Allostatic Load/Chronic Stress and Cardiovascular Outcomes in Patients Diagnosed With Breast, Lung, or Colorectal Cancer.

BACKGROUND: Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1-point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. METHODS AND RESULTS: Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010-2019) and followed up at a large, hybrid academic-community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0-11). Adjusted Fine-Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2-year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1-point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06-1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12-1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08-1.19]). When considering AL as a time-varying exposure, the peak associated MACE risk occurred with a 1-point AL rise between 6 and 12 months post- breast cancer, lung cancer, and colorectal cancer diagnosis. CONCLUSIONS: AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

Adulthood adiposity affects cardiac structure and function in later life.

BACKGROUND AND AIMS: Excess adiposity is associated with poorer cardiac function and adverse left ventricular (LV) remodelling. However, its importance over the adult life course on future cardiac structure and systolic and diastolic function is unknown. METHODS: A total of 1690 participants in the National Survey of Health and Development birth cohort underwent repeated adiposity [body mass index (BMI)/waist-to-hip ratio (WHR)] measurements over adulthood and investigation, including echocardiography at age 60-64 years. The relationship between LV structure [LV mass (LVM), relative wall thickness, and LV internal diameter in diastole (LVIDd)] and function (diastolic: E/e', e', and left atrial volume indexed to body surface area; systolic: ejection fraction, S', and myocardial contraction fraction) was investigated using multivariable linear regression models. RESULTS: Increased BMI from age 20 years onwards was associated with greater LVM and LVIDd independent of confounders. Associations remained independent of current BMI for LVIDd and at age 26, 43, and 53 years for LVM. Increased BMI from 43 years onwards was associated with greater relative wall thickness, but not when BMI at age 60-64 years was accounted for. Increased BMI at age 26, 36, and 53 years and at 20 years onwards was associated with lower ejection fraction and myocardial contraction fraction, respectively, but not independently of BMI at 60-64 years. Higher BMI from 20 years onwards was associated with poorer diastolic function independent of confounders. Associations between BMI and left atrial volume indexed to body surface area persisted from 26 years onwards after adjustment for BMI at 60-64 years. Similar relationships were observed for WHR from age 43 years onwards. CONCLUSIONS: Higher adiposity (BMI/WHR) over adulthood is associated with evidence of adverse cardiac structure and function. Some of these associations are independent of adiposity in later life.

Socioeconomic and Ethnic Disparities in the Process of Care and Outcomes Among Cancer Patients With Acute Coronary Syndrome.

Cancer and acute coronary syndrome (ACS) are the leading causes of morbidity and mortality globally, with many shared risk factors. There are several challenges to the management of patients with cancer presenting with ACS, owing to their higher baseline risk profile, the complexities of their cancer-related therapies and prognosis, and their higher risk of adverse outcomes after ACS. Although previous studies have demonstrated disparities in the care of both cancer and ACS among patients from ethnic minorities and socioeconomic deprivation, there is limited evidence around the magnitude of such disparities specifically in cancer patients presenting with ACS. This review summarises the current literature on differences in prevalence and management of ACS among patients with cancer from ethnic minorities and socioeconomically deprived backgrounds, as well as the gaps in evidence around the care of this high-risk population and potential solutions.

Heart Failure Readmission in Patients With ST-Segment Elevation Myocardial Infarction and Active Cancer.

Background: Although numerous studies have examined readmission with heart failure (HF) after acute myocardial infarction (AMI), limited data are available on HF readmission in cancer patients post-AMI. Objectives: This study aimed to assess the rates and factors associated with HF readmission in cancer patients presenting with ST-segment elevation myocardial infarction (STEMI). Methods: A nationally linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project registry and the UK national Hospital Episode Statistics Admitted Patient Care registry. Multivariable Fine-Gray competing risk models were used to evaluate HF readmission at 30 days and 1 year. Results: A total of 326,551 STEMI indexed admissions were included, with 7,090 (2.2%) patients having active cancer. The cancer group was less likely to be admitted under the care of a cardiologist (74.5% vs 81.9%) and had lower rates of invasive coronary angiography (62.2% vs 72.7%; P < 0.001) and percutaneous coronary intervention (58.4% vs. 69.5%). There was a significant prescription gap in the administration of post-AMI medications upon discharge such as an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (49.5% vs 71.1%) and beta-blockers (58.4% vs 68.0%) in cancer patients. The cancer group had a higher rate of HF readmission at 30 days (3.2% vs 2.3%) and 1 year (9.4% vs 7.3%). However, after adjustment, cancer was not independently associated with HF readmission at 30 days (subdistribution HR: 1.05; 95% CI: 0.86-1.28) or 1 year (subdistribution HR: 1.03; 95% CI: 0.92-1.16). The opportunity-based quality indicator was associated with higher rates of HF readmission independent of cancer diagnosis. Conclusions: Cancer patients receive care that differs in important ways from patients without cancer. Greater implementation of evidence-based care may reduce HF readmissions, including in cancer patients.

Advancing the care of individuals with cancer through innovation & technology: Proceedings from the cardiology oncology innovation summit 2020 and 2021.

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Cardiovascular risk in a contemporary cohort of patients with myeloproliferative neoplasms'.

BACKGROUND: Myeloproliferative neoplasms (MPNs) are a group of disorders of clonal haemopoiesis associated with an inherent risk of arterial and venous thrombotic complications. The prevalence of thrombotic complications and the impact of cardiovascular risk factors (CVRFs) in contemporary patient cohorts within the current era of MPN treatments have not been completely defined. OBJECTIVES: We aim to characterise the cardiovascular risk of patients with MPN by identifying the prevalence of CVRFs and describing the pattern of thrombotic events. We also aim to utilise the QRISK3 algorithm, which is a validated model used to estimate an individual's risk of developing cardiovascular disease, to further phenotype this cohort of patients. METHODS: We perform a retrospective analysis on a single-centre cohort of 438 patients with MPN. RESULTS: MPN patients continue to carry a high burden of vascular morbidity with a prevalence of arterial thrombotic events in 15.8 % (69/438) and venous thrombotic events in 13.2 % (58/438) of the cohort. The novel use of the QRISK3 algorithm, which showed a mean score of 13.7 % across the MPN population, provides further evidence to suggest an increased cardiovascular risk in MPN patients. CONCLUSION: With an increased risk of cardiovascular disease in patients with MPN, we propose an integrated approach between primary and specialised healthcare services using risk stratification tools such as QRISK3, which will allow aggressive optimisation of CVRFs to prevent thrombosis and reduce the overall morbidity and mortality in patients with MPN.

Global Cardio Oncology Registry (G-COR): Registry Design, Primary Objectives, and Future Perspectives of a Multicenter Global Initiative.

BACKGROUND: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry. METHODS: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative. RESULTS: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment. CONCLUSIONS: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated.

Anthracyclines and Biomarkers of Myocardial Injury: The Effect of Remote Ischemic Conditioning.

Background: Remote ischemic conditioning (RIC) has been beneficial in laboratory studies of anthracycline cardiotoxicity, but its effects in patients is not established. Objectives: The authors studied the effect of RIC on cardiac biomarkers and function during and after anthracycline chemotherapy. Methods: The ERIC-Onc study (Effect of Remote Ischaemic Conditioning in Oncology Patients; NCT02471885) was a randomized, single-blind, sham-controlled study of RIC at each chemotherapy cycle. The primary endpoint was troponin T (TnT) during chemotherapy and up to 1 year. Secondary outcomes included cardiac function, major adverse cardiovascular events (MACE), and MACE or cancer death. Cardiac myosin-binding-protein C (cMyC) was investigated in parallel with TnT. Results: The study was prematurely halted after the evaluation of 55 patients (RIC n = 28, sham n = 27). Biomarkers increased from baseline to cycle 6 of chemotherapy for all patients (median TnT 6 [IQR: 4-9] ng/L to 33 [IQR: 16-36)] ng/L; P ≤ 0.001; cMyC 3 (IQR: 2-5) ng/L to 47 (IQR: 18-49) ng/L; P ≤ 0.001). Mixed-effects regression analysis for repeated measures showed no difference in TnT between the 2 groups (RIC vs sham, mean difference 3.15 ng/L; 95% CI: -0.04 to 6.33; P = 0.053), or cMyC (RIC vs sham, mean difference 4.17 ng/L; 95% CI: -0.12 to 8.45; P = 0.056). There were more MACE and cancer deaths in the RIC group (11 vs 3; HR: 0.25; 95% CI: 0.07-0.90; P = 0.034), with more cancer deaths (8 vs 1; HR: 0.21; 95% CI: 0.04-0.95; P = 0.043) at 1 year. Conclusions: TnT and cMyC significantly increased during anthracycline chemotherapy with 81% having a TnT ≥14 ng/L at cycle 6. RIC did not affect the rise in biomarkers, but there was a small increase in early cancer deaths, possibly related to the greater proportion of patients with metastatic disease randomized to the RIC group (54%vs 37%). (Effect of Remote Ischaemic Conditioning in Oncology Patients [ERIC-ONC]; NCT02471885).

Essentials of cardio-oncology.

Cardio-oncology is a subspecialty that provides cardiac care for patients with cancer. Newer oncological agents have not only increased survivorship, but also sprouted novel cardiovascular toxicity (CVT) involving any component of the cardiovascular system, albeit with some preferential targets. Patients with cancer should undergo a baseline cardiovascular risk assessment and have individualised surveillance planned during cancer therapy and post treatment. The early diagnosis of CVT, by clinical history and examination along with imaging and laboratory analysis, is paramount. Management includes cardioprotective strategies and multidisciplinary decision-making regarding the risk-benefit ratio of oncological treatment based on CVT.

Cardiovascular complications of treatment for prostate cancer.

Prostate cancer, an androgen-dependent disease, is one of the leading causes of mortality in men. It can present as localised disease, locally advanced or distant metastatic disease. Treatment options for patients with prostate cancer include surgery, chemotherapy, brachytherapy, radiation therapy and hormonal therapy. There are multiple treatment options for each stage of the disease, but hormone therapy is usually reserved for advanced stages. Cardiovascular disease is the leading cause of death in patients with prostate cancer and both diseases share common risk factors. Hormone therapy improves prognosis in patients with more advanced disease, albeit at the cost of cardiovascular toxicity. Hormone therapy can be achieved with the use of agonists and antagonists of gonadotropin-releasing hormone receptors, androgen receptor blockers and enzyme inhibitors of androgen synthesis. Drug-specific cardiotoxicity caused by treatments for prostate cancer has not been fully elucidated. Cardiovascular disease in patients with prostate cancer is mainly managed via an ABCDE approach, a strategy to optimise common risk factors. With newer agents improving the prognosis for patients with prostate cancer, cardiovascular toxicity will have a greater impact on the outcomes of these patients. This article reviews cardiovascular risks associated with therapy for prostate cancer with a focus on hormonal therapy.

An Update on the Role of Cardiac Magnetic Resonance Imaging in Cancer Patients.

PURPOSE OF REVIEW: Cardiac magnetic resonance imaging has a significant and expanding role to play in contemporary cardio-oncology. This review seeks to explore the current and future roles of this imaging modality in the cardio-oncology setting. RECENT FINDINGS: Cardiac magnetic resonance imaging is required in diagnosing, monitoring and treating all types of cardiotoxicities (acute coronary syndromes, arrhythmias, myocarditis, pericardial disease, heart failure) and in all types of cancers (breast, gastrointestinal, renal, prostate, haematological etc.). Newer imaging sequences and techniques can help provide additional information and shorten imaging times. Cardiac magnetic resonance imaging is an integral part of the holistic management of cardio-oncology patients, with increasingly expanding applications in the area.

Advances in Multimodality Imaging in Cardio-Oncology: JACC State-of-the-Art Review.

The population of patients with cancer is rapidly expanding, and the diagnosis and monitoring of cardiovascular complications greatly rely on imaging. Numerous advances in the field of cardio-oncology and imaging have occurred in recent years. This review presents updated and practical approaches for multimodality cardiovascular imaging in the cardio-oncology patient and provides recommendations for imaging to detect the myriad of adverse cardiovascular effects associated with antineoplastic therapy, such as cardiomyopathy, atherosclerosis, vascular toxicity, myocarditis, valve disease, and cardiac masses. Uniquely, we address the role of cardiovascular imaging in patients with pre-existing cardiomyopathy, pregnant patients, long-term survivors, and populations with limited resources. We also address future avenues of investigation and opportunities for artificial intelligence applications in cardio-oncology imaging. This review provides a uniform practical approach to cardiovascular imaging for patients with cancer.

Chest Pain in the Cancer Patient.

Chest pain is one of the most common presenting symptoms in patients seeking care from a physician. Risk assessment tools and scores have facilitated prompt diagnosis and optimal management in these patients; however, it is unclear as to whether a standardised approach can adequately triage chest pain in cancer patients and survivors. This is of concern because cancer patients are often at an increased risk of cardiovascular mortality and morbidity given the shared risk factors between cancer and cardiovascular disease, compounded by the fact that certain anti-cancer therapies are associated with an increased risk of cardiovascular events that can persist for weeks and even years after treatment. This article describes the underlying mechanisms of the most common causes of chest pain in cancer patients with an emphasis on how their management may differ to that of non-cancer patients with chest pain. It will also highlight the role of the cardio-oncology team, who can aid in identifying cancer therapy-related cardiovascular side-effects and provide optimal multidisciplinary care for these patients.

Cardio-oncology Issues in Lymphoma Patients.

BACKGROUND: Advances in Lymphoma management have resulted in significant improvements in patient outcomes over the last 50 years. Despite these developments, cardiotoxicity from lymphoma treatments remains an important cause of mortality and morbidity in this cohort of patients. We outlined the most common cardiotoxicities associated with lymphoma treatments and their respective investigation and management strategies, including the role of cardiac pre-assessment and late effects monitoring.

Bradyarrhythmias in Cardio-Oncology.

The relationship between bradyarrhythmias and cancer therapies has not been well described but is increasingly recognized. There have been extensive advances in oncological pharmacotherapy, with several new classes of drugs available including targeted agents, immune checkpoint inhibitors and CAR T cell therapy. This increasing repertoire of available drugs has revolutionized overall prognosis and survival of cancer patients but the true extent of their cardiovascular toxicity is only beginning to be understood. Previous studies and published reviews have traditionally focused on conventional chemotherapies and in arrhythmias in general, particularly tachyarrhythmias. The number of patients with both cancer and cardiovascular problems is increasing globally and oncologists and cardiologists need to be adept at managing arrythmia based scenarios. Greater collaboration between the two specialties including studies with prospective data collection in Cardio-Oncology are much needed to fill in knowledge gaps in this arena. This case-based review summarizes current available evidence of cancer treatment-related bradyarrhythmia incidence (including its different subtypes), possible mechanisms and outcomes. Furthermore, we propose a stepwise surveillance and management protocol for patients with suspected bradyarrhythmia related to cancer treatment.

Corrigendum: Imaging Protocol, Feasibility, and Reproducibility of Cardiovascular Phenotyping in a Large Tri-Ethnic Population-Based Study of Older People: The Southall and Brent Revisited (SABRE) Study.

[This corrects the article DOI: 10.3389/fcvm.2020.591946.].

BSE and BCOS Guideline for Transthoracic Echocardiographic Assessment of Adult Cancer Patients Receiving Anthracyclines and/or Trastuzumab.

The subspecialty of cardio-oncology aims to reduce cardiovascular morbidity and mortality in patients with cancer or following cancer treatment. Cancer therapy can lead to a variety of cardiovascular complications, including left ventricular systolic dysfunction, pericardial disease, and valvular heart disease. Echocardiography is a key diagnostic imaging tool in the diagnosis and surveillance for many of these complications. The baseline assessment and subsequent surveillance of patients undergoing treatment with anthracyclines and/or human epidermal growth factor receptor (HER) 2-positive targeted treatment (e.g., trastuzumab and pertuzumab) form a significant proportion of cardio-oncology patients undergoing echocardiography. This guideline from the British Society of Echocardiography and British Cardio-Oncology Society outlines a protocol for baseline and surveillance echocardiography of patients undergoing treatment with anthracyclines and/or trastuzumab. The methodology for acquisition of images and the advantages and disadvantages of techniques are discussed. Echocardiographic definitions for considering cancer therapeutics-related cardiac dysfunction are also presented.

Entrectinib-related myocarditis in a young female patient with metastatic non-small cell lung cancer.

A 51-year-old woman presented with a 2-week history of off balance, left lower limb weakness and neglect and neck pain radiating down the right arm. Investigations revealed a metastatic, ROS1 fusion-positive, non-small cell lung cancer, and treatment with entrectinib, a recently approved multikinase inhibitor, was started. Two weeks after, she was admitted to the emergency department with new-onset pressure-like chest pain and dyspnoea. Laboratory evaluation showed elevated troponin and mild left ventricular systolic dysfunction with reduced global longitudinal strain on transthoracic echocardiogram. Cardiac magnetic resonance revealed mild oedema and non-ischaemic fibrosis. A diagnosis of drug-induced myocarditis was made. Cardioprotective medication with an angiotensin-converting enzyme inhibitor and a beta-blocker was started. Entrectinib was temporarily discontinued and restarted at a reduced dose after a multidisciplinary team meeting involving both the oncology and cardio-oncology teams. This is the second described case of entrectinib-induced myocarditis and the first one without eosinophilia.