Plasma MR-proADM is superior to NTproBNP for all-cause short term mortality prediction in acute pulmonary embolism.

Transcription

1 J. Pedowska-Wloszek, M. Kostrubiec, A. Labyk, S. Pacho, O. Dzikowska-Diduch, P. Bienias, B. Lichodziejewska, P. Palczewski, M. Ciurzynski, P. Pruszczyk Plasma MR-proADM is superior to NTproBNP for all-cause short term mortality prediction in acute pulmonary embolism. Medical University of Warsaw

2 Declaration of conflict of interest none

3 Risk stratification in APE

4 Markers of RV dysfunction Echo CT BNP NTproBNP New markers RadioGraphics, 2004, 24,

5 Proadrenomedullin Marker in risk stratification of patients with heart failure Maisel et al. J Am Coll Cardiol 2010 May 11;55(19):

6 Adrenomedullin Adrenomedullin 52 amino acid peptide, discovered in pheochromocytoma tissue Kitamura et al.biochem Biophys Res Commun 1993 April 30;192(2): Hypotensive effect decreases peripheral resistance and increases cardiac output Vasodilatory action in pulmonary vasculature Increases diuresis and natriuresis Inhibits renin angiotensin-aldosterone system

7 MRproADM (mid regional pro adrenomedullin) MRproADM (mid regional pro adrenomedullin)» secreted in equimolar amounts to ADM» more stable than ADM in plasma» w/o biological effects J Am Coll Cardiol, 2007; 49: Triggering factors: - Hypoxia - Ventricles strech

8 Proadrenomedullin when elevated Heart failure plasma levels? Maisel et al. J Am Coll Cardiol 2010,11; 55(19): Pulmonary hypertension Kakishita et al. Clinical Science 1999, 96; Myocardial infarction, arterial hypertension, chronic kidney disease, sepsis, pneumonia Nishikimi T. Adrenomedullin in Cardiovascular Disease. Springer 2005 Acute pulmonary embolism???

9 Hypothesis MRproADM plasma levels are related to the severity of APE and predicts short term mortality in APE. MRproADM is superior to NTproBNP for prediction of early mortality in APE.

10 Aim of the Study 1. Assesment of the relation between MRproADM plasma levels and NTproBNP, haemodynamic distrubances and the echocardiographical signs of RV dysfunction 2. Assesment of the prognostic value of MRproADM in APE pts 3. Comparison of MRproADM and NTproBNP prognostic value in 30-days outcome in APE pts

11 Methods 1 98 consecutive pts (51 F / 47 M, 59,6 ± 18,4 yr) with confirmed APE with multislice CT, hospitalized in the Department of Internal Medicine and Cardiology, The Medical University of Warsaw ( ) Exclusion criteria: severe valvular heart disease, ACS, EF < 40%. On admission, echocardiography and blood samples for MRproADM and NTproBNP. 40 healthy individuals (26 F / 14 M) control group - MRproADM

12 Methods 2 MRproADM - KRYPTOR (Thermo Fisher Scientific, B R A H M S AG, Hennigsdorf/Berlin, Niemcy), detection limit 0,05 nmol/l, sensivity 0,25 nmol/l NTproBNP - VIDAS ( BIOMERIEUX, France) measuring range pg/ml, detection limit > 20 pg/ml

13 Endpoints 30-days or in- hospital all-cause mortality 30-days APE related mortality Combined endpoint including at least one of following: hemodynamic collapse, need for catecholamines infusion, CPR, thrombolysis

14 Results Low risk APE 27pts.(27,6%) High risk APE 5 pts. (5,1%) Intermediate risk APE 66 pts. (67,3%) All- cause mortality 6 pts. (6,1%) APE related mortality 5 pts. (5,1%) Combined endpoint 11 pts (7,74%)

15 MRproADM plasma levels and severity of APE 0,99 ( 0,39-7,49) 0,73 ( 0,38 1,34) 2,06 (0,44 3,09) 0,65 (0,290,65 (0,29 1,19)1,194) LR -APE IR - APE HR -APE CG

16 MRproADM, NTproBNP plasma levels and severity of APE High-risk APE Intermediate- risk APE Low- risk APE p MR- proadm nmol/l 2,062 (0,447-3,098) 0,995 (0,394-7,499) 0,734 (0,384-1,342) 0,001 NT -probnp pg/ml 1334,0 (20,0-2294,0) 1716,0 (20, ,0) 85,5 (20,0-724,00) 0,015

17 MRproADM and all-cause mortality 2,12 (1,54 4,22) 0,290,65 (0,29 1,19)1,194 0,91 ( 0,38 7,44) Nonsurvivors Survivors Control group

18 MRproADM and APE- related mortality 2,06 (1,54 4,22) 0,20,65 (0,29 1,19)1,194 0,91 ( 0,79 1,001) Nonsurvivors Survivors na Control group

19 MRproADM and combined endpoint 1,77 (0,39 4,22) 0,91 ( 0,78 0,99) 0,290,65 (0,29 1,19)1,194 Adverse outcome Favorable course Control group

20 Sensitivity ROC analysis for all-cause mortality Sensitivity 100% Specificity 88% 100-Specificity

21 Sensitivity Sensitivity ROC analysis for APE - related mortality and combined endpoint Sensitivity 100% Specificity 86,96% Sensitivity 72,73% Specificity 86,96% 100-Specificity 100-Specificity

22 MRproADM and NTproBNP positive correlation between MRproADM blood concentrations and NTproBNP (r = 0,509, p < 0,0001).

23 Sensitivity Comparison of ROC curves for MRproADM and NTproBNP P = 0, Specificity AUC for MRproADM 0,94 (95% CI 0,86 0,97) AUC for NTproBNP 0,84 (95%CI 0,75 0, 91), p = 0,375.

24 Predictors of all-cause mortality: univariable analysis OR 95% CI p MRproADM nmol/l concetration 2,30 1,185 4,448 0,005 NTproBNP pg/ml concetration 1,00 1,000 1,0003 0,017 GFR (ml/min/1,73m 2 ) 0,92 0,877 0,977 0,0007 TRPG mmhg 1,06 1,011 1,112 0,013 Age 1,32 1,089 1,611 0,0001 age, heart failure, COPD, CAD, systolic BP, heart rate, shock index, MRproADM blood concetrations, NTproBNP, NTproBNP > 1000 pg/ml, Troponin I, GFR, echocariographical parameters (EF%, TRPG, AcT, RV diameter, LV diameter, RV/LV ratio, RV overload, RV hypokinesis, IVC diameter).

25 Predictors of all-cause mortality: univariable analysis-cox model HR χ 2 95% CI p MRproADM nmol/l concetration 1,65 5,97 1,214 2,249 0,015 Log 10 MRproADM 73,90 11,99 7, ,771 0,0005 NTproBNP pg/ml concetration 1,00 4,74 1,000 1,0002 0,029 Log 10 NTproBNP 9,87 9,64 1,724 55,996 0,002 GFR ml/min/1,73m 2 0,93 10,48 0,893 0,980 0,001 TRPG mmhg 1,05 5,89 1,013 1,095 0,015 Age 1,21 18,23 1,082 1,358 <0,0001 age, heart failure, COPD, CAD, systolic BP, heart rate, shock index, MRproADM blood concetrations, MRproADM > 1,4 nmol/l, NTproBNP, NTproBNP > 1000 pg/ml, Troponin I, GFR, echocariographical parameters (EF%, TRPG, AcT, RV diameter, LV diameter, RV/LV ratio, RV overload, RV hypokinesis, IVC diameter).

26 Multivariable analysis MRproADM 1. All-cause mortality HR 61,47 (95% CI 6, ,3, p=0,0008), 2. APE related mortality HR 43, 22 (95% CI 3, ,356, p=0,006) 3. Combined endpoint HR 51,17 (95% CI 2, ,4, p=0,019).

27 Conclusions 1. Proadrenomedullin concentration in the blood is elevated in some patients with PE and reflects the severity of pulmonary embolism. 2. Measurement of the blood concentration of MRproADM is useful in assessing the short term prognosis in patients with PE. 3. Although the concentrations of NTproBNP and MRproADM are of similar predictive value in the assessment of outcome, the proadrenomedullin shows superiority in predicting all cause mortality.

28 Thank you