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
Università di Palermo
Scuola di Medicina
Dipartimento di Medicina Interna e Specialistica
(DIBIMIS)
Sezione di Malattie Cardio
Cardio--Respiratorie e Endocrino
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
Direttore
Ruolo del BNP ed NTNT-pro
pro--BNP nella diagnosi
e followfollow-up dell’insufficienza cardiaca
Prof. Salvatore Novo
3 Dicembre 2014
PEPTIDI NATRIURETICI
Munagala VK et al. Curr Probl Cardiol 2004
BNP e NT
NT--pro
pro--BNP
What is BNP?
A 32-aa polypeptide
Belong to a class of structurally
similar natriuretic peptides
(classes A,B,C and D)
Similar to ANP (Atrial
Natriuretic Peptide has longer
t1/2 (~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
What is NT
NT--pro
pro--BNP?
BNP?
Is a biologically inactive
76 amino acid Nterminal fragment
Co-secreted with BNP
Even longer t1/2 than
BNP (~1-2hrs vs
~20mins)
In physiological
conditions the plasma
levels of NT-pro-BNP
should be < 400 pg / ml
ACTIONS OF BNP
Release of CNP
from Vascular
Endothelium
Release of
ANP from
Atria
Supression of
Renin--Angiotensin
Renin
and Endothelin
Release of BNP
from Ventricles
Decreased peripheral
vascular resistance
(decreased BP)
Increased
Natriuresis
Potential Causes of NT
NT--proBNP Elevation
Januzzi JL et al. Am J Cardiol
Cardiol,, 2008
BNP in diverse condizioni
cardiovascolari
Hirata Y et al Cardiovasc Res 2001
Correlations of ProPro-BNP and
Functional Mitral Regurgitation
LgPro-BNP(pg/m
L)
6
5
4
3
2
N =324
r =0.40
1
p <0.0001
0
0
5
10
15
MR (%)
Dini FL et al. Eur Heart J 2005;26:540-6.
20
25
Correlates of MR grade and RV function
with BNP
Troughton RW et al. J Am Coll Cardiol 2004;43:416-422
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;5:481-488
Clinical information that can be obtained
from BNP or NT
NT--proBNP assessment
Weber M. et al. Heart.
Heart. 2006
Recommendations for the diagnostic
investigations in ambulatory patients
suspected of having heart failure
ESC Guidelines for the Diagnosis and Treatment
of Acute and Chronic Heart Failure 2012
Diagnostic flowchart for patients with suspected
HF showing alternative “echocardiography
“echocardiography first”
first”
or “natriuretic
“natriuretic peptide first
first”” approaches
ESC Guidelines for the Diagnosis and Treatment of Acute and Chronic HF 2012
NTNT-proBNP Levels by Diagnosis
in Patients with Acute Dyspnea
Januzzi et al. Eur Heart J, 2006
Box Plots Showing Median Levels of
BNP Measured in the Emergency
Department in Three Groups of Patients
Maisel,, A.S
Maisel
A.S.. et al. N Engl J Med, 2002
BNP Levels in the General Population and HF
Macheret et al. NTproBNP in the General Community, JACC 2011
Median BNP in patients with HF
according to NYHA functional status
Weber M. et al. Heart 2006
NTNT-proBNP Levels in Acute HF as a
Function of HF Severity
Januzzi et al. Eur Heart J, 2006
VALEFT Study 2006
Masson et al. Clin Chem,
Chem, 2006
NTNT-proBNP Levels Predict Survival
in Patients with Acute HF
Januzzi et al. Eur Heart J, 2006
McKie P.M. et al. Mayo Clin Proc,
Proc, 2011
McKie P.M. et al. Mayo Clin Proc,
Proc, 2011
Elevated NTNT-proBNP and Renal Function
Predict Poor Outcome in Acute HF
Baggish et al. Am J Cardiol
Cardiol,, 2008
The potential role of NT
NT--proBNP in screening for HF
and in predicting prognosis in HF: a survival analysis
Taylor C.J. et al. BMJ Open 2014
PROTECT Study
Primary Endpoint
(Standard
of care)
PROTECT Study
Individual Endpoints
60
NB: 0 cerebral ischemia events in either arm
SOC
NT-proBNP
Number of events
50
40
NB: 3 of 4 CV deaths in NTNT-proBNP arm
occurred after elective withdrawal from study
30
20
10
P =.001
P =.002
P =.72
P =.41
P =.52
0
Worsening
HF
HF hosp
ACS
VT/VF
CV death
PROTECT Study
Kaplan--Meier Analysis
Kaplan
1.0
Event free survival
Log rank P =.03
0.8
0.6
0.4
NT
NT--proBNP (N=75)
0.2
Standard--ofStandard
of-care (N=76)
0
0
73
146
219
292
Days from enrollment
365
PROTECT Study
Events as a function of NTNT-proBNP
Changes in NT
NT--proBNP
Januzzi and Troughton.
Troughton. Usefulness of NPNP-Guided Therapy. Circulation 2013
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;127:500508
Copyright © American Heart Association, Inc. All rights reserved.
Therapies for Heart Failure that may
lower Natriuretic Peptide Values
Januzzi and Troughton.
Troughton. Usefulness of NP
NP--Guided Therapy.
Therapy.
Circulation 2013
Variazioni del NT
NT--proBNP durante
l’ospedalizzazione, in riferimento al
decorso clinico a breve termine
Lusiani L. et al. Cardiologia ambulatoriale. 2006
Esperienza Personale: Materiali e Metodi
•
104 pazienti, 43 donne e 61 uomini,
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.
Nt
Nt--proBNP e FE
• Per HFrEF (FE ≤
40
40%)
%) 10784,69
pg/ml;
• Per HFpEF
borderline (40% <
FE< 50%) 8994,33
pg/ml;
• Per HFpEF (FE ≥
50%) 5823,07
pg/ml.
NT
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.
NT
NT--proBNP e FollowFollow-up a 6 mesi
• Mortalità a 6 mesi 7,7%
• I soggetti deceduti avevano valori medi di NTproBNP al ricovero di 16.326 pg/ml rispetto
al dato medio dei sopravvissuti di 7643,3
pg/ml
Why NT
NT--proBNP?
proBNP?
CONCLUSIONI
BNP o NTproBNP UTILI PER:
1. DIAGNOSI DI INSUFFICIENZA CARDIACA
2. PROGNOSI
3. GUIDA ALLA TERAPIA