Potential role of left atrial strain in estimation of left atrial pressure in patients with chronic heart failure.

AIMS: In a large proportion of heart failure with reduced ejection fraction (HFrEF) patients, echocardiographic estimation of left atrial pressure (LAP) is not possible when the ratio of the peak early left ventricular filling velocity over the late filling velocity (E/A ratio) is not available, which may occur due to several potential causes. Left atrial reservoir strain (LASr) is correlated with LV filling pressures and may serve as an alternative parameter in these patients. The aim of this study was to determine whether LASr can be used to estimate LAP in HFrEF patients in whom E/A ratio is not available. METHODS AND RESULTS: Echocardiograms of chronic HFrEF patients were analysed and LASr was assessed with speckle tracking echocardiography. LAP was estimated using the current ASE/EACVI algorithm. Patients were divided into those in whom LAP could be estimated using this algorithm (LAPe) and into those in whom this was not possible because E/A ratio was not available (LAPne). We assessed the prognostic value of LASr on the primary endpoint (PEP), which comprised the composite of hospitalization for the management of acute or worsened HF, left ventricular assist device implantation, cardiac transplantation, and cardiovascular death, whichever occurred first in time. We studied 153 patients with a mean age of 58 years of whom 76% men and 82% who were in NYHA class I-II. A total of 86 were in the LAPe group and 67 in the LAPne group. LASr was significantly lower in the LAPne group as compared with the LAPe group (15.8% vs. 23.8%, P < 0.001). PEP-free survival at a median follow-up of 2.5 years was 78% in LAPe versus 51% in LAPne patients. An increase in LASr was significantly associated with a reduced risk of the PEP in LAPne patients (adjusted hazard ratio: 0.91 per %, 95% confidence interval 0.84-0.98). An abnormal LASr (<18%) was associated with a five-fold increase in reaching the PEP. CONCLUSIONS: In HFrEF patients in whom echocardiographic estimation of LAP is not possible due to due to unavailability of E/A ratio, assessing LASr potentially carries added clinical and prognostic value.

Persistently elevated levels of sST2 after acute coronary syndrome are associated with recurrent cardiac events.

PURPOSE: Higher soluble ST2 (sST2) levels at admission are associated with adverse outcome in acute coronary syndrome (ACS) patients. We studied the dynamics of sST2 over time in post-ACS patients prior to a recurrent ACS or cardiac death. METHODS: We used the BIOMArCS case cohort, consisting of 187 patients who underwent serial blood sampling during one-year follow-up post-ACS. sST2 was batch-wise quantified after completion of follow-up in a median of 8 (IQR: 5-11) samples per patient. Joint modelling was used to investigate the association between longitudinally measured sST2 and the endpoint, adjusted for gender, GRACE risk score and history of cardiovascular diseases. RESULTS: Median age was 64 years and 79% were men. The 36 endpoint patients had systematically higher sST2 levels than those that remained endpoint free (mean value 29.6 ng/ml versus 33.7 ng/ml, p-value 0.052). The adjusted hazard ratio for the endpoint per standard deviation increase of sST2 was 1.64 (95% confidence interval: 1.09-2.34; p = 0.019) at any time point. We could not identify a steady or sudden increase of sST2 in the run-up to the combined endpoint. CONCLUSION: Asymptomatic post-ACS patients with persistently higher sST2 levels are at higher risk of recurrent ACS or cardiac death during one-year follow-up.

Prognostic value of temporal patterns of global longitudinal strain in patients with chronic heart failure.

Background: We investigated whether repeatedly measured global longitudinal strain (GLS) has incremental prognostic value over repeatedly measured left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a single "baseline" GLS value, in chronic heart failure (HF) patients. Methods: In this prospective observational study, echocardiography was performed in 173 clinically stable chronic HF patients every six months during follow up. During a median follow-up of 2.7 years, a median of 3 (25th-75th percentile:2-4) echocardiograms were obtained per patient. The endpoint was a composite of HF hospitalization, left ventricular assist device, heart transplantation, cardiovascular death. We compared hazard ratios (HRs) for the endpoint from Cox models (used to analyze the first available GLS measurements) with HRs from joint models (which links repeated measurements to the time-to-event data). Results: Mean age was 58 ± 11 years, 76% were men, 81% were in New York Heart Association functional class I/II, and all had LVEF < 50% (mean ± SD: 27 ± 9%). The endpoint was reached by 53 patients. GLS was persistently decreased over time in patients with the endpoint. However, temporal GLS trajectories did not further diverge in patients with versus without the endpoint and remained stable during follow-up. Both single measurements and temporal trajectories of GLS were significantly associated with the endpoint [HR per SD change (95%CI): 2.15(1.34-3.46), 3.54 (2.01-6.20)]. In a multivariable model, repeatedly measured GLS maintained its prognostic value while repeatedly measured LVEF did not [HR per SD change (95%CI): GLS:4.38 (1.49-14.70), LVEF:1.14 (0.41-3.23)]. The association disappeared when correcting for repeatedly measured NT-proBNP. Conclusion: Temporal evolution of GLS was associated with adverse events, independent of LVEF but not independent of NT-proBNP. Since GLS showed decreased but stable values in patients with adverse prognosis, single measurements of GLS provide sufficient information for determining prognosis in clinical practice compared to repeated measurements, and temporal GLS patterns do not add prognostic information to NT-proBNP.

IGF-1 is not related to long-term outcome in hyperglycemic acute coronary syndrome patients.

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.

Temporal Evolution of Serum Concentrations of High-Sensitivity Cardiac Troponin During 1 Year After Acute Coronary Syndrome Admission.

Background Detailed insights in temporal evolution of high-sensitivity cardiac troponin following acute coronary syndrome (ACS) are currently missing. We aimed to describe and compare the post-ACS kinetics of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT), and to determine their intra- and interindividual variation in clinically stable patients. Methods and Results We determined hs-cTnI (Abbott) and hs-cTnT (Roche) in 1507 repeated blood samples, derived from 191 patients with ACS (median, 8/patient) who remained free from adverse cardiac events during 1-year follow-up. Post-ACS kinetics were studied by linear mixed-effect models. Using the samples collected in the 6- to 12-month post-ACS time frame, patients were then considered to have chronic coronary syndrome. We determined (differences between) the average hs-cTnI and average hs-cTnT concentration, and the intra- and interindividual variation for both biomarkers. Compared with hs-cTnT, hs-cTnI peaked higher (median 3506 ng/L versus 494 ng/L; P<0.001) and was quicker below the biomarker-specific upper reference limit (16 versus 19 days; P<0.001). In the post-6-month samples, hs-cTnI and hs-cTnT showed modest correlation (rspearman=0.60), whereas the average hs-cTnT concentration was 5 times more likely to be above the upper reference limit than hs-cTnI. The intraindividual variations of hs-cTnI and hs-cTnT were 14.0% and 18.1%, while the interindividual variations were 94.1% and 75.9%. Conclusions Hs-cTnI peaked higher after ACS and was quicker below the upper reference limit. In the post-6-month samples, hs-cTnI and hs-cTnT were clearly not interchangeable, and average hs-cTnT concentrations were much more often above the upper reference limit than hs-cTnI. For both markers, the within-patient variation fell largely below beween-patient variation. Registration URL: https://www.trialregister.nl; unique identifiers: NTR1698 and NTR1106.

Health-related quality of life and cardiac rehabilitation: Does body mass index matter?

OBJECTIVE: To investigate the relation between body mass index class and changes in health-related quality of life in patients participating in cardiac rehabilitation. DESIGN: Prospective cohort study. PATIENTS: A total of 503 patients with acute coronary syndrome. METHODS: Data from the OPTICARE trial were used, in which health-related quality of life was measured with the MacNew Heart Disease HRQOL Instrument at the start, directly after, and 9 months after completion of cardiac rehabilitation. Patients were classed as normal weight, overweight, or obese. RESULTS: During cardiac rehabilitation, global health-related quality of life improved in patients in all classes of body mass index. Patients classed as overweight had a significantly greater improvement in social participation than those classed as normal weight (5.51-6.02 compared with 5.73-5.93, respectively; difference in change 0.30, p = 0.025). After completion of cardiac rehabilitation, health-related quality of life continued to improve similarly in patients in all classes of body mass index. CONCLUSION: Health-related quality of life improved during cardiac rehabilitation in patients of all classes of body mass index. Patients classed as overweight showed the greatest improvement. The beneficial effects were maintained during extended follow-up after completion of cardiac rehabilitation.

Stabilization patterns and variability of hs-CRP, NT-proBNP and ST2 during 1 year after acute coronary syndrome admission: results of the BIOMArCS study.

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.

High-frequency metabolite profiling and the incidence of recurrent cardiac events in patients with post-acute coronary syndrome.

Purpose: The aim of this study was to study temporal changes in metabolite profiles in patients with post-acute coronary syndrome (ACS), in particular prior to the development of recurrent ACS (reACS).Methods: BIOMArCS (BIOMarker study to identify the Acute risk of a Coronary Syndrome) is a prospective study including patients admitted for ACS, who underwent high-frequency blood sampling during 1-year follow-up. Within BIOMArCS, we performed a nested case-cohort analysis of 158 patients (28 cases of reACS). We determined 151 metabolites by nuclear magnetic resonance in seven (median) blood samples per patient. Temporal evolution of the metabolites and their relation with reACS was assessed by joint modelling. Results are reported as adjusted (for clinical factors) hazard ratios (aHRs).Results: Median age was 64 (25th-75th percentiles; 56-72) years and 78% were men. After multiple testing correction (p < 0.001), high concentrations of extremely large very low density lipoprotein (VLDL) particles (aHR 1.60/SD increase; 95%CI 1.25-2.08), very large VLDL particles (aHR 1.60/SD increase; 95%CI 1.25-2.08) and large VLDL particles (aHR 1.56/SD increase; 95%CI 1.22-2.05) were significantly associated with reACS. Moreover, these longitudinal particle concentrations showed a steady increase over time prior to reACS. Among the other metabolites, no significant associations were observed.Conclusion: Post-ACS patients with persistent high concentrations of extremely large, very large and large VLDL particles have increased risk of reACS within 1 year.

Circulating Biomarkers of Cell Adhesion Predict Clinical Outcome in Patients with Chronic Heart Failure.

Cardiovascular inflammation and vascular endothelial dysfunction are involved in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. We evaluated temporal patterns of 12 blood biomarkers of cell adhesion in patients with CHF. In 263 ambulant patients, serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (1.4-2.5) years. The primary endpoint (PE) was a composite of cardiovascular mortality, HF hospitalization, heart transplantation and implantation of a left ventricular assist device and was reached in 70 patients. We selected the baseline blood samples in all patients, the two samples closest to a PE, or, for event-free patients, the last sample available. In these 567 samples, associations between biomarkers and PE were investigated by joint modelling. The median age was 68 (59-76) years, with 72% men and 74% New York Heart Association class I-II. Repeatedly measured levels of Complement component C1q receptor (C1qR), Cadherin 5 (CDH5), Chitinase-3-like protein 1 (CHI3L1), Ephrin type-B receptor 4 (EPHB4), Intercellular adhesion molecule-2 (ICAM-2) and Junctional adhesion molecule A (JAM-A) were independently associated with the PE. Their rates of change also predicted clinical outcome. Level of CHI3L1 was numerically the strongest predictor with a hazard ratio (HR) (95% confidence interval) of 2.27 (1.66-3.16) per SD difference in level, followed by JAM-A (2.10, 1.42-3.23) and C1qR (1.90, 1.36-2.72), adjusted for clinical characteristics. In conclusion, temporal patterns of C1qR, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A are strongly and independently associated with clinical outcome in CHF patients.

Longitudinal patterns of N-terminal pro B-type natriuretic peptide, troponin T, and C-reactive protein in relation to the dynamics of echocardiographic parameters in heart failure patients.

AIMS: To further elucidate the nature of the association between N-terminal pro-B type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-TnT), C-reactive protein (CRP), and clinical outcome, we examined the relationship between serial simultaneous measurements of echocardiographic parameters and these biomarkers in chronic heart failure (CHF) patients. METHODS AND RESULTS: In 117 CHF patients with ejection fraction ≤50%, NT-proBNP, hs-TnT, and CRP were measured simultaneously with echocardiographic evaluation at 6-month intervals until the end of 30 months follow-up or until an adverse clinical event occurred. Linear mixed effects models were used for data-analysis. Median follow-up was 2.2 years (interquartile range 1.5-2.6). We performed up to six follow-up evaluations with 55% of patients having at least three evaluations performed. A model containing all three biomarkers revealed that doubling of NT-proBNP was associated with a decrease in left ventricular ejection fraction by 1.83 (95% confidence interval -2.63 to -1.03)%, P < 0.0001; relative increase in mitral E/e' ratio by 12 (6-18)%, P < 0.0001; relative increase in mitral E/A ratio by 16 (9-23)%, P < 0.0001; decrease in tricuspid annular plane systolic excursion by 0.66 (-1.27 to -0.05) mm, P = 0.03; rise in tricuspid regurgitation peak systolic gradient by 2.74 (1.43-4.05) mmHg, P = 0.001; and increase in left ventricular and atrial dimensions, P < 0.05. Hs-TnT and CRP showed significant associations with some echocardiographic parameters after adjustment for clinical covariates, but after adjustment for the other biomarkers the associations were not significant. CONCLUSION: Serum NT-proBNP independently reflects changes in echocardiographic parameters of systolic function, left ventricular filling pressures, estimated pulmonary pressure, and chamber dimensions. Our results support further studies on NT-proBNP as a surrogate marker for haemodynamic congestion and herewith support its potential value for therapy guidance.

Details on high frequency blood collection, data analysis, available material and patient characteristics in BIOMArCS.

The Biomarker Study to Identify the Acute Risk of a Coronary Syndrome (BIOMArCS) is a prospective, observational study that has been designed to study the evolution of blood biomarkers in post-acute coronary syndrome (ACS) patients. In our recently published study "Temporal evolution of Myeloperoxidase and Galectin 3 during 1 year after acute coronary syndrome admission" [1] in the American Heart Journal, we demonstrated that repeatedly measuring MPO and Galectin-3 does not aid to differentiate between patients with and without adverse cardiac events during 1-year follow-up. In this Data-In-Brief article, we present further details on data collections and data analysis. In addition, a detailed description of baseline characteristics and the distribution of blood sampling moments is provided. The BIOMArCS dataset contains clinical information and follow-up data on all enrolled 844 patients. These patients underwent a median of 17 (25th -75th percentile 12-20) repeated blood samples in the first year after the index ACS. Blood samples were stored at -80 °C within a median of 82 (25th-75th percentile 58-117) minutes after withdrawal. We collected whole blood, citrate plasma, EDTA plasma, serum and DNA. The dataset used for the analysis in the accompanying research paper has been made available online. We welcome collaborations for further use of our data, whether or not in combination with other biobanks.

Longitudinally Measured Fibrinolysis Factors are Strong Predictors of Clinical Outcome in Patients with Chronic Heart Failure: The Bio-SHiFT Study.

OBJECTIVE: This article investigates whether longitudinally measured fibrinolysis factors are associated with cardiac events in patients with chronic heart failure (CHF). METHODS: A median of 9 (interquartile range [IQR] 5-10) serial, tri-monthly blood samples per patient were prospectively collected in 263 CHF patients during a median follow-up of 2.2 (IQR 1.4-2.5) years. Seventy patients (cases) reached the composite endpoint of cardiac death, heart failure hospitalization, left ventricular assist device, or heart transplantation. From all longitudinal samples, we selected baseline samples in all patients and the last two samples before the event in cases or the last sample available in event-free patients. Herein, we measured plasminogen activator inhibitor 1 (PAI-1), tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), and soluble urokinase plasminogen activator surface receptor (suPAR). Associations between temporal biomarker patterns during follow-up and the cardiac event were investigated using a joint model. RESULTS: Cases were on average older and showed higher New York Heart Association class than those who remained event-free. They also had lower blood pressures, and were more likely to have diabetes, renal failure, and atrial fibrillation. Longitudinally measured PAI-1, uPA, and suPAR were independently associated with adverse cardiac events after correction for clinical characteristics (hazard ratio [95% confidence interval]) per standard deviation increase of 2.09 (1.28-3.45) for PAI-1, 1.91 (1.18-3.24) for uPA, and 3.96 (2.48-6.63) for suPAR. Serial measurements of tPA were not significantly associated with the event after correction for multiple testing. CONCLUSION: Longitudinally measured PAI-1, uPA, and suPAR are strongly associated with adverse cardiac events during the course of CHF. If future research confirms our results, these fibrinolytic factors may carry potential for improved, and personalized, heart failure surveillance and treatment monitoring.

Anti-Oxidized LDL Antibodies and Coronary Artery Disease: A Systematic Review.

Antibodies to oxidized LDL (oxLDL) may be associated with improved outcomes in cardiovascular disease. However, analysis is restricted by heterogenous study design and endpoints. Our objective was to conduct a comprehensive systematic review assessing anti-oxLDL antibodies in relation to coronary artery disease (CAD). Through a systematic literature search, we identified all studies assessing the relationship of either, IgG or IgM ox-LDL/ copper-oxLDL/ malondialdehyde-LDL, with coronary atherosclerosis or cardiovascular events in populations with, and without, established CAD. Systematic review best practices were adhered to and study quality was assessed. An initial electronic database search identified 2059 records, which was subsequently followed by abstract and full-text review. Finally, we included 18 studies with over 1811 patients with CAD. The studies varied according to populations studied, conventional cardiovascular risk factors and interventional modalities used to assess CAD. IgM anti-oxLDL antibodies were found to indicate protection from more severe CAD and possibly cardiovascular events, whilst the relationship with IgG is more complex and difficult to elucidate, with studies reporting divergent results. In this systematic review, there is evidence that suggests a relationship between anti-oxLDL antibodies and CAD, especially for the IgM subclass. However, further studies, with well-characterized prospective cohorts, will be important to clarify these associations.

Repeated Echocardiograms Do Not Provide Incremental Prognostic Value to Single Echocardiographic Assessment in Minimally Symptomatic Patients with Chronic Heart Failure: Results of the Bio-SHiFT Study.

BACKGROUND: We aimed to compare the prognostic value of a single "baseline" echocardiogram with repeated echocardiography in stable chronic heart failure (CHF) patients. We hypothesized that repeated echocardiograms would contain incremental prognostic information. METHODS: In the prospective Bio-SHiFT study, we performed 332 echocardiograms in 106 patients during a median follow-up of 2.3 years. The endpoint comprised HF hospitalization, left ventricular (LV) assist device implantation, heart transplantation, and cardiovascular death. We compared hazard ratios (HRs; adjusted for N-terminal pro-brain natriuretic peptide) from Cox models for the first available measurement with HRs from joint models, which model individual trajectories based on the repeated measurements and link these to the time-to-event data. RESULTS: The mean age of the patients was 58.1 years; 78.3% were male, 12.6% had New York Heart Association class >II, all had reduced ejection fraction, and the most common HF etiologies were cardiomyopathies (51%) and ischemia (40%). The endpoint occurred in 25 patients. Both the single measurements and the temporal trajectories were significantly associated with the endpoint (adjusted HR Cox model [95% CI] vs adjusted HR joint model [95% CI]): LV ejection fraction, 1.47 (0.93-2.31) vs 1.77 (1.13-2.93); diastolic LV diameter, 1.64 (1.09-2.47) vs 1.68 (1.12-2.57); systolic LV diameter, 1.72 (1.10-2.69) vs 1.68 (1.13-2.63); systolic left atrial diameter, 1.88 (1.18-3.00) vs 2.60 (1.48-4.97); E/A ratio, 2.73 (1.42-5.26) vs 3.87 (1.75-10.13); and E/e' ratio, 2.30 (1.38-3.84) vs 2.99 (1.68-6.19). None of the trajectories from the investigated parameters showed worsening prior to events. CONCLUSIONS: Although single baseline or repeatedly measured echocardiographic parameters were associated with the endpoint, all parameters remained on average stable during the 2.3 years of follow-up in this largely minimally symptomatic CHF cohort. Thus, regular echocardiographic monitoring of systolic or diastolic LV function within this time frame does not carry incremental prognostic information over a single baseline measurement.

Temporal evolution of myeloperoxidase and galectin 3 during 1 year after acute coronary syndrome admission.

Prior studies reported that Myeloperoxidase and Galectin-3, which are biomarkers of coronary plaque vulnerability, are elevated in acute coronary syndrome (ACS) patients. We studied the temporal evolution of these biomarkers early after ACS admission and prior to a recurrent ACS event during 1 year follow-up.

Dataset on blood biomarkers and GRACE score measured at admission for myocardial infarction in a large secondary hospital.

The GRACE score is currently the most widely used model to assess patient prognosis after myocardial infarction (MI). We have demonstrated that the prognostic performance of the GRACE score can be improved by adding blood biomarkers measured routinely at hospital admission in our study recently published in the International Journal of Cardiology: "Addition of routinely measured blood biomarkers significantly improves GRACE risk stratification in patients with myocardial infarction". In this Data-in-Brief article we present additional original data from our dataset. This dataset consists of clinical and biomarker information and follow-up data of 2055 confirmed MI patients. In 143 of these patients the endpoint (all-cause mortality or reMI) occurred during six months follow-up. We describe the differences in baseline characteristics between ST-elevation MI (STEMI) patients and non-STEMI patients, differences in biomarker levels at admission between patients in whom the endpoint occurred and patients who remained endpoint-free, and associations of the biomarkers with the endpoint. Moreover, we show additional statistical results of analyses that compare the original GRACE-only model with our extended GRACE/biomarker model.

IgM anti-malondialdehyde low density lipoprotein antibody levels indicate coronary heart disease and necrotic core characteristics in the Nordic Diltiazem (NORDIL) study and the Integrated Imaging and Biomarker Study 3 (IBIS-3).

Background: Certain immunoglobulins (Ig) are proposed to have protective functions in atherosclerosis. Objectives: We tested whether serum levels of IgG and IgM autoantibodies against malondialdehyde low density lipoprotein (MDA-LDL) are associated with clinical coronary heart disease (CHD) and unfavorable plaque characteristics. Methods: NORDIL was a prospective study investigating adverse cardiovascular outcomes in hypertensive patients. IBIS-3 analyzed lesions in a non-culprit coronary artery with <50% stenosis using radiofrequency intravascular ultrasound (RF-IVUS) and near-infrared spectroscopy (NIRS). Imaging was repeated after a median of 386?days on rosuvastatin. Associations of antibodies with incident CHD and imaging parameters were assessed in the two sub-studies respectively. Findings: From 10,881 NORDIL patients, 87 had serum sampled at baseline and developed CHD over 4.5 years, matched to 227 controls. Higher titers of IgM anti-MDA-LDL had a protective effect on adverse outcomes, with odds ratio 0.29 (0.11, 0.76; p=0.012; p=0.016 for trend). Therefore, the effect was explored at the lesional level in IBIS-3. 143 patients had blood samples and RF-IVUS measurements available, and NIRS was performed in 90 of these. At baseline, IgM anti-MDA-LDL levels had a strong independent inverse relationship with lesional necrotic core volume (p=0.027) and percentage of plaque occupied by necrotic core (p=0.011), as well as lipid core burden index (p=0.024) in the worst 4 mm segment. Interpretation: Our study supports the hypothesis that lower circulating levels of IgM anti-MDA-LDL are associated with clinical CHD development, and for the first time relates these findings to atherosclerotic plaque characteristics that are linked to vulnerability.

Mid-term outcomes of the Absorb BVS versus second-generation DES: A systematic review and meta-analysis.

BACKGROUND: Bioresorbable Vascular Scaffolds (BVS) were introduced to overcome some of the limitations of drug-eluting stent (DES) for PCI. Data regarding the clinical outcomes of the BVS versus DES beyond 2 years are emerging. OBJECTIVE: To study mid-term outcomes. METHODS: We searched online databases (PubMed/Medline, Embase, CENTRAL), several websites, meeting presentations and scientific session abstracts until August 8th, 2017 for studies comparing Absorb BVS with second-generation DES. The primary outcome was target lesion failure (TLF). Secondary outcomes were all-cause mortality, myocardial infarction, target lesion revascularization (TLR) and definite/probable device thrombosis. Odds ratios (ORs) with 95% confidence intervals (CIs) were derived using a random effects model. RESULTS: Ten studies, seven randomized controlled trials and three propensity-matched observational studies, with a total of 7320 patients (BVS n = 4007; DES n = 3313) and a median follow-up duration of 30.5 months, were included. Risk of TLF was increased for BVS-treated patients (OR 1.34 [95% CI: 1.12-1.60], p = 0.001, I2 = 0%). This was also the case for all myocardial infarction (1.58 [95% CI: 1.27-1.96], p<0.001, I2 = 0%), TLR (1.48 [95% CI: 1.19-1.85], p<0.001, I2 = 0%) and definite/probable device thrombosis (of 2.82 (95% CI: 1.86-3.89], p<0.001 and I2 = 40.3%). This did not result in a difference in all-cause mortality (0.78 [95% CI: 0.58-1.04], p = 0.09, I2 = 0%). OR for very late (>1 year) device thrombosis was 6.10 [95% CI: 1.40-26.65], p = 0.02). CONCLUSION: At mid-term follow-up, BVS was associated with an increased risk of TLF, MI, TLR and definite/probable device thrombosis, but this did not result in an increased risk of all-cause mortality.

Reproducibility of the Pleth Variability Index in premature infants.

The aim was to assess the reproducibility of the Pleth Variability Index (PVI), developed for non-invasive monitoring of peripheral perfusion, in preterm neonates below 32 weeks of gestational age. Three PVI measurements were consecutively performed in stable, comfortable preterm neonates in the first 48 h of life. On each occasion, pulse oximeter sensors were attached to two different limbs for 5 min. Reproducibility was assessed with the intra-class correlation coefficient (ICC) and Bland-Altman analysis. A total of 25 preterm neonates were included. Inter-limb comparison showed fair to moderate ICC's with 95%-confidence intervals (95%-CI). Left hand-right hand ICC = 0.498, 95%-CI (0.119-0.753); right foot-right hand ICC = 0.314 (-0.088-0.644); right foot-left foot ICC = 0.315 (-0.089-0.628). Intra-limb comparison showed fair to moderate ICC for right foot-right foot ICC = 0.380 (-0.014-0.677); and good ICC for right hand-right hand ICC = 0.646 (0.194-0.852). Bland-Altman plots showed moderate reproducibility of measurements between different limbs and of the same limb in consecutive time periods, with large biases and wide limits of agreement. The findings from this study indicate that PVI measurement is poorly reproducible when measured on different limbs and on the same limb in stable and comfortable preterm neonates.