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dc.contributor.advisor Edelmann, Frank PD Dr.
dc.contributor.author Unkelbach, Ines Angela
dc.date.accessioned 2015-01-29T06:52:41Z
dc.date.available 2015-03-18T23:50:05Z
dc.date.issued 2015-01-29
dc.identifier.uri http://hdl.handle.net/11858/00-1735-0000-0022-5D9C-C
dc.language.iso deu de
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc 610 de
dc.title 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 de
dc.type doctoralThesis de
dc.title.translated 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 de
dc.contributor.referee Edelmann, Frank PD Dr.
dc.date.examination 2015-03-09
dc.description.abstracteng 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. de
dc.contributor.coReferee Zeisberg, Michael Prof. Dr.
dc.subject.ger Galectin-3 de
dc.subject.ger HFpEF de
dc.subject.ger Herzinsuffizienz de
dc.subject.ger Aldo-DHF de
dc.subject.ger Aldosterone-Rezeptorblockade de
dc.subject.eng HFPEF de
dc.subject.eng Aldosterone-receptor-blockade de
dc.subject.eng Aldo-DHF de
dc.subject.eng heartfailure de
dc.subject.eng Galectin-3 de
dc.identifier.urn urn:nbn:de:gbv:7-11858/00-1735-0000-0022-5D9C-C-0
dc.affiliation.institute Medizinische Fakultät de
dc.subject.gokfull Medizin (PPN619874732) de
dc.subject.gokfull Innere Medizin - Allgemein- und Gesamtdarstellungen (PPN619875747) de
dc.description.embargoed 2015-03-18
dc.identifier.ppn 816914591

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