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Purpose of Review Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum. Recent Findings A recent meta-analysis shows utility for troponin in monitoring patients at risk for CTRC during cancer therapy. The role for natriuretic peptides is less clear but may be useful in patients receiving proteasome inhibitors. Early studies explore use of myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and others as novel biomarkers in CTRC. Summary Biomarkers have potential to identify subclinical CTRC and may reveal opportunities for early intervention. Further research is needed to elucidate optimal biomarkers and surveillance strategies.

A powered gravity assist around the sun, also known as an Oberth maneuver, has the potential to achieve a solar system escape velocity of 20 astronomical units (AUs) per year, which is desirable for an interstellar mission. Unfortunately, current heat shields and propulsion technology struggle to outperform an unpowered Jupiter gravity assist, let alone 20 AUs/year, due to unfavorable mass tradeoffs. We are therefore developing an unconventional approach that simultaneously addresses the need for high specific impulse and close proximity to the sun: convert the heat of the sun into usable thrust by passing a propellant through the heat shield. To demonstrate the concept of a combined heat shield and solar thermal propulsion system, we designed and fabricated a [Formula: see text] prototype and exposed it to a 20-sun solar simulator. The reflective yttria-stabilized zirconia coating and [Formula: see text] helium gas flow maintained a temperature of 339 K. With a dark chrome oxide coating facing the simulator, it generated 1.3 N of thrust at a flow rate of [Formula: see text] and a temperature of 516 K. The agreement between theory and the experiment suggests that an escape velocity of 15 AUs/year is attainable at a mass ratio of two and a perihelion of 2.5 solar radii.

Oxaliplatin is a platinum-based alkylating chemotherapeutic agent used for cancer treatment. At high cumulative dosage, the negative effect of oxaliplatin on the heart becomes evident and is linked to a growing number of clinical reports. The aim of this study was to determine how chronic oxaliplatin treatment causes the changes in energy-related metabolic activity in the heart that leads to cardiotoxicity and heart damage in mice. C57BL/6 male mice were treated with a human equivalent dosage of intraperitoneal oxaliplatin (0 and 10 mg/kg) once a week for eight weeks. During the treatment, mice were followed for physiological parameters, ECG, histology and RNA sequencing of the heart. We identified that oxaliplatin induces strong changes in the heart and affects the heart’s energy-related metabolic profile. Histological post-mortem evaluation identified focal myocardial necrosis infiltrated with a small number of associated neutrophils. Accumulated doses of oxaliplatin led to significant changes in gene expression related to energy related metabolic pathways including fatty acid (FA) oxidation, amino acid metabolism, glycolysis, electron transport chain, and NAD synthesis pathway. At high accumulative doses of oxaliplatin, the heart shifts its metabolism from FAs to glycolysis and increases lactate production. It also leads to strong overexpression of genes in NAD synthesis pathways such asNmrk2. Changes in gene expression associated with energy metabolic pathways can be used to develop diagnostic methods to detect oxaliplatin-induced cardiotoxicity early on as well as therapy to compensate for the energy deficit in the heart to prevent heart damage.Significance StatementThis study uncovers the detrimental impact of chronic oxaliplatin treatment on heart metabolism in mice, linking high accumulative dosages to cardiotoxicity and heart damage. By identifying significant changes in gene expression related to energy metabolic pathways, the findings pave the way for the development of diagnostic methods to detect oxaliplatin-induced cardiotoxicity at an early stage. Furthermore, these insights may inform the creation of therapies that compensate for the energy deficit in the heart, ultimately preventing heart damage and improving patient outcomes in cancer treatment.

Background Immune checkpoint inhibitor (ICI) myocarditis is associated with high morbidity and mortality. While endomyocardial biopsy (EMB) is considered a gold standard for diagnosis, the sensitivity of EMB is not well defined. Additionally, the pathological features that correlate with the clinical diagnosis of ICI-associated myocarditis remain incompletely understood. Methods We retrospectively identified and reviewed the clinicopathological features of 26 patients with suspected ICI-associated myocarditis based on institutional major and minor criteria. Seventeen of these patients underwent EMB, and the histopathological features were assessed by routine hematoxylin and eosin (H&E) staining and immunohistochemical (IHC) staining for CD68, a macrophage marker. Results Only 2/17 EMBs obtained from patients with suspected ICI myocarditis satisfied the Dallas criteria. Supplemental IHC staining and quantification of CD68+ macrophages identified an additional 7 patients with pathological features of myocardial inflammation (> 50 CD68+ cells/HPF). Macrophage abundance positively correlated with serum Troponin I (P = 0.010) and NT-proBNP (N-terminal pro-brain natriuretic peptide, P = 0.047) concentration. Inclusion of CD68 IHC could have potentially changed the certainty of the diagnosis of ICI-associated myocarditis to definite in 6/17 cases. Conclusions While the Dallas criteria can identify a subset of ICI-associated myocarditis patients, quantification of macrophage abundance may expand the diagnostic role of EMB. Failure to meet the traditional Dallas Criteria should not exclude the diagnosis of myocarditis.

Aims The accuracy of an apical‐sparing strain pattern on transthoracic echocardiography (TTE) for predicting cardiac amyloidosis (CA) has varied in prior studies depending on the underlying cohort. We sought to evaluate the performance of apical sparing and other TTE strain findings to screen for CA in an unselected population and determine the frequency that patients with echocardiographic concern for CA undergo evaluation for amyloidosis in clinical practice. Methods and results As strain is routinely performed at our institution on all clinical TTEs, we identified all TTEs performed from 2016 through 2019 with reported concern for CA or apical sparing. We determined the performance characteristics for echocardiographic strain findings in discriminating CA including apical sparing, the ejection fraction to global longitudinal strain ratio (EF/GLS), and the septal apical–septal basal ratio (SA/SB); other clinical predictors of confirmed CA; and predictors of patients who underwent complete evaluation for CA. CA was confirmed by endomyocardial biopsy or diagnostic cardiac imaging. A total of 547 TTEs, representing 451 patients, reported concern for CA and had adequate strain for analysis. A total of 111 patients underwent complete evaluation for amyloidosis with 100 patients undergoing complete cardiac evaluation for CA. In those 100 patients, multivariable predictors of confirmed CA were age [odds ratio (OR) 3.37 per 5 years], a visual apical‐sparing pattern (OR 10.85), and left ventricular ejection fraction (LVEF)/GLS > 4.1 (OR 35.37). CA was less likely in those with coronary artery disease (OR 0.04), hypertension (OR 0.18), and increased systolic blood pressure (OR 0.60 per 5 mm Hg increase). SA/SB [area under the curve (AUC) 0.72, 95% confidence interval (CI) 0.60–0.84] and LVEF/GLS (AUC 0.72, 95% CI 0.60–0.84) both had improved discrimination for CA compared with the apical‐sparing ratio (AUC 0.66, 95% CI 0.54–0.79). Many patients with suggestive TTE findings did not receive an evaluation for amyloidosis. Complete evaluation was more likely with Caucasian race (OR 2.1), increased septal thickness (OR 1.4), increased body mass index (OR 1.2), and if the report specifically stated ‘amyloid’ (OR 1.9). Evaluations were less likely in patients with comorbidities. While hypertension reduced the likelihood of evaluating for CA, 34% of patients with CA had hypertension (>130/80 mm Hg) at time of diagnosis. Conclusions In a broad population of patients undergoing TTE, apical sparing on strain imaging increased the likelihood of CA diagnosis but with modest sensitivity and specificity. GLS/EF ratio may be a more reliable tool to screen for CA. The low rate of complete evaluation in patients with concerning TTE findings indicates a strong need for practice improvement and enhanced disease awareness.

The discipline of Cardio-Oncology has seen tremendous growth over the past decade. It is devoted to the cardiovascular (CV) care of the cancer patient, especially to the mitigation and management of CV complications or toxicities of cancer therapies, which can have profound implications on prognosis. To that effect, many studies have assessed CV toxicities in patients undergoing various types of cancer therapies; however, direct comparisons have proven difficult due to lack of uniformity in CV toxicity endpoints. Similarly, in clinical practice, there can be substantial differences in the understanding of what constitutes CV toxicity, which can lead to significant variation in patient management and outcomes. This document addresses these issues and provides consensus definitions for the most commonly reported CV toxicities, including cardiomyopathy/heart failure and myocarditis, vascular toxicity, and hypertension, as well as arrhythmias and QTc prolongation. The current document reflects a harmonizing review of the current landscape in CV toxicities and the definitions used to define these. This consensus effort aims to provide a structure for definitions of CV toxicity in the clinic and for future research. It will be important to link the definitions outlined herein to outcomes in clinical practice and CV endpoints in clinical trials. It should facilitate communication across various disciplines to improve clinical outcomes for cancer patients with CV diseases.

Heparin induced thrombocytopenia (HIT) and end stage kidney disease (ESKD) are independent conditions associated with increased mortality and morbidity, however, whether ESKD is an independent risk factor for increased mortality in HIT admissions is not well studied. Therefore, we aimed to compare in-hospital mortality in HIT admissions based on their ESKD status.This is a retrospective cohort study of HIT hospitalizations aged 18 and older using the 2016-2019 national inpatient sample (NIS) database.From 2016 to 2019 we had 12 161 admissions for HIT among 28 484 087 total hospitalizations. The annual incidence rate for HIT admissions per 100 000 admissions were: 47, 46, 41.1, and 36.6, respectively (p .001) in 2016, 2017, 2018, and 2019 respectively. Among HIT admissions, the mean age was 64.3 years, 46.8% were females, 68% were Whites and 16% were Blacks. Black patients have a significantly higher likelihood of in-hospital mortality than White patients (aOR 1.25; 95% CI: 1.06, 1.48; p = .007). Patients who did not have any insurance or self-pay had higher mortality compared to Medicare (aOR 1.64; 95% CI: 1.13, 2.38; p = .009). ESKD status was not associated with higher or lower in-hospital mortality among HIT admissions (aOR 1.002; 95% CI: 0.84, 1.19; p = .981) after adjusting for age, sex, race, and insurance status.There are no higher or lower odds of in-hospital mortality in the ESKD subgroup in HIT admissions in adults. Decreasing incidence of HIT hospitalizations was seen over the years from 2016 to 2019.

Background Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood. Objective This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following anthracycline and/or VEGF inhibitor therapy. Methods Data were extracted from electronic medical records over a fourteen-year period at a single institution. We utilized Cox proportional hazards regression modeling to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk. Results Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04–1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up). Conclusions CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy.

Radiation therapy is an important component of cancer therapy for many malignancies. With improvements in cardiac-sparing techniques, radiation-induced cardiac dysfunction has decreased but remains a continued concern. In this review, we provide an overview of the evolution of radiotherapy techniques in thoracic cancers and associated reductions in cardiac risk. We also highlight data demonstrating that in some cases radiation doses to specific cardiac substructures correlate with cardiac toxicities and/or survival beyond mean heart dose alone. Advanced cardiac imaging, cardiovascular risk assessment, and potentially even biomarkers can help guide post-radiotherapy patient care. In addition, treatment of ventricular arrhythmias with the use of ablative radiotherapy may inform knowledge of radiation-induced cardiac dysfunction. Future efforts should explore further personalization of radiotherapy to minimize cardiac dysfunction by coupling knowledge derived from enhanced dosimetry to cardiac substructures, post-radiation regional dysfunction seen on advanced cardiac imaging, and more complete cardiac toxicity data., Central Illustration, Highlights • Despite improvements in radiation techniques, radiation-induced cardiac dysfunction can occur in those with thoracic cancers. • Newer studies have examined associations between cardiac substructure doses and cardiac outcomes and/or survival. • Advanced cardiac imaging allows assessment of regional dysfunction after cardiac radiation exposure. • Enhanced dose tracking, imaging, and comprehensive clinical data hold promise for personalized approaches to minimize cardiotoxicity.

Several seminal papers over the last decade have furthered our recognition of radiation-induced heart disease (RIHD) as an important potential toxicity following radiation therapy (RT) to the chest. Investigators continue to evaluate the subacute and long-term effects of RT. In addition, studies are determining whether certain cardiac substructures are more sensitive to radiation, working to identify risk factors for the development of RIHD, and testing screening and mitigation strategies for RIHD. Multiple groups and expert consensus guidelines have published whole-heart and cardiac substructure dose constraints based on available data and cancer type. The authors recommend readers to familiarize themselves with the guidelines for screening and mitigating RIHD in adults and children, which advocate for cardiovascular risk assessment and reduction before and following RT, as well as cardiovascular imaging at appropriate follow-up intervals for early recognition of subclinical cardiovascular disease. Referrals to cardiology or cardio-oncology can also be helpful in prevention, screening, and mitigation strategies.

Radiation therapy (RT) is part of standard-of-care treatment of many thoracic cancers. More than 60% of patients receiving thoracic RT may eventually develop radiation-induced cardiac dysfunction (RICD) secondary to collateral heart dose. This article reviews factors contributing to a thoracic cancer patient's risk for RICD, including RT dose to the heart and/or cardiac substructures, other anticancer treatments, and a patient's cardiometabolic health. It is also discussed how automated tracking of these factors within electronic medical record environments may aid radiation oncologists and other treating physicians in their ability to prevent, detect, and/or treat RICD in this expanding patient population.

The purpose of this review is to provide an overview of the essential role that cardiovascular magnetic resonance (CMR) has in the field of cardio-oncology. Recent findings: CMR has been increasingly used for early identification of cancer therapy related cardiac dysfunction (CTRCD) due to its precision in detecting subtle changes in cardiac function and for myocardial tissue characterization. Summary: CMR is able to identify subclinical CTRCD in patients receiving potentially cardiotoxic chemotherapy and guide initiation of cardio protective therapy. Multiparametric analysis with myocardial strain, tissue characterization play a critical role in understanding important clinical questions in cardio-oncology.

Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS). Patients and Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled. Using the historical control of 4.6 months PFS for doxorubicin in the front-line setting, we tested whether the addition of dexrazoxane affected the efficacy of doxorubicin in STS. The study was powered so that a decrease of PFS to 3.7 months would be considered noninferior. Secondary aims included cardiac-related mortality, incidence of heart failure/cardiomyopathy, and expansion of cardiac monitoring parameters including three-dimensional echocardiography. Patients were allowed to continue on doxorubicin beyond 600 mg/m2 if they were deriving benefit and were not demonstrating evidence of symptomatic cardiac dysfunction. Results: At interim analysis, upfront use of dexrazoxane with doxorubicin demonstrated a PFS of 8.4 months (95% confidence interval: 5.1–11.2 months). Only 3 patients were removed from study for cardiotoxicity, all on > 600 mg/m2 doxorubicin. No patients required cardiac hospitalization or had new, persistent cardiac dysfunction with left ventricular ejection fraction remaining below 50%. The median administered doxorubicin dose was 450 mg/m2 (interquartile range, 300–750 mg/m2). Conclusions: At interim analysis, dexrazoxane did not reduce PFS in patients with STS treated with doxorubicin. Involvement of cardio-oncologists is beneficial for the monitoring and safe use of high-dose anthracyclines in STS. See related commentary by Benjamin and Minotti, p. 3809

Radiation-induced cardiac dysfunction is a critical healthcare concern facing survivors of thoracic cancers treated with radiation therapy. Despite cardiac-sparing advances in radiation therapy delivery, many patients with thoracic cancers receiving modern radiation therapy will still have incidental radiation exposure to the heart. Therefore, it is imperative that cardiovascular healthcare providers take appropriate measures to prevent, screen, and manage radiation-induced cardiac dysfunction in patients with a history of thoracic radiation therapy. In this review, we aim to provide healthcare providers with foundational information about radiation-induced cardiac pathophysiology and a chronology of advances in radiation technology. Subsequently, we provide an up-to-date review of treatment- and host-related factors that can influence a patient's risk for radiation-induced cardiac dysfunction. Finally, we culminate our discussion by detailing current screening and management guidelines to aid healthcare providers in caring for their patients with a history of thoracic radiation therapy.

Highlights •The NCDR PINNACLE registry tracks management and quality of 4 common cardiovascular conditions: HF, CAD, AF, and HTN. •By 2017, the registry contained information on 6,040,996 patients, cared for by 8,853 providers in 724 practices. Between 2013 and 2017, care processes for PINNACLE patients generally improved. •PINNACLE registry participation should be considered by practices seeking to monitor and improve practice patterns. •The PINNACLE registry should continue to monitor current practice patterns and opportunities for improvement.

Background With the results of the largest randomized controlled trial (RECOVERY) and the most extensive retrospective cohort study on coronavirus disease 2019 (COVID-19) recently published, we performed a meta-analysis on the association of aspirin with mortality of COVID-19. We aimed to investigate the role of aspirin in COVID-19 hospitalizations. Materials and Methods We searched PubMed, EMBASE and Cochrane databases for studies from 1 January 2020 until 20 July 2022, that compared aspirin versus non-aspirin use in hospitalized COVID-19 patients. We excluded case reports, review articles and studies on non-hospitalized COVID-19 infections. We used the inverse variance method and random effects model to pool the individual studies. Results Ten observational studies and one randomized controlled trial met the criteria for inclusion. There were 136 695 total patients, of which 27 168 were in the aspirin group and 109 527 were in the non-aspirin group. Aspirin use was associated with a 14% decrease in all-cause mortality compared with non-aspirin use in patients hospitalized with COVID-19 [relative risk (RR) 0.86, confidence interval (95% CI) 0.76–0.97; P = 0.002; I2 =64%]. Among subgroups of studies reporting in-hospital mortality in COVID-19 hospitalizations, aspirin use was associated with a 16% decrease in in-hospital mortality compared with non-aspirin use (RR 0.84, 95% CI 0.71–0.99; P = 0.007; I2 =64%). Conclusion Our study shows that aspirin decreases in-hospital mortality in patients hospitalized with COVID-19. Further studies are needed to assess which COVID-19 patient populations benefit most, such as patients on aspirin for primary versus secondary prevention of atherosclerotic disease. In addition, significant bleeding also needs to be considered when assessing the risk–benefit of aspirin use.

BackgroundCoronary artery calcium (CAC) is a measure of atherosclerotic burden and is well-validated for risk stratification in middle- to older-aged adults. Few studies have investigated CAC in younger adults, and there is no calculator for determining age-, sex-, and race-based percentiles among individuals aged0 and develop age-sex-race percentiles for U.S. adults aged 30-45 years.MethodsWe harmonized 3 datasets-CARDIA (Coronary Artery Risk Development in Young Adults), the CAC Consortium, and the Walter Reed Cohort-to study CAC in 19,725 asymptomatic Black and White individuals aged 30-45 years without known atherosclerotic cardiovascular disease. After weighting each cohort equally, the probability of CAC >0 and age-sex-race percentiles of CAC distributions were estimated using nonparametric techniques.ResultsThe prevalence of CAC >0 was 26% among White males, 16% among Black males, 10% among White females, and 7% among Black females. CAC >0 automatically placed all females at >90th percentile. CAC >0 placed White males at the 90th percentile at age 34 years compared with Black males at age 37 years. An interactive webpage allows one to enter an age, sex, race, and CAC score to obtain the corresponding estimated percentile.ConclusionsIn a large cohort of U.S. adults aged 30-45 years without symptomatic atherosclerotic cardiovascular disease, the probability of CAC >0 varied by age, sex, and race. Estimated percentiles may help interpretation of CAC scores among young adults relative to their age-sex-race matched peers and can henceforth be included in CAC score reporting.

Background Coronary artery calcium (CAC) is well‐validated for cardiovascular disease risk stratification in middle to older–aged adults; however, the 2019 American College of Cardiology/American Heart Association guidelines state that more data are needed regarding the performance of CAC in low‐risk younger adults. Methods and Results We measured CAC in 13 397 patients aged 30 to 49 years without known cardiovascular disease or malignancy between 1997 and 2009. Outcomes of myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE; MI, stroke, or cardiovascular death), and all‐cause mortality were assessed using Cox proportional hazard models, controlling for baseline risk factors (including atrial fibrillation for stroke and MACE) and the competing risk of death or noncardiac death as appropriate. The cohort (74% men, mean age 44 years, and 76% with ≤1 cardiovascular disease risk factor) had a 20.6% prevalence of any CAC. CAC was independently predicted by age, male sex, White race, and cardiovascular disease risk factors. Over a mean of 11 years of follow‐up, the relative adjusted subhazard ratio of CAC >0 was 2.9 for MI and 1.6 for MACE. CAC >100 was associated with significantly increased hazards of MI (adjusted subhazard ratio, 5.2), MACE (adjusted subhazard ratio, 3.1), stroke (adjusted subhazard ratio, 1.7), and all‐cause mortality (hazard ratio, 2.1). CAC significantly improved the prognostic accuracy of risk factors for MACE, MI, and all‐cause mortality by the likelihood ratio test ( P Conclusions CAC was prevalent in a large sample of low‐risk young adults. Those with any CAC had significantly higher long‐term hazards of MACE and MI, while severe CAC increased hazards for all outcomes including death. CAC may have utility for clinical decision‐making among select young adults.

OBJECTIVES: To identify predictors of healthy arterial aging [long-term coronary artery calcification (CAC) of 0] among individuals with metabolic syndrome (MetS) or type 2 diabetes (T2D), which may improve primary prevention strategies. BACKGROUND: Individuals with MetS or T2D have a heterogeneously increased risk of atherosclerotic cardiovascular disease (ASCVD) and not all have a high-intermediate risk. METHODS: We included 574 participants from the Multi-Ethnic Study of Atherosclerosis with MetS or T2D who had CAC=0 at baseline and a repeat CAC scan 10 years later. Multivariable logistic regression assessed the association of traditional and novel ASCVD risk factors and the MetS severity score (based on the five MetS criteria) with healthy arterial aging. RESULTS: The mean age of participants was 58.9 years, 67% were women, 422 participants had MetS, and 152 had T2D. The proportion with long-term CAC=0 was similar for MetS (42%) and T2D (44%). A younger age was the only individual low/normal traditional risk factor associated with an increased likelihood of long-term CAC=0 (OR=1.50, 95% CI: 1.22–1.85 per 10-years younger). The strongest associations of nontraditional risk factors were observed for an absence of thoracic calcification (OR=2.42, 95% CI: 1.24–4.72), absence of carotid plaque (OR=1.81, 95% CI: 1.25–2.61) and among persons with a high sensitivity troponin < 3 ng/mL (OR=1.55, 95% CI: 1.01–2.38). In addition, persons with the lowest quartile MetS severity score had a substantially higher odds of healthy long-term CAC=0 (OR=2.71, 95% CI: 1.27–5.76). CONCLUSION: More than 40% of adults with MetS or T2D and baseline CAC=0 had long-term absence of CAC, which was most strongly associated with an absence of extra-coronary atherosclerosis and a low MetS score. An optimal overall cardiovascular profile appears to be more important than an ideal value of any individual risk factor to maintain healthy arterial aging.

Background: Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is a frequently under-recognized cause of heart failure (HF) in older patients. To improve identification of patients at risk for the disease, we initiated a pilot program in which 9 cardiac/non-cardiac phenotypes and 20 high-performing phenotype combinations predictive of wild-type ATTR-CM were operationalized in electronic health record (EHR) configurations at a large academic medical center. Methods: Inclusion criteria were age >50 years and HF; exclusion criteria were end-stage renal disease and prior amyloidosis diagnoses. The different Epic EHR configurations investigated were a clinical decision support tool (Best Practice Advisory) and operational/analytical reports (Clarity™, Reporting Workbench™, and SlicerDicer); the different data sources employed were problem list, visit diagnosis, medical history, and billing transactions. Results: With Clarity, among 45 051 patients with HF, 4006 patients (8.9%) had ⩾1 phenotype combination associated with increased risk of wild-type ATTR-CM. Across all data sources, 2 phenotypes (cardiomegaly; osteoarthrosis) and 2 combinations (carpal tunnel syndrome + HF; atrial fibrillation + heart block + cardiomegaly + osteoarthrosis) generated the highest proportions of patients for wild-type ATTR-CM screening. Conclusion: All EHR configurations tested were capable of operationalizing phenotypes or phenotype combinations to identify at-risk patients; the Clarity report was the most comprehensive.

Objectives This study aimed to assess the long-term risk of death and atherosclerotic cardiovascular disease (ASCVD) outcomes, including stroke, in a real-world cohort that underwent coronary artery calcium (CAC) scoring. Background Large-scale, long-term studies assessing the independent relationship of CAC for prediction of ASCVD events, to include stroke, in young, low-risk patients are uncommon outside of the clinical trial setting. Methods A total of 23,637 consecutive subjects without ASCVD who underwent CAC scoring from 1997 to 2009 were studied. Subjects were assessed for myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE) (e.g., MI, stroke, or cardiovascular death), and all-cause mortality. Outcomes were extracted from the Military Data Repository and the National Death Index and assessed using Cox proportional hazards models, controlling for baseline risk factors, atrial fibrillation, and competing mortality. Results Patients (mean age 50.0 ± 8.5 years) were followed over a median of 11.4 years. The relative adjusted subhazard ratio (aSHR) for CAC 1 to 100, 101 to 400, and >400 was 2.2, 3.8, and 5.9 for MI; 1.2, 1.4, and 1.9 for stroke; 1.4, 2.0, and 2.8 for MACE; and 1.2, 1.5 and 2.1 for death (p 0; n = 848) was associated with an increased risk of MACE (aSHR: 1.67; 95% confidence interval: 1.16 to 2.39). Conclusions CAC scoring significantly improved long-term prognostic accuracy for MACE events and mortality, irrespective of age and risk factors. These results support CAC screening for improving individual ASCVD risk assessment and prevention in low-risk, young adults.

Robot-assisted thoracic surgery has emerged as an alternative to video-assisted thoracic surgery (VATS) for treating patients with resectable non-small cell lung cancer. The objective of this study was to evaluate the cost effectiveness of robotic-assisted lobectomy (RAL) compared with VATS and open lobectomy for adults with NSCLC.A decision analysis model was employed to compare the cost effectiveness of RAL, VATS, and open lobectomy with 1-year time horizon from both health care and societal perspectives. Health care costs (2020$) and quality-adjusted life-years were compared between the approaches. The incremental cost-effectiveness ratio was calculated in terms of cost per quality-adjusted life-years gained. Sensitivity analyses were performed to identify variables driving cost effectiveness across several willingness-to-pay thresholds.Open thoracotomy was not cost effective compared with both RAL and VATS lobectomy. From the health care sector perspective, RAL was $394.97 more expensive per case than VATS resulting in an incremental cost-effectiveness ratio of $180 755.10 per quality-adjusted life-year. From the societal perspective, RAL was $247.77 more expensive per case than VATS, resulting in an incremental cost-effectiveness ratio of $113 388.80 per quality-adjusted life-years. Robotic-assisted lobectomy becomes cost effective with marginally lower robotic instrument costs, shorter operating room times, lower conversion rates, shorter lengths of stay, higher hospital volumes, and improved quality of life. Robotic-assisted lobectomy is also cost effective if surgeons can increase the proportion of minimally invasive lobectomies using robotic technology.Compared with VATS, RAL is not cost effective for lung cancer lobectomy at lower willingness-to-pay thresholds. However, several factors may drive RAL to emerge as the more cost-effective approach for minimally invasive lung cancer resection.

Cardiac amyloidosis is increasingly recognized as an underdiagnosed cause of heart failure. Diagnostic delays of up to 3 years from symptom onset may occur, and patients may be evaluated by more than 5 specialists prior to receiving the correct diagnosis. Newly available therapies improve clinical outcomes by preventing amyloid fibril deposition and are usually more effective in early stages of disease, making early diagnosis essential. Better awareness among primary care providers of the clinical presentation and modern treatment landscape is essential to improve timely diagnosis and early treatment of this disease. In this review, we provide practical guidance on the epidemiology, clinical manifestations, diagnostic evaluation, and treatment of transthyretin and light chain cardiac amyloidosis to promote earlier disease recognition among primary care providers.

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

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

Aims Guideline-directed medical therapy (GDMT) is underutilized in patients with coronary artery disease (CAD). However, there are no studies evaluating the impact of GDMT adherence on mortality among patients with CAD and heart failure with reduced ejection fraction (HFrEF). We sought to investigate the association of GDMT adherence with long-term mortality in patients with CAD and HFrEF. Methods and results Surgical Treatment for Ischaemic Heart Failure (STICH) was a trial of patients with an left ventricular ejection fraction ≤35% and CAD amenable to coronary artery bypass graft surgery (CABG) who were randomized to CABG plus medical therapy (N = 610) or medical therapy alone (N = 602). Median follow-up time was 9.8 years. We defined GDMT for the treatment of CAD and HFrEF as the combination of at least one antiplatelet drug, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The primary outcome was all-cause mortality. Assessment of the independent association between GDMT and mortality was performed using multivariable Cox regression with GDMT as a time-dependent covariate. In the CABG arm, 63.6% of patients were on GDMT throughout the study period compared to 66.5% of patients in the medical therapy arm (P = 0.3). GDMT was independently associated with a significant reduction in mortality (hazard ratio 0.65, 95% confidence interval 0.56–0.76; P Conclusion GDMT is associated with reduced mortality in patients with CAD and HFrEF independent of revascularization with CABG. Strategies to improve GDMT adherence in this population are needed to maximize survival.

The burgeoning field of cardio-oncology (C-O) is now necessary for the delivery of excellent care for patients with cancer. Many factors have contributed to this increasing population of cancer survivors or those being treated with novel and targeted cancer therapies. There is a tremendous need to provide outstanding cardiovascular (CV) care for these patients; however, current medical literature actually provides a paucity of guidance. C-O therefore provides a novel opportunity for clinical, translational, and basic research to advance patient care. This review aims to be a primer for cardio-oncologists on how to develop a vibrant and comprehensive C-O program, use practical tools to assist in the construction of C-O services, and to proactively incorporate translational and clinical research into the training of future leaders as well as enhance clinical care.

Objectives: This study determined the diagnostic and prognostic usefulness of hepatocyte growth factor (HGF) in light chain and transthyretin cardiac amyloidosis. Background: Delays in diagnosis of cardiac amyloidosis are common, usually resulting from nonspecific findings on clinical examination and testing. A discriminatory plasma biomarker could result in earlier diagnosis and improve prognosis assessment. Methods: A total of 188 patients with cardiac amyloidosis, amyloidosis without cardiac involvement, symptomatic heart failure with left ventricular hypertrophy (LVH), or heart failure with a reduced ejection fraction (HFrEF) were enrolled prospectively. Serum biomarkers were measured at study enrollment, and all patients with amyloidosis were followed for all-cause mortality, cardiac transplantation, or left ventricular assist device implantation. Multinomial logistic regression and Kaplan-Meier survival estimates tested the association of biomarker levels with cardiac amyloidosis and clinical outcomes, respectively. Harrell’s C-statistic and the likelihood ratio test compared the prognostic accuracy of plasma biomarkers. Results: HGF was significantly higher in patients with cardiac amyloidosis (p < 0.001). An HGF level of 205 pg/ml discriminated cardiac amyloidosis from LVH and HFrEF with 86% sensitivity, 84% specificity, and an area under the curve of 0.88 (95% confidence interval: 0.83 to 0.94). In patients with amyloidosis, elevated HGF levels were associated with worse event-free survival over a median follow-up of 2.6 years (p < 0.001) with incremental prognostic accuracy over N-terminal pro-B-type natriuretic peptide and troponin T (p < 0.001). Conclusions: HGF discriminates light chain and transthyretin cardiac amyloidosis from patients with symptomatic heart failure with LVH or HFrEF and is associated with worse cardiac outcomes. Confirmation of these findings in a larger, multicenter study that is enrolling suspected cases of cardiac amyloidosis is underway.

When randomized controlled trials are not feasible, retrospective studies using big data provide an efficient and cost-effective alternative, though they are at risk for treatment selection bias. Treatment selection bias occurs in a non-randomized study when treatment selection is based on pre-treatment characteristics that are also associated with the outcome. These pre-treatment characteristics, or confounders, can influence evaluation of a treatment’s effect on the outcome. Propensity scores minimize this bias by balancing the known confounders between treatment groups. There are a few approaches to performing propensity score analyses, including stratifying by the propensity score, propensity matching, and inverse probability of treatment weighting (IPTW). Described here is the use of IPTW to balance baseline comorbidities in a cohort of patients within the US Military Health System Data Repository (MDR). The MDR is a relatively optimal data source, as it provides a contained cohort in which nearly complete information on inpatient and outpatient services is available for eligible beneficiaries. Outlined below is the use of the MDR supplemented with information from the national death index to provide robust mortality data. Also provided are suggestions for using administrative data. Finally, the protocol shares an SAS code for using IPTW to balance known confounders and plot the cumulative incidence function for the outcome of interest.

Background Prior studies have demonstrated underuse of optimal medical therapy (OMT) in patients with coronary artery disease (CAD) after revascularization. However, there are limited studies assessing compliance with OMT on long-term survival in patients with CAD and no studies evaluating the impact of OMT in patients with severe CAD and reduced left ventricular (LV) function. The Surgical Treatment for Ischaemic Heart Failure (STICH) Trial was a randomized clinical trial that compared coronary-artery bypass grafting (CABG) with medical therapy versus medical therapy alone in the treatment of ischemic cardiomyopathy. Purpose This study sought to determine compliance with OMT over time and the impact of OMT compliance on survival in patients with or without revascularization. Methods STICH was a multicenter, randomized clinical trial of patients with an LV ejection fraction of 35% or less and CAD amenable to CABG who were randomized to CABG plus medical therapy (N=610) or medical therapy alone (N=602). A medication history was obtained at hospital discharge or 30 days after enrollment, 1 year, 5 years, and 10 years. OMT was defined as the combination of at least 1 antiplatelet drug, a statin, a beta-blocker, and an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. The primary outcome was all-cause mortality. Comparison of mortality between the OMT and non-OMT groups was performed using multivariate Cox regression modeling with OMT as a time-dependent covariate. Results Of the 1212 patients randomized, at a median follow-up of 9.8 years, all-cause mortality was 58.9% in the CABG group and 66.1% in the medical therapy group. In the CABG arm, 63.6% of patients were on OMT throughout the study period compared to 66.5% of patients in the medical therapy arm (p=0.3). Those on OMT were younger (59.6 vs. 61.4 years, p Conclusions OMT improves long-term survival in patients with ischaemic cardiomyopathy regardless of revascularization status. Strategies to improve OMT use and adherence in this population is needed to maximize survival.

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

BACKGROUND: Compared to traditional risk factors, coronary artery calcium (CAC) scores improve prognostic accuracy for atherosclerotic cardiovascular disease (ASCVD) outcomes. However, the relative impact of statins on ASCVD outcomes stratified by CAC scores is unknown. OBJECTIVES: To determine if CAC can identify patients most likely to benefit from statin treatment. METHODS: We identified consecutive subjects without pre-existing ASCVD or malignancy who underwent CAC scoring from 2002 to 2009 at Walter Reed. The primary outcome was first major adverse cardiovascular event (MACE), a composite of acute myocardial infarction, stroke, and cardiovascular death. The effect of statin therapy on outcomes was analyzed stratified by CAC presence and severity, after adjusting for baseline comorbidities with inverse probability of treatment weights based on propensity scores. RESULTS: 13,644 patients (mean age 50 years; 71% men) were followed for a median of 9.4 years. Comparing patients with and without statin exposure, statin therapy was associated with reduced risk of MACE in patients with CAC (adjusted subhazard ratio [aSHR] 0.76, 95% CI 0.60–0.95, p=0.015) but not in patients without CAC (aSHR 1.00, 95% CI 0.79–1.27, p=0.99). The effect of statin use on MACE was significantly related to the severity of CAC (p 100). CONCLUSIONS: In a large-scale cohort without baseline ASCVD, the presence and severity of CAC identified patients most likely to benefit from statins for the primary prevention of cardiovascular diseases. CONDENSED ABSTRACT: Prior studies have shown that coronary artery calcium (CAC) screening improves risk prediction of atherosclerotic cardiovascular disease (ASCVD), but the true impact of statins on ASCVD outcomes stratified by CAC scores is unknown. In this retrospective cohort of 13,644 patients without pre-existing atherosclerotic cardiovascular disease or malignancy who underwent CAC scoring at Walter Reed Army Medical Center, increasing severity of CAC was associated with increased benefit from statin treatment for the prevention of cardiovascular morbidity and mortality. CAC presence and severity may help stratify patients most likely to benefit from statins.

Cardiac amyloidosis remains poorly diagnosed, with significant delays in diagnosis leading to increased morbidity and mortality. An apical sparing strain pattern on echocardiogram correlated with cardiac amyloidosis in a prior, small, selected patient population with a 93% sensitivity and 82%

While cancer survivors have been shown to be at a significantly increased risk for cardiovascular (CV) events, prior data have often been limited to breast cancer and childhood cancer survivors with the exception of a single recent study from a United Kingdom population. We sought to determine the

With increasing use of checkpoint inhibitors, there have been significant concerns for the potential for fulminant myocarditis. However, systematic analyses of the real-world cardiovascular (CV) effects of these medications, including myocardial infarction (MI) and heart failure (HF), are lacking.

The performance of low-radiation, non-contrast cardiac computed tomography to detect and quantify coronary artery calcium (CAC) is a well-studied, highly reproducible technique shown to significantly improve individual atherosclerotic cardiovascular disease risk prediction as compared to risk factor-based approaches. Using outcomes-based net reclassification, CAC testing has been shown to accurately reclassify 35–65% of patients estimated to be at intermediate and high risk according to standard risk scores. This improvement in prognostic accuracy may result in more precise and appropriate utilization of statins and aspirin for primary cardiovascular disease prevention, without a significant increase in overall costs. Accordingly, current European Society of Cardiology and other international guidelines and appropriateness criteria incorporate CAC testing for clinical use primarily among patients at intermediate risk for fatal cardiovascular disease by standard risk scores, and when the decision to use lifelong preventative medications remains unclear.