| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;106:416.)
© 2002 American Heart Association, Inc.
Clinical Investigation and Reports |
From the University of California (P.C., P.K., R.K., A.S.M.), Veterans Affairs Medical Center, San Diego; Henry Ford Hospital (R.M.N., J.M.), Detroit, Mich; University of Pennsylvania (J.E.H., H.C.H.), Philadelphia; Hopital Bichat (P.G.S., P.D.), Paris, France; Ullevål University Hospital (A.W., T.O., C.W.K.), Oslo, Norway; University of Cincinnati College of Medicine (A.B.S.), Cincinnati, Ohio; University of Kentucky College of Medicine (W.T.A., S.L.), Lexington; Hartford Hospital (A.H.B.W., A.P.), Hartford, Conn; and University of MissouriKansas City School of Medicine (P.A.M.), Truman Medical Center, Kansas City, Mo.
Correspondence to Peter A. McCullough, MD, MPH, University of MissouriKansas City School of Medicine, Truman Medical Centers, 2301 Holmes St, Kansas City, MO 64108. E-mail mcculloughp{at}umkc.edu
| Abstract |
|---|
|
|
|---|
Methods and Results The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons).
Conclusions The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.
Key Words: heart failure diagnosis natriuretic peptides lung tests
| Introduction |
|---|
|
|
|---|
| Methods |
|---|
|
|
|---|
Study Sample
A total of 1666 patients presenting to the emergency departments (EDs) of the study centers with a primary complaint of dyspnea were screened. Eighty patients were excluded from the study on the basis of the protocol exclusion criteria, which included the presence of advanced renal failure (calculated creatinine clearance <15 mL/min), acute myocardial infarction, and overt cause of dyspnea, including chest wall trauma or penetrating lung injury. A total of 1586 participants were enrolled in the present study. For those 1586 individuals, 48 had records that did not have the ED physician assessment of clinical probability of CHF; hence, those patients were excluded, leaving a final set of 1538 to be analyzed.
Data Collection
Baseline demographics, clinical history, and objective assessment of clinical signs were gathered by trained ED research personnel who were present continuously during the evaluation of the consenting individuals. All participants were seen and examined by an attending physician, and findings from the ECG, chest x-ray, and blood tests were categorized in a structured checklist. On disposition from the ED, research personnel recorded the attending physicians estimate of clinical probability of CHF on a visual analog scale.
Measurement of BNP
During initial evaluations, a blood sample (5 mL) was collected into tubes containing potassium EDTA (1 mg/mL blood). In a 15-minute period, BNP was measured by using the Triage BNP Test (Biosite Inc). The Triage BNP Test is a fluorescence immunoassay for the quantitative determination of BNP in whole-blood and plasma specimens. Precision, analytical sensitivity, and stability characteristics of the system have been previously described.12 In brief, the coefficient of variation for intra-assay precision has been reported to be 9.5%, 12.0%, and 13.9%, and the coefficient of variation for interassay precision is known to be 10.0%, 12.4%, and 14.8% for BNP levels of 28.8, 584.0, and 1180.0 pg/mL, respectively.13 The measurable range of the BNP assay was 5.0 to 1300.0 pg/mL. Consistent with concurrent research using the Triage BNP Test, each sample was tested in triplicate to minimize variation from single observations and for internal controls. Final results were reported as the mean of the 3 samples. Of note, the current approved clinical method is to measure BNP in a single run of the test. Test results were kept in separated data binders linked only by a study code; thus, both ED physicians and adjudicating cardiologists were blinded regarding the BNP results.
Reference Standard Definition of Heart Failure
Approximately 30 days after the ED visit, the case report form (excluding the estimate of CHF probability), ECG, chest x-ray, echocardiogram, and all other clinical tests and consultations were reviewed by 2 independent cardiologists at the local study center who were not treating physicians. In addition, case report information was used to calculate the Framingham scores (requiring 2 major or 1 major and 2 minor criteria for CHF) and National Health and Nutrition Examination Survey (NHANES) scores (requiring
3 points for CHF) for CHF. After reviewing all information, if agreement was achieved, then the case was categorized as one of the following: (1) dyspnea due to CHF, (2) history of CHF but dyspnea due to noncardiac cause, or (3) dyspnea due to noncardiac cause. In the event of disagreement (n=164; 10.7%, range 0% to 24.3% across 7 sites), cases were adjudicated by the study end-points committee. For binary analyses of CHF versus no CHF, groups 2 and 3 were combined.
Sample Size and Power
The primary end point was diagnostic accuracy at the optimum cutoff of BNP and at
80% ED physician estimate of clinical probability of CHF. The following assumptions were made in the sample size calculation: diagnostic accuracy of the ED physician, 85%; prevalence of CHF as a final diagnosis in the ED dyspnea population, 30%; and effect size of
5% absolute difference between clinical judgment and BNP, ß=0.20 and
=0.05 (2-sided). The calculated sample size of 1613 was set for study to have 80% power to observe a
5% absolute difference in diagnostic accuracy between the groups. With the 1538 participants evaluated in this analysis having a higher prevalence of CHF and larger effect size than expected, the observed power was 99%.
Statistical Analysis
Baseline characteristics were reported in counts and proportions or mean±SD values as appropriate. Univariate comparisons were made with
2 or 2-sample t tests as appropriate. Because this was the largest and most broadly inclusive population with dyspnea to be tested for BNP to date, we decided a priori to derive the optimum cut point for BNP from the parent population of 1586 participants. We arrived at the optimum cut point of 100 pg/mL by selecting the point on the receiver operating characteristic (ROC) curve that maximized both sensitivity and 1-specificity. The optimum cut point for ED clinical certainty of CHF was chosen at
80%, a cut point providing reasonable and actionable certainty of a cardiovascular syndrome.14 Decision statistics were computed from 2x2 tables and reported as sensitivity, specificity, and positive and negative predictive value. Diagnostic accuracy was computed as the sum of the concordant cells divided by the sum of all cells in the 2x2 table. Agreement between clinical judgment and BNP was quantified by using Cohens
statistic. The positive likelihood ratio was taken as the slope of the ROC curve for the optimum cut point and was expressed as sensitivity/1-specificity. Pairwise comparisons among the areas under ROC curves were made by using Delongs method.15 Logistic regression was used to combine clinical judgment with BNP data in predicting final adjudicated diagnosis, generating a graphic displayed as a heart failure diagnosis nomogram. Judgments of 0% were set to 1%, and judgments of 100% were set to 99% so that the log of the odds ratios could be computed.
| Results |
|---|
|
|
|---|
|
|
Symptoms and Physical Examination Findings
All participants in the present study required dyspnea on exertion or at rest for study inclusion. Table 2 indicates that the cardinal symptoms and signs (paroxysmal nocturnal dyspnea, elevated jugular venous pressure, pulmonary rales, cardiac enlargement, third heart sound, hepatic enlargement, and edema) of CHF were more common as ED clinical judgment was more certain of the diagnosis of CHF. Conversely, approximately one fourth of all participants had wheezing, regardless of pretest probability for CHF.
|
Diagnostic Testing Performed
All participants were subjected to ECG, and a majority, 1476 (96.0%), had chest x-rays performed in the ED. Table 3 lists the results of these tests stratified by the clinical probability of CHF as assessed by the ED physicians. Rates of all ECG abnormalities were more frequent in those with high clinical probabilities of CHF. Likewise, the rates of chest x-ray abnormalities indicating signs of CHF were more frequent in the high probability of CHF category. However, the presence of pneumonic infiltrate was not statistically significant across the categories (all <10%).
|
Reference Standard for Heart Failure
Two independent cardiologists at each study center evaluated all clinical data, including echocardiograms with reported ejection fractions in 689 (44.8%) cases. There was initial agreement between the 2 cardiologists in 1374 (89.3%) of the cases. The remaining 164 cases required adjudication locally between the 2 cardiologists, including requesting additional data from the treating physicians and, finally, review by the end-points committee if disagreement remained. The diagnosis of CHF (n=722) was supported by positive NHANES and Framingham scores in 599 (83.0%) and 621 (86.0%) individuals, respectively. The cardiologists reported that the diagnosis of CHF was supported in 587 (81.3%) by chest x-ray, 448 (62.0%) by echocardiography, 34 (4.7%) by nuclear ventriculography, and 55 (7.6%) by cardiac catheterization. In addition, the cardiologists reported that 490 (67.9%) of those with CHF had an expected response to CHF therapy. Conversely, 684 (91.4%) of those 748 found not to have CHF had cumulative evidence from chest x-ray, echocardiography, or ventriculography suggesting that CHF was not the cause of dyspnea.
Decision Statistics
The diagnostic accuracy for high (80% to 100%) ED probability of CHF on clinical grounds was 74.0%. The other decision statistics for this category were as follows: sensitivity 49% (95% CI 47% to 52%), specificity 96% (95% CI 95% to 97%), positive predictive value 91% (95% CI 90% to 92%), negative predictive value 68% (95% CI 66% to 71%), and positive likelihood ratio 11.5. Diagnostic accuracy for BNP
100 pg/mL was 81.2%. The other decision statistics for BNP were as follows: sensitivity 90% (95% CI 89% to 92%), specificity 73% (95% CI 71% to 73%), positive predictive value 75% (95% CI 72% to 77%), negative predictive value 90% (95% CI 88% to 91%), and positive likelihood ratio 3.4. For a composite decision based on clinical probability of 80% to 100% or BNP >100 pg/mL, or both, the diagnostic accuracy was 81.5%, sensitivity was 94% (95% CI 93% to 95%), specificity was 70% (95% CI 68% to 73%), positive predictive value was 74% (95% CI 71% to 76%), negative predictive value was 93% (95% CI 92% to 94%), and the positive likelihood ratio was 3.2. As an overall measure of diagnostic value, BNP levels
100 pg/mL would have added to clinical judgment, thus boosting accuracy from 74.0% to 81.5% (P<0.0001) (Figure 2). Overall, BNP at a cut point of 100 pg/mL and clinical judgment
80% certainty were relatively independent indicators, as reflected by a
value of 0.30 (P<0.0001). In participants without a self-reported history of CHF (n=1027), the diagnostic accuracy of BNP was 80.4%. In other important subgroups, including men, women, whites, African Americans, the elderly (aged >70 years), and those with ischemic heart disease, the diagnostic accuracy of BNP was 83.6%, 78.0%, 80.7%, 81.0%, 78.1%, and 81.2%, respectively. Compared through a range of values with the use of ROC curves (Figure 3), the areas under the ROC curve were 0.86, 0.90, and 0.93 for clinical judgment, for BNP, and for the 2 in combination, respectively (P<0.001 for all pairwise comparisons).
|
|
Heart Failure Diagnosis Nomogram
Figure 4 displays a CHF diagnosis nomogram with the estimate of pretest probability being the certainty in the ED that dyspnea is due to CHF. The rates of actual CHF by final adjudicated diagnosis were 17.1%, 33.6%, and 49.3% for the low-, intermediate-, and high-probability groups, respectively (P<0.0001 for trend). The middle line represents BNP level in picograms per milliliter at the time of presentation. When a straight line is drawn through the pretest probability and BNP level in picograms per milliliter, the posttest probability is found on the right line. For example, a clinical judgment of 20% probability of CHF with a BNP of 1000 pg/mL yields an
85% probability of CHF based on these 2 predictors. As indicated, BNP has the greatest value as a diagnostic test in the intermediate zone of probability. In this category, BNP
100 pg/mL correctly classified 315 (74.0%) of the 427 cases as CHF or not CHF. Importantly, in this intermediate group, only 30 (7.0%) of 427 had a BNP level <100 pg/mL and a final adjudicated diagnosis of CHF. Of note, in 721 participants with low (
20%) ED probability of CHF, 123 (17.1%) of 721 indeed had a final adjudicated diagnosis of CHF. Of these 123 individuals, 111 (90.2%) would have had the misdiagnosis corrected if the additional information of BNP >100 pg/mL had been provided. Conversely, in the cases in which the ED clinician was completely certain the diagnosis was not CHF (n=232), BNP was <100 pg/mL in 80.6% and would have been confirmatory of a final diagnosis of noncardiac dyspnea in 182 (85.4%) of 213 and would have corrected the diagnosis in 14 (73.7%) of 19. Conversely, in the cases in which the ED clinician was 100% certain that CHF was present (n=109), BNP was
100 pg/mL in 89.0% and would have been confirmatory of a final diagnosis of CHF in 96 (92.3%) of 104 and would have corrected the final diagnosis in 4 (80.0%) of 5.
|
| Discussion |
|---|
|
|
|---|
The present study confirms the value of the careful history and physical examination in patients with dyspnea.17 The sharpest gradients in the cardinal features of CHF were seen across our diagnostic probability categories. Indeed, the symptom of paroxysmal nocturnal dyspnea and the physical examination findings of rales, cardiac enlargement on palpation, third heart sound, and peripheral edema were all 2 to 3 times more likely in those patients with a high probability of CHF. Conversely, wheezing did not appear to be a factor in the clinicians ability to discriminate among cases. The ECG and chest x-ray appeared to be valuable in the development of a clinical probability discrimination for CHF. Of note, only a pneumonic infiltrate appeared to be of little help in making an assignment of CHF probability. Despite the value of a careful clinical examination seen in the present study, it has been shown in several prior studies that the clinical examination for CHF is limited.1822
The source of plasma BNP is cardiac ventricles, which suggests that BNP may be a more sensitive and specific indicator of ventricular disorders than other natriuretic peptides.23 This release appears to be responsive to wall tension, which, in turn, is affected by a variety of determinants that are deranged in CHF.2427 The results of the BNP Multinational Study reported in the present study suggest that the biological properties of this peptide make it an attractive test for the acute ED diagnosis of CHF.
The present study has multiple limitations related to any study that attempts to create a gold standard for a clinical syndrome. Blinded cardiologists used all possible information in making the final adjudicated CHF diagnosis. We attempted to aid in this process by creating standardized CHF scores from 2 prior validated methods for the cardiologists to view with all of the clinical data. We acknowledge that misclassification bias is possible and difficult to quantify. It is also possible that the measurement of BNP could have been confounded by other factors, including acute ischemia or renal insufficiency, in patients who were not excluded on these grounds.28,29 It is unlikely that missing data, either in the pretest, test, or posttest probability categories, have influenced the results, given the fact that the study sample was restricted to 1538 individuals, ensuring complete data in all cases.
We believe that the importance of the present study will be to advance the current state of certainty regarding the usefulness of BNP in the diagnosis of CHF as indicated by the most recently published set of CHF guidelines.11 Our findings are supportive of the recently published European guidelines for the diagnosis and treatment of CHF, which incorporate BNP as a diagnostic test for routine clinical practice.30 In addition to being a useful outpatient screening tool for left ventricular dysfunction, results of the BNP Multinational Study support the use of BNP in the ED.31 Routine use of BNP in the evaluation of suspected heart failure would be largely confirmatory, yet still valuable in cases in which the clinician has a high degree of certainty of the diagnosis. Importantly, BNP would clarify the final diagnosis in a large proportion of cases encountered in the ED. We anticipate that the published nomogram in this article will be useful to ED and other physicians in establishing the diagnosis of CHF in patients with dyspnea of uncertain etiology. This nomogram leverages an objective yet conservative approach, providing a safeguard for the highly subjective clinical assessment of patients who have CHF presenting as dyspnea of uncertain etiology. To put this in context, 90% of the patients who had CHF but were thought by the ED physician to be of low probability (
20%) would have been correctly diagnosed with a point-of-care blood test, allowing for rapid triage and appropriate care of these patients. Importantly, a final degree of clinical utility is achieved by integration of a careful history, physical examination, ECG, chest x-ray, and BNP level, as demonstrated in the ROC curves.
In conclusion, in a multinational sample of men and women seen in the ED with acute dyspnea, BNP measurement would have added to clinical judgment in establishing a final diagnosis of CHF. In those patients with an intermediate probability of CHF, BNP would have clarified the diagnosis in the majority of cases.
| Acknowledgments |
|---|
| Footnotes |
|---|
Drs McCullough, Omland, McCord, Wu, Maisel, Abraham, Kazanegra, Hollander, Storrow, and Duc and P. Clopton have received honoraria from Biosite. Drs McCullough, Maisel, McCord, Abraham, Hollander, Storrow, and Omland are consultants for Biosite. Drs McCord, Maisel, and McCullough are members of the speakers bureau for Biosite. Dr Wu has received grants from and owns stock in Biosite.
Received May 9, 2002; revision received May 21, 2002; accepted May 28, 2002.
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
E. C H J Michielsen, J. A Bakker, R. R J V. Kimmenade, Y. M Pinto, and M. P V. Dieijen-Visser The diagnostic value of serum and urinary NT-proBNP for heart failure Ann Clin Biochem, July 1, 2008; 45(4): 389 - 394. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. O. Maher, H. Reed, A. Cuadrado, J. Simsic, W. T. Mahle, M. DeGuzman, T. Leong, and S. Bandyopadhyay B-Type Natriuretic Peptide in the Emergency Diagnosis of Critical Heart Disease in Children Pediatrics, June 1, 2008; 121(6): e1484 - e1488. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. M. Green, A. Martinez-Rumayor, S. A. Gregory, A. L. Baggish, M. L. O'Donoghue, J. A. Green, K. B. Lewandrowski, and J. L. Januzzi Jr Clinical Uncertainty, Diagnostic Accuracy, and Outcomes in Emergency Department Patients Presenting With Dyspnea Arch Intern Med, April 14, 2008; 168(7): 741 - 748. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Okada, H. Makino, A. Nagumo, T. Sugisawa, M. Fujimoto, I. Kishimoto, Y. Miyamoto, A. Kikuchi-Taura, T. Soma, A. Taguchi, et al. Circulating CD34-Positive Cell Number Is Associated With Brain Natriuretic Peptide Level in Type 2 Diabetic Patients Diabetes Care, January 1, 2008; 31(1): 157 - 158. [Full Text] [PDF] |
||||
![]() |
R. D. Mainwaring, C. Parise, S. B. Wright, A. L. Juris, R. A. Achtel, and H. Fallah Brain Natriuretic Peptide Levels Before and After Ventricular Septal Defect Repair Ann. Thorac. Surg., December 1, 2007; 84(6): 2066 - 2069. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. P. Rivers, J. McCord, R. Otero, G. Jacobsen, and M. Loomba Clinical utility of B-type natriuretic peptide in early severe sepsis and septic shock. J Intensive Care Med, November 1, 2007; 22(6): 363 - 373. [Abstract] [PDF] |
||||
![]() |
M. Ring, H. Persson, M. Mejhert, and M. Edner Post-systolic motion in patients with heart failure - A marker of left ventricular dyssynchrony? Eur J Echocardiogr, October 1, 2007; 8(5): 352 - 359. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Breidthardt, K. Laule, A.-H. Strohmeyer, C. Schindler, S. Meier, M. Fischer, A. Scholer, M. Noveanu, M. Christ, A. P. Perruchoud, et al. Medical and Economic Long-term Effects of B-Type Natriuretic Peptide Testing in Patients with Acute Dyspnea Clin. Chem., August 1, 2007; 53(8): 1415 - 1422. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. R. deFilippi, S. L. Seliger, S. Maynard, and R. H. Christenson Impact of Renal Disease on Natriuretic Peptide Testing for Diagnosing Decompensated Heart Failure and Predicting Mortality Clin. Chem., August 1, 2007; 53(8): 1511 - 1519. [Abstract] [Full Text] [PDF] |
||||
![]() |
K.-S. Spanaus, F. Kronenberg, E. Ritz, R. Schlapbach, D. Fliser, M. Hersberger, B. Kollerits, P. Konig, A. von Eckardstein, and for the Mild-to-Moderate Kidney Disease Study Grou B-Type Natriuretic Peptide Concentrations Predict the Progression of Nondiabetic Chronic Kidney Disease: The Mild-to-Moderate Kidney Disease Study Clin. Chem., July 1, 2007; 53(7): 1264 - 1272. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. Greenberg Can We IMPROVE-CHF Management By Measuring Natriuretic Peptides? Circulation, June 19, 2007; 115(24): 3045 - 3047. [Full Text] [PDF] |
||||
![]() |
G. W. Moe, J. Howlett, J. L. Januzzi, H. Zowall, and for the Canadian Multicenter Improved Management o N-Terminal Pro-B-Type Natriuretic Peptide Testing Improves the Management of Patients With Suspected Acute Heart Failure: Primary Results of the Canadian Prospective Randomized Multicenter IMPROVE-CHF Study Circulation, June 19, 2007; 115(24): 3103 - 3110. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Shadman, M. A. Allison, and M. H. Criqui Glomerular Filtration Rate and N-Terminal Pro-Brain Natriuretic Peptide as Predictors of Cardiovascular Mortality in Vascular Patients J. Am. Coll. Cardiol., June 5, 2007; 49(22): 2172 - 2181. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Carrillo-Jimenez, S. Borzak, and C. H. Hennekens Brain Natriuretic Peptide: Clinical and Research Challenges Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2007; 12(2): 85 - 88. [Abstract] [PDF] |
||||
![]() |
D. M. Heublein, B. K. Huntley, G. Boerrigter, A. Cataliotti, S. M. Sandberg, M. M. Redfield, and J. C. Burnett Jr Immunoreactivity and Guanosine 3',5'-Cyclic Monophosphate Activating Actions of Various Molecular Forms of Human B-Type Natriuretic Peptide Hypertension, May 1, 2007; 49(5): 1114 - 1119. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Jourdain, G. Jondeau, F. Funck, P. Gueffet, A. Le Helloco, E. Donal, J. F. Aupetit, M. C. Aumont, M. Galinier, J. C. Eicher, et al. Plasma Brain Natriuretic Peptide-Guided Therapy to Improve Outcome in Heart Failure: The STARS-BNP Multicenter Study J. Am. Coll. Cardiol., April 24, 2007; 49(16): 1733 - 1739. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Kwan, S. R. Isakson, J. Beede, P. Clopton, A. S. Maisel, and R. L. Fitzgerald Short-Term Serial Sampling of Natriuretic Peptides in Patients Presenting With Chest Pain J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1186 - 1192. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bayes-Genis, D. M. Lloyd-Jones, R. R. J. van Kimmenade, J. G. Lainchbury, A. M. Richards, J. Ordonez-Llanos, M. Santalo, Y. M. Pinto, and J. L. Januzzi Jr Effect of Body Mass Index on Diagnostic and Prognostic Usefulness of Amino-Terminal Pro-Brain Natriuretic Peptide in Patients With Acute Dyspnea Arch Intern Med, February 26, 2007; 167(4): 400 - 407. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Ceconi and R. Ferrari One heart, two lungs together forever. Am. J. Respir. Crit. Care Med., November 1, 2006; 174(9): 962 - 963. [Full Text] [PDF] |
||||
![]() |
F. Abroug, L. Ouanes-Besbes, N. Nciri, N. Sellami, F. Addad, K. B. Hamda, A. B. Amor, M. F. Najjar, and J. Knani Association of Left-Heart Dysfunction with Severe Exacerbation of Chronic Obstructive Pulmonary Disease: Diagnostic Performance of Cardiac Biomarkers Am. J. Respir. Crit. Care Med., November 1, 2006; 174(9): 990 - 996. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Jelic and T. H. Le Jemtel Diagnostic Usefulness of B-Type Natriuretic Peptide and Functional Consequences of Muscle Alterations in COPD and Chronic Heart Failure. Chest, October 1, 2006; 130(4): 1220 - 1230. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. M. Felker, J. W. Petersen, and D. B. Mark Natriuretic peptides in the diagnosis and management of heart failure. Can. Med. Assoc. J., September 12, 2006; 175(6): 611 - 617. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Groban and J. Butterworth Perioperative management of chronic heart failure. Anesth. Analg., September 1, 2006; 103(3): 557 - 575. [Abstract] [Full Text] [PDF] |