Galectin-3 bei Patienten mit Herzinsuffizienz mit erhaltener Ejektionsfraktion (HFpEF) - Klinische Assoziationen, Einfluss einer Aldosteron-Rezeptor-Blockade und prognostische Bedeutung - Ergebnisse der Aldo-DHF- Studie

Galectin-3 in patients with heartfailure with preserved ejection fraction (HFpEF) -clinical associations, influence of an aldosterone receptor blockade and prognostic relevance - results of the Aldo-DHF-study

by Ines Angela Unkelbach
Doctoral thesis
Date of Examination:2015-03-09
Date of issue:2015-01-29
Advisor:PD Dr. Frank Edelmann
Referee:PD Dr. Frank Edelmann
Referee:Prof. Dr. Michael Zeisberg
Persistent Address: http://dx.doi.org/10.53846/goediss-4894

 

 

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Abstract

English

Half of patients with heart failure suffer from heart failure with preserved ejection fraction and cardiac fibrosis is believed to be a major pathophysiological component in this condition. Galectin-3 is a marker of myocardial fibrosis, and it mediates aldosterone-induced vascular inflammation and fibrosis. However, the effect of chronic aldosterone receptor blockade on galectin-3 levels in patients with heart failure and preserved ejection fraction (HF-PEF) has not been evaluated.  The Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial was a prospective, multicenter, randomized, placebo-controlled, double-blind study that included n=422 patients with New York Heart Association (NYHA) class II or III heart failure symptoms, left ventricular ejection fraction (LVEF) ≥50% at rest, echocardiographic evidence of grade ≥I diastolic dysfunction or present atrial fibrillation, and peak VO2 ≤25 mL/kg/min. Patients were randomized to spironolactone 25 mg once daily or matching placebo. Galectin-3 levels were obtained at baseline, 6 and 12 months after randomization. The interaction between baseline galectin-3 and treatment effect was evaluated. The association between baseline galectin-3, change in galectin-3 during follow-up, and the composite of all-cause death or hospitalization was also evaluated. The mean baseline value of galectin-3 was 12.11ng/mL. After multivariable adjustment, baseline galectin-3 inversely correlated with peak VO2, 6-minute walk distance, and SF-36 and directly correlated with NYHA class. However, the association to parameters of cardiac function such as E/é, LVMI or LAVI was lost after full adjustment. Contrary, NT-proBNP was, after adjustment, significantly associated with echocardiographic parameters, but not with objective and subjective measures of physical function. Increasing galectin-3 at 6 or 12 months was a significant predictor of all-cause death or hospitalization. This was also evident after multiple adjustments including established prognostic markers such as NT-proBNP. Interestingly, spironolactone did not influence galectin-3 levels during follow-up, and there was no interaction between galectin-3 and treatment effect on the primary outcome measures of Aldo-DHF E/e′ or peak VO2. In summary, galectin-3 concentrations are modestly elevated in patients with well-compensated HFpEF, and they are related to different measures of functional performance. Independent of aldosterone receptor blockade galectin-3 levels increase over time in these patients, and this increase independently predicts subsequent prognosis.  These results suggest that galectin-3 may have a role in the characterization of patients with HFpEF. However, future studies are needed to confirm our results and to justify the definite role of galectin-3 in HFpEF.
Keywords: HFPEF; Aldosterone-receptor-blockade; Aldo-DHF; heartfailure; Galectin-3
Schlagwörter: Galectin-3; HFpEF; Herzinsuffizienz; Aldo-DHF; Aldosterone-Rezeptorblockade
 
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