Copeptin in heart failure: Associations with clinical characteristics and prognosis

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1 Copeptin in heart failure: Associations with clinical characteristics and prognosis D. Berliner, N. Deubner, W. Fenske, S. Brenner, G. Güder, B. Allolio, R. Jahns, G. Ertl, CE. Angermann, S. Störk for the INH Study Group of the Competence Network Heart Failure Comprehensive Heart Failure Center, Würzburg, Germany Hannover Medical School, Dept. of Cardiology and Angiology, Hannover, Germany University of Würzburg, Department of Internal Medicine I, Würzburg, Germany

2 Disclosure of interest ThermoFisher Scientific - performed the CT-proAVP (Copeptin) measurements in a blinded fashion - was neither involved in the analysis nor the interpretation of the data

3 Background: Vasopressin (AVP) & Copeptin (CT-proAVP) Vasopressin (AVP) plays a pivotal role in the regulation of sodium, water homeostasis, and renal function. Synthesis of pro- AVP Hypothalamus Triggers - drop in blood pressure - change in osmotic pressure - acute stress (e.g. AMI) Cleavage Effects - stimulation of ACTH release - water retention in the kidney - vasoconstriction Transport via portal vessels Mediates ACTH release Ant. pituitary Post. pituitary Measurement - AVP: not feasible in clinical routine - CT-proAVP: stable NG Morgenthaler, Congest Heart Fail. 2010

4 Background: Vasopressin (AVP) & Copeptin (CT-proAVP) Diagnostic utility Copeptin has recently been shown to improve diagnosis in the setting of myocardial infarction. Prognostic utility Reichlin et al. J Am Coll Cardiol 2009;54:60-8 Keller et al. J Am Coll Cardiol 2010;55: Elevated Copeptin levels correlated with worse outcome in patients with heart failure (HF). Stoiser et al. Eur J Clin Invest. 2006;36: Gegenhuber et al. J Card Fail. 2007;13:42 49.

5 Aim of the study Investigation of associations of Copeptin with Clinical characteristics Laboratory parameters Comorbidities Outcome in the setting of HF.

6 Methods 926 patients of the Interdisciplinary Network Heart Failure Study (INH study) were included left ventricular ejection fraction (LVEF) 40% enrolled after best possible recompensation prior to discharge after hospitalisation for cardiac decompensation Besides comprehensive clinical assessment including ECG and echocardiography, an extensive blood testing profile was obtained. Patients underwent serial follow-up at six month intervals in our outpatients clinic or via a structured telephone interview. Follow-up time was 18 months.

7 Patients characteristics Age (years) 70 (61; 77) Male sex 659 (71.9%) Systolic BP (mmhg) 120 (110; 130) Diastolic BP (mmhg) 70 (60; 80) Sinus rhythm 578 (67.5%) Heart rate (bpm) 78 (66; 92) NYHA class III/IV 408 (44.5%) NT-proBNP (pg/ml) 3035 (1075; 7653) Ischemic cause of HF 460 (50.2%) LA(ES) (mm) 46 (42; 51) LVD(ED) (mm) 61 (55; 67) LVEF (%) 31 (25; 36) Copeptin (pmol/l) (10.1; 40.6) Copeptin 12 pmol/l 279 (30.1%) Renal insufficiency (GFR < 60 ml/min) 378 (41.3%) Diabetes mellitus 319 (34.8%) Anemia 284 (31%) ACE inhibitor or AT1-Blocker 808 (88.9%) Mineralocorticoid receptor antagonist 388 (42.6%) Betablocker 765 (83.5%) Digitalis glycosides 332 (36.4%) Diuretics 791 (86.4%) Mortality at 6 months 91 (9.8%) 12 months 143 (15.4%) 18 months 185 (20.0%)

8 Copeptin: age and gender Age Gender p=0.535

9 Copeptin and severity of HF NYHA class Left ventricular ejection fraction

10 Copeptin and other biomarkers NT-proBNP Troponine-I High sensitivity C-reactive Protein Interleukin-6

11 Copeptin and renal function Glomerular filtration rate Renal insufficiency* *GFR < 60 ml/min

12 Copeptin and comorbidities Diabetes mellitus HbA1c

13 Copeptin and comorbidities No diabetes mellitus Diabetes mellitus p=0.756

14 Copeptin and comorbidities Anemia Depression

15 Associations with Copeptin Copeptin (pmol/l) p Ischaemic cause of HF 111 (48%) 106 (46%) 117 (51%) 126 (56%) Sodium (mmol/l) 139 (137; 142) 140 (138; 142) 139 (137; 142) 140 (138; 142) 0.42 Cortisol (µg/dl) (9.8; 16.5) (10.1; 17.15) 14.9 (11.8; 18.4) (13.6; 22.2) <0.001 HbA1c (%) 5.8 (5.4; 6.4) 6.1 (5.6; 6.8) 6.2 (5.8; 6.9) 6.25 (5.8; 7.2) <0.001 Hemoglobin (g/dl) 13.8 (12.8; 14.9) 14.2 (12.6; 15.4) (12.2; 14.85) 12.8 (11.1; 14.4) <0.001 Erythropoietin (miu/ml) (8.2; 20.5) 12.7 (8.5; 18.2) 14.2 (8.9; 25.9) 21.2 (10.6; 38.7) <0.001 Sinus rhythm (ECG) 186 (85%) 149 (68%) 133 (64%) 110 (53%) <0.001 QRS duration (ms) 110 (94; 140) 101 (95.5; 127.5) 115 (100; 140) 110 (100; 140) 0.54 Heart rate (1/min) 75 (63; 85) 77 (67; 95) 81 (67; 95) 80 (67; 93) LA(ES) (mm) 44 (39; 48) 46 (41; 50) 48 (43; 52) 47 (43; 53) <0.001 LVD(ED) (mm) 60 (55; 66) 60 (54; 67) 62 (55; 68) 62 (56; 67) 0.67 LVEF (%) 31 (27; 38) 33 (26; 37) 30 (23; 35) 30 (25; 35) 0.001

16 Prognosis Mortality (%) Copeptin <= > p Mortality at 180 days 9 (3.9%) 15 (6.5%) 22 (9.5%) 45 (19.5%) < days 16 (6.9%) 23 (10%) 35 (15.1%) 69 (29.9%) < days 23 (9.9%) 28 (12.2%) 45 (19.4%) 89 (38.5%) < > Quartiles of CT-proAVP 540 days 360 days 180 days

17 Prognosis Copeptin measured at baseline Copeptin measured after 6 months HR 2.20 (95%CI ) p=0.003 adjusted for age, sex, NYHA class, and renal function HR 3.59 (95%CI ) p=0.033 adjusted for age, sex, NYHA class, and renal function

18 Summary Elevation of copeptin is frequent in HF patients (~70%). associated with factors and comorbidities known to adversely affect prognosis. Copeptin (pmol/l) 10,10 10,11-20,35 20,36-40,60 > 40,60 P for trend Age (years) <0.01 NYHA class III/IV 28% 41% 49% 61% <0.01 Renal insufficiency 12% 28% 48% 78% <0.01 Diabetes mellitus 25% 34% 37% 43% <0.01 Anaemia 20% 25% 32% 48% <0.01 NT-proBNP (pg/ml) <0.01 hs-crp (mg/l) <0.01

19 Summary Elevation of copeptin is frequent in HF patients (~70%). associated with factors and comorbidities known to adversely affect prognosis. Higher levels of copeptin independently predict an increased mortality risk. The potential clinical utility of such information needs to be tested in further studies.

20 Thank you for your attention!