Venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in cancer patients. Patients with cancer are six times more likely to develop VTE than their noncancer counterparts, and VTE is the second leading cause of death in cancer patients. Despite the publication of major consensus guidelines setting out recommendations for thromboprophylaxis in cancer patients, there remains a gulf between these guidelines and clinical practice. In general, thromboprophylaxis is recommended for most patients hospitalized with active cancer. Furthermore, outpatient thromboprophylaxis may be used in carefully selected high-risk ambulatory patients. Certain areas of controversy still remain. Although low-molecular-weight heparin has been shown to be superior to vitamin K antagonists in cancer patients, the role of direct oral anticoagulants is still uncertain. Moreover, recurrent thromboembolism, bleeding, and thrombocytopenia are frequently seen in cancer patients. Optimal anticoagulation in such instances presents a major challenge to clinicians. Modern computed tomography techniques have resulted in an increase in the detection of "incidental" VTE. Despite a growing body of evidence promulgating standard anticoagulant treatment in such cases, these cases present further challenges for members of the multidisciplinary team. The Oncologist 2017; 22:199-207 Implications for Practice: This article discusses venous thromboembolism (VTE) in patients with malignancy. Practical guidance is offered on how to prevent, diagnose, and treat VTE in cancer patients. The management of "challenging" cases of VTE is also discussed.

Targeted DNA methylation profiling of human cardiac tissue reveals novel epigenetic traits and gene deregulation across different Heart Failure patient sub-types Glezeva DNA methylation profiling of Heart Failure

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Aim Remnant cholesterol has been proposed to promote atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol, yet the underlying mechanisms are not well understood. We aimed to study the association of remnant cholesterol with coronary atheroma progression and clinical events. Methods We analyzed data from 5754 patients with coronary artery disease undergoing serial intravascular ultrasonography who were enrolled in 10 trials examining various medical therapies. Remnant cholesterol was calculated as (non-high-density lipoprotein cholesterol – low-density lipoprotein cholesterol (estimated using the Hopkins–Martin equation)). Changes in percentage atheroma volume and 2-year major adverse cardiovascular events were compared across various levels of remnant cholesterol, and multivariable models were used to assess the independent relationship of remnant cholesterol with changes in percentage atheroma volume. Results The mean age was 58.1 ± 9.2 years, 28% were women and 96% received a statin. Percentage atheroma volume progression (changes in percentage atheroma volume > 0) occurred in a linear fashion at on-treatment remnant cholesterol levels of 25 mg/dL or greater. The highest on-treatment remnant cholesterol quartile demonstrated greater percentage atheroma volume progression (+0.53 ± 0.26 vs. –0.15 ± 0.25%, P < 0.001) and 2-year major adverse cardiovascular events (23% vs. 14%, log–rank P < 0.001) compared with the lowest. In multivariable analyses, changes in percentage atheroma volume significantly correlated with on-treatment remnant cholesterol ( P < 0.001] independent of low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, high-density lipoprotein cholesterol levels and clinical risk factors. Changes in percentage atheroma volume also significantly correlated with changes in remnant cholesterol following multivariable adjustment. Conclusions In statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol was associated with coronary atheroma progression regardless of conventional lipid parameters, C-reactive protein or clinical risk factors. Higher remnant cholesterol levels also correlated with higher major adverse cardiovascular events. These data support further investigations into remnant cholesterol-lowering interventions in statin-treated patients harboring residual atherosclerotic cardiovascular disease risk.

bleeding, and disseminated intravascular coagulation 2 . Prevention and management of those complications in cancer patients can significantly affect patient treatment, prognosis, and quality of life.Venous thromboembolism (vte), which includes deep venous thrombosis (dvt) and pulmonary embolism, might precede or coincide with a diagnosis of cancer. In this patient group, vte can potentially complicate surgery, hospitalization, or systemic chemotherapy 3-5 . Risk for vte is increased by a factor of approximately 6 in patients with cancer compared with non-cancer patients, and patients with cancer account for 20% of all newly diagnosed cases of vte 6 . Postmortem studies suggest that the incidence of vte in cancer patients might be as high as 50%, in keeping with the finding that, after cancer itself, vte represents the second leading cause of death in hospitalized patients with cancer 7-9 .Venous thromboembolism is associated with high morbidity, mortality, and economic burden. Its diagnosis and management can interrupt essential cancer therapy and cause potentially serious bleeding complications 10 . Moreover, approximately 25% of cancer patients with vte require readmission because of bleeding or recurrent vte 11,12 . MECHANISMS UNDERLYING THE CANCER-ASSOCIATED PROTHROMBOTIC PHENOTYPEDirect and indirect mechanisms contribute to the pathogenesis of cancer-associated vte 13-15 (Figure 1

BackgroundCardiac disease after mediastinal radiotherapy for thoracic malignancy (chest radiotherapy [XRT]) often manifests as progressive aortic stenosis. In patients with XRT‐induced severe aortic stenosis undergoing surgical aortic valve replacement (SAVR), we sought to: (1) study long‐term survival and compare these patients with a matched cohort undergoing SAVR during the same time frame; and (2) identify potential predictors of long‐term mortality.Methods and ResultsWe studied patients with symptomatic severe aortic stenosis undergoing SAVR at our institution, of which there were 172 mediastinal XRT patients (63±13 years, 62% women) matched in a 1:1 fashion (based on age, sex, time of surgery, and aortic valve area) with 172 non‐XRT patients (comparison group). Baseline clinical and postoperative data were obtained. Society of Thoracic Surgeons score was calculated and mortality was recorded. In the XRT group, the median Society of Thoracic Surgeons score was 4% (interquartile range 2–13), while mean left ventricular ejection fraction, left ventricular stroke volume index, and mean aortic valve gradient were 54±11%, 38±14 mL/m2, and 39±11 mm Hg, respectively. In the entire cohort, 27% and 34% of patients underwent concomitant coronary artery bypass grafting and aortic surgery at the time of SAVR, respectively. Thirty‐day/in‐hospital deaths occurred in 4 (2%) patients in the XRT group and 0 patients in the comparison group. At 6±3 years of follow‐up, on matched group analysis, there were 95 (28%) deaths (83 [48%] in the XRT group versus 12 [7%] in the comparison group (log‐rank 89, P<0.001). On multivariable Cox survival analysis, in the whole cohort, higher Society of Thoracic Surgeons score (hazard ratio, 1.14; 95% CI, 1.03–1.26) and mediastinal XRT (hazard ratio, 8.12; 95% CI, 4.26–15.64) were associated with increased longer‐term mortality (both P<0.01).ConclusionsIn patients with severe aortic stenosis undergoing SAVR, patients with prior mediastinal XRT have significantly worse longer‐term survival versus a matched cohort.

Aims Obesity decreases arrhythmia-free survival after atrial fibrillation (AF) ablation by mechanisms that are not fully understood. We investigated the impact of pre-ablation bariatric surgery (BS) on AF recurrence after ablation. Methods and results In this retrospective observational cohort study, 239 consecutive morbidly obese patients (body mass index ≥40 kg/m2 or ≥35 kg/m2 with obesity-related complications) were followed for a mean of 22 months prior to ablation. Of these patients, 51 had BS prior to ablation, and our primary outcome was whether BS was associated with a lower rate of AF recurrence during follow-up. Adjustment for confounding was performed with multivariable Cox proportional hazard models and propensity-score based analyses. During a mean follow-up of 36 months after ablation, 10/51 patients (20%) in the BS group had recurrent AF compared with 114/188 (61%) in the non-BS group (P < 0.0001). In the BS group, 6 patients (12%) underwent repeat ablation compared with 77 patients (41%) in the non-BS group, (P < 0.0001). On multivariable analysis, the association between BS and lower AF recurrence remained significant. Similarly, after weighting and adjusting for the inverse probability of the propensity score, BS was still associated with a lower hazard of AF recurrence (hazard ratio 0.14, 95% confidence interval 0.05–0.39; P = 0.002). Conclusion Bariatric surgery is associated with a lower AF recurrence after ablation. Morbidly obese patients should be considered for BS prior to AF ablation, though prospective multicentre studies should be performed to confirm our novel finding.

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