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Abstract The protein corona formed on nanoparticles (NPs) has potential as a valuable diagnostic tool for improving plasma proteome coverage. Here, we show that spiking small molecules, including metabolites, lipids, vitamins, and nutrients into plasma can induce diverse protein corona patterns on otherwise identical NPs, significantly enhancing the depth of plasma proteome profiling. The protein coronas on polystyrene NPs when exposed to plasma treated with an array of small molecules allows for the detection of 1793 proteins marking an 8.25-fold increase in the number of quantified proteins compared to plasma alone (218 proteins) and a 2.63-fold increase relative to the untreated protein corona (681 proteins). Furthermore, we discovered that adding 1000 µg/ml phosphatidylcholine could singularly enable the detection of 897 proteins. At this specific concentration, phosphatidylcholine selectively depletes the four most abundant plasma proteins, including albumin, thus reducing the dynamic range of plasma proteome and enabling the detection of proteins with lower abundance. Employing an optimized data-independent acquisition approach, the inclusion of phosphatidylcholine leads to the detection of 1436 proteins in a single plasma sample. Our molecular dynamics results reveal that phosphatidylcholine interacts with albumin via hydrophobic interactions, H-bonds, and water bridges. The addition of phosphatidylcholine also enables the detection of 337 additional proteoforms compared to untreated protein corona using a top-down proteomics approach. Given the critical role of plasma proteomics in biomarker discovery and disease monitoring, we anticipate the widespread adoption of this methodology for the identification and clinical translation of biomarkers.

We present the results of the human genomic small variant calling benchmarking initiative of the German Research Foundation (DFG) funded Next Generation Sequencing Competence Network (NGS-CN) and the German Human Genome-Phenome Archive (GHGA). In this effort, we developed NCBench, a continuous benchmarking platform for the evaluation of small genomic variant callsets in terms of recall, precision, and false positive/negative error patterns. NCBench is implemented as a continuously re-evaluated open-source repository. We show that it is possible to entirely rely on public free infrastructure (Github, Github Actions, Zenodo) in combination with established open-source tools. NCBench is agnostic of the used dataset and can evaluate an arbitrary number of given callsets, while reporting the results in a visual and interactive way. We used NCBench to evaluate over 40 callsets generated by various variant calling pipelines available in the participating groups that were run on three exome datasets from different enrichment kits and at different coverages. While all pipelines achieve high overall quality, subtle systematic differences between callers and datasets exist and are made apparent by NCBench.These insights are useful to improve existing pipelines and develop new workflows. NCBench is meant to be open for the contribution of any given callset. Most importantly, for authors, it will enable the omission of repeated re-implementation of paper-specific variant calling benchmarks for the publication of new tools or pipelines, while readers will benefit from being able to (continuously) observe the performance of tools and pipelines at the time of reading instead of at the time of writing.

Background Cardiovascular disease (CVD) and cancer frequently co‐occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management. Methods and Results Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed. The cohort included 5127 participants with incident CVD (myocardial infarction, stroke, heart failure, coronary heart disease), of whom 1511 developed a first primary cancer. Follow‐up began at CVD diagnosis after Visit 1. Obesity was assessed using body mass index, waist circumference, and waist‐to‐hip ratio. Incidence rate differences between obesity groups were adjusted for age, sex, and center, whereas the obesity–cancer association was estimated using Fine‐Gray regression adjusted for shared risk factors including smoking. Cancer incidence in obese individuals with CVD (body mass index: rate differences=226.6/100 000 person‐years) was higher than in those with normal weight. Although obesity was not linked to overall cancer after adjusting for shared risk factors, it was nominally associated with obesity‐related cancers. Specifically, women with CVD and obesity had increased obesity‐related cancer risk (body mass index: hazard ratio, 1.67 [95% CI, 1.17–2.31]). No significant associations were found in men, even after excluding prostate cancer. Conclusions This study suggests that obesity is linked to higher obesity‐related cancer risk in women with incident CVD, independent of shared risk factors. Further research is needed to eliminate residual confounding, understand sex differences, and explore how CVD pathophysiologies and obesity together influence cancer risk.

Background: Cancer survivors face an elevated risk of cardiovascular disease (CVD) and cardiovascular disease mortality (CVDm) compared to the general population. Allostatic load (AL), a composite score reflecting cardiovascular, metabolic, and immune markers, assesses the cumulative impact of chronic stress and life events. Increased AL in cancer patients is linked to up to a 30 % higher CVD risk. We hypothesized that cancer diagnosis and therapy contribute to increased AL, mediating the association between cancer survivorship and CVDm. Methods: This retrospective cohort study analyzed National Health and Nutrition Examination Survey (NHANES) data linked with the National Death Index (NDI) from 1988 to 2019. Cancer survivorship (yes vs. no), AL, and CVDm were the exposure, mediator, and outcome variables, respectively. Mediation analyses adapted to survival outcomes were performed. Results: Among 14,416 participants, cancer survivors

Background Both cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Although our previous study detected a relationship between CVD and cancer incidence, limited evidence is available regarding the relationship between CVD, cardiovascular risk factors, and cancer mortality. Methods and Results A prospective cohort study using data from the continuous NHANES (National Health and Nutrition Examination Survey, 1999–2016) merged with Medicare and National Death Index mortality data, through December 31, 2018. We included individuals with no history of cancer at baseline. The primary exposure was CVD at baseline. We also conducted a comprehensive risk factor analysis as secondary exposure. The main outcome was cancer mortality data collected from Medicare and National Death Index. We included 44 591 adult individuals representing 1 738 423 317 individuals (52% female, 67% non‐Hispanic White, and 9% Hispanic). Competing risk modeling showed a significantly higher risk of cancer mortality in individuals with CVD (adjusted hazard ratio [aHR], 1.37 [95% CI 1.07–1.76], P=0.01) after adjusting for age, sex, and race and ethnicity. Notably, cancer mortality increased with aging (aHR, 1.08 [95% CI 1.05–1.11], P

Background: Evidence regarding the effect of long-term exposure to particulate matter (PM) 2.5 and comorbid cancer and cardiovascular disease (CVD) mortality is limited. Objectives: In this study, the author report the association between long-term exposure to PM 2.5 and CVD mortality, cancer mortality and comorbid cancer and CVD mortality in the U.S. population. Methods: The Centers for Disease Control and Prevention (CDC) WONDER (Wide-Ranging Online Data for Epidemiologic Research) multiple-cause-of-death database was used to obtain U.S. county-level mortality and population estimates from 2016 to 2020. Data on average daily density of PM 2.5 were abstracted from the 2018 CDC’s National Environmental Public Health Tracking system. Counties were divided into quartiles with Q1 representing counties with least average daily density and Q4 representing counties with maximum average daily density of PM 2.5. Age-adjusted mortality rates were abstracted for each quartile, for the overall population and subgroups of population. Results: The age-adjusted mortality rates for CVD, cancer, and comorbid cancer and CVD mortality were 505.3 (range: 505.0-505.7), 210.7 (range: 210.5-210.9), and 62.0 (range: 61.8-62.1) per 100,000 person-years, respectively. CVD mortality had the highest percentage excess mortality in Q4 compared with Q1, followed by comorbid cancer and CVD. Cancer had the least percentage excess mortality. A disproportionate effect of PM 2.5 exposure was noted on vulnerable and minority groups, based on Social Vulnerability Index and race stratification, respectively. Conclusions: Higher levels of long-term PM 2.5 exposure reported increased CVD mortality, cancer mortality and comorbid cancer and CVD disease mortality, with a pronounced detrimental effect in vulnerable and minority population.

Background Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1‐point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. Methods and Results Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010–2019) and followed up at a large, hybrid academic‐community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0–11). Adjusted Fine–Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2‐year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1‐point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06–1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12–1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08–1.19]). When considering AL as a time‐varying exposure, the peak associated MACE risk occurred with a 1‐point AL rise between 6 and 12 months post‐ breast cancer, lung cancer, and colorectal cancer diagnosis. Conclusions AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

Abstract Aims Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. Methods and results This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6 months after implantation were included. Among 10 717 patients, 1369 received CCBs 6 months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6 months had a similar 5 year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5–51.7% vs. 51.1%, 95% CI: 45.3–56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6 months after implantation was not associated with long‐term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91–1.17, P = 0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95–1.22, P = 0.260]. Consistently, in time‐varying models, CCB treatment was not linked to long‐term mortality (HR: 0.97, 95% CI: 0.87–1.09, P = 0.682 and SHR: 1.05, 95% CI: 0.94–1.18, P = 0.359). This null association remained in subgroup analysis according to device strategy and propensity‐matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. Conclusions In patients with LVAD, CCB therapy fails to show benefits in long‐term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

Introduction: This study aimed to investigate the relationship between risk factors of cancer among individuals with existing cardiovascular disease (CVD). Methods: The analysis included 438 and 2100 CVD patients aged 65+ from NHANES-III and Continuous datasets, respectively. Competing risk models with subdistribution hazards ratio (aHR) were used to identify risk factors. Results: Females in NHANES-III had lower cancer risk (aHR 0.39, P = 0.001) compared to males. Poor physical activity was associated with increased cancer risk in both datasets (aHR 2.59 in NHANES-III, aHR 1.59 in Continuous). In NHANES-Continuous, age (aHR 1.07, P

As cancer therapies increase in effectiveness and patients' life expectancies improve, balancing oncologic efficacy while reducing acute and long-term cardiovascular toxicities has become of paramount importance. To address this pressing need, the Cardiology Oncology Innovation Network (COIN) was formed to bring together domain experts with the overarching goal of collaboratively investigating, applying, and educating widely on various forms of innovation to improve the quality of life and cardiovascular healthcare of patients undergoing and surviving cancer therapies. The COIN mission pillars of innovation, collaboration, and education have been implemented with cross-collaboration among academic institutions, private and public establishments, and industry and technology companies. In this report, we summarize proceedings from the first two annual COIN summits (inaugural in 2020 and subsequent in 2021) including educational sessions on technological innovations for establishing best practices and aligning resources. Herein, we highlight emerging areas for innovation and defining unmet needs to further improve the outcome for cancer patients and survivors of all ages. Additionally, we provide actionable suggestions for advancing innovation, collaboration, and education in cardio-oncology in the digital era.

Abstract Background Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. Methods Leveraging two large U.S.‐based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension‐related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting‐odds‐ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug‐class, and individual drugs with the likelihood of excess hypertension. Results Overall, there were 5,464,401 BC‐admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in‐hospital mortality, which equilibrated over time. The mean incidence of hypertension‐related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non‐cancer patients (RR 7.71, p

Background Cyclin‐dependent kinase (CDK) 4 and 6 inhibitors have significantly improved survival in patients with hormone receptor–positive metastatic breast cancer. There are few data regarding the epidemiology of cardiovascular adverse events (CVAEs) with these therapies. Methods and Results Using the OneFlorida Data Trust, adult patients without prior cardiovascular disease who received at least 1 CDK4/6 inhibitor were included in the analysis. CVAEs identified from International Classification of Diseases, Ninth and Tenth Revisions (ICD‐9/10) codes included hypertension, atrial fibrillation(AF)/atrial flutter (AFL), heart failure/cardiomyopathy, ischemic heart disease, and pericardial disease. Competing risk analysis (Fine–Gray model) was used to determine the association between CDK4/6 inhibitor therapy and incident CVAEs. The effect of CVAEs on all‐cause death was studied using Cox proportional hazard models. Propensity‐weight analyses were performed to compare these patients to a cohort of patients treated with anthracyclines. A total of 1376 patients treated with CDK4/6 inhibitors were included in the analysis. CVAEs occurred in 24% (35.9 per 100 person‐years). CVAEs were slightly higher in patients who received CKD4/6 inhibitors compared with anthracyclines (P=0.063), with higher death rate associated with the development of AF/AFL or cardiomyopathy/heart failure in the CDK4/6 group. The development of cardiomyopathy/heart failure and AF/AFL was associated with increased all‐cause death (adjusted hazard ratio [HR], 4.89 [95% CI, 2.98–8.05]; and 5.88 [95% CI, 3.56–9.73], respectively). Conclusions CVAEs may be more common with CDK4/6 inhibitors than previously recognized, with increased death rates in these patients who develop AF/AFL or heart failure. Further research is needed to definitively determine cardiovascular risk associated with these novel anticancer treatments.

Abstract Background The aim of this study is to assess the burden of AF-related hospitalizations inclusive of inflation-adjusted cost-of-care and length-of-stay (LOS) among cancer patients and the impact of direct current cardioversion (DCCV) on these outcomes. Methods Using the National Inpatient Sample (NIS), patients hospitalized with either a primary or secondary diagnosis of AF and comorbid cancer were identified and both cost of hospitalization and LOS were evaluated for each group. Subgroup analyses were performed for specific cancer types (breast, lung, colon, prostate and lymphoma), and those receiving DCCV. Results The prevalence of co-morbid AF was 8.2 million (16%) and 35.5 million (10%) among those with vs. those without cancer, respectively (odds ratio = 1.6, 95% confidence interval = 1.5–1.7; P

Background Anthracyclines remain a key treatment for many malignancies but can increase the risk of heart failure or cardiomyopathy. Specific guidelines recommend echocardiography and serum cardiac biomarkers such as BNP (B‐type natriuretic peptide) or NT‐proBNP (N‐terminal proBNP) evaluation before and 6 to 12 months after treatment. Our objective was to evaluate associations between racial and ethnic groups in cardiac surveillance of survivors of cancer after exposure to anthracyclines. Methods and Results Adult patients in the OneFlorida Consortium without prior cardiovascular disease who received at least 2 cycles of anthracyclines were included in the analysis. Multivariable logistic regression was performed to estimate the odds ratios (ORs) and 95% CIs for receiving cardiac surveillance at baseline before anthracycline therapy, 6 months after, and 12 months after anthracycline exposure among different racial and ethnic groups. Among the entire cohort of 5430 patients, 63.4% had a baseline echocardiogram, with 22.3% receiving an echocardiogram at 6 months and 25% at 12 months. Non‐Hispanic Black (NHB) patients had a lower likelihood of receiving a baseline echocardiogram than Non‐Hispanic White (NHW) patients (OR, 0.75 [95% CI, 0.63–0.88]; P=0.0006) or any baseline cardiac surveillance (OR, 0.76 [95% CI, 0.64–0.89]; P=0.001). Compared with NHW patients, Hispanic patients received significantly less cardiac surveillance at the 6‐month (OR, 0.84 [95% CI, 0.72–0.98]; P=0.03) and 12‐month (OR, 0.85 [95% CI, 0.74–0.98]; P=0.03) time points, respectively. Conclusions There were significant racial and ethnic differences in cardiac surveillance among survivors of cancer at baseline and following anthracycline‐based treatment in NHB and Hispanic cohorts. Health care providers need to be cognizant of these social inequities and initiate efforts to ensure recommended cardiac surveillance occurs following anthracyclines.

IntroductionPatients with systemic lupus erythematosus (SLE) are at elevated risk for Q10 cardiovascular disease (CVD) due to accelerated atherosclerosis. Compared to heathy control subjects, lupus patients have higher volumes and densities of thoracic aortic perivascular adipose tissue (PVAT), which independently associates with vascular calcification, a marker of subclinical atherosclerosis. However, the biological and functional role of PVAT in SLE has not been directly investigated.MethodsUsing mouse models of lupus, we studied the phenotype and function of PVAT, and the mechanisms linking PVAT and vascular dysfunction in lupus disease. Results and discussionLupus mice were hypermetabolic and exhibited partial lipodystrophy, with sparing of thoracic aortic PVAT. Using wire myography, we found that mice with active lupus exhibited impaired endothelium-dependent relaxation of thoracic aorta, which was further exacerbated in the presence of thoracic aortic PVAT. Interestingly, PVAT from lupus mice exhibited phenotypic switching, as evidenced by “whitening” and hypertrophy of perivascular adipocytes along with immune cell infiltration, in association with adventitial hyperplasia. In addition, expression of UCP1, a brown/beige adipose marker, was dramatically decreased, while CD45-positive leukocyte infiltration was increased, in PVAT from lupus mice. Furthermore, PVAT from lupus mice exhibited a marked decrease in adipogenic gene expression, concomitant with increased pro-inflammatory adipocytokine and leukocyte marker expression. Taken together, these results suggest that dysfunctional, inflamed PVAT may contribute to vascular disease in lupus.

Summary: Background: The COVID-19 pandemic highlighted gaps in health surveillance systems, disease prevention, and treatment globally. Among the many factors that might have led to these gaps is the issue of the financing of national health systems, especially in low-income and middle-income countries (LMICs), as well as a robust global system for pandemic preparedness. We aimed to provide a comparative assessment of global health spending at the onset of the pandemic; characterise the amount of development assistance for pandemic preparedness and response disbursed in the first 2 years of the COVID-19 pandemic; and examine expectations for future health spending and put into context the expected need for investment in pandemic preparedness. Methods: In this analysis of global health spending between 1990 and 2021, and prediction from 2021 to 2026, we estimated four sources of health spending: development assistance for health (DAH), government spending, out-of-pocket spending, and prepaid private spending across 204 countries and territories. We used the Organisation for Economic Co-operation and Development (OECD)'s Creditor Reporting System (CRS) and the WHO Global Health Expenditure Database (GHED) to estimate spending. We estimated development assistance for general health, COVID-19 response, and pandemic preparedness and response using a keyword search. Health spending estimates were combined with estimates of resources needed for pandemic prevention and preparedness to analyse future health spending patterns, relative to need. Findings: In 2019, at the onset of the COVID-19 pandemic, US$9·2 trillion (95% uncertainty interval [UI] 9·1–9·3) was spent on health worldwide. We found great disparities in the amount of resources devoted to health, with high-income countries spending $7·3 trillion (95% UI 7·2–7·4) in 2019; 293·7 times the $24·8 billion (95% UI 24·3–25·3) spent by low-income countries in 2019. That same year, $43·1 billion in development assistance was provided to maintain or improve health. The pandemic led to an unprecedented increase in development assistance targeted towards health; in 2020 and 2021, $1·8 billion in DAH contributions was provided towards pandemic preparedness in LMICs, and $37·8 billion was provided for the health-related COVID-19 response. Although the support for pandemic preparedness is 12·2% of the recommended target by the High-Level Independent Panel (HLIP), the support provided for the health-related COVID-19 response is 252·2% of the recommended target. Additionally, projected spending estimates suggest that between 2022 and 2026, governments in 17 (95% UI 11–21) of the 137 LMICs will observe an increase in national government health spending equivalent to an addition of 1% of GDP, as recommended by the HLIP. Interpretation: There was an unprecedented scale-up in DAH in 2020 and 2021. We have a unique opportunity at this time to sustain funding for crucial global health functions, including pandemic preparedness. However, historical patterns of underfunding of pandemic preparedness suggest that deliberate effort must be made to ensure funding is maintained. Funding: Bill & Melinda Gates Foundation.

Abstract Cardiovascular diseases and cancer continue to be the two leading causes of death in the United States. While innovations in artificial intelligence, digital health, and telemedicine may revolutionize cardio-oncology clinical practice, barriers to widespread adoption continue to exist. The most effective way to advance these technologies is through a broad range of stakeholders sharing a common vision. Additionally, as we enter the digital era in healthcare, we must help lead this charge for the benefit of our cardiology and oncology patients. Bolstering collaborations in cardiology and oncology is key, in partnership with technology firms, industry, academia, and private practice, with an emphasis on various forms of innovation. The ultimate goal is to connect our patients and their health to informatics-based opportunities to advance cardiovascular disease prevention in cancer patients. We have established the Cardiology Oncology Innovation Network in accordance with this vision, to develop new care delivery options through the use of innovative technological strategies. Our tripartite mission – innovation, collaboration, and education – aims to increase access to and expertise in digital transformation to prevent cardiovascular diseases in cancer patients. Here we describe network initiatives, early accomplishments, and future milestones.

BackgroundCardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes.ObjectivesTo assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy.MethodsBreast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed.Results116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease.ConclusionsIn our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

The relationship between bradyarrhythmias and cancer therapies has not been well described but is increasingly recognized. There have been extensive advances in oncological pharmacotherapy, with several new classes of drugs available including targeted agents, immune checkpoint inhibitors and CAR T cell therapy. This increasing repertoire of available drugs has revolutionized overall prognosis and survival of cancer patients but the true extent of their cardiovascular toxicity is only beginning to be understood. Previous studies and published reviews have traditionally focused on conventional chemotherapies and in arrhythmias in general, particularly tachyarrhythmias. The number of patients with both cancer and cardiovascular problems is increasing globally and oncologists and cardiologists need to be adept at managing arrythmia based scenarios. Greater collaboration between the two specialties including studies with prospective data collection in Cardio-Oncology are much needed to fill in knowledge gaps in this arena. This case-based review summarizes current available evidence of cancer treatment-related bradyarrhythmia incidence (including its different subtypes), possible mechanisms and outcomes. Furthermore, we propose a stepwise surveillance and management protocol for patients with suspected bradyarrhythmia related to cancer treatment.

The rapid emergence of cardio-oncology has resulted in a rapid growth of cardio-oncology programs, dedicated professional societies sections and committees, and multiple collaborative networks that emerged to amplify the access to care in this new subspecialty. However, most existing data, position statements and guidelines are limited by the lack of availability of large clinical trials to support these recommendations. Furthermore, there are significant challenges regarding proper access to cardio-oncology care and treatment, particularly in marginalized and minority populations. The emergence and evolution of personalized medicine, artificial intelligence (AI), and machine learning in medicine and in cardio-oncology provides an opportunity for a more targeted, personalized approach to cardiovascular complications of cancer treatment. The proper implementation of these new modalities may facilitate a more equitable approach to adequate and universal access to cardio-oncology care, improve health related outcomes, and enable health care systems to eliminate the digital divide. This article reviews and analyzes the current status on these important issues.

Abstract Aims Improved cancer survivorship has led to a higher number of anthracycline‐induced cardiomyopathy patients with end‐stage heart failure. We hypothesize that outcomes following continuous‐flow LVAD (CF‐LVAD) implantation in those with anthracycline‐induced cardiomyopathy are comparable with other aetiologies of cardiomyopathy. Methods and results Using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2008 to 2017, we identified patients with anthracycline‐induced cardiomyopathy who received a CF‐LVAD and compared them with those with idiopathic dilated (IDM) and ischaemic cardiomyopathies (ICM). Mortality was studied using the Cox proportional hazards model. Other adverse events were evaluated using competing risk models. Overall, 248 anthracycline‐induced cardiomyopathy patients underwent CF‐LVAD implantation, with a median survival of 48 months, an improvement compared with those before 2012 [adjusted hazards ratio (aHR): 0.53; confidence interval (CI): 0.33–0.86]. At 12 months, 85.1% of anthracycline‐induced cardiomyopathy, 86.0% of IDM, and 80.2% of ICM patients were alive (anthracycline‐induced cardiomyopathy vs. IDM: aHR: 1.12; CI: 0.88–1.43 and anthracycline‐induced cardiomyopathy vs. ICM: aHR: 0.98; CI: 0.76–1.28). Anthracycline‐induced cardiomyopathy patients had a higher major bleeding risk compared with IDM patients (aHR: 1.23; CI: 1.01–1.50), and a lower risk of stroke and prolonged respiratory support compared to ICM patients (aHR: 0.31 and 0.67 respectively; both P

Abstract Background Cardiovascular adverse events (CVAEs) associated with BRAF inhibitors alone versus combination BRAF/MEK inhibitors are not fully understood. Methods This study included all adult patients who received BRAF inhibitors (vemurafenib, dabrafenib, encorafenib) or combinations BRAF/MEK inhibitors (vemurafenib/cobimetinib; dabrafenib/trametinib; encorafenib/binimetinib). We utilized the cross‐sectional FDA’s Adverse Events Reporting System (FAERS) and longitudinal Truven Health Analytics/IBM MarketScan database from 2011 to 2018. Various CVAEs, including arterial hypertension, heart failure (HF), and venous thromboembolism (VTE), were studied using adjusted regression techniques. Results In FAERS, 7752 AEs were reported (40% BRAF and 60% BRAF/MEK). Median age was 60 (IQR 49–69) years with 45% females and 97% with melanoma. Among these, 567 (7.4%) were cardiovascular adverse events (mortality rate 19%). Compared with monotherapy, combination therapy was associated with increased risk for HF (reporting odds ratio [ROR] = 1.62 (CI = 1.14–2.30); p = 0.007), arterial hypertension (ROR = 1.75 (CI = 1.12–2.89); p = 0.02) and VTE (ROR = 1.80 (CI = 1.12–2.89); p = 0.02). Marketscan had 657 patients with median age of 53 years (IQR 46–60), 39.3% female, and 88.7% with melanoma. There were 26.2% CVAEs (CI: 14.8%–36%) within 6 months of medication start in those receiving combination therapy versus 16.7% CVAEs (CI: 13.1%–20.2%) among those receiving monotherapy. Combination therapy was associated with CVAEs compared to monotherapy (adjusted HR: 1.56 (CI: 1.01–2.42); p = 0.045). Conclusions and Relevance In two independent real‐world cohorts, combination BRAF/MEK inhibitors were associated with increased CVAEs compared to monotherapy, especially HF, and hypertension.

Study objective: Cancer and heart disease are leading causes of mortality, and cardio-oncology is emerging as a new field addressing the cardiovascular toxicities related to cancer and cancer therapy. Interdisciplinary research platforms that incorporate digital health to optimize cardiovascular health and wellness in cancer survivors are therefore needed as we advance in the digital era. Our goal was to develop the Connected Health Innovation Research Program (C.H.I.R.P.) to serve as a foundation for future integration and assessments of adoption and clinical efficacy of digital health tools for cardiovascular health and wellness in the general population and in oncology patients. Design/setting/participants: Partner companies were identified through the American Medical Association innovation platform, as well as LinkedIn and direct contact by our team. Company leaders met with our team to discuss features of their technology or software. Non-disclosure agreements were signed and data were discussed and obtained for descriptive or statistical analysis. Results: A suite of companies with technologies focused on wellness, biometrics tracking, audio companions, oxygen saturation, weight trends, sleep patterns, heart rate variability, electrocardiogram patterns, blood pressure patterns, real-time metabolism tracking, instructional video modules, or integration of these technologies into electronic health records was collated. We formed an interdisciplinary research team and established an academia-industry collaborative foundation for connecting patients with wellness digital health technologies. Conclusions: A suite of software and device technologies accessible to the cardiology and oncology population has been established and will facilitate retrospective, prospective, and case research studies assessing adoption and clinical efficacy of digital health tools in cardiology/oncology.

Breast cancer and heart failure share several known clinical cardiovascular risk factors, including age, obesity, glucose dysregulation, cholesterol dysregulation, hypertension, atrial fibrillation and inflammation. However, to fully comprehend the complex interplay between risk of breast cancer and heart failure, factors attributed to both biological and social determinants of health must be explored in risk-assessment. There are several social factors that impede implementation of prevention strategies and treatment for breast cancer and heart failure prevention, including socioeconomic status, neighborhood disadvantage, food insecurity, access to healthcare, and social isolation. A comprehensive approach to prevention of both breast cancer and heart failure must include assessment for both traditional clinical risk factors and social determinants of health in patients to address root causes of lifestyle and modifiable risk factors. In this review, we examine clinical and social determinants of health in breast cancer and heart failure that are necessary to consider in the design and implementation of effective prevention strategies that altogether reduce the risk of both chronic diseases

Cardiovascular disease is a leading cause of death in cancer survivors. It is critical to apply new predictive and early diagnostic methods in this population, as this can potentially inform cardiovascular treatment and surveillance decision-making. We discuss the application of artificial intelligence (AI) technologies to cardiovascular imaging in cardio-oncology, with a particular emphasis on prevention and targeted treatment of a variety of cardiovascular conditions in cancer patients. Recently, the use of AI-augmented cardiac imaging in cardio-oncology is gaining traction. A large proportion of cardio-oncology patients are screened and followed using left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), currently obtained using echocardiography. This use will continue to increase with new cardiotoxic cancer treatments. AI is being tested to increase precision, throughput, and accuracy of LVEF and GLS, guide point-of-care image acquisition, and integrate imaging and clinical data to optimize the prediction and detection of cardiac dysfunction. The application of AI to cardiovascular magnetic resonance imaging (CMR), computed tomography (CT; especially coronary artery calcium or CAC scans), single proton emission computed tomography (SPECT) and positron emission tomography (PET) imaging acquisition is also in early stages of analysis for prediction and assessment of cardiac tumors and cardiovascular adverse events in patients treated for childhood or adult cancer. The opportunities for application of AI in cardio-oncology imaging are promising, and if availed, will improve clinical practice and benefit patient care.

Purpose: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in cancer survivors, particularly after chest radiation therapy (RT). However, the extent to which CVD events are consistently reported in contemporary prospective trials is unknown. Methods and Materials: From 10 high-impact RT, oncology, and medicine journals, we identified all latter phase trials from 2000 to 2019 enrolling patients with breast, lung, lymphoma, mesothelioma, or esophageal cancer wherein chest-RT was delivered. The primary outcome was the report of major adverse cardiac events (MACEs), defined as incident myocardial infarction, heart failure, coronary revascularization, arrhythmia, stroke, or CVD death across treatment arms. The secondary outcome was the report of any CVD event. Multivariable regression was used to identify factors associated with CVD reporting. Pooled annualized incidence rates of MACEs across RT trials were compared with contemporary population rates using relative risks (RRs). Results: The 108 trials that met criteria enrolled 59,070 patients (mean age, 58.0 ± 10.2 years; 46.0% female), with 273,587 person-years of available follow-up. During a median follow-up of 48 months, 468 MACEs were reported (including 96 heart failures, 75 acute coronary syndrome, 1 revascularization, 94 arrhythmias, 28 strokes, and 20 CVD deaths; 307 occurred in the intervention arms vs 144 in the control arms; RR, 1.96; P < .001). Altogether, 50.0% of trials did not report MACEs, and 37.0% did not report any CVD. The overall weighted-trial incidence was 376 events per 100,000 person-years compared with 1408 events per 100,000 person-years in similar nontrial patients (RR, 0.27; P < .001). There were no RT factors associated with CVD reporting. Conclusion: In contemporary chest RT–based clinical trials, reported CVD rates were lower than expected population rates.

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.

CD19-specific chimeric antigen receptor (CAR) T cell therapies have shown remarkable early success in highly refractory and relapsing hematological malignancies. However, this potent therapy is accompanied by significant toxicity. Cytokine release syndrome and neurotoxicity are the most widely reported, but the true extent and characteristics of cardiovascular toxicity remain poorly understood. Thus far, adverse cardiovascular effects observed include sinus tachycardia and other arrhythmias, left ventricular systolic dysfunction, profound hypotension, and shock requiring inotropic support. The literature regarding cardiovascular toxicities remains sparse; prospective studies are needed to define the cardiac safety of CAR T cell therapies to optimally harness their potential. This review summarizes the current understanding of the potential cardiovascular toxicities of CD19-specific CAR T cell therapies, outlines a proposed cardiac surveillance protocol for patients receiving this new treatment, and provides a roadmap of the future direction of cardio-oncology research in this area.

BackgroundT2D is an increasingly common disease that is associated with worse outcomes in patients with heart failure. Despite this, no contemporary study has assessed its impact on heart transplantation outcomes. This paper examines the demographics and outcomes of patients with type 2 diabetes (T2D) undergoing heart transplantation.MethodsUsing the United Network for Organ Sharing (UNOS) database, patients listed for transplant were separated into cohorts based on history of T2D. Demographics and comorbidities were compared, and cox regressions were used to examine outcomes.ResultsBetween January 1st, 2011 and June 12th, 2020, we identified 9,086 patients with T2D and 23,676 without T2D listed for transplant. The proportion of patients with T2D increased from 25.2% to 27.9% between 2011 and 2020. Patients with T2D were older, more likely to be male, less likely to be White, and more likely to pay with public insurance (pConclusionsOver the last ten years, the proportion of heart transplant recipients with T2D has increased. These patients are more likely to be from traditionally underserved populations. Patients with T2D have a lower likelihood of transplantation and a higher likelihood of post-transplant mortality. After the allocation system change, likelihood of transplantation has improved for patients with T2D.

Objective Antimicrotubular agents are among the most commonly used classes of chemotherapeutic agents, but the risk of cardiovascular adverse events (CVAEs) remains unclear. Our objective was to study the CVAEs associated with antimicrotubular agents.Methods The Food and Drug Administration’s Adverse Event Reporting System was used to study CVAEs in adults from 1990 to 2020. Reported single-agent (only taxane or vinca alkaloid) CVAEs were compared with combination therapy (with at least one of the four major cardiotoxic drugs: anthracycline, HER2Neu inhibitors, tyrosine kinase inhibitors and checkpoint inhibitors) using adjusted polytomous logistic regression.Results Over 30 years, 134 398 adverse events were reported, of which 18 426 (13.4%) were CVAEs, with 74.1% due to taxanes and 25.9% due to vinca alkaloids. In 30 years, there has been a reduction in the proportion of reported CVAEs for taxanes from 15% to 11.8% (Cochran-Armitage P-trends

Background Patients with obesity and advanced heart failure face unique challenges on the path to heart transplantation. There are limited data on waitlist and transplantation outcomes in this population. We aimed to evaluate the impact of obesity on heart transplantation outcomes, and to investigate the effects of the new organ procurement and transplantation network allocation system in this population. Methods and Results This cohort study of adult patients listed for heart transplant used the United Network for Organ Sharing database from January 2006 to June 2020. Patients were stratified by body mass index (BMI) (18.5–24.9, 25–29.9, 30–34.9, 35–39.9, and 40–55 kg/m2). Recipient characteristics and donor characteristics were analyzed. Outcomes analyzed included transplantation, waitlist death, and posttransplant death. BMI 18.5 to 24.9 kg/m2 was used as the reference compared with progressive BMI categories. There were 46 645 patients listed for transplantation. Patients in higher BMI categories were less likely to be transplanted. The lowest likelihood of transplantation was in the highest BMI category, 40 to 55 kg/m2 (hazard ratio [HR], 0.19 [0.05–0.76]; P=0.02). Patients within the 2 highest BMI categories had higher risk of posttransplantation death (HR, 1.29; P

Cardiovascular disease (CVD) and cancer often occur in the same individuals, in part due to the shared risk factors such as obesity. Obesity promotes adipose inflammation, which is pathogenically linked to both cardiovascular disease and cancer. Compared with Caucasians, the prevalence of obesity is significantly higher in African Americans (AA), who exhibit more pronounced inflammation and, in turn, suffer from a higher burden of CVD and cancer-related mortality. The mechanisms that underlie this association among obesity, inflammation, and the bidirectional risk of CVD and cancer, particularly in AA, remain to be determined. Socio-economic disparities such as lack of access to healthy and affordable food may promote obesity and exacerbate hypertension and other CVD risk factors in AA. In turn, the resulting pro-inflammatory milieu contributes to the higher burden of CVD and cancer in AA. Additionally, biological factors that regulate systemic inflammation may be contributory. Mutations in atypical chemokine receptor 1 (ACKR1), otherwise known as the Duffy antigen receptor for chemokines (DARC), confer protection against malaria. Many AAs carry a mutation in the gene encoding this receptor, resulting in loss of its expression. ACKR1 functions as a decoy chemokine receptor, thus dampening chemokine receptor activation and inflammation. Published and preliminary data in humans and mice genetically deficient in ACKR1 suggest that this common gene mutation may contribute to ethnic susceptibility to obesity-related disease, CVD, and cancer. In this narrative review, we present the evidence regarding obesity-related disparities in the bidirectional risk of CVD and cancer and also discuss the potential association of gene polymorphisms in AAs with emphasis on ACKR1.

Background Racial and ethnic disparities contribute to differences in access and outcomes for patients undergoing heart transplantation. We evaluated contemporary outcomes for heart transplantation stratified by race and ethnicity as well as the new 2018 allocation system. Methods and Results Adult heart recipients from 2011 to 2020 were identified in the United Network for Organ Sharing database and stratified into 3 groups: Black, Hispanic, and White. We analyzed recipient and donor characteristics, and outcomes. Among 32 353 patients (25% Black, 9% Hispanic, 66% White), Black and Hispanic patients were younger, more likely to be women and have diabetes mellitus or renal disease (all, P

Background Heart failure (HF) and atrial fibrillation (AF) frequently coexist and may be associated with worse HF outcomes, but there is limited contemporary evidence describing their combined prevalence. We examined current trends in AF among hospitalizations for HF with preserved (HFpEF) ejection fraction or HF with reduced ejection fraction (HFrEF) in the United States, including outcomes and costs. Methods and Results Using the National Inpatient Sample, we identified 10 392 189 hospitalizations for HF between 2008 and 2017, including 4 250 698 with comorbid AF (40.9%). HF hospitalizations with AF involved patients who were older (average age, 76.9 versus 68.8 years) and more likely White individuals (77.8% versus 59.1%; P

Abstract Aims Heart failure (HF) outcomes continue to improve with widespread use of new therapies. Concurrently, cancer survival has dramatically improved. Yet whether cancer patients share similar strategies and outcomes of inpatient HF treatment to those without HF is unknown. We sought to assess the contemporary impacts of cancer on inpatient HF outcomes over time. Methods and results The retrospective National Inpatient Sample (2003–15) and National Readmissions Database (2013–14) registries were queried for adults admitted for HF and stratified for cancer status, excluding cases of metastatic disease. Temporal trends in HF admissions, hospital charge rates, length of hospitalization, HF‐related procedure utilization, in‐hospital mortality, and hospital readmissions were analysed. Over 13 years of follow‐up, there were 12 769 077 HF admissions (mean age 73 years, 50.8% female, 30.8% non‐White), among which 1 413 287 (11%) had a co‐morbid cancer diagnosis. Cancer patients were older, were predominantly male, and tended to be smokers. Over time, HF admission rates among cancer patients increased, despite a concurrent decrease among patients without cancer (P

BackgroundIn 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.MethodsThis 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.ResultsBetween 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 (pConclusionsAmong 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.

Abstract Coronavirus disease 2019 (COVID‐19) has emerged as a global pandemic and public health crisis. Increasing waves of intermittent infectious outbreaks have dramatically influenced care among broad populations. Over the past 2 decades, there has been a rapid increase in cancer survival, with >400 000 new survivors each year. The increasingly common presence of cardiovascular disease in patients during or after cancer treatment led to the rapid growth of the field of cardio‐oncology with a mandate of identifying, treating, and preventing the various forms of cardiovascular disease seen among this population. This review evaluates the implications of the pandemic on the practice and study of cardio‐oncology. The evolving understanding of the relationship between comorbid disease and clinical outcomes among this population is assessed. With the impetus of the pandemic, cardio‐oncology can be deliberate in embracing changes to cardiac screening, monitoring, and intervention during oncology care. Bridging 2 specialties, consideration of the lessons learned in cancer and cardiovascular may pivotally inform ongoing therapeutic efforts. Further, the development of multicenter registries focused on understanding and optimizing outcomes among these patients should be considered. Together, these insights may critically inform strategies for the care of cardio‐oncology patients in future phases of the COVID‐19 pandemic and beyond.

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 rateTAVR versus relative use rateSAVR, 67.8% versus 57.2%; P

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

Abstract: 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.

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