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Objective: Heart failure (HF) pathophysiology in patients with obesity may be distinct. To study these features, we identified obesity‐related biomarkers from 4210 circulating proteins in patients with HF with reduced ejection fraction (HFrEF) and examined associations of these proteins with HF prognosis and biological mechanisms. Methods: In 373 patients with trimonthly blood sampling during a median follow‐up of 2.1 (25th–75th percentile: 1.1–2.6) years, we applied an aptamer‐based multiplex approach measuring 4210 proteins in baseline samples and the last two samples before study end. Associations between obesity (BMI > 30 kg/m2) and baseline protein levels were analyzed. Subsequently, associations of serially measured obesity‐related proteins with biological mechanisms and the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, left ventricular assist device implantation, and heart transplantation) were examined. Results: Obesity was identified in 26% (96/373) of patients. A total of 30% (112/373) experienced a PEP (with obesity: 26% [25/96] vs. without obesity: 31% [87/277]). A total of 141/4210 proteins were linked to obesity, reflecting mechanisms of neuron projection development, cell adhesion, and muscle cell migration. A total of 50/141 proteins were associated with the PEP, of which 12 proteins related to atherosclerosis or hypertrophy provided prognostic information beyond clinical characteristics, N‐terminal pro‐B‐type natriuretic peptide, and high‐sensitivity troponin T. Conclusions: Patients with HFrEF and obesity show distinct proteomic profiles compared to patients with HFrEF without obesity. Obesity‐related proteins are independently associated with HF outcome. These proteins carry potential to improve management of obesity‐related HF and could be leads for future research. [ABSTRACT FROM AUTHOR]

Aims: This study aims to provide insight into sex‐specific cardiovascular protein profiles and their associations with adverse outcomes, which may contribute to a better understanding of heart failure (HF) pathophysiology and the optimal use of circulating proteins for prognostication in women and men. Methods and results: In 250 stable patients with HF with reduced ejection fraction (HFrEF), we performed trimonthly blood sampling (median follow‐up: 26 [17–30] months). We selected all baseline samples and two samples closest to the primary endpoint (PEP; composite of cardiovascular death, heart transplantation, left ventricular assist device implantation, and HF hospitalization) or one sample closest to censoring and applied the Olink Cardiovascular III panel. We used linear regression to study sex‐based differences in baseline levels and joint models to study differences in the prognostic value of serially measured proteins. In 66 women and 184 men (mean age of 66 and 67 years, respectively), 21% and 28% reached the PEP, respectively. Mean baseline levels of fatty acid‐binding protein 4, secretoglobin family 3A member 2, paraoxonase 3, and trefoil factor 3 were higher in women (Pinteraction: 0.001, 0.007, 0.018, and 0.049, respectively), while matrix metalloproteinase‐3, interleukin 1 receptor‐like 1, and myoglobin were higher in men (Pinteraction: <0.001, 0.001, and 0.049, respectively), independent of clinical characteristics. No significant differences between sexes were observed in the longitudinal associations of proteins with the PEP. Only peptidoglycan recognition protein 1 showed a suggestive interaction with sex for the primary outcome (Pinteraction = 0.028), without multiple testing correction, and was more strongly associated with adverse outcome in women {hazard ratio [HR] 3.03 [95% confidence interval (CI), 1.42 to 6.68], P = 0.008} compared with men [HR 1.18 (95% CI, 0.84 to 1.66), P = 0.347]. Conclusions: Although multiple cardiovascular‐related proteins show sex differences at baseline, temporal associations with the adverse outcome do not differ between women and men with HFrEF. [ABSTRACT FROM AUTHOR]

Introduction Patients who have experienced an acute coronary syndrome (ACS) are at risk of a recurrent event, but their level of risk varies. Because of their close temporal relationship with vascular injury, longitudinal measurements of circulating endothelial cells (CECs) carry potential to improve individual risk assessment. Methods We conducted an explorative nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS, high-frequency blood sampling was performed during 1-year follow-up. CECs were identified using flow cytometric analyses in 15 cases with recurrent event, and 30 matched controls. Results Cases and controls had a median (25th-75thpercentile) age of 64.1 (58.1-75.1) years and 80% were men. During the months preceding the endpoint, the mean (95%CI) CEC concentration in cases was persistently higher than in controls (12.8 [8.2-20.0] versus 10.0 [7.0-14.4] cells/ml), although this difference was non-significant (P = 0.339). In controls, the mean cell concentration was significantly (P = 0.030) lower in post 30-day samples compared to samples collected within one day after index ACS: 10.1 (7.5-13.6) versus 17.0 (10.8-26.6) cells/ml. Similar results were observed for CEC subsets co-expressing CD133 and CD309 (VEGFR-2) or CD106 (VCAM-1). Conclusion Despite their close relation to vascular damage, no increase in cell concentrations were found prior to the occurrence of a secondary adverse cardiac event. [ABSTRACT FROM AUTHOR]

The prognostic value of SYNTAX score (SS), intravascular ultrasound (IVUS)-derived plaque burden (PB) and near-infrared spectroscopy (NIRS)-derived lipid core burden index(LCBI) for identification of high-risk patients for major adverse cardiovascular events (MACE) has been proven in previous studies. The majority of patients presenting in the cathlab however do not endure MACE over time, and identification of low-risk groups has remained underexposed. This study evaluates the combined prognostic value of SS, PB and LCBI in identifying patients with low MACE risk. This post-hoc analysis combines the ATHEROREMO and IBIS-3 studies and included 798 patients undergoing coronary angiography. Anatomical SS was calculated (N = 617) and ≥40mm non-stenotic segment of a non-target vessel was investigated with IVUS (N = 645) and NIRS (N = 273) to determine PB and maximum 4mm LCBI (LCBI4mm). During five-year follow-up, 191 MACE were observed. Patients with PB ≤70%, LCBI4mm ≤227 (median), or SS ≤8 (median) had lower MACE incidence than their counterparts with higher values. Combined into one model, LCBI4mm ≤227 (adjusted hazard ratio [aHR] 0.49, 95% confidence interval [CI] 0.30–0.78; p-value = 0.003) and SS ≤8 (aHR 0.67, 95%CI 0.48–0.96, p-value = 0.027) were independently associated with (lower) MACE rate, but PB was not. Additionally, negative predictive value (NPV) of this model was high (SS<8: 0.80, PB<70%: 0.77, LCBI4mm<227: 0.79). In this cohort, SS and LCBI4mm proved to be independent predictors of MACE-free survival during five-year follow-up. Combination of SS and LCBI4mm is useful to identify a low-risk population. Furthermore, NPV of SS, PB and LCBI4mm for prediction of MACE is high. [ABSTRACT FROM AUTHOR]

Aims The relation between non-cardiac comorbidities and health-related quality of life (HRQoL) in patients with heart failure (HF) has been studied to a limited extent. To investigate the HRQoL and their determinants among HF patients with and without comorbidities. Methods and results TRIUMPH (TRanslational Initiative on Unique and novel strategies for Management of Patients with Heart failure) is a Dutch prospective, multicentre study enrolling 496 acute HF patients between 2009 and 2014. We included 334 patients who had completed the HRQoL questionnaires at baseline. The HRQoL was measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) en EuroQuality-of-life five Dimensions (EQ-5D). Comorbidity was defined as having a history of at least one of the following comorbidities: chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and/or cerebrovascular accident. Patients with comorbidity (n  = 205, 61%) had lower scores on the physical limitation scale and clinical summary score of the KCCQ (P  = 0.03 and P  = 0.01, respectively). Female sex, COPD, previous HF, increasing body mass index (BMI), elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP), high systolic blood pressure, and the presence of anxiety and/or depression negatively influenced the HRQoL among HF patients with comorbidity. Besides anxiety and depression, we hardly found any other determinant of HRQoL in patients without comorbidity. Conclusion Heart failure patients without comorbidity had better HRQoL than patients with comorbidity. Sex, previous HF, BMI, COPD, systolic blood pressure, NT-proBNP levels, and also anxiety and depression were determinants of HRQoL in patients with comorbidity. In those without comorbidity, apart from anxiety and depression, no further determinants of HRQoL were found. [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]

Aims: This study aimed to investigate the left ventricular (LV) remodelling and long‐term prognosis of patients with new‐onset acute heart failure (HF) with reduced ejection fraction who were pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non‐ischaemic aetiology. Methods and results: This cohort study consisted of 111 patients admitted with new‐onset acute HF in the period 2008–2016 [62% non‐ischaemic aetiology, 48% supported by inotropes, vasopressors, or short‐term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22–34)]. LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow‐up. Both patients with non‐ischaemic and ischaemic HF had significant improvement in LVEF (P < 0.001 and P = 0.004, respectively) with significant higher improvement in those with non‐ischaemic HF (17% vs. 6%, P < 0.001). Patients with non‐ischaemic HF had reduction in LV end‐diastolic and end‐systolic diameters (6 and 10 mm, both P < 0.001), but this was not found in those with ischaemic HF [+3 mm (P = 0.09) and +2 mm (P = 0.07), respectively]. During a median follow‐up of 4.6 years, 98 patients (88%) did not reach the composite endpoint of LV assist device implantation, heart transplantation, or all‐cause mortality, with no difference between with ischaemic and non‐ischaemic HF [hazard ratio 0.69 (95% confidence interval 0.19–2.45)]. Conclusions: Patients with new‐onset acute HF with reduced ejection fraction discharged on optimal medical treatment have a good prognosis. We observed a considerable LV remodelling with improvement in LV function and dimensions, starting already at 6 months in patients with non‐ischaemic HF but not in their ischaemic counterparts. [ABSTRACT FROM AUTHOR]