The Interaction of Vasopressin with Hormones of the Hypothalamo-Pituitary-Adrenal Axis: The Significance for Therapeutic Strategies in Cardiovascular and Metabolic Diseases.

A large body of evidence indicates that vasopressin (AVP) and steroid hormones are frequently secreted together and closely cooperate in the regulation of blood pressure, metabolism, water-electrolyte balance, and behavior, thereby securing survival and the comfort of life. Vasopressin cooperates with hormones of the hypothalamo-pituitary-adrenal axis (HPA) at several levels through regulation of the release of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and multiple steroid hormones, as well as through interactions with steroids in the target organs. These interactions are facilitated by positive and negative feedback between specific components of the HPA. Altogether, AVP and the HPA cooperate closely as a coordinated functional AVP-HPA system. It has been shown that cooperation between AVP and steroid hormones may be affected by cellular stress combined with hypoxia, and by metabolic, cardiovascular, and respiratory disorders; neurogenic stress; and inflammation. Growing evidence indicates that central and peripheral interactions between AVP and steroid hormones are reprogrammed in cardiovascular and metabolic diseases and that these rearrangements exert either beneficial or harmful effects. The present review highlights specific mechanisms of the interactions between AVP and steroids at cellular and systemic levels and analyses the consequences of the inappropriate cooperation of various components of the AVP-HPA system for the pathogenesis of cardiovascular and metabolic diseases.

The Problem of Wound Healing in Diabetes-From Molecular Pathways to the Design of an 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).

Different Approaches in Therapy Aiming to Stabilize an Unstable Atherosclerotic Plaque.

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.

Pathophysiology of Atherosclerotic Plaque Development-Contemporary Experience and New Directions in Research.

Atherosclerotic plaque is the pathophysiological basis of important and life-threatening diseases such as myocardial infarction. Although key aspects of the process of atherosclerotic plaque development and progression such as local inflammation, LDL oxidation, macrophage activation, and necrotic core formation have already been discovered, many molecular mechanisms affecting this process are still to be revealed. This minireview aims to describe the current directions in research on atherogenesis and to summarize selected studies published in recent years-in particular, studies on novel cellular pathways, epigenetic regulations, the influence of hemodynamic parameters, as well as tissue and microorganism (microbiome) influence on atherosclerotic plaque development. Finally, some new and interesting ideas are proposed (immune cellular heterogeneity, non-coding RNAs, and immunometabolism) which will hopefully bring new discoveries in this area of investigation.

Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling-Current Experience and Perspectives.

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.

Guided de-escalation of DAPT in acute coronary syndrome patients undergoing percutaneous coronary intervention with BVS implantation: a post-hoc analysis from the randomized TROPICAL-ACS trial.

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.

MicroRNA regulation of extracellular matrix components in the process of atherosclerotic plaque destabilization.

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.

Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes.

PURPOSE: 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.

Multicentre early experience with totally subcutaneous cardioverter-defibrillators in Poland.

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.

Outcome of Patients With Prior Stroke/Transient Ischemic Attack and Acute Coronary Syndromes.

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.

Incidence, predictors and prognostic impact of intracranial bleeding within the first year after an acute coronary syndrome in patients treated with percutaneous coronary intervention.

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.

Impact of renin-angiotensin system blockade on the prognosis of acute coronary syndrome based on left ventricular ejection fraction.

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.

Initial experience with the subcutaneous implantable cardioverter-defibrillator with the real costs of hospitalization analysis in a single Polish center.

BACKGROUND: The recent introduction of an entirely subcutaneous implantable cardioverter-defibril-lator (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 depart-ment 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 pa-tients 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 im-plantation 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, espe-cially for patients without pacing requirements.

Gender-related differences in post-discharge bleeding among patients with acute coronary syndrome on dual antiplatelet therapy: A BleeMACS sub-study.

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.

Association of Beta-Blockers with Survival on Patients Presenting with ACS Treated with PCI: A Propensity Score Analysis from the BleeMACS Registry.

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.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy.

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, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral. CONCLUSION: 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).

Prediction of Post-Discharge Bleeding in Elderly Patients with Acute Coronary Syndromes: Insights from the BleeMACS Registry.

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.

Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: The BleeMACS score.

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.govIdentifier: NCT02466854.

Platelet distribution width predicts left ventricular dysfunction in patients with acute coronary syndromes treated with percutaneous coronary intervention.

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.