Michal Kowara

BleeMACS: rationale and design of the study.

Background 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. Design 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. Conclusion 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.

Impact of blood transfusion on in-hospital myocardial infarctions according to patterns of acute coronary syndrome: Insights from the BleeMACS registry

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.

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.

Baseline platelet indices and bleeding after transcatheter aortic valve implantation.

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 (<14.8) were associated with increased risk of any bleeding [odds ratio (OR) 4.08, 95% CI 1.66–10.07, P = 0.0022; and OR 3.82, 95% CI 1.41–10.36, P = 0.0084, respectively] and MLTB (OR 10.76, 95% CI 3.05–38, P = 0.0002; and OR 8.46, 95% CI 1.69–42.17, P = 0.0092, respectively). Additionally, high MPV independently correlated with the need for transfusion (OR 4.11, 95% CI 1.71–9.86, P = 0.0016). Larger and less heterogenic platelets may be associated with increased risk of short-term bleeding complications after TAVI.

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.

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).

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.

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.

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.

Pneumothorax after pacemaker implantation localized contralaterally to the side of implantation - rare, but possible complication.

Case report – An 86-year old patient developed pneumothorax a few hours after pacemaker implantation. Surprisingly, the pneumothorax localized contralaterally to the site of subclavian vein puncture. It was treated with chest tube puncture, under the care of a pneumonologist, resulting in full recovery. Although pneumothorax localized contralaterally to the site of subclavian vein puncture during pacemaker implantation is very rare, it has been reported in the literature.