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Observational Study
. 2022 Sep 1;12(9):e061611.
doi: 10.1136/bmjopen-2022-061611.

Soluble CD146 in the detection and grading of intravascular and tissue congestion in patients with acute dyspnoea: analysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort

Renata Juknevičienė  1   2 , Justas Simonavičius  3   4 , Aurimas Mikalauskas  3 , Kamilė Čerlinskaitė-Bajorė  1   5   6 , Mattia Arrigo  7   8 , Vytautas Juknevičius  1   3 , Irina Alitoit-Marrote  3 , Denis Kablučko  3 , Loreta Bagdonaitė  9   10 , Dalius Vitkus  9   10 , Mindaugas Balčiūnas  1   3 , Gitana Zuozienė  1   3 , Jūratė Barysienė  1   3 , Diana Žaliaduonytė  11 , Kęstutis Stašaitis  12 , Aušra Kavoliūnienė  11 , Alexandre Mebazaa #  5   6   13 , Jelena Čelutkienė #  14   15
Affiliations
Observational Study

Soluble CD146 in the detection and grading of intravascular and tissue congestion in patients with acute dyspnoea: analysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort

Renata Juknevičienė et al. BMJ Open. .

Abstract

Objectives: To evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea.

Design: Subanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.

Setting: Two Lithuanian university centres.

Participants: Adult patients with acute dyspnoea admitted to the emergency department.

Methods: Congestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing.

Results: The median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315-509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373-535) vs 400 (304-501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335-528) vs 394 (296-484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300-425), 404 (290-489) and 477 (363-572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (p<0.05).

Conclusion: sCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

Keywords: Adult cardiology; Echocardiography; Heart failure; Ultrasound; VASCULAR MEDICINE.

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Conflict of interest statement

Competing interests: AM received speaker’s honoraria from Orion, Otsuka, Philips, Roche and Servier; received fee as a member of advisory board and/or Steering Committee and/or research grant from Adrenomed, Epygon, Neurotronik, Roche, Sanofi and Sphyngotec. AM owns shares in S-Form Pharma. AK received speaker’s honoraria from Servier, Bayer, Berlin-Chemie-Menarini, Pfizer and KRKA. JČ received investigator and speaker fees from Sanofi, Amgen, Novartis, Roche Diagnostics, Servier, AstraZeneca and Boehringer Ingelheim. DŽ received speaker fees from Novartis and AstraZeneca. JS received personal fees from Novartis, Bayer, Boehringer Ingelheim and Servier. VJ received personal fees from Bayer, Boehringer Ingelheim, Servier and Pfizer. Other authors declared no conflict of interest.

Figures

Figure 1
Figure 1
sCD146 concentration in terciles of IVC diameter at expiration (A), IVC collapse (B) and eRAP subgroups (C). eRAP, estimated right atrial pressure; IVC, inferior vena cava; sCD146, soluble cluster of differentiation 146.
Figure 2
Figure 2
sCD146 concentration in terciles of ultrasound parameters: (A) average E/e’ ratio, (B) B-lines, (C) LVDD, (D) LAVI, (E) LVEF, (F) TAPSE, (G) RV free wall strain and (H) entire RV strain. LAVI, left atrial volume index; LVDD, left ventricular diastolic diameter; LVEF, left ventricular ejection fraction; RV, right ventricular; sCD146, soluble cluster of differentiation 146; TAPSE, tricuspid annular plane systolic excursion.
Figure 3
Figure 3
Frequency of peripheral oedema in patients stratified according to the median values of sCD146 and NT-proBNP (A) and prevalence of elevated eRAP in patients stratified according to the median values sCD146 and NT-proBNP (B). eRAP, estimated right atrial pressure; NT-proBNP, N-terminal pro-B-type natriuretic peptide; sCD146, soluble cluster of differentiation 146.
Figure 4
Figure 4
ROC curves of the predictive value of sCD146 and NT-proBNP and the combination of sCD146 and NT-proBNP: (A) IVCexp, (B) IVC collapse, (C) B-lines, (D) oedema, (E) LVEF, (F) rales. IVC, inferior vena cava; IVCexp, inferior vena cava at expiration; LVEF, left ventricular ejection fraction; NT-proBNP, N-terminal pro-B-type natriuretic peptide; ROC, receiver operating characteristic; sCD146, soluble cluster of differentiation 146.
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