Left ventricular systolic ejection time is an independent predictor of all-cause mortality in heart failure with reduced ejection fraction.

AIMS: Colour tissue Doppler imaging (TDI) M-mode through the mitral leaflet is an easy and precise method to obtain cardiac time intervals including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT) and systolic ejection time (SET). The myocardial performance index (MPI) is defined as [(IVCT + IVRT)/SET]. Whether cardiac time intervals obtained by the TDI M-mode method can be used to predict outcome in patients with heart failure with reduced ejection fraction (HFrEF) remains unknown. METHODS AND RESULTS: A total of 997 patients with HFrEF (mean age 67 ± 11 years, 74% male) underwent an echocardiographic examination including TDI. During a median follow-up of 3.4 years (interquartile range 1.9-4.8 years), 165 (17%) patients died. The risk of mortality increased by 9% per 10 ms decrease in SET [per 10 ms decrease: hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06-1.13; P < 0.001]. The association remained significant even after multivariable adjustment for clinical and echocardiographic parameters (per 10 ms decrease: HR 1.06, 95% CI 1.01-1.11; P = 0.030). The MPI was a significant predictor in an unadjusted model (per 0.1 increase: HR 3.06, 95% CI 1.16-8.06; P = 0.023). However, the association did not remain significant after multivariable adjustment. No significant associations between IVCT or IVRT and mortality were found in unadjusted nor adjusted models. Additionally, SET provided incremental prognostic information with regard to predicting mortality when added to established clinical predictors of mortality in patients with HFrEF. CONCLUSION: In patients with HFrEF, SET provides independent and incremental prognostic information regarding all-cause mortality.

Ratio of Transmitral Early Filling Velocity to Early Diastolic Strain Rate as a Predictor of Cardiovascular Morbidity and Mortality Following Acute Coronary Syndrome.

The ratio of early mitral inflow velocity (E) to early diastolic strain rate (E/e'sr) is a significant predictor of cardiac outcomes in various patient populations. This study aims to evaluate the predictive value of E/e'sr for heart failure, acute myocardial infarction, and death due to cardiovascular disease following acute coronary syndrome (ACS). In total, 432 ACS patients underwent echocardiography following percutaneous coronary intervention. The end point was the composite of heart failure, acute myocardial infarction, and death due to cardiovascular disease. Median follow-up was 4.4 (interquartile range 0.2 to 6.3) years. During the follow-up period, 199 (46.1%) met the composite outcome. Mean value of E/e'sr in patients was 0.70 ± 0.37 m. In univariable Cox regression, E/e'sr was a predictor of the composite outcome (hazard ratio [HR] 1.05 95% confidence interval [CI] 1.03 to 1.07, p <0.001, per 0.10 m increase). After multivariable adjustment for demographic and clinical parameters, E/e'sr remained an independent predictor (HR 1.03; 95% CI 1.01 to 1.06; p = 0.013, per 0.10 m increase). Global longitudinal strain (GLS) modified the relation between E/e'sr and outcome (p value for interaction = 0.011). In ACS patients with a relatively preserved systolic function assessed by GLS (GLS ≥ 13.2%), E/e'sr showed to be a significant predictor (HR 1.20; 95% CI 1.06 to 1.36; p = 0.005, per 0.10 m increase). In contrast, E/e'sr was not a significant predictor in ACS patients with impaired systolic function (GLS < 13.2%; HR 1.02; 95% CI 0.99 to 1.04; p = 0.28). In conclusion, E/e'sr provides important prognostic information regarding cardiovascular morbidity and mortality in ACS patients. However, E/e'sr was not an independent predictor over that of echocardiographic parameters. Furthermore, E/e'sr is a stronger prognosticator in patients with relatively preserved systolic function as opposed to patients with impaired systolic function.

Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction.

BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a marker for acute kidney injury and cardiovascular outcome. However, the relative importance of inflammation versus kidney function on plasma NGAL levels is uncertain, making the interpretation of plasma NGAL unclear. Accordingly, we investigated the relationship between plasma NGAL, inflammation and kidney function in patients with myocardial infarction (MI). METHODS: We prospectively included 584 patients with acute ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention (PCI) from 2006 to 2008. Blood samples were drawn immediately before PCI. Additionally, we included 42 patients who had 4 blood samples drawn before and after PCI. Plasma NGAL was measured using a time-resolved immunofluorometric assay. Cross-sectional analyses were performed in these two single-center, prospective study cohorts. RESULTS: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p < 0.001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. CONCLUSIONS: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI.

Interplay Between Adiponectin and Pro-Atrial Natriuretic Peptide and Prognosis in Patients With ST-Segment Elevation Myocardial Infarction.

Natriuretic peptides (NPs) may regulate adipocyte metabolism including adiponectin. Infusion of atrial natriuretic peptide (ANP) increases plasma adiponectin in patients with heart failure. However, this relation has not been examined in a clinical setting or in myocardial infarction (MI). Accordingly, we investigated the interplay between proANP and adiponectin and the prognostic implications in patients with MI. We prospectively included 680 patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention from September 2006 to December 2008. Blood samples were drawn immediately before percutaneous coronary intervention. Additionally, we included 40 patients with 4 obtained blood samples during STEMI. Adiponectin and proANP were measured in all plasma samples. All patients were followed for 5 years. End points were all-cause mortality (n = 137) and the combined end point (n = 170) of major adverse cardiovascular events (MACEs). Plasma adiponectin and proANP were strongly associated at admission (r = 0.34, p <0.001). In patients with increasing proANP during STEMI, adiponectin also increased (0.5 ± 0.3 vs -0.1 ± 0.1 mg/L, p = 0.026). During follow-up, patients with higher adiponectin at admission had increased risk of all-cause mortality and MACE (both, p <0.001). After adjustment for confounding risk factors by Cox regression analysis, adiponectin remained an independent predictor of all-cause mortality and MACE: hazard ratio 1.31 (95% confidence interval 1.07 to 1.60; p = 0.009) and 1.31 (95% confidence interval 1.09 to 1.57; p = 0.004), respectively, for each SD increase. However, the association vanished when proANP was included in the analysis. In conclusion, adiponectin is associated with an increased risk of all-cause mortality and MACE. However, concomitantly elevated proANP levels appear to confound the association between adiponectin and worsened outcome.

Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI patients.

OBJECTIVES: Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate the dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction. DESIGN AND METHODS: We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before pPCI, immediately after pPCI and again on the first and second following days. Left ventricular ejection fraction (LVEF) was evaluated 1-3 days after the pPCI and again at a median of 7months by echocardiography, and infarct size was measured by cardiac magnetic resonance. RESULTS: sRAGE levels were high in the early phase of AMI; sRAGE levels significantly increased after pPCI compared with sRAGE before pPCI (median ratio: 1.25, 95% CI: 1.15-1.35, P<0.001), and the increase was observed prior to Troponin I (TnI). sRAGE levels decreased notably the first day after pPCI (median ratio: 0.34, 95% CI: 0.30-0.39, P<0.001). Peak sRAGE independently associated with long-term cardiac dysfunction estimated by LVEF (P=0.008). Furthermore, sRAGE measured after pPCI associated with infarct size (P=0.038). CONCLUSIONS: sRAGE levels were high in the early phase rather than in the days after AMI and pPCI. The increase in sRAGE was seen before detectable changes in TnI. In addition, sRAGE was independently associated with long-term cardiac dysfunction.

Osteoprotegerin levels change during STEMI and reflect cardiac function.

BACKGROUND: High levels of circulating osteoprotegerin (OPG) predicts long-term outcome in patients with ST-elevation myocardial infarction (STEMI), possibly because of increased vascular inflammation resulting in myocardial damage. In the present study we aimed at elucidating the dynamic progress of OPG levels during STEMI treated with percutaneous coronary intervention (PCI) and additionally, the effect of OPG levels on cardiac function. METHODS: We prospectively included 42 patients with STEMI treated with primary PCI. Four consecutive blood samples were obtained before and after PCI treatment. Plasma OPG levels were determined using an in-house immunoassay. Cardiac function was increased according to echocardiography, estimating left ventricular ejection fraction (LVEF) 1-3 days after STEMI. RESULTS: During STEMI, OPG levels peaked after PCI and then decreased; mean concentrations (95% confidence interval) before PCI, after PCI, and on day 1 and day 2 of 2650 ng/L (2315-3036 ng/L), 2778 ng/L (2442-3363 ng/L), 2024 ng/L (1775-230 6 ng/L), and 1808 ng/L (1551-2106 ng/L), respectively (P < 0.001). Interestingly, the OPG response was observed before the response in troponin I and C-reactive protein. Patients with reduced LVEF (< 40%) exhibited an increased OPG response before, during, and after PCI (mean increase, 38%; 9%-75%; repeated measures analysis of variance, P = 0.009). Adjustment for age, sex, body mass index, and cardiovascular risk factors did not significantly affect the association between reduced LVEF and increased OPG response (mean increase 33% (4%-70%; F = 5.784; P = 0.023). CONCLUSIONS: Circulating OPG levels are altered during STEMI treated with primary PCI. A high OPG level is independently associated with impaired LVEF.

Comparison of osteoprotegerin to traditional atherosclerotic risk factors and high-sensitivity C-reactive protein for diagnosis of atherosclerosis.

Atherosclerosis is the main cause of cardiovascular disease, but the extent of atherosclerosis in individual patients is difficult to estimate. A biomarker of the atherosclerotic burden would be very valuable. The aim of the present study was to evaluate the association of plasma osteoprotegerin (OPG) to clinical and subclinical atherosclerotic disease in a large community-based, cross-sectional population study. In the Copenhagen City Heart Study, OPG concentrations were measured in 5,863 men and women. A total of 494 participants had been hospitalized for ischemic heart disease or ischemic stroke, and compared to controls, this group with clinical atherosclerosis had higher mean OPG (1,773 vs 1,337 ng/L, p <0.001) and high-sensitivity C-reactive protein (2.3 vs 1.6 mg/L, p <0.001). In a multivariate model with age, gender, body mass index, hypertension, diabetes, hypercholesterolemia, smoking status, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and OPG, OPG remained significantly associated with clinical atherosclerosis (p <0.01); high-sensitivity C-reactive protein, in contrast, did not (p = 0.74). In the control group without clinical atherosclerosis, OPG was independently associated with hypertension, diabetes, hypercholesterolemia, smoking, and subclinical peripheral atherosclerosis as measured by ankle brachial index. For each doubling of the plasma OPG concentration, the risk for subclinical peripheral atherosclerosis increased by 50% (p <0.001) after multivariate adjustment. In conclusion, OPG appears to be a promising biomarker of atherosclerosis that is independently associated with traditional risk factors of atherosclerosis, subclinical peripheral atherosclerosis, and clinical atherosclerotic disease such as ischemic heart disease and ischemic stroke.

Impact of abciximab in elderly patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention: an observational registry study.

BACKGROUND: An increasing proportion of patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI) are classified as elderly (aged ≥70 years). The glycoprotein IIb/IIIa inhibitor abciximab is known to reduce adverse outcomes in patients aged <70 years with high-risk ACS undergoing PCI, but conflicting findings relating to its effects in the elderly have been reported. OBJECTIVE: The aim of this study was to evaluate the effect of abciximab in elderly high-risk ACS patients undergoing PCI. METHODS: From our dedicated PCI registry we identified 2068 ACS patients with high-risk lesions that were treated with PCI. Baseline data were collected prospectively. All-cause mortality, target vessel revascularization (TVR), myocardial infarction (MI), and the combination of these were primary study endpoints. All endpoints within 1 year after PCI were registered and validated. The population was subsequently stratified according to age and use of abciximab. RESULTS: Elderly patients constituted 42% of the total population. They presented with more co-morbidities, were less frequently treated with abciximab and had a higher risk of reaching the combined endpoint and higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p=0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p=0.91; TVR: no abciximab 3.4% vs abciximab 5.5%, p=0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p=0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p=0.03; all-cause mortality: no abciximab 4.5% vs abciximab 1.7%, p=0.02; TVR: no abciximab 5.5% vs abciximab 4.3%, p=0.39; MI: no abciximab 7.2% vs abciximab 6.6%, p=0.80). These findings were confirmed in our adjusted analyses. CONCLUSIONS: In this large observational study we found no benefit of abciximab treatment in elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI.

Impact of abciximab in diabetic patients with acute coronary syndrome who undergo percutaneous coronary intervention: results from a high-volume, single-center registry.

BACKGROUND: The prevalence of diabetes mellitus (DM) and ischemic heart disease is increasing. Moreover, patients with DM experiencing an acute coronary syndrome (ACS) have an increased risk of adverse outcomes after revascularization compared to non-diabetics. Data have suggested that the glycoprotein IIb/IIIa inhibitor abciximab might be more efficient in diabetics than in those without DM. METHODS AND RESULTS: We evaluated the effect of abciximab in patients with DM and ACS from our percutaneous coronary intervention (PCI) registry. Among 5,003 patients with ACS who underwent PCI, 629 had DM. Patients were followed for up to 3 years with regard to mortality, myocardial infarction (MI) and target vessel revascularization (TVR). Despite a more severe risk profile, adjusted analyses revealed a marked reduction in TVR (hazard ratio [HR], 0.30; confidence interval [CI], 0.14-0.63; p = 0.002), mortality (HR, 0.53; CI, 0.28-0.97; p = 0.04) and the combined endpoint, also including MI (HR, 0.53; CI, 0.35-0.79; p = 0.002) in the DM patients who received abciximab compared to those who did not, resulting in a risk of reaching the endpoints at levels similar to the risk in patients without DM. The reduction in MI was not significant. CONCLUSION: Our findings suggest that abciximab administered to ACS patients with DM during PCI reduces mortality and the need for TVR to rates similar to those seen in patients without DM and far below the risk in DM patients who do not receive abciximab.