Statin use is associated with a lower risk of all-cause death in patients with breast cancer treated with anthracycline containing regimens: a global federated health database analysis.

Anthracyclines are associated with enhanced oxidative stress responsible for adverse events in patients with breast cancer. However, no study has investigated the potential anti-inflammatory role of statins in counteracting anthracycline toxicity. In this retrospective study utilizing a federated health network (TriNetX), patients with breast cancer (ICD code C50) treated with anthracyclines were categorized into two groups: statin users (for at least 6 months); and statin non-users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the risk of myocardial infarction, stroke, atrial fibrillation, ventricular arrhythmias, heart failure, and pulmonary embolism. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). We identified 3,701 statin users (68.8 ± 10.4 years) and 37,185 statin non-users (59.6 ± 12.8 years). After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.82, 95% CI 0.74-0.91) compared to statins non-users. Analyzing the risk for secondary outcomes, only the risk of stroke was significantly increased in statin users (HR 1.27, 95% CI 1.01-1.61), while no associations were found for the other cardiovascular events. The risk of all-cause death in statin users was the lowest during the first year after the anthracycline's initiation. No significant difference was found between lipophilic and hydrophilic statins. In patients with breast cancer treated with anthracyclines, statin use is associated with a reduced risk of all-cause death. Prospective studies are needed to investigate the potential beneficial effect of statin initiation in cancer patients without other indications.

Joint British Societies' position statement on bullying, harassment and discrimination in cardiology.

Inappropriate behaviour is an umbrella term including discrimination, harassment and bullying. This includes both actions and language and can affect any member of the cardiovascular workforce/team. Evidence has suggested that such behaviour is regularly experienced within UK cardiology departments, where inappropriate behaviour may represent longstanding cultural and practice issues within the unit. Inappropriate behaviour has negative effects on the workforce community as a whole, including impacts on recruitment and retention of staff and patient care. While only some members of the cardiology team may be directly impacted by inappropriate behaviour in individual departments, a wider group are significantly impacted as bystanders. As such, improving the culture and professional behaviours within UK cardiology departments is of paramount importance. As a negative workplace culture is felt to be a major driver of inappropriate behaviour, all members of the cardiovascular team have a role to play in ensuring a positive workplace culture is developed. Episodes of inappropriate behaviour should be challenged by cardiovascular team members. Informal feedback may be appropriate where 'one-off' episodes of inappropriate behaviour occur, but serious events or repeated behaviour should be escalated following formal human resources protocols.

Acute and Chronic Cardiopulmonary Effects of High Dose Interleukin-2 Therapy: An Observational Magnetic Resonance Imaging Study.

High dose interleukin-2 (IL-2) is known to be associated with cardiopulmonary toxicity. The goal of this study was to evaluate the effects of high dose IL-2 therapy on cardiopulmonary structure and function. Combined cardiopulmonary magnetic resonance imaging (MRI) was performed in 7 patients in the acute period following IL-2 therapy and repeated in 4 patients in the chronic period. Comparison was made to 10 healthy volunteers. IL-2 therapy was associated with myocardial and pulmonary capillary leak, tissue oedema and cardiomyocyte injury, which resulted in acute significant left ventricular (LV) dilatation, a reduction in LV ejection fraction (EF), an increase in LV mass and a prolongation of QT interval. The acute effects occurred irrespective of symptoms. In the chronic period many of the effects resolved, but LV hypertrophy ensued, driven by focal replacement and diffuse interstitial myocardial fibrosis and increased cardiomyocyte mass. In conclusion, IL-2 therapy is ubiquitously associated with acute cardiopulmonary inflammation, irrespective of symptoms, which leads to acute LV dilatation and dysfunction, increased LV mass and QT interval prolongation. Most of these effects are reversible but IL-2 therapy is associated with chronic LV hypertrophy, driven by interstitial myocardial fibrosis and increased cardiomyocyte mass. The findings have important implications for the monitoring and long term impact of newer immunotherapies. Future studies are needed to improve risk stratification and develop cardiopulmonary-protective strategies.

Chemotherapy-Induced Arrhythmias.

ABSTRACT: Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.

Trabectedin Cardiotoxicity in Soft Tissue Sarcoma: A Case Series and Clinical Insights.

Trabectedin is a chemotherapeutic used to treat advanced soft tissue sarcoma and relapsed platinum-sensitive ovarian cancer. Although it is associated with a low incidence of cardiotoxicity, when this occurs it can be fatal or significantly compromise the quality of life in patients with advanced cancer. Here, we present a series of 4 cases where trabectedin-treated sarcoma patients developed cardiovascular complications. Similar to previous literature describing this association, all patients had prior treatment with anthracyclines and presented at different time points following treatment initiation. Each patient presented with exertional breathlessness and was found to have severely impaired left ventricular systolic function (ejection fraction ≤35%), and 1 patient had concurrent atrial fibrillation with a fast ventricular rate. All of the patients were treated with neurohormonal blockade, and a multi-disciplinary decision was made to stop trabectedin in 3 patients and continue in 1 patient. Two of the 4 patients had an improvement in their left ventricular systolic function. It is unclear what effect preceeding anthracycline or tyrosine kinase inhibitor treatment has in priming patients to develop cardiotoxicity in this setting. Our case series adds to the evidence surrounding this association and highlights that trabectedin-associated cardiotoxicity can present in an insidious fashion.

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.

Chemotherapy-Induced Arrhythmia - Underrecognized and Undertreated.

Cancer is one of the leading causes of death worldwide. Chemotherapy-induced arrhythmia is a potential complication of treatment that confers increased morbidity and mortality. The relationship between chemotherapeutic agents and arrhythmias is poorly established. Atrial fibrillation, ventricular ectopic beats, and prolonged QTc are the most common arrhythmias suffered by cancer patients undergoing chemotherapy. The treatment of atrial fibrillation in cancer is complicated by complex drug-drug interactions and a lack of evidence guiding practice. Furthermore, the normal risk assessment scores utilized in the decision-making for anticoagulation in the normal population are not validated in the cancer population. Multiple agents are implicated in prolonging the QTc, and this can often have adverse consequences for both the patient and the treatment of their cancer. This can manifest as torsades de pointes and sudden cardiac death. It is advised that, during treatment, oncologists should have close liaison with cardio-oncologists to ensure optimum patient management.

British Society for Echocardiography and British Cardio-Oncology Society 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 (EGF) 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.

Cardio-oncology for the general physician: 'old' and 'new' cardiovascular toxicities and how to manage them.

Cardio-oncology is the care of cancer patients with cardiovascular disease. The need for a dedicated subspecialty emerged to address heart failure caused by drugs such as anthracyclines and anti-human epidermal growth factor receptor 2 (HER2) therapies, but over time has expanded into an exciting subspecialty with widening horizons. While still dealing with a lot of commonly recognised toxicities, such as heart failure, hypertension and coronary disease, new and revolutionary cancer therapies have been associated with challenging cardiovascular complications, requiring specialist input to manage effectively. Echocardiography is a key investigation, with advanced techniques such as three-dimensional and strain assessment allowing more accurate diagnosis and earlier detection of subtle changes. Cardiac magnetic resonance and biomarkers are useful adjuncts to aid diagnosis and management. With increasing cancer incidence and improved cancer survival rates, it is important that general cardiologists and physicians are aware of cardiac complications associated with cancer and how to manage them.

Hypertension management in cardio-oncology.

Cancer is one of the leading causes of death worldwide. During the last few decades prognosis has improved dramatically and patients are living longer and suffering long-term cardiovascular consequences of chemotherapeutic agents. Cardiovascular disease is a leading cause of morbidity and mortality in cancer survivors second only to recurrent cancer. In some types of cancer, cardiovascular disease is a more common cause of death than the cancer itself. This has led to a new sub-specialty of cardiology coined cardio-oncology to manage this specific population. Hypertension is one of the most common cardiovascular disease seen in this cohort. The aetiology of hypertension in cardio-oncology is complex and multifactorial based on the type of chemotherapy, type of malignancy and intrinsic patient factors such as age and pre-existing comorbidities. A variety of different oncological treatments have been implicated in causing hypertension. The effect can be transient whilst undergoing treatment or can be delayed occurring decades after treatment. A tailored management plan is recommended given the plethora of agents and their differing underlying mechanisms and speed of this mechanism in causing hypertension. Management by a multidisciplinary team consisting of oncology, general practice and cardiology is advised. There are currently no trials comparing antihypertensives in this specific cohort of patients. In the absence of evidence demonstrating otherwise, hypertension in cardio-oncology should be managed utilising the same treatment guidelines for the general population.

Sex Differences in Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve: Lessons From ADVANCE.

OBJECTIVES: This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFRCT) according to sex. BACKGROUND: Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFRCT improves sex-based patient management decisions compared to CCTA alone is unknown. METHODS: Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFRCT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFRCT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates. RESULTS: A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFRCT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFRCT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFRCT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFRCT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFRCT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm3/g vs. 24.76 ± 7.22 mm3/g; p < 0.0001) that is associated with higher FFRCT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFRCT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284). CONCLUSIONS: FFRCT differs between the sexes, as women have a higher FFRCT for the same degree of stenosis. In FFRCT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFRCT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679).