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Abnormal systemic vein development produces anomalous veins, which - in the case of persistent left superior vena cava and/or left brachiocephalic vein - exhibit considerable topographic and morphometric differences in comparison with their usual anatomy. The nature and extent of those developmental anomalies - detected during intravenous procedures, such as cardiac implantable electronic device (CIED) lead insertion or central venous catheter placement - may hinder the procedure itself and/or adversely affect its outcome, both at the stage of cardiac lead advancement through an abnormally shaped vessel and lead positioning within the heart. This may lead to problems in achieving optimal sensing and pacing parameters and in ensuring that the patient cannot feel the pacing impulses. These events accompanied a de novo CIED implantation procedure in the patient with a double superior vena cava and left brachiocephalic vein agenesis, who ultimately required reoperation.

Mateusz Mieczkowski,1 Beata Mrozikiewicz-Rakowska,1 Tomasz Siwko,1 Magdalena Bujalska-Zadrozny,2 Anna de Corde-Skurska,2 Renata Wolinska,2 Emilia Gasinska,2 Tomasz Grzela,3 Piotr Foltynski,4 Michal Kowara,5 Zofia Mieczkowska,1 Leszek Czupryniak1 1Department of Diabetology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland; 2Department of Pharmacodynamics, Medical University of Warsaw, Warsaw, Poland; 3Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland; 4Nalecz Institute of Biocybernetics and Biomedical Engineering Polish Academy of Sciences, Warsaw, Poland; 5Department of Cardiology, Medical University of Warsaw, Warsaw, PolandCorrespondence: Beata Mrozikiewicz-RakowskaDepartment of Diabetology and Internal Medicine, Medical University of Warsaw, Poland ul. Banacha 1A, Warsaw, 02-097, PolandTel +48 600 311 399Fax +48225992832Email rakowskab123@gmail.comPurpose: Optimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats with streptozotocin-induced diabetes.Methods: The study was conducted on 200 male Wistar rats with streptozotocin-induced diabetes. In the last phase of the study, 45 rats, with the most stable glucose levels in the range of 350– 500 mg/dL, were divided into three groups: group I received human non-protamine insulin subcutaneously (5 IU/kg body mass) once a day, group II received metformin intragastrically (500 mg/kg b.m.), and group III (control) was given saline subcutaneously. After 14 days of antidiabetic treatment, a 2 cm × 2 cm thin layer of skin was cut from each rat’s dorsum and a 4 cm disk with a hole in its center was sewn in to stabilize the skin and standardize the healing process. The wound healing process was followed up for 9 days, with assessment every 3 days. Biopsy samples were subjected to hematoxylin and eosin staining and immunohistochemical assays.Results: Analysis of variance revealed significant influence of treatment type (insulin, control, or metformin) on the relative change in wound surface area. The wound healing process in rats treated with insulin was more effective than in the metformin and control groups. Wound tissue samples taken from the insulin-treated animals presented significantly lower levels of inflammatory infiltration. Immunohistochemical assessment showed the greatest density of centers of proliferation Ki-67 in insulin-treated animals.Conclusion: These results suggest that an insulin-based treatment is more beneficial than metformin, in terms of accelerating the wound healing process in an animal model of streptozocin-induced diabetes.Keywords: diabetes mellitus, neuropathy, ulceration, animal model

Chronic wounds are becoming an increasingly common clinical problem due to an aging population and an increased incidence of diabetes, atherosclerosis, and venous insufficiency, which are the conditions that impair and delay the healing process. Patients with diabetes constitute a group of subjects in whom the healing process is particularly prolonged regardless of its initial etiology. Circulatory dysfunction, both at the microvascular and macrovascular levels, is a leading factor in delaying or precluding wound healing in diabetes. The prolonged period of wound healing increases the risk of complications such as the development of infection, including sepsis and even amputation. Currently, many substances applied topically or systemically are supposed to accelerate the process of wound regeneration and finally wound closure. The role of clinical trials and preclinical studies, including research based on animal models, is to create safe medicinal products and ensure the fastest possible healing. To achieve this goal and minimize the wide-ranging burdens associated with conducting clinical trials, a correct animal model is needed to replicate the wound conditions in patients with diabetes as closely as possible. The aim of the paper is to summarize the most important molecular pathways which are impaired in the hyperglycemic state in the context of designing an animal model of diabetic chronic wounds. The authors focus on research optimization, including economic aspects and model reproducibility, as well as the ethical dimension of minimizing the suffering of research subjects according to the 3 Rs principle (Replacement, Reduction, Refinement).

Background: The rate of intracranial haemorrhage after an acute coronary syndrome has been studied in detail in the era of thrombolysis; however, in the contemporary era of percutaneous coronary intervention, most of the data have been derived from clinical trials. With this background, we aim to analyse the incidence, timing, predictors and prognostic impact of post-discharge intracranial haemorrhage in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: We analysed data from the BleeMACS registry (patients discharged for acute coronary syndrome and undergoing percutaneous coronary intervention from Europe, Asia and America, 2003–2014). Analyses were conducted using a competing risk framework. Uni and multivariate predictors of intracranial haemorrhage were assessed using the Fine–Gray proportional hazards regression analysis. The endpoint was 1-year post-discharge intracranial haemorrhage. Results: Of 11,136 patients, 30 presented with intracranial haemorrhage during the first year (0.27%). The median time to intracranial haemorrhage was 150 days (interquartile range 55.7–319.5). The fatality rate of intracranial haemorrhage was very high (30%). After multivariate analysis, only age (subhazard ratio 1.05, 95% confidence interval 1.01–1.07) and prior stroke/transient ischaemic attack (hazard ratio 3.29, 95% confidence interval 1.36–8.00) were independently associated with a higher risk of intracranial haemorrhage. Hypertension showed a trend to associate with higher intracranial haemorrhage rate. The combination of older age (⩾75 years), prior stroke/transient ischaemic attack, and/or hypertension allowed us to identify most of the patients with intracranial haemorrhage (86.7%). The annual rate of intracranial haemorrhage was 0.1% in patients with no risk factors, 0.2% in those with one factor, 0.6% in those with two factors and 1.3% in those with three factors. Conclusion: The incidence of intracranial haemorrhage in the first year after an acute coronary syndrome treated with percutaneous coronary intervention is low. Advanced age, previous stroke/transient ischaemic attack, and hypertension are the main predictors of increased intracranial haemorrhage risk.

Introduction Implantable cardioverter-defibrillators (ICD) have a strong position in the prevention of sudden death. Nowadays, the most commonly used high-energy cardiac devices are transvenous ICDs. A new technology of totally subcutaneous ICDs (S-ICD) was invented and recently introduced into clinical practice in order to reduce lead-related complications of conventional ICDs. The aim of this paper is to present early experience with this new technology implemented in a few centres in Poland. Material and methods Medical records of patients who had S-ICD-related interventions in Poland were retrospectively analysed. Results During the first year of S-ICD introduction into the Polish health system 18 patients underwent surgery connected with S-ICDs. Majority of them (17 patients) were implanted de novo. In one patient surgical revision of a device implanted abroad was performed. Most of patients (78%) had S-ICDs implanted for secondary prevention. Inability of transvenous system implantation due to venous access obstruction or high risk of infection related with transvenous leads accounted for 83% of indications for S-ICD. Only in three patients were S-ICDs implanted due to young age and active mode of life. The implantations of S-ICDs were performed without important early or late complications. During follow-up one patient had episodes of ventricular arrhythmia successfully terminated with high-energy shocks. One patient died due to progression of heart failure. Conclusions S-ICD implantation procedure has been successfully and safely introduced in Polish clinical routine. Nevertheless, despite clear indications in recent ESC guidelines, this therapy is not directly reimbursed in Poland and needs individual application for refund.

Background: The recent introduction of an entirely subcutaneous implantable cardioverter-defibril­lator (S-ICD) represents an important progress in the defibrillation technology towards a less invasive approach. This is a single-center observational study of S-ICD implantations in Poland. Methods: The S-ICD was implanted in 11 patients with standard indications for an ICD. Patients in whom the device was implanted were evaluated for adverse events and device function at hospital discharge. All hospitalization costs were calculated and summed up for all patients. Costs were divided into following categories: medical materials, pharmaceuticals, operating theatre staff, cardiology depart­ment staff, laboratory tests, non-laboratory tests and additional non-medical costs. Results: The mean age of patients was 51.6 ± 16.4 years, 9 were men and 2 were women. Four pa­tients had atrial fibrillation as the basal rhythm, 1 patient had atrial flutter and 6 patients had sinus rhythm. All patients had at least one condition that precluded the use of a traditional ICD system or the S-ICD was preferred due to other conditions, i.e. a history complicated transvenous ICD therapy (18%), anticipated higher risk of infection (27%), lack or difficult vascular access (18%), young age and anticipated high cumulated risk of lifetime device therapy (36%). The mean duration of the im­plantation procedure was 2 h. One patient developed a postoperative pocket hematoma. Mean total time of hospitalization was 28 (6–92) days. Average cost of hospitalization per patient was 21,014.29 EUR (minimal = 19,332.71 EUR and maximal = 24,824.14 EUR). Conclusions: S-ICD implantation appears to provide a viable alternative to transvenous ICD, espe­cially for patients without pacing requirements.

Atherosclerotic plaque vulnerability is a vital clinical problem as vulnerable plaques tend to rupture, which results in atherosclerosis complications—myocardial infarctions and subsequent cardiovascular deaths. Therefore, methods aiming to stabilize such plaques are in great demand. In this brief review, the idea of atherosclerotic plaque stabilization and five main approaches—towards the regulation of metabolism, macrophages and cellular death, inflammation, reactive oxygen species, and extracellular matrix remodeling have been presented. Moreover, apart from classical approaches (targeted at the general mechanisms of plaque destabilization), there are also alternative approaches targeted either at certain plaques which have just become vulnerable or targeted at the minimization of the consequences of atherosclerotic plaque erosion or rupture. These alternative approaches have also been briefly mentioned in this review.

The aim of this article is to demonstrate the impact of physical exercise on the development of arrhytmias in athletes. The studies show that this relation exist and concerns endurance sports practiced for a long time. In addition, this article contains review of the most common arrhythmias in athletes and appropriate recommendations. The time of arrhythmias onset depends on the presence of structural heart diseases. If the cardiac disorder is absent the arrhythmias appear at the age 40-50. If the structural heart diseases exist, the arrhythmias occur in young athletes and are more dangerous (can lead to sudden cardiac arrest). The most common arrhythmia in endurance athletes is atrial fibrillation. In order to avoid negative results of endurance sports, such as cardiac arrhythmias, the reliable examinations are necessary, especially to exclude structural cardiac diseases. These examinations should be undertaken before initiation of endurance sport training and routinely later, in course of follow-up.

Purpose: The aim was to evaluate prognostic value of beta-blocker (BB) administration in acute coronary syndromes (ACS) patients in the percutaneous coronary intervention (PCI) era. Methods and Results: The BleeMACS project is a multicenter, observational, retrospective registry enrolling patients with ACS worldwide in 15 hospitals. Patients discharged with BB therapy were compared to those discharged without a BB before and after propensity score with matching. The primary endpoint was all-cause mortality at 1 year. Secondary endpoints included in-hospital reinfarction, in-hospital heart failure, 1-year myocardial infarction, 1-year bleeding and 1-year composite of death and recurrent myocardial infarction. After matching, 2935 patients for each group were enrolled. The primary endpoint of 1-year death was significantly lower in the group on BB therapy (4.5 vs 7%, p < 0.05), while only a trend was noted for recurrent acute myocardial infarction (4.5 vs 4.9%, p = 0.54). These results were consistent for patients older than 80 years of age, for ST-elevation myocardial infarction (STEMI) patients, and for those discharged with complete versus incomplete revascularization, but not for non-STEMI/unstable angina patients. Conclusions: BB therapy was related to 1-year lower risk of all-cause mortality, independently from completeness of revascularization, admission diagnosis, age and ejection fraction. Randomized controlled trials for patients treated with PCI for ACS should be performed.

Introduction: Bleeding is an independent risk factor of mortality in patients with acute coronary syndromes (ACS). BleeMACS project focuses on long-term bleeding events after hospital discharge, thus we evaluated gender-related differences in post-discharge bleeding among patients with ACS. Materials and methods: We investigated 13,727 ACS patients treated with percutaneous coronary intervention and discharged on dual antiplatelet therapy (either with clopidogrel or prasugrel/ticagrelor). Endpoint was defined as intracranial bleeding or any other bleeding leading to hospitalization and/or red blood transfusion. Results: Post-discharge bleeding was reported more frequently in females as compared with males (3.7% vs. 2.7%, log-rank P = 0.001). Females (n = 3165, 23%) were older compared to men (69.0 vs. 61.5 years, P < 0.001) and with more comorbidities. Hence, in multivariate analysis female sex was not identified as an independent risk factor of bleeding (HR 1.012, CI 0.805 to 1.274, P = 0.816). Administration of newer antiplatelet agents compared to clopidogrel was associated with over twofold greater bleeding rate in females (7.3% vs. 3.5%, log-rank P = 0.004), but not in males (2.6% vs. 2.7%, log-rank P = 0.887). Differences among females remained significant after propensity score matching (7.2% vs 2.4%, log-rank P = 0.020) and multivariate analysis confirmed that newer antiplatelet agents are independent risk factor for bleeding only in women (HR 2.775, CI 1.613 to 4.774, P < 0.001). Conclusions: Bleeding events occurred more frequently in women, but female sex itself was not independent risk factor. Administration of newer antiplatelet agents was identified as independent risk factor of bleeding after hospital discharge in female gender, but not in male patients.

Background: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. Methods and results: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, PConclusion: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Summary Background Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). Methods In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Findings Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (p non-inferiority =0·0004; hazard ratio [HR] 0·81 [95% CI 0·62–1·06], p superiority =0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; p non-inferiority =0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59–1·13]; p=0·23). Interpretation Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Funding Klinikum der Universitat Munchen, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.

The process of atherosclerotic plaque destabilization, leading to myocardial infarction, is still not fully understood. The pathway - composed of structural and regulatory proteins of the extracellular matrix (ECM) such as collagen, elastin, small leucine-rich proteoglycans, metalloproteinases, cathepsins and serine proteases - is one potential way of atherosclerotic plaque destabilization. The expression of these proteins is controlled by different microRNA molecules. The goal of this paper is to summarize the current investigations and knowledge about ECM in the process of atherosclerotic plaque destabilization, giving special attention to epigenetic expression regulation by microRNA.

Introduction and objectives For patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI), it is unclear whether angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are associated with reduced mortality, particularly with preserved left ventricular ejection fraction (LVEF). The goal of this study was to determine the association between ACEI/ARB and mortality in ACS patients undergoing PCI, with and without reduced LVEF. Methods Data from the BleeMACS registry were used. The endpoint was 1-year all-cause mortality. The prognostic value of ACEI/ARB was tested after weighting by survival-time inverse probability and after adjustment by Cox regression, propensity score, and instrumental variable analysis. Results Among 15 401 ACS patients who underwent PCI, ACEI/ARB were prescribed in 75.2%. There were 569 deaths (3.7%) during the first year after hospital discharge. After multivariable adjustment, ACEI/ARB were associated with lower 1-year mortality, ≤ 40% (HR, 0.62; 95%CI, 0.43-0.90; P = .012). The relative risk reduction of ACEI/ARB in mortality was 46.1% in patients with LVEF ≤ 40%, and 15.7% in patients with LVEF > 40% (P value for treatment-by-LVEF interaction = .008). For patients with LVEF > 40%, ACEI/ARB was associated with lower mortality only in ST-segment elevation myocardial infarction (HR, 0.44; 95%CI, 0.21-0.93; P = .031). Conclusion The benefit of ACEI/ARB in decreasing mortality after an ACS in patients undergoing PCI is concentrated in patients with LVEF ≤ 40%, and in those with LVEF > 40% and ST-segment elevation myocardial infarction. In non–ST-segment elevation-ACS patients with LVEF > 40%, further studies are needed to assess the prognostic impact of ACEI/ARB.

Myocardial infarction is one of the major causes of mortality worldwide and is a main cause of heart failure. This disease appears as a final point of atherosclerotic plaque progression, destabilization, and rupture. As a consequence of cardiomyocytes death during the infarction, the heart undergoes unfavorable cardiac remodeling, which results in its failure. Therefore, therapies aimed to limit the processes of atherosclerotic plaque progression, cardiac damage during the infarction, and subsequent remodeling are urgently warranted. A hopeful therapeutic option for the future medicine is targeting and regulating non-coding RNA (ncRNA), like microRNA, circular RNA (circRNA), or long non-coding RNA (lncRNA). In this review, the approaches targeted at ncRNAs participating in the aforementioned pathophysiological processes involved in myocardial infarction and their outcomes in preclinical studies have been concisely presented.

Background Blood transfusions (BTs) may worsen the prognosis of patients affected by acute coronary syndromes (ACS), although few data detail their impact on short-term events according to clinical presentation (ST Segment Elevation Myocardial Infarction, STEMI vs. Non-ST Segment Elevation ACS, NSTE-ACS). Methods Patients undergoing percutaneous coronary intervention (PCI) for ACS, with data on BTs, were selected from the BleeMACS registry. The primary end point was the incidence of myocardial infarction during hospitalization (reAMI), the secondary end-points were 30-day mortality and the combined end-point of 30-day mortality and reAMI. Sensitivity analyses were performed according to clinical presentation (STEMI vs. NSTE-ACS). Results Overall, 13,975 patients were included: mean age was 64.1years, 10,651 (76.2%) were male and 7711 (55.2%) had STEMI. BTs were administered during hospitalization to 465 (3.3%) patients, who were older and presented a more relevant burden of risk factors. The primary end-point of reAMI occurred in 197 (1.4%) patients, of whom 102 (1.1%) with STEMI. After controlling for confounding variables, BTs independently predicted the primary end-point reAMI in patients admitted for STEMI (OR 4.059, 95% CI 2244–7.344) and not in those admitted for NSTE-ACS. Moreover, BTs independently related to 30-day mortality in STEMI and NSTE-ACS patients and to the composite of 30-day mortality and reAMI in STEMI patients. Conclusions In patients undergoing PCI for ACS, BTs increase the risk of reAMI only in those admitted for STEMI, and not in those with NSTE-ACS. These results may help physicians to choose appropriate BT administration according to the admission diagnosis.

Resumen Introduccion y objetivos No esta clara la asociacion entre los inhibidores de la enzima de conversion de la angiotensina (IECA) o los antagonistas del receptor de la angiotensina II (ARA-II) y la mortalidad de los pacientes con sindrome coronario agudo (SCA) sometidos a intervencion coronaria percutanea (ICP) con fraccion de eyeccion del ventriculo izquierdo (FEVI) conservada. Nuestro objetivo es determinar dicha asociacion en pacientes con FEVI conservada o reducida. Metodos Se analizaron datos procedentes del registro BleeMACS. El objetivo principal fue la mortalidad a 1 ano. Se aplicaron ponderacion por la probabilidad inversa del tiempo de supervivencia y ajustes por regresion de Cox, puntuacion de propension y variables instrumentales. Resultados De los 15.401 pacientes con SCA sometidos a ICP, se prescribieron IECA/ARA-II al 75,2%. Se produjeron 569 muertes (3,7%) durante el primer ano tras el alta hospitalaria. Despues del ajuste multivariado, los IECA/ARA-II se asociaron con menor mortalidad, pero solo en los pacientes con FEVI ≤ 40% (HR = 0,62; IC95%, 0,43-0,90; p = 0,012). Con los IECA/ARA-II, la reduccion del riesgo relativo de la mortalidad estimada fue del 46,1% en los pacientes con FEVI ≤ 40% y del 15,7% en aquellos con FEVI > 40% (pinteraccion = 0,008). En los pacientes con FEVI > 40%, los IECA/ARA-II se asociaron con menor mortalidad solo por infarto agudo de miocardio con elevacion del segmento ST (HR = 0,44; IC95%, 0,21-0.93; p = 0,031). Conclusiones El beneficio de los IECA/ARA-II en mortalidad tras ICP por SCA se concentra en pacientes con FEVI ≤ 40% y aquellos con FEVI > 40% e infarto agudo de miocardio con elevacion del segmento ST. Se precisan estudios contemporaneos que analicen el impacto de los IECA/ARA-II en pacientes con SCA sin elevacion del segmento ST y FEVI > 40%.

The association between prior stroke/transient ischemic attack (TIA) and clinical outcomes in patients with acute coronary syndrome (ACS) has not been well explored. We evaluated the impact of prior stroke/TIA on this specific patient population. We conducted an international multicenter study including 15 401 patients with ACS from the Bleeding Complications in a Multicenter Registry of Patients Discharged With Diagnosis of Acute Coronary Syndrome registry. They were divided into 2 groups: patients with and without prior stroke/TIA. The primary end point was death at 1-year follow-up. Prior stroke/TIA was associated with higher rate of 1-year death (8.7% vs 3.4%; P < .001). It was an independent predictor of 1-year death even after adjustment for confounding variables (odds ratio, 1.705; 95% confidence interval, 1.046-2.778; P = .032). Besides, patients with prior stroke/TIA had significantly increased 1-year reinfarction (5.6% vs 3.8%, P = .015), in-hospital bleeding (8.7% vs 5.8%, P < .001), and 1-year bleeding (5.2% vs 3.0%, P < .001). No difference of antithrombotic therapies or dual antiplatelet therapy (DAPT) types on outcomes was observed in patients with prior stroke/TIA. Prior stroke/TIA was associated with higher 1-year death for patients with ACS who underwent percutaneous coronary intervention. No benefits or harms were observed with different antithrombotic therapies or DAPT types in these patients.

To investigate the safety and efficacy of an early platelet function testing (PFT)-guided de-escalation of dual antiplatelet treatment (DAPT) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) with bioresorbable vascular scaffolds (BVS). Early DAPT de-escalation is a new non-inferior alternative to 12-months DAPT in patients with biomarker positive ACS treated with stent implantation. In this post-hoc analysis of the TROPICAL-ACS trial, which randomized 2610 ACS patients to a PFT-guided DAPT de-escalation (switch from prasugrel to clopidogrel) or to control group (uniform prasugrel), we compared clinical outcomes of patients (n = 151) who received a BVS during the index PCI. The frequency of the primary endpoint (cardiovascular death, myocardial infarction, stroke or BARC ≥ 2 bleeding) was 8.8% (n = 6) in the de-escalation group vs. 12.0% (n = 10) in the control group (HR 0.72, 95% CI 0.26-1.98, p = 0.52) at 12 months. One early definite stent thrombosis (ST) occurred in the control group (day 19) and 1 possible ST (sudden cardiovascular death) in the de-escalation group (day 86), both despite prasugrel treatment and in a background of high on-treatment platelet reactivity assessed at day 14 after randomization (ADP-induced platelet aggregation values of 108 U and 59 U, respectively). A PFT-guided DAPT de-escalation strategy could potentially be a safe and effective strategy in ACS patients with BVS implantation but the level of platelet inhibition may be of particular importance. This hypothesis-generating post-hoc analysis requires verification in larger studies with upcoming BVS platforms. peerReviewed

Atherosclerosis is a common disease whose complications, such as myocardial infarction, are a leading cause of mortality worldwide. Therefore, ideas which try to explain the circumstances of atherosclerotic plaque initiation and progression are warranted. We hypothesize that low-grade inflammation in early life (especially an imbalance between pro- and anti-inflammatory macrophages) triggers a “butterfly effect” within the arterial wall by initiating a sequence of processes that finally leads to atherosclerotic plaque development and progression. Therefore, pharmacological and non-pharmacological interventions aimed to prevent atherosclerosis development should be applied not only in the adult population over 40 years old (according to current American and European guidelines) but should start in early life.

Bleeding complications are frequent and independently predict mortality after transcatheter aortic valve implantation (TAVI). It has been demonstrated that certain platelet parameters are indicative of platelet reactivity. We sought to determine the possible correlation between simple platelet indices and bleeding complications in patients undergoing TAVI. Platelet indices--platelet count, mean platelet volume (MPV), platelet distribution width and plateletcrit--were measured in 110 consecutive patients on the day preceding TAVI. In-hospital bleeding events after TAVI were assessed according to the Valve Academic Research Consortium-2 classification as any bleeding, major and life-threatening bleeding (MLTB) and need for transfusion. By receiver-operating characteristic analysis, only MPV was able to distinguish between patients with and without any bleeding [area under the curve (AUC) 0.629, 95% confidence interval (CI) 0.531-0.719, P = 0.0342], MLTB (AUC 0.730, 95% CI 0.637-0.811, P = 0.0004) and need for transfusion (AUC 0.660, 95% CI 0.563-0.747, P = 0.0045). By multivariate logistic regression, high MPV (>10.6) and low platelet distribution width (

Background A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients. Methods We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine–Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC). Results The BleeMACS registry included 15,401 patients of whom 3,376/15,401 (21.9%) were aged ≥ 75 years. Elderly patients were more commonly treated with clopidogrel and less often treated with ticagrelor or prasugrel. Of 3,376 elderly patients, 190 (5.6%) experienced post-discharge bleeding. The incidence of bleeding was moderately higher in elderly patients (hazard ratio [HR], 2.31, 95% confidence interval [CI], 1.92–2.77). The predictive ability of the BleeMACS score was moderately lower in elderly patients (AUC, 0.652 vs. 0.691, p = 0.001). Conclusion Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Background Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. Methods The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. Results Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68–0.74) in the derivation cohort and 0.72 (95% CI 0.67–0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64–0.66) for PCI patients and 0.63 (95% CI 0.62–0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. Conclusions The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.gov Identifier : NCT02466854

Aims: The benefit of complete or incomplete percutaneous coronary Intervention (PC in patients with myocardial infarction and multivessel disease remains debated. The aim of our study was to compare a complete vs. a "culprit only" revascularisation strategy hi patients with myocardial infarction distinguishing the different clinical subsets (STEM and NSTEMI) and to provide one-year clinical outcome from the "real-life" BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry. Methods and results: We conducted a multicentre study including all patients with myocardial infarction and multivessel coronary disease included in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronae Syndrome) registry. They were divided into two groups, complete revascularisation (CR) and incomplete revascularisation (IR). The primary end-point was the death rate at one-year follow-up. Secondary end-points were in-hospital repeat myocardial infarction (re-AM1), in-hospital heart failure (111:), major adverse cardiovascular events (MACE) and myocardial infarction at one year. Four thousand five hundred and twenty patients were included in our analysis, with a diagnosis of STEMI in 67.7% and NSTEMI in 32.3%. CR was performed in 27.2% and 42.4%, respectively. At univariate analysis, in-hospital and one-year outcomes were similar between CR and IR hi STEMI patients (all p-values >0.05). In NSTEMI patients, CR was associated with a lower one-year death rate (4.5% vs. 8.5%; 1)p=0.002), re-AMI (3.7% vs. 6.6%; p=0.016) and MACE (8.1% vs. 13.9%; p=0.001). After propensity score matching, CR also reduced events in STEM patients, including one-vear mortality (5.3% vs. 13.8%; p

Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy. The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up. The secondary endpoint was bleeding events during follow-up. We performed sub-study analyses according to whether β-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, or proton pump inhibitors (PPIs) were prescribed at discharge. We also calculated the propensity score for optimal medical therapy (OMT; combination of BB, ACEI/ARB, and statins). The study included 926 patients. According to the multivariate analysis, ACEIs/ARBs (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36–1.94; p = 0.03) and statins (HR 0.37, 95 % CI 0.23–0.61; p

Background: The role of platelets in the pathophysiology of acute coronary syndromes (ACS) is undeniable, but precise relationships between platelet activity and treatment outcomes are a matter of continuant investigation. Among platelet indices, mean platelet volume (MPV) has proven to be a valuable predicting factor in cardiac patients. However, platelet distribution width (PDW) is reported to be a more specific marker of platelet reactivity. Thus, application of PDW in risk stratification of ACS treatment is an up-to-date subject of research. PDW values in the assessment of left ventricular (LV) function have not been previously studied. Aim: The aim of the study was to evaluate whether admission PDW can predict LV systolic function in patients with ACS treated with stent implantation. Methods: On-admission PDW was measured in 278 consecutive patients with diagnosis of ACS, who underwent stent(s) implantation. Echocardiogram with LV ejection fraction (LVEF) estimation was performed within 24 h of percutaneous coronary intervention. Additionally, patients were under one-year follow-up, and one-year all-cause mortality was assessed. Results: According to receiver-operating characteristics (ROC) analysis, a PDW value greater than 12.8 fL could predict LVEF ≤ 35% with sensitivity of 81% and specificity of 39% (AUC 0.614; p = 0.0177). Only a trend was noted in ROC for PDW and one-year mortality (AUC 0.608; p = 0.0815). Multivariate logistic regression analysis has shown that the PDW parameter correlates independently with both systolic heart failure with LVEF ≤ 35% (PDW cut-off: 12.8 fL, OR 2.8107, CI 1.1401–6.9293, p = 0.0248) and one-year mortality (PDW cut-off: 16 fL, OR 2.6750, CI 1.0190–7.0225, p = 0.0457). Conclusions: Admission PDW may serve as a simple and widely available predictor of impaired LV function in patients with ACS. Association between PDW and mortality needs to be confirmed in larger studies.

Background: In the setting of the Acute Coronary Syndrome (ACS), differences in response to prasugrel and ticagrelor between East Asian and European patients have not been investigated yet. Methods: This is a sub-analysis of the "BleeMACS registry". Patients admitted for ACS and underwent PCI from between 2012 and 2014 were stratified first according to their provenance, Europe vs. East Asia (China and Japan), and then by country. The adjusted rate of 1-year serious bleeding - safety end-point-and 1-year death/re-infarction -effectiveness endpoint-of the new P2Y12r inhibitors were compared. Results: Data of 10004 patients in Europe and 2332 patients in East Asia were collected. At baseline prior stroke (6% vs 9%, p

Bleeding events after an acute coronary syndrome have a negative impact on prognosis. Available risk scores are limited by suboptimal accuracy, prediction of only in-hospital events and absence of patients treated with new antiplatelet agents in the current era of widespread use of percutaneous coronary intervention. The BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) project is a multicenter investigator-initiated international retrospective registry that enrolled more than 15 000 patients discharged with a definitive diagnosis of acute coronary syndrome and treated with percutaneous revascularization. The primary end point is the incidence of major bleeding events requiring hospitalization and/or red cell transfusion concentrates within 1 year. An integer risk score for bleeding within the first year after hospital discharge will be developed from a multivariate competing-risks regression. The BleeMACS registry collaborative will allow development and validation of a risk score for prediction of major bleeding during follow-up for patients receiving contemporary therapies for acute coronary syndrome

Histone deacetylases inhibitors (HDACi) have recently emerged as potent antitumor treatment modality. They are currently tested in many phase I, II and III clinical trials as single agents as wells as in combination schemes. They have demonstrated promising antitumor activity and favorable clinical outcome. Histone deacetylases (HDACs) are involved in the process of epigenetic regulation of gene expression. Epigenetic changes are believed to be crucial for the onset and progression of cancer and have recently gained remarkable attention. Since epigenetic regulation of gene expression is a reversible process, targeting histone deacetylases provides a good rationale for anticancer therapy. The acetylation status of histones regulates the organization of chromatin and the access of transcription factors. Moreover, functions of many non-histone proteins are controlled by acetylation. The broad and complicated influences of HDACi on various molecular processes may account for the observed pleiotropic effects. In this review we summarize recent advances in the understanding of biology of HDACs and mechanism of action of their inhibitors.