The association of atrial fibrillation (AF) with ischemic stroke has long been recognized; yet, the pathogenic mechanisms underlying this relationship are incompletely understood. Clinical schemas, such as the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score, incompletely account for thromboembolic risk, and emerging evidence suggests that stroke can occur in patients with AF even after sinus rhythm is restored. Atrial fibrosis correlates with both the persistence and burden of AF, and gadolinium-enhanced magnetic resonance imaging is gaining utility for detection and quantification of the fibrotic substrate, but methodological challenges limit its use. Factors related to evolution of the thrombogenic fibrotic atrial cardiomyopathy support the view that AF is a marker of stroke risk regardless of whether or not the arrhythmia is sustained. Antithrombotic therapy should be guided by a comprehensive assessment of intrinsic risk rather than the presence or absence of AF at a given time.

Target lesion calcification remains independently associated with adverse outcomes in patients treated with newer generation DES and modern devices.

Purpose of review-Cardiotoxicity is a well recognized adverse effect of human epidermal growth factor receptor 2 (HER2)-targeted therapies. The goal of this review is to highlight recent studies that have advanced our knowledge of the diagnosis, prevention, and management of cardiotoxicity associated with HER2-targeted agents. Recent findings-Several clinical risk factors for cardiotoxicity associated with HER2-targeted therapies have been identified including age, low-baseline left ventricular ejection fraction, and treatment with anthracyclines; however, these remain insufficient to identify all patients at risk for cardiotoxicity. Routine cardiac monitoring remains the standard for cardiotoxicity surveillance, although the optimal frequency and modality of monitoring remains uncertain. Global longitudinal strain, T1/T2 weighted CMR imaging protocols, and circulating biomarkers can detect early signs of cardiotoxicity, but studies are needed to investigate whether use of these markers in clinical practice improves patient outcomes. Cardioprotective medications (e.g. beta-blockers or ACEinhibitors) may be of benefit to patients at increased risk for cardiotoxicity from HER2-taregeted therapies, particularly those who are treated with an anthracycline-containing regimen. Summary-Improved risk stratification of patients during HER2-targeted therapy and effective prevention and management strategies for cardiotoxicity are needed to enhance the value of longitudinal cardiac monitoring and increase cardiac safety so that optimal breast cancer treatment can be delivered.

BackgroundInflammation is fundamental to the development of atherosclerosis. We examined the effect of anti‐inflammatory doses of salicylate on endothelium‐dependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects.Methods and ResultsWe performed a randomized, double‐blind, placebo‐controlled crossover trial evaluating the effects of 4 weeks of high‐dose salsalate (disalicylate) therapy on endothelium‐dependent flow‐mediated and endothelium‐independent vasodilation. Fifty‐eight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endothelium‐dependent flow‐mediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerin‐mediated, endothelium‐independent vasodilation was unchanged (P=0.97). Endothelium‐dependent flow‐mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P<0.02) but not in subjects with subtherapeutic levels (P>0.2).ConclusionsSalsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endothelium‐dependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of anti‐inflammatory doses of salsalate on cardiovascular risk.Clinical Trial RegistrationURL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827.

Objective-Reduced limb perfusion from arterial stenosis does not adequately account for intermittent claudication symptoms in peripheral artery disease (PAD). Insulin resistance is associated with PAD and may contribute to claudication by impairing skeletal muscle metabolism. We aimed to determine whether skeletal muscle glucose uptake, assessed by [ 18 F]fluorodeoxyglucose positron emission tomography, is reduced in patients with claudication. Methods and Results-Thirty-seven subjects with PAD and claudication and 11 healthy controls underwent [18 F]fluorodeoxyglucose-positron emission tomography imaging of the legs during hyperinsulinemic-euglycemic clamp. Calf glucose uptake was quantified by graphical Patlak analysis, and whole-body insulin sensitivity was assessed as the glucose disposal rate (M) from the insulin clamp. Compared with healthy controls, PAD subjects were insulin resistant (Mϭ3.4 mg/kg per minute [interquartile range, 2.7 to 4.8] versus 5.0 [3.7 to 6.6], Pϭ0.019). Calf muscle glucose uptake was significantly lower in PAD compared with healthy subjects (48.6Ϯ2.6 mol/kg per minute versus 62.9Ϯ6.5 mol/kg per minute, Pϭ0.009) and correlated with systemic insulin sensitivity (rϭ0.37, Pϭ0.03) in PAD subjects. These abnormalities persisted even after exclusion of PAD subjects with diabetes. Conclusion-Patients

The deteriorating health of the population and the increasing prevalence of chronic diseases are global problems whose causes are multifactorial and complex. The Western lifestyle does not promote healthy living, and the consequences are most devastating when social inequalities, together with the economic and population explosion of recent decades, are considered. The expansion of poor nutritional habits, obesity, sedentarism, and hypertension are increasingly contributing to the development of a cardiovascular disease epidemic. Recent data on the rates of compliance with lifestyle modification and adherence to prescribed medication are alarming. Over 50% of patients, on average, decide to abandon the treatment prescribed, and the objectives to improve their habits (quit smoking, lose weight, or engage in physical activity) are met by an equal or lower percentage. Beyond the impact it has on individual health, it carries a huge economic cost, as it is associated with a failure in achieving therapeutic goals, higher rate of hospitalization, and death. Improving communication between doctors and patients, the active involvement of other health professionals, and the development of combination drug formulations (polypill) are potential strategies for improving adherence and reducing costs.

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Human epidermal growth factor receptor 2 (ERBB2)-targeted therapies such as trastuzumab improve disease-free and overall survival for patients with ERBB2-positive breast cancer (BCA). 1 Cardiotoxic effects, characterized by reduced left ventricular ejection fraction (LVEF) or clinical heart failure (HF), are an important treatment-limiting adverse effect of ERBB2targeted therapy and the most common indication for early trastuzumab interruption. 2 Findings from the PHARE and PERSEPHONE trials on the noninferiority of 6-vs 12-month durations of trastuzumab are conflicting, thus the clinical significance of early trastuzumab interruption on BCA outcomes remains uncertain. 3,4 Our primary objective was to evaluate the association of early trastuzumab interruption with BCA outcomes in clinical practice.