5 Congresso Nazionale Federazione Italiana Tecnici di Laboratorio Biomedico

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1 5 Congresso Nazionale Federazione Italiana Tecnici di Laboratorio Biomedico Innovazione e Formazione nella Medicina di Laboratorio Sala Magna Complesso Monumentale dello Steri Palermo 2-4 Dicembre 2014

2 Università di Palermo Scuola di Medicina Dipartimento di Medicina Interna e Specialistica (DIBIMIS) Sezione di Malattie Cardio-Respiratorie e Endocrino-Metaboliche Cattedra di Malattie dell Apparato Cardiovascolare Master di Ecocardiografia Master di Malattie Vascolari Centro per la Diagnosi Precoce di Aterosclerosi Preclinica e Pluridistrettuale e per la Prevenzione Secondaria U.O.C. di Cardiologia Centro di Riferimento Regionale per la Diagnosi e Cura dello Scompenso Cardiaco - A.O.U. Policlinico P. Giaccone Direttore: Prof. Salvatore Novo Ruolo del BNP ed NT-pro pro-bnp nella diagnosi e follow-up dell insufficienza cardiaca Prof. Salvatore Novo 3 Dicembre 2014

3 PEPTIDI NATRIURETICI MunagalaVK etal. Curr Probl Cardiol 2004

4 BNP e NT-pro-BNP

5 What is BNP? A 32-aa polypeptide Belong to a class of structurally similar natriureticpeptides (classes A,B,C and D) Similar to ANP (Atrial Natriuretic Peptide has longer t 1/2 (~20 mins), double that of ANP) Produced with ventricular stretch and volume Increases with worsening heart failure In physiological conditions the plasma levels of BNP should be < 100 pg /ml

6 WhatisNT-pro-BNP? Is a biologically inactive 76 amino acid N- terminal fragment Co-secreted with BNP Even longer t 1/2 than BNP (~1-2hrs vs ~20mins) In physiological conditions the plasma levels of NT-pro-BNP should be < 400 pg / ml

7 ACTIONS OF BNP Release of CNP from Vascular Endothelium Release of ANP from Atria Supressionof Renin-Angiotensin and Endothelin Release of BNP from Ventricles Decreased peripheral vascular resistance (decreased BP) Increased Natriuresis

8 PotentialCausesofNT-proBNPElevation JanuzziJL JL etal. Am J Cardiol, 2008

9 BNP in diverse condizioni cardiovascolari HirataY etal Cardiovasc Res 2001

10 Correlations of Pro-BNP and Functional Mitral Regurgitation 6 Lg Pro-BNP (pg/ml) N =324 r =0.40 p < MR (%) Dini FL et al. Eur Heart J 2005;26:540-6.

11 Correlates of MR grade and RV function with BNP Troughton RW et al. J Am Coll Cardiol 2004;43:

12 The highest plasma levels of BNP were found in patients with left heart failure and concomitant right ventricular dysfunction Mariano-Goluart D. et al. Eur J Heart Fail 2003;5:

13 Clinicalinformation information thatcan beobtained frombnp or NT-proBNPassessment Weber M. etal. Heart. 2006

14 Recommendationsforthe diagnostic investigationsin ambulatorypatients suspectedofhavingheartfailure ESC Guidelines forthe Diagnosisand and Treatment ofacute and Chronic Heart Failure 2012

15 Diagnostic flowchart for patients with suspected HF showing alternative echocardiography first or natriuretic peptide first approaches ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic HF 2012

16 NT-proBNP Levels by Diagnosis in Patients with Acute Dyspnea Januzzietal. Eur Heart J, 2006

17 Box Plots Showing Median Levels of BNP Measured in the Emergency Department in Three Groups of Patients Maisel, A.S.. et al. N EnglJ Med, 2002

18 BNP Levels in the General Population and HF Macheret et al. NTproBNP in the General Community, JACC 2011

19 Median BNP in patients with HF according to NYHA functional status Weber M. et al. Heart 2006

20 NT-proBNP Levels in Acute HF as a Function of HF Severity Januzzietal. Eur Heart J, 2006

21 VALEFT Study 2006 Massonetal. Clin Chem, 2006

22 NT-proBNP Levels Predict Survival in Patients with Acute HF Januzzietal. Eur Heart J, 2006

23 McKieP.M. etal. Mayo Clin Proc, 2011

24 McKieP.M. etal. Mayo Clin Proc, 2011

25 Elevated NT-proBNP and Renal Function Predict Poor Outcome in Acute HF Baggishetal. Am J Cardiol, 2008

26 The potentialroleof of NT-proBNP in screening for HF and in predicting prognosisin in HF: a survival analysis Taylor C.J.et al. BMJ Open 2014

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28 PROTECT Study Primary Endpoint (Standard of care)

29 PROTECT Study Individual Endpoints 60 NB: 0 cerebral ischemia events in either arm Number of events P =.001 SOC NT-proBNP NB:3 of 4 CV deaths in NT-proBNP probnparm occurred after elective withdrawal from study P =.002 P =.72 P =.41 P =.52 0 Worsening HF HF hosp ACS VT/VF CV death

30 PROTECT Study Kaplan-Meier Analysis 1.0 Log rank P=.03 Event free survival NT-proBNP(N=75) Standard-of-care (N=76) Days from enrollment

31 PROTECT Study Events as a function of NT-proBNP

32 Changesin NT-proBNP Januzziand and Troughton. Usefulness of NP-Guided Therapy. Circulation 2013

33 The 36-month mortality rates for subjects <75 years of age in the NT-proBNP-Assisted Treatment to Lessen Serial Cardiac Readmissions and Death (BATTLESCARRED) study as a function of treatment allocation. Januzzi J L, and Troughton R Circulation. 2013;127: Copyright American Heart Association, Inc. All rights reserved.

34 Therapies for Heart Failure that may lower Natriuretic Peptide Values Januzziand and Troughton. Usefulness ofnp NP-Guided Therapy. Circulation2013

35 Variazioni del NT-proBNPdurante l ospedalizzazione, in riferimento al decorso clinico a breve termine LusianiL. L. et al. Cardiologia ambulatoriale. 2006

36 Esperienza Personale: Materiali e Metodi 104pazienti,43donnee61uomini, di età media 74,4±11,7. Livelli sierici di Nt-proBNP dosati all inizio del ricovero, alla dimissione e dopo 30 giorni. Follow-up a 6 mesi.

37 Nt-proBNP e FE Per HFrEF (FE 40%) 10784,69 pg/ml; Per HFpEF borderline (40% < FE< 50%) 8994,33 pg/ml; Per HFpEF (FE 50%) 5823,07 pg/ml.

38 NT-proBNP in vs out Nei pazienti responsivi alla terapia in cui è stato osservato un miglioramento clinico, si nota un abbassamento dei livelli plasmatici di NT-proBNP con valori medi al momento del ricovero di 8174,9 pg/ml e alla dimissione di 4850,7 pg/ml.

39 NT-proBNP e Follow-up a 6 mesi Mortalità a 6 mesi 7,7% I soggetti deceduti avevano valori medi di NTproBNP al ricovero di pg/ml rispetto al dato medio dei sopravvissuti di 7643,3 pg/ml

40 WhyNT-proBNP?

41 CONCLUSIONI BNP ontprobnp UTILI PER: 1. DIAGNOSI DI INSUFFICIENZA CARDIACA 2. PROGNOSI 3. GUIDA ALLA TERAPIA

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