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Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population.Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors.A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials.

Background: Inflammation plays a major role in the development and progression of cardiovascular disease (CVD) morbidity and mortality. The well-established relationship between periodontal disease (PD) and CVD may be causal. Left untreated, PD can lead to high systemic inflammation, thus contributing to inflammatory CVD, such as atherosclerosis. Multiple mechanisms have been proposed to elucidate the causal relationship between PD and its contribution to CVD. Objective: This review article highlights the current evidence supporting the role of PD in the development and progression of atherosclerosis. Methods: After creating a list of relevant medical subject heading (MeSH) terms, a systematic search within PubMed in English for each MeSH term between 2000 and 2019 was used to generate evidence for this review article. Conclusion: There is overwhelming evidence in the current literature that supports an association between PD and CVD that is independent of known CVD risk factors. However, the supporting evidence that PD directly causes CVD in humans continues to remain elusive. Multiple biologically plausible mechanisms have been proposed and investigated, yet most studies are limited to mouse models and in vitro cell cultures. Additional studies testing the various proposed mechanisms in longitudinal human studies are required to provide deeper insight into the mechanistic link between these 2 related diseases.

To evaluate diagnostic accuracy of different protocols of contrast enhanced computed tomography venogram (CTV) for LAA thrombus detection in patients undergoing AF ablation and study the correlation of the novel LAA enhancement index (LAA-EI) to LAA flow velocity obtained using transesophageal echocardiography (TEE).Study comprised of patients undergoing CTV and TEE on the same day from October 2016 to December 2017. Three CTV scanning protocols (described in results), were evaluated wherein ECG gating was used only for those with sinus rhythm on day of CTV. LAA-EI was calculated as Hounsfield Unit (HU) in the LAA divided by the HU unit in the center of the LA. The diagnostic accuracy for CTV was calculated in comparison to TEE. The LAA-EI was compared to LAA emptying velocities as obtained from TEE.590 patients with 45.6% non-ECG-gated without delayed imaging, 26.9% non-ECG-gated with delayed imaging and 27.5% ECG-gated with delayed imaging, were included in the study. All three protocols had 100% negative predictive value with improvement in specificity from 61.8% to 98.1% upon adding delayed imaging. The LAA-EI correlated significantly with reduced LAA flow velocities (r = 0.45, p .0001). The mean LAA emptying velocity in patients with LAA-EI of ≤ 0.6 was significantly lower than in those with LAA-EI of0.6 (36.2 cm/s [95% CI: 32.6-39.7] vs, (58 cm/s [95% CI 55.3-60.8]), respectively (p .0001).CTV with delayed imaging (with or without ECG gating) is highly specific in ruling out LAA thrombus. The novel LAA-EI can detect low LAA flow velocities.

Atherosclerotic cardiovascular disease (ASCVD) shares many risk factors with atrial fibrillation (AF). Obtaining computed tomography images of the pulmonary veins (CTPV) before AF ablation procedures is common and can incidentally detect coronary artery calcification (CAC). The purpose of this study was to investigate the prevalence of CAC on pre-ablation CTPV, the frequency of CAC reporting on CTPV reports, and its impact on statin therapy among patients hospitalized for AF procedures. We retrospectively evaluated consecutive patients undergoing CTPV and AF procedures from October 2016 to December 2017 in a single-center tertiary hospital. The patients&rsquo, demographic and clinical characteristics were analyzed. The CAC presence on CTPV was visually assessed. The severity was classified qualitatively. The statin therapy status was evaluated using the patient&rsquo, s admission and discharge medication lists. A total of 638 subjects were included in our study, with 34.5% female. The mean age was 63.3 &plusmn, 10.8 years. CAC was detected in 70.1% of all patients, and in 58.1% of patients without a history of ASCVD. When present, CAC was documented in 92.6% of the clinical CTPV reports. While coronary artery atherosclerosis was present in a majority of AF patients, and its presence was widely reported, it was not associated with increased statin therapy at discharge.

Cardiac masses are rare, but remain an important component of cardio-oncology practice. These include benign tumors, malignant tumors (primary and secondary) and tumor-like conditions (e.g., thrombus, Lambl’s excrescences, and pericardial cyst). The advent of multimodality imaging has enabled identification of the etiology of cardiac masses in many cases, especially in conjunction with information from clinical settings. This paper provides a comprehensive review of the epidemiology, clinical presentation, imaging, diagnosis, management, and outcomes of cardiac masses., Central Illustration, Highlights • Cardiac tumors are rare and should be considered as part of the differential diagnosis of any space-occupying mass noted on cardiovascular and/or thoracic imaging modalities. • It may be possible to get close to a diagnosis without biopsy using a structured imaging approach. • The prognosis and treatment of each tumor is different, although early diagnosis is usually associated with a better outcome.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.

Chimeric antigen receptor (CAR) T cell therapy is approved in the United States for the treatment of acute lymphocytic leukemia and aggressive B cell lymphomas. Multiple cardiovascular adverse events (CVEs) associated with CAR-Ts have been observed in small studies, but no large-scale studies exist. Leveraging the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS), we identified all reported adverse events (AEs) associated with CAR-T therapy (tisagenlecleucel and axicabtagene ciloleucel) from 2017 to 2019. Reports with missing age and sex were excluded. CVEs were classified into arrhythmias, heart failure (HF), myocardial infarction (MI), and other CVEs. Logistic regression and hierarchical clustering were used to identify factors associated with CVEs. A total of 996 reported AEs were observed (39.1% associated with tisagenlecleucel and 60% with axicabtagene ciloleucel). Of all patients experiencing AEs, the median age was 54 (interquartile range, 21 to 65) years; 38.9% were females. In total, 19.7% (196) of all AEs reported to the FDA were CVEs. The most common CVEs were arrhythmia (77.6%), followed by HF (14.3%) and MI (0.5%). In adjusted analysis a positive association was observed between those presenting with CVE with neurotoxicity (odds ratio, 1.76; 95% confidence interval, 1.20 to 2.60; P = .004). Additionally, when both CVE and cytokine release syndrome (CRS) are present, neurotoxicity is the most common noncardiac AE, which clusters with them (Jaccard similarity: 73.1). The mortality rate was 21.1% overall but 30.1% for those reporting CVEs. In FAERS, reported CVEs with CAR-T are associated with high reported mortality. The development of either CRS or neurotoxicity should prompt vigilance for cardiovascular events.

BackgroundMultiple reports have pointed towards involvement of community and socioeconomic characteristics of people in the United States may be associated with COVID-19 cases and deaths.MethodsIn this study, zip-code level data from 5 major metropolitan areas, was utilized to study the effect of multiple demographic & socioeconomic factors – including race, age, income, chronic disease comorbidity, population density, number of people per household on number of positive cases and ensuing death. Adjusted linear regression analysis using 13 to 16 such variables was performed.ResultsOverall, 442 zip codes reporting 93,170 positive COVID-19 cases and 138 zip codes reporting mortality ranging from 0 to 25 were included in this study. A multivariable linear regression model noted that 1% increase in the proportion of residents above the age of 65 years, proportion of African American residents, proportion of females, persons per household and population density of the zip code increased the proportion of positive cases by 0.77%, 0.23%, 1.64%, 1.83% and 0.46% respectively (PConclusionThis study gives early signals of gender, and racial inequalities while providing overwhelming evidence of how population density may contribute to an increase in the number of positive cases of COVID-19.

Background Patients with cancer and severe aortic stenosis are often ineligible for surgical aortic valve replacement ( SAVR ). Patients with cancer may likely benefit from emerging transcatheter aortic valve replacement ( TAVR ), given its minimally invasive nature. Methods and Results The US ‐based National Inpatient Sample was queried between 2012 and 2015 using International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ), codes to identify all hospitalized adults (aged ≥50 years), who had a primary diagnosis of aortic stenosis. We examined the effect modification of cancer on the relative use rate, outcomes, and dispositions associated with propensity‐matched cohort TAVR versus SAVR . Overall, 47 295 TAVRs (22.6% comorbid cancer) and 113 405 SAVRs (15.2% comorbid cancer) were performed among admissions with aortic stenosis between 2012 and 2015. In the year 2015, patients with cancer saw relatively higher rates of TAVR use compared with SAVR (relative use rate TAVR versus relative use rate SAVR , 67.8% versus 57.2%; P TAVR was associated with lower odds of acute kidney injury (odds ratio, 0.64; 95% CI, 0.54–0.75) and major bleeding (odds ratio, 0.44; 95% CI , 0.38–0.51]), with no differences in in‐hospital mortality and stroke compared with SAVR . In addition, TAVR was associated with higher odds of home discharge (odds ratio, 1.92; 95% CI, 1.68–2.19) compared with SAVR among patients with cancer. Lower risk of acute kidney injury was noted in cancer versus noncancer ( P TAVR versus SAVR in effect modification analysis. Conclusions TAVR use has increased irrespective of cancer status, with a greater increase in cancer versus noncancer. In patients with cancer, there was an association of TAVR with lower periprocedural complications and better disposition when compared with patients undergoing SAVR .

Background Thrombolytic therapy significantly improves outcomes among patients with acute ischemic stroke. While cancer outcomes have dramatically improved, the utilization, safety, and mortality outcomes of patients with cancer who receive thrombolytic therapy for acute ischemic stroke are unknown. Methods Using a national database, we identified all hospitalizations for acute ischemic stroke requiring thrombolytic therapy between 2003 and 2015. Patients with contraindications to thrombolytic therapy were excluded. Following propensity score matching for comorbidity burden, trends in thrombolytic therapy use and its effect on in-hospital mortality, intracranial or all-cause bleeding, and the combined endpoint of mortality and all-cause bleeding, by presence/absence of cancer were evaluated. We also evaluated 30- and 90-day readmission rates post-thrombolytic therapy administration. Results We identified 237,687 acute ischemic stroke hospitalizations requiring thrombolytic therapy, of which 26,328 (11%) had an underlying cancer. Over the study period, thrombolytic therapy use increased across all acute ischemic stroke admissions, irrespective of cancer presence (12.4/1000 in 2003 to 81.1/1000 in 2015, P Conclusions Contemporary thrombolytic therapy use for acute ischemic stroke has risen, irrespective of presence of cancer. Yet, patients with comorbid cancer appear to see lower rates of thrombolytic therapy use for acute ischemic stroke, despite no difference in the rate of intracranial bleeding or mortality after adjustment for comorbidities.

To characterize the contemporary efficacy and utilization patterns of coronary artery bypass grafting (CABG) in specific cancer types.We leveraged the data from the National Inpatient Sample and plotted trends of utilization and outcomes of isolated CABG (with no other additional surgeries during the same hospitalization) procedures from January 1, 2003, through September 1, 2015. Propensity score matching was used to assess for potential differences in outcomes by type of cancer status among contemporary (2012-2015) patients.Overall, the utilization of CABG decreased over time (250,677 in 2003 vs 134,534 in 2015, P.001). However, the proportion of those with comorbid cancer increased (7.0% vs 12.6%, P.001). Over time, in-hospital mortality associated with CABG use in cancer remained unchanged (.9% vs 1.0%, P=.72); yet, cancer patients saw an increase in associated major bleeding (4.5% vs 15.3%, P.001) and rate of stroke (.9% vs 1.5%, P.001) over time. In-hospital cost-of-care associated with CABG-use in cancer also increased over time ($29,963 vs $33,636, P.001). When stratified by cancer types, in-hospital mortality was not higher in breast, lung, prostate, colon cancer, or lymphoma versus non-cancer CABG patients (all P.05). However, there was a significantly higher prevalence of major bleeding but not stroke in patients with breast and prostate cancer only compared with non-cancer CABG patients (P.01). Discharge dispositions were not found to be different between cancer sub-groups and non-cancer patients (P.05), except for breast cancer patients who had lower home care, but higher skilled care disposition (P.001).Among those undergoing CABG, the prevalence of comorbid cancer has steadily increased. Outside of major bleeding, these patients appear to share similar outcomes to those without cancer indicating that CABG utilization should be not be declined in cancer patients when otherwise indicated. Further research into the factors underlying the decision to pursue CABG in specific cancer sub-groups is needed.

Background: Expert opinion recommends performing exercise testing with initiation of Class Ic antiarrhythmic medication. Objective: To evaluate the rate and reason for discontinuation of Ic agent within the first year of follow up, with particular attention to rate of proarrhythmia and the value of routine treadmill testing. Methods: This is a single center retrospective cohort study including consecutive patients with atrial arrhythmias who were initiated on a Class Ic agent from 2011 to 2016. Data was collated from chart review and pharmacy database. Results: The study population included 300 patients (55% male, mean age 61; mean ejection fraction, 56%) started on flecainide (n = 153; 51%) and propafenone (n = 147; 49%). Drug initiation was completed while hospitalized on telemetry and the staff electrophysiologists directed dosing. There was one proarrhythmic event during initiation (0.3%). The primary reason for not being discharged on Ic agent was due to detection of proarrhythmia (n = 15) or ischemia (n = 1) with treadmill testing (5.3%). Exercise testing was the single significant variable to affect the decision to discontinue Ic drug, p

Background In the United States, both cannabis use disorder (CUD) and opioid use disorder (OUD) have increased in prevalence. The prevalence, demographics, and costs of CUD and OUD are not well known in heart failure (HF) admissions. This study aimed to use a national database to examine the prevalence, demographics, and costs associated with CUD and OUD in HF. Methods This study used the National Inpatient Sample from 2008 to 2018 to identify all primary HF admissions with and without the co-diagnosis of OUD or CUD using International Classification for Diagnosis, diagnosis codes. Demographics, costs, and trends were examined. Results Between 2008 and 2018, we identified 11,692,995 admissions for HF of which 84,796 (0.8%) had a co-diagnosis of CUD only, and 67,137 (0.6%) had a co-diagnosis of OUD only. The proportion of HF admissions with CUD significantly increased from 0.3% in 2008 to 1.3% in 2018 (p Conclusions Among discharge records for HF, CUD and OUD are increasing in prevalence, significantly affect underserved populations and are associated with higher costs of stay. Future research is essential to better delineate the cause of these increased costs and create interventions, particularly in underserved populations.

Background Pacemakers (PM) are used for managing sick sinus syndrome (SSS). This study evaluates predictors and trends of PM implantation for SSS. Methods Patients were identified from the National Inpatient Sample dataset (2003-13). Included patients were ≥18 years old, had a diagnosis of sinus node dysfunction and atrial arrhythmia (i.e., SSS). Patients who died, transferred out, who had prior device or had a defibrillator or resynchronization therapy device implanted were excluded. Included patients were then stratified by if a PM was implanted. Data regarding SSS, trends of PM utilization and multivariable models of factors associated with PM implantation are presented. Results 328,670 patients satisfied study criteria. This study compared patients who underwent (87.4%) PM implantation to those who did not undergo (12.6%) PM implantation. The annual trends for hospitalization with SSS and PM placement have been decreasing (p < 0.001). Variables associated with lower likelihood for PM implantation include young age, female sex, non-Caucasian race, chronic heart failure, Charlson Comorbidity Score ≥1, emergency room and weekend admission, hospital stay ≤3 days, and high cardiology inpatient volume. Greater likelihood for PM implantation was associated with hyperlipidemia, hypertension, and hospitals that were either private, large, Northeastern location, or with high cardiac procedural volume. Conclusions Analyzing 11-year data from a national inpatient database demonstrate a number of relevant variables that impact PM utilization that include not only clinical but also nonclinical variables such as socioeconomic status, gender, and hospital features. Racial and gender bias toward PM implantation are unchanged and persist through 2013. This article is protected by copyright. All rights reserved

Importance Severe mitral valve insufficiency (MR) is managed using mitral valve replacement or repair. Transcatheter mitral valve repair (TMVR) is an emerging non-invasive treatment option for MR. Cancer patients stand to benefit from non-invasive treatment of MR given the nature of this intervention. Objective:We sought to assess the relative utilization, outcomes, and dispositions associated with TMVR vs. surgical mitral valve procedures (SMVP) in cancer patients. Methods The 2012–2015 National Inpatient Sample, a retrospective observational study was queried using ICD-9 codes for adults >18 years with comorbid MR (ICD-9 – 424.0) and cancer without metastatic disease. To maintain a homogenous study population and to limit confounding, those with mitral stenosis, rheumatic disease, infective endocarditis, aortic valve disease, or those undergoing any other vascular or cardiac surgery in the same admission were excluded from the analysis. Multiple in-hospital and disposition outcomes were evaluated. Since the baseline population undergoing SMVP (ICD-9: 35.23, 35.24, 35.12) is quite different from TMVR (ICD-9: 35.97), parallel analyses for outcomes and dispositions were presented but no direct statistical comparisons. Results A total of 410,175 out of 2,449,010 patients with mitral insufficiency were found to have non-metastatic cancer (16.7%). A total of 3,600 TMVR procedures were performed during the study period. Over the study period, there has been an increase in the proportion of patients undergoing TMVR among all patients undergoing mitral valve procedures (figure). The increase is higher in cancer patients in the most recent year (14.2% vs. 8.2%, p TMVR percent in mitral valve procedures Conclusion TMVR utilization for MR in cancer has steadily increased in both cancer and non-cancer patients, although it is proportionately higher among cancer patients in recent years. Overall, TMVR was associated with low in-hospital mortality and a similar safety profile in cancer and non-cancer patients, while SMVP appears to have a slightly worse safety profile in cancer patients. Our findings, suggest that TMVR is a reasonable strategy in selective cancer patients with MR.

Importance Cancer patients with severe AS are often ineligible for surgical aortic valve replacement (SAVR). Transcatheter aortic valve replacement (TAVR) is an emerging non-invasive treatment option for severe AS. Cancer patients likely stand to benefit from TAVR given its non-invasive nature; however, there is a paucity of data regarding the comparative effectiveness of TAVR vs. SAVR in cancer. We sought to assess the relative utilization, outcomes, and dispositions associated with TAVR vs. SAVR in cancer and non-cancer patients. Methods The US-based National Inpatient Sample was queried between 2012 and 2015 using ICD-9 codes for adults>18 years with comorbid AS and cancer without metastatic disease. Multiple in-hospital and disposition outcomes were evaluated. Comparison of TAVR vs SAVR required propensity score estimation using demographic, socio-economic, comorbidity, and hospital specific variables. A standardized morbidity ratio (SMR) weight was calculated by assigning TAVR a weight of 1, and those undergoing SAVR weight of PS/(1-PS). SMR-weighted generalized logistic regression was conducted to estimate the average effect of TAVR compared with SAVR. Finally, the Cochran–Mantel–Haenszel (CMH) test for propensity-matched data was utilized to compare the effect modification of cancer on these outcomes. Results A total of 979,912 out of 5,611,173 patients with AS were found to have non-metastatic cancer (17.5%). Average Elixhauser's mortality score of patients undergoing TAVR and SAVR was 8.9 vs. 8.1 and 8.5 vs. 7.1 for cancer vs. non-cancer respectively (p Conclusions Compared to patients without cancer, the utilization of AVR in cancer patients has steadily increased. The benefits of TAVR over SAVR appear to extend to patients, regardless of cancer status. TAVR might be a more suitable procedure for cancer patients with AS.

There is a growing body of evidence that diabetes represents a significant and largely modifiable risk factor for cardiovascular disease (CVD). It is known to markedly increase the risk of CVD—with CVD accounting for 2 of every 3 deaths in patients with diabetes. It is suggested that once patients with diabetes develop clinical coronary disease, they have a grim prognosis. In 2008, the Food and Drug Association mandated the evidence of CV safety in any new diabetic therapy, leading to a multitude of large CV outcome trials to assess CV risk from these medications. However, several of these outcome trials with novel antidiabetic therapies have demonstrated not only safety but a clear and definite CV advantage in patients with type 2 diabetes. In this review, we discuss 2 relatively newer classes of diabetic drugs, sodium glucose cotransport 2 inhibitors and glucagon-like peptide 1 agonists, evaluate their efficacy in improving CV outcomes, and discuss the future of CV prevention with these agents.

Determine whether the CHAThe 2014 National Readmissions Database was analyzed to identify readmissions following the index hospitalization for AF and CV. A CHAA total of 109,420 weighted index admissions for AF and CV were identified in between January 1, 2014, and November 30, 2014. Of these, 16,535 (15.1%) had a CHAThis study demonstrated the utility of CHA

Supplemental material, WSO895709 Supplemental Material for Contemporary utilization patterns and outcomes of thrombolytic administration for ischemic stroke among patients with cancer by Jocelyn Owusu-Guha, Avirup Guha, P Elliott Miller, Sumeet Pawar, Amit K Dey, Tariq Ahmad, Hatim Attar, Farrukh T Awan, Darrion Mitchell, Nihar R Desai and Daniel Addison in International Journal of Stroke

Background Octogenarians have low physiologic reserve and may benefit more from transcatheter aortic valve replacement (TAVR) than surgical aortic valve replacement (SAVR). Methods and Results This retrospective cohort study based on the National Inpatient Sample included octogenarians who underwent TAVR or SAVR from 2012 to 2015. Crude and standardized‐morbidity‐ratio‐weighted regression models were used to compare in‐hospital outcomes. Among 19 145 TAVR and 9815 SAVR hospitalizations, TAVR patients had higher Charlson Comorbidity Index (CCI) scores (2.0 versus 0.8, P, See Editorial by Himbert et al

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in < 1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%.

e15100 Background: Immune checkpoint inhibitors (ICIs) can cause unique, high-grade immune-related adverse events. Although rare, ICI related myocarditis has the highest fatality rate (~50%). Cardiovascular monitoring is not routinely performed in patients on ICI treatment, thus risk factors remain unknown. Characterizing rare but fatal cardiac toxicities requires integration of real-world data. Methods: U.S claims data (IBM MarketScan) of over 30 million commercially insured individuals was leveraged to identify 2,687,301 cancer patients between 2011-2018. Patients ≥18 years of age treated with ICIs (targeting CTLA4 (ipilimumab) and/or the PD1 (nivolumab, pembrolizumab)/PDL1 (atezolizumab, avelumab, durvalumab) alone or in combination with ICI and/or chemotherapy were identified and followed until disenrollment. Myocarditis, comorbidities, and treatment details were identified using diagnosis and billing codes. Analyses included descriptive statistics and Cox proportional hazards regression. Results: 16,541 ICI treated cancer patients were included (median age 60; 58% male). Myocarditis was identified in 252 (1.5%) patients, majority (90%) ≥50 years old (median 63) with 12,040 person-years of follow up. 62% received anti-PD1 monotherapy, 12% anti-CTLA4, and 15% received combination treatment with other ICIs and/or chemotherapy. Most common cancer types were lung (48%), melanoma (25%), and renal cancer (14%). Cumulative incidence of myocarditis at 1 year was 2.06%; 95% CI (1.78-2.37), median onset of 80.5 days, 42% occurring within 60 days of treatment. By univariate analyses, age, cancer type, diabetes (DM), hypertension (HTN), kidney, liver disease, atrial fibrillation (AF) were related to myocarditis. Risk was lower in patients who received anti-CTLA4 monotherapy (HR: 0.490; 95% CI: 0.26-0.92; p = 0.0251). On multivariable regression analyses only age, cancer type (renal, lung cancer), comorbidities DM and liver disease were significantly associated with myocarditis (Table). Conclusions: This is the largest real-world longitudinal study for ICI associated myocarditis showing higher than reported incidence and identifiable risk factors. [Table: see text]

Introduction CART-cell therapy is associated with dramatic efficacy in patients with relapsed/refractory diffuse large B-cell lymphoma and B-acute lymphoblastic leukemia. However, the efficacy of CART therapy is limited by potentially fatal toxicities including cytokine release syndrome (CRS) and neurotoxicity. Increasingly, emerging reports have suggested the potential for significant hemodynamic collapse following CART therapy. Yet, whether the occurrence of these hemodynamic shifts or any other cardiovascular disease (CVD) events have bearing on clinical outcomes after CART initiation is unknown. Methods We evaluated all patients treated with CART therapy for lymphoid malignancies at The Ohio State University James Comprehensive Cancer Center between 2016-2019 and assessed the incidence of CVD events and severe hemodynamic collapse [systolic blood pressure (SBP) cutoff of less than 80 mmHg]. We also evaluated the relationship of CVD events, hemodynamic collapse, and the presence of preceding CVD on overall survival (OS) and progression-free-survival (PFS) following infusion of CART cells utilizing univariate log-rank comparison. Results We evaluated 66 patients with 62% male and 38% female with an average age of 60 years (range 23-80). 49 (74%) patients received Yescarta and 17 (26%) patients received Kymriah. With a median follow-up time of 21 months, OS and PFS at 1 year were 72% and 43%, respectively, in concordance with previously reported ZUMA1 and JULIET survival rates. Overall, from 66 CART-treated patients, 14 (21.2%) developed incident CVD events, including 11 patients with arrhythmias and 2 with CHF. The median decrease in peak systolic blood pressure after infusion was 32 mmHg (IQR 22-47 mmHg), noted at a median of 4 days post-CART. Furthermore, after infusion, 17 (25.8%) saw falls in systolic pressure to Conclusion The development of significant early hypotension is associated with a marked decrease in survival among patients receiving CART therapy. Further understanding of this finding, and its relation to CRS is urgently needed in order to maximize the effectiveness of this novel anticancer therapy.

BRAF and MEK inhibitors have revolutionized the treatment of melanoma, lung and colon cancers. Recent reports suggest increased cardiovascular toxicity with the combination (BRAF/MEK inhibition) therapy but large-scale post-marketing data is lacking. We used the FDA adverse events reporting system

Chimeric Antigen Receptor (CAR-T) cell therapy is approved in the US for treatment of Leukemias/Lymphomas. Multiple cardiovascular adverse events (CVAE) after CAR-T have been noted in small studies. We used the FDA adverse events reporting system (FAERS) to identify all reported adverse events (AEs

There have been significant advances in the field of oncology leading to improved survival as a result of novel targeted and immunotherapies. Despite these improved outcomes, there is increased recognition of cardiotoxicities associated with these therapies that can lead to significant morbidity and mortality. As such, the field of cardio-oncology has seen significant growth over the last several years. In this review, we discuss recent advances in the field of cardio-oncology and provide a detailed discussion of the cardiovascular complications associated with novel cancer therapeutics including tyrosine kinase inhibitors, proteasome inhibitors, histone deacetylase inhibitors, CDK4/6 inhibitors and immunotherapies.

Atrial fibrillation (AF) has been reported in up to 16% of patients taking ibrutinib. Data regarding the management of AF in this patient population are limited, and stroke prevention poses a challenge because of increased risk of bleeding with ibrutinib treatment. Our study sought to describe the incidence of AF in adult patients treated with ibrutinib for a hematologic malignancy, assess management strategies, evaluate stroke and bleeding outcomes, and identify risk factors for occurrence. Of 582 patients treated with ibrutinib, 76 developed AF. With a median follow-up of 32 months, the estimated cumulative incidence at 6 months, 1 year, and 2 years was 5.9% (95% confidence interval [CI]: 4.2-8.0), 7.5% (95% CI: 5.5-9.9), and 10.3% (95% CI: 8.0-13.0), respectively. Median time to onset of AF was 7.6 months. History of AF and Framingham Heart Study (FHS) AF risk score were found to be significant risk factors for development of AF. Most patients were treated with rate control-only strategies (61.8%), and concomitant aspirin or anticoagulant therapy with ibrutinib was used in 52.6% and 28.9% of patients, respectively. One patient on aspirin developed symptoms consistent with stroke. Nine major bleeds were noted in 7 patients, and 34 clinically relevant nonmajor bleeds were noted in 24 patients. Twenty-one bleeds (4 major bleeds) occurred in 18 patients on aspirin, and 10 bleeds (all clinically relevant nonmajor bleeds) occurred in 6 patients with anticoagulant therapy. These results provide risk factor assessment, impact of management strategies, and outcomes of patients with AF on ibrutinib and serve as basis for formal guidelines.

Ibrutinib is a new Bruton’s tyrosine kinase inhibitor associated with improvements in the outcomes of various B-cell hematologic malignancies and is now standard lifelong therapy in those without intolerance or disease progression [(1)][1]. However, there is a >4-fold increased risk of incident

Cardiovascular disease (CVD) is common among new cancer patients. Cancer patients with concurrent CVD have poorer outcomes. Despite the high prevalence of CVD and its prognostic significance, there is limited evidence to guide CVD care and monitoring during cancer treatment. Clinical trials of new

Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury. In addition, we will attempt to point out areas of current controversy, as well as propose areas in which further experimental studies are likely to move the field forward. The content of the following review was presented as part of the Water and Electrolyte Homeostasis Section New Investigator Award talk at Experimental Biology 2014.

Background Ibrutinib (IB), a nonselective Bruton's tyrosine kinase inhibitor, is associated with significantly improved disease control rates, progression free, and overall survival in several B-cell malignancies. Yet, IB's nonselective actions may result in a number of unintended adverse effects and complications that can lead to drug discontinuation. New or worsening hypertension (HTN) has been reported in 10-29% of those receiving IB within clinical trials. However, recent observational data suggest that this rate may be much higher in clinical practice and resistant to treatment. The management of IB-related HTN has not been previously well described. Furthermore, the relationship between IB-associated HTN and serious cardiovascular (CV) complications is unknown. Therefore, we sought to characterize the incidence, risk factors, management, and CV complications associated with IB-related HTN across long-term follow-up. Methods We performed a retrospective, single-center cohort study of all consecutive adult patients treated with IB for a hematologic malignancy from 2009-2016. Patient demographics, blood pressure (BP), antihypertensive therapy, cancer variables, and CV complications were collected throughout the duration of IB therapy. HTN was defined as systolic BP of ≥ 130 mmHg on 2 separate visits within 3 months. Worsened HTN was defined as an increase in HTN grade by Common Terminology Criteria for Adverse Events (CTCAE) or an increase an antihypertensive therapy. The composite of major adverse CV endpoint (MACE), including atrial fibrillation, ventricular arrhythmia, myocardial infarction, cerebrovascular accident, heart failure, and CV death, as stratified by HTN status was assessed. Univariate and multivariate Fine and Gray regression analyses accounting for competing risks of death and IB-discontinuation were preformed to determine the association between baseline covariates and outcomes, and survival analysis techniques were used to estimate the cumulative incidence of events. To assess whether any antihypertensive agent(s) was more effective in preventing IB-related HTN, the use of these agents at baseline was assessed by class, as protective factors against worsened HTN. Results Overall, 562 patients treated with IB were identified, a majority of which had CLL (73%) and were male (70%); mean age 64 ± 11 years. Sixty-two percent had preexisting HTN at the time of starting IB with 35% requiring at least one antihypertensive medication. During follow-up, 440 (78%) developed new or worsening HTN (figure 1A), with a mean increase in systolic BP of 5.2 mmHg (± 20.7). In those without baseline HTN, 72% developed new HTN while on IB, with a mean increase in systolic BP of 13.4 mmHg (± 20.1). Among patients with preexisting HTN, 82% saw worsening of their BP (mean increase in systolic BP of 4.1 mmHg (± 21.4)), including increased CTCAE grade in 77% and new antihypertensive medications in 46% of patients. Estrogen/progestin use [HR 3.47, 95% CI (1.25-9.64)] and history of diabetes [HR 1.66, 95% CI (1.03-2.66)] were risk factors for new, but not worsened HTN on multivariable analysis. MACE occurred in 19.1% of patients with new or worsened HTN, compared to 8.2% of patients with no HTN (figure 1B). In a multivariable model containing traditional HTN risk factors, new or worsened HTN was not significantly associated with MACE [HR 1.98, 95% CI (0.74-5.31)]. No specific class of antihypertensive agent was associated with the prevention of worsened HTN. Conclusion In this retrospective study, IB-therapy was associated with a substantial increase in the incidence and severity of HTN. Further research into the mechanisms, early detection strategies, optimal management, and clinical impacts of this complication are needed. Disclosures No relevant conflicts of interest to declare.

Ant Colony Optimization (ACO) is a nature-inspired swarm intelligence technique and a metaheuristic approach which is inspired by the foraging behavior of the real ants, where ants release pheromones to find the best and shortest route from their nest to the food source. ACO is being applied to various optimization problems till date and has been giving good quality results in the field. One such popular problem is known as Vehicle Routing Problem(VRP). Among many variants of VRP, this paper presents a comprehensive survey on VRP with Time Window constraints(VRPTW). The survey is presented in a chronological order discussing which of the variants of ACO is used in each paper followed by the advantages and limitations of the same.

Hospital outcomes in women with adult congenital heart disease (ACHD) are poorly understood. We aimed to define cardiovascular risk factors (CVRF) and major adverse cardiovascular events (MACE) in ACHD. Men and women with ACHD ≥18 years old in the National Inpatient Sample (2003-2014) were

Background: Non—ST-segment elevation myocardial infarction (NSTEMI) comprises the majority of MI worldwide, yet mortality remains high. Management of NSTEMI is relatively delayed and heterogeneous compared with the “time is muscle” approach to ST-segment elevation MI, though it is unknown to what extent comorbid conditions drive NSTEMI mortality.Objectives: We sought to quantify mortality due to MI versus comorbid conditions in patients with NSTEMI.Methods: Participants of the ARIC (Atherosclerosis Risk in Communities) study cohort ages 45 to 64 years, who developed incident NSTEMI were identified and incidence-density matched to participants who did not experience an MI by age group, sex, race, and study community. We estimated hazard ratios for all-cause mortality, comparing those who developed NSTEMI to those who did not experience an MI.Results: ARIC participants with incident NSTEMI were more likely at baseline to be smokers, have diabetes and renal dysfunction, and take blood pressure or cholesterol-lowering medications than were participants who did not have an MI. Over one-half of participants experiencing NSTEMI died over a median follow-up of 8.4 years; incident NSTEMI was associated with 30% higher risk of mortality after adjusting for comorbid conditions (hazard ratio: 1.30; 95% confidence interval: 1.11 to 1.53).Conclusions: NSTEMI confers a significantly higher mortality hazard beyond what can be attributed to comorbid conditions. More consistent and effective strategies are needed to reduce mortality in NSTEMI amid comorbid conditions.HighlightsThis is the first study which uses long-term follow-up data of a clinical national dataset (ARIC) to find hazards of mortality conferred by NSTEMI event after controlling for a majority of comorbid conditions.NSTEMI confers a 30% higher risk of mortality beyond what can be attributed to comorbid conditions.Recognition that the myocardial injury event itself contributes to excess risk of subsequent death should motivate strategies that limit myocardial damage in patients with NSTEMI similar to management of STEMI.