Search

Purpose: Insulin-like growth factor-1 (IGF-1) has been associated with both protective and detrimental effects on the development of ischemic heart disease. The relationship between IGF-1 levels and major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients remains unclear. This study aimed to investigate the relationship between IGF-1 admission levels in hyperglycemic ACS patients and: (1) MACE over a 5 years follow-up, (2) type 2 diabetes at discharge, and (3) post-ACS myocardial infarct size and dysfunction., Methods: This was a post hoc analysis of the BIOMArCS-2 randomized controlled trial. From July 2008 to February 2012, 276 ACS patients with admission plasma glucose level between 140 and 288 mg/dL were included. Records of the composite of all-cause mortality and recurrent non-fatal myocardial infarction were obtained during 5 years follow-up. Venous blood samples were collected on admission. IGF-1 was measured batchwise after study completion. Oral glucose tolerance test was performed to diagnose type 2 diabetes, whereas infarct size and left ventricular function were assessed by myocardial perfusion scintigraphy (MPS) imaging, 6 weeks post-ACS., Results: Cumulative incidence of MACE was 24% at 5 years follow-up. IGF-1 was not independently associated with MACE (HR:1.00 (95%CI:0.99-1.00), p = 0.29). Seventy-eight patients (28%) had type 2 diabetes at discharge, and the highest quartile of IGF-1 levels was associated with the lowest incidence of diabetes (HR:0.40 (95%CI:0.17-0.95), p = 0.037). IGF-1 levels were not associated with post-ACS myocardial infarct size and dysfunction., Conclusions: IGF-1 carries potential for predicting type 2 diabetes, rather than long-term cardiovascular outcomes and post-ACS myocardial infarct size and dysfunction, in hyperglycemic ACS patients.

Chemokines are involved in the remodeling of the heart; however, their significance as biomarkers in heart failure is unknown. We observed that circulating CXCR3 receptor chemokines CXCL9 and CXCL10 in a rat model of heart failure were increased 1 week after myocardial infarction. CXCL10 was also increased in both remote and infarcted regions of the heart and remained elevated at 16 weeks; CXCL9 was elevated in the remote area at 1 week. In humans, hierarchical clustering and principal component analysis revealed that circulating CXCL10, MIP-1α, and CD40 ligand were the best indicators for differentiating healthy and heart failure subjects. Serum CXCL10 levels were increased in patients with symptomatic heart failure as indexed by NYHA classification II through IV. The presence of CXCL10, MIP-1α, and CD40 ligand appears to be dominant in patients with advanced heart failure. These findings identify a distinct profile of inflammatory mediators in heart failure patients.

Aims: Early risk stratification is important in patients with cardiogenic shock from ST-elevation myocardial infarction (STEMI). We aimed to develop a simple risk chart that includes clinical parameters that are readily available at time of hospital admission to assess risk of 30-day mortality., Methods and Results: A series of 544 STEMI patients admitted to undergo primary percutaneous coronary intervention and presenting with cardiogenic shock were included between 2000 and 2012. Overall 30-day mortality was 38.4% and did not change over the years (p-trend=0.64). Baseline variables that were available at time of hospital admission were entered into a logistic regression model in a forward stepwise manner. Only age (odds ratio (OR) per year 1.05, 95% confidence interval (CI) 1.04-1.07, p<0.001), initial serum lactate level (OR per mmol/l 1.17, 95% CI 1.11-1.24, p<0.001) and initial creatinine level above the upper limit of normal (OR 2.89, 95% CI 1.90-4.37, p<0.001) remained independent predictors, and were subsequently used to develop a risk chart that stratifies risk of 30-day mortality into categories ranging from 0-20% to 80-100%. The calibration plot showed a close relationship between expected and observed mortality. The risk chart had a higher discriminative accuracy than the GRACE score (c-index 0.75 vs. 0.66, p=0.009). Adding variables that were obtained from coronary angiography and during clinical course did not significantly improve discriminative accuracy of risk chart (c-index 0.77, p=0.48)., Conclusion: Mortality of patients with cardiogenic shock from STEMI undergoing primary percutaneous coronary intervention can be well predicted already at time of hospital admission by a risk chart that uses only three variables, namely, age, initial serum lactate and creatinine level., (© The European Society of Cardiology 2015.)

Objectives: Several risk factors for coronary heart disease (CHD) have been associated with improved in-hospital survival after myocardial infarction (MI). We aimed to confirm this paradox and assess whether it extends to long-term outcome. In addition, we investigated temporal mortality trends., Methods: We examined the relation between the presence of four modifiable risk factors for CHD (hypertension, dyslipidaemia, diabetes mellitus and smoking) and mortality in 14,434 consecutive patients admitted with MI to a coronary care unit from 1985 to 2008., Results: Two-thirds of MI patients (n = 10,003) had at least one risk factor for CHD on hospital admission. The presence of at least one compared to no CHD risk factors was associated with a favourable 30-day mortality rate (5% vs. 7%, adjusted odds ratio 0.72, 95% confidence interval (CI): 0.62-0.83). There was significant interaction between the presence of CHD risk factors and decade of hospitalization (p = 0.001). The adjusted 10-year mortality hazard ratio (HR) of at least one CHD risk factor compared to none, was 1.2 (95% CI: 1.0--1.4), 0.89 (0.65--1.2) and 0.89 (0.79--0.99) in 1985--1990, 1990--2000 and 2000--2008, respectively. Survival improved over time. Adjusted 10-year mortality fell (adjusted HR [2000--2008 vs. 1985--1990] 0.59 [95% CI: 0.52--0.66] in patients with, and 0.76 [95% CI: 0.65-0.89] in those without CHD risk factors)., Conclusions: The presence of at least one modifiable CHD risk factor was associated with improved outcome after MI. Patients with CHD risk factors benefited from more substantial mortality reductions during the past few decades.

Importance: Elevated plasma glucose levels in patients with acute coronary syndrome (ACS) on hospital admission are associated with increased mortality. Clinical trials of glucose regulation have provided inconsistent results with respect to cardiovascular outcomes, perhaps because target glucose levels have been suboptimal., Objective: To study the effectiveness and safety of intensive glucose management in patients with ACS who have hyperglycemia, aiming at strict blood glucose normalization., Design, Setting, and Participants: Single-center, prospective, open-label, randomized clinical trial in a large teaching hospital. Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012. Patients with insulin-dependent diabetes mellitus were excluded. Informed consent was obtained from 294 patients, who were randomized. Of these, 93.6% received percutaneous coronary intervention (PCI)., Interventions: Intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, or to conventional expectative glucose management., Main Outcomes and Measures: End points were assessed according to the intention-to-treat principle. The primary end point was high-sensitivity troponin T value 72 hours after admission (hsTropT72); secondary end points, area under the curve of creatine kinase, myocardial band (AUC-CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks' follow-up., Results: In the intensive management arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution, 541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41). Median AUC-CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe hypoglycemia (<50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04). CONCLUSIONS AND RELEVANCE Intensive glucose regulation did not reduce infarct size in hyperglycemic patients with ACS treated with PCI, and was associated with harm. Future studies should focus on patients with ACS who have persistently elevated blood glucose after PCI, and should evaluate alternative strategies for optimizing glycemia., Trial Registration: www.trialregister.nl Identifier: NTR1205.

Background: Little evidence is available on the optimal sequence of intra-aortic balloon pump (IABP) support initiation and primary percutaneous coronary intervention (PCI) in patients who present with cardiogenic shock from ST-elevation myocardial infarction (STEMI). The aim of this study was to evaluate the order of IABP insertion and primary PCI and its association with infarct size and mortality., Methods: A series of 173 consecutive patients admitted with cardiogenic shock from STEMI and treated with primary PCI and IABP between 2000 and 2009 were included. The order of IABP insertion and primary PCI was left at the discretion of the interventional cardiologist., Results: All baseline characteristics were similar in patients who first received IABP (n=87) and patients who received IABP directly after PCI (n=86). In these two groups, cumulative 30-day mortality was 44% and 37% respectively (p=0.39). Median peak serum creatine kinase (CK) concentrations were 5692 U/l and 4034 U/l respectively (p=0.048). In multivariable analysis, IABP insertion before PCI was independently associated with higher CK levels (p=0.046). In patients who survived 30 days, IABP insertion before PCI was not associated with late mortality evaluated at five years of follow-up (HR1.5, 95% CI 0.7-3.3; p=0.34)., Conclusions: Early IABP insertion before primary PCI might be associated with higher peak CK levels, indicating a larger infarct size. A possible explanation may be the increased reperfusion delay. Our study suggests that early reperfusion could have priority over routine early IABP insertion in STEMI patients with cardiogenic shock. Randomized studies are needed to determine the optimal timing of IABP insertion relative to primary PCI., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To determine whether age-dependent inequalities in care and outcome changed over a 24 year period for patients admitted with a myocardial infarction (MI)., Methods: We examined four age groups (<55, 55-65, 65-75, and >75 years) and treatment and mortality in 14,434 consecutive patients admitted for MI to an intensive coronary care unit from 1985 to 2008. Temporal trend analyses were performed by comparing decades of admission (1985-1990 vs. 1990-2000 vs. 2000-2008)., Results: A total of 2040 (14%) of the patients were >75 years of age. Older patients more often were female and less often presented with an ST-segment elevation MI (STEMI). Systematic differences in care were present between the age groups: older patients were less likely to receive evidence-based medical care and reperfusion therapy during the last 24 years, although the differences became smaller over time. In 2000-2008, 30-day (adjusted OR 0.28, 95%CI: 0.23-0.34) and 5-year (adjusted HR 0.61, 95%CI: 0.54-0.68) mortality were lower compared to 1985-1990. These temporal trends were equal across all age groups. Hence, the change in mortality over the 24-year study period is similar among the spectrum of ages. Patients aged <55, 55-65, 65-75, and >75 years had a 20-year mortality of 38, 63, 87 and >95%, respectively., Conclusions: Older patients with an MI remained less likely to receive evidence-based care during 24 years of observation. Temporal reductions in mortality were similar among all age groups. The application of proven MI therapies to appropriate patients regardless of age may even further improve these outcomes., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: We aimed to study sex-related differences in temporal trends in short- and long-term mortality from 1985 to 2008 in patients hospitalized for acute myocardial infarction., Methods and Results: We included a total of 14 434 consecutive patients admitted to our intensive coronary care unit between 1985 and 2008 for myocardial infarction. A total of 4028 patients (28%) were women. Women were more likely to present with a higher risk profile and were equally likely to receive pharmacological and invasive reperfusion therapy compared with men. Women had a higher unadjusted mortality rate at 30 days (odds ratio, 1.3; 95% confidence interval, 1.1-1.5) and during 20 years (hazard ratio, 1.1; 95% confidence interval, 1.0-1.2) of follow-up. After adjustment for baseline characteristics, 30-day mortality was equal (adjusted odds ratio, 1.0; 95% confidence interval, 0.85-1.2) but the hazard for 20-year mortality was lower (adjusted hazard ratio, 0.77; 95% confidence interval, 0.66-0.90) in women compared to men. For 30-day mortality, there was no significant interaction between sex and age, diagnosis, or diabetes mellitus. Survival improved between 1985 and 2008. Temporal mortality reductions between 1985 and 2008 were at least as high in women as in men with myocardial infarction for both 30-day mortality and long-term mortality hazard., Conclusions: The fact that adjusted mortality rates for men and women treated for myocardial infarction in an intensive coronary care unit were similar and declined markedly over a 24-year period suggests that both sexes benefit from the evidence-based therapies that have been developed and implemented during this time period.

Objective: To study temporal trends in short- and long-term outcome after myocardial infarction (MI) according to diabetes status., Research Design and Methods: We included all 14,434 consecutive patients admitted for ST-segment elevation MI or non-ST-segment elevation MI at our center between 1985 and 2008. The study patients were compared according to prevalent diabetes. Temporal trend analyses were performed by comparing decades of admission (1985-1989 vs. 1990-1999 vs. 2000-2008)., Results: A total of 2,015 (14%) of the patients had prevalent diabetes. The risk of presenting with diabetes increased from 8 to 17% from 1985 to 2008. Diabetic patients presented with a higher prevalence of cardiovascular risk factors. With time, the use of evidence-based therapies increased in both patients with and without diabetes. Diabetes is associated with a 1.5-fold increased risk of mortality at the 20-year follow-up. Ten-year mortality decreased over time in patients with diabetes, from 53% in 1985-1989 to 39% in 2000-2008 (adjusted hazard ratio 0.56 [95% CI 0.43-0.73]), and in those without diabetes, from 38% in 1985-1989 to 29% in 2000-2008 (0.66 [0.60-0.73]; P interaction = 0.83). Patients with diabetes benefitted from a higher 30-day and 10-year absolute survival increase., Conclusions: Temporal mortality reductions after MI between 1985 and 2008 were at least as high in patients with diabetes compared with those without diabetes. However, long-term mortality remained higher in diabetic patients. Awareness of the high-risk profile of diabetic patients is warranted and might stimulate optimal medical care and outcome.

Objectives: To determine the risk of short- and long-term mortality and major adverse cardiac events (MACE) in acute myocardial infarction (AMI) patients complicated by cardiogenic shock (CS) in the contemporary practice of primary percutaneous coronary intervention with stenting., Methods: Of the 1,755 consecutive AMI patients undergoing percutaneous coronary intervention with stenting enrolled, 103 had CS at admission. Primary endpoints were early mortality (within 30 days after the index event) and late mortality (from day 31 up to 4 years). Secondary endpoints included MACE [all-cause death, myocardial infarction or target vessel revascularization (TVR)], myocardial infarction, TVR and stent thrombosis., Results: Thirty-day mortality was higher among CS patients, and CS was a strong independent predictor of a higher risk of early death (adjusted HR 3.64, 95% CI 2.44-5.44). The late mortality rate was significantly higher in CS patients, and CS was also a predictor of higher risk of death at a 4-year follow-up (adjusted HR 1.95, 95% CI 1.11-3.45). Recurrent AMI, TVR and stent thrombosis rates were similar among patients with and without CS., Conclusion: CS complicating AMI is still a severe clinical event, mainly with regard to a significant higher risk of early mortality, but also associated with a worse prognosis in 30-day survivors., (Copyright © 2012 S. Karger AG, Basel.)

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration >or=120 ms, respectively (p <0.0001). Annualized event rates for cardiac death/nonfatal infarction were 2.8% in patients with QRS duration <120 ms and 4.8% in patients with QRS duration >or=120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >or=120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia.

Background: Potent inhibition of the platelet glycoprotein IIb/IIIa receptor has improved the acute outcome of patients presenting with acute coronary syndromes (ACS). For patients with ACS undergoing percutaneous balloon angioplasty without coronary stenting in the era of platelet glycoprotein IIb/IIIa blockade, the long-term prognosis is less clear., Objective: To examine the six-month outcome of patients who received eptifibatide within a randomized clinical trial and subsequently underwent balloon angioplasty., Methods: Patients included in this substudy were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized study evaluating the efficacy of eptifibatide in reducing the incidence of death or nonfatal myocardial infarction (MI) in non-ST segment elevation ACS. During the index hospitalization, 1151 (12.2%) of the PURSUIT patients underwent percutaneous balloon angioplasty without coronary stenting., Results: Eptifibatide was associated with a significant reduction in the adjudicated composite end point of death or MI at six months after randomization in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (P=0.037). A trend toward a beneficial effect was evident before the procedure (4.7% versus 6.9%; P=0.13) and at 30 days (12.1% versus 15.3%; P=0.12). The incidence of repeat revascularization was relatively low for patients undergoing PTCA, with no difference observed between the eptifibatide and placebo groups (16.3% versus 14.8%; P=0.51)., Conclusions: Eptifibatide was associated with a sustained beneficial effect to six months in patients with ACS undergoing PTCA. It reduced the incidence of preprocedural MI. The rate of repeat revascularization at six months was low and was not significantly altered by eptifibatide.

Background: The relevance of the adverse prognostic implications of CK-MB elevation after percutaneous coronary intervention (PCI) remains controversial. Therefore, we compared the relationship between the level of postprocedural CK-MB elevation and 6-month mortality in patients undergoing PCI with the relationship between the level of spontaneous, non-PCI-related CK-MB elevation and 6-month mortality in patients with acute coronary syndromes (ACS) treated medically., Methods and Results: In the PURSUIT trial, 5583 of 9461 patients who presented with a non-ST-elevation ACS did not undergo PCI or CABG and had at least 1 CK-MB sample collected during index-hospitalization. There was a gradual increase in 6-month mortality with higher CK-MB levels: 4.1%, 8.6%, 9.0%, 14.3%, 15.5% for CK-MB ratios 0 to 1, >1 to 3, >3 to 5, >5 to 10, and >10 times the upper limit of normal. A combined analysis in 8838 patients undergoing PCI in 5 large, clinical trials revealed a proportional relationship between postprocedural CK-MB levels (1 to 3, >3 to 5, >5 to 10, and >10, the risk of death was 1.3%, 2.0%, 2.3%, 4.3%, and 7.4%, respectively. The absolute mortality rates were lower after procedure-related infarcts compared with spontaneous infarcts. Yet, the relative increase in 6-month mortality with each increase in peak CK-MB level was similar for PCI-related myocardial necrosis and spontaneous myocardial necrosis, as all tests for heterogeneity of the odds ratios were nonsignificant., Conclusions: The present analysis indicates that the adverse prognostic implications of periprocedural myocardial necrosis should be considered similar to the adverse consequences of spontaneous myocardial necrosis.

Objectives: Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods: BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results: On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions: Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients. [ABSTRACT FROM AUTHOR]

The article focuses on a randomized trial BIOMArCS-2 Glucose which was conducted to evaluate the effect of using intensive glucose control (IGC) in myocardial infarction (MI). Topics discussed include no association between use of IGC in hyperglycemic MI patients and improved outcomes, lowering blood glucose in hyperglycemic causes excess mortality and risk of higher mortality during long term follow-up.