Impact of platelet turnover on long-term adverse cardiovascular outcomes in patients undergoing percutaneous coronary intervention.

BACKGROUND: Increased platelet turnover and high platelet reactivity are associated with short-term major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) or stable coronary artery disease (SCAD). We investigated the impact of platelet turnover on long-term MACE. METHODS: Consecutive patients presenting with ACS or SCAD undergoing PCI between 2009 and 2010 were included. All patients received clopidogrel and aspirin as dual antithrombotic therapy regimen. Multivariable Cox proportional hazard models were applied to assess the prognostic impact of platelet turnover (reticulated platelet count [RPC], mean platelet volume [MPV]) and function on long-term MACE, a composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke. RESULTS: In total, 477 patients were eligible. Mean age was 64.3 ± 12.7 years, 68.8% were male. Median follow-up was 5.8 (IQR 4.2-6.5) years. Median RPC was 7.6 (IQR 5.6-10.4) g/L and median MPV was 10.7 (IQR 10.1-11.3) fL. In univariable analysis, RPC was associated with MACE, both as continuous (HR 1.064 [95%CI 1.021-1.111]; P = .006) and dichotomized (HR 1.693 [95%CI 1.156-2.481]; P = .006) variable. After adjustment, continuous RPC (HR 1.055 [95%CI 1.012-1.099]; P = .010) and dichotomized RPC (HR 1.716 [95%CI 1.152-2.559]; P = .007) remained significantly associated with MACE. Neither MPV nor platelet function testing was associated with long-term adverse outcome. CONCLUSION: Increased platelet turnover is associated with long-term adverse outcome in patients with coronary artery disease undergoing PCI. Platelet turnover represents a new marker of atherothrombotic risk and might help to guide composition or duration of antiplatelet therapy.

Incidence and outcomes associated with early heart failure pharmacotherapy in patients with ongoing cardiogenic shock.

OBJECTIVES: Guidelines recommend ß-blockers and renin-angiotensin-aldosterone system blockers to improve long-term survival in hemodynamically stable myocardial infarction patients with a reduced left ventricular ejection fraction. The prevalence and outcomes associated with ß and renin-angiotensin-aldosterone system blocker therapy in patients with ongoing cardiogenic shock is unknown. DESIGN: Secondary analysis of a randomized controlled trial. SETTING: In patients with cardiogenic shock lasting more than 24 hours enrolled in Tilarginine Acetate Injection in a Randomized International Study in Unstable Myocardial Infarction Patients With Cardiogenic Shock, we compared 30-day mortality in patients who received ß or renin-angiotensin-aldosterone system blockers (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or aldosterone antagonists) within 24 hours of randomization with those who did not. INTERVENTIONS: None. PATIENTS: The final study population included 240 patients. A total of 66 patients (27.5%) had either ß blocker or renin-angiotensin-aldosterone system blocker administered within the first 24 hours after the diagnosis of cardiogenic shock. ß-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and aldosterone antagonists were prescribed in 18.8%, 10.6%, and 5.0% of patients, respectively. MEASUREMENTS AND MAIN RESULTS: The observed 30-day mortality among patients was higher in patients who received ß or renin-angiotensin-aldosterone system blockers prior to cardiogenic shock resolution (27.3% vs 16.9%; adjusted hazard ratio, 2.36; 95% CI, 1.06-5.23; p = 0.035). Compared with patients not given ß or renin-angiotensin-aldosterone system blockers, the 30-day mortality was higher among patients treated only with ß-blockers (33.3% vs 16.9%, p = 0.017) but not among those only treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (18.2% vs 16.9%, p = 1.000). CONCLUSIONS: The administration of ß or renin-angiotensin-aldosterone system blockers is common in North America and Europe in patients with myocardial infarction and cardiogenic shock prior to cardiogenic shock resolution. This therapeutic practice was independently associated with higher 30-day mortality, although a statistically significant difference was only observed in the subgroup of patients administered ß-blockers.

The use of mechanical circulatory support in elective high-risk percutaneous coronary interventions: a literature-based review.

Contemporary medical practices allow complete percutaneous coronary intervention (PCI) in a considerable number of patients who previously would have been considered too 'high-risk' for such procedures. The use of mechanical circulatory support (MCS) devices during these high-risk PCIs (HR-PCIs) is thought to reduce the potential risk for major adverse events during and after revascularization. The intra-aortic balloon pump (IABP), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), and the Impella are the most common MCS devices in use. This review aims to summarize the clinical evidence for each of these devices and the potential mechanisms for the improvement in patient outcomes in HR-PCI. The IABP use has rapidly declined in recent years due to no evidence of benefit in HR-PCI and cardiogenic shock. The V-A ECMO results in low rates of major adverse cardiac and cerebrovascular events (MACCEs) but higher rates of acute kidney injury and increased need for transfusions. In initial studies, Impella resulted in a reduced need for repeat interventions and reduced rates of hypotension, but no benefit in mortality. However, MACCE rates with Impella have gradually declined over the last 10 years, reflecting increased operator experience and technical improvements. Thus, a large, randomized trial is needed to assess the efficacy of Impella in HR-PCI with contemporary standards of care. There is currently no individual parameter that can identify patients who would benefit from MCS use in elective HR-PCI. To address this gap, we propose an algorithm that combines anatomical complexity, comorbidities, and clinical presentation to accurately identify candidates for MCS-assisted HR-PCI.

Long-term outcome in patients with takotsubo syndrome : A single center study from Vienna.

BACKGROUND: There is an increasing amount of evidence suggesting multiple fatal complications in takotsubo syndrome; however, findings on the long-term outcome are scarce and show inconsistent evidence. METHODS: This is a single center study of long-term prognosis in takotsubo patients admitted to the Klinik Ottakring, Vienna, Austria, from September 2006 to August 2019. We investigated the clinical features, prognostic factors and outcome of patients with takotsubo syndrome. Furthermore, survivors and non-survivors and patients with a different cause of death were compared. RESULTS: Overall, 147 patients were included in the study and 49 takotsubo patients (33.3%) died during the follow-up, with a median of 126 months. The most common cause of death was a non-cardiac cause (71.4% of all deaths), especially malignancies (26.5% of all deaths). Moreover, non-survivors were older and more often men with more comorbidities (chronic kidney disease, malignancy). Patients who died because of cardiovascular disease were older and more often women than patients who died due to non-cardiovascular cause. Adjusted analysis showed no feature of an independent predictor of cardiovascular mortality for takotsubo patients. Female gender (HR = 0.32, CI: 0.16-0.64, p < 0.001), cancer (HR = 2.35, CI: 1.15-4.8, p = 0.019) and chronic kidney disease (HR = 2.61, CI: 1.11-6.14, p = 0.028) showed to be independent predictors of non-cardiovascular mortality. CONCLUSION: Long-term prognosis of takotsubo patients is not favorable, mainly due to noncardiac comorbidities. Hence, consequent outpatient care in regular intervals after a takotsubo event based on risk factor control and early detection of malignancies seems justified.

Infarction-Related Cardiogenic Shock- Diagnosis, Monitoring and Therapy­A German-Austrian S3 Guideline.

BACKGROUND: The second edition of the German-Austrian S3 guideline contains updated evidence-based recommendations for the treatment of patients with infarction-related cardiogenic shock (ICS), whose mortality is several times higher than that of patients with a hemodynamically stable myocardial infarction (1). METHODS: In five consensus conferences, the experts developed 95 recommendations-including two statements-and seven algorithms with concrete instructions. RESULTS: Recanalization of the coronary vessel whose occlusion led to the infarction is crucial for the survival of patients with ICS. The recommended method of choice is primary percutaneous coronary intervention (pPCI) with the implantation of a drug-eluting stent (DES). If multiple coronary vessels are diseased, only the infarct artery (the "culprit lesion") should be stented at first. For cardiovascular pharmacotherapy-primarily with dobutamine and norepinephrine-the recommended hemodynamic target range for mean arterial blood pressure is 65-75 mmHg, with a cardiac index (CI) above 2.2 L/min/m2. For optimal treatment in intensive care, recommendations are given regarding the type of ventilation (invasive rather than non-invasive, lungprotective), nutrition (no nutritional intake in uncontrolled shock, no glutamine supplementation), thromboembolism prophylaxis (intravenous heparin rather than subcutaneous prophylaxis), und further topics. In case of pump failure, an intra-aortic balloon pump is not recommended; temporary mechanical support systems (Impella pumps, veno-arterial extracorporeal membrane oxygenation [VA-ECMO], and others) are hemodynamically more effective, but have not yet been convincingly shown to improve survival. CONCLUSION: Combined cardiological and intensive-care treatment is crucial for the survival of patients with ICS. Coronary treatment for ICS seems to have little potential for further improvement, while intensive-care methods can still be optimized.

2020 update of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGHTG) on the position statement of the ÖKG and ÖGHTG for transcatheter aortic valve implantation 2011.

This position statement is an update to the 2011 consensus statement of the Austrian Society of Cardiology (ÖKG) and the Austrian Society of Cardiac Surgery (ÖGTHG) for transfemoral transcatheter aortic valve implantation.Due to a number of recently published studies, broadening of indications and recommendations of medical societies and our own national developments, the ÖKG and the ÖGHTG wish to combine the 2017 ESC/EACTS guidelines for the management of valvular heart disease with a national position paper and to focus on certain details for the application in Austria. Thus, this position statement serves as a supplement and further interpretation of the international guidelines.

EAPCI Core Curriculum for Percutaneous Cardiovascular Interventions (2020): Committee for Education and Training European Association of Percutaneous Cardiovascular Interventions (EAPCI). A branch of the European Society of Cardiology.

The proposed 2020 Core Curriculum for Percutaneous Cardiovascular Interventions aims to provide an updated European consensus that defines the level of experience and knowledge in the field of percutaneous cardiovascular intervention (PCI). It promotes homogenous education and training programmes among countries, and is the cornerstone of the new EAPCI certification, designed to support the recognition of competencies at the European level and the free movement of certified specialists in the European Community. It is based on a thorough review of the ESC guidelines and of the EAPCI textbook on percutaneous interventional cardiovascular medicine. The structure of the current core curriculum evolved from previous EAPCI core curricula and from the "2013 core curriculum of the general cardiologist" to follow the current ESC recommendations for core curricula. In most subject areas, there was a wide - if not unanimous - consensus among the task force members on the training required for the interventional cardiologist of the future. The document recommends that acquisition of competence in interventional cardiology requires at least two years of postgraduate training, in addition to four years devoted to cardiology. The first part of the curriculum covers general aspects of training and is followed by a comprehensive description of the specific components in 54 chapters. Each of the chapters includes statements of the objectives, and is further subdivided into the required knowledge, skills, behaviours, and attitudes.

Impella in cardiogenic shock following acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Cardiogenic shock (CS) conveys a high mortality risk. A cardiac assist device may serve as bridge to patient recovery. We aimed to provide a pooled estimate on mortality and complications from studies evaluating the use of the left ventricular assist device Impella in CS following acute myocardial infarction. In addition, we evaluated whether mortality risk differed with device placement before or after percutaneous coronary intervention (PCI). METHODS: We searched Medline, Embase and Web of Science from 2005 until July 2019 for observational studies or clinical trials on this specific patient group. Studies were required to report on 30-day all-cause mortality and device-related complications. We calculated pooled proportions with 95% confidence intervals (CI) using random effects models and the inverse variance method. RESULTS: Overall, 671 patients from 11 studies (2 randomized and 9 observational) were included. Pooled proportions showed a 30-day mortality of 54.6% (95% CI 47.3-61.8; P = 0.22; I2 = 65.8%). Among complications, major bleeding was found in 19.9% (95% CI 14.2-27.3; P < 0.05; I2 = 69.1%), hemolysis in 10.5% (95% CI 7.2-15.0; P < 0.05; I2 = 52.1%), limb ischemia in 5.0% (95% CI 2.6-9.5; P < 0.05; I2 = 48.3%) and stroke in 3.8% of patients (95% CI 2.4-5.9; P < 0.05; I2 = 0%). Sensitivity analysis demonstrated a statistically significant risk reduction in 30-day mortality when Impella was implanted prior to PCI as compared to after PCI, risk ratio (RR): 0.71, CI 0.58-0.86, P = 0.001, I2 = 0%. CONCLUSION: Pooled estimates of Impella use in myocardial infarction with CS revealed a high 30-day mortality; however, as compared to post-PCI, Impella initiation prior to PCI was associated with a survival benefit.

Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome.

AIMS: Concomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS. METHODS AND RESULTS: A total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), 99m Tc-DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)-CA. Voltage/mass ratio (VMR; Sokolow-Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan-Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)-CA and one AL-CA. While global longitudinal strain by echo did not reliably differentiate AS from CA-AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972). CONCLUSION: Both TTR- and AL-CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA-AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR.

Predictors of 30-day mortality in patients with refractory cardiogenic shock following acute myocardial infarction despite a patent infarct artery.

BACKGROUND: Little is known about predictors of survival in patients with persistent shock following acute myocardial infarction (MI) despite a patent infarct artery. METHODS: We examined data from TRIUMPH, a multicenter randomized clinical trial of the nitric oxide synthase inhibitor, L-N(G)-monomethyl-arginine, in patients with persistent vasopressor-dependent cardiogenic shock complicating acute MI at least 1 hour after established infarct-related artery patency. Patients who died within 30 days were compared with those who survived. Continuous variables were assessed using the Wilcoxon rank sum and categorical variables using the chi(2) test. Prespecified baseline variables were included in a multivariable logistic regression model to predict mortality. A second model incorporating baseline vasopressors and dosages and a third model including change in systolic blood pressure at 2 hours were also developed. Bootstrapping was used to assess the stability of model variables. RESULTS: Of 396 patients, 180 (45.5%) died within 30 days. Systolic blood pressure (SBP), measured on vasopressor support, and creatinine clearance were significant predictors of mortality in all models. The number of vasopressors and norepinephrine dose were also predictors of mortality in the second model, but the latter was no longer significant when change in SBP at 2 hours was added as a covariate in the third model. CONCLUSIONS: The SBP, creatinine clearance, and number of vasopressors are significant predictors of mortality in patients with persistent vasopressor-dependent cardiogenic shock following acute MI despite a patent infarct artery. These prognostic variables may be useful for risk-stratification and in selecting patients for investigation of additional therapies.

Early assessment of outcome in cardiogenic shock: relevance of plasma N-terminal pro-B-type natriuretic peptide and interleukin-6 levels.

OBJECTIVE: Plasma N-terminal pro-B-type natriuretic peptide (Nt-pro-BNP) levels are frequently elevated in critically ill patients and are associated with an increased mortality. In this study, we determined Nt-pro-BNP levels in patients with cardiogenic shock (CS) and evaluated its association with clinical and hemodynamic parameters and 30-day mortality. DESIGN: Retrospective study. SETTING: Two, eight-bed intensive care units at a university and a community hospital. PATIENTS: Retrospective study on stored plasma samples of 58 patients with CS, obtained at admission to the intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Massively elevated Nt-pro-BNP concentrations showed no significant association with duration of shock, total Sequential Organ Failure Assessment score, or invasive hemodynamic parameters at the time of blood sampling but a significant association with estimated glomerular filtration rate (p < 0.001), C-reactive protein (p = 0.03), age (p = 0.005), and body weight (p = 0.03). Both in univariate and multivariate survival analyses, Nt-pro-BNP levels above the median (>12,782 pg/mL) were significant predictors of 30-day mortality (p < 0.001) and showed a complementary role with interleukin (IL)-6 in predicting outcome. Patients with IL-6 >195 pg/mL and Nt-pro-BNP above the median value had the highest 30-day mortality (93.7%), whereas patients with lower IL-6 levels together with lower Nt-pro-BNP levels had significantly better survival (mortality rate 26.3%). Among patients who had acute myocardial infarction, those with Nt-pro-BNP concentrations above the median level showed a highly impaired clinical course even if coronary revascularization was successful (30-day mortality 90.9% vs. 29.4%, p = 0.001), whereas survival of patients with unsuccessful revascularization did not differ significantly with respect to the median of Nt-pro-BNP (30-day survival rate 81.8% vs. 75.0%, p = 0.71). CONCLUSION: The massive elevations of Nt-pro-BNP observed in the early phase of CS seem to be independent of ventricular performance. Nt-pro-BNP levels are nevertheless predictive of 30-day survival in patients with CS especially in those with successful revascularization and might be used in combination with IL-6 for estimation of outcome early on.

Increased platelet reactivity in dyslipidemic patients with coronary artery disease on dual anti-platelet therapy.

INTRODUCTION: The optimal duration of dual anti-platelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still a matter of debate. Biomarkers may help to identify patients who will benefit from extended DAPT. The aim of the study was to test the interaction between lipid parameters and platelet function in patients with coronary artery disease (CAD) on DAPT. MATERIAL AND METHODS: Overall, 58 patients on DAPT were prospectively included following PCI in stable CAD. Platelet markers, i.e. mean platelet volume (MPV), platelet distribution width (PDW), fraction of reticulated thrombocytes (RT) and ADP-induced multiple electrode aggregometry (MEA), as well as serum lipids, i.e. high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG) and remnant cholesterol (RC), were assessed after intake of a maintenance dose of ASA and P2Y12 inhibitor. RESULTS: A significant inverse correlation was found for HDL-C levels and markers of platelet activation: MPV (r = -0.351, p = 0.009), PDW (r = -0.391, p = 0.003), fraction of RT (r = -0.402, p = 0.003) and ADP-induced MEA (r = -0.345, p = 0.011). Only a weak or no association was found between other lipid parameters and platelet markers. After multivariable adjustment, HDL-C levels served as a strong and significant predictor of MPV (95% CI: -0.039 to -0.009; p = 0.002), PDW (95% CI: -0.094 to -0.034; p < 0.0001), RT (95% CI: -0.107 to -0.031; p = 0.001) and MEA (95% CI: -0.540 to -0.170; p < 0.0001), while TG, LDL-C, RC and TC were not significantly associated with platelet function. CONCLUSIONS: Within lipid parameters, only HDL-C levels are strongly associated with markers of platelet activation in CAD patients on DAPT. Accordingly, detection of dyslipidemia might indicate the need for prolongation of DAPT.

Impact of On-Site Cardiac Surgery on Clinical Outcomes After Transfemoral Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to investigate the outcome of high-risk and inoperable patients with severe symptomatic aortic stenosis undergoing transfemoral transcatheter aortic valve replacement (TAVR) in hospitals with (iOSCS) versus without institutional on-site cardiac surgery (no-iOSCS). BACKGROUND: Current guidelines recommend the use of TAVR only in institutions with a department for cardiac surgery on site. METHODS: In this analysis of the prospective multicenter Austrian TAVI registry, 1,822 consecutive high-risk patients with severe symptomatic aortic stenosis undergoing transfemoral TAVR were evaluated. A total of 290 (15.9%) underwent TAVR at no-iOSCS centers (no-iOSCS group), whereas the remaining 1,532 patients (84.1%) were treated in iOSCS centers (iOSCS group). RESULTS: Patients of the no-iOSCS group had a higher perioperative risk defined by the logistic EuroSCORE (20.9% vs. 14.2%; p < 0.001) compared with patients treated in hospitals with iOSCS. Procedural survival was 96.9% in no-iOSCS centers and 98.6% in iOSCS centers (p = 0.034), whereas 30-day survival was 93.1% versus 96.0% (p = 0.039) and 1-year survival was 80.9% versus 86.1% (p = 0.017), respectively. After propensity score matching for confounders procedural survival was 96.9% versus 98.6% (p = 0.162), 93.1% versus 93.8% (p = 0.719) at 30 days, and 80.9% versus 83.4% (p = 0.402) at 1 year. CONCLUSIONS: Patients undergoing transfemoral TAVR in hospitals without iOSCS had a significantly higher baseline risk profile. After propensity score matching short- and long-term mortality was similar between centers with and without iOSCS.

Activated protein C levels and outcome in patients with cardiogenic shock complicating acute myocardial infarction.

INTRODUCTION: In patients with severe sepsis, low levels of activated protein C are associated with high morbidity and mortality. In an observational study we investigated whether patients with cardiogenic shock have decreased circulatory levels of activated protein C, and if these are associated with increased mortality. METHODS: We measured serum activated protein C and interleukin-6 levels in 43 patients with cardiogenic shock following acute myocardial infarction and in 15 control patients with uncomplicated myocardial infarction at days 0-5 and 7 after the onset of shock/myocardial infarction. RESULTS: Activated protein C levels were significantly lower in patients with cardiogenic shock compared to controls. In cardiogenic shock patients, there was no difference in activated protein C levels at baseline, whereas activated protein C levels significantly declined in 28-day non-survivors at day 2, compared with 28-day survivors. Lower levels of activated protein C were associated with a higher degree of vasopressor need, whereas there was no significant association with multiple organ failure in the first days. Regarding the inflammatory response, a strong inverse correlation was observed between interleukin-6 and activated protein C levels. CONCLUSION: Patients with cardiogenic shock who did not survive up to 28 days showed a decline in activated protein C levels during the course of the disease, which was inversely correlated with interleukin-6. This study underlines sustained inflammatory mechanisms in the development and persistence of cardiogenic shock, highlighting a potential effect of anti-inflammatory interventions early during cardiogenic shock.

Usefulness of Elevated Levels of Growth Differentiation Factor-15 to Classify Patients With Acute Coronary Syndrome Having Percutaneous Coronary Intervention Who Would Benefit from High-Dose Statin Therapy.

The aim of this study was to evaluate whether growth differentiation factor-15 (GDF-15) plasma concentration at the time of percutaneous coronary intervention (PCI) might help identify those patients with acute coronary syndrome (ACS), who benefit most from high-dose statin treatment. Two hundred eighty-four consecutive patients, who underwent percutaneous coronary intervention (PCI) for ACS, were included in a prospective registry. The combined end point at 3 months after PCI consisted of cardiovascular death, nonfatal myocardial infarction, and unstable angina. Patients were divided into those with elevated levels of GDF-15 and those with lower levels in relation to the median plasma concentration. Results were compared between patients receiving high-dose, highly efficient statins and patients receiving low-dose statins or no statins. The median GDF-15 plasma concentration was 3.31 ng/ml. One hundred six patients (74.6%) of the high GDF-15 group and 122 patients (85.9%) of the low GDF-15 group received high-dose statins. The combined end point was statistically lower in patients with high levels of GDF-15 treated with high-dose statins compared with patients treated with low-dose statins or without statin treatment (3.8% vs 22.2%, hazard ratio [HR] = 0.156; 95% confidence interval [CI], 0.047 to 0.519; p = 0.002). After propensity score adjustment, the results remained significant (adjusted HR for high-dose statins = 0.148; 95% CI, 0.045 to 0.494; p = 0.002). In contrast, in patients with lower levels of GDF-15, there was no significant reduction in combined end point rates associated with high-dose statin treatment (1.6% vs 5.0%, HR = 0.320; 95% CI 0.029 to 3.534; p = 0.353). In conclusion, increased GDF-15 plasma concentrations at the time of PCI and stent implantation might classify high-risk patients with ACS who benefit from high-dose, highly efficient statins.

An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.

OBJECTIVES: The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system. BACKGROUND: Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation. METHODS: We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm. RESULTS: Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO. CONCLUSIONS: Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.

Impact of bivalirudin on mortality and bleeding complications in acute coronary syndrome patients undergoing invasive revascularization : A real world experience.

BACKGROUND: In a retrospective analysis of a prospective single center registry we compared the use of bivalirudin, unfractionated heparin (UFH) monotherapy, UFH + abciximab in 1240 consecutive patients with acute coronary syndrome (ACS) undergoing stent implantation. RESULTS: Bivalirudin was associated with tendentially reduced in-hospital minor or major bleeding rates compared to UFH monotherapy (5.9 % vs. 9.4 % adjusted odds ratio (OR) 0.82, 95 % confidence interval CI 0.45-1.51, p = 0.53) and compared to the pooled UFH group (5.9 % vs. 11.9 %, adjusted OR 0.62, 95 % CI 0.36-1.08, p = 0.09) but with significantly lower bleeding hazards compared to UFH + abciximab (5.9 % vs. 16 %, adjusted OR 0.41, 95 % CI 0.22-0.78, p < 0.01). After 3 years of follow-up, adjusted cardiovascular mortality rates were similar between all groups, particularly between bivalirudin vs. UFH monotherapy (hazard ratio HR 1.12, 95 % CI 0.58-2.16, p = 0.73) and vs. UFH + abciximab (HR 0.91, 95 % CI 0.40-2.10, p = 0.83). Acute or subacute stent thrombosis occurred at a rate of 0.8 % with no significant differences between the groups. CONCLUSIONS: This retrospective analysis in a real world situation of medium to high-risk ACS patients undergoing invasive revascularization confirmed the results of most large-scale randomized trials by demonstrating reduced bleeding rates in favor of bivalirudin vs. UFH + GPI but with no significant differences between treatment strategies for long-term all-cause and cardiovascular mortality.

[Direct and indirect antithrombins in acute coronary syndromes]. / Direkte und indirekte Antithrombine bei akuten Coronarsyndromen.

Unfractionated heparin (UFH) as well as low-molecular-weight heparins (LMWH), especially enoxaparin, are recommended by the current international guidelines for routine used in the conservative treatment of patients with acute coronary syndromes (ACS). UFH is still the recommended antithrombin as soon as percutaneous coronary interventions (PCI) are performed, although the results of different trials clearly have demonstrated the benefit of enoxaparin also in interventional cardiology. Bleeding complications along PCI procedures can be minimized by avoiding crossover from enoxaparin to UFH or vice versa and by reducing the dosage of indirect antithrombins, particularly of enoxaparin, in patients with chronic renal dysfunction and/or the elderly. Especially for those patient groups, bivalirudin offers already today an effective alternative. There is increasing expectation concerning the use of bivalirudin in patients undergoing PCI procedures but firm data exist at present only for low- and medium-risk patients with non ST-elevation ACS. Results of still ongoing trials (ACUITY, HORIZONS) will help to further confirm the role of bivalirudin in patients with high-risk acute coronary syndromes. For other direct antithrombins, e.g., fondaparinux (a pentasaccharide) or melagatran, comparably few data are available at present. Whether these agents will make their way into clinical use, future will tell.

Dynamics of inflammation parameters prior to tachyarrhythmias in critically ill patients.

BACKGROUND: The aim of this study was to assess the dynamics of inflammation parameters prior to a tachyarrhythmic event in critically ill patients. We evaluated the course of inflammation parameters over 48 hours before the occurrence of tachyarrhythmias. METHODS: Prospective observational study conducted at a cardiologic medical-postoperative tertiary intensive care unit at the Vienna university hospital. Between November 1996 and July 1999 all consecutive patients (n = 756) were screened for the occurrence of arrhythmias. Patients with sustained tachyarrhythmias (n = 119) form the basis of the report. The tachyarrhythmia episodes were related to the evolution of C-reactive protein, leukocytes and fibrinogen during the 48 hours before the arrhythmic event. RESULTS: A total of 278 tachyarrhythmia episodes was identified (wide QRS complex tachycardia, n = 168; narrow QRS complex tachycardia, n = 108; ventricular fibrillation, n = 2). The body temperature on the day of arrhythmia was 37.4 +/- 1 degrees C. Overall, there was no statistically significant change in any inflammation parameter within 48 hours prior to tachyarrhythmias (C-reactive protein: 17.4 +/- 12 [-48 h], 16.2 +/- 11 [-24 h], 15.2 +/- 12 [0 h] mg/dl, p = 0.2). When stratifying for different levels of C-reactive protein on the day of arrhythmia, the trend was inhomogenous. For lower strata, values were significantly decreasing towards arrhythmias; for higher strata, an increase in C-reactive protein was observed (stratum A: 8.5 +/- 7.2 [-48 h], 6.6 +/- 4.9 [-24 h], 4.8 +/- 2.9 mg/dl [0 h], p = 0.0001; stratum B: 16.0 +/- 7.1 [-48 h], 13.8 +/- 6.0 [-24 h], 14.4 +/- 2.6 mg/dl [0 h], p = 0.09; stratum C: 21.2 +/- 7.4 [-48 h], 21.5 +/- 7.5 [-24 h], 24.9 +/- 3.0 mg/dl [0 h], p = 0.008; stratum D: 34.3 +/- 13.4 [-48 h], 35.7 +/- 9.0 [-24 h], 39.7 +/- 5.5 mg/dl [0 h], p = 0.13). CONCLUSION: In this group of critically ill patients inflammation parameters did not change significantly during the 48 hours prior to the arrhythmic event. For different levels of C-reactive protein at the time of arrhythmia, no clear dynamics of inflammatory signs were observed.