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Background: Autonomic dysfunction (AD) as measured by heart rate variability (HRV) is associated with increased risk of cardiovascular disease (CVD) and breast cancer. No study has utilized a large prospective multi-center cohort of diverse women to assess differences in HRV associated with incident breast cancer. Objectives: To identify heart rate variability changes in women with breast cancer compared to controls in the Women’s Health Initiative (WHI). Methods: In a retrospective cohort study, we utilized 5,031 women in the WHI CT cohort who were breast cancer free at baseline and compared 1) those with incident breast cancer v. 2) those who were breast cancer free during the ECG follow-up period as controls. HRV was calculated utilizing 10-second ECG with two measures of two-domain HRV: standard deviation of all normal-to-normal RR intervals (SDNN) and the root mean square of successive differences in normal-to-normal RR intervals (rMSSD). HRV was measured from ECGs collected at baseline, years 3, 6, and 9 in the comparison groups. An adjusted mixed linear model was used to evaluate the differences in SDNN and rMSSD comparing women with incident breast cancer to controls. Cardiovascular risk factors utilized in the adjusted model were determined via questionnaire at baseline. Results: At baseline, women with incident breast cancer diagnosed by years 3, 6, or 9 were significantly older (median age 63 vs. 61, PFigure 1 ). Conclusions: HRV as a measure of AD is significantly lower in women with incident breast cancer compared to women without breast cancer. Reduction in HRV is associated with CVD outcomes in the literature. Our study suggests HRV may predict CVD in breast cancer patients.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Objective\ud To assess the temporal trends, patient characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery.\ud \ud Patients and Methods\ud We analysed delivery hospitalisations with or without current or historical cancer between January 1, 2004 and December 31, 2014 from the United States National Inpatient Sample database. \ud \ud Results\ud We included 43,132,097 delivery hospitalisations with no cancer, 39,118 with current cancer and 67,336 with historical diagnosis of cancer. The five most common types of current cancer were haematological, thyroid, cervical, skin and breast cancer. Women with current and historical cancer were older (29 and 32 vs. 27 years) and incurred higher hospital costs ($4,131 and $4,078 vs. $3,521), compared to women without cancer. Most of the cancer types were associated with preterm birth (haematological: adjusted odds ratio (aOR) 1.48, 95% confidence interval (CI) 1.35-1.62; cervical: aOR 1.47, 95% CI 1.32-1.63; breast: aOR 1.93, 95% CI 1.72-2.16). Current haematological cancer was associated with the highest risk of peripartum cardiomyopathy (aOR 12.19, 95% CI 7.75-19.19), all-cause mortality (aOR 6.50, 95% CI 2.22-19.07), arrhythmia (aOR 3.82, 95% CI 2.04-7.15) and postpartum haemorrhage (aOR 1.31, 95% CI 1.11-1.54). Having current or historical cancer diagnosis did not confer additional risk for stillbirth; however metastases increased the risk of maternal mortality and preterm birth.\ud \ud Conclusion\ud Women with current or historical diagnosis of cancer at delivery have more comorbidities compared to women without cancer. Clinicians should communicate the risks of multi-system complications to this complex patient group.

PURPOSE: HER2-targeted therapies are associated with cardiotoxicity which is usually asymptomatic and reversible. We report the updated cardiac safety assessment of patients with compromised heart function receiving HER2-targeted therapy for breast cancer, enrolled in the SAFE-HEaRt trial, at a median follow-up of 3.5 years. METHODS: Thirty patients with stage I-IV HER2-positive breast cancer receiving trastuzumab with or without pertuzumab, or ado-trastuzumab emtansine (T-DM1), with asymptomatic LVEF (left ventricular ejection fraction) 40–49%, were started on cardioprotective medications, with the primary endpoint being completion of HER2-targeted therapy without cardiac events (CE) or protocol-defined asymptomatic worsening of LVEF. IRB-approved follow-up assessment included 23 patients. RESULTS: Median follow-up as of June 2020 is 42 months. The study met its primary endpoint with 27 patients (90%) completing their HER2-targeted therapies without cardiac issues. Of the 23 evaluable patients at long-term f/u, 14 had early stage breast cancer, and 9 had metastatic disease, 8 of whom remained on HER2-targeted therapies. One patient developed symptomatic heart failure with no change in LVEF. There were no cardiac deaths. The mean LVEF improved to 52.1% from 44.9% at study baseline, including patients who remained on HER2-targeted therapy, and those who received prior anthracyclines. CONCLUSIONS: Long-term follow-up of the SAFE-HEaRt study continues to provide safety data of HER2-targeted therapy use in patients with compromised heart function. The late development of cardiac dysfunction is uncommon and continued multi-disciplinary oncologic and cardiac care of patients is vital for improved patient outcomes.

Echocardiographic imaging is crucial for patient management during cardiotoxic cancer therapy. Left ventricular ejection fraction is the most commonly used parameter for identifying left ventricular dysfunction. However, it lacks sensitivity to detect subclinical changes in cardiac function due to cardiotoxic treatment. Global longitudinal strain (GLS) is the best studied strain parameter with established diagnostic and prognostic value. Multiple studies have demonstrated changes in GLS as an early marker of cardiotoxicity. This document serves as a primer to help clinicians in the acquisition and interpretation of strain in cardio-oncology. Cases with embedded videos illustrate a step-by-step approach to obtaining GLS measurements and common pitfalls to avoid. The document includes a concise summary of the indications of GLS in cardio-oncology and its role in guiding oncological therapy. Practical approaches on how to implement strain in the echo laboratory with guidance on training and quality assurance are also discussed., Central Illustration, Highlights • Compared with LVEF, GLS is a more sensitive and reproducible measure of LV systolic function and has emerged as an early marker of cardiotoxicity. • Despite evidence supporting the clinical utility of GLS imaging, familiarity with the practical process of strain imaging among clinicians is lacking. • Although each vendor has its own proprietary software for strain imaging, the basic steps of measuring GLS are similar. • Education is needed to enhance the performance, analysis, and interpretation of GLS for the management of cardio-oncology patients.

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Purpose: This study aimed to prospectively evaluate the early effects of radiation on cardiac structure and function following neoadjuvant chemoradiation for distal esophageal cancer. Methods and Materials: Patients with non-metastatic esophageal cancer who were suitable for tri-modality therapy with concurrent chemoradiotherapy followed by esophagectomy were enrolled. Cardiac magnetic resonance imaging (CMR) was obtained at baseline and 3–5 months following completion of chemoradiation. Standardized myocardial segmentation was used to identify regions on post-treatment CMR with new T2 signal or late gadolinium enhancement (LGE). Pre and post-treatment cardiac function was assessed with quantitative end points including left ventricle end-systolic volume (LSESV). Serum biomarkers of cardiac damage including troponin I, CRP, and BNP were collected at baseline and time of follow-up CMR. Results: A total of 11 patients were enrolled from 2016 to 2018. Patients had clinical stage T2 (18%) and T3 (82%) disease with clinical N0 (27%) and N1 (73%) nodal stage. All patients completed baseline CMR and completed chemoradiotherapy. One patient did not complete follow-up CMR or serum biomarkers and was excluded from the analysis. The median time from completion of chemoradiation to follow-up CMR was 3.9 months. Three out of 10 patients (30%) developed new structural findings of myocardial fibrosis and/or reversible ischemia involving the basal and mid-inferior and inferoseptal walls. In these three patients, the LVESV was significantly increased from baseline following radiation. There were no differences in other quantitative end points or serum biomarkers between the patients with myocardial damage and those without. Conclusions: Our study is the first to our knowledge to prospectively demonstrate radiation associated structural and functional heart damage as early as 3 months following neoadjuvant chemoradiation for distal esophageal cancer. Given the early onset of this subclinical heart damage, strategies should be developed to identify patients at risk for future clinically significant heart toxicity.

Aims Primary percutaneous coronary intervention (pPCI) is the gold standard, guideline-recommended revascularization strategy in patients presenting with ST-elevation myocardial infarction (STEMI). However, there are limited data on its use and effectiveness among patients with active cancer presenting with STEMI. Methods and results All STEMI hospitalizations between 2004 and 2015 from the National Inpatient Sample were retrospectively analysed, stratified by cancer type. Propensity score matching was performed to estimate the average treatment effect of pPCI in each cancer on in-hospital adverse events, including major adverse cardiovascular and cerebrovascular events (MACCE) and its individual components, and compare treatment effect between cancer and non-cancer patients. Out of 1 870 815 patients with STEMI, 38 932 (2.1%) had a current cancer diagnosis [haematological: 11 251 (28.9% of all cancers); breast: 4675 (12.0%); lung: 9538 (24.5%); colon: 3749 (9.6%); prostate: 9719 (25.0%)]. Patients with cancer received pPCI less commonly than those without cancer (from 54.2% for lung cancer to 70.6% for haematological vs. 82.3% in no cancer). Performance of pPCI was strongly associated with lower adjusted probabilities of MACCE and all-cause mortality in the cancer groups compared with the no cancer group. There was no significant difference in estimated average pPCI treatment effect between the cancer groups and non-cancer group. Conclusion Primary percutaneous coronary intervention is underutilized in STEMI patients with current cancer despite its significantly lower associated rates of in-hospital all-cause mortality and MACCE that is comparable to patients without cancer. Further work is required to assess the long-term benefit and safety of pPCI in this high-risk group.

Introduction: myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). While corticosteroids are the cornerstones of the treatment, there are no data to guide the dose and timing. Methods: from an international registry of patients with ICI myocarditis diagnosed between 2013 and 2019, data on the type, dose (in methylprednisolone equivalent dose) and timing of steroids were extracted. Major cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically-significant complete heart block. Results: in total, 143 ICI myocarditis patients (67±13 years old, 29% women) were included. Among them, 125 received corticosteroids (87%), with the initial agent being either methylprednisolone (95, 76%), prednisone (25, 20%), hydrocortisone (2, 1.6%) or dexamethasone (3, 2.4%). The rates of overall MACE (by admission time tertile 1: 45.8%, tertile 2: 43.8%, tertile 3: 38.3%, P=0.746) and individual elements of MACE were unchanged from 2013 to 2019. The initial corticosteroid dose was categorized as low (500mg). There was an inverse relationship between the occurrence of MACE and initial dose of corticosteroid, where MACE declined with increasing doses (low 61.9%, intermediate 54.6%, high 20.4%, P72 hours (85.7%, P

Background Cardiotoxicity is a serious adverse event associated with some of the most effective breast cancer therapies. Currently, it is difficult to predict which patients will develop cardiotoxicity due to the multiplicity of clinical, behavioral, and biological factors involved. MethodsHere we describe an effort to apply biomedical informatics approaches to patient data from MedStar Health’s EHR systems to discover and characterize factors that contribute to cardiotoxicity in a real world breast cancer population.ResultsData wrangling techniques including merging data from disparate clinical systems, data transformation, and de-identification of personal health information (PHI)were appliedto the raw clinical data to produce a structured integrated dataset for predictive analysis and hypothesis generation. Using this dataset as input, weshowed howpredictive models can be developed to identify patients at high risk for cardiotoxicity. ConclusionsWe demonstrate how suchmodels can be used for hypothesis generation and data exploration with the ultimate goal of developing applications for precision medicine.

The innovative development of cancer therapies has led to an unprecedented improvement in survival outcomes and a wide array of treatment-related toxicities, including those that are cardiovascular in nature. Aging of the population further adds to the number of patients being treated for cancer, especially those with comorbidities. Such pre-existing and developing cardiovascular diseases pose some of the greatest risks of morbidity and mortality in patients with cancer. Addressing the complex cardiovascular needs of these patients has become increasingly important, resulting in an imperative for an intersecting discipline: cardio-oncology. Over the past decade, there has been a remarkable rise of cardio-oncology clinics and service lines. This development, however, has occurred in a vacuum of standard practice and training guidelines, although these are being actively pursued. In this council perspective document, the authors delineate the scope of practice in cardio-oncology and the proposed training requirements, as well as the necessary core competencies. This document also serves as a roadmap toward confirming cardio-oncology as a subspecialty in medicine.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration (Pint < 5×10−8). Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively (Pint < 5×10−8). Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3 (Pint < 5×10−8). This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.

In response to the coronavirus disease 2019 (COVID-19) pandemic, the Cardio-Oncology and Imaging Councils of the American College of Cardiology offers recommendations to clinicians regarding the cardiovascular care of cardio-oncology patients in this expert consensus statement. Cardio-oncology patients—individuals with an active or prior cancer history and with or at risk of cardiovascular disease—are a rapidly growing population who are at increased risk of infection, and experiencing severe and/or lethal complications by COVID-19. Recommendations for optimizing screening and monitoring visits to detect cardiac dysfunction are discussed. In addition, judicious use of multimodality imaging and biomarkers are proposed to identify myocardial, valvular, vascular, and pericardial involvement in cancer patients. The difficulties of diagnosing the etiology of cardiovascular complications in patients with cancer and COVID-19 are outlined, along with weighing the advantages against risks of exposure, with the modification of existing cardiovascular treatments and cardiotoxicity surveillance in patients with cancer during the COVID-19 pandemic.

Heart failure and breast cancer have shared risks and morbidities. Multimodality therapies for breast cancer, including conventional chemotherapy, targeted therapeutics, radiation therapy, and hormonal agents, may make patients more susceptible to asymptomatic left ventricular dysfunction and clinical heart failure during and after treatment. New or preexisting left ventricular dysfunction may lead to interruptions in cancer treatment and limit options of breast cancer systemic therapy, leading to adverse outcomes. Early recognition and management of cardiovascular risk factors before, during, and after cancer treatment are of utmost importance. This review presents advances, challenges, and opportunities for cardiovascular care in contemporary breast cancer treatment.

Učinak sakubitril/valsartana na funkciju lijeve klijetke nakon 3 mjeseca liječenja u pacijenata s akutnim dekompenziranim srčanim zatajivanjem Podaci o učinku sakubitril/valsartana na ehokardiografske parametre u pacijenata s akutnim dekompenziranim srčanim zatajivanjem (ADHF) su još uvijek manjkavi u dostupnoj literaturi. Prospektivno smo uključili 68 uzastopnih pacijenata hospitaliziranih zbog ADHF-a, koji su liječeni sakubitril/valsartanom (N=34, S/V grupa) ili terapijom baziranoj na inhibiciji angiotenzina (N=34, ACEi/ARB grupa). Dvodimenzionalna speckle- tracking ehokardiografska (2D-STE) analiza je urađena pri uključivanju u istraživanje i nakon 3 mjeseca liječenja. Promjene u parametrima 2D-STE, uključujući globalnu uzdužnu longitudinalnu deformaciju lijeve klijetke (LVGLS), su uspoređivane među grupama t-testom i ANCOVA-om. Nije bilo značajnih razlika u bazalnim demografskim, kliničkim i ehokardiografskim osobitostima među grupama. Nakon 3 mjeseca liječenja zabilježeno je značajno poboljšanje LVEF-a i LVGLS-a u S/V grupi (prosječni porast LVEF od 27 % na 34.5 % i LVGLS od -6.6 % na -9.4 %), ali ne i u ACEi/ARB grupi. Navedeno poboljšanje LVEF-a i LVGLS-a je bilo izraženije u onih s neishemijskom etiologijom srčanog zatajivanja.

Advances in cancer screening and improved treatment approaches have led to an increase in survivorship and, consequently, recognition of an association between cancer treatments and the development of cardiovascular complications. In addition, as the population becomes proportionally older, comorbid cardiovascular risk factors are more prevalent in the population and compound the risk of developing cancer treatment–related cardiovascular toxicity. Cardio-oncology has emerged as a new subspecialty of medicine that provides a multidisciplinary approach, bringing together oncologists, cardiologists, and allied health care providers who are tasked with optimizing the cardiovascular health of patients exposed to potentially cardiotoxic cancer therapy. Using a case-based approach, practical advice on how to identify, monitor, and treat patients with cancer who are at risk for developing cancer treatment–related cardiovascular dysfunction is discussed. Cardiovascular risk factors (e.g., age, hypertension, diabetes) and cancer therapies (chemotherapy, targeted therapy, radiation) associated with cardiovascular toxicity are presented. Current cardiac monitoring strategies such as two- and three-dimensional echocardiography, cardiac MRI, and biomarkers (troponin and brain natriuretic peptide [BNP]) are discussed. Last, the current literature on pharmacologic (e.g., angiotensin-converting enzyme inhibitors, β-blockers, statins) and lifestyle (diet and exercise) strategies to mitigate cardiovascular toxicity during and following completion of cancer therapy are reviewed.

Author(s): Zhang, Lili; Awadalla, Magid; Mahmood, Syed S; Nohria, Anju; Hassan, Malek Z O; Thuny, Franck; Zlotoff, Daniel A; Murphy, Sean P; Stone, James R; Golden, Doll Lauren Alexandra; Alvi, Raza M; Rokicki, Adam; Jones-O'Connor, Maeve; Cohen, Justine V; Heinzerling, Lucie M; Mulligan, Connor; Armanious, Merna; Barac, Ana; Forrestal, Brian J; Sullivan, Ryan J; Kwong, Raymond Y; Yang, Eric H; Damrongwatanasuk, Rongras; Chen, Carol L; Gupta, Dipti; Kirchberger, Michael C; Moslehi, Javid J; Coelho-Filho, Otavio R; Ganatra, Sarju; Rizvi, Muhammad A; Sahni, Gagan; Tocchetti, Carlo G; Mercurio, Valentina; Mahmoudi, Michael; Lawrence, Donald P; Reynolds, Kerry L; Weinsaft, Jonathan W; Baksi, A John; Ederhy, Stephane; Groarke, John D; Lyon, Alexander R; Fradley, Michael G; Thavendiranathan, Paaladinesh; Neilan, Tomas G | Abstract: Myocarditis is a potentially fatal complication of immune checkpoint inhibitors (ICI). Sparse data exist on the use of cardiovascular magnetic resonance (CMR) in ICI-associated myocarditis. In this study, the CMR characteristics and the association between CMR features and cardiovascular events among patients with ICI-associated myocarditis are presented.From an international registry of patients with ICI-associated myocarditis, clinical, CMR, and histopathological findings were collected. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. In 103 patients diagnosed with ICI-associated myocarditis who had a CMR, the mean left ventricular ejection fraction (LVEF) was 50%, and 61% of patients had an LVEF ≥50%. Late gadolinium enhancement (LGE) was present in 48% overall, 55% of the reduced EF, and 43% of the preserved EF cohort. Elevated T2-weighted short tau inversion recovery (STIR) was present in 28% overall, 30% of the reduced EF, and 26% of the preserved EF cohort. The presence of LGE increased from 21.6%, when CMR was performed within 4 days of admission to 72.0% when CMR was performed on Day 4 of admission or later. Fifty-six patients had cardiac pathology. Late gadolinium enhancement was present in 35% of patients with pathological fibrosis and elevated T2-weighted STIR signal was present in 26% with a lymphocytic infiltration. Forty-one patients (40%) had MACE over a follow-up time of 5 months. The presence of LGE, LGE pattern, or elevated T2-weighted STIR were not associated with MACE.These data suggest caution in reliance on LGE or a qualitative T2-STIR-only approach for the exclusion of ICI-associated myocarditis.

Aims To study the outcomes of cancer patients undergoing cardiac implantable electronic device (CIED) implantation. Methods and results De novo CIED implantations (2004–15; n = 2 670 590) from the National Inpatient Sample were analysed for characteristics and in-hospital outcomes, stratified by presence of cancer (no cancer, historical and current cancers) and further by current cancer type (haematological, lung, breast, colon, and prostate). Current and historical cancer prevalence has increased from 3.3% to 7.8%, and 5.8% to 7.8%, respectively, between 2004 and 2015. Current cancer was associated with increased adjusted odds ratio (OR) of major adverse cardiovascular events (MACE) [composite of all-cause mortality, thoracic and cardiac complications, and device-related infection; OR 1.26, 95% confidence interval (CI) 1.23–1.30], all-cause mortality (OR 1.43, 95% CI 1.35–1.50), major bleeding (OR 1.38, 95% CI 1.32–1.44), and thoracic complications (OR 1.39, 95% CI 1.35–1.43). Differences in outcomes were observed according to cancer type, with significantly worse MACE, mortality and thoracic complications with lung and haematological malignancies, and increased major bleeding in colon and prostate malignancies. The risk of complications was also different according to CIED subtype. Conclusion The prevalence of cancer patients amongst those undergoing CIED implantation has significantly increased over 12 years. Overall, current cancers are associated with increased mortality and worse outcomes, especially in patients with lung, haematological, and colon malignancies whereas there was no evidence that historical cancer had a negative impact on outcomes.

PURPOSE Observational studies of dietary fat intake and breast cancer have reported inconsistent findings. This topic was addressed in additional analyses of the Women’s Health Initiative (WHI) Dietary Modification (DM) clinical trial that evaluated a low-fat dietary pattern influence on breast cancer incidence. METHODS In the WHI DM trial, 48,835 postmenopausal women, ages 50-79 years, with no prior breast cancer, and a dietary fat intake of ≥ 32% of energy were randomly assigned at 40 US centers to a usual diet comparison group (60%) or dietary intervention group (40%). The goals were to reduce fat intake to 20% of energy and increase vegetable, fruit, and grain intake. Breast cancers were confirmed after central medical record review and serial National Death Index linkages to enhance mortality findings. RESULTS During 8.5 years of dietary intervention, breast cancer incidence and deaths as a result of breast cancer were nonsignificantly lower in the intervention group, while deaths after breast cancer were statistically significantly lower both during intervention and through a 16.1-year (median) follow-up. Now, after a long-term, cumulative 19.6-year (median) follow-up, the significant reduction in deaths after breast cancer persists (359 [0.12%] v 652 [0.14%] deaths; hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.96; P = .01), and a statistically significant reduction in deaths as a result of breast cancer (breast cancer followed by death attributed to the breast cancer) emerged (132 [0.037%, annualized risk] v 251 [0.047%] deaths, respectively; HR, 0.79; 95% CI, 0.64 to 0.97; P = .02). CONCLUSION Adoption of a low-fat dietary pattern associated with increased vegetable, fruit, and grain intake, demonstrably achievable by many, may reduce the risk of death as a result of breast cancer in postmenopausal women.

The immune checkpoint inhibitors have brought about a paradigm shift in the treatment of many cancers and are being used as the first line therapy in increasing number of aggressive malignancies, including metastatic melanoma. Their adverse effects, mostly mediated by an uncontrolled overactivation of the immune system, may compromise the therapeutic benefit. Combination immune checkpoint therapies in particular, have higher therapeutic efficacy, but have also been associated with a higher incidence of severe immune-related adverse effects including autoimmune lymphocytic myocarditis. Recent clinical reports of this rare and life threatening condition indicated rapid progression of severe hemodynamic and electrical instability, with or without acute decompensated heart failure, reduced ejection fraction and shock, pointing to the need for early recognition, diagnosis and prompt management. Current guidelines for management of other immune-related adverse effects recommend high-dose glucocorticoids, with consideration of immunomodulators, such as infliximab in patients with severe colitis. However, knowledge about the treatment approaches in immune-related myocarditis remains extremely scarce. Here we report a case of severe, steroid refractory, lymphocytic myocarditis that occurred after the first cycle of combination immunotherapy with the programmed cell death protein-1 inhibitor, nivolumab, and the cytotoxic T-lymphocyte-associated protein 4 blocker, ipilimumab, for metastatic melanoma. We discuss treatment approaches including the role for transvenous pacemaker, advanced heart failure support, and interdisciplinary decision making.

Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides an opportunity to mitigate cardiac injury and risk of developing late cardiac events. Echocardiography serves as the cornerstone in the detection and surveillance of CTRCD in patients during and after cancer therapy. Guidelines from professional societies and regulatory agencies have been published on approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption as standard of care remains limited given the lack of evidence on the prognostic value of asymptomatic left ventricular (LV) dysfunction in the oncology population. The frequency of cardiac monitoring and the appropriateness of the Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all patients receiving trastuzumab for breast cancer has been challenged. Interruption versus continuation of oncological therapy in the setting of asymptomatic LV dysfunction remains a clinical conundrum given the uncertain balance of the risk of cardiac dysfunction and benefit of oncology efficacy. Despite their limitations, echocardiographic measures of LV function continue to play a pivotal role in clinical decision making, with global longitudinal strain emerging as a promising tool in informing and facilitating the selection of cancer treatment and optimizing cardiovascular outcomes. This review highlights the key recommendations of the existing guidelines and discusses recent developments in cardio-oncology imaging practices with the aim of providing practical guidance on the role and use of echocardiography in challenging clinical cases in cardio-oncology.

Contemporary cancer therapies have dramatically improved cancer-free and overall survival but have been accompanied by increasing cancer treatment-related cardiovascular toxicity, including left ventricular (LV) systolic dysfunction. Previously, systemic chemotherapy with anthracyclines and radiation therapy were the only cancer treatments with significant cardiotoxicity. However, modern targeted cancer therapies, including HER2 inhibitors, tyrosine kinase inhibitors (TKIs), proteasome inhibitors, and immune checkpoint inhibitors, have all been associated with adverse cardiovascular events. As cancer treatment paradigms successfully move toward prolonged targeted therapy, cardiologists are increasingly needed to assess cardiotoxicity risk and manage asymptomatic and symptomatic LV systolic dysfunction. This state of the art review summarizes the present knowledge about the mechanisms and clinical practices of screening, diagnosis, and management of LV dysfunction associated with cancer therapeutic regimens. We utilize the framework of the ACCF/AHA stages of heart failure (HF) to summarize current evidence for risk stratification and modification (Stage A HF), asymptomatic structural heart disease detection and treatment (Stage B HF), and reduction of HF morbidity and mortality (Stages C and D HF) during cancer treatment and in survivorship. We also present new clinical practice challenges and opportunities for active engagement of cardiologists with multidisciplinary cancer treatment teams in order to ensure optimal patient outcomes.

Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology. The article discusses challenges in predicting, monitoring, and treating cardiac dysfunction and heart failure associated with ErbB-targeted cancer therapeutics and highlights opportunities for researchers and clinical investigators.

Background Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. Current U.S. Food and Drug Administration recommendations limit the use of HER2 targeted agents to patients with normal left ventricular (LV) systolic function. Methods The objective of the SAFE-HEaRt study is to evaluate the cardiac safety of HER2 targeted therapy in patients with HER2 positive breast cancer and mildly reduced left ventricular ejection fraction (LVEF) with optimized cardiac therapy. Thirty patients with histologically confirmed HER2 positive breast cancer (stage I-IV) and reduced LVEF (40% to 49%) who plan to receive HER2 targeted therapy for ≥3 months will be enrolled. Prior to initiation on study, optimization of heart function with beta-blockers and angiotensin converting enzyme inhibitors will be initiated. Patients will be followed by serial echocardiograms and cardiac visits during and 6 months after completion of HER2 targeted therapy. Myocardial strain and blood biomarkers, including cardiac troponin I and high-sensitivity cardiac troponin T, will be examined at baseline and during the study. Discussion LV dysfunction in patients with breast cancer poses cardiac and oncological challenges and limits the use of HER2 targeted therapies and its oncological benefits. Strategies to prevent cardiac dysfunction associated with HER2 targeted therapy have been limited to patients with normal LVEF, thus excluding patients who may receive the highest benefit from those strategies. SAFE-HEaRt is the first prospective pilot study of HER2 targeted therapies in patients with reduced LV function while on optimized cardiac treatment that can provide the basis for clinical practice changes. The Oncologist 2017;22:518-525 IMPLICATIONS FOR PRACTICE: Human epidermal growth receptor 2 (HER2) targeted therapies have survival benefit in adjuvant and metastatic HER2 positive breast cancer but are associated with cardiac dysfunction. To our knowledge, SAFE-HEaRt is the first clinical trial that prospectively tests the hypothesis that HER2 targeted therapies may be safely administered in patients with mildly reduced cardiac function in the setting of ongoing cardiac treatment and monitoring. The results of this study will provide cardiac safety data and inform consideration of clinical practice changes in patients with HER2 positive breast cancer and reduced cardiac function, as well as provide information regarding cardiovascular monitoring and treatment in this population.

PurposeCardiac dysfunction is a serious adverse effect of certain cancer-directed therapies that can interfere with the efficacy of treatment, decrease quality of life, or impact the actual survival of the patient with cancer. The purpose of this effort was to develop recommendations for prevention and monitoring of cardiac dysfunction in survivors of adult-onset cancers.MethodsRecommendations were developed by an expert panel with multidisciplinary representation using a systematic review (1996 to 2016) of meta-analyses, randomized clinical trials, observational studies, and clinical experience. Study quality was assessed using established methods, per study design. The guideline recommendations were crafted in part using the Guidelines Into Decision Support methodology.ResultsA total of 104 studies met eligibility criteria and compose the evidentiary basis for the recommendations. The strength of the recommendations in these guidelines is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms.RecommendationsIt is important for health care providers to initiate the discussion regarding the potential for cardiac dysfunction in individuals in whom the risk is sufficiently high before beginning therapy. Certain higher risk populations of survivors of cancer may benefit from prevention and screening strategies implemented during cancer-directed therapies. Clinical suspicion for cardiac disease should be high and threshold for cardiac evaluation should be low in any survivor who has received potentially cardiotoxic therapy. For certain higher risk survivors of cancer, routine surveillance with cardiac imaging may be warranted after completion of cancer-directed therapy, so that appropriate interventions can be initiated to halt or even reverse the progression of cardiac dysfunction.

Angiogenesis inhibitors, also known as vascular endothelial growth factor (VEGF) or vascular signaling pathway (VSP) inhibitors, have improved care of neoplastic diseases over the past decade. However, cardiovascular toxicities associated with these agents, such as hypertension and less commonly left ventricular systolic dysfunction and heart failure, have often been a limiting factor for continued use. Balancing the benefits of these agents with the associated toxicities is critical to ensure these therapies do not negatively impact oncological outcomes. The care of cancer patients with cardiovascular risks is challenging due to the heterogeneity of cardiovascular complications, paucity of evidence-based guidelines, and lack of channels for collaboration among healthcare providers. Herein, we provide a team-based approach for treatment of angiogenesis inhibitor-induced hypertension along with recommendations on monitoring and appropriate selection of anti-hypertensive agents.

We investigated time trends and factors associated with the use of cardiac imaging among women with early-stage breast cancer prior to the initiation of treatment. Of 11,732 women ages 24-64, diagnosed with stage I-III breast cancer in 2006-2011, 2550 (22%) received anthracycline-based chemotherapy. Baseline cardiac imaging was used in 79% of patients receiving anthracyclines and increased over time. Of 2277 (20%) women who received non-anthracycline therapy, 16% received cardiac imaging. Women receiving cardiac imaging in non-anthracycline therapy group were more likely to have higher cardiovascular risk, as well as higher cancer stage and worse histological tumor grade suggesting that results of imaging might have influenced the choice of cancer therapy. Our findings indicate the need for cardio-oncology collaboration in identification and treatment of women at high risk for adverse oncology and cardiovascular outcomes.

International audience; Serum biomarkers are an important tool in the baseline risk assessment and diagnosis of cardiovascular disease in cancer patients receiving cardiotoxic cancer treatments. Increases in cardiac biomarkers including cardiac troponin and natriuretic peptides can be used to guide initiation of cardioprotective treatments for cancer patients during treatment and to monitor the response to cardioprotective treatments, and they also offer prognostic value. This position statement examines the role of cardiac biomarkers in the management of cancer patients. The Cardio-Oncology Study Group of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) in collaboration with the Cardio-Oncology Council of the ESC have evaluated the current evidence for the role of cardiovascular biomarkers in cancer patients before, during and after cardiotoxic cancer therapies. The characteristics of the main two biomarkers troponin and natriuretic peptides are discussed, the link to the mechanisms of cardiovascular toxicity, and the evidence for their clinical use in surveillance during and after anthracycline chemotherapy, trastuzumab and HER2-targeted therapies, vascular endothelial growth factor inhibitors, proteasome inhibitors, immune checkpoint inhibitors, cyclophosphamide and radiotherapy. Novel surveillance clinical pathways integrating cardiac biomarkers for cancer patients receiving anthracycline chemotherapy or trastuzumab biomarkers are presented and future direction in cardio-oncology biomarker research is discussed.

OBJECTIVE Direct medical cost of diabetes in the U.S. has been estimated to be 2.3 times higher relative to individuals without diabetes. This study examines trends in healthcare expenditures by expenditure category in U.S. adults with diabetes between 2002 and 2011. RESEARCH DESIGN AND METHODS We analyzed 10 years of data representing a weighted population of 189,013,514 U.S. adults aged ≥18 years from the Medical Expenditure Panel Survey. We used a novel two-part model to estimate adjusted mean and incremental medical expenditures by diabetes status, while adjusting for demographics, comorbidities, and time. RESULTS Relative to individuals without diabetes ($5,058 [95% CI $4,949–$5,166]), individuals with diabetes ($12,180 [$11,775–$12,586]) had more than double the unadjusted mean direct expenditures over the 10-year period. After adjusting for confounders, individuals with diabetes had $2,558 ($2,266–$2,849) significantly higher direct incremental expenditures compared with those without diabetes. For individuals with diabetes, inpatient expenditures rose initially from $4,014 in 2002/2003 to $4,183 in 2004/2005 and then decreased continuously to $3,443 in 2010/2011, while rising steadily for individuals without diabetes. The estimated unadjusted total direct expenditures for individuals with diabetes were $218.6 billion/year and adjusted total incremental expenditures were approximately $46 billion/year. CONCLUSIONS Our findings show that compared with individuals without diabetes, individuals with diabetes had significantly higher health expenditures from 2002 to 2011 and the bulk of the expenditures came from hospital inpatient and prescription expenditures.

Early detection and improved treatment in breast cancer have resulted in an increased number of survivors. Cardiovascular disease now remains an important cause for morbidity and mortality in this population. There is a growing gap in the knowledge about the optimal long-term cardiovascular management of this population. Breast cancer and cardiovascular disease share a number of common risk factors. Different breast cancer treatment modalities, including anthracyclines, radiation, and hormonal therapy, can act in synergy with preexisting and/or new cardiovascular risk factors to result in significant cardiovascular disease. We summarize the recent evidence about cardiovascular effects of breast cancer therapy and recommendations for their diagnosis and management during the cancer treatment continuum into survivorship. We also present current research initiatives and how they inform clinical care.

ObjectiveTo enhance the understanding of cardiovascular care delivery in childhood cancer patients and survivors.Study designA 20-question survey was created by the Pediatric Cardio-oncology Work Group of the American College of Cardiology (ACC) Cardio-oncology Section to assess the care, management, and surveillance tools utilized to manage pediatric/young adult cardio-oncology patients. The survey distribution was a collaborative effort between Cardio-oncology Section and membership of the Adult Congenital and Pediatric Cardiology Section (ACPC) of the ACC.ResultsSixty-five individuals, all self-identified as physicians, responded to the survey. Most respondents (n = 58,89%) indicated childhood cancer patients are regularly screened prior to and during cancer therapy at their centers, predominantly by electrocardiogram (75%), standard echocardiogram (58%) and advanced echocardiogram (50%) (i.e. strain, stress echo). Evaluation by a cardiologist prior to/during therapy was reported by only 8(12%) respondents, as compared to post-therapy which was reported by 28 (43%,p n = 31,48%) and history of chemotherapy exposure (n = 27,42%). Of note, during post-treatment counseling, common cardiovascular risk-factors like blood pressure (31,48%), lipid control (22,34%), obesity & smoking (30,46%) and diet/exercise/weight loss (30,46%) were addressed by fewer respondents than was LV function (72%).ConclusionsThe survey data demonstrates that pediatric cancer patients are being screened by EKG and/or imaging prior to/during therapy at most centers. Our data, however, highlight the potential for greater involvement of a cardiovascular specialist for pre-treatment evaluation process, and for more systematic cardiac risk factor counseling in posttreatment cancer survivors.

Background The effect of ethnicity on in-hospital outcomes of takotsubo cardiomyopathy (TC) is unknown. Purpose To investigate ethnic variations in hospital outcomes of TC in a large nationwide sample. Methods The National Inpatient Sample (NIS) database was searched from 2004 to 2014 for the ICD-9-CM code 429.83 to obtain weighted estimates of TC hospitalizations. Based on self-reported ethnicity, African-Americans (AA) and Hispanics were compared to Caucasians for differences in baseline characteristics and in-hospital outcomes. Multivariate regression models were used to adjust for potential confounders. Results Of 103891 hospital admissions identified, 89624 (86.3%) were Caucasians, 8026 (7.7%) were AA and 6241 (6%) were Hispanics. Caucasians were older with more females as compared to AA and Hispanics (67.5 [0.13] vs 61.8 [0.45] vs 63.2 [0.52] years, p Table 1. Patients' demographics and baseline characteristics Parameter Caucasians African Americans Hispanics Total p-value Age, years 67.46 (0.13) 61.77 (0.45) 63.15 (0.52) 66.76 (0.12) Figure 1. In-Hospital Outcomes Conclusion There is ethnic variation in hospital outcomes of takotsubo cardiomyopathy, some of which may be related to differences in patients' demographics and baseline characteristics. Acknowledgement/Funding Medstar Georgetown University Hospital/ Washington Hospital Center graduate medical education department funded the purchase of the database

With advances in breast cancer therapy, there has been substantial improvement in cancer-specific prognosis for women with breast cancer. As expected, with greater breast cancer survival, risks for competing causes of death have increased in this group of patients, specifically the risk of

Cancer and cardiovascular (CV) disease are the most prevalent diseases in the developed world. Evidence increasingly shows that these conditions are interlinked through common risk factors, coincident in an ageing population, and are connected biologically through some deleterious effects of anticancer treatment on CV health. Anticancer therapies can cause a wide spectrum of short- and long-term cardiotoxic effects. An explosion of novel cancer therapies has revolutionised this field and dramatically altered cancer prognosis. Nevertheless, these new therapies have introduced unexpected CV complications beyond heart failure. Common CV toxicities related to cancer therapy are defined, along with suggested strategies for prevention, detection and treatment. This ESMO consensus article proposes to define CV toxicities related to cancer or its therapies and provide guidance regarding prevention, screening, monitoring and treatment of CV toxicity. The majority of anticancer therapies are associated with some CV toxicity, ranging from asymptomatic and transient to more clinically significant and long-lasting cardiac events. It is critical however, that concerns about potential CV damage resulting from anticancer therapies should be weighed against the potential benefits of cancer therapy, including benefits in overall survival. CV disease in patients with cancer is complex and treatment needs to be individualised. The scope of cardio-oncology is wide and includes prevention, detection, monitoring and treatment of CV toxicity related to cancer therapy, and also ensuring the safe development of future novel cancer treatments that minimise the impact on CV health. It is anticipated that the management strategies discussed herein will be suitable for the majority of patients. Nonetheless, the clinical judgment of physicians remains extremely important; hence, when using these best clinical practices to inform treatment options and decisions, practitioners should also consider the individual circumstances of their patients on a case-by-case basis.

Chimeric antigen receptor (CAR) T-cell therapy has significantly advanced the treatment of patients with relapsed and refractory hematologic malignancies and is increasingly investigated as therapeutic option of other malignancies. The main adverse effect of CAR T-cell therapy is potentially life-threatening cytokine release syndrome (CRS). Clinical cardiovascular (CV) manifestations of CRS include tachycardia, hypotension, troponin elevation, reduced left ventricular ejection fraction (LVEF), pulmonary edema and cardiogenic shock. Although insults related to CRS toxicity might be transient and reversible in most instances in patients with adequate CV reserve, they can be particularly challenging in higher-risk, often elderly patients with pre-existing CV disease. As the use of CAR T-cell therapy expands to include wider patient population, careful patient selection, pre-treatment cardiac evaluation and CV risk stratification should be considered within the CAR T-cell treatment protocol. Early diagnosis and management of CV complications in patients with CRS require awareness and multidisciplinary collaboration.

Cardiovascular disease is a competing cause of death in patients with cancer with early-stage disease. This elevated cardiovascular disease risk is thought to derive from both the direct effects of cancer therapies and the accumulation of risk factors such as hypertension, weight gain, cigarette smoking, and loss of cardiorespiratory fitness. Effective and viable strategies are needed to mitigate cardiovascular disease risk in this population; a multimodal model such as cardiac rehabilitation may be a potential solution. This statement from the American Heart Association provides an overview of the existing knowledge and rationale for the use of cardiac rehabilitation to provide structured exercise and ancillary services to cancer patients and survivors. This document introduces the concept of cardio-oncology rehabilitation, which includes identification of patients with cancer at high risk for cardiac dysfunction and a description of the cardiac rehabilitation infrastructure needed to address the unique exposures and complications related to cancer care. In this statement, we also discuss the need for future research to fully implement a multimodal model of cardiac rehabilitation for patients with cancer and to determine whether reimbursement of these services is clinically warranted.

BACKGROUND: Trastuzumab is highly effective for HER2-positive breast cancer but is associated with a decline in left ventricular ejection fraction. OBJECTIVE: To determine whether angiotensin converting enzyme (ACE) inhibitors or beta blockers (BB) reduce the rate of trastuzumab-induced cardiotoxicity (LVEF decrease >10%, or >5% if less than 50%) and limit treatment interruptions. METHODS: In this double-blind, multicenter, placebo-controlled trial, cardiotoxicity and treatment interruptions in patients with HER2-positive breast cancer treated with trastuzumab for 12 months were evaluated over a 2-year period. Patients were stratified by anthracycline use and then randomized to receive lisinopril, carvedilol, or placebo. RESULTS: The study included 468 women, 51±10.7 years old. For the entire cohort, cardiotoxicity was comparable in the three arms and occurred in 32% patients on placebo, 29% on carvedilol, and 30% on lisinopril. For patients receiving anthracyclines, the event rates were higher in the placebo group (47%) than in the lisinopril (37%) and the carvedilol (31%) groups. Cardiotoxicity-free survival was longer on both carvedilol (HR 0.49, 95% confidence intervals 0.27, 0.89, p=0.009) or lisinopril (HR 0.53, CI 0.30, 0.94, p=0.015) than on placebo. In the whole cohort, as well as in the anthracycline arm, patients on active therapy with either ACE inhibitor or BB experienced fewer interruptions in trastuzumab than those on placebo. CONCLUSIONS: In patients with HER2-positive breast cancer treated with trastuzumab, both lisinopril and carvedilol prevented cardiotoxicity in patients receiving anthracyclines. For such patients, lisinopril or carvedilol should be considered to minimize interruptions of trastuzumab.

Cardio-oncology is a growing multi-disciplinary field that focuses on treating and preventing cardiovascular complications in cancer survivors and patients. This review summarizes the current clinical needs and system-based approaches to target barriers of care. The field of cardio-oncology has experienced significant growth in recent years, and an increasing number of programs have been developed across the nation to provide improved and multi-disciplinary care to this patient population. Despite this burgeoning growth, practitioners in the field continue to face important challenges which include lack of administrative and departmental support, funding limitations, and gaps in the areas of mentoring, education, and research. Despite continued growth, cardio-oncology providers continue to face a multitude of challenges. Early inclusion of multi-disciplinary stakeholders, oncologists, cardiovascular team members, and administrative leadership provides an opportunity to collaborate and achieve unique patient care and health system benefits, such as prevention of adverse cardiovascular outcomes, and facilitates the delivery of optimal oncologic treatment.

Cardio-oncology has organically developed as a new discipline within cardiovascular medicine as a result of the cardiac and vascular adverse sequelae of the major advances in cancer treatment. Patients with cancer and cancer survivors are at increased risk of vascular disease for a number of reasons. First, many new cancer therapies, including several targeted therapies, are associated with vascular and metabolic complications. Second, cancer itself serves as a risk factor for vascular disease, especially by increasing the risk for thromboembolic events. Finally, recent data suggest that common modifiable and genetic risk factors predispose to both malignancies and cardiovascular disease. Vascular complications in patients with cancer represent a new challenge for the clinician and a new frontier for research and investigation. Indeed, vascular sequelae of novel targeted therapies may provide insights into vascular signaling in humans. Clinically, emerging challenges are best addressed by a multidisciplinary approach in which cardiovascular medicine specialists and vascular biologists work closely with oncologists in the care of patients with cancer and cancer survivors. This novel approach realizes the goal of providing superior care through the creation of cardio-oncology consultative services and the training of a new generation of cardiovascular specialists with a broad understanding of cancer treatments.

e19335 Background: Left ventricular assist devices (LVAD) are increasingly utilized in advanced heart failure (HF). There is a paucity of data regarding outcomes of cancer-directed therapies (CDT) in patients with LVAD. The aim of this study was to describe outcomes in this newly identified group of patients. Methods: Institutional LVAD database review to identify patients with cancer diagnosis who had at least 6 months of follow up. Chart review to capture cancer history, CDT and high-severity complications. Results: 12 of the 588 patients who received LVAD were diagnosed with cancer and received CDT. Six patients were males, 9 African Americans and 3 Caucasians. Ischemic cardiomyopathy (CM) was the etiology of HF in 4 (33%) patients, 9 (66%) patients had non-ischemic CM (including: chemotherapy induced n = 3, idiopathic n = 3, myocarditis n = 1, sarcoidosis n = 1). Cancer diagnoses, staging and high severity complications are described in table. The median age of cancer diagnosis was 59 (41-72). The median time from LVAD placement to cancer diagnosis was 21.5 months (3-47). The median number of hospitalizations was 4 (range 1-7). Conclusions: Cancer diagnosis after LVAD placement requires a multidisciplinary approach due to high rates of adverse cardiovascular and cancer related outcomes. To the best of our knowledge this is the first report of patients with LVAD receiving chemo-immunotherapy, they did not tolerate the combination and immunotherapy was discontinued after one cycle, a larger study is required to assess safety in LVAD patients. Larger prospective studies are required to determine outcomes in this complex patient population. [Table: see text]

e13618 Background: Previous investigations have demonstrated an inconclusive relationship between lipid biomarkers and mortality after cancer. Methods: We used data from 2,279 postmenopausal women diagnosed with 13 obesity-related cancers, who were part of the Women’s Health Initiative (WHI) lipid biomarkers cohort, to evaluate the relationship between lipid levels measured at study entry prior to cancer diagnosis, and mortality after cancer. Baseline lipid measurements consisted of HDL-Cholesterol, LDL-Cholesterol, and non-HDL-Cholesterol with ranges of measurement listed in the table. Obesity-related cancers included: meningioma, thyroid, adenocarcinoma of esophagus, breast, multiple myeloma, liver, kidney, gallbladder, stomach, uterus, pancreas, ovaries, and colorectal. The age adjusted relationship between baseline lipids and all-cause mortality as well as mortality due to cancer were estimated using Cox proportional hazards models and Fine-Gray models, respectively. Results: The majority of women in the cohort had either desirable or acceptable lipid levels (86% HDL-C, 30% LDL-C and 61% non-HDL-C. Low vs. desirable HDL-C levels were associated with higher risk of all-cause mortality (hazard ratio (HR) 1.54, 95% confidence interval [CI] [1.48, 1.60], p