The prognostic value of sST2 and galectin-3 considering different aetiologies in non-ischaemic heart failure

David Binas, Hanna Daniel, Anette Richter, Volker Ruppert, Klaus-Dieter Schlüter, Bernhard Schieffer, Sabine Pankuweit, David Binas, Hanna Daniel, Anette Richter, Volker Ruppert, Klaus-Dieter Schlüter, Bernhard Schieffer, Sabine Pankuweit

Abstract

Objective: Several studies indicate a prognostic value of sST2 and galectin-3 in heart failure (HF). While previous studies focused on ischaemic cause of HF, we investigated the role of sST2 and galectin-3 in patients with non-ischaemic dilated cardiomyopathy (DCM).

Methods: sST2 and galectin-3 serum concentrations were measured in 262 subjects with DCM. Survival rates were determined for all-cause mortality (ACM) and cardiac mortality (CM).

Results: In a univariate model, sST2 as a continuous variable was a predictor of ACM (HR 1.05; 95% CI 1.03 to 1.07, P<0.001) and CM (HR 1.03; 95% CI 1.00 to 1.06, P=0.040). In the subgroup of patients with inflammatory and/or viral DCM (DCMi⋎viral), the endpoints ACM (HR 1.10; 95% CI 1.05 to 1.17, P<0.001) and CM (HR 1.10; 95% CI 1.02 to 1.18, P=0.013) were significant. In the subgroup of patients with idiopathic DCM, the endpoint ACM (HR 1.04; 95% CI 1.01 to 1.07, P=0.019) was significant. In a multivariate model, the prognostic value of the sST2 main group remained intact for ACM (HR 1.04; 95% CI 1.02 to 1.07, P=0.003).Univariate and multivariate analysis of galectin-3 as continuous variable did not show any significant result. However, in a quartile model, intermediate values of galectin-3 were significantly associated with a lower event rate of ACM and CM.

Conclusion: The study revealed that sST2 predicts ACM and CM in patients with non-ischaemic HF and could be useful especially in patients with inflammatory background. Our findings that intermediate levels of galectin-3 allow for better prognosis were new and different to other investigations.

Trial registration number: NCT03090425; Results.

Keywords: Dilated Cardiomyopathy; Galectin-3; Heart failure; sST2; soluble ST2.

Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
(A) Kaplan-Meier survival analysis for all-cause mortality according to sST2 quartiles. (B) Kaplan-Meier survival analysis for cardiac mortality according to galectin-3 quartiles.

References

    1. McMurray JJ, Adamopoulos S, Anker SD, 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 J Heart Fail 2012;14:803–69. 10.1093/eurjhf/hfs105
    1. Dickstein K, Cohen-Solal A, Filippatos G, et al. . ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur Heart J 2008;29:2388–442. 10.1093/eurheartj/ehn309
    1. Yancy CW, Jessup M, Bozkurt B, et al. . 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240–327. 10.1161/CIR.0b013e31829e8807
    1. Ponikowski P, Voors AA, Anker SD, et al. . 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891–975. 10.1002/ejhf.592
    1. Kakkar R, Lee RT. The IL-33/ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov 2008;7:827–40. 10.1038/nrd2660
    1. Weinberg EO, Shimpo M, De Keulenaer GW, et al. . Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation 2002;106:2961–6. 10.1161/01.CIR.0000038705.69871.D9
    1. Kunes P, Holubcova Z, Kolackova M, et al. . Interleukin-33, a novel member of the IL-1/IL-18 cytokine family, in cardiology and cardiac surgery. Thorac Cardiovasc Surg 2010;58:443–9. 10.1055/s-0030-1250436
    1. Barondes SH, Castronovo V, Cooper DN, et al. . Galectins: a family of animal beta-galactoside-binding lectins. Cell 1994;76:597–8. 10.1016/0092-8674(94)90498-7
    1. de Boer RA, Voors AA, Muntendam P, et al. . Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail 2009;11:811–7. 10.1093/eurjhf/hfp097
    1. Broch K, Ueland T, Nymo SH, et al. . Soluble ST2 is associated with adverse outcome in patients with heart failure of ischaemic aetiology. Eur J Heart Fail 2012;14:268–77. 10.1093/eurjhf/hfs006
    1. Ky B, French B, McCloskey K, et al. . High-sensitivity ST2 for prediction of adverse outcomes in chronic heart failure. Circ Heart Fail 2011;4:180–7. 10.1161/CIRCHEARTFAILURE.110.958223
    1. Ahmad T, Fiuzat M, Neely B, et al. . Biomarkers of myocardial stress and fibrosis as predictors of mode of death in patients with chronic heart failure. JACC Heart Fail 2014;2:260–8. 10.1016/j.jchf.2013.12.004
    1. Bayes-Genis A, de Antonio M. Head-to-head comparison of 2 myocardial fibrosis biomarkers for long-term heart failure risk stratification: ST2 versus galectin-3. J Am Coll Cardiol 2014;63:158–66.
    1. Miller WL, Saenger AK, Grill DE, et al. . Prognostic value of serial measurements of soluble suppression of tumorigenicity 2 and galectin-3 in ambulatory patients with chronic heart failure. J Card Fail 2016;22:249–55. 10.1016/j.cardfail.2015.07.017
    1. French B, Wang L, Ky B, et al. . Prognostic value of galectin-3 for adverse outcomes in chronic heart failure. J Card Fail 2016;22:256–62. 10.1016/j.cardfail.2015.10.022
    1. Caforio AL, Pankuweit S, Arbustini E, et al. . European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2013;48:2648a–d.
    1. Pankuweit S, Moll R, Baandrup U, et al. . Prevalence of the parvovirus B19 genome in endomyocardial biopsy specimens. Hum Pathol 2003;34:497–503. 10.1016/S0046-8177(03)00078-9
    1. Aretz HT, Billingham ME, Edwards WD, et al. . Myocarditis. A histopathologic definition and classification. Am J Cardiovasc Pathol 1987;1:3–14.
    1. Mestroni L, Rocco C, Gregori D, et al. . Familial dilated cardiomyopathy: evidence for genetic and phenotypic heterogeneity. Heart Muscle Disease Study Group. J Am Coll Cardiol 1999;34:181–90.
    1. R&D Systems; Product Datasheet. Human ST2/IL-33 R immunoassay quantikine ELISA kit. Catalog Number DST200.
    1. R&D Systems; Product Datasheet. Human galectin-3 immunoassay quantikine® ELISA kit. Catalog Number DGAL30.
    1. Broch K, Andreassen AK, Ueland T, et al. . Soluble ST2 reflects hemodynamic stress in non-ischemic heart failure. Int J Cardiol 2015;179:378–84. 10.1016/j.ijcard.2014.11.003
    1. Mueller T, Leitner I, Egger M, et al. . Association of the biomarkers soluble ST2, galectin-3 and growth-differentiation factor-15 with heart failure and other non-cardiac diseases. Clin Chim Acta 2015;445:155–60. 10.1016/j.cca.2015.03.033
    1. Kumar S, Tzimas MN, Griswold DE, et al. . Expression of ST2, an interleukin-1 receptor homologue, is induced by proinflammatory stimuli. Biochem Biophys Res Commun 1997;235:474–8. 10.1006/bbrc.1997.6810
    1. Hu DJ, Xu J, Du W, et al. . Cardiac magnetic resonance and galectin-3 level as predictors of prognostic outcomes for non-ischemic cardiomyopathy patients. Int J Cardiovasc Imaging 2016;32:1725–33. 10.1007/s10554-016-0958-1

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel