Transcript 1st PRESENTATION

Accuracy of natriuretic
peptides levels in the
diagnosis of left ventricular
dysfunction
Introduction to Medicine – 1st year
Class 11 2006-2007
12th december 2006
Porto Medical Faculty
Systematic Review
Introduction
• Left ventricular dysfunction;
• Type-B natriuretic peptides;
• Use of type-B natriuretic peptides on
diagnosis of left ventricular dysfunction;
Left ventricular dysfunction
• Left ventricular dysfunction or heart failure
(HF) is the pathophysiologic state in which the
heart is enable to pump blood at a rate
commensurate with the requirements of the
metabolizing tissues. [1]
•
Complex clinical syndrome that can result
from any structural or functional cardiac
disorders that impairs the ability of the
ventricle to fill with or eject blood. [2]
[1] - Braunwald. A textbook of Cardiovascular Medicine. Elsevier Saunders, 7th
Edition
[2] - Hunt S. ACC/AHA 2005 Guideline for the Diagnosis and Management of CHF
in the adult. JACC 2005
Left ventricular dysfunction
•
4,9 million persons in USA are being treated for heart failure [3]
•
550,000 new cases diagnosed each year
•
10% of patients older than 75 years have heart failure
•
Heart failure is the most common cause of hospitalization due
to cardiovascular disease in patients over 65 years of age [4]
•
The number of HF deaths has increased steadly despite
advances in treatment, in part because of increasing numbers
of patients with heart failure [5]
[3] - Ho K. The epidemiology of heart failure: the Framingham Study. JACC 1993
[4] - Louis A. A systematic review of telemonitoring for the management of heart
failure. Eur J Heart Failure 2003
[5] - American Heart Association. Heart disease and stroke statistics: 2005 update.
Dallas; American Heart Association
Left ventricular dysfunction
• Is a major health care problem and one of the most
frequent reasons for patients to be admitted to hospital;
• Despite significant advances in treatment, the
prognosis remains poor. [6]
• A simple objective definition of CHF is currently
impossible as there is no cutoff value of cardiac or
ventricular dysfunction or change in flow, pressure,
dimension, or volume that can be used reliably to
identify patients with heart failure. [7]
[6] – Sliwa, K. Heart Failure:Making a cardiac failure diagnosis as early as
possible. The Medicine Journal, 2002
[7] - Denolin H. The definition of heart failure. Eur Heart J 1983.
Diagnosing Left Ventricular
Dysfunction
• The clinical diagnosis of heart failure or left
ventricular dysfunction is complex, especially in
the presence of other pathologies such as
respiratory disease or obesity [8, 9]
• There are three types of tests for the diagnosis
of this pathology:
– Echocardiography and Doppler flow studies;[10]
– ECG and Chest X-rays;
– Blood tests for heart failure. [11]
[8] – Remes J. Validity of clinical diagnosis of heart failure in primary health care. Eur Heart J 1991.
[9] – Stevenson LW. The limited reliability of physical signs for estimating hemodynamics in chronic heart
failure. JAMA 1989.
[10] – Nielsen OW. Retrospective analysis of the cost-effectiveness of using plasma brain natiuretica
peptide in screening for LVD in the general population. JACC 2003.
[11] – McCullough PA. B tpe natriuretic peptide and clinical judgment in emergency diagnosis of HF:
analysis from Breathing Not Properly Multinational Study. Circulation 2002
Echocardiography and Doppler
flow studies
• The single most useful diagnostic test evaluating
patients with suspected heart failure is without doubt
the 2-dimentional echocardiogram, coupled with
Doppler flow studies [12]
• With the help of echocardiography the degree of left
ventricular systolic dysfunction can be determined
which has important prognostic implications;
• Doppler echocardiography assists in the diagnosis of
diastolic dysfunction. [6]
• Its limited availability and high costs prohibit its use in
general screening test [13]
[12] – Sim V. The use of brain natriuretic peptide as a screening test for left ventricular
systolic dysfunction – cost-effectivenedd in relation to open access echocardiography.
Fam Pract 2003.
[13] – Cheitlin MD. ACC/AHA/ASE 2003 Guideline update for clinical application of
echocardiography. JACC 2003
ECG and Chest X-rays
• Both chest radiography and 12-lead
electrocardiograms are important in providing
baseline information in most patients,
• Are both insensitive and nonspecific,
• Neither the ECG nor the chest radiograph
should form the primary bases for determining
the specific cardiac abnormality responsible
for the development of heart failure. [6]
[6] – Sliwa K.Heart Failure: Making a cardiac failure diagnosis as early
as possible, The Medicine Journal, March 2002
Blood tests for heart failure
• Recently the measurement of circulating
levels of brain natriuretic peptide (NTproBNP by Roche diagnostics) has become
available as a means of identifying patients
with elevated left ventricular filling
pressures who are likely to have signs and
symptoms of heart failure. [14]
[14] - Peacock W. The B-type natriuretic peptide assay: A rapid test
for heart failure, Cleveland Clinic Journal of Medicine 2002
Natriuretic Peptides
• There are three types of natriuretic peptides (NP):
– Type-A: produced by atrials myocite cells;
– Type-B: produced by ventricular myocites cells;
– Type-C: predominantly secreted by noncardiac
tissues (e.g., endothelium). [15]
• The most relevant type of NP for the diagnosis of left
ventricular dysfunction is the type-B. [16]
[15] – Vanderheyden M. Brain and other natriuretic peptides: molecular aspects. Eur J
Heart Failure 2004
[16] – Pfister R. Use of NT-proBNP in routine testing and comparison to BNP. Eur J Heart
Failure 2004
Type-B Natriuretic Peptides
• They are produced in the form of an inactive hormone,
proBNP;
• This inactive hormone is enzimaticly cleaved to two
peptides: one active, BNP; and another inactive, NTproBNP;
• In this reaction, NT-proBNP is produced in the same
proportion as BNP [17]
• This hormones are metabolized mostly in the kidneys;
• Although the proportion of this reaction is 1:1, the blood
levels of NT-proBNP are higher, since BNP is also
metabolized by endopeptidases and endotelial
receptores.[18]
[17] – Hulsmann M. Incidence of normal values of natriuretic peptides in patients with
chronic heart failure and impact on survival: A direct comparison of N-terminal atrial
natriuretic peptide, N-terminal brain natriuretic peptide and brain natriuretic peptide.. Eur J
Heart Failure 2005
[18] – Wu A. Biological variation of natriuretic peptides and their role in monitoring patients
with heart failure. Eur J Heart Failure 2004
Type-B Natriuretic Peptides
• The active form, BNP, induces the relaxation
of the cardiac muscle in response to
hemodinamic stress;
• The increase of the hemodinamic stress
causes the rise of the plasmatic levels of the
NP;
• This rise is commonly a sign of heart
failure.[19]
[19] – Larsen A. The effect of altering haemodynamics on the plasma
concentrations of natriuretic peptides in heart failure. Eur J Heart Failure
2006
Natriuretic Peptides on the Diagnosis of
Left Ventricular Dysfunction
• The assay that determines the levels of NP consists
on a blood test of imunofluorescence that measures
the plasmatic levels of BNP or NT-proBNP;
• The cut value for the concentration of BNP is 100
pg/mL and for the concentration of NT-proBNP is 175
pg/mL; above this levels, the patient is considered in
risk of suffering of an heart failure;
• It is economically viable and it is easy to
perform.[14, 20]
[14] – Peacock W. The B-type natriuretic peptide assay: A rapid test for heart failure,
Cleveland Clinic Journal of Medicine 2002
[20] – Mueller C. Use of B-type natriuretic peptide in the evaluation and management of
acute dyspnea. NEJM 2004.
Natriuretic Peptides on the Diagnosis of
Left Ventricular Dysfunction
• The test is, nowadays used to diagnose
patients in risk of heart failure and to
decide which patients need internment;
• It can also be used to stratify the patients,
according to the severity of the pathology;
• In the future, clinicians may be able to
adjust the therapy bearing in mind the
levels of NP of the patients;
• This levels can also be used to predict the
evolution (prognosis) of the patient. [21]
[21] – Isakson S. Natriuretic peptides as prognosticators in congestive
heart failure. BMJ 2006
Aim of the study
• To evaluate the sensibility and specify
of natriuretic peptide levels in the
diagnosis of systolic left ventricular
dysfunction.
Methods
Systematic review
Bibliographic research in medical databases:
 Cochrane’s
 PubMed’s
Query used to search PubMed:
(("Ventricular Dysfunction, Left"[MeSH ] OR "Heart Failure,
Congestive"[MeSH] OR "Cardiac failure" OR "ventricular dysfunction"
OR "heart failure" OR "cardiac dysfunction" OR "heart dysfunction")
AND
("Natriuretic Peptide, Brain"[MeSH] OR "natriuretic peptide" OR
"probnp" OR "bnp" OR "ntprobnp")
AND
("Sensitivity and Specificity"[MeSH] OR sensitivity OR specificity OR
"ROC Curve"[MeSH] OR "ROC Curve" OR "likelihood ratio" OR accuracy
OR “ Predivtive value of tests”[MeSH] OR "predictive value"))
NOT review
Methods
Query used to search Cochrane:
(("Ventricular Dysfunction, Left" OR "Heart Failure, Congestive"
OR "Cardiac failure" OR "ventricular dysfunction" OR "heart
failure" OR "cardiac dysfunction" OR "heart dysfunction")
AND
("Natriuretic Peptide, Brain” OR "natriuretic peptide" OR
"probnp" OR "bnp" OR "ntprobnp")
AND
("Sensitivity and Specificity" OR sensitivity OR specificity OR
"ROC Curve" OR "ROC Curve" OR "likelihood ratio" OR
accuracy OR "Predictive Value of Tests"))
Methods
• Definition of exclusion criteria (tracing): this task was
performed by one group made of three reviewers.
• Definition of inclusion criteria (tracing): this task was
performed by one group made of four reviewers.
• The selection of the articles will be made under the overall
approval.
Criterias
•
Inclusion
 Publications on the accuracy or sensitivity and
specificity of BNP levels in the diagnosis of heart failure
or left ventricular dysfunction.
 Compare the diagnostic accuracy of NTproBNP or BNP to
the traditional means of diagnosing the heart failure,
such as echocardiography, or clinical criterias.
 Be written in English, Portuguese, French or Spanish.
Criterias
•
Exclusion
 To be a randomized clinical trial.
 To be limited to very restrictive study groups such as patients
with Duchenne disease, Chagas disease or Brugada
syndrome.
 To be performed in non human population
 To associate the cardiac failure to congenital or hereditary
diseases.
Data Extraction
•
Data on study identification, year of publication, diagnostic
cross table, spectrum of patients and methodological
aspects are to be extracted from original studies;
•
The study population data is going to incorporate the
inclusion/exclusion criteria, type of assay (extractive,
immunofluorescence) and the reference standard evaluated
(cardiac failure vs left ventricular systolic dysfunction)
•
The methodological quality of the individual studies is going
to be appraised using QUADAS tool [22]
[22] – Whiting P. The development of QUADAS: a tool for the quality
assessment of studies of diagnostic accuracy included in systematic reviews.
BMC Med Res Methodol 2003
Work Planning - Gantt Map
•
gant chart