Untersuchungen zur dilatativen Kardiomyopathie: Docosahexaensäure als neuer Biomarker für die Dilatation und minimal invasiver Herzbeutelzugang (AttachLifter)

Im Serum von Patienten mit dilatativer Herzinsuffizienz war der Spiegel hoch ungesättigter Fettsäuren signifikant reduziert ("HUFA Mangel"). N-3 und n-6 Fettsäuren waren negativ mit gesättigten und einfach ungesättigten (n-9 und n-7) Fettsäuren korreliert. Da keine oder nur schwache Korrel...

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Bibliographic Details
Main Author: Rupp, Thomas Philipp
Contributors: Maisch, Bernhard (Prof.Dr.) (Thesis advisor)
Format: Dissertation
Published: Philipps-Universität Marburg 2012
Innere Medizin
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Table of Contents: In the serum of patients with dilative heart failure, the level of highly unsaturated fatty acids (HUFA) was significantly reduced ("HUFA deficiency"). N-3 (omega-3) and n-6 (omega-6) fatty acids were negatively correlated with saturated and monounsaturated (n-9 and n-7) fatty acids. Since no or only a weak correlation was observed with the precursor fatty acids α-linolenic acid and linoleic acid, influences of heart function were examined. Patients were stratified according to LVEDD. A markedly dilated left ventricle (LVEDD 69-90 mm) was associated with a significant decrease of serum EPA, DHA and arachidonic acid while 18:1n-9 was increased. DHA and arachidonic acid were also reduced in patients with dilated left atrium. A DHA level >1.24% had a negative predictive value of 91% for the absence of a severely dilated (LVEDD >70 mm) left ventricle, whereby the sensitivity was 84%. An increased enddiastolic wall stress (>4 kPa) was associated with a reduced heart rate variability (SDNN). Since LVEDD is influenced by LVEF, patients were also stratified according to tertiles of LVEF. A reduced LVEF (9-25% vs. 26-35%) was associated with lower serum EPA, DHA and arachidonic acid levels and an increase of 16:0 and 18:1n-9. Since a reduced DHA concentration can have also non cardiac causes, patients were stratified according to DHA. LVEDD and left atrial diameter were increased in the lower and middle tertile when compared with the upper tertile. While non-failing cardiac overload cannot induce these alterations, sympathetic activation and associated metabolic changes such as insulin resistance and hyperinsulinemia could contribute. In favor of this contention are fatty acid alterations in pressure overloaded non-failing DOCA-salt rats with a dietary induced insulin resistance. The reduction of HUFA is rated as adverse in the progression of heart failure and it is proposed to assess the therapeutic substitution of EPA and DHA in a clinical trial particularly in dilative heart failure. In addition to the studies on fatty acid profile in patients with dilative heart failure, novel instruments for accessing the normal pericardial sac (AttachLifter) and intrapericardial navigation (AttachGuider) were co-developed. The AttachLifter permits the safe delivery of drugs into the pericardial sac. For example, intrapericardially administered n-3 HUFA could be used as potentially antiarrhythmic agents in the future and prove beneficial in heart failure therapy. For the AttachLifter, the European patent was already granted and the clinical evaluation is awaited.