Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications. This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043). Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding. Bayer AG.

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries and rapidly growing in developing countries. The most common cause of MI is the rupture of an atherosclerotic plaque with subsequent thrombotic occlusion in the coronary circulation. This causes cardiomyocyte death and myocardial necrosis, with subsequent inflammation and fibrosis. Current therapies aim to restore coronary flow by thrombus dissolution with pharmaceutical treatment and/or intravascular stent implantation and to counteract neurohormonal activation. Despite these therapies, the injury caused by myocardial ischemia leads to left ventricular remodeling; this process involves changes in cardiac geometry, dimension and function and eventually progression to heart failure (HF). This review describes the pathophysiological mechanism that leads to cardiac remodeling and the therapeutic strategies with a role in slowing the progression of remodeling and improving cardiac structure and function.

Peripheral arterial disease (PAD) is a common manifestation of generalized atherosclerosis, which affects more than 200 million patients worldwide. Currently, there is no ideal biomarker for PAD risk stratification and diagnosis. The goal of this research was to investigate the levels of inflammation biomarkers and cystatin C and to explore their utility for the diagnosis of PAD. The study included 296 participants, distributed in two groups: 216 patients diagnosed with PAD and 80 patients without PAD as controls. All studied biomarker levels (C-reactive protein, CRP; fibrinogen; erythrocyte sedimentation rate, ESR; neopterin; beta 2-microglobulin, B2-MG; and cystatin C) were significantly higher in the PAD group and indirectly correlated with the ankle–brachial index (ABI). The final logistic regression model included an association of neopterin, fibrinogen, and cystatin C as the most efficient markers for the prediction of PAD diagnosis. When comparing the area under the curve (AUC) for all biomarkers, the value for neopterin was significantly higher than those of all the other analyzed biomarkers. In agreement with previous studies, this research shows that markers such as fibrinogen, CRP, ESR, B2-MG, and cystatin C have significant value for the diagnosis of PAD, and also clearly underlines the accuracy of neopterin as a leading biomarker in PAD prediction.

A persistent left superior vena cava (PLSVC) is the most frequent anomaly of the venous drainage system. While both a right and left superior vena cava (SVC) are usually present, a unique, left-sided SVC, also known as an isolated PLSVC, accounts for only 10–20% of cases. It is frequently associated with arrhythmias and other congenital cardiac anomalies. Though it is usually an asymptomatic condition, it may pose significant problems whenever central venous access is needed. We report a case of an isolated PLSVC that was diagnosed incidentally during pacemaker implantation for sinus node dysfunction. The venous anomaly was associated with subvalvular aortic stenosis determined by a subaortic membrane; this particular association of congenital cardiovascular anomalies is a rare finding, with only a few cases reported in the literature. We aim to highlight the clinical and practical implications of this condition, as well as to discuss the embryonic development and diagnostic methods of this congenital defect.

Implantable cardioverter defibrillators (ICDs) are the cornerstone of primary and secondary prevention of sudden cardiac death (SCD) all around the globe. In almost 40 years of technological advances and multiple clinical trials, there has been a continuous increase in the implantation rate. The purpose of this review is to highlight the grey areas related to actual ICD recommendations, focusing specifically on the primary prevention of SCD. We will discuss the still-existing controversies strongly reflected in the differences between the international guidelines regarding ICD indication class in non-ischemic cardiomyopathy, and also address the question of early implantation after myocardial infarction in the absence of clear protocols for patients at high risk of life-threatening arrhythmias. Correlating the insufficient data in the literature for 40-day waiting times with the increased risk of SCD in the first month after myocardial infarction, we review the pros and cons of early ICD implantation.