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European Journal of Heart Failure 2003 5(4):481-488; doi:10.1016/S1388-9842(03)00041-2
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© 2003 European Society of Cardiology

Major increase in brain natriuretic peptide indicates right ventricular systolic dysfunction in patients with heart failure

Denis Mariano-Goularta,*, Marie-Claude Eberléa, Vincent Boudousqa, Azadeh Hejazi-Mougharia, Christophe Piotb, Charles Caderas de Kerleaua, Régis Verdierc, Marie-Luce Bargea, Frédéric Comtea, Nicole Bressota, Michel Rossia and Pierre-Olivier Kotzkia

a Department of Nuclear Medicine, Montpellier University Hospital 371, Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France
b Department of Cardiology B, Montpellier University Hospital 371, Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France
c Department of Statistics and Epidemiology, Montpellier University Hospital 371, Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France

* Corresponding author. Service Central de Médecine Nucléaire, Centre Hospitalier Universitaire Lapeyronie, 371, Avenue du Doyen Gaston Giraud, 34295 Montpellier Cedex 5, France. Tel.: +33-4-67-33-85-98; fax: +33-4-67-33-84-65 E-mail address: d-mariano_goulart{at}chu-montpellier.fr


   Abstract
Top
 Abstract
1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 
This study sought to investigate whether the presence of right ventricular systolic dysfunction with pre-existing left ventricular systolic dysfunction is associated with higher plasma brain natriuretic peptide (BNP) levels, compared with patients with isolated left ventricular dysfunction. Eighty-five patients referred for evaluation of isotopic ventricular function were prospectively included in the study. Left (LVEF) and right (RVEF) ventricular ejection fractions were evaluated by gated blood pool scintigraphy and compared with plasma BNP levels. BNP correlated negatively with LVEF, except in patients with ischaemic heart disease (P=0.09) and in patients with LVEF<40% (P=0.11). In contrast, BNP levels correlated negatively with RVEF for all subgroups. Among patients with RVEF<40%, no significant BNP difference was found between patients with or without additional left ventricular systolic dysfunction (P=0.51). Among patients with LVEF<40%, plasma BNP levels were significantly higher in patients with RVEF<40% than in patients with RVEF≥40% (P=0.004) whereas age, renal function, clinical findings, ventricular volumes, LVEF or medication were not significantly different. In conclusion, an important increase in BNP levels in patients with left ventricular systolic dysfunction should be considered by cardiologists as an indication of high risk of right ventricular dysfunction and should justify further investigation.

Key Words: Right ventricle • Ejection fraction • Brain natriuretic peptide

Received August 2, 2002; Revised November 18, 2002; Accepted February 17, 2003


   1. Introduction
Top
 Abstract
 1. Introduction
2. Materials and methods
 3. Results
 4. Discussion
 References
 
The natriuretic peptide system comprises at least four endogenous peptides including the atrial and brain natriuretic peptides (ANP, BNP) and three receptors. ANP and BNP are synthesized, stored and released from atrial and ventricular tissue in response to increased transmural pressure [1–3]. These cardiac hormones are implicated in the control of blood pressure, body fluid homeostasis and vascular remodeling [4,5]. They have a compensatory function in heart failure. Increased concentrations of these peptides has been shown to be a sensitive marker of asymptomatic left ventricular systolic dysfunction [6], but accumulated evidence indicates that plasma BNP is a better indicator of left ventricular dysfunction than ANP and can be used to guide therapy [7–13].

Over the last few years, BNP has moved from being a research tool to being a clinically useful test [14]. Since a normal BNP concentration virtually excludes left ventricular dysfunction, BNP can help clinicians in the diagnosis of heart failure. Moreover, plasma BNP measured after acute myocardial infarction is a powerful neurohormonal predictor of subsequent progressive ventricular dilation, remodeling, heart failure and cardiovascular mortality [9,15–17]. Therefore, BNP may help assess prognosis and the need for more intensive treatment [14,18,19]. However, a high concentration can be associated with various heart diseases including myocardial infarction, hypertrophic and dilated cardiomyopathy, aortic and mitral stenosis, tachycardia or essential hypertension [20]. BNP increases have also been described in various other clinical situations, such as doxorubicin cardiotoxicity [21], pacemakers [22], chronic renal failure [23–25], chronic pulmonary diseases [26–32], diabetes [33] and congenital vascular malformations [34,35].

On the other hand, right ventricular ejection fraction (RVEF) has proved to be an important and independent prognostic factor in chronic heart failure [36,37]. Thus, the assessment of right ventricular dysfunction is an important variable for monitoring the therapy of heart failure. Most studies indicate that BNP is secreted mainly from left ventricular myocytes in normal adult humans as well as in patients with left ventricular dysfunction [38]. However, a recent study demonstrated that plasma BNP levels are elevated in patients with isolated pulmonary artery hypertension [31]. Recently, the immunohistocytochemical localization of BNP in right and left ventricles of dilated cardiomyopathy was analyzed [39]. In this study, all of the left ventricular endomyocardial biopsy specimens, but only some of the right ventricular specimens, showed immunoreactivity for BNP. In contrast, none of the normal controls showed immunoreactivity for this peptide [39]. Similarly, BNP gene expression was found to be increased at the messenger ribonucleic acid level in right ventricles after heart transplantation in children or after exposure to experimental pulmonary hypertension [40,41]. These results suggest that the diuretic, natriuretic and vasodilatator effects of BNP may have also played an important role, through a reduction in preload and afterload in patients with right ventricular pressure overload. However, in routine settings, right ventricular dysfunction is often associated with left ventricular dysfunction, so that the exact influence of right ventricular function on the secretion of BNP is still unclear. There have been no quantitative data regarding the importance of plasma BNP increases among patients with right and left ventricular dysfunction, compared with patients with isolated left ventricular dysfunction.

Thus the purpose of this study was to investigate the links between plasma BNP levels and right or left equilibrium ejection fractions, and to determine whether the presence of right ventricular systolic dysfunction with a pre-existing left ventricular systolic dysfunction is associated with higher plasma BNP levels compared with patients with isolated left ventricular dysfunction.


   2. Materials and methods
Top
 Abstract
 1. Introduction
 2. Materials and methods
3. Results
 4. Discussion
 References
 
2.1. Study design and patient population
The study was approved by the ethics committee of Montpellier Medical University and all patients gave written informed consent to participate. The investigation conformed with the principles outlined in the Declaration of Helsinki. Eighty-five patients (16 women and 69 men, mean age 57.5 years, median 62 years, range 15–85 years) referred for the evaluation of isotopic right and left systolic ventricular function were prospectively included in the study. All patients were hospitalized in the cardiology department of a University hospital. Reasons for referral included evaluation for non-ischaemic dilated cardiomyopathy (47 patients), ischaemic heart disease (18 patients), valvular disease (5 patients), obstructive bronchopneumopathy (6 patients), non-obstructive hypertrophic cardiomyopathy (2 patients), muscular dystrophy with cardiac involvement (3 patients), obstructive cardiomyopathy (1 patient), arrhythmogenic right ventricular cardiomyopathy (1 patient), toxemia of pregnancy (1 patient) and pericarditis (1 patient). Exclusion criteria included severe arrhythmia and patients with abnormal renal function (plasma creatinine level>150 µmol/l). All patients underwent clinical examination and echocardiography for evaluation of left ventricular chamber diameters. The same cardiologist performed these examinations and was blinded to the results of isotopic ejection fractions and BNP measurements.

According to a preliminary analysis of the data, a threshold of 40% was used for left and right ejection fraction to define four groups (left ventricular ejection fraction (LVEF)>=40% and RVEF>=40%: 36 patients; LVEF<40% and RVEF>=40%: 20 patients; LVEF>=40% and RVEF<40%: 9 patients; LVEF<40% and RVEF<40%: 20 patients). The clinical characteristics of the 40 patients with LVEF<40% are shown in Table 1.


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  		Table 1 Clinical characteristics of patients with LVEF<40%

 
2.2. BNP measurements
One hour before scintigraphic examinations, blood samples were drawn by venipuncture and collected into plastic tubes containing ethylenediaminetetraacetic acid (1.5 mg/ml) and aprotinin (500 kIU/ml). After equilibrating to room temperature (10 min), the plasma was separated by centrifugation (5 °C, 10 min) from mixed blood samples and transferred into two plastic test tubes, which were stored at –80 °C until analysis. For samples with high BNP levels, the content of the second tube was diluted and the BNP level was checked. Plasma BNP concentrations were determined by use of a solid phase sandwich immunoradiometric assay (Shionoria BNP kit manufactured by CIS Bio International). This assay uses two monoclonal antibodies prepared against sterically remote sites, which recognize the carboxyterminal sequence and the ring structure of human BNP, respectively. The first antibody was coated onto the bead solid phase, and the second was radiolabeled with iodine 125 and used as a tracer. After the washing step, the radioactivity bound to the solid phase is proportional to the amount of BNP present at the beginning of the assay. The assay was performed in duplicate for seven standards (0,4,10,40,150,600 and 2000 pg/ml; 1 pg/ml=0.289 pmol/l), two control samples and all patient samples. According to the manufacturer, the detection limit has been assessed as 2.0 pg/ml. In our laboratory, intra- and inter-assay coefficients of variation have been measured between 5–7% and 9–14%, respectively, in the concentration range 10–2000 pg/ml. Normal values of BNP levels in our laboratory are 14.3±9.5 pg/ml.

2.3. Gated equilibrium blood pool scintigraphy
Patients were injected with 740–925 MBq (effective dose equivalent: 5.4–6.7 mSv) of in vitro labeled erythrocyte solution. Data were acquired on a dual-head gamma camera (Sopha DST) using low-energy high-resolution parallel-hole collimators.

Planar gated blood pool scintigraphy was obtained in the best septal left anterior oblique projection for 4.25 million counts (266 kcounts/frame). Acquisition variables were as follows: 10% R–R interval acceptance window, 16 frames per cardiac cycle, 64x64 matrix and image magnification of 2. After magnification, the pixel size was 3.4 mm.

Tomographic gated blood pool scintigraphy immediately followed planar acquisitions. Acquisition parameters were as follows: 5.6°/step (16 steps over 90° per head) for 180°, 1 min acquisition time/step, 10% R–R interval acceptance window, 8 gated intervals, 64x64 matrix and image magnification of 2. Voxel size was 0.08 cc/voxel. The choice of only 8 frames per cardiac cycle was made to achieve acceptable examination duration in routine settings.

Planar and tomographic gated blood pool scintigraphies were processed using an IBM RISC 6000 workstation by the same nuclear medicine physician blinded to the patient's BNP levels and clinical data. The SMV-GE Medical Systems software was used to calculate LVEF from planar gated blood pool studies. In our department, the normal range for LVEF was 65±13%.

RVEF was calculated from tomographic gated blood pool scintigraphies. Projection data were compensated for scattered photons by subtracting half of the pixel values acquired within a secondary pulse-height window (92–125 keV) from the data acquired within the photopeak pulse-height window (127–153 keV) [42]. The compensated projection data were backprojected using a depth-dependent deblurring filter (SMV-GE Medical Systems RestoreTM software). This filter is a combination of an inverse filter, for resolution recovery and a low pass Butterworth filter, for noise suppression [43]. The roll off from the inverse to the low pass component occurs when the filter's gain reaches 1.6 or when the frequency reaches 25 cycles/pixel. The order of the Butterworth filter is 6. Attenuation artifacts were not corrected during the reconstruction process. Equilibrium RVEF were processed from transverse slices by a watershed-based semi-automated segmentation algorithm that has been fully described in previous works [44–46]. The normal range for RVEF was 64±10% [45].

2.4. Statistical methods
Statistical significance was defined as a P value <0.05. A Shapiro–Wilk test was used to check the normality of the distributions for plasma BNP levels and right or left ejection fraction. For plasma BNP levels only, log transformation was used to normalize the distribution and all the comparisons involving BNP levels were made after this log transformation. However, BNP levels and ejection fractions are presented as nontransformed mean value±standard deviation (S.D.).

A two-way analysis of variance was used to look for a link between left and right ejection fraction as a determinant of plasma BNP levels. Regression analysis was undertaken to determine whether an association of left and right ejection fraction are more correlated with plasma levels of BNP than left or right ejection fraction alone. Coefficients of determination (r2) were calculated to determine variability in relation to the regression line. Spearman correlation coefficients (R) were also evaluated between BNP levels and right or left ejection fraction among patients having non-ischaemic dilated cardiomyopathy (Group A, 47 patients), ischaemic heart diseases (Group B, 18 patients) or non-ischaemic and non-dilated cardiac diseases (Group C, 20 patients). Mean ejection fractions and plasma BNP levels were compared between the different subgroups by unpaired Student's t-test.


   3. Results
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
4. Discussion
 References
 
In the whole population studied, LVEF averaged 43±17% (range 11–83%) and RVEF 50±17% (range 17–90%). The mean plasma BNP level was 205±254 pg/ml (range 2–1024 pg/ml). A two-way analysis of variance showed that the effects of left and RVEFs on plasma BNP levels were significantly associated (P=0.008). For the whole population, plasma BNP levels correlated negatively with LVEF (r2=0.30; P=0.0001) and with RVEF (r2=0.35; P=0.0001).

Age, NYHA class, creatinine level and left ventricular diameter did not differ significantly between the two subgroups of patients having LVEF<40% (Table 1; P=0.43 for age, P=0.37 for NYHA, P=0.27 for creatinine level, P=0.29 for left ventricular diastolic diameter). Among patients with LVEF<40% (40 patients), plasma BNP levels correlated negatively with RVEF (r2=0.27; P=0.001) but not with LVEF (r2=0.06; P=0.11). Moreover, regression analysis showed that BNP levels correlated negatively with the association of left and RVEFs (r2=0.54; P=0.0001).

Among patients having non-ischaemic heart diseases (Group A and C), plasma BNP levels correlated negatively with LVEF (R=–0.49, P=0.0004 for group A; R=–0.66, P=0.0015 for group C) and with RVEF (R=–0.65; P=0.0001 for group A; R=–0.46, P=0.04 for group C). Among patients with ischaemic heart disease (Group B), BNP levels also correlated with RVEF (R=–0.63; P=0.005) but not with LVEF (R=–0.41; P=0.09).

As shown in Fig. 1 45 patients (53%) had a LVEF>=40%. Among these patients, plasma BNP level averaged 103±177 pg/ml (range 2–935 pg/ml). In this sub-group, 36 patients (42%) had RVEF>=40% (BNP level 37±37 pg/ml; range 2–165 pg/ml) and 9 patients (11%) had RVEF<40% (BNP level 365±263 pg/ml; range 64–935 pg/ml). Forty patients (47%) had a LVEF<40%, suggesting severe left ventricular dysfunction. Among these patients, plasma BNP levels averaged 320±279 pg/ml (range 16–1024 pg/ml). In this sub-group, 20 patients (23.5%) had RVEF>=40% (BNP level 168±164 pg/ml; range 16–574 pg/ml) and 20 patients (23.5%) had RVEF<40% (BNP level 472±290 pg/ml; range 49–1024 pg/ml).


Figure 1
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  		Fig. 1 Mean plasma BNP level vs. left (LVEF) and right (RVEF) ejection fraction. N is the number of patients and error bars represent ±S.D. Mean BNP levels are significantly different (P=0.0001) except between the two groups marked by a star (*: P=0.51).

 
Among patients with RVEF>=40%, mean plasma BNP level was significantly higher in patients with LVEF<40% than in patients with LVEF>=40% (P=0.0001). In contrast, among patients with RVEF<40%, mean plasma BNP level was not significantly different in patients with LVEF<40% than in patients with LVEF>=40% (P=0.51). For patients with LVEF>=40% and for patients with LVEF<40%, mean plasma BNP levels were significantly higher in patients with RVEF<40% than in patients with RVEF>=40% (P=0.0001). Additionally, for patients with LVEF<40%, the value of the LVEF was not significantly different in patients with RVEF>=40% (LVEF=26.6±3.2%; range 22–33%) than in patients with RVEF<40% (LVEF=28.6±6.9%; range 11–37%) (P=0.25).

Receiver-operating-characteristic (ROC) curves were constructed to assess the sensitivity and the specificity of BNP thresholds ranging 25–600 pg/ml to detect right ventricular systolic dysfunction (RVEF<40%).

Fig. 2 shows the ROC curves in patients with pre-existing left ventricular dysfunction and in the whole study population. For BNP thresholds ranging from 200 to 300 pg/ml, the sensitivity and specificity of BNP range 80–70% and 60–90%, respectively, for patients with LVEF<40%. For the whole population, these values of sensitivity and specificity range 79–66% and 86–96%, respectively.


Figure 2
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  		Fig. 2 ROC curves showing the sensitivity and the specificity of BNP thresholds ranging 25–600 pg/ml to detect right ventricular systolic dysfunction (RVEF<40%) in patients with pre-existing left ventricular dysfunction (LVEF<40%, solid line) and in the whole study population (dashed line).

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
References
 
Although the left ventricle is traditionally regarded as the heart's main pumping chamber, numerous recent studies have stressed the importance of the RVEF. In addition to the New York Heart Association classification, LVEF and the percentage of maximal predicted peak oxygen consumption, RVEF is an independent and crucial predictor of short-term prognosis in patients with moderate or severe congestive heart failure [36,37,47–50]. Similarly, impaired RVEF is an adverse prognostic factor in patients surviving an acute myocardial infarction [51–56]. Moreover, right ventricular systolic function is an important determinant of exercise capacity in patients with chronic heart failure [57,58]. Finally, in addition to a higher left ventricular inotropic reserve, patients having non-ischaemic cardiomyopathy with normal RVEF derive a higher increase in LVEF from long-term beta-blocker therapy [59].

Although it is of relevance, the clinical use of the RVEF was impeded by the difficulties of its measurement. In the past decade, the development of magnetic resonance imaging and gated blood pool emission tomography have made RVEF measurement more readily available in routine settings [44–46,60–68]. However, considering the receptiveness of medical imaging departments and the incidence of heart failure, a biochemical marker would be useful to identify patients who are at high risk of right ventricular systolic dysfunction and to help the clinicians to select the patients who will benefit from further imaging assessment.

A recent study has shown that plasma BNP levels are elevated in patients with isolated pulmonary artery hypertension [31]. However, as right ventricular dysfunction is often associated with left ventricular dysfunction, the usefulness of plasma BNP as a marker for right ventricular dysfunction depends on the importance of plasma BNP increase among patients with right and left ventricular dysfunction, compared with patients with isolated left ventricular dysfunction. The link found in our population between left and right ejection fraction as predictors for BNP plasma levels confirms this point. In this study, plasma BNP levels correlate negatively with LVEF and are significantly higher when LVEF is decreased. This confirms that plasma BNP is a good indicator of left ventricular dysfunction [7,8,10–13]. On the contrary, the correlation between BNP levels and LVEF was not significant in the subgroup of patients having heart failure secondary to ischaemic heart disease. However, the P-value (P=0.09) and the small number of patients (18 patients) may suggest a lack of statistical significance. Also, as plasma BNP is known to be remarkably high and to carry prognostic import in patients after acute myocardial infarction [15,16], the release of BNP in heart failure secondary to myocardial infarction may be driven by other factors than ejection fraction alone.

If patients with impaired right ventricular systolic function (RVEF<40%) show higher BNP levels, no significant BNP difference is found between patients with or without additional left ventricular systolic dysfunction. In contrast, plasma BNP shows better correlations with RVEF than with LVEF, as well in the whole population as in ischaemic or non-ischaemic sub-groups. Similarly, the class analysis shows that impaired right ventricular systolic function is always associated with higher BNP levels, whatever the status of left ventricular function. Finally, for patients with left ventricular systolic dysfunction (LVEF<40%), plasma BNP levels correlate with RVEF but not with LVEF. All these results suggest that impaired right ventricular systolic function may be more efficient than left ventricular dysfunction in inducing elevation of plasma BNP levels. Indeed, this study shows that, among patients with impaired LVEF, mean plasma BNP level is remarkably and significantly higher in patients with impaired right ventricular systolic function. The most important aspect of this result is that the increase in plasma BNP level is not the consequence of major left ventricular dysfunction. In our population, patients with LVEF<40% did not have significantly different LVEF, whatever their RVEF. Moreover, the higher BNP levels found among patients with right ventricular systolic dysfunction do not appear to be the consequence of other factors that might account for differences in BNP levels such as age, NYHA functional class, renal function, left ventricular volumes or medication (Table 1).

In a study based on patients presenting to the emergency department with acute dyspnea, patients with congestive heart failure had BNP levels significantly higher than the group of patients with a final diagnosis of acute pulmonary disease [69]. The apparent inconsistency between this study and the results presented in the present paper is likely to be due to the fact that most of the patients with acute pulmonary disease did not have severe right ventricular dysfunction. Indeed, higher plasma BNP levels was found in patients with right ventricular dysfunction due to pulmonary embolism compared to patients with pulmonary embolism and normal right ventricular function [70,71]. The results of the present paper are consistent with the results published in a recent study where a significant inverse correlation was found between RVEF and BNP levels in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease [72].

In humans, BNP is expressed predominantly in myocytes in the interstitial fibrous area in dilated cardiomyopathy. For the thin right ventricular free wall, recent studies have suggested that local stimuli caused by hemodynamic overload, induce cardiac hypertrophy and its associated increase in BNP expression [73]. Moreover, a paper by Kim demonstrated that the receptor for BNP is the predominant guanyl cyclase-coupled natriuretic peptide receptor in the ventricular endocardium and that the most important binding sites for natriuretic peptides are located in the right ventricle [74]. This study demonstrated that the ventricular hypertrophy induced by pulmonary hypertension downregulates the natriuretic peptide receptors only in the hypertrophied right ventricular endocardium. These results are consistent with the very high levels of plasma BNP found in this study when right ventricular systolic function is impaired. Moreover, the strong links described in the present paper between the impairment of right ventricular systolic function and high BNP plasma levels may explain why many recent studies suggested that BNP is a good marker of increased mortality in patients with end-stage chronic respiratory disease [75] or pulmonary hypertension [76].

In conclusion, an important increase in plasma BNP levels should be regarded by cardiologists as an indication of high risk of right ventricular dysfunction and should justify further investigation.


   Acknowledgements
 
The authors thank CIS Bio International for providing the BNP kits used in this study, and staff members of Lapeyronie University Hospital for their assistance.


   References
Top
 Abstract
 1. Introduction
 2. Materials and methods
 3. Results
 4. Discussion
 References
 

  1. Magga J., Vuolteenaho O., Tokola H., Martila M., Ruskoaho H. B-type natriuretic peptide: a myocyte specific marker for characterizing load-induced alterations in cardiac gene expression. Ann Med (1998) 30:39–45.[Web of Science][Medline]
  2. Edwards B.S., Zimmerman R.S., Schwab T.R., Heublein D.M., Burnett J.C. Jr. Atrial stretch, not pressure, is the principal determinant controlling the acute release of atrial natriuretic factor. Circ Res (1988) 62:191–195.[Abstract/Free Full Text]
  3. Haug C., Metzele A., Kochs M., Hombach V., Grunert A. Plasma brain natriuretic peptide and atrial natriuretic peptide concentrations correlate with left ventricular end-diastolic pressure. Clin Cardiol (1993) 16:553–557.[Web of Science][Medline]
  4. Nakao K., Itoh H., Suga S., Ogawa Y., Imura H. The natriuretic peptide family. Curr Opin Nephrol Hypertens (1993) 2:45–50.[Medline]
  5. Stevens T.L., Rasmussen T.E., Wei C.M., Kinoshita M., Matsuda Y., Burnett J.C. Jr. Renal role of the endogenous natriuretic peptide system in acute congestive heart failure. J Card Fail (1996) 2:119–125.[CrossRef][Medline]
  6. Mc Donagh T.A., Robb S.D., Murdoch D.R., et al. Biochemical detection of left ventricular systolic dysfunction. Lancet (1998) 351:9–13.[CrossRef][Web of Science][Medline]
  7. Omland T., Aakvaag A., Bonarjee V.V.S., et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction: comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide. Circulation (1996) 93:1963–1969.[Abstract/Free Full Text]
  8. Lear W., Boer P.H. Rapid activation of the type B versus the type A natriuretic factor gene by aortocaval shunt induced cardiac volume overload. Cardiovasc Res (1995) 29:676–681.[Abstract/Free Full Text]
  9. Sumida H., Yasue H., Yoshimura M., et al. Comparison of secretion pattern between A-type and B-type natriuretic peptides in patients with old myocardial infarction. J Am Coll Cardiol (1995) 25:1105–1110.[Abstract]
  10. Yamamoto K., Burnett J.C., Jougasaki M., et al. Superiority of BNP as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. Hypertension (1996) 28:988–994.[Abstract/Free Full Text]
  11. Cowie M.R., Struthers A.D., Coats A.J.S., Thompson S.G., Poole-Wilson P.A., Sutton G.C. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet (1997) 350:1347–1351.
  12. Kohno M., Horio T., Yokokawa K., et al. Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor. Am J Med (1995) 98:257–265.[CrossRef][Web of Science][Medline]
  13. Luchner A., Muders F., Dietl O., et al. Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction. Cardiovasc Res (2001) 51:601–607.[Abstract/Free Full Text]
  14. Cowie M.R. BNP: soon to become a routine measure in the care of patients with heart failure? Heart (2000) 83:617–618.[Free Full Text]
  15. Morita E., Yasue H., Yoshimura M., et al. Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction. Circulation (1993) 88:82–91.[Abstract/Free Full Text]
  16. De Lemos J.A., Morrow D.A., Bentley J.H., et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med (2001) 345:1014–1021.[Abstract/Free Full Text]
  17. Nagaya N., Nishikimi T., Goto Y., et al. Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction. Am Heart J (1998) 135:21–28.[CrossRef][Web of Science][Medline]
  18. Troughton R.W., Frampton C.M., Yandle T.G., Espiner E.A., Nicholls M.G., Richards A.M. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet (2000) 355:1126–1130.[CrossRef][Web of Science][Medline]
  19. Dries D., Warner Stevenson L. Brain natriuretic peptide as bridge to therapy for heart failure (commentary). Lancet (2000) 355:1112–1113.[CrossRef][Web of Science][Medline]
  20. Sagnella G.A. Measurement and significance of circulated natriuretic peptides in cardiovascular diseases. Clin Sci (1998) 95:519–529.[CrossRef][Web of Science][Medline]
  21. Nousiainen T., Jantunen E., Vanninen E., et al. Natriuretic peptides as markers of cardiotoxicity during doxorubicin treatment for non-Hodgkin's lymphoma. Eur J Haematol (1999) 62:135–141.[Web of Science][Medline]
  22. Horie H., Tsutamoto T., Ishimoto N., et al. Plasma brain natriuretic peptide as a biochemical marker for atrioventricular sequence in patients with pacemakers. Pacing Clin Electrophysiol (1999) 22:282–290.[CrossRef][Medline]
  23. Buckley M.G., Sethi D., Markandu M.D., et al. Plasma concentrations and comparisons of brain natriuretic peptide and atrial natriuretic peptide in normal subjects, cardiac transplant recipients and patients with dialysis-independant or dialysis-dependant chronic renal failure. Clin Sci (1992) 83:437–444.[Web of Science][Medline]
  24. Lang C.C., Choy A.M., Henderson I.S., et al. Effect of haemodialysis on plasma levels of brain natriuretic peptide in patients with chronic renal failure. Clin Sci (1992) 82:127–131.[Web of Science][Medline]
  25. Nitta K., Kawashima A., Yumura W., et al. Plasma concentration of brain natriuretic peptide as an indicator of cardiac ventricular function in patients on haemodialysis. Am J Nephrol (1998) 18:411–415.[CrossRef][Web of Science][Medline]
  26. Lang C.C., Coutie W.J., Struthers A.D., et al. Elevated levels of brain natriuretic peptide in acute hypoxaemic chronic obstructive pulmonary disease. Clin Sci (1992) 83:529–533.[Web of Science][Medline]
  27. Davies M., Espiner E., Richards G., et al. Plasma brain natriuretic peptide in assessment of acute dyspnoea. Lancet (1994) 343:440–444.[CrossRef][Web of Science][Medline]
  28. Ando T., Ogawa K., Yamaki K., et al. Plasma concentrations of atrial, brain and C-type natriuretic peptides and endothelin-1 in patients with chronic respiratory diseases. Chest (1996) 110:462–468.[Abstract/Free Full Text]
  29. Mitaka C., Hirata Y., Nagura T., et al. Increased plasma concentration of brain natriuretic peptide in patients with acute lung injury. J Crit Care (1997) 12:66–71.[CrossRef][Web of Science][Medline]
  30. Fleisher D., Espiner A.E., Yandle T.G., et al. Rapid assay of plasma brain natriuretic peptide in the assessment of acute dyspnoea. NZ Med J (1997) 110:71–74.[Web of Science][Medline]
  31. Nagaya N., Nishikimi T., Okano Y., et al. Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension. J Am Coll Cardiol (1998) 31:202–208.[Abstract/Free Full Text]
  32. Fujii T., Otsuka T., Tanaka S., et al. Plasma endothelin-1 level in chronic obstructive pulmonary disease: relationship with natriuretic peptide. Respiration (1999) 66:212–219.[CrossRef][Web of Science][Medline]
  33. Yano Y., Katsuki A., Gabazza E.C., et al. Plasma brain natriuretic peptide levels in normotensive noninsulin-dependant diabetic patients with microalbuminuria. J Clin Endocrinol Metab (1999) 84:2353–2356.[Abstract/Free Full Text]
  34. Ationu A., Singer D.R.J., Smith A., et al. Study of cardiopulmonary bypass in children: implications for the regulation of brain natriuretic peptides. Cardiovasc Res (1993) 27:1538–1541.[Abstract/Free Full Text]
  35. Hayabuchi Y., Matsukoa S., Kuroda Y. Plasma concentrations of atrial and brain natriuretic peptides and cyclic guanosine monophosphate in response to dobutamine infusion in patients with surgically repaired tetralogy of Fallot. Pediatr Cardiol (1999) 20:343–350.[CrossRef][Web of Science][Medline]
  36. Ghio S., Gavazzi A., Campana C., et al. Independent and additive prognostic value of right ventricular systolic function and pulmonary artery pressure in patients with chronic heart failure. J Am Coll Cardiol (2001) 37:183–188.[Abstract/Free Full Text]
  37. De Groote P., Millaire A., Foucher-Hossein C., et al. Right ventricular ejection fraction is an independent predictor of survival in patients with moderate heart failure. J Am Coll Cardiol (1998) 32:948–954.[Abstract/Free Full Text]
  38. Yasue H., Yoshimura M., Sumida H., et al. Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure. Circulation (1994) 90:195–203.[Abstract/Free Full Text]
  39. Hasegawa K., Fujiwara H., Doyama K., et al. Ventricular expression of atrial and brain natriuretic peptides in dilated cardiomyopathy. An immunohistocytochemical study of the endomyocardial biopsy specimens using specific monoclonal antibodies. Am J Pathol (1993) 142:107–116.[Abstract]
  40. Ationu A., Sorensen K., Whitehead B., Singer D., Burch M., Carter N.D. Ventricular expression of brain natriuretic peptide gene following orthotopic cardiac transplantation in children—a three year follow up. Cardiovasc Res (1993) 27:2135–2139.[Abstract/Free Full Text]
  41. Nakanishi K., Tajima F., Itoh H., et al. Changes in atrial natriuretic peptide and brain natriuretic peptide associated with hypobaric hypoxia-induced pulmonary hypertension in rats. Virchows Arch (2001) 439:808–817.[Web of Science][Medline]
  42. Jaszczak R.J., Floyd C.E., Coleman R.E. Scatter compensation techniques for SPECT. IEEE Trans Nucl Sci (1985) 32:786–793.[CrossRef][Web of Science]
  43. Rigo P., Van Boxem P., Foulon J., Safi M., Engdahl J., Links J. Quantitative evaluation of a comprehensive motion, resolution, and attenuation program: initial experience. J Nucl Cardiol (1998) 5:458–468.[CrossRef][Web of Science][Medline]
  44. Mariano-Goulart D., Collet H., Kotzki P.O., Zanca M., Rossi M. Semi-automatic segmentation of gated blood pool emission tomographic images by watersheds: application to the determination of right and left ejection fractions. Eur J Nucl Med (1998) 25:1300–1307.[CrossRef][Web of Science][Medline]
  45. Mariano-Goulart D., Collet H., Eberlé M.C., et al. Routine measurements of right and left ejection fractions thanks to the segmentation of gated blood pool tomographic images by a watershed algorithm. Eur J Nucl Med (1999) 26:1078. abstr.
  46. Mariano-Goulart D., Piot C., Boudousq V., et al. Routine measurements of left and right ventricular output by gated blood pool emission tomography in comparison with thermodilution measurements: a preliminary study. Eur J Nucl Med (2001) 28:506–513.[CrossRef][Web of Science][Medline]
  47. Di Salvo T.G., Mathier M., Semigran M.J., Dec G.W. Preserved right ventricular ejection fraction predicts exercise capacity and survival in advanced heart failure. J Am Coll Cardiol (1995) 25:1143–1153.[Abstract]
  48. Gavazzi A., Berzuini C., Campana C., et al. Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure. J Heart Lung Transplant (1997) 16:774–785.[Web of Science][Medline]
  49. Juilliere Y., Barbier G., Feldmann L., Grentzinger A., Danchin N., Cherrier F. Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy. Eur Heart J (1997) 18:276–280.[Abstract/Free Full Text]
  50. Karatasakis G.T., Karagounis L.A., Kalyvas P.A., et al. Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure. Am J Cardiol (1998) 82:329–334.[CrossRef][Web of Science][Medline]
  51. Pfisterer M., Emmenegger H., Muller-Brand J., Burkart F. Prevalence and extent of right ventricular dysfunction after myocardial infarction—relation to location and extent of infarction and left ventricular function. Int J Cardiol (1990) 28:325–332.[CrossRef][Web of Science][Medline]
  52. Melchior T., Gadsboll N., Hildebrandt P., Kober L., Torp-Pedersen C. Clinical characteristics, left and right ventricular ejection fraction, and long-term prognosis in patients with non-insulin-dependent diabetes surviving an acute myocardial infarction. Diabet Med (1996) 13:450–456.[CrossRef][Web of Science][Medline]
  53. Gil V.M., Ferreira J., Mendes M., Seabra-Gomes R. Relationship between radionuclide right ventricular ejection fraction and clinical status in patients with left ventricular dysfunction after myocardial infarction. Rev Port Cardiol (1999) 18:791–798.[Medline]
  54. Candell Riera J., Rius Davi A., Castell Conesa J., et al. The postinfarct prognostic value of right ventricular systolic function. Rev Esp Cardiol (1995) 48:115–121.[Medline]
  55. Marwick T.H., Birbara T.M., Allman K.C., Morris J.G., Kelly D.T., Harris P.J. Prognostic significance of right ventricular ejection fraction following inferior myocardial infarction. Int J Cardiol (1991) 31:205–211.[CrossRef][Web of Science][Medline]
  56. Polak J.F., Holman B.L., Wynne J., Colucci W.S. Right ventricular ejection fraction: an indicator of increased mortality in patients with congestive heart failure associated with coronary artery disease. J Am Coll Cardiol (1983) 2:217–224.[Abstract]
  57. Baker B.J., Wilen M.M., Boyd C.M., Dinh H., Franciosa J.A. Relation of right ventricular ejection fraction to exercise capacity in chronic left ventricular failure. Am J Cardiol (1984) 54:596–599.[CrossRef][Web of Science][Medline]
  58. Montes Orbe P.M., Ormaetxe J.M., Martinez J.D., Rodriguez E., Ruiz de Azua E., Iriarte M.M. Right ventricular function and effort tolerance in patients with chronic congestive heart insufficiency. A cross-over double-blind study. Rev Esp Cardiol (1990) 43:137–141.[Medline]
  59. Ramahi T.M., Longo M.D., Cadariu A.R., et al. Left ventricular inotropic reserve and right ventricular function predict increase of left ventricular ejection fraction after beta-blocker therapy in nonischemic cardiomyopathy. J Am Coll Cardiol (2001) 37:818–824.[Abstract/Free Full Text]
  60. Daou D., Harel F., Helal B.O., et al. Electrocardiographically gated blood-pool sepct and left ventricular function: comparative value of 3 methods for ejection fraction and volume estimation. J Nucl Med (2001) 42:1043–1049.[Abstract/Free Full Text]
  61. Groch M.W., Erwin W.D., Murphy P.H., et al. Validation of knowledge-based boundary detection algorithm: a multicenter study. Eur J Nucl Med (1996) 23:662–668.[CrossRef][Web of Science][Medline]
  62. Groch M.W., DePuey E.G., Belzberg A.C., et al. Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study. J Nucl Med (2001) 42:1773–1779.[Abstract/Free Full Text]
  63. Vanhove C., Franken P.R. Left ventricular ejection fraction and volumes from gated blood pool tomography: comparison between two automatic algorithms that work in three-dimensional space. J Nucl Cardiol (2001) 8:466–471.[CrossRef][Web of Science][Medline]
  64. Vanhove C., Franken P.R., Defrise M., Momen A., Everaert H., Bossuyt A. Automatic determination of left ventricular ejection fraction from gated blood-pool tomography. J Nucl Med (2001) 42:401–407.[Abstract/Free Full Text]
  65. Bartlett M.L., Seaton D., McEwan L., Fong W. Determination of right ventricular ejection fraction from reprojected gated blood pool SPET: comparison with first-pass ventriculography. Eur J Nucl Med (2001) 28:608–613.[CrossRef][Web of Science][Medline]
  66. Chin B.B., Bloomgarden D.C., Xia W., et al. Right and left ventricular volume and ejection fraction by tomographic gated blood-pool scintigraphy. J Nucl Med (1997) 38:942–948.[Abstract/Free Full Text]
  67. Pretorius P.H., Xia W., King M.A., Tsui B.M.W., Pan T.S., Villegas B.J. Evaluation of right and left ventricular volumes and ejection fraction using a mathematical cardiac torso phantom. J Nucl Med (1997) 38:1528–1535.[Abstract/Free Full Text]
  68. Botvinick E.H., O'Connell J.W., Kadkade P.P., et al. Potential added value of three-dimensional reconstruction and display of single photon emission computed tomographic gated blood pool images. J Nucl Cardiol (1998) 5:245–255.[CrossRef][Web of Science][Medline]
  69. Morrison L.K., Harrison A., Krishnaswamy P., Kazanegra R., Clopton P., Maisel A. Utility of rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol (2002) 39:202–209.[Abstract/Free Full Text]
  70. Tulevski I.I., Hirsch A., Sanson B.J., et al. Increased brain natriuretic peptide as a marker for right ventricular dysfunction in acute pulmonary embolism. Thromb Haemost (2001) 86:1193–1196.[Web of Science][Medline]
  71. Tulevski I.I., Mulder B.J., Van Veldhuisen D.J. Utility of a BNP as a marker for RV dysfunction in acute pulmonary embolism. J Am Coll Cardiol (2002) 39:2080.[Free Full Text]
  72. Tulevski I.I., Groenink M., Van Der Wall E.E., et al. Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction. Heart (2001) 86:27–30.[Abstract/Free Full Text]
  73. Adachi S., Ito H., Ohta Y., et al. Distribution of mRNAs for natriuretic peptides in RV hypertrophy after pulmonary arterial banding. Am J Physiol (1995) 268:162–169.
  74. Kim S.Z., Cho K.W., Kim S.H. Modulation of endocardial natriuretic peptide receptors in right ventricular hypertrophy. Am J Physiol (1999) 277:2280–2289.
  75. Ishii J., Nomura M., Ito M., et al. Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease. Clin Chim Acta (2000) 301:19–30.[CrossRef][Web of Science][Medline]
  76. Nagaya N., Nishikimi T., Uematsu M., et al. Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension. J Cardiol (2001) 37:110–111.[Medline]

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