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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. [ABSTRACT FROM AUTHOR]

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. 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. 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. Asymptomatic post-ACS patients with persistently higher sST2 levels are at higher risk of recurrent ACS or cardiac death during one-year follow-up. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]