Ann Lab Med.  2018 Jul;38(4):306-315. 10.3343/alm.2018.38.4.306.

Galectin-3 Reflects the Echocardiographic Grades of Left Ventricular Diastolic Dysfunction

Affiliations
  • 1First Department of Medicine, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany: DZHK (German Center for Cardiovascular Research) partner site Mannheim. uzair.ansari@umm.de
  • 2Institute of Clinical Chemistry, Laboratory Medicine and Transfusion Medicine, General Hospital Nuremberg, Paracelsus Medical University, Nuremberg, Germany.

Abstract

BACKGROUND
The level of Galectin-3 (Gal-3) protein purportedly reflects an ongoing cardiac fibrotic process and has been associated with ventricular remodeling, which is instrumental in the development of heart failure with preserved ejection fraction (HFpEF) syndrome. The aim of this study was to investigate the potential use of Gal-3 in improved characterization of the grades of diastolic dysfunction as defined by echocardiography.
METHODS
Seventy HFpEF patients undergoing routine echocardiography were prospectively enrolled in the present monocentric study. Blood samples for measurements of Gal-3 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) were collected within 24 hours pre- or post-echocardiographic examination. The classification of patients into subgroups based on diastolic dysfunction grade permitted detailed statistical analyses of the derived data.
RESULTS
The Gal-3 serum levels of all patients corresponded to echocardiographic indices, suggesting HFpEF (E/A, P=0.03 and E/E', P=0.02). Gal-3 was also associated with progressive diastolic dysfunction, and increased levels corresponded to the course of disease (P=0.012). Detailed analyses of ROC curves suggested that Gal-3 levels could discriminate patients with grade III diastolic dysfunction (area under the curve [AUC]=0.770, P=0.005).
CONCLUSIONS
Gal-3 demonstrates remarkable effectiveness in the diagnosis of patients suffering from severe grade diastolic dysfunction. Increasing levels of Gal-3 possibly reflect the progressive course of HFpEF, as classified by the echocardiographic grades of diastolic dysfunction.

Keyword

Galectin-3; Preserved ejection fraction; NT-proBNP; Diastolic dysfunction

MeSH Terms

Classification
Diagnosis
Echocardiography*
Galectin 3*
Heart Failure
Humans
Prospective Studies
ROC Curve
Ventricular Remodeling
Galectin 3

Figure

  • Fig. 1 Box plots showing increased levels of Galectin-3 (A) and increased levels of NT-proBNP (B) in patients with different grades of diastolic dysfunction. Significantly highest levels of Galectin-3 and NT-proBNP were noted in Grade III diastolic dysfunction, indicating a progressive increase in their levels along the course of the disease.Abbreviation: NT-proBNP, amino-terminal pro-brain natriuretic peptide.

  • Fig. 2 Receiver-operating characteristic (ROC) curve revealing an effective discrimination of patients with diastolic dysfunction III. ROC=diastolic dysfunction grade 3 curve. AUC–Area under the Curve.Abbreviation: NT-proBNP, amino-terminal pro-brain natriuretic peptide.


Reference

1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014; 129:e28–e292. PMID: 24352519.
2. McMurray JJ, 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; 33:1787–1847. PMID: 22611136.
3. Cheng JM, Akkerhuis KM, Battes LC, van Vark LC, Hillege HL, Paulus WJ, et al. Biomarkers of heart failure with normal ejection fraction: a systematic review. Eur J Heart Fail. 2013; 15:1350–1362. PMID: 23845797.
4. de Boer RA, Edelmann F, Cohen-Solal A, Mamas MA, Maisel A, Pieske B. Galectin-3 in heart failure with preserved ejection fraction. Eur J Heart Fail. 2013; 15:1095–1101. PMID: 23650131.
5. Tribouilloy C, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, et al. Prognosis of heart failure with preserved ejection fraction: a 5 year prospective population-based study. Eur Heart J. 2008; 29:339–347. PMID: 18156618.
6. González A, López B, Díez J. Fibrosis in hypertensive heart disease: role of the renin-angiotensin-aldosterone system. Med Clin North Am. 2004; 88:83–97. PMID: 14871052.
7. Mitchell JA, Ventura HO, Mehra MR. Early recognition and treatment of hypertensive heart disease. Curr Opin Cardiol. 2005; 20:282–289. PMID: 15956824.
8. de Boer RA, Pinto YM, Van Veldhuisen DJ. The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities. Microcirculation. 2003; 10:113–126. PMID: 12700580.
9. Henderson NC, Sethi T. The regulation of inflammation by Galectin-3. Immunol Rev. 2009; 230:160–171. PMID: 19594635.
10. Reifenberg K, Lehr HA, Torzewski M, Steige G, Wiese E, Küppr I, et al. Interferon-γ induces chronic active myocarditis and cardiomyopathy in transgenic mice. Am J Pathol. 2007; 171:463–472. PMID: 17556594.
11. Lok DJ, Van Der Meer P, de la Porte PW, Lipsic E, van Wijngaarden J, Hillege HL, et al. Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study. Clin Res Cardiol. 2010; 99:323–328. PMID: 20130888.
12. Shah RV, Chen-Tournoux AA, Picard MH, van Kimmenade RR, Januzzi JL. Galectin-3, cardiac structure and function, and long-term mortality in patients with acutely decompensated heart failure. Eur J Heart Fail. 2010; 12:826–832. PMID: 20525986.
13. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF 3rd, Dokainish H, Edvardsen T, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2016; 29:277–314. PMID: 27037982.
14. Penicka M, Vanderheyden M, Bartunek J. Diagnosis of heart failure with preserved ejection fraction: role of clinical Doppler echocardiography. Heart. 2014; 100:68–76. PMID: 23543282.
15. Gruson D, Mancini M, Ahn SA, Rousseau MF. Measurement of Galectin-3 with the ARCHITECT assay: Clinical validity and cost-effectiveness in patients with heart failure. Clin Biochem. 2014; 47:1006–1009. PMID: 24925289.
16. Carrasco-Sánchez FJ, Aramburu-Bodas O, Salamanca-Bautista P, Morales-Rull JL, Galisteo-Almeda L, Páez-Rubio MI, et al. Predictive value of serum galectin-3 levels in patients with acute heart failure with preserved ejection fraction. Int J Cardiol. 2013; 169:177–182. PMID: 24207066.
17. de Boer RA, Lok DJ, Jaarsma T, van der Meer P, Voors AA, Hillege HL, et al. Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction. Ann Med. 2011; 43:60–68. PMID: 21189092.
18. Zile MR, DeSantis SM, Baicu CF, Prescott CB, Stroud RE, Thompson SB, et al. Plasma galectin-3 levels in patients with structural and clinical manifestation of hypertensive heart disease: relationship to determination of matrix composition. Circulation. 2010; 122(S1):A12433.
19. Sharma UC, Pokharel S, van Brakel TJ, van Berlo JH, Cleutjens JP, Schroen B, et al. Galectin-3 marks activated macrophages in failure-prone hypertrophied hearts and contributes to cardiac dysfunction. Circulation. 2004; 110:3121–3128. PMID: 15520318.
20. Liu YH, d'Ambrosio M, Liu YD, Peng H, Rhaleb NE, Sharma U, et al. Nacetyl-seryl-aspartyl-lysyl-proline prevents cardiac remodeling and dysfunction induced by galectin-3, a mammalian adhesion/growth-regulatory lectin. Am J Physiol Heart Circ Physiol. 2009; 296:H404–H412. PMID: 19098114.
21. de Boer RA, Voors AA, Muntendam P, van Gilst WH, van Veldhuisen DJ. Galectin-3: a novel mediator of heart failure development and progression. Eur J Heart Fail. 2009; 11:811–817. PMID: 19648160.
22. van Kimmenade RR, Januzzi JL Jr, Ellinor PT, Sharma UC, Bakker JA, Low AF, et al. Utility of amino-terminal pro-brain natriuretic peptide, galectin-3, and apelin for the evaluation of patients with acute heart failure. J Am Coll Cardiol. 2006; 48:1217–1224. PMID: 16979009.
23. Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol. 2012; 60:1249–1256. PMID: 22939561.
24. de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, et al. The fibrosis marker galectin-3 and outcome in the general population. J Intern Med. 2012; 272:55–64. PMID: 22026577.
25. Edelmann F, Holzendorf V, Wachter R, Nolte K, Schmidt AG, Kraigher-Krainer E, et al. Galectin-3 in patients with heart failure with preserved ejection fraction: results from the Aldo-DHF trial. Eur J Heart Fail. 2015; 17:214–223. PMID: 25418979.
26. deFilippi CR. Evolving role of galectin-3 as a cardiac biomarker. Heart failure with preserved ejection fraction and renal function, important pieces of the puzzle. JACC Heart Fail. 2015; 3:253–256. PMID: 25742763.
27. AbouEzzeddine OF, Haines P, Stevens S, Nativti-Nicolau J, Felker GM, Borlaug BA, et al. Galectin-3 in heart failure with preserved ejection fraction: a RELAX trial substudy (phosphodiesterase-5 inhibition to improve clinical status and exercise capacity in diastolic heart failure). JACC Heart Fail. 2015; 3:245–252. PMID: 25742762.
28. Gopal DM, Kommineni M, Ayalon N, Koelbl C, Ayalon R, Biolo A, et al. Relationship of plasma galectin-3 to renal function in patients with heart failure: effects of clinical status, pathophysiology of heart failure, and presence or absence of heart failure. J Am Heart Assoc. 2012; 1:e000760. PMID: 23316284.
29. Gurel OM, Yilmaz H, Celik TH, Cakmak M, Namuslu M, Bilgiç AM, et al. Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients. Herz. 2015; 40:788–794. PMID: 25990624.
30. Smilde TD, Damman K, van der Harst P, Navis G, Westenbrink BD, Voors AA, et al. Differential associations between renal function and “modifiable” risk factors in patients with chronic heart failure. Clin Res Cardiol. 2009; 98:121–129. PMID: 18979056.
31. Bošnjak I, Selthofer-Relatić K, Včev A. Prognostic value of galectin-3 in patients with heart failure. Dis Markers. 2015; 2015:690205. PMID: 25960597.
32. Christenson RH, Duh SH, Wu AHB, Smith A, Abel G, deFilippi CR, et al. Multi-center determination of galectin-3 assay performance characteristics: anatomy of a novel assay for use in heart failure. Clin Biochem. 2010; 43:683–690. PMID: 20153309.
33. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, 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. J Am Coll Cardiol. 2013; 62:e147–e239. PMID: 23747642.
34. Van der Velde AR, Gullestad L, Ueland T, Aukrust P, Guo Y, Adourian A, et al. Prognostic Value of Changes in Galectin-3 levels over time in Patients with Heart failure. Clinical Perspective Data from CORONA and CóACH. Circ Heart Fail. 2013; 6:219–226. PMID: 23395934.
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