Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study

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1 Papers in Press. Published October 25, 2016 as doi: /clinchem The latest version is at Clinical Chemistry 63: (2017) General Clinical Chemistry Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study Mattia Arrigo, 1,2,3,4 Quynh A. Truong, 5,6 Duygu Onat, 7 Jackie Szymonifka, 5,6 Etienne Gayat, 1,2 Heli Tolppanen, 1 Malha Sadoune, 1 Ryan T. Demmer, 7 Ka Y. Wong, 7 Jean Marie Launay, 8 Jane-Lise Samuel, 1 Alain Cohen-Solal, 1,3 James L. Januzzi Jr., 6 Jagmeet P. Singh, 6 Paolo C. Colombo, 7 and Alexandre Mebazaa 1,2* BACKGROUND: Soluble CD146 (scd146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, scd146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of scd146 in HF. METHODS: In a peripheral venous stress study, plasma concentrations of scd146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, scd146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years. RESULTS: The induction of venous stress was associated with a pronounced increase in circulating concentrations of scd146 in the congested arm ( 60 g/l) compared to the control arm ( 16 g/l, P 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NTproBNP, median scd146 concentrations were lower in CS than in PV (396 vs 434, P 0.001), indicating a predominantly extracardiac source of scd146. Finally, increased PV concentrations of scd146 were associated with higher risk of MACE at 2 years. CONCLUSIONS: Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients American Association for Clinical Chemistry Heart failure (HF) 9 is one of the leading causes of mortality and is associated with substantial morbidity (1, 2). Hospital readmissions, mostly due to the presence of organ congestion, are particularly frequent in patients with chronic heart failure (CHF) and are associated with adverse outcome (3). The congestive cascade, which often begins several days or weeks before symptom onset, includes a subclinical increase of venous pressures ( hemodynamic congestion ), which may further lead to redistribution of fluids within the lungs and visceral organs ( organ congestion ) and finally to overt signs and symptoms of volume overload ( clinical congestion ) (4). Several strategies for early detection of subclinical organ congestion have been proposed (e.g., daily body weight measurement, or more recently, intrathoracic impedance monitoring and implantable hemodynamic monitoring) (5 8). However, there is still an unmet need for reliable detection of congestion at an early stage to, hopefully, reduce hospitalizations and improve outcome. The use of biomarkers, in particular natriuretic peptides (NPs), was advocated for this purpose (9, 10). However, concentrations of circulating NPs released by the failing heart reflect the severity of myocardial dysfunction and only indirectly systemic congestion (11). 1 INSERM UMR-S 942, Paris, France; 2 Université Paris Diderot, PRES Sorbonne Paris Cité, France; Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France; 3 Université Paris Diderot, PRES Sorbonne Paris Cité, France, Department of Cardiology, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France; 4 Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland; 5 Dalio Institute of Cardiovascular Imaging, New York- Presbyterian Hospital and Weill Cornell Medical College, New York, NY; 6 Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; 7 Division of Cardiology, Columbia University Medical Center, New York NY; 8 Université Paris Diderot, PRES Sorbonne Paris Cité, France, Department of Biochemistry, AP-HP, Lariboisière University Hospitals, Paris, France. Mattia Arrigo and Quynh A. Truong contributed equally to the work, and both should be considered as first authors. * Addresscorrespondencetothisauthorat: SaintLouisLariboisièreUniversityHospitals, 2, rue Ambroise Paré, Paris, France. Fax ; alexandre. mebazaa@aphp.fr. Received May 17, 2016; accepted August 23, Previously published online at DOI: /clinchem American Association for Clinical Chemistry 9 Nonstandard abbreviations: HF, heart failure; CHF, chronic HF; NP, natriuretic peptide; scd146, soluble CD146; NYHA, New York Heart Association; LVEF, left-ventricular ejection fraction; CS, coronary sinus; PV, peripheral vein; CRT, cardiac resynchronization therapy; MACE, major adverse cardiovascular event; LVAD, left-ventricular assist device; NT-proBNP, N-terminal probrain natriuretic-peptide; MMPs, matrix metalloproteinases. 1 Copyright (C) 2016 by The American Association for Clinical Chemistry

2 CD146 is a junctional adhesion molecule, expressed on human vascular endothelial cells and is involved in the control of vessel integrity (12). The soluble form of CD146 (scd146) is generated by ectodomain shedding of surface CD146 (13), possibly in response to endothelial cell stretch. We recently described circulating scd146 as a potential diagnostic biomarker of decompensated HF (14) with similar ability as plasma NPs to identify cardiac origin of acute dyspnea and associated organ congestion (15). While NPs are quasi-exclusively released by failing cardiac myocytes, the main source of plasma scd146 in HF remains undefined. We hypothesized that, differently from NPs, scd146 might have a predominant vascular, extracardiac origin in HF patients and its release might be triggered by vascular endothelial stretch induced by congestion. In this context, we investigated (a) the source, (b) effects of vascular stress on release, and (c) prognostic properties of scd146 in severe chronic HF patients. Methods STUDY POPULATION The study population consisted of 181 stable chronic HF patients, New York Heart Association (NYHA) functional class II IV with reduced left-ventricular ejection fraction (LVEF). A first cohort of patients (n 44) underwent a mechanistic peripheral venous stress study aimed at investigating the effect of venous congestion on scd146 release. A second cohort of patients (n 137) underwent the transcardiac gradient clinical study, where coronary sinus (CS) and peripheral vein (PV) blood samples were obtained, to assess the source (cardiac vs extracardiac) of scd146 and its long-term prognostic value. PERIPHERAL VENOUS STRESS STUDY Peripheral venous stress was created by inflating a pressure cuff around the dominant arm (test arm), increasing venous arm pressure up to 30 mmhg above baseline irrespective of arterial pressure in chronic HF outpatients without clinical evidence of congestion on physical exam and on stable medical therapy, as previously described (16). Venous lactate has been previously shown to remain stable during the venous stress test, suggesting adequate perfusion (16). Blood was sampled through an indwelling venous catheter from the antecubital or basilic vein of the test arm after 90 min and from the control contralateral arm (lacking an inflated cuff) at baseline and after 90 min. Arterial oximetry and forearm circumference were measured at baseline and after 90 min of venous congestion. This study was performed at the Columbia University Medical Center (New York), inclusion and exclusion criteria are summarized in Table S1 in the Data Supplement that accompanies the online version of this article at clinchem.org/content/vol63/issue1. TRANSCARDIAC GRADIENT CLINICAL STUDY Blood of chronic HF patients undergoing cardiac resynchronization therapy (CRT) device implantation was drawn from the CS through the guiding catheter before delivering the CS lead, and simultaneously, from 1 of the upper extremity veins (PV blood). Baseline characteristics, including medical history, 12-lead electrocardiography, and 2-dimensional transthoracic echocardiography were documented. Patients returned for regular clinic visits at 1, 3, and 6 months after device implantation and were followed for events up to 2 years. Major adverse cardiovascular event (MACE) was defined as the composite endpoint of death, cardiac transplant, left ventricular assist device (LVAD) implantation, and HF hospitalization at 2 years. An outcome panel consisting of 2 cardiologists, blinded to the biomarker results, determined the clinical response of each patient based on review of the medical record, with disagreement resolved by consensus with a third cardiologist. This study, performed at Massachusetts General Hospital (Boston), has been previously described in detail (Clinical Trials.gov number NCT ), inclusion and exclusion criteria are summarized in the online Supplemental Table S2 (17). BLOOD SAMPLES STORAGE AND ANALYSIS All samples were centrifuged within 6 h, and the aliquot portions of EDTA plasma were stored in microcentrifuge tubes at 80 C until assayed in a standardized way. Deidentified samples were sent to an independent core laboratory for analysis. Measurements of concentrations of N-terminal probrain natriuretic-peptide (NTproBNP) were performed using a 1-step sandwich chemiluminescent immunoassay (Cobas, Roche Diagnostics) with detection limit of 5 ng/l and coefficients of variation for both repeatability and reproducibility 3.5% in the measured range. Concentrations of scd146 were determined by ELISA (CY-QUANT ELISA scd146, Biocytex) with detection limit of scd146 of 10 g/l and coefficients of variation for both repeatability and reproducibility 20% in the measured range. STATISTICAL ANALYSIS Continuous variables are expressed, after testing for normality using the Shapiro-Wilk test, as mean (SD) or median (interquartile range), as appropriate. Nominal variables are expressed as frequency (percentages). The Wilcoxon signed rank test was used to examine the differences between the transcardiac gradients of CS and PV samples and the differences between test and control arm before and after venous congestion. Differences between 2 independent groups were assessed with a t-test, Wilcoxon rank sum test or Fisher s exact test, as appropriate. Unadjusted and adjusted Cox proportional hazards mod- 2 Clinical Chemistry 63:1 (2017)

3 Soluble CD146, Marker of Congestion in Heart Failure els were used to evaluate the association of scd146 and first occurrence of MACE. Adjustments were performed for age, sex, LVEF, and estimated GFR. The null hypothesis was rejected with an adjusted 2-sided P value Analyses were performed with the use of IBM SPSS Statistics, Version (IBM Corp) and SAS, Version 9.4. (SAS Institute Inc). ETHICAL CONSIDERATIONS The study was performed in observance of national laws and in accordance with the ethical standards of the Declaration of Helsinki, and was approved by local Ethical Committees. All patients provided written informed consent. Results BASELINE CHARACTERISTICS The studied stable chronic HF patients, were predominantly middle-aged men with severely reduced LVEF and NYHA functional class II IV (Table 1 and the online Supplemental Table S3). Cardiovascular risk factors were highly prevalent and ischemic heart disease accounted for at least a third of HF etiologies. Most patients were treated with disease-modifying therapies according to current guidelines (9). PERIPHERAL VENOUS STRESS STUDY Baseline concentrations of scd146 and NT-proBNP were 454 ( g/l) and 341 ( ng/l), respectively. The induction of venous stress was associated with a pronounced increase in circulating concentrations of scd146 in the congested arm [ 60 ( 13; 102) g/l] compared to the control arm [ 16 ( 2; 64) g/l, P 0.025]. After 90 min of venous congestion, plasma concentrations of scd146 in the congested arm and in the control arm were 481 (371; 553) and 442 ( ) g/l, respectively. By contrast, no difference in plasma concentrations of NT-proBNP in the congested arm [ 1.0 ( 12; 89) ng/l] compared to the control arm [ 0.9 ( 20; 29) ng/l, P 0.29] was found (Fig. 1). After 90 min of venous congestion, plasma concentrations of NT-proBNP in the congested arm and in the control arm were 308 ( ) and 327 ( ) ng/l, respectively. Forearm circumference of the congested arm increased after venous stress test from 25.8 to 26.7 cm (P 0.001) while remaining unchanged in the control arm (data not shown). Arterial oximetry of the congested arm after 90 min showed no difference compared to baseline (97.3 vs 97.5%, P 0.6), supporting the evidence of maintained perfusion during venous congestion. There was no clinical adverse event associated with the peripheral venous stress study. TRANSCARDIAC GRADIENT CLINICAL STUDY Transcardiac gradients of NT-proBNP and SCD146 Fig. 2 shows that median NT-proBNP concentrations were higher in CS than in PV [1814 (742; 3560) vs 1718 (628; 3156) ng/l, P 0.001], with a positive transcardiac gradient (difference between CS - PV) of 237 (43; 653) ng/l. By contrast, median scd146 concentrations were lower in CS than in PV [396 (306; 529) vs 434 (339; 587), P 0.001], indicating a negative transcardiac gradient of 31 ( 80; 10) g/l. Concentrations of NTproBNP and scd146 in CS and PV were both associated with the severity of mitral regurgitation (all P 0.01, see online Supplemental Fig. 1). Long-term prognostic value of SCD146. There were 35 (25%) patients with MACE by 2 years, including 14 deaths, 32 HF hospitalizations, 2 patients requiring LVAD implantation and 3 heart transplants. Fig. 3 shows the association of baseline concentrations of scd146 with MACE at 2 years in patients with HF with CRT. PV plasma concentrations of scd146 were associated with 2-fold increase of adjusted risk of MACE per log-unit of scd146, while there was no association between CS values of scd146 and MACE. Likewise, less negative transcardiac gradient (i.e., low PV concentrations) of scd146 was associated with approximately 40% reduced risk of MACE; this remained true after various adjustments (Fig. 3), including concentrations of NT-proBNP (hazard ratio 0.55, 95% CI , P 0.001) Discussion The present study demonstrated that soluble CD146 has a predominant extracardiac source and is rapidly released in the presence of venous congestion. To our knowledge, this is the first biomarker reflecting systemic venous congestion in chronic HF. In addition, scd146 exhibits prognostic value in severe HF patients with CRT. Surface CD146 plays a central role in endothelial cell-cell cohesion and vascular permeability (12, 18). Soluble form of CD146 is generated by active matrix metalloproteinases (MMPs)-dependent ectodomain shedding of surface CD146 (13). Hence, increased surface CD146 shedding leads to scd146 release but also to increased endothelial permeability to many proteins including albumin (13, 19). Using unbiased proteomics, our group previously showed that scd146 was highly present in plasma of HF patients (14). The present study confirmed high circulating scd146 above the upper reference limit (19) in HF patients. Though generated by endothelial cells, the exact source of scd146 in HF was uncertain. The present study strongly suggests extracardiac origin of scd146 in HF patients. Indeed, an in- Clinical Chemistry 63:1 (2017) 3

4 Table 1. Baseline characteristics of patients included in the transcardiac gradient clinical study. Patient characteristics Overall (n = 137) No MACE a (n = 102) MACE a (n = 35) P value Age, years 66 (57 77) b 66 (56 77) 65 (59 75) 0.95 Male, % BMI, c kg/m ( ) 27.9 ( ) 26.5 ( ) 0.23 Diabetes, % <0.001 Hypertension, % Hyperlipidemia, % History of smoking, % Ischemic cardiomyopathy, % History of atrial fibrillation, % History of myocardial infarction,% History of valve replacement NYHA class, % 0.65 II, % III, % IV, % Minnesota QoL Score 44 (19 60) 39 (18 59) 56 (33 64) 0.07 Six-minute walk test, feet 934 ± ± ± Medications ACEi/ARB, % blockers, % Aldosterone antagonists, % Diuretics, % Laboratory results Creatinine, mg/dl d 1.22 ( ) 1.16 ( ) 1.40 ( ) egfr, ml/min 61 ± ± ± ECG parameters Normal sinus rhythm, % Atrial fibrillation, % Heart rate, bpm 72 ± ± ± QRS duration, msec 160 ( ) 164 ( ) 150 ( ) 0.02 LBBB, % Echocardiographic parameters LVEF, % 26 ± 7 26 ± 7 24 ± LV dimensions, mm EDD 62 (57 67) 62 (57 66) 63 (58 70) 0.27 ESD 54 (48 58) 53 (48 58) 54 (49 62) 0.41 LV volumes, cm 3 EDV 217 ( ) 208 ( ) 235 ( ) 0.04 ESV 157 ( ) 152 ( ) 168 ( ) 0.02 Left atrial diameter, mm 45 (41 49) 44 (40 49) 47 (43 50) 0.07 Mitral regurgitation None 1/126 (1) 0/93 (0) 1/33 (3) Trace 26/126 (21) 22/93 (24) 4/33 (12) Mild 43/126 (34) 38/93 (41) 5/33 (15) Moderate 42/126 (33) 26/93 (28) 16/33 (48) Severe 14/126 (11) 7/93 (8) 7/33 (21) RV systolic pressure, mmhg 42 (35 51) 42 (35 48) 48 (38 57) 0.04 a Occurrence for MACE was followed for 2 years. b Numbers represent range. c BMI, body mass index; ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; egfr, estimated glomerular filtration rate; LBBB, left bundle branch block; EDD, end-diastolic dimension; ESD, end-systolic dimension; EDV, end-diastolic volume; ESV, end-systolic volume; QoL, quality of life; RV, right ventricular. d To convert mg/dl to mmol/l for creatinine concentrations, multiply by Clinical Chemistry 63:1 (2017)

5 Soluble CD146, Marker of Congestion in Heart Failure Fig. 1. Median differences in plasma concentrations of scd146 (A) and NT-proBNP (B) after peripheral venous stress test compared to baseline (n = 44). Median and interquartile range of plasma values of NT-proBNP and scd146 are reported. crease in pressure in forearm veins raised plasma concentrations of scd146, but not of NT-proBNP, in the congested arm. Our data are in line with other studies showing in vivo and in vitro release of endothelial markers such as endothelin, nitric oxide, prostaglandin after acute endothelial stretch (13, 16). Our data are also in line with in vitro/ex vivo studies showing rapid stimulation of MMPs during mechanical stress in the form of endothelial cell stretching or acute venous occlusion (20 24). Measures of transcardiac gradient of scd146 confirmed the predominant extracardiac origin of scd146 in our HF patients. In contrast to the positive transcardiac gradient of NT-proBNP, we observed a negative transcardiac gradient of scd146, with plasma concentrations in peripheral veins higher than in the coronary sinus of HF patients. This finding strongly suggests a predominant systemic origin of scd146 in HF patients, presumably venous. Whether the negative transcardiac gradient suggests extraction is speculative (17). Fig. 2. Plasma concentrations of NT-proBNP (A) and scd146 (B) in peripheral vein (PV) and coronary sinus (CS) in 137 HF patients. Median and interquartile range of plasma values of NT-proBNP and scd146 are reported. Our group previously showed that scd146 was higher in HF patients with peripheral edema and/or dilated vena cava than in those with no signs of congestion (15). The present study further highlights that the severity of mitral regurgitation was associated with higher plasma concentrations of scd146. Since severity of mitral regurgitation is a major determinant of pulmonary venous congestion, our data further support a strong association between plasma concentrations of scd146 and HF-induced venous congestion. The present study further showed that plasma concentrations of scd146 and its transcardiac gradient provided important long-term prognostic information in patients with severe HF who were treated with CRT. High peripheral plasma concentrations of scd146 were associated with greater risk of adverse outcome at 2 years. A 10-fold increase in baseline concentrations of scd146 was associated with doubled risk of MACE. Our results are in line with previous studies showing that systemic congestion is a major determinant of organ dysfunction, readmissions, and death in HF (25, 26). Our study might bring several benefits in the management of HF patients including those with CRT. Early assessment of the degree of congestion, to adjust diuretic therapy, is not always easy in HF patients. Various tools for early, reliable and noninvasive detection of subclinical organ congestion have been proposed, but, despite many efforts, data on body weight measurement, congestion scores, and bioimpedance remain inconclusive (5 7, 27). Our study shows that scd146 is a biomarker of systemic congestion, and possibly of increased endothelial permeability in HF. The diagnostic and prognostic value of scd146 and its potential to guide decongestive therapy in left and right ventricular HF should be validated in larger, multicenter, prospective cohorts. Several limitations are noted. This study was performed in chronic HF outpatients with reduced LVEF and therefore the generalizability of the findings to the overall HF population requires additional research. The correlation between plasma concentrations of scd146 and hemodynamic congestion (right-atrial pressure, leftatrial or pulmonary-artery occlusion pressure) should be further investigated, in particular with invasive or noninvasive pressure measurement. Hydrostatic pooling from diminished flow and/or reduced peptide clearance might have contributed to the observed changes in scd146 concentrations after venous stress test. This needs to be further explored. However, normal oxygen saturation in the extremities suggests that flow was maintained in the tested arm and more importantly scd146 also increased in the control arm, though to a much smaller extent than in the congested arm, suggesting that increased secretion of scd146 with peripheral spillover from the congested arm into the systemic circulation is the leading explanation of the observed findings. Cuff inflation during the Clinical Chemistry 63:1 (2017) 5

6 Fig. 3. Prognostic value of plasma scd146 on composite of death, transplant, LVAD implantation, and readmission at 2 years. Hazard ratios per log-unit change in scd146 and 95% CI are shown. EF ejection fraction, egfr estimated glomerular filtration rate. venous stress test not only promoted congestion, but necessarily reduced arterial perfusion pressure by impinging on the brachial artery. However, a reduction in perfusion pressure is a typical clinical feature of severe HF where arterial blood pressure progressively declines (28), thus making our model even more relevant, from a pathophysiological standpoint. Of note, this human model of venous congestion previously has been shown to mimic on a local scale, notable aspects of the phenotype that is typical of acute HF such as inflammation, neurohormonal and endothelial cell activation (16). The transcardiac gradient was calculated using the CS and PV samples, since the collection of aortic blood sample was not feasible. Although this might limit accuracy of measurements, our study was able to demonstrate a positive gradient for NT-proBNP and, conversely, a negative gradient of scd146. The small number of MACE limits our ability to perform multivariable adjustments beyond 1 additional variable for the transcardiac gradient study. In conclusion, scd146 is rapidly released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients. Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article. Authors Disclosures or Potential Conflicts of Interest: Upon manuscript submission, all authors completed the author disclosure form. Disclosures and/or potential conflicts of interest: Employment or Leadership: J.L. Januzzi, member of Clinical Endpoints Committees or Data Safety Monitoring, Boards for Novartis, Amgen, Janssen, and Boeringer Ingelheim. Consultant or Advisory Role: E. Gayat, Magnisense; J.L. Januzzi, Roche Diagnostics, Phillips, Metanomics, Sphingotec, Critical Diagnostics, and Novartis; J.P. Singh, Boston Scientific, Medtronic, St. Jude Medical, Impulse Dynamics, and LivaNova; A. Mebazaa, Cardiorentis, Adrenomed, MyCartis, ZS Pharma, and Critical Diagnostics. Stock Ownership: None declared. Honoraria: A. Mebazaa, Abbott, Novartis, Orion, Roche, and Servier. Research Funding: The European Commission s Seventh Framework program under grant agreement number (HOMAGE), the National Institute of Health (NIH grant number HL092144A), and the A. L. Mailman Family Foundation;A. L. M. Arrigo, Fellowship of the Collège de Médecine des Hôpitaux de Paris; Q.A. Truong, NIH/ NHLBI K23HL and L30HL093896, St. Jude Medical and ACRIN; J. Szymonifka, NIH/NHLBI K23HL098370; J.L. Januzzi, Roche Diagnostics, Singulex, and Prevencio; J.P. Singh, St Jude Medical, Medtronic, BostonScientific, SorinGroup, Biotronik, BG Medicine, and Siemens; P.C. Colombo, NIH R01. Expert Testimony: None declared. Patents: None declared. Role of Sponsor: The funding organizations played no role in the design of study, choice of enrolled patients, review and interpretation of data, and final approval of manuscript. 6 Clinical Chemistry 63:1 (2017)

7 Soluble CD146, Marker of Congestion in Heart Failure References 1. Mebazaa A, Yilmaz MB, Levy P, Ponikowski P, Peacock WF, Laribi S, et al. Recommendations on pre-hospital and early hospital management of acute heart failure: a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine - short version. Eur Heart J 2015; 36: Townsend N, Nichols M, Scarborough P, Rayner M. Cardiovascular disease in Europe epidemiological update Eur Heart J 2015;36: Ambrosy AP, Pang PS, Khan S, Konstam MA, Fonarow GC, Traver B, et al. Clinical course and predictive value of congestion during hospitalization in patients admitted for worsening signs and symptoms of heart failure with reduced ejection fraction: findings from the EVEREST trial. Eur Heart J 2013;34: Picano E, Gargani L, Gheorghiade M. Why, when, and how to assess pulmonary congestion in heart failure: pathophysiological, clinical, and methodological implications. Heart Fail Rev 2010;15: Bourge RC, Abraham WT, Adamson PB, Aaron MF, Aranda JM, Magalski A, et al. Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol 2008;51: Chaudhry SI, Mattera JA, Curtis JP, Spertus JA, Herrin J, Lin Z, et al. Telemonitoring in patients with heart failure. N Engl J Med 2010;363: Hindricks G, Taborsky M, Glikson M, Heinrich U, Schumacher B, Katz A, et al. Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial. Lancet 2014;384: Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet 2011;377: McMurray JJV, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33: Troughton R, Michael Felker G, Januzzi JL. Natriuretic peptide-guided heart failure management. Eur Heart J 2014;35: Sabatine MS, Morrow DA, de Lemos JA, Omland T, Desai MY, Tanasijevic M, et al. Acute changes in circulating natriuretic peptide levels in relation to myocardial ischemia. J Am Coll Cardiol 2004;44: Bardin N, Francès V, Lesaule G, Horschowski N, George F, Sampol J. Identification of the S-Endo 1 endothelialassociated antigen. Biochem Biophys Res Commun 1996;218: Boneberg E-M, Illges H, Legler DF, Fürstenberger G. Soluble CD146 is generated by ectodomain shedding of membrane CD146 in a calcium-induced, matrix metalloprotease-dependent process. Microvasc Res 2009;78: Mebazaa A, Vanpoucke G, Thomas G, Verleysen K, Cohen-Solal A, Vanderheyden M, et al. Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure. Eur Heart J 2012;33: Gayat E, Caillard A, Laribi S, Mueller C, Sadoune M, Seronde M-F, et al. Soluble CD146, a new endothelial biomarker of acutely decompensated heart failure. Int J Cardiol 2015;199: Colombo PC, Onat D, Harxhi A, Demmer RT, Hayashi Y, Jelic S, et al. Peripheral venous congestion causes inflammation, neurohormonal, and endothelial cell activation. Eur Heart J 2014;35: Truong QA, Januzzi JL, Szymonifka J, Thai W-E, Wai B, Lavender Z, et al. Coronary sinus biomarker sampling compared to peripheral venous blood for predicting outcomes in patients with severe heart failure undergoing cardiac resynchronization therapy: the BIOCRT study. Heart Rhythm 2014;11: Bardin N, Anfosso F, Massé JM, Cramer E, Sabatier F, Le Bivic A, et al. Identification of CD146 as a component of the endothelial junction involved in the control of cellcell cohesion. Blood 2001;98: Bardin N, Moal V, Anfosso F, Daniel L, Brunet P, Sampol J, et al. Soluble CD146, a novel endothelial marker, is increased in physiopathological settings linked to endothelial junctional alteration. Thromb Haemost 2003; 90: Meng X, Mavromatis K, Galis ZS. Mechanical stretching of human saphenous vein grafts induces expression and activation of matrix-degrading enzymes associated with vascular tissue injury and repair. Exp Mol Pathol 1999;66: Yamaguchi S, Yamaguchi M, Yatsuyanagi E, Yun S-S, Nakajima N, Madri JA, et al. Cyclic strain stimulates early growth response gene product 1-mediated expression of membrane type 1 matrix metalloproteinase in endothelium. Lab Invest 2002;82: Haseneen NA, Vaday GG, Zucker S, Foda HD. Mechanical stretch induces MMP-2 release and activation in lung endothelium: role of EMMPRIN. Am J Physiol Lung Cell Mol Physiol 2003;284:L Wang B-W, Chang H, Lin S, Kuan P, Shyu K-G. Induction of matrix metalloproteinases-14 and -2 by cyclical mechanical stretch is mediated by tumor necrosis factoralpha in cultured human umbilical vein endothelial cells. Cardiovasc Res 2003;59: Alsaigh T, Pocock ES, Bergan JJ, Schmid-Schönbein GW. Acute venous occlusion enhances matrix metalloprotease activity: implications on endothelial dysfunction. Microvasc Res 2011;81: Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 2009;53: Nikolaou M, Parissis J, Yilmaz MB, Seronde M-F, Kivikko M, Laribi S, et al. Liver function abnormalities, clinical profile, and outcome in acute decompensated heart failure. Eur Heart J 2013;34: Gheorghiade M, Follath F, Ponikowski P, Barsuk JH, Blair JEA, Cleland JG, et al. Assessing and grading congestion in acute heart failure: a scientific statement from the acute heart failure committee of the heart failure association of the European Society of Cardiology and endorsed by the European Society of Intensive Care Medicine. Eur J Heart Fail 2010;12: Barlera S, Tavazzi L, Franzosi MG, Marchioli R, Raimondi E, Masson S, et al. Predictors of mortality in 6975 patients with chronic heart failure in the Gruppo Italiano per lo Studio della Streptochinasi nell Infarto Miocardico-Heart Failure trial: proposal for a nomogram. Circ Heart Fail 2013;6:31 9. Clinical Chemistry 63:1 (2017) 7

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