Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

BACKGROUND: Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. METHODS: Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. RESULTS: Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). CONCLUSIONS: Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Mortality After Major Cardiovascular Events in Survivors of Childhood Cancer.

BACKGROUND: Adult survivors of childhood cancer are at risk for cardiovascular events. OBJECTIVES: In this study, we sought to determine the risk for mortality after a major cardiovascular event among childhood cancer survivors compared with noncancer populations. METHODS: All-cause and cardiovascular cause-specific mortality risks after heart failure (HF), coronary artery disease (CAD), or stroke were compared among survivors and siblings in the Childhood Cancer Survivor Study (CCSS) and participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Cox proportional hazard regression models were used to estimate HRs and 95% CIs between groups, adjusted for demographic and clinical factors. RESULTS: Among 25,658 childhood cancer survivors (median age at diagnosis 7 years, median age at follow-up or death 38 years) and 5,051 siblings, 1,780 survivors and 91 siblings had a cardiovascular event. After HF, CAD, and stroke, 10-year all-cause mortalities were 30% (95% CI: 26%-33%), 36% (95% CI: 31%-40%), and 29% (95% CI: 24%-33%), respectively, among survivors vs 14% (95% CI: 0%-25%), 14% (95% CI: 2%-25%), and 4% (95% CI: 0%-11%) among siblings. All-cause mortality risks among childhood cancer survivors were increased after HF (HR: 7.32; 95% CI: 2.56-20.89), CAD (HR: 5.54; 95% CI: 2.37-12.93), and stroke (HR: 3.57; 95% CI: 1.12-11.37). CAD-specific mortality risk was increased (HR: 3.70; 95% CI: 1.05-13.02). Among 5,114 CARDIA participants, 345 had a major event. Although CARDIA participants were on average decades older at events (median age 57 years vs 31 years), mortality risks were similar, except that all-cause mortality after CAD was significantly increased among childhood cancer survivors (HR: 1.85; 95% CI: 1.16-2.95). CONCLUSIONS: Survivors of childhood cancer represent a population at high risk for mortality after major cardiovascular events.

Examining hypertension risk among Black and White breast cancer survivors.

PURPOSE: Breast cancer survivors are at increased risk of cardiovascular dysfunction following their diagnosis; however, hypertension remains underexplored within this context. This retrospective cohort study examined the incidence of hypertension in breast cancer survivors and the association of race with hypertension risk among them. METHODS: Data for this study were abstracted from the electronic health records of women diagnosed with Stages I-III breast cancer. Incident hypertension diagnosis was identified through International Classification of Diseases codes. Bivariate associations were tested using Student's t-test and chi-squared test of independence. Bivariable Cox regression analysis was used to determine demographic and clinical factors that may have been associated with the development of hypertension. RESULTS: A total of 664 women were included. Most women were 50 years of age or younger (52.0%), White (33.0% Black), and received a mastectomy (80.6%). Overall, 45.5% of the cohort developed hypertension. The 1-year hypertension-free survival estimates were 47% (95% confidence interval [CI], 41-54) in Black women and 73% (95% CI, 69-77) in White women (p < 0.0001). Besides race, statistically significant predictors of hypertension included: age greater than 50 (vs. ≤50) (adjusted Hazard Ratio [HR]: 1.40; 95% CI, 1.09-1.80) and residing in a non-metropolitan area (vs. metropolitan) (adjusted HR: 1.60; 95% CI, 1.19-2.16). CONCLUSIONS: This study suggests that breast cancer survivors who are older, Black, or residing in non-metropolitan areas may benefit from added surveillance and hypertension prevention strategies during treatment. Future studies are needed to identify contributors to the observed racial and geographic disparities.

Cardiovascular impact of near complete estrogen deprivation in premenopausal women with breast cancer: The CROWN study.

Survival with operable breast cancer has improved markedly in recent decades, however, treatment-related cardiovascular toxicities threaten to offset these gains. Ovarian function suppression paired with aromatase inhibition, for premenopausal women with hormone receptor (HR)-positive breast cancer, is a newer widely adopted therapy with the potential for significant long-term cardiovascular toxicity. Abrupt estrogen deprivation for non-cancer reasons is associated with accelerated coronary artery disease. Women with breast cancer treated with aromatase inhibition in addition to ovarian function suppression experience a dual hit with regards to estrogen exposure. The CaRdiac Outcomes With Near-complete estrogen deprivation (CROWN) study seeks to understand the early, subclinical natural history of cardiovascular compromise in young women undergoing near-complete estrogen deprivation (NCED) therapy. It is critical to understand the early subclinical development of cardiovascular disease to identify a window for therapeutic intervention before overt cardiovascular events occur. This three-site regional study (Atrium Health Wake Forest, Duke, and Virginia Commonwealth University) uses serial stress cardiac magnetic resonance (CMR) imaging and cardiac computed tomography angiography (CCTA) obtained during the initial two years of NCED therapy to study myocardial prefusion reserve (MPR), large cardiovascular vessel changes, left ventricular function, and other cardiovascular parameters. The CROWN cohort will consist of 90 premenopausal women with breast cancer, 67 with HR-positive disease receiving NCED and 23 comparators with HR-negative disease. Participants will undergo three annual CMR scans and 2 CCTA scans during the 2-year study period. After initial activation hurdles, accrual has been brisk, and the study is expected to complete accrual in December 2024. Efforts are in place to encourage participant retention with the study primary outcome, change in MPR between the two groups, to be reported in 2026 to 2027. The results of this study will enable premenopausal women with breast cancer to balance the health burdens of cancer at a young age and treatment-related cardiovascular morbidity. Finally, the tools developed here can be utilized to study cardiovascular risk across a range of cancer types and cancer therapies with the ultimate goals of both developing generalizable risk stratification tools as well as validating interventions which prevent overt cardiovascular compromise.

Massive Mysteries.

Papillary fibroelastomas are benign masses often originating from the endocardium of the aortic and mitral valves. Rarely, these neoplasms are found in areas of the heart embryonically distinct from the aortic and mitral valves. Diagnosis of a papillary fibroelastoma relies on multimodal imaging as well as histologic assessment. A case series of papillary fibroelastomas in unusual locations is presented, highlighting the role of multimodal imaging techniques in identifying these intra-cardiac masses. Differential diagnoses, imaging characteristics, histopathology, and preferred management strategies for cardiac masses are reviewed. The unique imaging qualities of cardiac masses are discussed.

Cardiovascular Implications of Vascular Endothelial Growth Factor Inhibition Among Adolescents/Young Adults in ECOG-ACRIN E2805.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among adolescents and young adults (AYAs) diagnosed with cancer. The aim of this study was to assess the incidence and predictors of left ventricular systolic dysfunction (LVSD) and hypertension among AYAs receiving VEGF inhibition compared with non-AYAs. METHODS: This retrospective analysis used data from the ASSURE trial (ClinicalTrials.gov identifier: NCT00326898), in which participants with nonmetastatic, high-risk, renal cell cancer were randomized to sunitinib, sorafenib, or placebo. The incidence of LVSD (left ventricular ejection fraction decrease >15%) and hypertension (blood pressure ≥140/90 mm Hg) were compared using nonparametric tests. Multivariable logistic regression examined the association between AYA status, LVSD, and hypertension while adjusting for clinical factors. RESULTS: AYAs represented 7% (103/1,572) of the population. Over a study treatment period of 54 weeks, the incidence of LVSD was not significantly different among AYAs (3%; 95% CI, 0.6%-8.3%) versus non-AYAs (2%; 95% CI, 1.2%-2.7%). The incidence of hypertension was significantly lower among AYAs (18%; 95% CI, 7.5%-33.5%) compared with non-AYAs (46%; 95% CI, 41.9%-50.4%) in the placebo arm. In the sunitinib and sorafenib groups, the incidence of hypertension for AYAs compared with non-AYAs was 29% (95% CI, 15.1%-47.5%) versus 47% (95% CI, 42.3%-51.7%), and 54% (95% CI, 33.9%-72.5%) versus 63% (95% CI, 58.6%-67.7%), respectively. AYA status (odds ratio, 0.48; 95% CI, 0.31-0.75) and female sex (odds ratio, 0.74; 95% CI, 0.59-0.92) were each associated with a lower risk of hypertension. CONCLUSIONS: LVSD and hypertension were prevalent among AYAs. CVD among AYAs is only partially explained by cancer therapy. Understanding CVD risk among AYA cancer survivors is important for promoting cardiovascular health in this growing population.

Myocardial Strain during Surveillance Screening Is Associated with Future Cardiac Dysfunction among Survivors of Childhood, Adolescent and Young Adult-Onset Cancer.

Cardiovascular disease is a leading contributor to mortality among childhood, adolescent and young adult (C-AYA) cancer survivors. While serial cardiovascular screening is recommended in this population, optimal screening strategies, including the use of echocardiography-based myocardial strain, are not fully defined. Our objective was to determine the relationship between longitudinal and circumferential strain (LS, CS) and fractional shortening (FS) among survivors. This single-center cohort study retrospectively measured LS and CS among C-AYAs treated with anthracycline/anthracenedione chemotherapy. The trajectory of LS and CS values over time were examined among two groups of survivors: those who experienced a reduction of >5 fractional shortening (FS) units from pre-treatment to the most recent echocardiogram, and those who did not. Using mixed modeling, LS and CS were used to estimate FS longitudinally. A receiver operator characteristic curve was generated to determine the ability of our model to correctly predict an FS ≤ 27%. A total of 189 survivors with a median age of 14 years at diagnosis were included. Among the two survivor groups, the trajectory of LS and CS differed approximately five years from cancer diagnosis. A statistically significant inverse relationship was demonstrated between FS and LS -0.129, p = 0.039, as well as FS and CS -0.413, p < 0.001. The area under the curve for an FS ≤ 27% was 91%. Among C-AYAs, myocardial strain measurements may improve the identification of individuals with cardiotoxicity, thereby allowing earlier intervention.

A simulation-enhanced, spaced learning, interprofessional "code blue" curriculum improves ACLS algorithm adherence and trainee resuscitation skill confidence.

In-hospital cardiac arrest resuscitation training often happens in silos, with minimal interprofessional training. The aim of this study was to implement and evaluate a simulation-enhanced, interprofessional cardiac arrest curriculum in a university hospital. The curriculum ran monthly for 12 months, training interprofessional teams of internal medicine residents, nurses, respiratory therapists, and pharmacy residents. Teams participated in a 90-min high-fidelity simulation including "code blue" (30 min) followed by a 30-min debriefing and a repeat identical simulated "code blue" scenario. Teams were tested in an unannounced mock Code Blue the following month. Advanced Cardiac Life Support (ACLS) algorithm adherence was assessed using a standardized checklist. In-hospital cardiac arrest (IHCA) incidence and survival was tracked for 2 years prior, during, and 1 year after curriculum implementation. Team ACLS-algorithm adherence at baseline varied from 47% to 90% (mean of 71 ± 11%) and improved immediately following training (mean 88 ± 4%, range 80-93%, p = .011). This improvement persisted but decreased in magnitude over 1 month (mean 81 ± 7%, p = .013). Medical resident self-reported comfort levels with resuscitation skills varied widely at baseline, but improved for all skills post-curriculum. This simulation-enhanced, spaced practice, interprofessional curriculum resulted in a sustained improvement in team ACLS algorithm adherence.

Mitigating, monitoring, and managing long-term chemotherapy- and radiation-induced cardiac toxicity.

Five-year survival for childhood cancer now exceeds 85%. However, for many patients, treatment requires the use of intensive anthracycline-based chemotherapy and radiotherapy, both of which are associated with significant long-term cardiovascular toxicity. As such, late cardiovascular disease is now one of the leading causes of premature morbidity and mortality among childhood cancer survivors. Recent advances over the past decade have refined the cardiotoxic potential of various chemotherapeutics, and ongoing work seeks to determine the efficacy of various cardioprotective strategies in children receiving active cancer therapy. The development of risk prediction models offers an additional strategy to define risk for both newly treated and long-term survivors. Current screening strategies are primarily based on echocardiography, although there is active research investigating methods to further optimize screening through myocardial strain, cardiac magnetic resonance imaging, blood biomarkers, and genetics, along with the cost-effectiveness of different screening strategies. Active research is also underway investigating the efficacy of prevention strategies for childhood cancer survivors who have completed cancer therapy. This ranges from the use of medications to mitigate potential pathologic ventricular remodeling to reducing adverse and modifiable cardiovascular risk factors (eg, hypertension, dyslipidemia, insulin resistance, physical inactivity, tobacco exposure), many of which may be more common in cancer survivors vs the general population and are often underrecognized and undertreated in relatively young adult-aged survivors of childhood cancer.

Cardiac MRI assessment of anthracycline-induced cardiotoxicity.

The objective of this review article is to discuss how cardiovascular magnetic resonance (CMR) imaging measures left ventricular (LV) function, characterizes tissue, and identifies myocardial fibrosis in patients receiving anthracycline-based chemotherapy (Anth-bC). Specifically, CMR can measure LV ejection fraction (EF), volumes at end-diastole (LVEDV), and end-systole (LVESV), LV strain, and LV mass. Tissue characterization is accomplished through T1/T2-mapping, late gadolinium enhancement (LGE), and CMR perfusion imaging. Despite CMR's accuracy and efficiency in collecting data about the myocardium, there are challenges that persist while monitoring a cardio-oncology patient undergoing Anth-bC, such as the presence of other cardiovascular risk factors and utility controversies. Furthermore, CMR can be a useful adjunct during cardiopulmonary exercise testing to pinpoint cardiovascular mediated exercise limitations, as well as to assess myocardial microcirculatory damage in patients undergoing Anth-bC.

Hypertension in Cancer Survivors: A Review of the Literature and Suggested Approach to Diagnosis and Treatment.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among cancer survivors. Hypertension, which is common among cancer survivors with a prevalence of greater than 70% by age 50, potentiates the risk for CVD in a more than additive fashion. For example, childhood cancer survivors who develop hypertension may have up to a 12 times higher risk for heart failure than survivors who remain normotensive. Studies have shown that mild valvular disease (28% incidence), cardiomyopathy (7.4%), arrhythmias (4.6%), and coronary artery disease (3.8%) are among the most common CVDs in childhood cancer survivors. Among adolescent and young adult cancer survivors, the most common reasons for cardiovascular-related hospital admission are venous/lymphatic disease (absolute excess risk 19%), cardiomyopathy and arrhythmia (15%), hypertension (13%), and ischemic heart disease (12%). In addition, cancer therapies can increase the risk for hypertension and CVD. Therefore, early detection and treatment of hypertension is essential to reducing cardiovascular morbidity and mortality among survivors. METHODS: We present a literature review, which identified over 20 clinical trials, systemic reviews, and meta-analyses (13 clinical trials, 8 systemic reviews or meta-analyses) by searching PubMed, Google Scholar, and the Cochrane Library for relevant articles addressing hypertension in cancer survivors. RESULTS: Although our understanding of the complex relationship between cancer therapies and CVD has grown significantly over the past 2 decades, there remain several gaps in knowledge when specifically addressing CVD in the survivor population. This review provides an up-to-date survivor-centered approach to the screening and treatment of hypertension, which considers survivor-specific cardiovascular risk, applies guideline directed therapies when appropriate, screens for survivor-specific factors that may influence antihypertensive medication selection, and finally considers the prohypertensive mechanisms of antineoplastic agents as a potential target for antihypertensive medications. CONCLUSIONS: Screening for and treating hypertension among survivors can promote cardiovascular health in this vulnerable population.

Transient left ventricular dysfunction following chimeric antigen receptor T-cell-mediated encephalopathy: A form of stress cardiomyopathy.

Chimeric antigen receptor (CAR) T-cell therapy represents a new strategy in treating lymphoid malignancies, such as relapsed-refractory diffuse large B-cell lymphoma (DLBCL). Several toxicities including cytokine release syndrome (CRS), neurotoxicity, and cardiovascular toxicity have been linked to CAR T-cell therapy. Transient impairment in left ventricular systolic function is described after CAR-T, however, the mechanism remains poorly understood. This paper reports the clinical presentation and outcome of two patients with relapsed-refractory DLBCL who experienced encephalopathy and CRS following CAR T-cell therapy and developed transient left ventricular dysfunction consistent with stress cardiomyopathy.

Emerging cancer therapies and cardiovascular risk.

The cardiovascular (CV) toxicity profiles of traditional cancer therapies such as anthracyclines and radiation therapy are familiar to many cardiologists. With the development and widespread use of additional cancer therapeutics, CV toxicities related to these agents are becoming more common. Cardiovascular specialists are often integrated into the care team for individuals with cancer and knowledge of the CV toxicities of cancer therapeutics has become essential. In this review, we provide a clinically focused summary of the current data regarding CV toxicities of common cancer therapies and identify potential management strategies for the CV specialist.

The Role of Cardiovascular MRI in Cardio-Oncology.

"Cardiac imaging is an essential tool in the field of cardio-oncology. Cardiovascular magnetic resonance (CMR) stands out for its accuracy, reproducibility, and ability to provide tissue characterization. These attributes are particularly helpful in screening and diagnosing cardiotoxicity, infiltrative disease, and inflammatory cardiac disease. The ability of CMR to detect subtle changes in cardiac function and tissue composition has made it a useful tool for understanding the pathophysiology of cardiotoxicity. Because of these unique features, CMR is gaining prominence in both the clinical and research aspects of cardio-oncology."