Effect of variable left ventricular ejection fraction assessed by equilibrium radionuclide angiocardiography using different software packages on the diagnosis of cardiotoxicity in patients with cancer.

BACKGROUND: The equilibrium radionuclide angiocardiography (ERNA) scan is an established imaging modality for assessing left ventricular ejection fraction (LVEF) in oncology patients. This study aimed to explore the interchangeability of two commercially available software packages (MIM and JS) for LVEF measurement for a cancer-therapy-related cardiac dysfunction (CTRCD) diagnosis. METHODS: This is a single-center retrospective study among 322 patients who underwent ERNA scans. A total of 582 scans were re-processed using MIM and JS for cross-sectional and longitudinal LVEF measurements. RESULTS: The median LVEF for MIM and JS were 56% and 66%, respectively (P < 0.001). LVEF processed by JS was 9.91% higher than by MIM. In 87 patients with longitudinal ERNA scans, serial studies processed by MIM were classified as having CTRCD in a higher proportion than serial studies processed by JS (26.4% vs 11.4%, P = 0.020). There were no significant differences in intra- or inter-observer LVEF measurement variability (R = 0.99, P < 0.001). CONCLUSIONS: Software packages for processing ERNA studies are not interchangeable; thus, reports of ERNA studies should include details on the post-processing software. Serial ERNA studies should be processed on the same software when feasible to avoid discrepancies in the diagnosis and management of CTRCD.

Equity in Cardio-Oncology Care and Research: A Scientific Statement From the American Heart Association.

Advances in cancer therapeutics have revolutionized survival outcomes in patients with cancer. However, cardiovascular toxicities associated with specific cancer therapeutics adversely affect the outcomes of patients with cancer. Recent studies have uncovered excess risks of these cardiotoxic events, especially in traditionally underrepresented populations. Despite advances in strategies to limit the risks of cardiovascular events among cancer survivors, relatively limited guidance is available to address the rapidly growing problem of disparate cardiotoxic risks among women and underrepresented patient populations. Previously decentralized and sporadic evaluations have led to a lack of consensus on the definitions, investigation, and potential optimal strategies to address disparate cardiotoxicity in contemporary cancer care (eg, with immunotherapy, biologic, or cytotoxic therapies) settings. This scientific statement aims to define the current state of evidence for disparate cardiotoxicity while proposing uniform and novel methodological approaches to inform the identification and mitigation of disparate cardio-oncology outcomes in future clinical trials, registries, and daily clinical care settings. We also propose an evidence-based integrated approach to identify and mitigate disparities in the routine clinical setting. This consensus scientific statement summarizes and clarifies available evidence while providing guidance on addressing inequities in the era of emerging anticancer therapies.

Inequity in care delivery in cardio-oncology: dissecting disparities in underrepresented populations.

It is well known that patients with cancer have a significantly higher cardiovascular mortality risk than the general population. Cardio-oncology has emerged to focus on these issues including risk reduction, detection, monitoring, and treatment of cardiovascular disease or complications in patients with cancer. The rapid advances in early detection and drug development in oncology, along with socioeconomic differences, racial inequities, lack of support, and barriers to accessing quality medical care, have created disparities in various marginalized populations. In this review, we will discuss the factors contributing to disparities in cardio-oncologic care in distinct populations, including Hispanic/Latinx, Black, Asian and Pacific Islander, indigenous populations, sex and gender minorities, and immigrants. Some factors that contribute to differences in outcomes in cardio-oncology include the prevalence of cancer screening rates, genetic cardiac/oncologic risk factors, cultural stressors, tobacco exposure rates, and physical inactivity. We will also discuss the barriers to cardio-oncologic care in these communities from the racial and socioeconomic context. Appropriate and timely cardiovascular and cancer care in minority groups is a critical component in addressing these disparities, and there need to be urgent efforts to address this widening gap.

Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV.

OBJECTIVE: Women with HIV (WWH) have heightened heart failure risk. Plasma OPN (osteopontin) is a powerful predictor of heart failure outcomes in the general population. Limited data exist on relationships between plasma OPN and surrogates of HIV-associated heart failure risk. DESIGN: Prospective, cross-sectional. METHODS: We analyzed relationships between plasma OPN and cardiac structure/function (assessed using cardiovascular magnetic resonance imaging) and immune activation (biomarkers and flow cytometry) among 20 WWH and 14 women without HIV (WWOH). RESULTS: Plasma OPN did not differ between groups. Among WWH, plasma OPN related directly to the markers of cardiac fibrosis, growth differentiation factor-15 (ρ = 0.51, P = 0.02) and soluble interleukin 1 receptor-like 1 (ρ = 0.45, P = 0.0459). Among WWH (but not among WWOH or the whole group), plasma OPN related directly to both myocardial fibrosis (ρ = 0.49, P = 0.03) and myocardial steatosis (ρ = 0.46, P = 0.0487). Among the whole group and WWH (and not among WWOH), plasma OPN related directly to the surface expression of C-X3-C motif chemokine receptor 1 (CX3CR1) on nonclassical (CD14-CD16+) monocytes (whole group: ρ = 0.36, P = 0.04; WWH: ρ = 0.46, P = 0.04). Further, among WWH and WWOH (and not among the whole group), plasma OPN related directly to the surface expression of CC motif chemokine receptor 2 (CCR2) on inflammatory (CD14+CD16+) monocytes (WWH: ρ = 0.54, P = 0.01; WWOH: ρ = 0.60, P = 0.03), and in WWH, this held even after controlling for HIV-specific parameters. CONCLUSION: Among WWH, plasma OPN, a powerful predictor of heart failure outcomes, related to myocardial fibrosis and steatosis and the expression of CCR2 and CX3CR1 on select monocyte subpopulations. OPN may play a role in heart failure pathogenesis among WWH. CLINICALTRIALSGOV REGISTRATION: NCT02874703.

Cardiac strain is lower among women with HIV in relation to monocyte activation.

BACKGROUND: Women with HIV (WWH) face heightened risks of heart failure; however, insights on immune/inflammatory pathways potentially contributing to left ventricular (LV) systolic dysfunction among WWH remain limited. SETTING: Massachusetts General Hospital, Boston, Massachusetts. METHODS: Global longitudinal strain (GLS) is a sensitive measure of LV systolic function, with lower cardiac strain predicting incident heart failure and adverse heart failure outcomes. We analyzed relationships between GLS (cardiovascular magnetic resonance imaging) and monocyte activation (flow cytometry) among 20 WWH and 14 women without HIV. RESULTS: WWH had lower GLS compared to women without HIV (WWH vs. women without HIV: 19.4±3.0 vs. 23.1±1.9%, P<0.0001). Among the whole group, HIV status was an independent predictor of lower GLS. Among WWH (but not among women without HIV), lower GLS related to a higher density of expression of HLA-DR on the surface of CD14+CD16+ monocytes (ρ = -0.45, P = 0.0475). Further, among WWH, inflammatory monocyte activation predicted lower GLS, even after controlling for CD4+ T-cell count and HIV viral load. CONCLUSIONS: Additional studies among WWH are needed to examine the role of inflammatory monocyte activation in the pathogenesis of lower GLS and to determine whether targeting this immune pathway may mitigate risks of heart failure and/or adverse heart failure outcomes. TRIAL REGISTRATION: Clinical trials.gov registration: NCT02874703.

Increasing statin prescription rates to prevent cardiovascular disease among high-risk populations: a quality improvement intervention centred on a novel interactive tool.

Statins are indicated for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Our previous study of 1042 consecutive patient encounters at our large urban academic institution found that one in five patients were not prescribed an appropriate statin therapy. Only one-third of patients had follow-up cholesterol levels ordered to monitor treatment efficacy. In order to improve adherence to cholesterol guidelines at our institution, a quality improvement project was undertaken. We implemented interventions over a 4-month period to improve statin prescription rates: (a) development of an online interactive tool, (b) physician education on updated cholesterol guidelines and utilisation of the tool, (c) display of guideline summary in the workspace and (d) a documentation reminder in the electronic health record. We randomly selected encounter dates, from which 622 consecutive patient encounters were analysed. The primary outcome measures were prescription rates of statins, documentation of a 10-year ASCVD risk score and follow-up cholesterol levels ordered to monitor treatment efficacy. Out of the 622 patient encounters, 232 met statin indication. In this post-intervention group, statin prescription rates improved when compared with the pre-intervention group (90.5% vs 82.3%, p=0.006). Among patients who met statin indication solely via a 10-year ASCVD risk score ≥7.5%, there was an increase in documentation of the calculated 10-year ASCVD risk score (72.3% vs 57.8%; p=0.039) and in statin prescription rate (90.8% vs 67.6%; p<0.001). In addition, there was an increase in follow-up cholesterol levels ordered in all patients included in our study who met statin indication (64.1% vs 33.3%; p<0.001). Our quality improvement project showed higher rates of statin prescription, 10-year ASCVD risk score documentation and treatment monitoring after multiple interventions, centred on an easily accessible online interactive tool.

Sodium-Glucose Co-Transporter-2 Inhibitors and Cardiac Outcomes Among Patients Treated With Anthracyclines.

BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors improve outcomes among patients with established heart failure. Despite supportive basic science studies, there are no data on the value of SGLT2 inhibitors among patients treated with anthracyclines. OBJECTIVES: This study sought to test the cardiac efficacy and overall safety of SGLT2 inhibitors in patients treated with anthracyclines. METHODS: This study identified 3,033 patients with diabetes mellitus (DM) and cancer who were treated with anthracyclines. Cases were patients with cancer and DM who were on SGLT2 inhibitor therapy during anthracycline treatment (n = 32). Control participants (n = 96) were patients with cancer and DM who were also treated with anthracyclines, but were not on an SGLT2 inhibitor. The primary cardiac outcome was a composite of cardiac events (heart failure incidence, heart failure admissions, new cardiomyopathy [>10% decline in ejection fraction to <53%], and clinically significant arrhythmias). The primary safety outcome was overall mortality. RESULTS: Age, sex, ethnicity, cancer type, cancer stage, and other cardiac risk factors were similar between groups. There were 20 cardiac events over a median follow-up period of 1.5 years. The cardiac event incidence was lower among case patients in comparison to control participants (3% vs 20%; P = 0.025). Case patients also experienced lower overall mortality when compared with control participants (9% vs 43%; P < 0.001) and a lower composite of sepsis and neutropenic fever (16% vs 40%; P = 0.013). CONCLUSIONS: SGLT2 inhibitors were associated with lower rate of cardiac events among patients with cancer and DM who were treated with anthracyclines. Additionally, SGLT2 inhibitors appeared to be safe. These data support the conducting of a randomized clinical trial testing SGLT2 inhibitors in patients at high cardiac risk treated with anthracyclines.

Cardiac AL amyloidosis presenting as recurrent dyspnoea in a patient with cancer: an important clinical clue to an early diagnosis.

Cardiac amyloidosis (CA) is challenging to diagnose due to its non-specific clinical manifestations early in the disease process. We report the case of a patient who presented with dyspnoea, abdominal distension and leg swelling. Medical history was notable for hypertension, recurrent vulvar squamous cell carcinoma and polysubstance abuse. Over 1 year before the official diagnosis of CA, the patient had multiple hospital readmissions for dyspnoea. Our case illustrates the importance of having a high index of clinical suspicion for an early diagnosis of CA. Furthermore, it highlights the need to re-evaluate a presumed diagnosis when a patient's symptoms recur or do not respond to appropriate treatment and to consider the influence of social factors on diagnostic processes.

Atherosclerosis With Immune Checkpoint Inhibitor Therapy: Evidence, Diagnosis, and Management: JACC: CardioOncology State-of-the-Art Review.

As the clinical applications of immune checkpoint inhibitors (ICIs) expand, our knowledge of the potential adverse effects of these drugs continues to broaden. Emerging evidence supports the association between ICI therapy with accelerated atherosclerosis and atherosclerotic cardiovascular (CV) events. We discuss the biological plausibility and the clinical evidence supporting an effect of inhibition of these immune checkpoints on atherosclerotic CV disease. Further, we provide a perspective on potential diagnostic and pharmacological strategies to reduce atherosclerotic risk in ICI-treated patients. Our understanding of the pathophysiology of ICI-related atherosclerosis is in its early stages. Further research is needed to identify the mechanisms linking ICI therapy to atherosclerosis, leverage the insight that ICI therapy provides into CV biology, and develop robust approaches to manage the expanding cohort of patients who may be at risk for atherosclerotic CV disease.

An Analysis of Global Research Trends and Top-Cited Research Articles in Cardio-Oncology.

BACKGROUND: As novel cancer therapies continue to improve patient outcomes, there is an increased need for prevention and management of the cardiovascular side effects of these therapies. For this reason, the field of cardio-oncology has experienced significant scientific growth, particularly during the last decade. This study aims to assess the global publication trends and highlight the top-cited scientific articles related to cardio-oncology. METHODS: A comprehensive bibliometric analysis of multiple scientific databases was performed to characterize global publication trends in cardio-oncology from 1864 to 2020 and to determine the top-cited papers addressing cardio-oncology as a field of study. RESULTS: We identified 1,294 publications with 14,494 citations that describe cardio-oncology as a field. Cardio-oncology was the most prevalent term in the literature and was first mentioned in an article from Italy in 1996. There was no further mention of the term "cardio-oncology" until 2003, and later again in 2008. After 2010, there was a consistent increase in the number of publications and citations in cardio-oncology. Among the top 50 most cited papers, there was a noticeable trend of higher number of review articles (n = 28, 56%, with 3,208 citations), followed by guidelines and position papers (n = 9, 18%, with 2,299 citations) and original research articles (n = 9, 18%, with 1,451 citations). The most common specialty for the senior corresponding authors of the top 50 most cited papers was cardiology (n = 36; 72%), followed by oncology (n = 5; 10%); and the most prevalent countries of origin were the USA (n = 26; 52%), Italy (n = 8; 16%), and Canada (n = 6; 12%). CONCLUSION: Our quantitative analysis of publication trends in the field of cardio-oncology objectively showed the growing scientific interest in the field. To our knowledge, this is the first bibliometric analysis that determined the top 50 most cited articles in the field of cardio-oncology.

Phantom Shocks Associated With a Wearable Cardioverter Defibrillator.

Wearable cardioverter defibrillators (WCDs) are external devices capable of continuous cardiac rhythm monitoring as well as automatic detection and defibrillation of potentially life-threatening arrhythmias such as ventricular tachycardia (VT) and ventricular fibrillation (VF). They are an alternative approach for patients when an implantable cardioverter defibrillator (ICD) is not appropriate. Although treatment with ICD is considered highly effective for the primary and secondary prevention of sudden cardiac death (SCD) in high-risk patients susceptible to VT and VF, patients may still experience psychological difficulties such as fear of shock, avoidance of normal behaviors and reduced quality of life. One of these phenomena is phantom shock (PS), which is defined as a perception of having received a shock with no evidence of recorded defibrillation upon device interrogation. While PS has been reported in the ICD literature, to the best of our knowledge, we present the first known case of WCD-related PS. We also present a review of the current literature to explore the prevalence of PS, the factors associated with its pathogenesis and interventional studies aimed at reducing its occurrence. We highlight this case because PS is considered a phenomenon that few recognize, which should be discriminated from real device shocks before clinicians initiate treatment, device reprogramming or device discontinuation. We describe the psychosocial factors associated with PS to emphasize the importance of managing any associated psychiatric disorders and psychosocial factors both before and after initiation of device treatment.

Nilotinib-Associated Atherosclerosis Presenting as Multifocal Intracranial Stenosis and Acute Stroke.

Nilotinib, a BCR-ABL tyrosine kinase inhibitor (TKI), has been associated with vascular events and accelerated arterial stenosis, presumably of atherosclerotic etiology. Studies of nilotinib-associated atherosclerosis are mainly associated with progressive peripheral artery occlusive disease (PAOD), and only a few cases of coronary artery disease (CAD), and cerebrovascular disease (CVD) have been reported. The mechanisms by which nilotinib promotes atherosclerosis are poorly understood but endothelial and perivascular factors, mast cell depletion, and metabolic factors such as promotion of dyslipidemia and impaired glucose metabolism are thought to play a role. We present a case of a patient with chronic myelogenous leukemia (CML) treated with nilotinib who developed intracranial atherosclerosis leading to acute onset of stroke. Our patient had no cardiovascular risk factors prior to treatment with nilotinib and developed accelerated atheromatous cerebrovascular disease with severe left middle cerebral artery (MCA) stenosis. These findings suggest that nilotinib may be associated with the development of intracranial atherosclerotic disease (ICAD) independently of any preexisting vascular risk factors leading to acute stroke. Clinicians should have increased awareness of the association between nilotinib and the development of progressive atheromatous disease and vascular adverse events including PAOD, CAD, and CVD. In certain patients, these events can be severe and life threatening. Thus, screening for vascular risk factors including CVD prior to starting nilotinib and close follow up during treatment is crucial.

Orbit and sinonasal metastasis as presenting sign of renal cell carcinoma.

Orbit and sinonasal metastases are rare. Renal cell carcinoma (RCC) can metastasise to this region. We present the case of a 49-year-old woman with weight loss, diplopia and a rapidly growing facial mass. The initial diagnosis was a primary tumour and patient underwent excisional biopsy, which showed findings consistent with a diagnosis of RCC. On a subsequent focused review of system, the patient reported having intermittent haematuria. Imaging studies revealed a complex right renal mass as the primary tumour. Metastatic RCC should be in the differential diagnosis of patients with facial masses, especially if associated with symptoms suggestive of a systemic involvement such as haematuria. Despite treatment, patients with metastatic RCC tend to have a dismal prognosis. However, early stage diagnosis of metastatic disease can considerably limit surgical complications and improve survival rate in these patients.

Would you use novel oral anticoagulants (NOACs) for thromboprophylaxis in patients with an underlying hypercoagulable state? A literature review through a case report.

Antiphospholipid syndrome (APLS) is an autoimmune condition that predisposes to venous and arterial thrombosis. Warfarin is the agent of choice for anticoagulation. However, a need for routine international normalised ratio (INR) checks and multiple drug interactions are some of the difficulties with warfarin. Currently, there is mixed evidence for and against the use of novel oral anticoagulants (NOACs) for thromboprophylaxis. We present a case report of a patient with APLS on a NOAC for secondary thromboprophylaxis who developed a stroke and discuss current evidence regarding the use of NOACs in patients with APLS. The patient was switched to warfarin for secondary thromboprophylaxis with an INR goal of 2-3. Literature review revealed mixed case reports for and against NOACs for secondary prevention of thrombotic events in patients with APLS. There needs to be further randomised controlled trials to evaluate the efficacy of NOACs for thromboprophylaxis in patients with APLS.

Factors Associated with Disparities in Appropriate Statin Therapy in an Outpatient Inner City Population.

Lipid-lowering therapies are essential for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to identify discrepancies between cholesterol management guidelines and current practice with a focus on statin treatment in an underserved population based in a large single urban medical center. Among 1042 reviewed records, we identified 464 statin-eligible patients. Age was 61.0 ± 10.4 years and 53.9% were female. Most patients were black (47.2%), followed by Hispanic (45.7%) and white (5.0%). In total, 82.1% of patients were prescribed a statin. An appropriate statin was not prescribed in 32.4% of statin-eligible patients who qualified based only on a 10-year ASCVD risk of ≥7.5%. After adjustment for gender and health insurance status, appropriate statin treatment was independently associated with age >55 years (OR = 4.59 (95% CI 1.09-16.66), p = 0.026), hypertension (OR = 2.38 (95% CI 1.29-4.38), p = 0.005) and chronic kidney disease (OR = 3.95 (95% CI 1.42-14.30), p = 0.017). Factors independently associated with statin undertreatment were black race (OR = 0.42 (95% CI 0.23-0.77), p = 0.005) and statin-eligibility based solely on an elevated 10-year ASCVD risk (OR = 0.14 (95% CI 0.07-0.25), p < 0.001). Hispanic patients were more likely to be on appropriate statin therapy when compared to black patients (86.8% vs. 77.2%). Statin underprescription is seen in approximately one out of five eligible patients and is independently associated with black race, younger age, fewer comorbidities and eligibility via 10-year ASCVD risk only. Hispanic patients are more likely to be on appropriate statin therapy compared to black patients.

Multiple recurrent ischaemic strokes in a patient with cancer: is there a role for the initiation of anticoagulation therapy for secondary stroke prevention?

A 52-year-old woman with a medical history of cervical and thyroid cancer, hypertension, dyslipidaemia, uncontrolled diabetes and heavy smoking was diagnosed with a new metastatic cholangiocarcinoma. While undergoing palliative chemotherapy, she developed dysarthria and left-sided weakness. Imaging studies showed multiple bilateral ischaemic strokes. On hospital days 2 and 5, she developed worsening neurological symptoms and imaging studies revealed new areas of ischaemia on respective days. Subsequent workup did not revealed a clear aetiology for the multiple ischaemic events and hypercoagulability studies were only significant for a mildly elevated serum D-dimer level. Although guidelines are unclear, full-dose anticoagulation with low molecular weight heparin was initiated given her high risk of stroke recurrence. She was discharged to acute rehabilitation but, within a month, she experienced complications of her malignant disease progression and a new pulmonary thromboembolism. The patient died soon after being discharged home with hospice care.