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Journal ArticleDOI

Plasma natriuretic peptide levels reflect changes in heart failure symptoms, left ventricular size and function after surgical mitral valve repair.

01 Apr 2007-International Journal of Cardiovascular Imaging (Kluwer Academic Publishers)-Vol. 23, Iss: 2, pp 159-165

TL;DR: Patients with decreasing NT-proBNP levels revealed a significant improvement in heart failure symptoms (NYHA class) and changes in left atrial and ventricular dimensions and function.
Abstract: N-terminal pro-B-type natriuretic peptide (NT-proBNP) has diagnostic and prognostic value in patients with heart failure. The present prospective study was designed to assess whether changes in NT-proBNP levels after surgical mitral valve repair reflect changes in heart failure symptoms and changes in left atrial size, left ventricular size and left ventricular function. The study population consisted of 22 patients (mean age: 62.8 ± 14.2 years, 68% male) undergoing surgical mitral valve repair. Serial NT-proBNP measurements, transthoracic echocardiography and New York Heart Association (NYHA) class assessment were performed before and 6 months after surgery. All patients underwent successful mitral valve repair and no patients died during follow-up. The decrease in NT-proBNP level was associated with the reduction in left atrial dimension (r = 0.72, P < 0.001), left ventricular end-systolic dimension (r = 0.63, P = 0.002), left ventricular end-diastolic dimension (r = 0.46, P = 0.031), and the increase in fractional shortening (r = − 0.63, P = 0.002). Finally, patients with decreasing NT-proBNP levels revealed a significant improvement in heart failure symptoms (NYHA class). Changes in NT-proBNP after surgical mitral valve repair reflect changes in heart failure symptoms and changes in left atrial and ventricular dimensions and function.
Topics: Mitral valve (69%), Mitral valve repair (67%), Heart failure (58%), Ventricular remodeling (58%), Systole (57%)

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Abstract
Background and aim N-terminal pro-B-type
natriuretic peptide (NT-proBNP) has diagnostic
and prognostic value in patients with heart fail-
ure. The present prospective study was designed
to assess whether changes in NT-proBNP levels
after surgical mitral valve repair reflect changes in
heart failure symptoms and changes in left atrial
size, left ventricular size and left ventricular
function. Methods The study population con-
sisted of 22 patients (mean age: 62.8 ± 14.2 years,
68% male) undergoing surgical mitral valve
repair. Serial NT-proBNP measurements, trans-
thoracic echocardiography and New York Heart
Association (NYHA) class assessment were per-
formed before and 6 months after surgery.
Results All patients underwent successful mitral
valve repair and no patients died during follow-
up. The decrease in NT-proBNP level was asso-
ciated with the reduction in left atrial dimension
(r = 0.72, P < 0.001), left ventricular end-systolic
dimension (r = 0.63, P = 0.002), left ventricular
end-diastolic dimension (r = 0.46, P = 0.031), and
the increase in fractional shortening (r = 0.63,
P = 0.002). Finally, patients with decreasing NT-
proBNP levels revealed a significant improve-
ment in heart failure symptoms (NYHA class).
Conclusion Changes in NT-proBNP after sur-
gical mitral valve repair reflect changes in heart
failure symptoms and changes in left atrial and
ventricular dimensions and function.
Keywords Heart failure Æ Left ventricular
function Æ Mitral valve repair Æ
Natriuretic peptides
1 Introduction
The natriuretic peptides are endogenous cardiac
hormones that include atrial natriuretic peptide
(ANP), brain natriuretic peptide (BNP), and its
amino-terminal portion N-terminal pro-B-type
natriuretic peptide (NT-proBNP) [1, 2]. The BNP
peptides are synthesized in the ventricular myo-
cardium and released in response to ventricular
wall stress [3, 4]. In the clinical setting, both BNP
and NT-proBNP have been demonstrated to
provide important diagnostic and prognostic
information in patients with heart failure [58].
Recently, elevated plasma BNP levels have
been demonstrated in patients with chronic
H. H. H. Feringa (&) Æ P. Klein Æ J. Braun Æ
R. J. M. Klautz Æ A. van der Laarse Æ
E. E. van der Wall Æ R. A. E. Dion Æ J. J. Bax
Department of Cardiothoracic Surgery/Cardiology,
C-5, Leiden University Medical Center, Albinusdreef 2,
2333 ZA, Leiden, The Netherlands
e-mail: h.feringa@erasmusmc.nl
D. Poldermans Æ R. T. van Domburg
Cardiology, Erasmus Medical Center, Rotterdam,
The Netherlands
Int J Cardiovasc Imaging (2007) 23:159–165
DOI 10.1007/s10554-006-9138-z
123
ORIGINAL PAPER
Plasma natriuretic peptide levels reflect changes in heart
failure symptoms, left ventricular size and function
after surgical mitral valve repair
Harm H. H. Feringa Æ Don Poldermans Æ Patrick Klein Æ Jerry Braun Æ
Robert J. M. Klautz Æ Ron T. van Domburg Æ Arnoud van der Laarse Æ
Ernst E. van der Wall Æ Robert A. E. Dion Æ Jeroen J. Bax
Received: 7 June 2006 / Accepted: 15 July 2006 / Published online: 29 August 2006
Ó Springer Science+Business Media B.V. 2006

valvular disease [911]. In patients with chronic
mitral regurgitation, the severity of regurgitation
was directly related to the BNP levels [911]. The
effect of mitral valve repair on BNP levels how-
ever, has not been studied. Accordingly, the topic
of the current study was to evaluate the change in
BNP levels after surgical correction of severe
mitral regurgitation and to relate the findings to
left ventricular reverse remodeling and improve-
ment in clinical status after surgery.
2 Material and methods
2.1 Study population
Between July 2005 and September 2005, 22 con-
secutive patients undergoing mitral valve repair for
severe mitral regurgitation were prospectively
enrolled. All patients gave informed consent to
participate in the study and the study was conducted
in accordance with the Declaration of Helsinki.
Patients with mitral valve stenosis (mitral valve
area < 1.5 cm
2
)oraorticvalvedisease(severe
aortic stenosis or regurgitation) were not included.
Mitral regurgitation was related to cardiomy-
opathy in 11 patients, and to degenerative disease
in 11 patients.
2.2 Assessment of symptoms and follow-up
Clinical evaluation and assessment of symptoms
using New York Heart Association (NYHA)
class was conducted by the patient’s referring
cardiologist and was confirmed by an independent
cardiothoracic surgeon at the time of hospital
admission. A clinical follow-up was performed at
6 months after mitral valve repair to evaluate the
change in NYHA class. During the 6-month fol-
low-up period, adverse events including non-fatal
myocardial infarction, repeat mitral valve sur-
gery, cerebrovascular events, renal dysfunction
and hospitalization for heart failure were noted.
2.3 Echocardiography
Prior to surgery, transthoracic echocardiography
was performed in all patients. The patients were
imaged in the left lateral decubitus position by
using a commercially available system (Vingmed
Vivid Seven, General Electric—Vingmed,
Milwaukee, WI, USA). Using a 3.5 MHz trans-
ducer, images were obtained at a depth of 16 cm
in the parasternal (long- and short-axis images)
and apical views (2- and 4-chamber images).
From parasternal M-mode acquisitions, the left
atrial diameter and left ventricular dimensions
(end-systolic and end-diastolic diameter) were
determined and the fractional shortening was
calculated. The severity of mitral regurgitation
was graded semi-quantitatively from color-flow
Doppler in the conventional parasternal long-axis
and apical 4-chamber images. Mitral regurgitation
was characterized as mild = 1+ (jet area/left atrial
area < 10%), moderate = 2+ (jet area/left atrial
area 10–20%), moderately severe = 3+ (jet area/
left atrial area 20–45%), and severe = 4+ (jet
area/left atrial area > 45%) [12]. Immediately
after surgery, transesophageal echocardiography
was performed to assess residual mitral valve
regurgitation. A transthoracic echocardiogram
was repeated at 6 months follow-up to assess left
atrial and ventricular dimensions, fractional
shortening, the presence of residual mitral valve
regurgitation, the transmitral diastolic gradient,
the length of leaflet coaptation and the mitral
valve area. Two experienced cardiologists who
were blinded to the BNP levels and clinical data
analyzed the echocardiographic data.
2.4 NT-proBNP measurement
Venous blood samples were collected on the day
before and 6 months after surgery with the
patient at rest and in semi-supine position. The
samples were collected in chilled ethylene-dia-
mine-tetra-acetic acid vacutainers and were
immediately placed on ice. After centrifugation,
the plasma samples were stored at 80°C until
assay. Plasma NT-proBNP concentrations was
measured with an electrochemiluminescence
immunoassay kit (Elecsys 2010, Roche GmbH,
Mannheim, Germany). The method is a ‘sand-
wich’-type quantitative immunoassay based on
polyclonal antibodies against epitopes in the
N-terminal part of pro-BNP [13]. Assays were
performed by a laboratory technician blinded to
the patient’s clinical data.
160 Int J Cardiovasc Imaging (2007) 23:159–165
123

2.5 Statistical analysis
The change in NT-proBNP levels from baseline
to 6 months follow-up was calculated and
expressed as percentage values. Changes in left
atrial dimension, left ventricular end-systolic and
end-diastolic dimensions and fractional shorten-
ing were also calculated and expressed as per-
centage values. Continuous data were expressed
as mean (±SD) or median (interquartile range)
when the distributions were skewed and compared
using the Student t-test or the Mann–Whitney U-
test when appropriate. Categorical data were
compared using the Fisher’s exact test. Group
comparisons were performed with analysis of
variance (ANOVA) techniques. The Pearson
correlation coefficient was used to assess the
association between changes in NT-proBNP levels
and changes in echocardiographic variables. For
all tests, a P value < 0.05 was considered signifi-
cant. All analysis was performed using SPSS-11.0
statistical software (SPSS Inc., Chicago, Illinois).
3 Results
3.1 Baseline characteristics
The baseline characteristics of the 22 patients
(mean age 62.8 ± 14.2 years, 68% male) are
summarized in Table 1. Eight patients (36%)
were in NYHA class II, 5 (23%) in class III and 9
(41%) in class IV (mean NYHA class 3.1 ± 0.9).
Prior to surgery, all patients presented with se-
vere mitral valve regurgitation (grade 3–4+), with
a mean regurgitation grade of 3.6 ± 0.5. Mean left
atrial dimension was 4.9 ± 0.7 cm, mean left
ventricular end-systolic dimension 4.5 ± 0.8 cm,
mean left ventricular end-diastolic dimension
6.1 ± 0.8 cm and mean fractional shortening
26.8 ± 7.3%. Median NT-proBNP level at base-
line was 418 ng/l (interquartile range: 204–
1258 ng/l).
3.2 Surgical results and follow-up
Mean length of hospital stay was 9.8 ± 4.3 days.
Transesophageal echocardiography immediately
after surgery demonstrated competent valves with
minimal residual mitral valve regurgitation in all
patients (mitral regurgitation grade 0 in 13
patients, 59% and grade 1 in 9 patients, 41%). All
patients survived the 6-month follow-up period
and no patients were lost to follow-up. During
hospital stay and follow-up, none of the patients
required repeat mitral valve surgery. Adverse
events, including nonfatal myocardial infarction,
cerebrovascular events, hospitalization for heart
failure or endocarditis were not observed. Two
patients (9%) developed renal dysfunction in the
postoperative period which was successfully
treated with a short period of renal dialysis. None
of the patients presented with renal dysfunction at
6 months follow-up. Median NT-proBNP level at
6 months follow-up was 426 ng/l (interquartile
range 196–1172 ng/l). In 10 patients (45%), NT-
proBNP levels decreased >10% and in 12
patients (55%) NT-proBNP level remained
unchanged or increased >10% as compared to
baseline values.
The patient population was subsequently
divided into patients with a decrease in plasma
NT-proBNP level versus patients with unchanged/
increased NT-proBNP plasma levels (Table 1).
Baseline characteristics were comparable between
the 2 groups, including baseline NT-proBNP lev-
els. Only left atrial dimension was somewhat lar-
ger in patients with decreasing NT-proBNP levels
after surgery as compared to those with increasing
NT-proBNP levels (P = 0.04).
3.3 Changes in NT-proBNP levels
and symptoms
NYHA class deteriorated in 3 patients (14%),
remained unchanged in 5 (23%) and improved in
14 (64%). The 10 patients with decreased NT-
proBNP levels exhibited a mean improvement in
NYHA class of 2.0 ± 1.1, whereas the 12 patients
with unchanged/increased NT-proBNP levels
revealed a small but significant worsening in
NYHA class (0.3 ± 0.9, P < 0.001 versus baseline).
3.4 Changes in NT-proBNP levels
and echocardiographic variables
The transthoracic echocardiogram at 6 months
follow-up revealed a mean mitral regurgitation
Int J Cardiovasc Imaging (2007) 23:159–165 161
123

grade of 0.5 ± 0.7, mean length of leaflet coapta-
tion of 0.9 ± 0.2 cm, mean mitral valve area of
2.6 ± 0.9 cm
2
, and mean transmitral diastolic
gradient of 3.3 ± 1.2 mmHg. At follow-up, mean
left atrial dimension was 4.4 ± 0.5 cm, mean left
ventricular end-systolic dimension 4.2 ± 0.9 cm,
mean left ventricular end-diastolic dimension
5.8 ± 0.6 cm, and mean fractional shortening
28.0 ± 10.7%. The 10 patients with decreased NT-
proBNP levels demonstrated significant reverse
left ventricular remodeling, with a reduction in
left ventricular end-systolic dimension from
4.7 ± 1.0 cm to 3.8 ± 0.9 cm (P = 0.042), a
reduction in left ventricular end-diastolic dimen-
sion from 6.5 ± 0.8 cm to 5.7 ± 0.6 cm
(P = 0.036) and a reduction in left atrial dimen-
sion from 5.3 ± 0.6 cm to 4.3 ± 0.5 cm
(P = 0.001). Conversely, reverse left ventricular
remodeling was not observed in the 12 patients
with unchanged/increased NT-proBNP levels.
Mean left ventricular end-systolic dimension was
4.3 ± 0.6 cm at baseline versus 4.5 ± 0.7 cm
(P = 0.43) at follow-up, and mean left ventricular
end-diastolic dimension was 5.9 ± 0.9 cm at
baseline versus 5.8 ± 0.6 cm at follow-up
(P = 0.66). Mean left atrial dimension did also
not change (4.7 ± 0.7 cm versus 4.5 ± 0.6 cm,
P = 0.67). Scatter plots demonstrating the corre-
lation between changes in NT-proBNP level and
changes in echocardiographic variables during the
6-month follow-up period after mitral valve sur-
gery are presented in Fig. 1. Decreases in NT-
proBNP levels at follow-up were significantly
correlated with reductions in left atrial dimension
(r = 0.72, P < 0.001), left ventricular end-systolic
dimension (r = 0.63, P = 0.002), and left ventric-
ular end-diastolic dimension (r = 0.46, P = 0.031),
indicating reverse remodeling; conversely,
increases in NT-proBNP levels were related to
increases in the different dimensions, indicating
Table 1 Baseline clinical characteristics of the study population divided into patients with increasing and decreasing
N-terminal pro-B-type natriuretic peptide levels
Overall (n = 22) Decreasing
NT-proBNP levels
(n = 10)
Increasing
NT-proBNP levels
(n = 12)
P value
Clinical variables
Age (years) 62.8 ± 14.2 63.3 ± 13.5 62.4 ± 15.3 0.89
Male gender 15 (68.2) 7 (70.0) 8 (66.7) 1.00
Hypertension 4 (18.2) 3 (30.0) 1 (8.3) 0.29
Diabetes mellitus 3 (13.6) 2 (20.0) 1 (8.3) 0.57
Chronic obstructive pulmonary disease 4 (18.2) 1 (10.0) 3 (25.0) 0.59
Peripheral arterial disease 3 (13.6) 3 (30.0) 0 (0) 0.078
History of stroke 0 (0) 0 (0) 0 (0)
New York Heart Association class 2.9 ± 1.0 3.3 ± 0.9 2.8 ± 0.8 0.23
Medication
Angiotensin-converting enzyme inhibitors 10 (45.5) 6 (60.0) 4 (33.3) 0.39
Beta-blockers 8 (36.4) 5 (50.0) 3 (25.0) 0.38
Diuretics 9 (40.9) 4 (40.0) 5 (41.7) 1.00
Reason of mitral regurgitation
Degenerative disease 11 (50.0) 5 (50.0) 6 (50.0) 1.00
Cardiomyopathy 11 (50.0) 5 (50.0) 6 (50.0) 0.17
Echocardiographic measurements
Mitral regurgitation, grade 3.6 ± 0.5 3.7 ± 0.5 3.6 ± 0.5 0.54
Left atrial dimension (cm) 4.9 ± 0.7 5.2 ± 0.6 4.7 ± 0.7 0.040
Left ventricular end-systolic dimension (cm) 4.5 ± 0.8 4.7 ± 1.0 4.3 ± 0.6 0.21
Left ventricular end-diastolic dimension (cm) 6.1 ± 0.8 6.3 ± 0.7 5.9 ± 0.9 0.27
Fractional shortening (%) 26.8 ± 7.3 25.4 ± 8.3 28.0 ± 6.6 0.42
Baseline LN NT-proBNP level (ng/l) 6.2 ± 1.5 6.6 ± 1.4 5.8 ± 1.5 0.18
Values are expressed in mean ± standard deviation or in number (%). NT-proBNP denotes N-terminal pro-B-type
natriuretic peptide
162 Int J Cardiovasc Imaging (2007) 23:159–165
123

ongoing dilatation. Moreover, decreases in
NT-proBNP levels at follow-up were significantly
correlated with improved fractional shorting
(r = 0.63, P = 0.002), indicating improved sys-
tolic function.
4 Comments
BNP has been used extensively in the diagnosis
and prognosis of patients with heart failure [58].
More recently, Sutton and colleagues demon-
strated in 49 patients with mitral regurgitation
and preserved left ventricular ejection fraction
that plasma levels of BNP and NT-proBNP levels
were directly related to the severity of mitral
valve regurgitation [11]. In addition, Detaint et al.
evaluated 124 patients with chronic mitral regur-
gitation and demonstrated that BNP levels were
correlated with long-term outcome [14]. In par-
ticular, higher BNP levels independently pre-
dicted mortality and the combined endpoint of
mortality and heart failure. Moreover, the authors
demonstrated that BNP levels in chronic mitral
Fig. 1 Scatter plots demonstrating the correlation
between changes in plasma N-terminal pro-B-type natri-
uretic peptide level (NT-proBNP) and changes in
echocardiographic variables (A. left atrial dimension; B.
left ventricular end-systolic dimension; C. left ventricular
end-diastolic dimension; D. fractional shortening) during
the 6-month follow-up period after mitral valve surgery.
Of note, negative changes in left atrial dimension, left
ventricular end-systolic dimension and left ventricular
end-diastolic dimension indicate reductions in dimensions
(reverse remodeling), whereas positive changes indicate
ongoing dilatation. A positive change in fractional
shortening indicates an increase in systolic function,
whereas a negative change in fractional shortening
indicates a decrease in systolic function. Negative changes
in NT-proBNP indicate a reduction in plasma levels after
surgery, whereas positive changes indicate an increase in
plasma levels after surgery
Int J Cardiovasc Imaging (2007) 23:159–165 163
123

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  • ...The severity of regurgitation is directly correlated with NT-proBNP level in patients with mitral regurgitation [33], and, particularly, decreased NT-proBNP indicates reduced left atrial size, reversal of left ventricular remodeling, and improved symptoms for those who undergo successful mitral valve surgery [34]....

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TL;DR: En pacientes con insuficiencia cardiaca en clase II-III y disfuncion sistolica ventricular izquierda, los principales predictores ecocardiograficos de capacidad de ejercicio se relacionan con the presencia of insufICiencia mitral significativa.
Abstract: Resumen Introduccion y objetivos Pacientes con insuficiencia cardiaca y similar disfuncion sistolica del ventriculo izquierdo tienen diferente capacidad de ejercicio. El objetivo de este estudio es detectar predictores ecocardiograficos de capacidad de ejercicio en pacientes con insuficiencia cardiaca y disfuncion sistolica. Metodos Se incluyo a 150 pacientes con insuficiencia cardiaca en clase II (70%) o III (30%) con fraccion de eyeccion ventricular izquierda Resultados Se detecto insuficiencia mitral en 112 pacientes (75%), que fue significativa en 40 (27%). El grupo 1 evidencio mas insuficiencia mitral significativa (el 35 frente al 18%), area auricular izquierda (27 ± 1 frente a 24 ± 1 cm2), amplitud de E mitral (88 ± 5 frente a 72 ± 3 cm/s) y presion sistolica pulmonar (37 ± 1 frente a 32 ± 1 mmHg; todos p Conclusiones En pacientes con insuficiencia cardiaca en clase II-III y disfuncion sistolica ventricular izquierda, los principales predictores ecocardiograficos de capacidad de ejercicio se relacionan con la presencia de insuficiencia mitral significativa.

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References
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TL;DR: Examination of the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure concludes that BNP is secreted mainly from the left ventricle in normal adult humans as well as in Patients with left ventricular dysfunction.
Abstract: BACKGROUNDB-type or brain natriuretic peptide (BNP) is a novel natriuretic peptide secreted from the heart that forms a peptide family with A-type or atrial natriuretic peptide (ANP), and its plasma level has been shown to be increased in patients with congestive heart failure. This study was designed to examine the sources and mechanisms of the secretion of BNP in comparison with those of ANP in control subjects and in patients with heart failure.METHODS AND RESULTSWe measured the plasma levels of BNP as well as ANP in 16 patients with dilated cardiomyopathy (11 men and 5 women; mean age, 59 years) and 18 control subjects (9 men and 9 women; mean age, 54 years) by sampling blood from the femoral vein, the aortic root, the anterior interventricular vein (AIV), and the coronary sinus using the newly developed immunoradiometric assay systems. In the control subjects, there was no significant difference in the plasma ANP level between the aortic root and the AIV (24.0 +/- 5.2 pg/mL versus 32.2 +/- 17.0 pg/mL...

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  • ...cardium and released in response to ventricular wall stress [3, 4]....

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Abstract: Background— Heart failure (HF) is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal–pro-brain natriuretic peptide (NT-proBNP) in predicting death or hospital readmission after discharge of HF patients. Methods and Results— We included 182 patients consecutively admitted to hospital because of decompensated HF. Patients were followed up for 6 months. The primary end point was death or readmission. Twenty-six patients died in hospital. The median admission NT-proBNP level was 6778.5 pg/mL, and the median level at discharge was 4137.0 pg/mL (P<0.001). Patients were classified into 3 groups: (1) decreasing NT-proBNP levels by at least 30% (n=82), (2) no significant modifications on NT-proBNP levels (n=49), and (3) increasing NT-proBNP levels by at least 30% (n=25). The primary end point was observed in 42.9% patients. Variables associated with an increased hazard of death and/or hospital readmission in univariate analysis were length of hospitalization, heart rat...

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Michihiro Yoshimura1, Hirofumi Yasue1, Ken Okumura1, Hisao Ogawa1  +4 moreInstitutions (2)
TL;DR: It is concluded that plasma levels of BNP mainly reflect the degree of ventricular overload and that the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.
Abstract: BACKGROUNDThe plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.METHODS AND RESULTSWe measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher...

602 citations


"Plasma natriuretic peptide levels r..." refers background in this paper

  • ...cardium and released in response to ventricular wall stress [3, 4]....

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Journal ArticleDOI
Christian Hall1Institutions (1)
TL;DR: While the plasma concentration of NT‐proBNP and BNP is approximately equal in normal controls, NT‐ proBNP plasma concentration is 2–10 times higher than BNP in patients with heart failure, which relative change in peptide levels may be explained by shifts in cardiac secretion and/or clearance mechanisms.
Abstract: Brain natriuretic peptide (BNP) is a 32 amino acid cardiac natriuretic peptide hormone originally isolated from porcine brain tissue. The human BNP gene is located on chromosome 1 and encodes the prohormone proBNP. The biologically active BNP and the remaining part of the prohormone, NT-proBNP (76 amino acids) can be measured by immunoassay in human blood. Cardiac myocytes constitute the major source of BNP related peptides. The main stimulus for peptide synthesis and secretion is myocyte stretch. Recently, cardiac fibroblasts have also been shown to produce BNP. Other neurohormones may stimulate cardiac BNP production in different cardiac cell types. In contrast to atrial natriuretic peptides (ANP/NT-proANP), which originate mainly from atrial tissue, BNP related peptides are produced mainly from ventricular myocytes. Ventricular (NT-pro)BNP production is strongly upregulated in cardiac failure and locally in the area surrounding a myocardial infarction. In peripheral organs BNP binds to the natriuretic peptide receptor type A causing increased intracellular cGMP production. The biological effects include diuresis, vasodilatation, inhibition of renin and aldosterone production and of cardiac and vascular myocyte growth. In mice BNP gene knockout leads to cardiac fibrosis, gene over-expression to hypotension and bone malformations. BNP is cleared from plasma through binding to the natriuretic peptide clearance receptor type C, but it seems relatively resistant to proteolysis by neutral endopeptidase NEP 24.11. Clearance mechanisms for NT-proBNP await further study. While the plasma concentration of NT-proBNP and BNP is approximately equal in normal controls, NT-proBNP plasma concentration is 2-10 times higher than BNP in patients with heart failure. This relative change in peptide levels may be explained by shifts in cardiac secretion and/or clearance mechanisms.

434 citations


Journal ArticleDOI
Roy S. Gardner1, F Ozalp, A J Murday, S D Robb  +1 moreInstitutions (1)
TL;DR: A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2or HFSS.
Abstract: Aims The selection of patients for cardiac transplantation (CTx) is notoriously difficult and traditionally involves clinical assessment and an assimilation of markers of the severity of CHF such as the left ventricular ejection fraction (LVEF), maximum oxygen uptake (peak VO2) and more recently, composite scoring systems e.g. the heart failure survival score (HFSS). Brain natriuretic peptide (BNP) is well established as an independent predictor of prognosis in mild to moderate chronic heart failure (CHF). However, the prognostic ability of NT-proBNP in advanced heart failure is unknown and no studies have compared NT-proBNP to standard clinical markers used in the selection of patients for transplantation. The purpose of this study was to examine the prognostic ability of NT-proBNP in advanced heart failure and compare it to that of the LVEF, peak VO2and the HFSS. Methods and results We prospectively studied 142 consecutive patients with advanced CHF referred for consideration of CTx. Plasma for NT-proBNP analysis was sampled and patients followed up for a median of 374 days. The primary endpoint of all-cause mortality was reached in 20 (14.1%) patients and the combined secondary endpoint of all-cause mortality or urgent CTx was reached in 24 (16.9%) patients. An NT-proBNP concentration above the median was the only independent predictor of all cause mortality (χ2=6.03, P =0.01) and the combined endpoint of all cause mortality or urgent CTx (χ2=12.68, P =0.0004). LVEF, VO2and HFSS were not independently predictive of mortality or need for urgent cardiac transplantation in this study. Conclusion A single measurement of NT-proBNP in patients with advanced CHF, can help to identify patients at highest risk of death, and is a better prognostic marker than the LVEF, VO2or HFSS.

379 citations