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Galectin-3 as a marker for clinical prognosis and cardiac remodeling in acute heart failure

Galektin-3 als Marker der klinischen Prognose und des kardialen Remodeling bei akuter Herzinsuffizienz

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Abstract

Background

Galectin-3 has been reported as a mediator of heart failure (HF) development and progression. Most studies, however, have been conducted on patients with chronic HF rather than acute HF (AHF).

The aim of this study was to confirm galectin-3 as a prognostic marker in subjects with AHF and to investigate its possible relationship with left ventricular (LV) remodeling.

Methods

A total of 69 patients hospitalized with a primary diagnosis of AHF were followed up for 18 months. Galectin-3 and echocardiographic parameters were measured at baseline and after 6 months. Survival analysis and exploratory analysis of LV remodeling were performed.

Results

Patients with high baseline galectin-3 values (>16.5 ng/ml) had a significantly worse survival profile over the 18-month follow-up (log-rank test, p = 0.017), with Cox proportional hazards modeling showing a crude hazard ratio (HR) of 4.66 (95% CI = 1.16–18.67; likelihood-ratio test, p = 0.037) for all-cause mortality. Changes in galectin-3 levels (1 SD increase over 6 months) proved to be a significant explanatory factor for HF hospital re-admission in the short term when compared with quasi-stationary galectin-3 levels: worse Kaplan–Meier survival curves (log-rank test, p = 0.001) and a crude HR of 4.44 (95% CI = 1.76–11.18; likelihood-ratio test, p = 0.004). A significant association was found between the pathological evolution of relative wall thickness, LV end-diastolic diameter, LV end-diastolic volume, and increasing levels of galectin-3 in the short term (Cochran–Mantel–Haenszel test, p < 0.01).

Conclusion

Galectin-3 can predict long-term mortality in patients with AHF. The results of our study suggest a possible relation between left ventricular remodeling and increasing galectin-3 levels.

Zusammenfassung

Hintergrund

Galektin-3 wurde als Mediator der Entstehung und Progression einer Herzinsuffizienz beschrieben. Jedoch wurden die meisten Studien eher bei Patienten mit chronischer als mit akuter Herzinsuffizienz durchgeführt. Ziel der vorliegenden Studie war es, Galektin-3 als prognostischen Marker bei akuter Herzinsuffizienz zu bestätigen und seine mögliche Beziehung zum linksventrikulären (LV-)Remodeling zu untersuchen.

Methoden

Insgesamt wurden 69 Patienten mit primärer Diagnose einer akuten Herzinsuffizienz bis zu 18 Monate nachbeobachtet. Zu Beginn und nach 6 Monaten wurden Galektin-3 und echokardiographische Parameter gemessen. Es erfolgte eine Analyse des Überlebens sowie eine exploratorische Analyse des LV-Remodeling.

Ergebnisse

Patienten mit anfänglichen hohen Galektin-3-Werten (>16,5 ng/ml) wiesen ein signifikant schlechteres Überlebensprofil während der 18-monatigen Nachbeobachtung auf (Log-Rank-Test, p = 0,017), dabei ergab das Cox-Proportional-Hazards-Modell eine rohe Hazard Ratio (HR) von 4,66 (95%-Konfidenzintervall, 95%-KI: 1,16–18,67; Likelihood-Ratio-Test, p = 0,037) für die Mortalität aus sämtlichen Ursachen. Die Veränderungen der Galektin-3-Werte (Anstieg von 1 Standardabweichung, SD, über 6 Monate) erwiesen sich auf kurze Sicht als signifikanter erklärender Faktor für die erneute stationäre Aufnahme wegen Herzinsuffizienz im Vergleich zu quasi-stationären Galektin-3-Werten: schlechtere Kaplan-Meier-Überlebenskurven (Log-Rank-Test, p = 0,001) und eine rohe HR von 4,44 (95%-KI: 1,76–11,18; Likelihood-Ratio-Test, p = 0,004). Ein signifikanter Zusammenhang stellte sich kurzfristig zwischen pathologischen Befunden bei der relativen Wanddicke, LV enddiastolischem Durchmesser, LV enddiastolischem Volumen und ansteigenden Galektin-3-Werten heraus (Cochran–Mantel–Haenszel test, p < 0,01).

Schlussfolgerung

Galektin-3 ermöglicht die Vorhersage der Langzeitmortalität bei Patienten mit akuter Herzinsuffizienz. Die Ergebnisse der vorliegenden Studie weisen auf eine mögliche Beziehung zwischen LV-Remodeling und ansteigenden Galektin-3-Werten hin.

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Acknowledgements

R.I. Lala was partly supported in his research by the Operational Programme for Human Resources Development (SOPHRD), financed by the European Social Fund and the Romanian Government under contract number POSDRU 141531.

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Authors and Affiliations

  1. “Vasile Goldis” West University Arad, Arad, Romania

    R. I. Lala, D. Darabantiu & M. Puschita

  2. Department of Cardiology, Arad County Emergency Clinical Hospital, Arad, Romania

    R. I. Lala, D. Darabantiu & M. Puschita

  3. Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania

    D. Lungeanu & L. Pilat

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  1. R. I. Lala
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  2. D. Lungeanu
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  3. D. Darabantiu
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Correspondence to R. I. Lala.

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Conflict of interest

R.I. Lala, D. Lungeanu, D. Darabantiu, L. Pilat, and M. Puschita declare that they have no competing interests.

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.

Appendix

Appendix

Table 5 Baseline descriptive statistics according to quintiles (i. e., 20% quintiles) of galectin-3
Full size table
Table 6 Six-month follow-up descriptive statistics according to quintiles (i. e., 20% quintiles) of galectin-3
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Lala, R.I., Lungeanu, D., Darabantiu, D. et al. Galectin-3 as a marker for clinical prognosis and cardiac remodeling in acute heart failure. Herz 43, 146–155 (2018). https://doi.org/10.1007/s00059-017-4538-5

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