagulant regimens to forestall embolic events, with surgical intervention seldom warranted. Non-bacterial thrombotic endocarditis frequently coexists with malignancies and autoimmune conditions, such as lupus and antiphospholipid antibody syndrome, and, more recently, has been associated with COVID-19. Its pathogenesis is underpinned by a complex interplay of endothelial dysfunction, hypercoagulability, hypoxia, and immune complex deposition. Clinical manifestations typically manifest as embolic phenomena, particularly cerebrovascular accidents, bearing substantial mortality rates. Diagnosis necessitates a high index of suspicion and meticulous exclusion of infective endocarditis, often facilitated by advanced cardiac imaging modalities. Anticoagulation, typically employing low molecular weight heparin or warfarin, constitutes the cornerstone of pharmacological intervention. Surgical recourse may be warranted in instances of refractory heart failure or recurrent embolic events. Given its multifaceted nature, the management of NBTE mandates a multidisciplinary approach, with prognosis contingent upon individual clinical intricacies. Future endeavours should prioritize further research to refine therapeutic strategies and enhance patient outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: The Coronavirus Disease - 2019 (COVID-19) pandemic significantly impacted healthcare service provision and put diabetic patients at increased risk of adverse health outcomes. We aimed to assess the impact of the COVID-19 pandemic on the incidence and demographic shift of major lower-limb amputation in diabetic patients., Methods: We performed a retrospective analysis of diabetic patient records undergoing major lower-limb amputation between 01/03/2019 and 01/03/2021 at the Royal Sussex County Hospital, the regional arterial hub for Sussex. Primary outcomes were amputation incidence rates and patient demographics compared between the prepandemic and pandemic cohorts., Results: The incidence rate ratio of major lower-limb amputations shows a drop in amputations during the pandemic compared to pre-pandemic (IRR 0.82; 95% CI 0.57-1.18). Data suggests a shift in the social deprivation background of patients receiving amputations to disproportionately affect those in the more deprived 50% of the population (p=0.038). Younger patients received more amputations during the pandemic compared to prepandemic levels (p=0.001)., Conclusion: Results suggest that during the COVID-19 pandemic there was a paradoxical reduction in amputations compared to prepandemic levels. However, changes to the demographic makeup of patient's receiving amputations are alarming as younger, and more deprived patients have been disproportionately affected by the pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 AlMajali, Richards, Yusuf and Telgenkamp.)

Introduction: The impact of peripheral cytokine levels on the prognosis and treatment of immune checkpoint inhibitor (ICI) myocarditis has not been well studied., Objectives: This study aimed to identify cytokines that can prognosticate and direct the treatment of ICI myocarditis., Methods: This was a single-center, retrospective cohort study of patients with ICI myocarditis who had available peripheral cytokine levels between January 2011 and May 2022. Major adverse cardiovascular events (MACEs) were defined as a composite of heart failure with/without cardiogenic shock, arterial thrombosis, life-threatening arrhythmias, pulmonary embolism, and sudden cardiac death., Results: In total, 65 patients with ICI myocarditis had cytokine data available. Patients were mostly males (70%), with a mean age of 67.8 ± 12.7 years. Interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) were the most common cytokines to be elevated with 48/65 (74%) of patients having a peak IL-6 above normal limits (>5 pg/mL) and 44/65 (68%) of patients with peak TNF-α above normal limits (>22 pg/mL). Patients with elevated peak IL-6 had similar 90-day mortality and MACE outcomes compared to those without (10.4% vs. 11.8%, p = 0.878 and 8.8% vs. 17.7%, p = 0.366, respectively). Similarly, those with elevated peak TNF-α had similar 90-day mortality and MACEs compared to those without (29.6% vs. 14.3%, p = 0.182 and 13.6% vs. 4.8%, p = 0.413, respectively). Kaplan-Meier survival analysis also showed that there was not a significant difference between MACE-free survival when comparing elevated and normal IL-6 and TNF-α levels ( p = 0.182 and p = 0.118, respectively). MACEs and overall survival outcomes were similar between those who received infliximab and those who did not among all patients and those with elevated TNF-α ( p -value 0.70 and 0.83, respectively)., Conclusion: Peripheral blood levels of IL-6 and TNF-α are the most commonly elevated cytokines in patients with ICI myocarditis. However, their role in the prognostication and guidance of immunomodulatory treatment is currently limited.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay., Competing Interests: SHL is an Advisory Board member of AstraZeneca, Beyond Spring Pharmaceuticals, STCube Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Jain, Casanova, Padilla, Paniagua Bojorges, Kotla, Ko, Samanthapudi, Chau, Nguyen, Wen, Hernandez Gonzalez, Rodgers, Olmsted-Davis, Hamilton, Reyes-Gibby, Yeung, Cooke, Herrmann, Chini, Xu, Yusuf, Yoshimoto, Lorenzi, Hobbs, Krishnan, Koutroumpakis, Palaskas, Wang, Deswal, Lin, Abe and Le.)

This case illustrates the unusual clinical presentation and natural progression of type A aortic dissection, found incidentally on echocardiogram in a patient with breast cancer. Possible association of tyrosine kinase inhibitor with aortic dissection is reviewed in the light of this case., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Carcinoid heart disease is increasingly recognized and challenging to manage due to limited outcomes data. This is the largest known cohort study of valvular pathology, treatment (including pulmonary and tricuspid valve replacements [PVR and TVR]), dispairties, mortality, and cost in patients with malignant carcinoid tumor (MCT)., Methods: Machine learning-augmented propensity score-adjusted multivariable regression was conducted for clincal outcomes in the 2016-2018 U.S. National Inpatient Sample (NIS). Regression models were weighted by the complex survey design and adjusted for known confounders and the likelihood of undergoing valvular procedures., Results: Among 101,521,656 hospitalizations, 55,910 (0.06%) had MCT. Patients with MCT vs. those without had significantly higher inpatient mortality (2.93 vs. 2.04%, p = 0.002), longer mean length of stay (12.20 vs. 4.62, p < 0.001), and increased mean total cost of stay ($70,252.18 vs. 51,092.01, p < 0.001). There was a ste p- wise increased rate of TVR and PVR with each subsequent year, with significantly more TV (0.16% vs. 0.01, p < 0.001) and PV (0.03 vs. 0.00, p = 0.040) diagnosed with vs. without MCT for 2016, with comparable trends in 2017 and 2018. There were no significant procedural disparities among patients with MCT for sex, race, income, urban density, or geographic region, except in 2017, when the highest prevalence of PV procedures were performed in the Western North at 50.00% ( p = 0.034). In machine learning and propensity score augmented multivariable regression, MCT did not significantly increase the likelihood of TVR or PVR. In sub-group analysis restricted to MCT, neither TVR nor PVR significantly increased mortality, though it did increase cost (respectively, $141,082.30, p = 0.015; $355,356.40, p = 0.012)., Conclusion: This analysis reflects a favorable trend in recognizing the need for TVR and PVR in patients with MCT, with associated increased cost but not mortality. Our study also suggests that pulmonic valve pathology is increasingly recognized in MCT as reflected by the upward trend in PVRs. Further research and updated societal guidelines may need to focus on the "forgotten pulmonic valve" to improve outcomes and disparities in this understudied patient population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Monlezun, Badalamenti, Javaid, Marmagkiolis, Honan, Kim, Patel, Akhanti, Halperin, Dasari, Koutroumpakis, Kim, Lopez-Mattei, Yusuf, Cilingiroglu, Mamas, Gregoric, Yao, Hassan and Iliescu.)

Introduction: This study examined the role of echocardiographic and cardiac histomorphology parameters in predicting mortality in patients with cardiac AL amyloidosis., Methods: Patients with endomyocardial biopsy-proven cardiac AL amyloidosis treated at MD Anderson Cancer Center between 6/2011 and 6/2020 were identified. Stored echocardiographic images and endomyocardial biopsy samples were processed for myocardial strain analysis and a detailed histomorphology characterization., Results: Of 43 patients; 44% were women and 63% white. Median age was 65 years; 51% underwent stem cell transplantation (SCT). Thirty patients (70%) died during follow up (median follow up: 4.1 years). Lower LA strain (<13.5%) and absence of SCT as a time-varying covariate were significantly associated with increased risk of death in the multivariate cox regression analysis. Higher LV mass and lower RV tricuspid annular plane systolic excursion were associated with increased odds of having ≥5% interstitial amyloid deposition on biopsy in the multivariate logistic regression analysis., Conclusion: Lower LA strain independently predicted mortality in our cohort, and its performance in the routine assessment of AL amyloidosis may be beneficial. Furthermore, SCT for cardiac AL amyloidosis was associated with improved OS. These findings need to be confirmed by larger studies in the era of contemporary systemic therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Koutroumpakis, Niku, Black, Ali, Sadaf, Song, Palaskas, Iliescu, Durand, Yusuf, Lee, Buja, Deswal and Banchs.)

Radiation therapy (RT) to the chest increases the patients' risk of cardiovascular disease (CVD). A complete understanding of the mechanisms by which RT induces CVD could lead to specific preventive, therapeutic approaches. It is becoming evident that both genotoxic chemotherapy agents and radiation induce mitochondrial dysfunction and cellular senescence. Notably, one of the common phenotypes observed in cancer survivors is accelerated senescence, and immunosenescence is closely related to both cancer risk and CVD development. Therefore, suppression of immunosenescence can be an ideal target to prevent cancer treatment-induced CVD. However, the mechanism(s) by which cancer treatments induce immunosenescence are incompletely characterized. We isolated peripheral blood mononuclear cells (PBMCs) before and 3 months after RT from 16 thoracic cancer patients. We characterized human immune cell lineages and markers of senescence, DNA damage response (DDR), efferocytosis, and determinants of clonal hematopoiesis of indeterminant potential (CHIP), using mass cytometry (CyTOF). We found that the frequency of the B cell subtype was decreased after RT. Unsupervised clustering of the CyTOF data identified 138 functional subsets of PBMCs. Compared with baseline, RT increased TBX21 (T-bet) expression in the largest B cell subset of Ki67 - /DNMT3a + naïve B cells, and T-bet expression was correlated with phosphorylation of p90RSK expression. CD38 expression was also increased in naïve B cells (CD27 - ) and CD8 + effector memory CD45RA T cells (T EMRA ). In vitro , we found the critical role of p90RSK activation in upregulating (1) CD38 + /T-bet + memory and naïve B, and myeloid cells, (2) senescence-associated β-gal staining, and (3) mitochondrial reactive oxygen species (ROS) after ionizing radiation (IR). These data suggest the crucial role of p90RSK activation in immunosenescence. The critical role of p90RSK activation in immune cells and T-bet induction in upregulating atherosclerosis formation has been reported. Furthermore, T-bet directly binds to the CD38 promoter region and upregulates CD38 expression. Since both T-bet and CD38 play a significant role in the process of immunosenescence, our data provide a cellular and molecular mechanism that links RT-induced p90RSK activation and the immunosenescence with T-bet and CD38 induction observed in thoracic cancer patients treated by RT and suggests that targeting the p90RSK/T-bet/CD38 pathway could play a role in preventing the radiation-associated CVD and improving cancer prognosis by inhibiting immunosenescence., Competing Interests: Author E-aA was employed by the company Astrolabe Diagnostics, Inc. SL was an Advisory Board member of AstraZeneca, Beyond Spring Pharmaceuticals, STCube Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Imanishi, Cheng, Kotla, Deswal, Le, Chini, Ko, Samanthapudi, Lee, Herrmann, Xu, Reyes-Gibby, Yeung, Schadler, Yusuf, Liao, Nurieva, Amir, Burks, Palaskas, Cooke, Lin, Kobayashi, Yoshimoto and Abe.)

Myocardial dysfunction in patients with cancer is a major cause of morbidity and mortality. Cancer therapy-related cardiotoxicities are an important contributor to the development of cardiomyopathy in this patient population. Furthermore, cardiac AL amyloidosis, cardiac malignancies/metastases, accelerated atherosclerosis, stress cardiomyopathy, systemic and pulmonary hypertension are also linked to the development of myocardial dysfunction. Herein, we summarize current knowledge on the mechanisms of myocardial dysfunction in the setting of cancer and cancer-related therapies. Additionally, we briefly outline key recommendations on the surveillance and management of cancer therapy-related myocardial dysfunction based on the consensus of experts in the field of cardio-oncology., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: This study investigated the factors predicting survival and the recurrence of pericardial effusion (PE) requiring pericardiocentesis (PCC) in patients with cancer., Materials and Methods: We analyzed the data of patients who underwent PCC for large PEs from 2010 to 2020 at The University of Texas MD Anderson Cancer Center. The time to the first recurrent PE requiring PCC was the interval from the index PCC with pericardial drain placement to first recurrent PE requiring drainage (either repeated PCC or a pericardial window). Univariate and multivariate Fine-Gray models accounting for the competing risk of death were used to identify predictors of recurrent PE requiring drainage. Cox regression models were used to identify predictors of death., Results: The study cohort included 418 patients with index PCC and pericardial drain placement, of whom 65 (16%) had recurrent PEs requiring drainage. The cumulative incidences of recurrent PE requiring drainage at 12 and 60 months were 15.0% and 15.6%, respectively. Younger age, anti-inflammatory medication use, and solid tumors were associated with an increased risk of recurrence of PE requiring drainage, and that echocardiographic evidence of tamponade at presentation and receipt of immunotherapy were associated with a decreased risk of recurrence. Factors predicting poor survival included older age, malignant effusion on cytology, non-use of anti-inflammatory agents, non-lymphoma cancers and primary lung cancer., Conclusion: Among cancer patients with large PEs requiring drainage, young patients with solid tumors were more likely to experience recurrence, while elderly patients and those with lung cancer, malignant PE cytology, and non-use of anti-inflammatory agents showed worse survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ahmed, Mouhayar, Song, Koutroumpakis, Palaskas, Yusuf, Lopez-Mattei, Hassan, Kim, Cilingiroglu, Marmagkiolis, Vaporciyan, Swisher, Deswal and Iliescu.)

Purpose of Review: Despite the advancements of modern radiotherapy, radiation-induced cardiovascular disease (RICVD) remains a common cause of morbidity and mortality among cancer survivors., Recent Findings: Proposed pathogenetic mechanisms of RICVD include endothelial cell damage with accelerated atherosclerosis, pro-thrombotic alterations in the coagulation pathway as well as inflammation and fibrosis of the myocardial, pericardial, valvular, and conduction tissues. Prevention of RICVD can be achieved by minimizing the exposure of the cardiovascular system to radiation, by treatment of underlying cardiovascular risk factors and cardiovascular disease, and possibly by prophylactic pharmacotherapy post exposure. Herein we summarize current knowledge on the mechanisms underlying the pathogenesis of RICVD and propose prevention and treatment strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Improvement in cancer survival has led to an increased focus on cardiovascular disease as the other major determinant of survivorship. As a result, there has been an increasing interest in managing cardiovascular disease during and post cancer treatment., Areas Covered: This article reviews the current literature on the pathogenesis, risk factors, presentation, treatment and clinical outcomes of acute coronary syndrome (ACS) in patients with cancer., Expert Opinion: There is growing evidence that both medical therapy and invasive management of ACS improve outcomes in patients with cancer. Appropriate patient selection, risk stratification and tailored therapy represents the cornerstone of management in these patients.

Background: There is a paucity of data regarding the association between radiation exposure of heart substructures and the incidence of major coronary events (MCEs) in patients with esophageal cancer (ESOC) undergoing chemoradiation therapy. We studied radiation dosimetric determinants of MCE risk and measured their impact on patient prognosis using a cohort of ESOC patients treated at a single institution. Methods: Between March 2005 and October 2015, 355 ESOC patients treated with concurrent chemoradiotherapy were identified from a prospectively maintained and institutional-regulatory-board-approved clinical database. Dose-distribution parameters of the whole heart, the atria, the ventricles, the left main coronary artery, and three main coronary arteries were extracted for analysis. Results: Within a median follow-up time of 67 months, 14 patients experienced MCEs at a median of 16 months. The incidence of MCEs was significantly associated with the left anterior descending coronary artery (LAD) receiving ≥30 Gy (V30Gy) (p = 0.048). Patients receiving LAD V30Gy ≥ 10% of volume experienced a higher incidence of MCEs versus the LAD V30Gy < 10% group (p = 0.044). The relative rate of death increased with the left main coronary artery (LMA) mean dose (Gy) (p = 0.002). Furthermore, a mutual promotion effect of hyperlipidemia and RT on MCEs was observed. Conclusion: Radiation dose to coronary substructures is associated with MCEs and overall survival in patients with ESOC. In this study, the doses to these substructures appeared to be better predictors of toxicity outcomes than mean heart dose (MHD) or whole-heart V30Gy. These findings have implications for reducing coronary events through radiation therapy planning.

Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. Senescence-associated secretory phenotype (SASP) can be induced by telomere dysfunction. Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. In this review, we will discuss the role of NAD + depletion in instigating SASP and its downstream signaling and regulatory mechanisms that lead to the premature onset of atherosclerotic cardiovascular diseases in cancer survivors., Competing Interests: Conflicts of interest All authors declare that there are no conflicts of interest.

The incidence of cardiovascular disease (CVD) is higher in cancer survivors than in the general population. Several cancer treatments are recognized as risk factors for CVD, but specific therapies are unavailable. Many cancer treatments activate shared signaling events, which reprogram myeloid cells (MCs) towards persistent senescence-associated secretory phenotype (SASP) and consequently CVD, but the exact mechanisms remain unclear. This study aimed to provide mechanistic insights and potential treatments by investigating how chemo-radiation can induce persistent SASP. We generated ERK5 S496A knock-in mice and determined SASP in myeloid cells (MCs) by evaluating their efferocytotic ability, antioxidation-related molecule expression, telomere length, and inflammatory gene expression. Candidate SASP inducers were identified by high-throughput screening, using the ERK5 transcriptional activity reporter cell system. Various chemotherapy agents and ionizing radiation (IR) up-regulated p90RSK-mediated ERK5 S496 phosphorylation. Doxorubicin and IR caused metabolic changes with nicotinamide adenine dinucleotide depletion and ensuing mitochondrial stunning (reversible mitochondria dysfunction without showing any cell death under ATP depletion) via p90RSK-ERK5 modulation and poly (ADP-ribose) polymerase (PARP) activation, which formed a nucleus-mitochondria positive feedback loop. This feedback loop reprogramed MCs to induce a sustained SASP state, and ultimately primed MCs to be more sensitive to reactive oxygen species. This priming was also detected in circulating monocytes from cancer patients after IR. When PARP activity was transiently inhibited at the time of IR, mitochondrial stunning, priming, macrophage infiltration, and coronary atherosclerosis were all eradicated. The p90RSK-ERK5 module plays a crucial role in SASP-mediated mitochondrial stunning via regulating PARP activation. Our data show for the first time that the nucleus-mitochondria positive feedback loop formed by p90RSK-ERK5 S496 phosphorylation-mediated PARP activation plays a crucial role of persistent SASP state, and also provide preclinical evidence supporting that transient inhibition of PARP activation only at the time of radiation therapy can prevent future CVD in cancer survivors., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Infective endocarditis (IE) is more common in patients with cancer as compared with the general population. Due to an immunocompromised state, the need for invasive procedures, hypercoagulability and the presence of indwelling catheters, patients with cancer are particularly predisposed to the development of IE., Objectives: Limited information exists about IE in patients with cancer. We aimed to evaluate the characteristics of patients with cancer and IE at our tertiary care centre, including a comparison of the microorganisms implicated and their association with mortality., Methods: A retrospective chart review of patients with cancer who had echocardiography for suspicion of endocarditis was conducted. A total of 56 patients with a confirmed diagnosis of cancer and endocarditis, based on the modified Duke criteria, were included in the study. Baseline demographics, risk factors for developing IE, echocardiography findings, microbiology and mortality data were analysed., Results: Following the findings of vegetations by echocardiography, the median survival time was 8.5 months. Staphylococcus aureus was the most common organism identified as causing endocarditis. The mitral and aortic valves were the most commonly involved sites of endocarditis. Patients with S. aureus endocarditis (SAE) had a significantly poorer survival when compared with patients without SAE (p=0.0217) over the 12-month period from diagnosis of endocarditis., Conclusions: Overall survival of patients with cancer and endocarditis is poor, with a worse outcome in patients with SAE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Contralateral gate cannulation is one of the key steps of endovascular aortic aneurysm repair (EVAR), and multiple different techniques and tips have been described to ensure accurate and swift performance of this step. In some cases, a crossover approach, entailing an up-and-over wire access from the ipsilateral limb into the contralateral gate followed by snaring the wire to the contralateral groin and proceeding with contralateral limb deployment is needed. The risks with this technique include the necessity of completely deploying the stent-graft main body, ipsilateral limb, and release of its trigger wires which essentially render the graft untethered, and cause concerns about the graft migrating upwards or "buckling" during advancement of the contralateral limb in challenging anatomy. To overcome this issue, we describe a modification of this technique which involves retaining the through and through wire used for crossover cannulation as a stabilizing mechanism for the stent-graft and advancing a second "buddy wire" into the contralateral gate for deployment of the contralateral limb., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with cancer and aortic stenosis (AS) are exposed to several factors that could accelerate the progression of AS. This study aimed to determine the cumulative incidence of AS progression and associated factors in these patients. This retrospective cohort study included patients with cancer, mild or moderate AS and at least two echocardiograms 6 months apart between 1996 and 2016 at MD Anderson Cancer Center. AS progression was defined by an increase in mean gradient of 20 mmHg or peak velocity of 2 m/s by spectral Doppler echocardiography or as requiring aortic valve replacement. Univariate and multivariable Fine-Gray models to account for the competing risk of death were used. One hundred and two patients were included and median follow-up was 7.3 years. Overall, 30 patients (29%) developed AS progression, while 48 (47%) died without it. Yearly rate of mean gradient change was 4.9 ± 3.9 mmHg and yearly rate of peak velocity change was 0.23 ± 0.29 m/s for patients who developed AS progression. In the univariate analysis, coronary artery disease (CAD), dyspnea, prevalent cyclophosphamide and beta-blocker use were associated with AS progression. In multivariable analysis, CAD and prevalent cyclophosphamide use for the time interval of more than 3 years of follow-up remained significantly associated with increased cumulative incidence of AS progression. In conclusion, patients with mild or moderate AS and cancer are more likely to die before having AS progression. AS progression is associated with CAD and prevalent cyclophosphamide use., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bravo-Jaimes, Palaskas, Banchs, Abelhad, Altaf, Gouni, Song, Hassan, Iliescu, Deswal and Yusuf.)

The recent surge in cancer drug approval has provided us in cardio-oncology with a new and unique era, which modern medicine has not experienced before: the diminishing availability of "conventional" evidence-based medicine. The drastic and quick changes in oncology has made it difficult, and at times even impossible, to establish a meaningful evidence-based cardio-oncology practice by simply following the oncologists' practice. For the modern cardio-oncologist, it seems that a more proactive approach and methodology is needed. We believe that only through such an approach (learn from the old, and apply to the new) the cardio-oncologist will obtain meaningful evidence to perform their every-day practice in this new era., (Copyright © 2020 Abe, Yusuf, Deswal and Herrmann.)

Previously, we reported that post-translational modifications (PTMs) of MAGI1, including S741 phosphorylation and K931 de-SUMOylation, both of which are regulated by p90RSK activation, lead to endothelial cell (EC) activation. However, roles for p90RSK and MAGI1-PTMs in regulating EC permeability remain unclear despite MAGI1 being a junctional molecule. Here, we show that thrombin (Thb)-induced EC permeability, detected by the electric cell-substrate impedance sensing (ECIS) based system, was decreased by overexpression of dominant negative p90RSK or a MAGI1-S741A phosphorylation mutant, but was accelerated by overexpression of p90RSK, siRNA-mediated knockdown of magi1 , or the MAGI1-K931R SUMOylation mutant. MAGI1 depletion also increased the mRNA and protein expression of the large tumor suppressor kinases 1 and 2 (LATS1/2), which inhibited YAP/TAZ activity and increased EC permeability. Because the endothelial barrier is a critical mediator of tumor hypoxia, we also evaluated the role of p90RSK activation in tumor vessel leakiness by using a relatively low dose of the p90RSK specific inhibitor, FMK-MEA. FMK-MEA significantly inhibited tumor vessel leakiness at a dose that does not affect morphology and growth of tumor vessels in vivo . These results provide novel insights into crucial roles for p90RSK-mediated MAGI1 PTMs and the Hippo pathway in EC permeability, as well as p90RSK activation in tumor vessel leakiness., (Copyright © 2020 Abe, Savage, Imanishi, Banerjee, Kotla, Paez-Mayorga, Taunton, Fujiwara, Won, Yusuf, Palaskas, Banchs, Lin, Schadler, Abe and Le.)

Introduction: Late cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin's lymphoma has been well-reported. However, the relatively higher cardiac dose exposure for esophageal cancer (EC) may result in the earlier onset of cardiac diseases. In this report, we examined the incidence, onset, and long-term survival outcomes of high-grade cardiac events after RT in a large cohort of patients with EC., Methods: Between March 2005 and August 2017, a total of 479 patients with EC from a prospectively maintained institutional database at The University of Texas MD Anderson Cancer Center were analyzed. All patients were treated with either intensity-modulated RT or proton beam therapy, either preoperatively or definitively. We focused on any grade 3 or higher (G3+) cardiac events according to the Common Terminology Criteria for Adverse Events, version 5.0., Results: G3+ cardiac events occurred in 18% of patients at a median of 7 months with a median follow-up time of 76 months. Preexisting cardiac disease (p = 0.001) and radiation modality (intensity-modulated RT versus proton beam therapy) (p = 0.027) were significantly associated with G3+ cardiac events. Under multivariable analysis, the mean heart dose, particularly of less than 15 Gy, was associated with reduced G3+ events. Furthermore, G3+ cardiac events were associated with worse overall survival (p = 0.041)., Conclusions: Severe cardiac events were relatively common in patients with early onset EC after RT, especially those with preexisting cardiac disease and higher radiation doses to the heart. Optimal treatment approaches should be taken to reduce cumulative doses to the heart, especially for patients with preexisting cardiac disease., (Copyright © 2020 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Introduction: About 234 million major surgical procedures are performed each year worldwide, of which >60 million surgeries are performed in the United States. Though postoperative major adverse cardiac complications are relatively low, patients with postoperative myocardial infarction have higher in-hospital mortality. Thus, comprehensive cardiac evaluations, and in some cases, elective coronary revascularizations, are performed prior to surgery with an intent to minimize these complications. In 2009, approximately 4% of all elective percutaneous coronary interventions were performed in preparation for noncardiac surgery., Areas Covered: We discuss relevant articles from the last 50 years regarding elective preoperative coronary revascularization prior to noncardiac surgery., Expert Opinion: In the early years there was an interest in preemptive revascularization to reduce postoperative cardiac events; however, subsequent studies in patients with stable coronary artery disease have mostly shown that a strategy of routine prophylactic coronary revascularization prior to noncardiac surgery does not reduce postoperative cardiac complications.

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer therapy, but also in patients with a variety of other clinical conditions. This review and case series examine the clinical applications and overall usefulness of speckle-tracking echocardiography in cardio-oncology and, more broadly, in clinical cardiology., (© 2020 by the Texas Heart® Institute, Houston.)

Despite the advancements of modern radiotherapy, radiation-induced heart disease remains a common cause of morbidity and mortality amongst cancer survivors. This review outlines the basic mechanism, clinical presentation, risk stratification, early detection, possible mitigation, and treatment of this condition., (© 2020 S. Karger AG, Basel.)

Purpose of Review: Carcinoid heart disease is a rare disorder that is associated with significant morbidity and mortality. In this review of the literature, we will present current concepts in diagnosis and management of carcinoid heart disease., Recent Findings: Recent expert consensus guidelines highlight the role of echocardiography and screening with NT-proBNP for the evaluation of carcinoid heart disease. Advances in medical therapy along with better surgical outcomes highlight the experience and expertise that has been gained in the treatment of carcinoid heart disease. Carcinoid heart disease occurs in patients with neuroendocrine tumors who have carcinoid syndrome. Serotonin appears to play a central role in the development of carcinoid heart disease. Cardiac biomarkers and multimodality imaging can be used to aid in screening and diagnosis. The mainstay of treatment of carcinoid heart disease is surgery.

With increasing survival from cancer, the incidence of cardiovascular diseases is increasing as a chronic side effect of radiation therapy. Prevention, early recognition, and prompt intervention should be the major focus in the care of these patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)