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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.

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

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 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.

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.

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.

We are thankful for the comments submitted in the 3 letters written in response to our original paper [(1)][1] and appreciate the opportunity to clarify our findings. Regarding Dr. Bansal’s question of whether the discriminating benefit of coronary artery calcium (CAC) holds in younger patients

Stable coronary artery disease[1][1] (CAD) or stable ischemic heart disease[2][2] are terms preferred in Europe and the United States, respectively, that generally refer to the same patients––those with angina, its equivalent, or no symptoms who experience episodes of reversible myocardial

Soldiers with combat-related traumatic injury are at high risk for venous thromboembolism (VTE) and often require regional anesthesia (RA) for pain control. We evaluated whether the recommended reduction in chemoprophylaxis in the presence of RA increases VTE rates.We collected data each hospital day for all soldiers admitted to the Walter Reed Army Medical Center following injury in Iraq or Afghanistan. We analyzed thromboprophylaxis and RA rates and assessed risk factors for VTE. We separated outcomes by whether RA was central neuraxial (cNAB) or peripheral blockade.Among 1,259 patients, 323 received RA for a median of 12 days (5-27 days). Those with RA were younger and more likely to have been injured in combat or by an improvised explosive device. They also received more packed red blood cell transfusions and had longer admissions. Patients with RA spent a greater percentage of days on enoxaparin 40 mg daily compared with those without RA (34.4% vs. 22.0%, p0.001) and more hospital days without any chemoprophylaxis (2.0 [1.0-6.0] vs. 1.0 [0.0-3.0], p0.001). Patients with cNAB were less likely to be placed on enoxaparin 30 mg twice daily. Patients with RA in place had mechanical prophylaxis ordered at the same rate as those without RA. Neither the presence of any RA nor cNAB specifically was associated with an increased risk for VTE. No bleeding or neurologic complications occurred in those receiving RA.Despite changes to chemoprophylaxis, soldiers wounded in combat who receive RA are not at increased risk for VTE.Therapeutic study, level III.

The acknowledgement of cardiovascular disease as one of the leading causes of mortality and morbidity among cancer survivors is the cornerstone of the growing field of cardio-oncology. Although standardizing treatment for any given disease is often considered ideal, it is important to recognize the value of pursuing a practical and personalized approach when caring for an oncology patient to minimize the risk of treatment-related cardiotoxicity. We hereby discuss a series of cases that illustrate the ways vascular toxicity can manifest in patients with cancer and, when appropriate, provide scientific evidence that supports clinical decision making. We also raise questions about the complex management of these patients while shedding light on future research in this growing field.

Summary. Background: Compliance with venous thromboembolism (VTE) prophylaxis is poor. Objectives: We sought to determine whether a simple electronic reminder applicable to all hospitalized patients would increase prophylaxis rates and reduce VTE rates. Methods: An electronic reminder was added to the electronic medical record admission note used by all services in our hospital. Prophylaxis, VTE and bleeding rates before and after implementation were compared. Data were analyzed with sas version 9.1. Results: Among all adult medical and surgical patients admitted to our hospital during the time periods studied, 42.8% (1236/2888) before and 60.0% (1410/2350) after the reminder was added received appropriate prophylaxis as per American College of Chest Physicians (ACCP) guidelines (P

Objectives The purpose of this study was to systematically review and perform a meta-analysis of the ability of cardiac computed tomography angiography (CCTA) to predict future cardiovascular events and death. Background The diagnostic accuracy of CCTA is well reported. The prognostic value of CCTA has been described in several studies, but many were underpowered. Pooling outcomes increases the power to predict rare events. Methods We searched multiple databases for longitudinal studies of CCTA with at least 3 months follow-up of symptomatic patients with suspected coronary artery disease (CAD) reporting major adverse cardiovascular events (MACE), consisting of death, myocardial infarction (MI), and revascularization. Annualized event rates were pooled using a bivariate mixed-effects binomial regression model to calculate summary likelihood ratios and receiver-operating characteristic curves. Results Eighteen studies evaluated 9,592 patients with a median follow-up of 20 months. The pooled annualized event rate for obstructive (any vessel with >50% luminal stenosis) versus normal CCTA was 8.8% versus 0.17% per year for MACE (p Conclusions Adverse cardiovascular events among patients with normal findings on CCTA are rare. There are incrementally increasing future MACE with increasing CAD by CCTA.

Background: Cardiac troponin (cTn) has high sensitivity and specificity for myocardial injury in acute coronary syndrome. Our objective was to review the published literature regarding the incidence of cTn elevations in marathon runners. Methods: Systematic review and meta-analysis of observational studies published before September 2009. We included studies of patients who had completed a marathon and had serum cTn levels within 24 hours. The primary outcome was the odds ratio for conversion of a normal pre-marathon cTn to an elevated post-marathon cTn. Secondary outcomes included the pooled prevalence of cTn elevation and comparison of the odds ratio for post-marathon elevation of cTnI versus cTnT. Results: Sixteen studies of 939 participants met criteria for inclusion. The mean age was 39 ± 4 years and patients were 74 ± 14% male. There were 6 pre-marathon cTn elevations and 579 post-race elevations. The pooled odds ratio for converting from a normal pre-race to an elevated post-race cTn was 51.84 (95% CI 16–168, I2= 66%, P < 0.001). The pooled incidence of a post-marathon cTn elevation was 51% (95% CI 33–69, I2= 98%, P < 0.001) of all runners. For the primary outcome there was no significant publication bias. Age and gender were not associated, but publication date and assay sensitivity was associated with cTn elevation. cTnI was less commonly elevated versus cTnT. Conclusions: The available data demonstrate that cTn levels are frequently elevated after a marathon with unclear cardiovascular significance. This elevation of cTn appears to be consistent among a diverse patient population. (J Interven Cardiol 2010;23:443–450)

While coronary artery calcium progression is predictive of cardiovascular outcomes, the optimal definition of CAC progression remains unclear, and the impact of statins on CAC progression is not fully understood. We sought to better define measures of CAC progression that were most associated with

The absence of coronary artery calcium (CAC) has been shown to be a strong negative risk factor for cardiovascular events; though, there is limited data on the optimal time interval for re-assessing for development of CAC on future scans. A previous study suggested that patients rarely convert from

Despite previous studies and trials, controversy continues to exist as to the benefit of an invasive strategy for patients with Non-ST Elevation Myocardial Infarction (NSTEMI). We sought to determine the potential impact on survival for in-hospital invasive evaluation of patients admitted for NSTEMI

Objective: Left ventricular assist devices (LVADs) are commonly used for critically ill patients awaiting heart transplantation, although their effect on long-term outcomes, relative to inotropic support alone, is still debated. Method: Data from Status 1 patients who underwent heart transplantation at our institution between 1990 and 2005 were reviewed (n = 180). They were divided into two groups: those who underwent LVAD implantation as a bridge to transplant (n = 31) and those treated with inotropic agents without the support of LVAD (n = 149). They were compared in terms of demographics and clinical outcome. Results: Both groups were similar in terms of patient and donor demographics. Relative to the inotrope group, the LVAD group did have a longer ischemic time (p = 0.032), a greater incidence of pretransplant transfusion (p < 0.00001), and a greater maximum level of pretransplant panel reactive antibodies (p < 0.001). Creatinine at listing significantly improved in LVAD patients awaiting transplantation (p < 0.0001). Comparisons of 5-year survival in addition to freedom from posttransplant infection, malignancy, revascularization, and acute rejection did not show significant difference between the two groups. The LVAD group did benefit from increased freedom from chronic rejection compared to the inotrope group (p = 0.049). Stepwise Cox Regression did not identify any independent factors affecting patient survival during the first 5 years after transplant. Conclusions: Status 1 patients successfully bridged to heart transplantation with LVADs had similar long-term clinical outcomes compared to those treated with inotropic agents.

Background Recent guidelines recommend assessing medical inpatients for bleeding risk prior to providing chemical prophylaxis for VTE. The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) bleeding risk score (BRS) was derived from a well-defined population of medical inpatients but it has not been validated externally. We sought to externally validate the IMPROVE BRS. Methods We prospectively collected characteristics on admission and VTE prophylaxis data each hospital day for all patients admitted for a medical illness to the Walter Reed Army Medical Center over an 18-month period. We calculated the IMPROVE BRS for each patient using admission data and reviewed medical records to identify bleeding events. Results From September 2009 through March 2011, 1,668 inpatients met the IMPROVE inclusion criteria. Bleeding events occurred during 45 separate admissions (2.7%); 31 events (1.9%) were major and 14 (0.8%) were nonmajor but clinically relevant. Two hundred fifty-six patients (20.7%) had an IMPROVE BRS ≥ 7.0. Kaplan-Meier curves showed a higher cumulative incidence of major ( P = .02) and clinically important (major plus clinically relevant nonmajor) ( P = .06) bleeding within 14 days in patients with an IMPROVE BRS ≥ 7.0. An IMPROVE BRS ≥ 7.0 was associated with major bleeding in Cox-regression analysis adjusted for administration of chemical prophylaxis (OR, 2.6; 95% CI, 1.1-5.9; P = .03); there was a trend toward a significant association with clinically important bleeding (OR, 1.9; 95% CI, 0.9-3.7; P = .07). Conclusions The IMPROVE BRS calculated at admission predicts major bleeding in medical inpatients. This model may help assess the relative risks of bleeding and VTE before chemoprophylaxis is administered.

An important ethical and safety concern that geriatricians, primary care providers, and home health professionals need to address is gun ownership by elderly adults. Those aged 65 and older now have the highest rate of gun ownership in America, and they also have a high prevalence of depression and suicide. Dementia can add additional layers of risk. Even older gun owners who are otherwise intellectually intact may benefit from information about gun safety with the increasing numbers of children being cared for by grandparents. Health professionals should ask patients, "Is there a gun in the home?" in the clinic and during home visits. Healthcare professionals must have knowledge and skills to address safe gun ownership in elderly adults. The 5 L's (Locked, Loaded, Little children, feeling Low, Learned owner) will assist professionals in addressing all aspects of safe ownership. Language: en

Objectives US soldiers suffer catastrophic injuries during combat. We sought to define risk factors and rates for VTE in this population. Methods We gathered data each hospital day on all patients injured in Afghanistan or Iraq who were admitted to the Walter Reed Army Medical Center (WRAMC). We analyzed prophylaxis rates and efficacy and identified risk factors for VTE. Results We recorded data on 506 combat casualties directly admitted to WRAMC after medical air evacuation. The average injury severity score for the group was 18.4 ± 11.7, and the most common reason for air evacuation was injury by improvised explosive device (65%). As part of the initial resuscitation, patients received 4.7 ± 9.0 and 4.00 ± 7.8 units of packed RBCs and fresh frozen plasma, respectively, and 42 patients received factor VIIa. Forty-six patients (9.1%) were given a diagnosis of VTE prior to discharge, 18 (3.6%) during air evacuation, and 28 (5.5%) during the hospital stay. In Cox regression analysis, administration of 1 unit of packed RBCs was associated with a hazard ratio (HR) of 1.04 (95% CI, 1.02-1.07; P = .002), and enoxaparin, 30 mg bid, administered subcutaneously for the majority of hospital days was associated with a HR of 0.31 (95% CI, 0.11-0.86; P = .02) for VTE during the hospitalization. Conclusions Patients who suffer traumatic injuries in combat overseas are at high risk for VTE during evacuation and recovery. Those with large resuscitations are at particularly high risk, and low-molecular-weight heparin is associated with a decrease in VTE.

Patients with HIV may have increased risk of atherosclerotic cardiovascular disease owing to multiple biological mechanisms.To evaluate the evidence for subclinical atherosclerosis among patients with HIV.Systematic review of observational studies.We searched Medline, Cochrane DSR, ACP Journal Club, DARE, CMR, HTA, NHSEED, Embase and the Cochrane Controlled Trials Register for studies published before November 2008.Eligible studies were cross-sectional, cohort, or case-control studies reporting carotid ultrasound intima-media thickness (CIMT), focal plaque incidence, or coronary artery calcium (CAC), as determined by HIV positivity or protease inhibitor (PI) exposure.Two independent reviewers abstracted data using a standardised form. The primary outcome was weighted mean difference (WMD) for CIMT comparing HIV positive versus negative patients. Other outcomes included WMD by PI exposure and the odds ratio (OR) for a focal carotid plaque or CAC. Data from six cross-sectional, seven case-control and 13 cohort studies were included, involving 5456 HIV positive and 3600 HIV negative patients.The weighted mean CIMT was 0.04 mm thicker among patients with HIV than among non-HIV patients (95% CI 0.02 to 0.06; p0.001). HIV positivity was not associated with carotid plaque or CAC. PI exposure did not significantly affect CIMT, carotid plaque, or CAC. There was evidence of publication bias and stratified analysis and meta-regression showed outcomes were influenced by study design, age, gender and smoking. However, HIV positivity slightly increased CIMT even after sensitivity analyses.HIV infection and PI exposure are not strong independent risk factors for subclinical atherosclerosis. Confounding may contribute to overestimation of the risk associated with HIV and PI exposure.

Immunofluorescence staining of endomyocardial biopsy (EMB) specimens to detect the complement fragment C4d is used to diagnose antibody-mediated rejection. However, data are limited regarding the utility of routine staining for C4d in clinical care.This study retrospectively reviewed the clinical course of adult cardiac transplant recipients who underwentor = 2 EMBs with immunofluorescence C4d staining at the University of Texas Southwestern Medical Center since September 2006. C4d staining was performed by the immunohistochemistry laboratory and interpreted by the members of the surgical pathology department, in conjunction with interpretation of the routine hematoxylin and eosin staining. Donor-specific antibodies (DSA) were routinely assessed at the time of clinical rejection.Of 67 patients, specimens were positive for C4d (C4d+) in 14 and negative for C4d (C4d-) in 53. The frequency of acute cellular rejection (ACR) in these 2 groups was 57% (8 of 14, designated C4d+/ACR+) vs 11% (6 of 53, designated C4d-/ACR+; p0.001). Significantly more patients with a positive C4d specimen had a positive retrospective donor specific crossmatch, presence of DSA after transplantation, and depressed graft function (p0.01 for each).Positive C4d immunofluorescence staining on EMB specimens was associated with ACR, reduced allograft function, a positive retrospective crossmatch, and the presence of DSA after transplantation. The latter 2 observations support the contention that C4d deposition is a marker of antibody-mediated rejection. Routine evaluation of C4d staining is feasible in the clinical setting and may identify variable patterns of rejection.

Background Although the Cylex immune assay has been proposed as a means of tailoring immunosuppression after organ transplantation, there are limited data regarding its utility in cardiac transplant recipients. Therefore, we sought to determine the utility of the Cylex assay in assessing the risk of infection or rejection in cardiac transplant recipients. Methods This study is a retrospective review of the clinical course of all adult cardiac transplant recipients who underwent a Cylex assay at UT Southwestern Medical Center between January 2004 and September 2007. Results One hundred eleven patients were free of significant rejection or infection at the time of the first Cylex assay. Most patients (92%) were >1 year post-transplant. Over the next 157 ± 41 (mean ± SD) days, 2 patients had 3 episodes of rejection requiring therapy and 7 patients had 8 infections requiring therapy. The Cylex responses ranged from 17 to 894 ng/ml. No correlation was observed between the baseline Cylex response and subsequent risk of either infection or rejection within 6 months. Lower white blood cell count and African American ethnicity were correlated with a lower Cylex response. Conclusions In this study, the Cylex assay had limited utility as an adjunct to routine clinical evaluation in assessing risk of infection or rejection in cardiac transplant recipients.

Background Cytomegalovirus (CMV) infection remains a serious problem after heart transplantation. Recipients with D + /R − CMV serostatus often receive prophylaxis with valganciclovir, but the optimal duration of such therapy after heart transplant is unknown. Methods We retrospectively reviewed the clinical course of all adult cardiac transplant recipients with D + /R − CMV serostatus at the UT Southwestern Medical Center between January 2003 and December 2006. Standard immunosuppression included basiliximab induction therapy and the CMV prophylaxis included CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of oral valganciclovir. Results Seven patients met the study criteria. Six of the 7 patients (86%) developed CMV disease. Five of these 6 patients presented with CMV disease within 3 months of the cessation of valganciclovir prophylaxis. Conclusions There was a high incidence of CMV disease in D + /R − heart transplant recipients despite CMV hyperimmune globulin, 2 weeks of intravenous ganciclovir and 3 months of valganciclovir prophylaxis. CMV infection occurred consistently within 2 to 3 months of cessation of valganciclovir. Alternative strategies for CMV prophylaxis, including an extension of valganciclovir prophylaxis to 6 months after heart transplantation, needs to be investigated.

Objective Substance dependence is common in bipolar disorder and is associated with an increase in Axis I and II comorbidity. Little research has compared the relative rates of comorbidity among bipolar patients with dependence on different substances. Methods The Mini International Neuropsychiatric Interview (MINI) was used to assess 166 outpatients involved in one of three clinical trials of medications for bipolar disorder and substance dependence. Patients had concurrent alcohol dependence, cocaine dependence, or both conditions. Results Generalized anxiety disorder and current depressed mood were significantly more common in bipolar patients with alcohol dependence than bipolar patients with cocaine dependence. Those with cocaine dependence had significantly higher rates of post-traumatic stress disorder and antisocial personality disorder and were more likely to present in a mixed mood state than patients dependent on alcohol. Cocaine ENC dependent patients were more likely than alcohol dependent patients to have Bipolar I relative to Bipolar II. Limitations This is a retrospective, cross-sectional data analysis using the MINI for diagnosis. Conclusions Cocaine dependence and alcohol dependence were associated with different clinical features and comorbid disorders in bipolar patients. The results may help confirm the validity of integrative models of mood, behavioral, anxiety, and personality disorders. Further studies on the causal relationship between substance dependence and concurrent and lifetime Axis I disorders for patients with bipolar disorders are indicated.

Managing immunosuppression is a significant aspect of posttransplantation patient care. Previously, our institution reported that prednisone could be withdrawn in cardiac allograft recipients without jeopardizing midterm survival. We returned to this group of patients to investigate the long-term effects of our steroid taper protocol.We reviewed the records of 162 consecutive cardiac transplant recipients from our institution. Patients who underwent transplantation between 1988 and 1990 were treated with traditional triple-therapy immunosuppression (cyclosporine, azathioprine, and prednisone). Beginning June 1990, we instituted a protocol of early steroid taper with discontinuation by 6 months after transplant. The two groups were comparable with respect to age, sex, ethnicity, cause of heart failure, ischemic time, body mass index, and creatinine at the time of transplantation.Fifty-seven percent of the patients in the early steroid taper group were successfully withdrawn from steroids at 6 months after transplantation. This group had a decreased freedom from and increased frequency of acute rejection (p0.01 for each) when compared with the traditional therapy group. There was, however, no difference in freedom from posttransplant coronary artery disease (p = 0.53). The early steroid taper group enjoyed an increased freedom from malignancy (p = 0.01) and trended toward a decreased frequency of infection (p = 0.10) and improved survival (p = 0.06).Steroid withdrawal is possible in 57% of patients at 6 months after transplantation. The institution of an early steroid taper protocol improves the overall freedom from malignancies and may decrease the frequency of infection and prolong overall survival without increasing the risk of posttransplant coronary artery disease.