Clin Res Cardiol 107, Suppl 1, April 2018

Prognostic potential of evening salivary cortisol levels and circadian cortisol changes in patients with systolic heart failure and depression – impact of escitalopram therapy

L. Barthel1, M. Kroiss2, S. Sehner3, S. Lezius3, H. Gunold4, F. Edelmann5, R. Wachter6, T. Graf7, S. Pankuweit8, D. Knappe9, C. Prettin10, S. Störk1, G. Ertl11, M. Fassnacht2, C. E. Angermann12, für die Studiengruppe: MOOD-HF

1Deutsches Zentrum für Herzinsuffizienz, Universitätsklinikum Würzburg, Würzburg; 2Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Würzburg; 3Institut für Medizinische Biometrie und Epidemiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg; 4Klinik für Innere Medizin/Kardiologie, Herzzentrum der Universität Leipzig, Leipzig; 5Kardiologie, Leitung / Mittelallee 11 / 2. Stock, Charité - Universitätsmedizin Berlin, Berlin; 6Universitätsmedizin Göttingen, Göttingen; 7Medizinische Klinik II / Kardiologie, Angiologie, Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Lübeck; 8Klinik für Innere Medizin - Schwerpunkt Kardiologie, Universitätsklinikum Giessen und Marburg GmbH, Marburg; 9Universitäres Herzzentrum Hamburg GmbH, Hamburg; 10Koordinierungszentrum für Klinische Studien Leipzig, Universität Leipzig, Leipzig; 11Zentrum Innere Medizin , Universitätsklinikum Würzburg, Würzburg; 12DZHI Med. Klinik und Poliklinik I, Universitätsklinikum Würzburg, Würzburg;

Background: Depression is frequent in heart failure (HF) and associated with adverse clinical outcomes. A double-blind multicenter trial (MOOD-HF) showed that in depressed patients with systolic heart failure (HF) the selective serotonin reuptake inhibitor escitalopram (E) improved neither the composite primary endpoint (all-cause death or unplanned hospitalization) nor depression compared to placebo (P), but suggested unfavourable outcome changes in E-treated patients. The hypothalamic-pituitary-adrenocortical (HPA) axis is altered in response to stressors as depression or HF. This MOOD-HF substudy aimed to clarify whether circadian salivary cortisol levels (CSCL) were predictive of adverse events in depressed MOOD-HF participants, and whether outcomes differ according to CSCL and / or treatment with E in MOOD-HF participants. Methods & Results: MOOD-HF participants (all suffering from symptomatic systolic HF, current major depression and a left ventricular ejection fraction (LVEF) <45%) were eligible for the present analysis if providing at the baseline visit (BL) samples for CSCL determination (commercial luminescence immunoassay IBL, Hamburg, Germany), and if not on oral therapy with glucocorticosteroids. Depression severity was determined with the Montgomery–Åsberg Depression Rating Scale (MADRS) and LVEF measured by echocardiography. In the total study cohort, the median morning saliva cortisol level (SCL) was 0.210 µg/dL (0.141 - 0.338 µg/dL) and the median evening (pm) SCL 0.067 µg/dL (0.036 - 0.128 µg/dL) at BL (p<0.001). The median circadian change was 0.124 µg/dL (0.044 - 0.239 µg/dL). In patients with a BL pm-SCL >median the MADRS-score was 21.7±9.1 and LVEF 33.7±8.4%, respectively, in patients with a BL pm-SCL <median these values were 19.6±9.1 and 36.5±7.8% (p=0.048 and 0.004, respectively). Among 147 patients with a pm-SCL <median 73 were randomized to E vs 74 receiving P; among 146 patients with a pm-SCL >median 73 were randomized to E vs 73 patients receiving P. During 12 months follow-up the composite primary endpoint occurred least in E-treated patients with low pm-SCL and most often in E-treated patients with high pm-SCL under E (Hazard Ratio (HR) 2.02, 95% confidence interval (CI) 1.12-3.65, p=0.010); patients receiving P had comparable event rates irrespective of BL pm-SCLs (Figure A). Thus, numerically patients on E with low BL pm-SCL had lower event rates compared with corresponding P-treated patients (HR 0.76, CI 0.41-1.40, p=0.796), while patients with high BL pm-SCL had higher event rates (HR 1.29, CI 0.74-2.24, p=0.799) than corresponding P-treated patients. Patients with circadian SCL changes >median receiving P experienced the composite primary endpoint least, while both subgroups with circadian SCL changes <median and also patients with circadian SCL changes >median on E had higher event rates (HR 0.66, CI 0.45-0.97, p=0.033, Figure B) Conclusion: In depressed patients with systolic HF high pm-SCL are associated with more severe disease (depression and cardiac dysfunction). Extending primary MOOD-HF results indicating unfavourable outcomes related to E, the current findings suggest a SCL x treatment interaction with higher event rates in (sicker) patients with high pm-SCL and lower event rates in (less sick) patients with low pm-SCL when treated with the antidepressant. Low circadian SCL changes were always associated with higher event rates.

http://www.abstractserver.de/dgk2018/jt/abstracts//P1691.htm