Accuracy of Several Lung Ultrasound Methods for the Diagnosis of Acute Heart Failure in the ED

A Multicenter Prospective Study
Published:August 02, 2019DOI:https://doi.org/10.1016/j.chest.2019.07.017

      Background

      Early appropriate diagnosis of acute heart failure (AHF) is recommended by international guidelines. This study assessed the value of several lung ultrasound (LUS) strategies for identifying AHF in the ED.

      Methods

      This prospective study, conducted in four EDs, included patients with diagnostic uncertainty based on initial clinical judgment. A clinical diagnosis score for AHF (Brest score) was quantified, followed by an extensive LUS examination performed according to the 4-point (BLUE protocol) and 6-, 8-, and 28-point methods. The primary outcome was AHF discharge diagnosis adjudicated by two senior physicians blinded to LUS measurements. The C-index was used to quantify discrimination.

      Results

      Among the 117 included patients, AHF (n = 69) was identified in 27.4%, 56.2%, 54.8%, and 76.7% of patients with the 4-point (two bilateral positive points), 6-point, 8-point (≥ 1 bilateral positive point), and 28-point (B-line count ≥ 30) methods, respectively. The C-index (95% CI) of the Brest score was 72.8 (65.3-80.3), whereas the C-index of the 4-, 6-, 8-, and 28-point methods were 63.7 (58.5-68.8), 72.4 (65.0-79.8), 74.0 (67.1-80.9), and 72.4 (63.9-80.9). The highest increase in the C-index on top of the BREST score was observed with the 8-point method in the whole population (6.9; 95% CI, 1.6-12.2; P = .010) and in the population with an intermediate Brest score, followed by the 6-point method.

      Conclusions

      In patients with diagnostic uncertainty, the 6-point/8-point LUS method (using the 1 bilateral positive point threshold) improves AHF diagnosis accuracy on top of the BREST score.

      Trial Registry

      ClinicalTrials.gov; No.: NCT03194243; URL: www.clinicaltrials.gov.

      Key Words

      Abbreviations:

      AHF (acute heart failure), LUS (lung ultrasound)
      FOR EDITORIAL COMMENT, SEE PAGE 3
      Dyspnea is one of the most frequent causes of admission to the ED
      • Hunold K.M.
      • Caterino J.M.
      High diagnostic uncertainty and inaccuracy in adult emergency department patients with dyspnea: a national database analysis.
      and represents a significant diagnostic challenge for emergency physicians. Acute heart failure (AHF) is one of the most common etiologies of acute dyspnea.
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      Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis.
      Guidelines recommend that diagnosis should be made as soon as possible to promptly begin appropriate early treatment.
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      2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC.
      • Mebazaa A.
      • Yilmaz M.B.
      • Levy P.
      • et al.
      Recommendations on pre-hospital & early hospital management of acute heart failure: a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine.
      Prognosis is related to initiation time of specific therapies.
      • Matsue Y.
      • Damman K.
      • Voors A.A.
      • et al.
      Time-to-furosemide treatment and mortality in patients hospitalized with acute heart failure.
      In-hospital mortality is typically reported to be > 10%
      • Chouihed T.
      • Buessler A.
      • Bassand A.
      • et al.
      Hyponatraemia, hyperglycaemia and worsening renal function at first blood sample on emergency department admission as predictors of in-hospital death in patients with dyspnoea with suspected acute heart failure: retrospective observational analysis of the PARADISE cohort.
      and has remained stable in the last 30 years.
      Diagnostic approaches include clinical evaluation, chest radiograph, biological tests, and specific biomarkers. Nevertheless, diagnosis remains difficult, especially in ED patients, many of whom feature atypical clinical presentation due to several previous comorbidities and mixed/concomitant etiologies of acute dyspnea.
      • Ray P.
      • Birolleau S.
      • Lefort Y.
      • et al.
      Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis.
      Basset et al
      • Basset A.
      • Nowak E.
      • Castellant P.
      • Gut-Gobert C.
      • Le Gal G.
      • L’Her E.
      Development of a clinical prediction score for congestive heart failure diagnosis in the emergency care setting: the Brest score.
      developed the Brest score for the diagnosis of AHF in ED patients. However, this score classified 50% of cases in the intermediate probability group, hence supporting the importance of developing and promoting “new tools”
      • Girerd N.
      • Seronde M.F.
      • Coiro S.
      • et al.
      Integrative assessment of congestion in heart failure throughout the patient journey.
      that are complementary to clinical scores to achieve a quick diagnosis of AHF in patients admitted for acute dyspnea in the ED.
      Ultrasound has gained widespread use in recent years and is now a highly valuable tool in the ED. Lung ultrasound (LUS) is a quick, reliable, and easy-to-use examination that can improve the diagnostic accuracy for dyspneic patients.
      • Pirozzi C.
      • Numis F.G.
      • Pagano A.
      • Melillo P.
      • Copetti R.
      • Schiraldi F.
      Immediate versus delayed integrated point-of-care-ultrasonography to manage acute dyspnea in the emergency department.
      • Silva S.
      • Biendel C.
      • Ruiz J.
      • et al.
      Usefulness of cardiothoracic chest ultrasound in the management of acute respiratory failure in critical care practice.
      Lichtenstein and Mezière
      • Lichtenstein D.A.
      • Mezière G.A.
      Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol.
      further highlighted the advantages of LUS in ICUs for the evaluation of patients with respiratory distress (ie, the BLUE protocol). Several methods have been secondarily proposed to assess pulmonary congestion using different analysis points, interpretation thresholds, and various assessment conditions.
      • Pivetta E.
      • Goffi A.
      • Lupia E.
      • et al.
      Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study.
      • Volpicelli G.
      • Mussa A.
      • Garofalo G.
      • et al.
      Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome.
      • Volpicelli G.
      • Elbarbary M.
      • Blaivas M.
      • et al.
      International evidence-based recommendations for point-of-care lung ultrasound.
      However, most of these studies focused on patients outside of the ED.
      Given these factors, the current study aimed to evaluate and compare the diagnostic performance of currently available ultrasound protocols for pulmonary congestion assessment (ie, the 4-point [BLUE protocol] and 6-, 8-, and 28-point methods) in patients admitted for acute dyspnea in the ED. The study further aimed to evaluate the diagnostic performance of these methods in patients with intermediate Brest scores (ie, 4-8).

      Methods

       Study Protocol and Design

      This study is a part of the prospective Pathway and Urgent Care of Dyspneic Patient at Emergency Department in Lorraine District (PURPLE) study (CNIL DR-2017-098).

      Pathway and Urgent caRe of dyspneic Patient at the emergency department in LorrainE District (PURPLE). ClinicalTrials.gov. NCT03194243.

      Patients admitted to the ED in four different hospitals, including a university hospital, over a 3-month period were included. All patients aged > 50 years admitted for acute dyspnea for whom the treating physician had diagnostic uncertainty based on his or her initial clinical evaluation were included. Exclusion criteria consisted of traumatic dyspnea and systolic BP < 70 mm Hg.
      For each patient, the Brest score was calculated,
      • Basset A.
      • Nowak E.
      • Castellant P.
      • Gut-Gobert C.
      • Le Gal G.
      • L’Her E.
      Development of a clinical prediction score for congestive heart failure diagnosis in the emergency care setting: the Brest score.
      and a standardized LUS was performed. All clinical and ultrasound analysis data were collected by the emergency physicians and entered into the Clinical Research Form of the study.

       Ultrasound Methods

      Ultrasounds were performed by ultrasound-certified emergency physicians. Twenty-eight-point LUS were performed in all patients: for each point, a B-line grading from 0 to 10 was used. Using the data of this 28-point method, patients were able to be classified according to four published methods (Fig 1).
      • Lichtenstein D.A.
      • Mezière G.A.
      Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol.
      • Pivetta E.
      • Goffi A.
      • Lupia E.
      • et al.
      Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study.
      • Volpicelli G.
      • Mussa A.
      • Garofalo G.
      • et al.
      Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome.
      • Frassi F.
      • Gargani L.
      • Tesorio P.
      • Raciti M.
      • Mottola G.
      • Picano E.
      Prognostic value of extravascular lung water assessed with ultrasound lung comets by chest sonography in patients with dyspnea and/or chest pain.
      Figure thumbnail gr1
      Figure 1A-C, LUS methods: 4- to 28-point method described on a frontal (A) and lateral (B) view. Examples of LUS recordings showing 0 to 3 B-lines (C). LUS = lung ultrasound.

       Four-point method (BLUE protocol)
      • Lichtenstein D.A.
      • Mezière G.A.
      Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol.

      Two scanning sites on each hemithorax: Second intercostal space, mid-clavicular line and fourth intercostal space, anterior axillary line. A positive point was defined as the presence of at least three B-lines. A positive examination was defined, according to the seminal publication,
      • Lichtenstein D.
      • Goldstein I.
      • Mourgeon E.
      • Cluzel P.
      • Grenier P.
      • Rouby J.J.
      Comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome.
      by the presence of at least three B-lines on each scanning site.

       Six-point method
      • Pivetta E.
      • Goffi A.
      • Lupia E.
      • et al.
      Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study.

      Three scanning sites on each hemithorax: Second intercostal space, mid-clavicular line, fourth intercostal space, anterior axillary line, fifth intercostal space, mid-axillary line. A positive point was defined as the presence of at least three B-lines in a given scanning site.

       Eight-point method
      • Volpicelli G.
      • Mussa A.
      • Garofalo G.
      • et al.
      Bedside lung ultrasound in the assessment of alveolar-interstitial syndrome.

      Four scanning sites on each hemithorax: Two anterior points, between the sternum and the anterior axillary line, comprising two scanning sites. Two lateral points between the anterior and the posterior axillary line, comprising two scanning sites. A positive point was defined as the presence of at least three B-lines in a given scanning site.

       Twenty-eight-point method
      • Frassi F.
      • Gargani L.
      • Tesorio P.
      • Raciti M.
      • Mottola G.
      • Picano E.
      Prognostic value of extravascular lung water assessed with ultrasound lung comets by chest sonography in patients with dyspnea and/or chest pain.
      • Jambrik Z.
      • Monti S.
      • Coppola V.
      • et al.
      Usefulness of ultrasound lung comets as a nonradiologic sign of extravascular lung water.

      Sixteen points on the right side and 12 points on the left as described in Figure 1. This examination was used both as a continuous count of overall B-lines as well as in the form of dichotomous variables (≥ 15 or ≥ 30).
      A positive point was defined as the presence of at least three B-lines in a given scanning site. The examinations were then categorized according to the presence and number of bilateral positive points. We considered two definitions of positive examinations: a positive examination was either defined as at least one positive zone bilaterally (ie, at least one on the right lung and at least one on the left lung) or as at least two positive zones bilaterally. The presence of two positive points on each hemithorax, irrespective of their locations (ie, positive points on the superior part of the right thorax and on the inferior part of the left thorax), qualified for being considered as having “≥ 2 bilateral positive points.”

       Outcome

      Diagnostic outcome was the final diagnosis at discharge collected from the patients’ medical records. The final diagnosis of the hospital stay was adjudicated by two senior physicians (emergency physician and cardiologist) blinded to the LUS measurements.

       Sample Size

      A random sample of 120 patients (60 with AHF and 60 without AHF) was necessary, when the sample C-index was equal to 80%, to achieve a two-sided 95% CI width of 16% (ie, with a lower limit equal to 72% and a upper limit equal to 88%) according to the Hanley and McNeil method. This setting also allows use of a CI width < 0.18 for a C-index equal to 75% and a CI width of 0.14 for a C-index of 0.85.

       Statistical Analysis

      All analyses were performed by using R software (the R foundation for Statistical Computation). The two-tailed significance level was set at P < .05.
      Baseline characteristics are described as mean ± SD or median (interquartile range) for continuous variables and frequency (percentage) for categorical variables. Comparison of baseline characteristics according to the AHF and non-AHF groups were conducted by using the nonparametric Wilcoxon test for continuous variables and the χ2 or Fisher exact tests for categorical variables.
      Associations between LUS measurements and AHF were assessed by using logistic regression. ORs with 95% CIs are reported. For certain variables, quasi-complete separation was detected. ORs with CIs were therefore estimated by using a logistic regression model with Firth’s penalized likelihood method. This method provides a solution to the phenomenon of monotone likelihood, which causes parameter estimates of the usual logistic regression model to diverge, with infinite SEs.
      Individual performance of LUS measurements for diagnosing AHF was assessed by the calculation of the C-index, which is very similar to the area under the curve of the receiver-operating characteristic used on univariable data. In addition, the increase in the C-index was calculated to assess the additional value of LUS measurements in addition to the Brest score for the diagnosis of AHF.

      Results

      A total of 117 patients were included, 62% of whom had a hospital discharge diagnosis of AHF (n = 73); only 54% (n = 63) had an AHF diagnosis in the ED (three patients with AHF at the ED had a non-AHF discharge diagnosis and 13 had an AHF diagnosis at discharge but not in the ED), however (Table 1). The population was elderly (mean age, 79.6 ± 11.8 years), mainly female (56%), and frequently had comorbidities. The majority of patients were hospitalized subsequent to ED admission (96%; n = 112), primarily in medical wards (n = 68; 58%); 25% (n = 29) were admitted to ICUs, and only 13% (n = 15) were admitted to a cardiology ward. A majority of patients had an intermediate Brest score (64%; n = 75), both in the AHF group (67%; n = 49) and in the non-AHF group (59%; n = 26).
      Table 1Characteristics of the Study Population
      CharacteristicPopulation (N = 117)No AHF (n = 44)AHF (n = 73)P Value
      No.Mean ± SD or No. (%)No.Mean ± SD or No. (%)No.Mean ± SD or No. (%)
      Clinical characteristics
       Age, y11779.6 ± 11.84477.0 ± 13.67381.2 ± 10.3.088
       Male sex11752 (44)4416 (36)7336 (49).19
       Chronic heart failure11719 (16)443 (7)7316 (22).039
       Chronic pulmonary disease11738 (33)4418 (41)7320 (27).16
       SBP, mm Hg117137.1 ± 25.044131.8 ± 21.273140.3 ± 26.7.11
       DBP, mm Hg11773.1 ± 15.54470.6 ± 12.77374.6 ± 16.9.18
       Heart rate, beats/min11793.6 ± 24.64495.8 ± 21.27392.2 ± 26.5.25
       Respiratory rate, beats/min10627.3 ± 8.63928.6 ± 10.66726.6 ± 7.3.54
       Spo2, %11793.5 ± 5.84491.7 ± 8.27394.6 ± 3.4.045
       NYHA functional score117
       NYHA class III51 (44)20 (45)31 (42)
       NYHA class IV59 (50)22 (50)37 (50)
       Jugular venous distension11719 (16)441 (2)7318 (24).0001
       Hepato-jugular reflux11719 (16)443 (7)7316 (22).039
       Peripheral edema11764 (54)4418 (41)7346 (63).026
       Lungs auscultation1174473< .0001
       Crackles52 (44)4 (9)48 (66)
       Focal auscultatory findings18 (15)12 (27)6 (8)
       Rhonchi23 (20)13 (29.5)10 (13)
       Wheezing8 (7)7 (16)1 (1)
      Biology
       eGFR MDRD, mL/min/1.73 m211660.1 ± 27.54471.6 ± 26.77253.1 ± 25.7.0004
       Natremia, mmol/L115135.9 ± 5.644135.7 ± 5.971136.0 ± 5.4.81
       BNP, pg/mL86946 ± 101727274 ± 281591,254 ± 1,083< .0001
       NT-proBNP, pg/mL152,815 ± 3,7415575 ± 448103,936 ± 4,183.13
       Hemoglobin, g/dL11712.4 ± 2.04413.2 ± 1.97311.9 ± 2.0.0004
       Hematocrit, %11338.6 ± 5.84340.8 ± 5.47037.2 ± 5.6.0008
      Radiology
       Cardiomegaly11768 (58)4413 (29)7355 (75)< .0001
       Pulmonary congestion11759 (50)447 (16)7352 (71)< .0001
       Pleural effusion11735 (30)4412 (27)7323 (3).68
       Pulmonary infection11739 (33)4422 (50)7317 (23).004
      Brest score1174473
      Continuous5.9 ± 2.74.1 ± 2.07.0 ± 2.4< .0001
      Categorized
       0-322 (19)17 (38)5 (7)< .0001
       4-875 (64)26 (59)49 (67)
       9-1520 (17)1 (2)19 (26)
      Diagnosis: AHF
       ED11763 (54)443 (7)7360 (82)< .0001
       At hospitalization discharge11773 (62)4407373 (100)< .0001
      LUS
       Ultrasound quality1157.1 ± 1.6436.9 ± 1.7727.3 ± 1.5.21
       4-point method1174473
      B-line count8.4 ± 8.93.6 ± 3.911.3 ± 9.8< .0001
      ≥1 bilateral positive point40 (34)5 (11)35 (47)< .0001
      ≥2 bilateral positive points20 (17)020 (27)< .0001
       6-point method1174473
      B-line count12.6 ± 12.85.2 ± 5.417.0 ± 13.8< .0001
      ≥1 bilateral positive point46 (39)5 (11)41 (56)< .0001
      ≥2 bilateral positive points29 (25)029 (39)< .0001
       8-point method (superomedial point)1174473
      B-line count15.5 ± 16.65.3 ± 5.821.6 ± 18.0< .0001
      ≥1 bilateral positive point43 (37)3 (7)40 (54)< .0001
      ≥2 bilateral positive points31 (26)1 (2)30 (41)< .0001
       28-point method1174473
      B-line count57.3 ± 58.622.0 ± 21.378.5 ± 63.6< .0001
      B-lines ≥ 1590 (77)25 (57)65 (89)< .0001
      B-lines ≥ 3070 (60)14 (32)56 (78)< .0001
      Hospitalization117112 (95)4440 (91)7372 (98).009
       Medical ward68 (58)32 (73)36 (49)
       ICU29 (24)7 (16)22 (30)
       Cardiology ward15 (12)1 (2)14 (19)
      AHF = acute heart failure; BNP = brain natriuretic peptide; eGFR = estimated glomerular filtration rate; LUS = lung ultrasound; MDRD = Modification of Diet in Renal Disease; NT-proBNP = N-terminal pro-B-type natriuretic peptide; NYHA = New York Heart Association; SBP/DPB = systolic/diastolic blood pressure; Spo2 = blood oxygen saturation.

       Diagnostic Performances in the Overall Study Population

      In a first instance, the Brest score had a good diagnostic value when considered as a continuous variable (C-index = 81.8; 95% CI, 74.2-89.4), which subsequently decreased when using BREST score categories (C-index = 72.8; 95% CI, 65.3-80.3).
      Among the LUS methods, the 4-point method (two bilateral positive points) had the lowest C-index (63.7; 95% CI, 58.5-68.8), whereas the other methods had very similar C-indices (6-point method for ≥ 1 bilateral positive point, 72.4 [95% CI, 65.0-79.8]; 8-point method for ≥ 1 bilateral positive point, 74.0 [95% CI, 67.1-80.9]; and 28-point method for B-lines ≥30, 72.4 [95% CI, 63.9-80.9]) (Table 2).
      Table 2Association Between the Different Lung Ultrasound Techniques and AHF Diagnosis (in Univariable Analysis and Following Adjustment on the Brest Score)
      VariableUnivariable AssociationAdjusted on Brest Score (Continuous)
      OR (CI 95%)P ValueOR (CI 95%)P Value
      4-point method
       B-line count1.20 (1.09-1.31)< .00011.22 (1.10-1.36).0003
       ≥ 1 bilateral positive point7.18 (2.54-20.29).00027.49 (2.29-24.53).0009
       ≥ 2 bilateral positive points34.10 (4.46-4381.20)< .000123.96 (2.57-3248.84).002
      6-point method
       B-line count1.14 (1.07-1.22)1.17 (1.08-1.26).0002
       ≥ 1 bilateral positive point9.99 (3.53-28.26)12.08 (3.51-41.53)< .0001
       ≥ 2 bilateral positive points59.00 (7.84-7559.37)< .000151.15 (6.08-6740.40)< .0001
      8-point method
       B-line count1.15 (1.08-1.23)< .00011.15 (1.07-1.24)< .0001
       ≥ 1 bilateral positive point16.57 (4.70-58.38)< .000115.68 (3.87-63.48).0001
       ≥ 2 bilateral positive points30.00 (3.91-229.96).00138.75 (4.19-358.43).001
      See Table 1 legend for expansion of abbreviation.
      The 6-point method (≥ 1 bilateral positive point) had a specificity near 90% with a relatively low sensitivity (56.2%; 95% CI, 41.1-67.8). The 8-point method (≥ 1 bilateral positive point) had a higher specificity (93.2%; 95% CI, 81.3-98.6) and similar sensitivity (54.8%; 95% CI, 42.7-66.5). In contrast, the 28-point method had high sensitivity (B-lines ≥ 15, 89.0 [95% CI, 79.5-95.1]; B-lines ≥ 30, 76.7 [95% CI, 65.4-85.8]) but low specificity (B-lines ≥ 15, 43.2 [95% CI, 28.3-59.0]; B-lines ≥ 30, 68.2 [95% CI, 52.4-81.4]) (Table 2).
      For the 6- and 8-point methods, the use of the ≥ 1 bilateral positive point threshold yielded a higher C-index as well as a better sensitivity (13% and 6%, respectively) and moderately lower specificity (–4% and –11%) (Table 2).
      Each method provided significant added value to the Brest score as assessed by changes in the C-index. However, the highest increase in the C-index was observed for the 6-point method (6.7; 95% CI, 0.9-12.5; P = .024) and the 8-point method (6.9; 95% CI, 1.6-12.2; P = .010) (Fig 2, Table 3).
      Figure thumbnail gr2
      Figure 2Receiver-operating characteristic curves for acute heart failure diagnosis (B-line count). See legend for expansion of abbreviation.
      Table 3Diagnostic Performance of the Various LUS Techniques in Conjunction With the Brest Score for Pulmonary Congestion Assessment
      VariablePerformanceDiagnostic Value of LUS Techniques in Addition to the Brest Score
      C-Index Value of the Considered Parameter (95% CI)Specificity (95% CI)Sensitivity (95% CI)C-Index Value of Brest Score and Considered Parameter (95% CI)P ValueC-Index Increase in Addition to the Brest Score (95% CI)P Value
      Overall population
       Brest score
      Continuous81.8 (74.2 to 89.4)
       Categories (0-3, 4-8, 9-15)72.8 (65.3 to 80.3)
       4-point method
      B-line count76.7 (68.2 to 85.1)88.1 (82.0 to 94.1)< .00016.3 (1.0 to 11.6).020
      ≥ 1 bilateral positive point68.3 (60.8 to 75.8)88.6 (75.4 to 96.2)47.9 (36.1 to 60.0)86.6 (80.1 to 93.1)< .00014.8 (–0.1 to 9.6).053
      ≥ 2 bilateral positive points63.7 (58.5 to 68.8)100.0 (92.0 to 100.0)27.4 (17.6 to 39.1)85.3 (78.6 to 91.9)< .00013.5 (0.4 to 6.5).026
       6-point method
      B-line count78.2 (70.1 to 86.4)89.1 (83.3 to 94.8)< .00017.3 (1.7 to 12.8).010
      ≥ 1 bilateral positive point72.4 (65.0 to 79.8)88.6 (75.4 to 96.2)56.2 (44.1 to 67.8)88.5 (82.5 to 94.5)< .00016.7 (0.9 to 12.5).024
      ≥ 2 bilateral positive points69.9 (64.2 to 75.5)100.0 (92.0 to 100.0)39.7 (28.5 to 51.9)88.4 (82.6 to 94.2)< .00016.6 (2.3 to 10.8).002
       8-point method
      B-line count81.8 (74.3 to 89.3)….90.6 (85.2 to 96.0)< .00018.8 (2.8 to 14.7).004
      ≥1 bilateral positive point74.0 (67.1 to 80.9)93.2 (81.3 to 98.6)54.8 (42.7 to 66.5)88.7 (82.9 to 94.6)< .00016.9 (1.6 to 12.2).010
      ≥ 2 bilateral positive points69.4 (63.3 to 75.5)97.7 (88.0 to 99.9)41.1 (29.7 to 53.2)88.7 (82.8 to 94.7)< .00016.9 (1.7 to 12.1).009
      Patients with intermediate Brest score
       Brest score
      Continuous71.7 (59.9 to 83.6)NA
       4-point method
      B-line count75.9 (65.0 to 86.8)81.6 (71.7 to 91.5)< .00019.9 (0.1 to 19.6).047
      ≥ 1 bilateral positive point68.7 (59.3 to 78.2)88.5 (69.8 to 97.6)49.0 (34.4 to 63.7)78.5 (67.8 to 89.2)< .00016.8 (–2.1 to 15.7).13
      ≥ 2 bilateral positive points61.2 (55.3 to 67.1)100.0 (86.8 to 100.0)22.4 (11.8 to 36.6)76.5 (65.9 to 87.1)< .00014.8 (0.3 to 9.3).037
       6-point method
      B-line count78.4 (68.0 to 88.7)83.4 (74.0 to 92.7)< .000111.6 (1.9 to 21.4).020
      ≥1 bilateral positive point71.8 (62.4 to 81.2)88.5 (69.8 to 97.6)49.0 (34.4 to 63.7)80.6 (70.4 to 90.8)< .00018.9 (–0.2 to 17.9).054
      ≥2 bilateral positive points69.4 (62.5 to 76.3)100.0 (86.8 to 100.0)22.4 (11.8 to 36.6)81.4 (71.9 to 90.8)< .00019.6 (3.1 to 16.1).004
       8-point method
      B-line count81.0 (71.2 to 90.8)85.4 (76.4 to 94.3)< .000113.6 (3.4 to 23.8).009
      ≥ 1 bilateral positive point72.7 (63.9 to 81.5)92.3 (74.9 to 99.1)53.1 (38.3 to 67.5)82.4 (72.6 to 92.2)< .000110.7 (1.7 to 19.7)0.020
      ≥ 2 bilateral positive points67.5 (59.6 to 75.3)96.2 (80.4 to 99.9)38.8 (25.2 to 53.8)80.4 (70.3 to 90.4)< .00018.6 (0.9 to 16.4)0.029
      NA = not appropriate.
      See Table 1 legend for expansion of other abbreviations.

       Diagnostic Performances With Intermediate Brest Scores

      In patients (n = 75) with intermediate Brest scores (4-8), the 4-point method (two positive points bilaterally) had a C-index of 61.2 (95% CI, 55.3-67.1) and an added value to the Brest score of < 5 as measured by an increase in the C-index. In contrast, the 6- and 8-point methods had a C-index > 70 when considering ≥ 1 positive point bilaterally (71.8 [95% CI, 62.4-81.2] and 72.7 [95% CI, 63.9-81.5], respectively).
      Similarly to the results in the overall population, the 6- and 8-point methods (≥ 1 bilateral positive point) had a specificity near 90% and a sensitivity near 50%. For the 8-point method, the use of the ≥ 1 bilateral positive point threshold yielded a higher C-index as well as better sensitivity (14% increase) and moderately lower specificity (4% decrease).
      A significant increase in C-index over the BREST score was only identified for the 8-point method (increase in C-index = 10.7; 95% CI, 1.7 to 19.7; P = .020). However, the increase in the C-index with the 6-point method had a very similar point estimate (increase in C-index = 8.9; 95% CI, –0.2 to 17.9; P = .054). Importantly, the 28-point method had a lower increase in the C-index of 6.8 (95% CI, –2.6 to 16.1), which was not statistically significant (P = .16) (Fig 2, Table 3).

      Discussion

      In the present study, the 6- and 8-point methods were found to be the most relevant LUS methods for establishing an AHF diagnosis in the ED. This result was further confirmed among patients with intermediate Brest scores. In addition, all ultrasound methods (particularly the 6- and 8-point methods) provided a diagnostic added value in addition to the Brest score, both in the whole population (increase in C-index 8-point method = 6.9; 95% CI, 1.6-12.2; P = .010) and in patients with intermediate Brest scores (increase in C-index 8-point method = 10.7; 95% CI, 1.7-19.7; P = .020). The main results and techniques used are summarized in Figure 2.
      Importantly, we identified a somewhat lower C-index for the diagnosis of AHF than that previously reported in a meta-analysis
      • Martindale J.L.
      • Wakai A.
      • Collins S.P.
      • et al.
      Diagnosing acute heart failure in the emergency department: a systematic review and meta-analysis.
      in which AHF identified on LUS proved to be a diagnostic variable with discriminatory value (positive likelihood ratio, 7.4 [95% CI, 4.2-12.8]; negative likelihood ratio, 0.16 [95% CI, 0.05-0.51]) (e-Tables 1, 2) and for which the authors acknowledged the high statistical heterogeneity for these pooled estimates (I2 = 78% and I2 = 99%, respectively). However, contrary to the aforementioned studies, the current analysis was conducted in the specific setting of “real-life” patients admitted to the ED for whom the treating physician had diagnostic uncertainty based on his or her initial clinical evaluation. Our results can be summarized as shown in Figure 3.
      Figure thumbnail gr3
      Figure 3Diagnostic performance of the Brest score and LUS methods. See legend for expansion of abbreviation.

       Brest Score and AHF

      Brest score is a clinical score recently developed for AHF diagnosis, with three probability categories: low, intermediate, and high. Our study confirmed its good diagnostic capacity when considered as a continuous value analysis, although it was decreased (C-index, 72.8; 95% CI, 65.3-80.3) when dichotomized as risk categories. Indeed, the Brest score efficiently rules out AHF diagnosis for scores < 4 and affirms the diagnosis for scores > 9. However, for patients with an intermediate score (4-8), other complementary tools (biomarkers and/or LUS)
      • Pirozzi C.
      • Numis F.G.
      • Pagano A.
      • Melillo P.
      • Copetti R.
      • Schiraldi F.
      Immediate versus delayed integrated point-of-care-ultrasonography to manage acute dyspnea in the emergency department.
      seemingly appear necessary to improve diagnostic accuracy.
      • Chouihed T.
      • Coiro S.
      • Zannad F.
      • Girerd N.
      Lung ultrasound: a diagnostic and prognostic tool at every step in the pathway of care for acute heart failure.

       LUS Methods Using Six or More Scanning Sites

      LUS is recommended by international guidelines.
      • Mebazaa A.
      • Yilmaz M.B.
      • Levy P.
      • et al.
      Recommendations on pre-hospital & early hospital management of acute heart failure: a consensus paper from the Heart Failure Association of the European Society of Cardiology, the European Society of Emergency Medicine and the Society of Academic Emergency Medicine.
      It is reliable, reproducible, quick, and easy to use, which prompted its increasing use in patients with acute dyspnea. Its diagnostic performance was reported to be excellent in a large meta-analysis (sensitivity, 94.1% [95% CI, 81.3-98.3]; specificity, 92.4% [95% CI, 84.2-96.4]) for an AHF diagnosis.
      • Al Deeb M.
      • Barbic S.
      • Featherstone R.
      • Dankoff J.
      • Barbic D.
      Point-of-care ultrasonography for the diagnosis of acute cardiogenic pulmonary edema in patients presenting with acute dyspnea: a systematic review and meta-analysis.
      In addition, Zanobetti et al
      • Zanobetti M.
      • Scorpiniti M.
      • Gigli C.
      • et al.
      Point-of-care ultrasonography for evaluation of acute dyspnea in the ED.
      reported that the diagnostic accuracy of LUS is better for AHF than for other etiologies of acute dyspnea and that 30 min of training is sufficient to provide good expertise.
      • Chiem A.T.
      • Chan C.H.
      • Ander D.S.
      • Kobylivker A.N.
      • Manson W.C.
      Comparison of expert and novice sonographers’ performance in focused lung ultrasonography in dyspnea (FLUID) to diagnose patients with acute heart failure syndrome.
      • Noble V.E.
      • Lamhaut L.
      • Capp R.
      • et al.
      Evaluation of a thoracic ultrasound training module for the detection of pneumothorax and pulmonary edema by prehospital physician care providers.
      However, in these previous studies, a number of LUS methods were used, such that the indicated method in the aforementioned meta-analysis is unclear. Moreover, a head-to-head comparison of each available method for AHF diagnosis was not conducted. In addition, previous studies typically did not specify if the clinical setting of the patients required the use of LUS. Indeed, it is likely that in patients with very unequivocal clinical pictures, the value of LUS is moderate. Importantly, to the best of our knowledge, its added value on top of the Brest score, a recent and powerful clinical diagnostic tool, has not been previously assessed.
      In the current study, the 6- and 8-point methods were the most discriminative LUS tools for identifying AHF in elderly patients (mean age, 79.6 years) in whom the ED physicians perceived diagnostic uncertainty. Importantly, in our study, uncertainty was purely physician driven. This explains why only two-thirds of the population would qualify for uncertainty (ie, intermediate risk of HF) using the Brest score. In this “real-life” clinical setting, the 6- or 8-point method significantly increased the discrimination for AHF diagnosis in addition to the Brest score (Table 3) along with an isolated C-index (ie, not taking into account clinical features) > 70. In addition, the diagnostic performance of LUS was maintained in patients with intermediate BREST scores, which further strengthens the ability of LUS to correctly identify AHF in patients with the most clinical uncertainty.
      Although the current study reports less evocative C-index values than in previous reports,
      • Martindale J.L.
      • Wakai A.
      • Collins S.P.
      • et al.
      Diagnosing acute heart failure in the emergency department: a systematic review and meta-analysis.
      • Wang Y.
      • Shen Z.
      • Lu X.
      • Zhen Y.
      • Li H.
      Sensitivity and specificity of ultrasound for the diagnosis of acute pulmonary edema: a systematic review and meta-analysis.
      it should be emphasized that only patients with true diagnostic uncertainty were considered in this analysis, which could have decreased the diagnostic performance of LUS. In this particular setting, an isolated C-index ≥ 70% together with a significant increase of 6% to 10% in the C-index suggest a strong and clinically relevant improvement in diagnostic accuracy for AHF in actual clinical settings focusing on the most difficult cases. These results further confirm the strong diagnostic ability of LUS.

       LUS Methods Using Four Scanning Sites

      The BLUE protocol technique, developed in an ICU by Lichtenstein and Mezière,
      • Lichtenstein D.A.
      • Mezière G.A.
      Relevance of lung ultrasound in the diagnosis of acute respiratory failure: the BLUE protocol.
      is the most widely used and taught LUS technique. However, in the current study, the diagnostic ability of a 4-point LUS technique for diagnosing AHF was somewhat less than that of other methods which rely on a greater number of scanning points (6-28). The BLUE protocol, relying on four anterior scanning sites to identify AHF, may be less effective in ED patients due to the lower severity of patients with dyspnea (and subsequent pulmonary features/lesions) admitted in the ED compared with patients admitted in ICUs. Patients admitted in the ED are likely to exhibit less extensive pulmonary abnormalities than patients admitted in the ICU and may therefore benefit from LUS techniques involving six or more scanning sites.

       Perspectives

      LUS is a new helpful tool in the ED as well as in the prehospital setting. Although echocardiography can assess cardiac dysfunction and filling pressures, the latter requires trained practitioners and can be difficult to perform in the setting of acute dyspnea. Our results show that LUS using a 6- or 8-point method, as in other reports,
      • Pivetta E.
      • Goffi A.
      • Nazerian P.
      • et al.
      Lung ultrasound integrated with clinical assessment for the diagnosis of acute decompensated heart failure in the emergency department: a randomized controlled trial.
      improves the diagnostic accuracy of AHF in the ED. Notwithstanding, although the specificity of LUS using either a 6- or 8-point method herein was similar to other reports, the sensitivity documented in the current study was only about 50%, which is much lower than the 90.5% (87.4-93) reported by Pivetta et al.
      • Pivetta E.
      • Goffi A.
      • Lupia E.
      • et al.
      Lung ultrasound-implemented diagnosis of acute decompensated heart failure in the ED: a SIMEU multicenter study.
      However, this previous study was performed by an ED group with extensive experience in LUS, which may have resulted in its higher diagnostic performance. In addition, the differences in diagnostic performance could also be partly related to the absence of identification of lung sliding and condensation in the current study. In addition, LUS alone may not be sufficient to fully identify AHF in patients with high diagnostic uncertainty. Nazerian et al
      • Nazerian P.
      • Vanni S.
      • Zanobetti M.
      • et al.
      Diagnostic accuracy of emergency Doppler echocardiography for identification of acute left ventricular heart failure in patients with acute dyspnea: comparison with Boston criteria and N-terminal prohormone brain natriuretic peptide.
      reported a good diagnostic performance for simplified echocardiography performed by emergency physicians for AHF diagnosis. Other studies also suggest that using the size and collapsibility of the inferior vena cava, or other markers, can improve diagnostic accuracy in dyspneic patients.
      • Bataille B.
      • Riu B.
      • Ferre F.
      • et al.
      Integrated use of bedside lung ultrasound and echocardiography in acute respiratory failure: a prospective observational study in ICU.
      • Laffin L.J.
      • Patel A.V.
      • Saha N.
      • et al.
      Focused cardiac ultrasound as a predictor of readmission in acute decompensated heart failure.
      • Öhman J.
      • Harjola V.P.
      • Karjalainen P.
      • Lassus J.
      Rapid cardiothoracic ultrasound protocol for diagnosis of acute heart failure in the emergency department.
      Furthermore, Laursen et al
      • Laursen C.B.
      • Sloth E.
      • Lambrechtsen J.
      • et al.
      Focused sonography of the heart, lungs, and deep veins identifies missed life-threatening conditions in admitted patients with acute respiratory symptoms.
      showed that an algorithm using cardiac, vascular, and LUS resulted in an improved early diagnostic accuracy. Thus, the use of an ultrasound-based algorithm rather than an LUS-centered algorithm may be needed to further improve the accuracy of AHF diagnosis. Importantly, studies advocating a multimodal ultrasound approach for improving early diagnostic accuracy do not provide a precise algorithm. We believe that such an algorithm should be validated. It is hoped that the Evaluation of the Feasibility and Accuracy of an Ultrasound Algorithm for Acute Dyspnea Diagnosis in the Emergency Department (EMERALD-US) study will be able to provide reliable evidence regarding an integrated ultrasound algorithm in the field of acute dyspnea admitted in the ED.

      Feasibility and Accuracy of an Ultrasound Algorithm for Acute Dyspnea Diagnosis in the Emergency Department (EMERALD-US). ClinicalTrials.gov. NCT03691857.

       Limitations

      The present prospective multicenter study has certain limitations. First, various ultrasound devices were used as well as various patient positions
      • Frasure S.E.
      • Matilsky D.K.
      • Siadecki S.D.
      • Platz E.
      • Saul T.
      • Lewiss R.E.
      Impact of patient positioning on lung ultrasound findings in acute heart failure.
      (it is, however, likely that most patients were in a semi-seated position), which could have resulted in some heterogeneity. However, given that LUS is likely to occupy an increasing place in emergency settings, including with various ultrasound devices, in various positions, pragmatic studies such as the current one more aptly reflect this intrinsic heterogeneity.
      Uncertainty was an inclusion criteria but was purely physician-driven. This could have introduced some heterogeneity in the data as the perception of uncertain situations might vary across physicians.
      The adjudicated diagnosis used for the current analysis was based on the hospitalization report extracted from the medical record. This diagnosis could have been influenced by the LUS results. However, the final diagnosis was adjudicated by two senior physicians blinded to the LUS measurements.

      Conclusions

      The current study suggests that LUS using the 8-point/6-point method improves AHF diagnosis in addition to the BREST score, especially in patients with intermediate BREST scores. Validated algorithms centered not only on the positive diagnosis of AHF but also on the competing diagnosis of dyspnea (eg, pneumonia) using LUS, vascular ultrasound, and simplified echocardiography could further improve LUS diagnostic accuracy in the ED.

      Acknowledgments

      Author contributions: A. B. U. and T. C. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis, including and especially any adverse effects. A. B. served as principal author. T. C. and N. G. contributed substantially to the study design. K. D., T. C., and N. G. contributed substantially to data analysis and interpretation, and A. B. U., T. C., K. D., A. B., M. H. M., Y. G., A. P., E. A., L. N., D. J., M. K., S. C., P. R., and N. G. contributed substantially to the writing of the manuscript.
      Financial/nonfinancial disclosures: The authors have reported to CHEST the following: P. R. and N. G. are funded by a public grant overseen by the French National Research Agency (ANR) as part of the second “Investissements d’Avenir” program FIGHT-HF [reference: ANR-15-RHU-0004] and by the French PIA project “Lorraine Université d’Excellence” [reference ANR-15-IDEX-04-LUE]. P. R. has received board membership fees from Novartis, Relypsa, and Steathpeptides. T. C. reports honoraria from Novartis. N. G. reports honoraria from Novartis, Boehringer, and Servier. None declared (A. Buessler, K.D., A. Bassand, M. H.-M., Y. G., A. P., E. A., L. N., D. J., M. K., S. C.).
      Additional information: The e-Tables can be found in the Supplemental Materials section of the online article.

      Supplementary Data

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