The clinical utility of brain natriuretic peptide in paediatric left ventricular failure
Great Ormond Street Hospital, London WC1 3NJH, UK
* Corresponding author. Tel: +44 207 4059200, Fax: +44 207 8138440, Email: burchm{at}gosh.nhs.uk
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Abstract |
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Aims: To assess the role of brain natriuretic peptide (BNP) in both the acute and chronic settings in children with left ventricular (LV) failure.
Methods and results: We undertook a retrospective review of all BNP levels taken over a 2-year period in our institution. Minimum follow-up was 90 days. Ninety-two BNP samples from 48 patients were reviewed. Twenty patients (42%) reached the combined endpoint of death, transplantation, or listing for transplantation. Median age was 3 years and 3 months. Mean BNP levels in NYHA or Ross classes I–IV were 29, 239, 744, and 1593 pg/mL, respectively, with significant differences between mean logBNP in classes I–III (P < 0.001). LogBNP levels correlated with fractional shortening (P < 0.001), LVEDd z-score (P < 0.001), and tissue Doppler velocities (P < 0.02). From serial data there was a strong correlation between change in BNP and change in clinical status (F 9.5, P < 0.001). Receiver-operator curve (ROC) demonstrated that BNP > 290 pg/mL predicts poor outcome with sensitivity of 0.80, specificity of 0.87, and likelihood ratio of 6.4 in paediatric patients with chronic LV dysfunction. A separate ROC from acute presentations did not demonstrate superiority of BNP over other assessments.
Conclusion: BNP levels in paediatric heart failure (HF) patients show a strong correlation to both impaired heart function on echocardiogram and clinical status. Serial BNP levels follow the clinical course. In chronic HF, a BNP level of >290 pg/mL is predictive of an adverse outcome.
Key Words: Brain natriuretic peptide • BNP • Heart failure • Dilated cardiomyopathy
Received March 24, 2007; Revised June 26, 2008; Accepted July 21, 2008
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Introduction |
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Assessment of children in heart failure (HF) can be difficult. Basic echocardiography is not independent of loading conditions and detailed scanning is limited in restless young children. Metabolic exercise testing is impossible in small children. Therefore, the neurohormonal responses to heart failure have the potential of being a vital clinical tool in the paediatric HF clinic.
Of the recently characterized natriuretic peptides, measures of brain natriuretic peptides (BNP) or N-terminal-proBNP (NT-proBNP) appear to be the most representative of chronic left ventricular (LV) dysfunction both to volume load1–3 and pressure load.4 However, there are some limitations in transferring the experience of BNP from adult practise to paediatrics. Most obviously, in the adult population with impaired ventricular function, the aetiology is predominately ischaemic heart disease.5 Whereas in the paediatric population, the aetiology is more heterogeneous.6,7 Although paediatric BNP studies have been published,8,9 most of the data are from heterogeneous groups of patients. Many include those with single ventricle morphology and varying pressure or volume loading pathologies. Homogenous study populations are difficult in children. We limited our study population to children with biventricular circulation and dilated cardiomyopathy. There is only one substantive study in this area, but unlike the only previous study of this group,10 we have included both acute and chronic patients and serial data. As very little is known about BNP in paediatric HF, further exploration of its clinical use appears appropriate.
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Methods |
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Near-patient BNP testing using the Triage assay (Biosite Diagnostics, Inc., San Diego, CA, USA) was introduced in our institution in 2004. It is used in those patients attending for transplant assessment and in the paediatric HF clinic based on emerging data.11–14 We undertook a retrospective review of all BNP levels taken over a 2-year period (April 2004 to April 2006) in our institution. The local research committee approved the study. We excluded all patients with congenital heart disease, primary right ventricular dysfunction, pulmonary hypertension, restrictive cardiomyopathy, hypertrophic cardiomyopathy, congenital, and acquired mitral or aortic valve disease. We only included children with LV dysfunction in whom simultaneous clinical evaluation (by a paediatric cardiologist) and echocardiography had been performed. The minimum follow-up period was 90 days. Clinical evaluation was based on symptoms and examination findings. These were summarized using the New York Heart Association (NYHA) scoring.15 The Ross classification was used for younger non-ambulatory children.16,17 In our HF clinic, the echocardiographic study and the clinical evaluation by the cardiologist are always performed prior (and therefore blind) to the BNP result being available. Echocardiographic assessment included: LV end-diastolic dimension (LVEDd) and fractional shortening both measured in the parasternal long-axis. LVEDd was corrected for body surface area (LVEDd z-score).18 Transmitral Doppler peak early velocity (E) and duration of transmitral flow in atrial systole were recorded. Tissue Doppler velocities were obtained from: the lateral mitral annulus peak E (Lateral Ea), peak S (Lateral Sa), septal mitral annulus peak E (Septal Ea), and peak S (Septal Sa). From this data, E/Ea ratio was calculated. Duration of transmitral flow in atrial systole was deducted from the duration of pulmonary venous flow reversal in atrial systole (
A duration). During the time of the study, BNP levels were not being used as part of the transplant decision-making process. BNP samples were acquired when phlebotomy was being performed in the HF clinic or on transplant assessment. The indication for phlebotomy in the HF clinic was to ensure therapeutic doses of digoxin, amiodarone, and warfarin. It was also used to monitor side-effects of selective beta-blockers, angiotensin-converting enzyme-inhibitor (ACE)-inhibitors, and diuretics used in this patient population. The minimum amount of whole blood taken was 250 µL. Samples were immediately placed in ethylene diamine tetraacetic acid-containing tubes and then processed using the Biosite Triage Meter plus assay. This system is based on fluorescence intensity of labelled murine monoclonal antibodies to the ring structure of BNP. Precision of the system is reported with an interassay coefficient of variation of 8.8% with mean BNP of 71.3 pg.mL, 11% with mean BNP of 629.9 pg/mL, and 11.6% with mean BNP of 4087.9 pg/mL.19 Each BNP level sample was correlated to simultaneous clinical and echocardiographic evaluation.
All the analyses was carried out using SPSS version 14 (SPSS Inc., Chicago, IL, USA). Where appropriate to enable better correlation, BNP was substituted by logBNP. Non-parametric data were correlated using Spearman's test. Parametric data were correlated with Pearson's one-tailed test. To examine the relationship between BNP level and outcomes, we used receiver-operator curves (ROC) and Cox regression analysis. To test the difference between means, a univariate analysis of variance model was used. Analysis of covariance (ANCOVA) model was used to establish an association between changes in echocardiographic variables, clinical status, and BNP levels in patients who had serial sampling.
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Results |
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In total, 92 BNP samples were obtained from 48 patients. The mean age of patients was 5 years and 8 months, median age was 3 years and 3 months (range 3 weeks to 16 years and 7 months), and 58% (n = 28) were male. Forty-two percent of patients (n = 20) reached the combined endpoint of death (n = 6), or transplantation/listing for transplantation (n = 14). Of the remaining 28 patients, 2% (n = 1) made a complete recovery and 56% (n = 27) remained under medical follow-up.
The causes of dilated cardiomyopathy varied, in 56.3% of cases no aetiology was found and these were categorized as idiopathic. The remainder comprised: viral myocarditis 10.4%; anthracycline cardiotoxicity 10.4%; ischaemic cardiomyopathy 8.4%; familial cardiomyopathy 4.2%; metabolic disease 4.2%; incessant tachycardia 4.2%; and hypocalcaemia 2.1%. Medication at initial sampling included: diuretics in 83%, ACE-inhibitor in 82%; digoxin in 54%; beta-blockers in 46%; anticoagulation in 44%; amiodarone in 13%, and inotropes in 24%. The time between sampling and first presentation was a mean of 13 months, with a median of 3 months (range 0 days to 12 years and 4 months).
Rising logBNP levels correlated strongly with NYHA and Ross classifications of clinical severity (n = 92, r 0.82, P < 0.001) (Figure 1). Mean BNP levels in classes I–IV were: 29, 239, 744, and 1593 pg/mL, respectively. There were significant differences between mean logBNP in Ross and NYHA classes I–III (P < 0.001). The difference in mean logBNP between classes III and IV was not significant. LogBNP levels correlated well with fractional shortening (n = 92, r –0.66, P < 0.001). Significant correlations were also seen with LVEDd z-score (n = 85, r 0.34, P < 0.001). LogBNP correlated with tissue Doppler velocities Lateral Sa (n = 33, r –0.36, P < 0.02), Septal Ea (n = 25, r –0.69, P < 0.001), and Septal Sa (n = 22, r –0.58, P < 0.002). No significant correlation was seen between BNP and E:Ea ratio (n = 24, r–0.17, P 0.22), BNP to lateral Ea velocity (n = 33, r 0.01, P 0.46), or BNP and A duration in our patients (n = 17, r–0.17, P 0.26).
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We constructed ROC curves relating outcome to fractional shortening, clinical status (NYHA or Ross classification), LVEDd z-score, and BNP. In the first (ROC 1), serial samples and samples taken within 1 month of an acute presentation were excluded. The age range in the 34 patients included was 0–15 years (mean 5 years), and 30% (n = 10) of these patients reached the combined endpoint of death, transplantation, or listing for transplantation. The combined endpoint was taken at least 90 days from the time of the sample. ROC 1 demonstrated both clinical status and BNP as good indicators of outcome [area under the curve (AUC) 0.937 and 0.914, respectively]. Fractional shortening and LVEDd z-score were inferior predictors of outcome (AUC 0.808 and 0.73, respectively). Figure 2 compares the ROC 1 as generated from BNP and fractional shortening. Taking the optimum point on the curve (i.e. balance of sensitivity and specificity) BNP > 290 pg/mL predicts poor outcome with sensitivity of 0.80, specificity of 0.87, and likelihood ratio of 6.4. Based on the highest likelihood ratio, a BNP level of >500 pg/mL predicts poor outcome with sensitivity of 0.70, specificity of 0.96, and a likelihood ratio of 16. We were able to generate a separate ROC curve from samples taken within 1 month of an acute presentation, again excluding serial samples (ROC 2). The age range in the 21 patients included was 0–15 years (mean 3.5 years), and 71% (n = 15) of these patients reached the combined endpoint of death, transplantation, or listing for transplantation taken at least 90 days from the time of the sample. This demonstrated clinical status (AUC 0.769) to be a superior predictor of outcome compared with fractional shortening (AUC 0.723), BNP (AUC 0.646), and LVEDd z-score (AUC 0.577). From this subgroup, there was no significant difference in mean BNP, mean z-score, mean fractional shortening, and mean clinical status group (NYHA/Ross classification) between patients who survived at 90-day follow-up and those who had an adverse event.
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From the data used for ROC 1 (again with serial samples and data taken within a month of an acute presentation excluded), a Cox regression model was constructed. The model was stratified by patients with BNP greater than or less than 290 pg/mL. Age, clinical status (NYHA/Ross classification), fractional shortening, and Lateral Sa tissue Doppler velocity were included in the model as covariates. Cox regression analysis confirms a poor predicted survival in patients with BNP > 290 pg/mL at mean of covariates (Figure 3). Hazard ratios generated by the model were: fractional shortening 1.62, clinical status 0.89, age 1.06; however, none of these were statistically significant.
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We were able to analyse 62 serial samples taken from 18 patients. Thirty-nine percent of patients (n = 7) reached the combined endpoint of death, transplantation, or listing for transplantation. ANCOVA analysis of serial data demonstrated a strong correlation between change in BNP and change in clinical status (NYHA or Ross classification), F 9.5, P < 0.001 (Figure 4). The model was structured with clinical status as the dependent variable, patients as fixed factors, and logBNP as covariant. The ANCOVA analysis allows all the trends of BNP to clinical status from each patient (as plotted in Figure 4) to be correlated with each other. With a similar ANCOVA analysis, there was correlation between changes in fractional shortening and change in clinical status, however this was less strong (F 5.3, P < 0.08). There was no significant correlation between change in BNP and fractional shortening, between change in BNP and LVEDd z-score or between change in clinical status and LVEDd z-score. In four of the seven patients who had adverse events, BNP levels trended upwards during the follow-up period (this was not a statistically significant correlation). In the remaining three patients, the levels trended both up and down. However, overall BNP levels in these seven patients remained above 1000 pg/mL.
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Discussion |
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The significance of natriuretic peptides in HF is becoming better understood particularly in the adult population.20–22 In children, characterization of BNP is also developing rapidly.10,23–26 However, most of the published data in children with cardiac dysfunction is from heterogeneous groups including single ventricle physiology and obstructive lesions. Prior to this report, data from paediatric populations with biventricular circulations and impaired LV function was limited to only one substantial paediatric paper.10 We have confirmed some of the findings from the previous homogenous group study done by Price et al.,10 therefore providing a greater evidence base for the clinical use of BNP in children. In addition, we have extended their findings to a younger population, studied both acute and chronic patients and included serial data.
Correlations between BNP and clinical status are integral to its use in the clinical setting. Encouragingly, we have confirmed a strong correlation between both clinical state and the echocardiographic assessment of fractional shortening to BNP. We also found the relation with tissue Doppler parameters (mitral valve septal Ea/Sa and mitral valve lateral Ea) was statistically significant. Interestingly, similar to the findings of Price et al.,10 our data show that E:Ea ratio did not correlate with BNP levels. Data from adults suggest that this is a robust measurement of diastolic dysfunction.27,28 This in part may be explained by technical limitations in non-sedated paediatric echocardiograms and the physiological differences in heart rate/stroke volume relationships in children when compared with adults. Price et al. found no significant correlation between LVEDd and BNP levels. However, we found that the correlation between logBNP and LVEDd was significant and we believe that the difference reflects the characteristics of the patient group. Over half of our cases underwent BNP testing within 3 months of presentation. Hence, there were relatively fewer patients with chronically dilated ventricles, who were stable on medical therapy (ACE-inhibitors, beta-blockers, diuretics). Although we have found a strong correlation between BNP levels and clinical status, the spread of BNP values in each NYHA or Ross class is wide. This may reflect the difficulty of defining functional class in children.
The most important potential clinical use of BNP is as a predictor of outcome. Our data suggest that BNP is indeed a useful tool in predicting adverse outcome in children with predominantly LV systolic dysfunction. In fact, BNP appears superior to conventional echocardiographic parameters. The work of Price et al. in chronic paediatric HF showed that the outcome was worse for children with BNP > 300 pg/mL. Importantly, our data are from a younger and more acute population. Despite this, our data from the ROC 1 curve suggest that a similar cut-off at 290 pg/mL will identify most patients at least 1 month after an acute event who are at risk of a poor outcome. However, our data have shown that it would seem prudent to interpret BNP cautiously in the acute presentation of paediatric HF. In the latter setting, BNP does not appear to add an advantage as a predictor of outcome over clinical status. The Cox regression analysis gives some insight as to how the combination of fractional shortening, age, and clinical status (as defined by NYHA/Ross) may help predict which patients have a worse outcome. The model does confirm a difference in expected survival in patients with BNP > 290 pg/mL particularly if they have a poor fractional shortening on echocardiogram. However, this data are not statistically significant.
Unlike earlier work, our study did include a number of children who had serial BNP levels taken. Our findings suggest that improvement, or conversely decompensation, can be mapped with BNP levels with superior accuracy than conventional echocardiographic parameters. BNP therefore has the potential to alert non-specialists and specialists alike to the occurrence of decompensation, potentially prompting earlier and more effective intervention.
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This study was not prospective. Detailed assessment of right heart function was not performed other than assessment with two-dimensional echo, and colour Doppler of tricuspid valve regurgitation. We did not formally assess renal function, although no children were in renal failure. We acknowledge that repeated measures obtained from echocardiography carry an inherent margin of error. Although our study was unusual for paediatrics in being limited to LV failure, the aetiologies of the LV dysfunction were varied.
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Conclusions |
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BNP levels in paediatric HF patients show a strong correlation with both impaired heart function on echocardiogram and clinical status. Serial BNP levels in the paediatric HF clinic follow the clinical course. In chronic HF, a BNP level of >290 pg/mL is predictive of an adverse outcome. BNP does not appear to be predictive during acute presentation.
Conflict of interest: none declared.
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References |
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- Ruskoaio I. Cardiac hormones as diagnostic tools in heart failure. Endocr Rev (2003) 24:3441–3356.
- Nakagawa O, Ogawa Y, Itoh H, Suga S, Komatsu Y, Kishimoto I, Nishino K, Yoshimasa T, Nakao K. Rapid transcriptional activation and early mRNA turnover of brain natriuretic peptide in cardiocyte hypertrophy: evidence for brain natriuretic peptide as an ‘emergency’ cardiac hormone against ventricular overload. J Clin Invest (1995) 96:1280–1287.[Web of Science][Medline]
- Hama N, Itoh H, Shirakami G, Nakagawa O, Suga S, Ogawa Y, Masuda I, Nakanishi K, Yoshimasa T, Hashimoto Y, Yamaguchi M, Hori R, Yasue H, Nakao K. Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation (1995) 92:1558–1564.
[Abstract/Free Full Text] - Lim P, Monin J, Monchi M, Garot J, Pasquet A, Hittinger L, Vanoverschelde J, Carayon A, Gueret P. Predictors of outcome in patients with severe aortic stenosis and normal left ventricular function: role of B-type natriuretic peptide. Eur Heart J (2004) 25:2048–2053.
[Abstract/Free Full Text] - Cowie M, Wood D, Coats A, Thompson S, Poole-Wilson P, Suresh V, Sutton G. Incidence and aetiology of heart failure: a population-based study. Eur Heart J (1999) 20:421–428.
[Abstract/Free Full Text] - Nugent A, Daubeney P, Chondros P, Carlin J, Cheung M, Wilkinson L, Davis A, Kahler S, Chow C, Wilkinson J, Weintraub R, the National Australian Childhood Cardiomyopathy Study. The epidemiology of childhood cardiomyopathy in Australia. N Engl J Med (2003) 348:1639–1646.
[Abstract/Free Full Text] - Lipshultz S, Sleeper L, Towbin J, Lowe A, Orav E, Cox G, Lurie P, McCoy K, McDonald M, Messere J, Colan S. The incidence of pediatric cardiomyopathy in two regions of the United States. N Engl J Med (2003) 348:1647–1655.
[Abstract/Free Full Text] - Yoshibayashi M, Kamiya T, Saito Y, Nakao K, Nishioka K, Temma S, Itoh H, Shirakami G, Matsuo H. Plasma brain natriuretic peptide concentrations in healthy children from birth to adolescence: marked and rapid increase after birth. Eur J Endocrinol (1995) 133:207–209.
[Abstract/Free Full Text] - Koch A, Singer H. Normal values of B type natriuretic peptide in infants, children, and adolescents. Heart (2003) 89:875–878.
[Abstract/Free Full Text] - Price JF, Thomas AK, Grenier M, Eidem BW, O'Brian Smith E, Denfield S, Towbin JA, Dreyer WJ. B-type natriuretic peptide predicts adverse cardiovascular events in paediatric outpatients with chronic left ventricular systolic dysfunction. Circulation (2006) 114:1063–1069.
[Abstract/Free Full Text] - Ohuchi H, Takasugi H, Ohashi H, Okada Y, Yamada O, Ono Y, Yagihara T, Echigo S. Stratification of pediatric heart failure on the basis of neurohormonal and cardiac autonomic nervous activities in patients with congenital heart disease. Circulation (2003) 108:2368–2376.
[Abstract/Free Full Text] - Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, Omland T, Storrow AB, Abraham WT, Wu AH, Clopton P, Steg PG, Westheim A, Knudsen CW, Perez A, Kazanegra R, Herrman HC, McCullough PA, for the Breathing Not Properly Multinational Study Investigators. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med (2002) 347:161–167.
[Abstract/Free Full Text] - Berger R, Huelsman M, Strecker K, Bojic A, Moser P, Stanek B, Pacher R. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation (2002) 105:2392–2397.
[Abstract/Free Full Text] - Koglin J, Pehlivanli S, Schwaiblmair M, Vogeser M, Cremer P, vonScheidt W. Role of brain natriuretic peptide in risk stratification of patients with congestive heart failure. J Am Coll Cardiol (2001) 38:1934–1941.
[Abstract/Free Full Text] - The Criteria Committee of the New York Heart Association. Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis. (1964) 6th ed. Boston: Little, Brown & Co. p112.
- Ross R, Bollinger R, Pinsky W. Grading the severity of heart failure in infants. Pediatr Cardiol (1992) 13:72–75.[CrossRef][Web of Science][Medline]
- Rosenthal D, Chrisant MR, Edens E, Mahony L, Canter C, Colan S, Dubin A, Lamour J, Ross R, Shaddy R, Addonizio L, Beerman L, Berger S, Bernstein D, Blume E, Boucek M, Checchia P, Dipchand A, Drummond-Webb J, Fricker J, Friedman R, Hallowell S, Jaquiss R, Mital S, Pahl E, Pearce B, Rhodes L, Rotondo K, Rusconi P, Scheel J, Pal Singh T, Towbin J. International Society for Heart and Lung Transplantation: Practice guidelines for management of heart failure in children. J Heart Lung Transplant (2004) 23:1313–1333.[CrossRef][Web of Science][Medline]
- First T, Skovranek J, Marek J. Normal Values of two-dimensional echocardiographic parameters in children. Cesk Pediatr (1992) 47:260–264.[Medline]
- Vogeser M, Jacob K. B-type natriuretic peptide (BNP)—validation of an immediate response assay. Clin Lab (2001) 47:29–33.[Medline]
- Maisel A, Hollander J, Guss D, McCullough P, Nowak R, Green G, Saltzberg M, Ellison SR, Bhalla MA, Bhalla V, Clopton P, Jesse R. Primary results of the Rapid Emergency Department Heart Failure Outpatient Trial (REDHOT): a multicenter study of B-type natriuretic peptide levels, emergency department decision making, and outcomes in patients presenting with shortness of breath. J Am Coll Cardiol (2004) 44:1328–1333.
[Abstract/Free Full Text] - Kruger S, Graf J, Kunz D, Stickel T, Hanrath P, Janssens U. Brain natriuretic peptide levels predict functional capacity in patients with chronic heart failure. J Am Coll Cardiol (2002) 40:718–722.
[Abstract/Free Full Text] - Watanabe J, Shiba N, Shinozaki T, Koseki Y, Karibe A, Komaru T, Miura M, Fukuchi M, Fukahori K, Sakuma M, Kagaya Y, Shirato K. Prognostic value of plasma brain natriuretic peptide combined with left ventricular dimensions in predicting sudden death of patients with chronic heart failure. J Card Fail (2005) 11:50–55.[CrossRef][Medline]
- Westerlind A, Wahlander H, Lindstedt G, Lundberg PA, Homgren D. Clinical signs of heart failure are associated with increased levels of natriuretic peptide types B and A in children with congenital heart defects or cardiomyopathy. Acta Paediatr (2004) 93:340–345.[CrossRef][Web of Science][Medline]
- Koulouri S, Acherman RJ, Wong PC, Chang LS, Lewis AB. Utility of B-type natriuretic peptide in differentiating congestive heart failure from lung disease in pediatric patients with respiratory distress. Pediatr Cardiol (2004) 25:341–346.[Web of Science][Medline]
- Koch A, Zink S, Singer H. B-type natriuretic peptide in paediatric patients with congenital heart disease. Eur Heart J (2006) 27:861–866.
[Abstract/Free Full Text] - Law Y, Keller B, Feingold B, Boyle G. Usefulness of plasma B-type natriuretic peptide to identify ventricular dysfunction in pediatric and adult patients with congenital heart disease. Am J Cardiol (2005) 95:474–478.[CrossRef][Web of Science][Medline]
- Dokainish H, Zoghbi WA, Lakkis NM, Quinones MA, Nagueh SF. Comparative accuracy of B-type natriuretic peptide and tissue Doppler echocardiography in the diagnosis of congestive heart failure. Am J Cardiol (2004) 93:1130–1135.[CrossRef][Web of Science][Medline]
- Dokainish H, Zoghbi WA, Lakkis NM, Ambriz EA, Patel R, Quinones MA, Nagueh SF. Incremental predictive power of B-type natriuretic peptide and tissue Doppler echocardiography in the prognosis of patients with congestive heart failure. J Am Coll Cardiol (2005) 45:1223–1226.
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