sST2 als Biomarker bei chronischer Herzinsuffizienz mit erhaltener Ejektionsfraktion – Ergebnisse der Aldo-DHF-Studie –

sST2 as a biomarker in chronic heart failure with preserved ejection fraction. - Results of the Aldo-DHF study -

by Lilian Tögemann
Doctoral thesis
Date of Examination:2021-08-10
Date of issue:2021-07-30
Advisor:Prof. Dr. Frank Edelmann
Referee:Prof. Dr. Frank Edelmann
Referee:PD Dr. Steffen Unkel
Persistent Address: http://dx.doi.org/10.53846/goediss-8769

 

 

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Abstract

English

Chronic heart failure with preserved ejection fraction (HFpEF), with a left ventricular ejection fraction (LVEF) ≥ 50%, is a worldwide growing disease with a prevalence of about one percent.  Prognosis improving treatment options and precise methods to evaluate treatment success are not yet available. These are of immense importance due to the progressing prevalence and immoderate disease costs of HFpEF. Important pathophysiological mechanisms leading to HFpEF are inflammatory and fibrotic processes, which are presumed to be represented by higher levels of the biomarker sST2. The Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial was a double blind, randomized, placebo-controlled, multicenter clinical trial including 422 patients investigating the effect of the aldosterone antagonist spironolactone (25mg daily dose) on HFpEF patients.  Serum sST2 concentrations were analyzed from 415 patients at the baseline visit, and a total of 378 patients at 6- and 12-month follow-up visit using a sandwich ELISA. The baseline sST2 median was 27.1ng/ml with a 3.5ng/ml higher value for males (29.0 ng/ml) than females (25.5ng/ml). During the 12 months period there were only slight changes in the sST2 levels overall. Baseline patient characteristics and their outcome in physical exercise tests and cardiological examinations were correlated with their sST2 levels at the baseline visit. After multivariable adjustment an independent influence on sST2 baseline levels could be demonstrated for uric acid, LVEF and left atrial volume index (LAVI) as well as gender affiliation (being male). The inclusion of the measured sST2 values up to the 12-month follow-up showed similar results. Contrary to expectations there was no correlation to the original end points of the Aldo-DHF study (peakVO2 and E/e') over time.  Furthermore, no influence of a spironolactone treatment on the sST2 concentrations could be proven. The low mortality and hospitalization rates within the study period could not be prognostically related to serum sST2 levels, not even after further subdivision into therapy group with aldosterone or placebo. In conclusion, the effects of an independent influence of gender affiliation, uric acid, LVEF, and LAVI on serum sST2 levels in HFpEF patients were discovered. Further research is needed to determine the possible use of sST2 in HFpEF patients to improve their therapy and prognosis.
Keywords: chronic heart failure; HFpEF; sST2; heart failure; Aldo-DHF
Schlagwörter: HFpEF; chronische Herzinsuffizienz; sST2; Aldo-DHF
 
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