0
Original Research: Pulmonary Vascular Disease |

Lung Ultrasound-Implemented Diagnosis of Acute Decompensated Heart Failure in the EDLung Ultrasound in Diagnosing Acute Heart Failure: A SIMEU Multicenter Study FREE TO VIEW

Emanuele Pivetta, MD; Alberto Goffi, MD; Enrico Lupia, MD, PhD; Maria Tizzani, MD; Giulio Porrino, MD; Enrico Ferreri, MD; Giovanni Volpicelli, MD, FCCP; Paolo Balzaretti, MD; Alessandra Banderali, MD; Antonello Iacobucci, MD; Stefania Locatelli, MD; Giovanna Casoli, MD; Michael B. Stone, MD; Milena M. Maule, PhD; Ileana Baldi, PhD; Franco Merletti, MD; Gian Alfonso Cibinel, MD; for the SIMEU Group for Lung Ultrasound in the Emergency Department in Piedmont
Author and Funding Information

From the Cancer Epidemiology Unit (Drs Pivetta, Maule, Baldi, and Merletti), Department of Medical Sciences, CeRMS and University of Turin, Turin, Italy; Department of Emergency Medicine (Drs Pivetta and Cibinel), “E. Agnelli” General Hospital, Pinerolo, Turin, Italy; Department of Emergency Medicine (Drs Pivetta and Stone), Brigham and Women’s Hospital, Boston, MA; Department of Emergency Medicine (Drs Pivetta, Lupia, Tizzani, Porrino, Ferreri, and Locatelli), A.O.U. Città della Salute e della Scienza di Torino and University of Turin, Turin, Italy; Interdepartmental Division of Critical Care Medicine (Dr Goffi), University of Toronto, Toronto, ON, Canada; Toronto Western Hospital (Dr Goffi), University Health Network, Toronto, ON, Canada; Department of Medical Sciences (Dr Lupia), University of Turin, Turin, Italy; Department of Emergency Medicine (Dr Volpicelli), “San Luigi Gonzaga” University Hospital, Orbassano, Turin, Italy; Department of Emergency Medicine (Dr Balzaretti), “Ordine Mauriziano” Hospital, Turin, Italy; Department of Emergency Medicine (Dr Banderali), “Cardinal Massaia” Hospital, Asti, Italy; Department of Emergency Medicine (Dr Iacobucci), “Santa Croce e Carle” Hospital, Cuneo, Italy; Department of Emergency Medicine (Dr Casoli), “Martini” Hospital, Turin, Italy; and Department of Cardiac, Thoracic, and Vascular Sciences (Dr Baldi), University of Padova, Padova, Italy.

CORRESPONDENCE TO: Emanuele Pivetta, MD, Department of Medical Sciences, Cancer Epidemiology Unit, A.O.U. Città della Salute e della Scienza di Torino, Via Santena 7, 10126, Torino, Italy; e-mail: emanuele.pivetta@gmail.com


Partial data from this study were presented at the European Society of Cardiology 2013 Annual Meeting, August 31-September 4, 2013, Amsterdam, The Netherlands; American College of Emergency Physicians 2012 Scientific Assembly, October 8-11, 2012, Denver, CO; and the American Institute of Ultrasound in Medicine 2013 Annual Meeting, April 7-11, 2013, New York, NY.

FUNDING/SUPPORT: The authors have reported to CHEST that no funding was received for this study.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(1):202-210. doi:10.1378/chest.14-2608
Text Size: A A A
Published online

BACKGROUND:  Lung ultrasonography (LUS) has emerged as a noninvasive tool for the differential diagnosis of pulmonary diseases. However, its use for the diagnosis of acute decompensated heart failure (ADHF) still raises some concerns. We tested the hypothesis that an integrated approach implementing LUS with clinical assessment would have higher diagnostic accuracy than a standard workup in differentiating ADHF from noncardiogenic dyspnea in the ED.

METHODS:  We conducted a multicenter, prospective cohort study in seven Italian EDs. For patients presenting with acute dyspnea, the emergency physician was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea after (1) the initial clinical assessment and (2) after performing LUS (“LUS-implemented” diagnosis). All patients also underwent chest radiography. After discharge, the cause of each patient’s dyspnea was determined by independent review of the entire medical record. The diagnostic accuracy of the different approaches was then compared.

RESULTS:  The study enrolled 1,005 patients. The LUS-implemented approach had a significantly higher accuracy (sensitivity, 97% [95% CI, 95%-98.3%]; specificity, 97.4% [95% CI, 95.7%-98.6%]) in differentiating ADHF from noncardiac causes of acute dyspnea than the initial clinical workup (sensitivity, 85.3% [95% CI, 81.8%-88.4%]; specificity, 90% [95% CI, 87.2%-92.4%]), chest radiography alone (sensitivity, 69.5% [95% CI, 65.1%-73.7%]; specificity, 82.1% [95% CI, 78.6%-85.2%]), and natriuretic peptides (sensitivity, 85% [95% CI, 80.3%-89%]; specificity, 61.7% [95% CI, 54.6%-68.3%]; n = 486). Net reclassification index of the LUS-implemented approach compared with standard workup was 19.1%.

CONCLUSIONS:  The implementation of LUS with the clinical evaluation may improve accuracy of ADHF diagnosis in patients presenting to the ED.

TRIAL REGISTRY:  Clinicaltrials.gov; No.: NCT01287429; URL: www.clinicaltrials.gov

Figures in this Article

Missed or delayed diagnosis of acute decompensated heart failure (ADHF) in the ED is associated with prolonged hospital stay, higher rates of ICU admission, higher mortality, and increased costs.13 However, although the worldwide incidence of heart failure is reaching epidemic proportions,4 the initial diagnostic workup of ADHF has remained fundamentally unchanged over decades46 and may be heavily undermined by several factors, such as the poor sensitivity of the physical examination, ECG inaccuracy, and unreliability of chest radiography (CXR) findings.1,7,8

Lung ultrasonography (LUS) has emerged as a rapid, noninvasive, bedside tool for the diagnosis of several pulmonary and pleural diseases.917 LUS detection of multiple and diffuse reverberation artifacts (B-lines) has been correlated with extravascular lung water content1820 and with surrogate markers of pulmonary edema,21,22 leading a consensus conference to recommend LUS for the diagnosis of ADHF.15 However, LUS accuracy may be limited by its low specificity (as low as 54% in some studies), since B-lines may be detected in lung diseases with diffuse interstitial involvement other than ADHF.10,15,18,21,23 Furthermore, conflicting results on the correlation of B-lines with pulmonary artery wedge pressure have been published,19,24,25 which led some authors to raise concerns on LUS use for ADHF diagnosis.19,23,24 In this study, we evaluated the performance of a diagnostic approach implementing LUS with the clinical assessment in differentiating ADHF from noncardiac causes of acute dyspnea in the ED.

Study Design

This was a prospective, observational, multicenter, cohort study conducted in seven Italian EDs (two academic, one university-affiliated, and four community hospitals). Patients were enrolled from October 2010 to September 2012; each center recruited for a 6-month period. The protocol was approved by the institutional review board of the “Città della Salute e della Scienza di Torino” Hospital (project approval number 2CEI-105/0068893) and by the institutional review boards of the other participant hospitals. All patients gave informed written consent to participate. All patient data, after enrollment, were deidentified. The study was conducted in accordance with the principles of the Declaration of Helsinki for clinical research involving human subjects and registered on ClinicalTrials.gov (Identifier: NCT01287429).

Participants

We considered eligible all adult subjects (age > 18 years) presenting to the ED with acute dyspnea, defined as either sudden onset of shortness of breath or increase in the severity of chronic dyspnea in the last 48 h. We excluded patients with dyspnea obviously not due to ADHF (eg, traumatic injury), and those already invasively ventilated at the time of evaluation. The presence of an emergency physician with expertise in LUS (training performed according to Italian Society of Emergency Medicine [SIMEU] guidelines; > 40 examinations completed) was required for patient enrollment.

Study Protocol

After the initial standard workup, which included past medical history, history of the present illness, physical examination, ECG, and arterial blood gas analysis,6 the emergency physician responsible for patient care was asked to categorize the diagnosis as ADHF or noncardiogenic dyspnea. The diagnosis of ADHF was based on the most updated guidelines available.6,26 In a pragmatic “real world” approach, we decided not to define a strict diagnostic protocol nor to reinforce existing guidelines for the diagnosis of ADHF in the recruiting centers. Immediately after clinical workup, the same physician performed LUS, and the new presumptive etiology, based on the results of both clinical assessment and LUS findings, was recorded (“LUS-implemented” diagnosis).

After hospital discharge, an expert emergency physician and a cardiologist, blinded to LUS results, independently reviewed the entire medical record and indicated the cause of patient’s acute dyspnea (“final diagnosis”). In case of disagreement, a third expert emergency physician reviewed the medical records and adjudicated the case.

The etiology of dyspnea was categorized as a dichotomous variable (ADHF or noncardiogenic). If both etiologies were concomitantly present, the reviewers were asked to indicate the one they considered more relevant in determining patient’s acute dyspnea.

For all patients, a CXR report interpreted by a radiologist was available. To evaluate CXR accuracy, mention of pulmonary venous congestion and/or of bilateral interstitial and/or alveolar edema was considered diagnostic for ADHF.

In a subgroup of patients, brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-pro-BNP) levels were measured, although it was not expressly required by the study protocol. The cutoff values for diagnosing ADHF were set at 400 pg/mL for BNP,27 and at 450, 900, and 1,800 pg/mL for patients < 50 years old, between 50 and 75 years old, and > 75 years of age, respectively, for NT-pro-BNP.28 Finally, two emergency physicians with limited LUS training (< 10 examinations performed) and a physician expert in LUS blindly reviewed LUS images from 200 randomly selected patients, and both intra- and interobserver variability were evaluated.

Lung Ultrasonography

Patients were examined using a curvilinear transducer (5-3 MHz), according to a previously described, six-zone scanning protocol (Fig 1).29 Diffuse interstitial syndrome (IS) was defined as the bilateral presence of two or more zones showing the presence of at least three B-lines: vertical, hyperechoic reverberation artifacts extending from the pleural line to the bottom of the screen.9,15 The accuracy of LUS alone was determined by reanalyzing, a posteriori, the sonographic images; the presence of diffuse IS was considered diagnostic for ADHF.

Figure Jump LinkFigure 1 –  Six-zone scanning protocol used for lung ultrasonography evaluation. The anterior chest wall was divided into three zones. Two zones were located anteriorly, in the second intercostal space on the mid-clavicular line, and in the fourth intercostal space on the anterior axillary line, respectively. The third zone was located laterally in the fifth intercostal space on the mid-axillary line. An additional scan was performed on the posterior axillary line at the base of the lungs to assess for the presence of pleural effusion. AAL = anterior axillary line; MAL = mid-axillary line; MC = mid-clavicular line. (The patient provided written consent for the use of this photograph.)Grahic Jump Location
Statistical Analysis

The sample size calculation assumed a prevalence of ADHF ranging from 45% to 55%, with sensitivity and specificity of the clinical assessment alone ranging from 70% to 85% and from 75% to 85%, respectively.1,3,30 We estimated that a sample size of 915 patients could achieve a power of 90% to test an absolute difference of 10% in both sensitivity and specificity between clinical and LUS-implemented evaluation, with 5% α error (two-sided test). Descriptive data are presented as mean (± SD) or median (with interquartile range [IQR]) for continuous variables, and as numbers and percentages for categorical variables.

The accuracy of each diagnostic tool is expressed as sensitivity, specificity, predictive values, and likelihood ratios obtained using 2 × 2 tables. For each test, “positive” and “negative” results were considered the diagnosis of ADHF or noncardiac dyspnea, respectively. Receiver operating characteristic (ROC) and area under the curve (AUC) statistics31,32 are also shown.

We used the McNemar test for paired data33 to compare the accuracy in the detection of ADHF of the different diagnostic tests. Diagnostic improvement obtained with LUS implementation to the initial standard workup was assessed by the net reclassification improvement (NRI), which estimates the percentage of subjects moving from one clinical diagnosis to the other.34 Intra- and interobserver agreement was assessed using Cohen κ with associated 95% CI. Data were collected in a Microsoft Excel (Microsoft Inc) spreadsheet, and statistical analyses were conducted using Stata 11.0/SE (Stata Corp).

Patients

Of 1,007 patients eligible for this study, two denied consent to enrollment; therefore, 1,005 patients were included in the analyses. Of these, 544 (54.1%) were enrolled in community hospitals and 461 (45.9%) in academic or university-affiliated centers. Sixty-two emergency physicians participated in the study, each enrolling a median number of 44 patients (IQR, 22).

Final diagnosis was ADHF for 463 patients (46%) and noncardiac dyspnea for 542 (54%). Interrater agreement between the two expert physicians adjudicating the final diagnosis of ADHF was very high (κ, 0.93; 95% CI, 0.91–0.95; P < .01). Of the 35 discordant cases, 16 were categorized as ADHF by the third expert.

Admissions were 821 (81.7%), 176 patients were discharged home, and eight patients died in the ED. Among admitted patients, 602 were admitted to general internal medicine/cardiology units, 175 to ICU or high-dependency units, 12 to surgical units, and 32 to short-stay units (with five patients subsequently admitted to internal medicine units, and 27 discharged home).

Table 1 shows patient demographic and clinical data. Table 2 reports symptoms associated with dyspnea and findings detected during the initial clinical assessment.

Table Graphic Jump Location
TABLE 1 ]  Demographic Characteristics and Medications of Patients Enrolled

Data given as No. (%) unless otherwise indicated. ACE = angiotensin-converting-enzyme; ADHF = acute decompensated heart failure; CAD = coronary artery disease; CKD = chronic kidney disease; IQR = interquartile range.

a 

χ2 test for categorical variables, or Mann-Whitney U test for continuous variables.

b 

Current or remote use.

c 

Any type and/or grade of disorder/disease.

d 

Any type of cardiac rhythm disorders (eg, atrial fibrillation, paroxysmal, persistent or permanent; atrial flutter; sick sinus syndrome; atrioventricular blocks; supraventricular paroxysmal tachycardia).

e 

CKD defined as chronic renal failure with creatinine level > 2 mg/dL (177 μmol/L).

f 

Acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor, ticlopidine, tirofiban, and dypiridamole.

g 

Warfarin, acenocoumarol, any type of heparin, fondaparinux.

Table Graphic Jump Location
TABLE 2 ]  Symptoms Associated With Acute Dyspnea and Clinical Findings Detected at the Time of Patient Presentation in the ED

Data given as No. (%) unless otherwise indicated. See Table 1 legend for expansion of abbreviations.

a 

χ2 test for categorical variables, Mann-Whitney U test, or Student t test for continuous variables.

b 

Tympanic temperature > 38.3°C.

c 

The ratio of Pao2 and Fio2 was calculated using Pao2 (mm Hg) measured at the time of the first arterial blood gas analysis and Fio2 provided, as reported in the case report form. In 83.1% of cases, the blood gas analysis was performed with patients breathing room air (Fio2, 0.21).

d 

Any type of noninvasive mechanical ventilation.

Outcomes

Figures 2 and 3 show accuracy, ROC, and AUC of the different diagnostic approaches evaluated. Clinical workup and LUS alone had relatively high accuracy in the identification of ADHF, whereas CXR showed only moderate accuracy. Sensitivity and specificity were significantly higher for LUS alone compared with CXR (P < .01). The LUS-implemented protocol had the highest accuracy, with a significant increase in sensitivity and specificity in comparison with clinical workup alone (P < .01) (Fig 2). The NRI of LUS-implemented approach compared with standard clinical workup was 19.1% (95% CI, 14.6%-23.6%; P < .01) (Table 3). The accuracy of BNP/NT-pro-BNP values, available in a subgroup of 486 patients, was significantly lower than that of the LUS-implemented approach (P < .01) (Fig 2).

Figure Jump LinkFigure 2 –  Diagnostic accuracy of the different approaches to acute dyspnea in the ED. BNP = brain natriuretic peptide; LR = negative likelihood ratio; LR+ = positive likelihood ratio; LUS = lung ultrasonography; NPV = negative predictive value; NT-pro-BNP = N-terminal pro-brain natriuretic peptide; PPV = positive predictive value.Grahic Jump Location
Figure Jump LinkFigure 3 –  A, Receiver operating characteristic (ROC) curve comparing accuracy of clinical workup, LUS-implemented diagnosis, LUS alone, and chest radiography. B, ROC curve comparing accuracy of clinical workup, LUS-implemented diagnosis, LUS alone, and BNP/NT-pro-BNP levels. See Figure 2 legend for expansion of other abbreviations.Grahic Jump Location
Table Graphic Jump Location
TABLE 3 ]  Net Reclassification Improvementa

LUS = lung ultrasonography. See Table 1 legend for expansion of other abbreviation.

a 

Net reclassification improvement was calculated as ([63 / 463] − [9 / 463]) + ([47 / 542] − [7 / 542]) = 19.1% (95% CI, 14.6%-23.6%; P < .01).

Finally, when two emergency physicians with limited LUS training (< 10 examinations performed) and a physician expert in LUS blindly reviewed LUS images from 200 randomly selected patients, the κ statistic for agreement for the diagnosis of IS was 0.94 (95% CI, 0.89-0.98; P < .01). Intraobserver agreement was 0.97 for the expert operator (95% CI, 0.95-0.99; P < .01) and 0.92 for the physicians with limited LUS training (95% CI, 0.88-0.96; P < .01).

In this study, we found that, in adult subjects with acute dyspnea in the ED, a LUS-implemented approach had higher diagnostic accuracy than other commonly used diagnostic tools (ie, initial clinical workup, CXR, LUS alone, and BNP/NT-pro-BNP levels) in differentiating ADHF from noncardiac causes of acute dyspnea. To overcome LUS limitations in ADHF diagnosis,1,6,35,36 we adopted an integrated approach that paired LUS with the pretest probability of the clinical assessment. Moreover, we strictly defined diffuse IS as the bilateral presence of two or more positive zones, to decrease false-positive diagnoses due to the appearance of B-lines in several primary lung diseases (eg, pneumonia, atelectasis). By using this strategy, we obtained sensitivity, specificity, and AUC values for the diagnosis of ADHF as high as 97.0%, 97.4%, and 0.972, respectively.

In agreement with previous data,1,3,37,38 the accuracy of the initial clinical workup for ADHF diagnosis was only moderate. The LUS-implemented approach increased the sensitivity and specificity of clinical assessment by 11.7% and 7.4%, respectively, with an NRI of 19.1%, which shows a relevant diagnostic impact of LUS in this setting.

CXR is still considered a fundamental component of the initial assessment of a patient with suspected ADHF.39 However, in our study, CXR sensitivity, although higher than that reported in other studies,1,7 was as low as 69.5%, confirming that the absence of pulmonary venous congestion/interstitial edema/alveolar edema is not sufficient to exclude the diagnosis of ADHF.1 The superiority of LUS in the detection of diffuse IS may be at least partially related to the more rapid sonographic detection of signs of pulmonary congestion, which have been shown in experimental studies to appear only 15 min after the induction of pulmonary injury and to even precede changes in Pao2/Fio2 ratio.40

The LUS-implemented approach resulted in absolute increases in sensitivity and specificity of 6.5% and 3.9%, respectively, when compared with LUS-alone, although, in our study, the sensitivity, specificity, and AUC of LUS alone were higher than in previous studies.10,11,41 This discrepancy may be related to the difference in clinical setting21,41 or to the timing of LUS performance.10

In a subgroup of patients (486 of 1,005), we evaluated the diagnostic accuracy of serum concentrations of BNP/NT-pro-BNP, extensively studied biomarkers of ADHF.1,6,36 In agreement with previous studies,6,11,28,38 natriuretic peptides had higher sensitivity (85.0%) than specificity (61.7%), and a moderate AUC (0.733). It is known that this relatively low specificity is due to the increase of BNP/NT-pro-BNP levels in several other diseases, such as pulmonary embolism, left ventricle dysfunction without ADHF, atrial fibrillation, and cor pulmonale.4244 In our study, both LUS-implemented approach and LUS alone outperformed BNP/NT-pro-BNP values in differentiating ADHF from noncardiac causes of dyspnea. Previously published studies reported results apparently not consistent with ours.11,35,41 However, the differences in the clinical setting, LUS timing, and/or BNP/NT-pro-BNP sampling may at least partially account for this discrepancy. Therefore, it can be hypothesized that detection of sonographic IS may be useful in recognizing those conditions where myocardial wall stress is increased but extravascular lung water content remains unchanged (eg, pulmonary embolism, atrial fibrillation, and cor pulmonale). In addition, LUS may be helpful in patients with only slightly elevated BNP/NT-pro-BNP levels (“grey zone”), or in situations where this analysis is not available in a timely manner (eg, remote areas, peripheral EDs, low-income countries).

A strength of our study may be considered the high degree of generalizability. We enrolled 1,005 patients with acute dyspnea in seven EDs, from both academic and community hospitals. As in previous similar studies,7,11,45 patients were usually elderly, with several comorbidities, and taking multiple medications chronically (Table 1). Pragmatically, the physicians were not limited by a strict diagnostic protocol, but were free to evaluate patients according to real-world practices. Moreover, they had heterogeneous clinical and LUS expertise, ranging from residents to experienced attending physicians.

Finally, we found a very good intra- and interobserver agreement between inexperienced operators and a physician expert in LUS when interpreting LUS images. These findings confirm previous results,10,11,29 indicating that LUS can be easily learned and its interpretation is highly reproducible.

These results are of particular interest when considering that echocardiography, the recommended test for the assessment of patients presenting with suspected ADHF and acute onset of symptoms, requires extensive training, especially to assess diastolic dysfunction. It also is often not readily available in emergency setting.6

Although we did not specifically collect data on the time elapsed between onset of symptoms and ED referral or between ED admission and LUS performance, LUS was performed within 40 min from presentation to the ED in the vast majority of patients enrolled in our study. LUS was delayed in 16 patients, due to lack of availability of the ultrasound system, but the time between ED admission and LUS performance was still < 1 h.

Several limits have to be taken into account in interpreting our results. First, we did not enroll consecutively all patients presenting to the ED with acute dyspnea. Moreover, patient enrollment required the presence of an emergency physician with expertise in LUS. Therefore, we cannot exclude a selection bias leading to an overestimation of LUS accuracy. However, patients’ characteristics, consistent with previous studies, the number of centers and of physicians participating in the study, and the physicians’ heterogeneous expertise in LUS make this possibility unlikely. Second, a common problem in studies on patients with ADHF is the lack of a standard criterion to determine the final diagnosis. As others have done,11,38 we used the independent review of the medical records by two expert physicians, with a third physician reviewing discordant cases. Despite the clear limitation of such analysis, we observed a high interrater agreement. An additional limitation exists, since the same emergency physician performed both the initial clinical workup and LUS, and so was not blinded to the results of clinical workup. Therefore, LUS findings may have not been completely independent from the clinical diagnosis, and the diagnostic accuracy of the LUS-implemented approach could be subject to bias. Even the final diagnosis, although the reviewers were blinded to LUS results, may have been indirectly affected by this bias, since the therapeutic management of the patients may have been influenced by the LUS results. Additionally, in patients with multiple concomitant causes of dyspnea (eg, pneumonia and ADHF), we asked both investigators and reviewers to indicate the one they considered more relevant in determining the patient’s acute dyspnea. Therefore, we are not able to assess the diagnostic accuracy of the LUS-implemented approach in those patients with acute dyspnea with mixed etiology. Finally, the study protocol did not allow us to compare the accuracy of the LUS-implemented approach with a CXR-implemented approach, which is the standard diagnostic approach currently used. However, LUS alone was significantly more accurate than CXR; therefore, it is highly unlikely that a less accurate test would have outperformed a more accurate test when integrated with the clinical assessment. In conclusion, our study demonstrates that the implementation of LUS with the clinical assessment improves the diagnostic accuracy for ADHF and has a significant diagnostic impact in adult patients presenting to the ED with acute dyspnea.

Author contributions: E. P., A. G., E. L., F. M., and G. A. C. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. E. P. served as principal author. E. P., A. G., E. L., M. M. M., I. B., F. M., and G. A. C. contributed to the study concept; E. P., A. G., E. L., M. T., G. P., E. F., G. V., P. B., A. B., A. I., S. L., G. C., M. M. M., F. M., and G. A. C. contributed to the study design and data acquisition; E. P., A. G., E. L., M. M. M., I. B., and F. M. contributed to statistical analyses; E. P., A. G., E. L., M. M. M., and I. B. contributed to preparation of figures and tables; E. P., A. G., E. L., M. T., G. P., E. F., G. V., P. B., A. B., A. I., S. L., G. C., M. B. S., M. M. M., I. B., F. M., and G. A. C. contributed to interpretation of the results and to revising the manuscript; and E. P., A. G., M. B. S., M. M. M., I. B., F. M., and G. A. C. contributed to writing the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Collaborators: Members of the Group for Lung Ultrasound in the Emergency Department in Piedmont, Italy, are the following: Paolo Baron, MD; Stefania Battista, MD; Giuseppina Buonafede, MD; Valeria Busso, MD; Andrea Conterno, MD; Paola Del Rizzo, MD; Patrizia Ferrera, MD; Paolo Fascio Pecetto, MD; Corrado Moiraghi, MD; Fulvio Morello, MD; Fabio Steri, MD; Giovannino Ciccone, MD; Cosimo Calasso, MD; Mimma A Caserta, MD; Marina Civita, MD; Carmen Condo’, MD; Vittorio D’Alessandro, MD; Sara Del Colle, MD; Stefania Ferrero, MD; Giulietta Griot, MD; Emanuela Laurita, MD, PhD; Alberto Lazzero, MD; Francesca Lo Curto, MD; Marianna Michelazzo, MD; Vincenza Nicosia, MD; Nicola Palmari, MD; Alberto Ricchiardi, MD; Andrea Rolfo, MD; Roberto Rostagno, MD; Fabrizio Bar, MD; Enrico Boero, MD; Mauro Frascisco, MD; Ilaria Micossi, MD; Alessandro Mussa, MD; Valerio Stefanone, MD; Renzo Agricola, MD; Gabriele Cordero, MD; Federica Corradi, MD; Cristina Runzo, MD; Aldo Soragna, MD; Daniela Sciullo, MD; Domenico Vercillo, MD; Attilio Allione, MD; Nicoletta Artana, MD; Fabrizio Corsini, MD; Luca Dutto, MD; Giuseppe Lauria, MD; Teresa Morgillo, MD; Bruno Tartaglino, MD; Daniela Bergandi, MD; Ilaria Cassetta, MD; Clotilde Masera, MD; Mario Garrone, MD; Gianluca Ghiselli, MD; Livia Ausiello, MD; Letizia Barutta, MD; Emanuele Bernardi, MD; Alessia Bono, MD; Daniela Forno, MD; Alessandro Lamorte, MD; Davide Lison, MD; Bartolomeo Lorenzati, MD; Elena Maggio, MD; Ilaria Masi, MD; Matteo Maggiorotto, MD; Giulia Novelli, MD; Francesco Panero, MD; Massimo Perotto, MD; Marco Ravazzoli, MD; Elisa Saglio, MD; Flavia Soardo, MD; Alessandra Tizzani, MD; Pietro Tizzani, MD; Mattia Tullio, MD; Marco Ulla, MD; and Elisa Romagnoli, MD.

Other contributions: We would like to thank all the colleagues of participating emergency medicine units for their work and collaboration.

ADHF

acute decompensated heart failure

AUC

area under the curve

BNP

brain natriuretic peptide

CXR

chest radiography

IQR

interquartile range

IS

interstitial syndrome

LUS

lung ultrasonography

NRI

net reclassification improvement

NT-pro-BNP

N-terminal pro-brain natriuretic peptide

ROC

receiver operating characteristic

Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA. 2005;294(15):1944-1956. [CrossRef] [PubMed]
 
Peacock WF, Braunwald E, Abraham W, et al. National Heart, Lung, and Blood Institute working group on emergency department management of acute heart failure: research challenges and opportunities. J Am Coll Cardiol. 2010;56(5):343-351. [CrossRef] [PubMed]
 
Ray P, Birolleau S, Lefort Y, et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Crit Care. 2006;10(3):R82. [CrossRef] [PubMed]
 
Redfield MM. Heart failure—an epidemic of uncertain proportions. N Engl J Med. 2002;347(18):1442-1444. [CrossRef] [PubMed]
 
McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002;106(4):416-422. [CrossRef] [PubMed]
 
McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-1847. [CrossRef] [PubMed]
 
Collins SP, Lindsell CJ, Storrow AB, Abraham WT; ADHERE Scientific Advisory Committee, Investigators and Study Group. Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure. Ann Emerg Med. 2006;47(1):13-18. [CrossRef] [PubMed]
 
Gillespie ND, McNeill G, Pringle T, Ogston S, Struthers AD, Pringle SD. Cross sectional study of contribution of clinical assessment and simple cardiac investigations to diagnosis of left ventricular systolic dysfunction in patients admitted with acute dyspnoea. BMJ. 1997;314(7085):936-940. [CrossRef] [PubMed]
 
Lichtenstein DA, Mezière GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest. 2008;134(1):117-125. [CrossRef] [PubMed]
 
Volpicelli G, Mussa A, Garofalo G, et al. Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome. Am J Emerg Med. 2006;24(6):689-696. [CrossRef] [PubMed]
 
Liteplo AS, Marill KA, Villen T, et al. Emergency thoracic ultrasound in the differentiation of the etiology of shortness of breath (ETUDES): sonographic B-lines and N-terminal pro-brain-type natriuretic peptide in diagnosing congestive heart failure. Acad Emerg Med. 2009;16(3):201-210. [CrossRef] [PubMed]
 
Grimberg A, Shigueoka DC, Atallah AN, Ajzen S, Iared W. Diagnostic accuracy of sonography for pleural effusion: systematic review. Sao Paulo Med J. 2010;128(2):90-95. [PubMed]
 
Reissig A, Copetti R, Mathis G, et al. Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study. Chest. 2012;142(4):965-972. [CrossRef] [PubMed]
 
Picano E, Frassi F, Agricola E, Gligorova S, Gargani L, Mottola G. Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc Echocardiogr. 2006;19(3):356-363. [CrossRef] [PubMed]
 
Volpicelli G, Elbarbary M, Blaivas M, et al; International Liaison Committee on Lung Ultrasound (ILC-LUS) for International Consensus Conference on Lung Ultrasound (ICC-LUS). International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012;38(4):577-591. [CrossRef] [PubMed]
 
Alrajab S, Youssef AM, Akkus NI, Caldito G. Pleural ultrasonography versus chest radiography for the diagnosis of pneumothorax: review of the literature and meta-analysis. Crit Care. 2013;17(5):R208. [CrossRef] [PubMed]
 
Noble VE, Murray AF, Capp R, Sylvia-Reardon MH, Steele DJ, Liteplo A. Ultrasound assessment for extravascular lung water in patients undergoing hemodialysis. Time course for resolution. Chest. 2009;135(6):1433-1439. [CrossRef] [PubMed]
 
Jambrik Z, Monti S, Coppola V, et al. Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol. 2004;93(10):1265-1270. [CrossRef] [PubMed]
 
Agricola E, Bove T, Oppizzi M, et al. “Ultrasound comet-tail images”: a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water. Chest. 2005;127(5):1690-1695. [CrossRef] [PubMed]
 
Baldi G, Gargani L, Abramo A, et al. Lung water assessment by lung ultrasonography in intensive care: a pilot study. Intensive Care Med. 2013;39(1):74-84. [CrossRef] [PubMed]
 
Lichtenstein D, Mézière G, Biderman P, Gepner A, Barré O. The comet-tail artifact. An ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med. 1997;156(5):1640-1646. [CrossRef] [PubMed]
 
Xirouchaki N, Magkanas E, Vaporidi K, et al. Lung ultrasound in critically ill patients: comparison with bedside chest radiography. Intensive Care Med. 2011;37(9):1488-1493. [CrossRef] [PubMed]
 
Sperandeo M, Varriale A, Sperandeo G, et al. Assessment of ultrasound acoustic artifacts in patients with acute dyspnea: a multicenter study. Acta Radiol. 2012;53(8):885-892. [CrossRef] [PubMed]
 
Lichtenstein DA, Mezière GA, Lagoueyte JF, Biderman P, Goldstein I, Gepner A. A-lines and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery occlusion pressure in the critically ill. Chest. 2009;136(4):1014-1020. [CrossRef] [PubMed]
 
Volpicelli G, Skurzak S, Boero E, et al. Lung ultrasound predicts well extravascular lung water but is of limited usefulness in the prediction of wedge pressure. Anesthesiology. 2014;121(2):320-327. [CrossRef] [PubMed]
 
Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977-2016. [CrossRef] [PubMed]
 
Maisel A. B-type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure: what’s next? Circulation. 2002;105(20):2328-2331. [CrossRef] [PubMed]
 
Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J. 2006;27(3):330-337. [CrossRef] [PubMed]
 
Cibinel GA, Casoli G, Elia F, et al. Diagnostic accuracy and reproducibility of pleural and lung ultrasound in discriminating cardiogenic causes of acute dyspnea in the emergency department. Intern Emerg Med. 2012;7(1):65-70. [CrossRef] [PubMed]
 
Delerme S, Ray P. Acute respiratory failure in the elderly: diagnosis and prognosis. Age Ageing. 2008;37(3):251-257. [CrossRef] [PubMed]
 
Lusted LB. Signal detectability and medical decision-making. Science. 1971;171(3977):1217-1219. [CrossRef] [PubMed]
 
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837-845. [CrossRef] [PubMed]
 
McNemar Q. Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika. 1947;12(2):153-157. [CrossRef] [PubMed]
 
Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-172. [CrossRef] [PubMed]
 
Anderson KL, Jenq KY, Fields JM, Panebianco NL, Dean AJ. Diagnosing heart failure among acutely dyspneic patients with cardiac, inferior vena cava, and lung ultrasonography. Am J Emerg Med. 2013;31(8):1208-1214. [CrossRef] [PubMed]
 
Knudsen CW, Omland T, Clopton P, et al. Diagnostic value of B-Type natriuretic peptide and chest radiographic findings in patients with acute dyspnea. Am J Med. 2004;116(6):363-368. [CrossRef] [PubMed]
 
García X, Simon P, Guyette FX, et al. Noninvasive assessment of acute dyspnea in the ED. Chest. 2013;144(2):610-615. [CrossRef] [PubMed]
 
Maisel AS, Krishnaswamy P, Nowak RM, et al; 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(3):161-167. [CrossRef] [PubMed]
 
Peacock WF, Fonarow GC, Ander DS, et al. Society of Chest Pain Centers recommendations for the evaluation and management of the observation stay acute heart failure patient-parts 1-6. Acute Card Care. 2009;11(1):3-42. [CrossRef] [PubMed]
 
Gargani L, Lionetti V, Di Cristofano C, Bevilacqua G, Recchia FA, Picano E. Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets. Crit Care Med. 2007;35(12):2769-2774. [CrossRef] [PubMed]
 
Gargani L, Frassi F, Soldati G, Tesorio P, Gheorghiade M, Picano E. Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides. Eur J Heart Fail. 2008;10(1):70-77. [CrossRef] [PubMed]
 
Januzzi JL Jr, Chen-Tournoux AA, Moe G. Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms. Am J Cardiol. 2008;101(3A):29-38. [CrossRef] [PubMed]
 
Maisel AS, Clopton P, Krishnaswamy P, et al; BNP Multinational Study Investigators. Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study. Am Heart J. 2004;147(6):1078-1084. [CrossRef] [PubMed]
 
Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol. 2002;39(2):202-209. [CrossRef] [PubMed]
 
Eurlings LW, Sanders-van Wijk S, van Kimmenade R, et al. Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score. J Am Coll Cardiol. 2012;60(17):1668-1677. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1 –  Six-zone scanning protocol used for lung ultrasonography evaluation. The anterior chest wall was divided into three zones. Two zones were located anteriorly, in the second intercostal space on the mid-clavicular line, and in the fourth intercostal space on the anterior axillary line, respectively. The third zone was located laterally in the fifth intercostal space on the mid-axillary line. An additional scan was performed on the posterior axillary line at the base of the lungs to assess for the presence of pleural effusion. AAL = anterior axillary line; MAL = mid-axillary line; MC = mid-clavicular line. (The patient provided written consent for the use of this photograph.)Grahic Jump Location
Figure Jump LinkFigure 2 –  Diagnostic accuracy of the different approaches to acute dyspnea in the ED. BNP = brain natriuretic peptide; LR = negative likelihood ratio; LR+ = positive likelihood ratio; LUS = lung ultrasonography; NPV = negative predictive value; NT-pro-BNP = N-terminal pro-brain natriuretic peptide; PPV = positive predictive value.Grahic Jump Location
Figure Jump LinkFigure 3 –  A, Receiver operating characteristic (ROC) curve comparing accuracy of clinical workup, LUS-implemented diagnosis, LUS alone, and chest radiography. B, ROC curve comparing accuracy of clinical workup, LUS-implemented diagnosis, LUS alone, and BNP/NT-pro-BNP levels. See Figure 2 legend for expansion of other abbreviations.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Demographic Characteristics and Medications of Patients Enrolled

Data given as No. (%) unless otherwise indicated. ACE = angiotensin-converting-enzyme; ADHF = acute decompensated heart failure; CAD = coronary artery disease; CKD = chronic kidney disease; IQR = interquartile range.

a 

χ2 test for categorical variables, or Mann-Whitney U test for continuous variables.

b 

Current or remote use.

c 

Any type and/or grade of disorder/disease.

d 

Any type of cardiac rhythm disorders (eg, atrial fibrillation, paroxysmal, persistent or permanent; atrial flutter; sick sinus syndrome; atrioventricular blocks; supraventricular paroxysmal tachycardia).

e 

CKD defined as chronic renal failure with creatinine level > 2 mg/dL (177 μmol/L).

f 

Acetylsalicylic acid, clopidogrel, prasugrel, ticagrelor, ticlopidine, tirofiban, and dypiridamole.

g 

Warfarin, acenocoumarol, any type of heparin, fondaparinux.

Table Graphic Jump Location
TABLE 2 ]  Symptoms Associated With Acute Dyspnea and Clinical Findings Detected at the Time of Patient Presentation in the ED

Data given as No. (%) unless otherwise indicated. See Table 1 legend for expansion of abbreviations.

a 

χ2 test for categorical variables, Mann-Whitney U test, or Student t test for continuous variables.

b 

Tympanic temperature > 38.3°C.

c 

The ratio of Pao2 and Fio2 was calculated using Pao2 (mm Hg) measured at the time of the first arterial blood gas analysis and Fio2 provided, as reported in the case report form. In 83.1% of cases, the blood gas analysis was performed with patients breathing room air (Fio2, 0.21).

d 

Any type of noninvasive mechanical ventilation.

Table Graphic Jump Location
TABLE 3 ]  Net Reclassification Improvementa

LUS = lung ultrasonography. See Table 1 legend for expansion of other abbreviation.

a 

Net reclassification improvement was calculated as ([63 / 463] − [9 / 463]) + ([47 / 542] − [7 / 542]) = 19.1% (95% CI, 14.6%-23.6%; P < .01).

References

Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency department have congestive heart failure? JAMA. 2005;294(15):1944-1956. [CrossRef] [PubMed]
 
Peacock WF, Braunwald E, Abraham W, et al. National Heart, Lung, and Blood Institute working group on emergency department management of acute heart failure: research challenges and opportunities. J Am Coll Cardiol. 2010;56(5):343-351. [CrossRef] [PubMed]
 
Ray P, Birolleau S, Lefort Y, et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Crit Care. 2006;10(3):R82. [CrossRef] [PubMed]
 
Redfield MM. Heart failure—an epidemic of uncertain proportions. N Engl J Med. 2002;347(18):1442-1444. [CrossRef] [PubMed]
 
McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002;106(4):416-422. [CrossRef] [PubMed]
 
McMurray JJ, Adamopoulos S, Anker SD, et al; ESC Committee for Practice Guidelines. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33(14):1787-1847. [CrossRef] [PubMed]
 
Collins SP, Lindsell CJ, Storrow AB, Abraham WT; ADHERE Scientific Advisory Committee, Investigators and Study Group. Prevalence of negative chest radiography results in the emergency department patient with decompensated heart failure. Ann Emerg Med. 2006;47(1):13-18. [CrossRef] [PubMed]
 
Gillespie ND, McNeill G, Pringle T, Ogston S, Struthers AD, Pringle SD. Cross sectional study of contribution of clinical assessment and simple cardiac investigations to diagnosis of left ventricular systolic dysfunction in patients admitted with acute dyspnoea. BMJ. 1997;314(7085):936-940. [CrossRef] [PubMed]
 
Lichtenstein DA, Mezière GA. Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol. Chest. 2008;134(1):117-125. [CrossRef] [PubMed]
 
Volpicelli G, Mussa A, Garofalo G, et al. Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome. Am J Emerg Med. 2006;24(6):689-696. [CrossRef] [PubMed]
 
Liteplo AS, Marill KA, Villen T, et al. Emergency thoracic ultrasound in the differentiation of the etiology of shortness of breath (ETUDES): sonographic B-lines and N-terminal pro-brain-type natriuretic peptide in diagnosing congestive heart failure. Acad Emerg Med. 2009;16(3):201-210. [CrossRef] [PubMed]
 
Grimberg A, Shigueoka DC, Atallah AN, Ajzen S, Iared W. Diagnostic accuracy of sonography for pleural effusion: systematic review. Sao Paulo Med J. 2010;128(2):90-95. [PubMed]
 
Reissig A, Copetti R, Mathis G, et al. Lung ultrasound in the diagnosis and follow-up of community-acquired pneumonia: a prospective, multicenter, diagnostic accuracy study. Chest. 2012;142(4):965-972. [CrossRef] [PubMed]
 
Picano E, Frassi F, Agricola E, Gligorova S, Gargani L, Mottola G. Ultrasound lung comets: a clinically useful sign of extravascular lung water. J Am Soc Echocardiogr. 2006;19(3):356-363. [CrossRef] [PubMed]
 
Volpicelli G, Elbarbary M, Blaivas M, et al; International Liaison Committee on Lung Ultrasound (ILC-LUS) for International Consensus Conference on Lung Ultrasound (ICC-LUS). International evidence-based recommendations for point-of-care lung ultrasound. Intensive Care Med. 2012;38(4):577-591. [CrossRef] [PubMed]
 
Alrajab S, Youssef AM, Akkus NI, Caldito G. Pleural ultrasonography versus chest radiography for the diagnosis of pneumothorax: review of the literature and meta-analysis. Crit Care. 2013;17(5):R208. [CrossRef] [PubMed]
 
Noble VE, Murray AF, Capp R, Sylvia-Reardon MH, Steele DJ, Liteplo A. Ultrasound assessment for extravascular lung water in patients undergoing hemodialysis. Time course for resolution. Chest. 2009;135(6):1433-1439. [CrossRef] [PubMed]
 
Jambrik Z, Monti S, Coppola V, et al. Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water. Am J Cardiol. 2004;93(10):1265-1270. [CrossRef] [PubMed]
 
Agricola E, Bove T, Oppizzi M, et al. “Ultrasound comet-tail images”: a marker of pulmonary edema: a comparative study with wedge pressure and extravascular lung water. Chest. 2005;127(5):1690-1695. [CrossRef] [PubMed]
 
Baldi G, Gargani L, Abramo A, et al. Lung water assessment by lung ultrasonography in intensive care: a pilot study. Intensive Care Med. 2013;39(1):74-84. [CrossRef] [PubMed]
 
Lichtenstein D, Mézière G, Biderman P, Gepner A, Barré O. The comet-tail artifact. An ultrasound sign of alveolar-interstitial syndrome. Am J Respir Crit Care Med. 1997;156(5):1640-1646. [CrossRef] [PubMed]
 
Xirouchaki N, Magkanas E, Vaporidi K, et al. Lung ultrasound in critically ill patients: comparison with bedside chest radiography. Intensive Care Med. 2011;37(9):1488-1493. [CrossRef] [PubMed]
 
Sperandeo M, Varriale A, Sperandeo G, et al. Assessment of ultrasound acoustic artifacts in patients with acute dyspnea: a multicenter study. Acta Radiol. 2012;53(8):885-892. [CrossRef] [PubMed]
 
Lichtenstein DA, Mezière GA, Lagoueyte JF, Biderman P, Goldstein I, Gepner A. A-lines and B-lines: lung ultrasound as a bedside tool for predicting pulmonary artery occlusion pressure in the critically ill. Chest. 2009;136(4):1014-1020. [CrossRef] [PubMed]
 
Volpicelli G, Skurzak S, Boero E, et al. Lung ultrasound predicts well extravascular lung water but is of limited usefulness in the prediction of wedge pressure. Anesthesiology. 2014;121(2):320-327. [CrossRef] [PubMed]
 
Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119(14):1977-2016. [CrossRef] [PubMed]
 
Maisel A. B-type natriuretic peptide levels: diagnostic and prognostic in congestive heart failure: what’s next? Circulation. 2002;105(20):2328-2331. [CrossRef] [PubMed]
 
Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study. Eur Heart J. 2006;27(3):330-337. [CrossRef] [PubMed]
 
Cibinel GA, Casoli G, Elia F, et al. Diagnostic accuracy and reproducibility of pleural and lung ultrasound in discriminating cardiogenic causes of acute dyspnea in the emergency department. Intern Emerg Med. 2012;7(1):65-70. [CrossRef] [PubMed]
 
Delerme S, Ray P. Acute respiratory failure in the elderly: diagnosis and prognosis. Age Ageing. 2008;37(3):251-257. [CrossRef] [PubMed]
 
Lusted LB. Signal detectability and medical decision-making. Science. 1971;171(3977):1217-1219. [CrossRef] [PubMed]
 
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44(3):837-845. [CrossRef] [PubMed]
 
McNemar Q. Note on the sampling error of the difference between correlated proportions or percentages. Psychometrika. 1947;12(2):153-157. [CrossRef] [PubMed]
 
Pencina MJ, D’Agostino RB Sr, D’Agostino RB Jr, et al. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27(2):157-172. [CrossRef] [PubMed]
 
Anderson KL, Jenq KY, Fields JM, Panebianco NL, Dean AJ. Diagnosing heart failure among acutely dyspneic patients with cardiac, inferior vena cava, and lung ultrasonography. Am J Emerg Med. 2013;31(8):1208-1214. [CrossRef] [PubMed]
 
Knudsen CW, Omland T, Clopton P, et al. Diagnostic value of B-Type natriuretic peptide and chest radiographic findings in patients with acute dyspnea. Am J Med. 2004;116(6):363-368. [CrossRef] [PubMed]
 
García X, Simon P, Guyette FX, et al. Noninvasive assessment of acute dyspnea in the ED. Chest. 2013;144(2):610-615. [CrossRef] [PubMed]
 
Maisel AS, Krishnaswamy P, Nowak RM, et al; 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(3):161-167. [CrossRef] [PubMed]
 
Peacock WF, Fonarow GC, Ander DS, et al. Society of Chest Pain Centers recommendations for the evaluation and management of the observation stay acute heart failure patient-parts 1-6. Acute Card Care. 2009;11(1):3-42. [CrossRef] [PubMed]
 
Gargani L, Lionetti V, Di Cristofano C, Bevilacqua G, Recchia FA, Picano E. Early detection of acute lung injury uncoupled to hypoxemia in pigs using ultrasound lung comets. Crit Care Med. 2007;35(12):2769-2774. [CrossRef] [PubMed]
 
Gargani L, Frassi F, Soldati G, Tesorio P, Gheorghiade M, Picano E. Ultrasound lung comets for the differential diagnosis of acute cardiogenic dyspnoea: a comparison with natriuretic peptides. Eur J Heart Fail. 2008;10(1):70-77. [CrossRef] [PubMed]
 
Januzzi JL Jr, Chen-Tournoux AA, Moe G. Amino-terminal pro-B-type natriuretic peptide testing for the diagnosis or exclusion of heart failure in patients with acute symptoms. Am J Cardiol. 2008;101(3A):29-38. [CrossRef] [PubMed]
 
Maisel AS, Clopton P, Krishnaswamy P, et al; BNP Multinational Study Investigators. Impact of age, race, and sex on the ability of B-type natriuretic peptide to aid in the emergency diagnosis of heart failure: results from the Breathing Not Properly (BNP) multinational study. Am Heart J. 2004;147(6):1078-1084. [CrossRef] [PubMed]
 
Morrison LK, Harrison A, Krishnaswamy P, Kazanegra R, Clopton P, Maisel A. Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in patients presenting with dyspnea. J Am Coll Cardiol. 2002;39(2):202-209. [CrossRef] [PubMed]
 
Eurlings LW, Sanders-van Wijk S, van Kimmenade R, et al. Multimarker strategy for short-term risk assessment in patients with dyspnea in the emergency department: the MARKED (Multi mARKer Emergency Dyspnea)-risk score. J Am Coll Cardiol. 2012;60(17):1668-1677. [CrossRef] [PubMed]
 
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543