5948Circulating biomarkers of cell adhesion in relation to clinical outcomes in patients with chronic heart failure: the Bio-SHiFT study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Bouwens ◽  
V J Van Den Berg ◽  
K M Akkerhuis ◽  
S Baart ◽  
K Caliskan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Adhesion ◽  
Chronic Heart Failure ◽  
Adhesion Molecule ◽  
Nyha Class ◽  
Temporal Patterns ◽  
Blood Biomarkers ◽  
Mixed Effect ◽  
Two Samples

Abstract Background Cardiovascular inflammation and vascular endothelial dysfunction are present in chronic heart failure (CHF), and cellular adhesion molecules are considered to play a key role in these mechanisms. The temporal patterns of the blood biomarkers involved could provide further insights into these processes. Purpose We aimed to evaluate the prognostic value of the temporal patterns of blood biomarkers of cell adhesion in stable patients with CHF. Methods In 263 patients, a median of 9 (IQR: 5–10) serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The composite primary endpoint (PE) of cardiovascular mortality, HF-hospitalization, heart transplantation and LVAD was reached in 70 patients. For efficiency, we selected all baseline samples, the two samples closest to a PE, and the last sample available for event-free patients. Thus, in 567 samples we measured twelve biomarkers of cell adhesion using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and first PE were investigated by combining linear mixed effect models and Cox regression (so-called joint model). Results Median age was 68 (IQR: 59–76) years, with 72% men and 74% NYHA class I-II. Levels of CD93 (Complement component C1q receptor), CDH5 (VE cadherin), CHI3L1 (Chitinase-3-like protein 1), EPHB4 (Ephrin type-B receptor 4) and JAM-A (Junctional adhesion molecule A) differed at baseline already. The average biomarker evolutions of these markers, and additionally of ICAM-2 (Intercellular adhesion molecule-2), showed different patterns in patients approaching the PE versus those who remained event-free (Figure 1). Repeatedly measured levels of these biomarkers were independently associated with the PE. Corresponding HRs [95% CI] per 1SD increase in log2 level (arbitrary unit) were: CD93: 1.85 [1.29–2.70], CDH5: 1.72 [1.23–2.44], CHI3L1: 2.45 [1.73–3.56], EPHB4: 1.83 [1.33–2.55], ICAM2: 1.74 [1.24–2.46] and JAM-A: 2.07 [1.39–3.18], adjusted for clinical characteristics (age, sex, diabetes, atrial fibrillation, baseline NYHA class, diuretics, systolic blood pressure and eGFR). Figure 1. Average temporal patterns of cell adhesion biomarkers during follow-up. Conclusion CD93, CDH5, CHI3L1, EPHB4, ICAM2 and JAM-A show different patterns as adverse events approach in CHF patients, and their temporal patterns strongly predict clinical outcome. These findings demonstrate the incremental value of repeated measurements of biomarkers of cell adhesion in stable patients with CHF. Acknowledgement/Funding This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

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

2020 ◽  
Vol 9 (1) ◽  
pp. 195 ◽  
Author(s):  
Elke Bouwens ◽  
Victor J. van den Berg ◽  
K. Martijn Akkerhuis ◽  
Sara J. Baart ◽  
Kadir Caliskan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cell Adhesion ◽  
Chronic Heart Failure ◽  
Clinical Outcome ◽  
Adhesion Molecule ◽  
Temporal Patterns ◽  
Cellular Adhesion ◽  
Left Ventricular ◽  
Blood Samples ◽  
Two Samples

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.

scholarly journals Serially measured cytokines and cytokine receptors in relation to clinical outcome in patients with stable heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Bouwens ◽  
A Schuurman ◽  
K.M Akkerhuis ◽  
S.J Baart ◽  
K Caliskan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcome ◽  
Primary Endpoint ◽  
Nyha Class ◽  
Cytokine Receptors ◽  
Funding Source ◽  
Compensatory Mechanism ◽  
Blood Samples ◽  
Two Samples

Abstract Background Activation of the inflammatory response in heart failure (HF) may initially serve as a compensatory mechanism. However, on the longer term, this physiological phenomenon can become disadvantageous. Temporal patterns of inflammatory proteins other than CRP have not yet been investigated in patients with stable HF. Purpose We aimed to evaluate the association of 17 serially measured cytokines and cytokine receptors with clinical outcome in patients with stable heart failure. Methods In 263 patients, 1984 serial, tri-monthly blood samples were collected during a median follow-up of 2.2 (IQR: 1.4–2.5) years. The primary endpoint (PE) composed of cardiovascular mortality, HF-hospitalization, heart transplantation, and LVAD. We selected baseline blood samples in all patients, as well as the two samples closest to the primary endpoint, and the last sample available in event-free patients. Thus, in 567 samples we measured 17 cytokines and cytokine receptors using the Olink Proteomics Cardiovascular III multiplex assay. Associations between biomarkers and PE were investigated by joint modelling. Results Median age was 68 (IQR: 59–76) years, with 72% men, 74% NYHA class I-II and a median ejection fraction of 30% (23–38%). 70 patients reached a PE. After adjustment for clinical characteristics (age, sex, diabetes, atrial fibrillation, NYHA class at baseline, diuretics and systolic blood pressure), 7 biomarkers were associated with the PE (Figure). Interleukin-1 receptor type 1 (IL1RT1) showed the strongest association: HR 2.65 [95% CI: 1.78–4.21]) per standard deviation change in level (NPX) at any point in time during follow-up, followed by Tumor necrosis factor receptor 1 (TNF-R1): 2.25 [1.66–3.08], and C-X-C motif chemokine 16 (CXCL16): 2.18 [1.59–3.04]. After adjustment for baseline N-terminal pro–B-type natriuretic peptide, high-sensitive troponin T and C-reactive protein however, only IL1RT1 and TNF-R1 remained significantly associated with the PE. Conclusion Repeatedly measured levels of several cytokines and cytokine receptors are independently associated with clinical outcome in stable HF patients. These results suggest that repeated measurements of these biomarkers, in addition to established cardiac biomarkers, may contribute to personalized risk assessment and herewith better identify high-risk patients. Figure 1. Associations between levels of cytokines and cytokine receptors and the primary endpoint. Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the Jaap Schouten Foundation and the Noordwest Academie.

Abstract 2803: Multiple Biomarkers For The Prediction Of Cardiac Events In Chronic Heart Failure Patients

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Takeshi Niizeki ◽  
Yasuchika Takeishi ◽  
Yo Koyama ◽  
Tatsuro Kitahara ◽  
Satoshi Suzuki ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Risk Stratification ◽  
Nyha Class ◽  
Cardiac Events ◽  
High Tertile ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Multiple Biomarkers

Backgrounds: Chronic heart failure (CHF) still represents the major cause of death and hospitalization. Although there is substantial interest in the use of newer biomarkers to identify CHF patients (risk assessment and prevention for cardiac events) recently, few investigations have evaluated the incremental usefulness of combination of multiple biomarkers. Measurement of several biomarkers simultaneously could enhance risk stratification. We therefore evaluated the usefulness of 7 known biomarkers for predicting cardiac events. Methods and Results: We analyzed 7 biomarkers (BNP, uric acid, Na, hemoglobin, creatinine, creatinine clearance, high sensitive CRP) which are known as established prognostic markers for CHF in consecutive 399 CHF patients. When there was an abnormal value, we scored it for one point to calculate multimarker score. Patients were categorized tertiles according to multimarker score. Patients with the high tertile were older and had more severe NYHA class and lower ejection fraction than those with low and intermediate tertiles. There were 135 cardiac events including cardiac deaths and readmissions for worsening CHF during follow-up period. A Cox proportional hazard model showed that patients with high tertile were associated with the highest risk of cardiac events compared with other two tertiles (Figure A ). Kaplan-Meier analysis revealed that tertile analysis effectively risk stratified CHF patients for cardiac events (Figure B ). Conclusions: These findings suggest that the combination of the multi-biomarkers could potentially improve the risk stratification of CHF patiens for the prediction of cardiac events.

Prognostic impact of haemostatic derangements in chronic heart failure

2009 ◽  
Vol 102 (08) ◽  
pp. 314-320 ◽  
Author(s):  
Nina Vene ◽  
Barbara Salobir ◽  
Miran Šebeštjen ◽  
Mišo Šabovic ◽  
Irena Keber ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Independent Predictor ◽  
Nyha Class ◽  
Prognostic Impact ◽  
Prognostic Predictor ◽  
Baseline Levels ◽  
Pai 1 ◽  
D Dimer

SummaryHeart failure is characterised by activation of haemostasis. We sought to explore the prognostic impact of deranged haemostasis in chronic heart failure. In stable, optimally managed outpatients with chronic heart failure, baseline levels of prothrombin fragment F1+2, D-dimer, and tPA and PAI-1 antigens were determined. Clinical follow-up was obtained and the rate of events (heart failure related deaths or hospitalisations) was recorded. We included 195 patients [32.3% female, NYHA class II (66.2%) or III (33.8%), mean age 71 years]. During a median follow up of 693 (interquartile range [IQR] 574–788) days, 63 (30.9%) patients experienced an event; those with an event had higher levels of tPA antigen (median 11.8 [IQR 8.7–14.0] vs. 9.4 [7.9–12.1] µg/l; p=0.033) and D-dimer (938 [485–1269] vs. 620 [37–1076] µg/l; p=0.018). However, on Cox multivariate analysis, only tPA levels above optimal cut-off value of 10.2 µg/l (but not D-dimer) emerged as an independent predictor of prognosis (HRadjusted 2.695, 95% confidence interval 1.233–5.363; p=0.017). Our findings suggest that elevated tPA antigen levels are an independent prognostic predictor in patients with chronic stable heart failure.

Estimation of the right atrial pressure by ultrasound-assessed internal jugular vein in patients with advanced chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Ammirati ◽  
D Marchetti ◽  
G Colombo ◽  
A Garascia ◽  
F Macera ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Internal Jugular Vein ◽  
Validation Cohort ◽  
Jugular Vein ◽  
Nyha Class ◽  
Left Ventricular ◽  
Right Atrial ◽  
Class Iii

Abstract Background In patients with systolic chronic heart failure (CHF) clinical signs of congestion cannot always be evident at clinical examination. Right atrial pressure (RAP) measured by right heart catheterization (RHC) is an accurate and reproducible marker of blood volume. A non-invasive accurate tool to identify CHF patients with normal RAP would be desirable to tailor therapy. Purpose To validate an ultrasound (US)-assessed internal jugular vein distensibility (JVD) ratio to identify patients with normal mean RAP (defined as 7 mmHg or less) measured by RHC. Methods We first identify the JVD ratio that allows the most accurate identification of patients with normal RAP in a prospective calibration cohort of 100 patients with systolic CHF. Then, we tested the JVD ratio threshold to identify patients with normal RAP in a validation cohort of 101 consecutive patients with systolic CHF. All patients had a left ventricular ejection fraction (LVEF)<50% and underwent RHC in the setting of heart transplant work-up. At the time of jugular vein puncture, we recorded the internal jugular vein diameter by conventional linear probes. JVD ratio was calculated as the ratio between maximum diameter (during Valsalva maneuver) and rest diameter of the vein (FIGURE). Finally, we assessed the prognostic value of the JVD ratio in the follow up of the first 100 patients. Results In the calibration cohort (mean age 53 years, 13% female; median LVEF 25%, 81% in NYHA class III/IV) we define the best threshold of the JVD ratio to identify patients with normal RAP that has 1.6 with an area under the curve (AUC of 0.74; p<0.0001). Based on this JVD ratio threshold we defined patients with low JVD ratio (≤1.6; n=58; median RAP 8 mmHg) and patients with high JVD ratio (>1.6, n=42; median RAP 4 mmHg). High JVD ratio and low JVD ratio groups had similar clinical and laboratory characteristics. In the validation cohort (mean age 55 years, 13% female; median LVEF 25%; 56% in NYHA class III/IV) using the previously defined 1.6 JVD ratio threshold, we identified 51 patients with low JVD ratio (median RAP 8 mmHg) and 50 patients with high JVD ratio (median RAP 3 mmHg; p<0.0001) The JVD ratio threshold has an accuracy to identify patients with a normal RAP with an AUC of 0.82 (p<0.0001); a predictive positive value of 0.94, negative predictive value of 0.51, specificity of 0.90, and sensitivity of 0.65. Finally, in the calibration cohort, the CHF patients with low JVD ratio (≤1.6) had a higher cumulative incidence of overall death, heart transplant, or left ventricular assist device (42.7% vs. 16.1% in the high JVD ratio group, p log-rank 0.006) at a median of 13-month follow-up. Conclusions We found that US-assessed JVD ratio is a convenient and accurate diagnostic tool to identify patients with advanced systolic CHF with normal vs. increased RAP. This tool could be tested in the ambulatory setting to modulate therapies, particularly diuretics and vasodilators. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Clinical effects of the enhanced external counterpulsation therapy in patients with ischemic chronic heart failure exacerbation COVID-19

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
I Shashenkov ◽  
S.A Gabrusenko ◽  
S.L Babak ◽  
A.G Maliavin
Keyword(s):  
Heart Failure ◽  
Treatment Group ◽  
Chronic Heart Failure ◽  
Nyha Class ◽  
Functional Class ◽  
Clinical Effects ◽  
External Counterpulsation ◽  
Nyha Functional Class ◽  
Enhanced External Counterpulsation

Abstract Objectives The aim of the study was to assess the effects of the enhanced external counterpulsation (EECP) therapy as a rehabilitation method in patients with ischemic chronic heart failure (CHF) after COVID-19. Methods 54 (n=54) stable symptomatic CHF (NYHA, functional class I-II; 35%≤LVEF≤50%) subjects (44 male and 10 female; mean age 61±9,8) with prior anamnesis of CAD, at least one myocardial infarction got the exacerbation of CHF after COVID-19 episode. They were randomized in a 2:1 manner into either 35 1-hour 250–300 mm Hg sessions of EECP (n=36; 30 male, 6 female) or Sham-EECP (n=18; 14 male, 4 female). All subjects had been received optimal CHF and CAD drug therapy. At baseline, a month and half a year after EECP course every subject was examined with echocardiography and 6-minute walk test. Results All 36 active EECP treatment group subjects improved by at least 1 NYHA class, 66% of them had no heart failure symptoms post treatment (p<0.01). 84% of treatment group pts. had sustained NYHA class improvement at half a year follow-up (p<0.01), compared with baseline. There was significant difference between LVEF 44±6,5% at baseline vs post-EECP LVEF 50±4,6% (p<0.01) in active EECP treatment group subjects. At the same time there were no significant changes of NYHA class and LVEF in Sham-EECP subjects. No one subject dies after half a year of follow up. Conclusions Enhanced external counterpulsation (EECP) therapy sustainably improves NYHA functional class and LVEF in patients with ischemic CHF exacerbation after COVID-19. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Cardiometabolic Biomarkers and Their Temporal Patterns Predict Poor Outcome in Chronic Heart Failure (Bio-SHiFT Study)

2018 ◽  
Vol 103 (11) ◽  
pp. 3954-3964 ◽  
Author(s):  
Milos Brankovic ◽  
K Martijn Akkerhuis ◽  
Henk Mouthaan ◽  
Jasper J Brugts ◽  
Olivier C Manintveld ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Troponin T ◽  
Temporal Patterns ◽  
Left Ventricular ◽  
Clinical Predictors ◽  
Igf Binding Proteins ◽  
Fatty Acid Binding ◽  
End Point

Abstract Purpose Multiple hormonal and metabolic alterations occur in chronic heart failure (CHF), but their proper monitoring during clinically silent progression of CHF remains challenging. Hence, our objective was to explore whether temporal patterns of six emerging cardiometabolic biomarkers predict future adverse clinical events in stable patients with CHF. Methods In 263 patients with CHF, we determined the risk of a composite end point of heart failure hospitalization, cardiac death, left ventricular assist device implantation, and heart transplantation in relation to serially assessed blood biomarker levels and slopes (i.e., rate of biomarker change per year). During 2.2 years of follow-up, we repeatedly measured IGF binding proteins 1, 2, and 7 (IGFBP-1, IGFBP-2, IGFBP-7), adipose fatty acid binding protein 4 (FABP-4), resistin, and chemerin (567 samples in total). Results Serially measured IGFBP-1, IGFBP-2, IGFBP-7, and FABP-4 levels predicted the end point [univariable hazard ratio (95% CI) per 1-SD increase: 3.34 (2.43 to 4.87), 2.86 (2.10 to 3.92), 2.45 (1.91 to 3.13), and 2.46 (1.88 to 3.24), respectively]. Independently of the biomarkers’ levels, their slopes were also strong clinical predictors [per 0.1-SD increase: 1.20 (1.11 to 1.31), 1.27 (1.14 to 1.45), 1.23 (1.11 to 1.37), and 1.27 (1.12 to 1.48)]. All associations persisted after multivariable adjustment for patient baseline characteristics, baseline N-terminal pro-hormone brain natriuretic peptide and cardiac troponin T, and pharmacological treatment during follow-up. Main Conclusions The temporal patterns of IGFBP-1, IGFBP-2, IGFBP-7, and adipose FABP-4 predict adverse clinical outcomes during outpatient follow-up of patients with CHF and may be clinically relevant as they could help detect more aggressive CHF forms and assess patient prognosis, as well as ultimately aid in designing more effective biomarker-guided therapy.

Association between self-care and prognosis in 1123 patients with chronic heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Calero ◽  
E Hidalgo ◽  
R Marin ◽  
L Rosenfeld ◽  
I Fernandez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Acute Heart Failure ◽  
Nyha Class ◽  
Self Care ◽  
P Value ◽  
Funding Source ◽  
Class Iii ◽  
Cox Models ◽  
Lower Tertile

Abstract Background Self-care is a crucial factor in the education of patients with heart failure (HF) and directly impacts in the progression of the disease. However, little is published about its major clinical implications as admission or mortality in patients with HF. Aims and methods The aim of the study was to analyze time to admission due to acute heart failure and mortality associated with poor self-care in patients with chronic HF. We prospectively recruited consecutive patients with stable chronic HF referred to a nurse-led HF programme. Selfcare was evaluated at baseline with the 9 item European Heart Failure Self-Care Behavior Scale. Scores were standardized and reversed from 0 (worst selfcare) to 100 (better self care). For the purpose of this study we analyzed the associations of worse self-care (defined as scores below the lower tertile of the scale) with demographic, disease-related (clinical) and psychosocial factors in all patients at baseline. Results We included 1123 patients, mean age 72±11, 639 (60%) were male, mean LVEF 45±17 and 454 (40,4%) were in NYHA class III or IV. Mean score of the 9-item ESCBE was 69±28. Score below 55 (lower tertile) defined impaired selfcare behaviour. Those patients with worse self-care had more ischaemic heart disease, more COPD, and they achieved less distance in the 6 minute walking test. Regarding psychosocial items patients in lower tertile of self-care needed a caregiver more frequently, they present more cognitive impairment, depressive symptoms and worse score in terms of health self-perception. Multivariate Cox Models showed that a score below 55 points in 9-item ESCBE was independently associated with higher readmission due to acute heart failure [HR 1.26 (1.02–1.57), p value=0.034] and with mortality [HR 1.24 CI95% (1.02–1.50), p value=0.028] Conclusion Poor self-care measured with the modified 9-item ESCBE was associated with higher risk of admission due to acute decompensation and higher risk of mortality in patients with chronic heart failure. These results highlight the importance of assessing self-care and provide measures to improve them. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Hospital Univesitario de Bellvitge

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