Rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating heart failure from pulmonary disease as the cause of acute dyspnea in the emergency setting
© Kajimoto et al.; licensee BioMed Central Ltd. 2012
Received: 10 September 2012
Accepted: 29 November 2012
Published: 4 December 2012
Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the emergency setting is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, and decrease mortality. In the present study, we examined the screening potential of rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating acute heart failure syndromes (AHFS) from primary pulmonary disease in patients with acute dyspnea in the emergency setting.
Between March 2011 and March 2012, 90 consecutive patients (45 women, 78.1 ± 9.9 years) admitted to the emergency room of our hospital for acute dyspnea were enrolled. Within 30 minutes of admission, all patients underwent conventional physical examination, rapid ultrasound (lung-cardiac-inferior vena cava [LCI] integrated ultrasound) examination with a hand-held device, routine laboratory tests, measurement of brain natriuretic peptide, and chest X-ray in the emergency room.
The final diagnosis was acute dyspnea due to AHFS in 53 patients, acute dyspnea due to pulmonary disease despite a history of heart failure in 18 patients, and acute dyspnea due to pulmonary disease in 19 patients. Lung ultrasound alone showed a sensitivity, specificity, negative predictive value, and positive predictive value of 96.2, 54.0, 90.9, and 75.0%, respectively, for differentiating AHFS from pulmonary disease. On the other hand, LCI integrated ultrasound had a sensitivity, specificity, negative predictive value, and positive predictive value of 94.3, 91.9, 91.9, and 94.3%, respectively.
Our study demonstrated that rapid evaluation by LCI integrated ultrasound is extremely accurate for differentiating acute dyspnea due to AHFS from that caused by primary pulmonary disease in the emergency setting.
KeywordsAcute dyspnea Ultrasound device Emergency department Acute heart failure syndromes
Acute dyspnea is one of the main reasons for admission to the emergency department (ED). Physicians working in the ED often need to make a rapid diagnosis and devise a treatment plan on the basis of limited clinical information[2, 3]. In paticular, acute heart failue syndromes (AHFS) are challenging, since the clinical, radiographic, and laboratory parameters have variable diagnostic value because AHFS are a heterogeneous set of clinical syndromes. Traditional diagnostic criteria for heart failure are based on the history, physical examination, and chest radiograph findings[5–8]. However, these criteria are often not very useful for ED patients because of only having intermediate accuracy, i.e., high specificity with lower sensitivity. Bedside maneuvers and tests that deliver rapid and reliable results represent a cornerstone of ED diagnostics[1, 2]. Recently, it was reported that detection of pulmonary interstitial edema by lung ultrasound evaluation of B-lines has a high diagnostic accuracy for differentiating cardiac-related acute dyspnea from that due to chronic obstructive pulmonary disease (COPD) or bronchial asthma in the ED[3, 10–14]. However, it can be very challenging to differentiate AHFS from severe bilateral pneumonia, pulmonary fibrosis, acute lung injury, or acute respiratory distress syndrome (ARDS) by lung ultrasound alone, because B-lines are not specific for cardiogenic pulmonary edema despite being a very sensitive indicator[12, 13, 15]. In order to rapidly and accurately identify the etiology in patients with acute dyspnea, assessment of LV systolic function, the severity of valvular regurgitation, and the severity of volume overload is mandatory, not only to confirm the diagnosis of AHFS but also to help determine the optimal initial treatment[2, 16–21]. To assess the severity of volume overload, it has been reported that the right atrial pressure can be estimated by measuring the diameter of the inferior vena cava (IVC) using echocardiography[22–24]. Recently, Gargani suggested that adding lung ultrasound to echocardiography (integrated cardiopulmonary ultrasound) could help to differentiate the main causes of acute dyspnea. However, the usefulness of integrated ultrasound evaluation of the lungs, heart, and IVC for determining the etiology of acute dyspnea in the ED has not been adequately studied. Therefore, we examined the screening potential of rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound for differentiating AHFS from primary pulmonary disease in ED patients with acute dyspnea.
The study protocol was approved by our local ethics committee. From March 2011 to March 2012, 90 consecutive patients admitted to the ED of our hospital with acute dyspnea were enrolled. Patients with acute coronary syndrome or chest injury were excluded from this study. In addition, patients who had acute dyspnea due to neither cardiac nor pulmonary cause were excluded from this study. Within 30 minutes of admission, all enrolled patients received conventional physical examination, rapid lung, cardiac, and inferior vena cava [IVC] ultrasound with a hand-held device (Vscan®), electrocardiography, blood tests (including brain natriuretic peptide assay), and chest X-ray in the emergency room. This study is being conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from the patient for publication of this report and any accompanying images.
Rapid lung, cardiac, and IVC integrated ultrasound
Assay of brain natriuretic peptide (BNP)
Peripheral venous blood samples were obtained from each patient at admission, and then 5 ml of whole blood was placed into a prechilled vacuum tube containing EDTA for subsequent measurement of BNP. Immediately after blood sampling, each tube was placed on ice and centrifuged at 2,500 rpm and 4°C to obtain plasma. Then the plasma BNP level was measured by immunoradiometric assay using an antibody for human BNP (Shionogi Co. Ltd., Tokyo, Japan).
Confirmation of diagnosis
The initial diagnosis was determined for each patient by one or two cardiologists, who performed lung-cardiac-IVC (LCI) integrated ultrasound evaluation within 3 minutes on each patient in the ED. Confirmation that acute dyspnea was due to a cardiac etiology (AHFS) was based on a positive lung ultrasound examination combined with abnormal findings on either cardiac or IVC ultrasound in the ED (Figure 1). To determine the final diagnosis, two cardiologists and one pneumologist, who were blinded to the results of the LCI integrated ultrasound at admission, independently reviewed each patient’s medical records and classified them as having acute dyspnea due to AHFS, a history of HF but acute dyspnea due to a non-cardiac cause, or non-cardiac acute dyspnea. Confirmation of AHFS was based on the generally accepted Framingham criteria (two major criteria or one major and two minor criteria), with corroborative information including the medical history, hospital course (response to diuretics and vasoactive agents, or results of hemodynamic monitoring), and routine laboratory test data (including BNP)[5, 38]. The category of pulmonary acute dyspnea included pulmonary embolism and primary lung diseases (pneumonia, asthma, COPD, pulmonary fibrosis, or acute respiratory distress syndrome), with or without underlying LV systolic dysfunction but with no evidence of decompensated HF at admission.
Analyses were performed with SAS 9.1 software (SAS Institute, Cary, North Carolina). Quantitative variables were compared by using Student’s t-test, and dichotomous variables were compared with the chi-square test. The area under the receiver operating characteristic curves and the Youden index were calculated to define the optimum cut-off value of BNP for differentiating AHFS from pulmonary disease. The sensitivity, specificity, negative predictive value, and positive predictive value were calculated according to standard definitions. Two-tailed P values of less than 0.05 were considered to indicate a statistically significant difference. All analyses were performed by an independent biostatistics center (Statz Institute, Inc., Tokyo, Japan).
Baseline characteristics in overall patients and according to final diagnosis
All patients (n = 90)
AHFS group (n = 53)
Pulmonary group (n = 37)
Mean age, yrs
78.1 ± 9.9
77.7 ± 10.3
78.6 ± 9.2
Prior hospitalization for heart failure
Chronic obstructive pulmonary disease
History of atrial fibrillation
Medications prior to admission
Spironolactone or Eplerenone
ACE inhibitor or ARB
Calcium channel blocker
Brain natriuretic peptide, pg/ml
461.1 ± 451.9
622.0 ± 505.3
230.7 ± 208.2
Blood urea nitrogen, mg/dl
25.6 ± 14.3
26.0 ± 15.2
24.8 ± 13.0
Serum creatinine, mg/dl
1.07 ± 0.51
1.12 ± 0.58
0.99 ± 0.36
C-reactive protein, mg/dl
3.64 ± 5.73
1.96 ± 3.17
6.05 ± 7.52
Symptoms on admission
Paroxysmal nocturnal dyspnea
Signs on admission
Jugular venous distension
Reduced EF (LVEF <40%)
MR ≥ moderate
0 ( 0.0)
TR ≥ moderate
IVC collapsibility <50%
Relation between plasma BNP and final diagnosis
Patients with acute dyspnea due to AHFS had a BNP level of 622.0 ± 505.3 pg/ml, which was significantly higher than the BNP level of 230.7 ± 208.2 pg/ml in patients with a final diagnosis of pulmonary disease (p < 0.001). In the group with acute dyspnea due to pulmonary disease, the 18 patients with a history of heart failure had a significantly higher BNP level compared to the 19 patients without a history of heart failure (396.7 ± 176.5 vs. 73.4 ± 59.6 pg/ml, p < 0.001). The BNP level of patients with a history of heart failure and dyspnea due to pulmonary disease showed no significant difference from that of the patients with acute dyspnea due to AHFS (396.7 ± 176.5 vs. 622.0 ± 505.3 pg/ml; p = 0.069). In addition, the BNP level of patients with ARDS (n = 5) showed no significant difference from that of patients with acute dyspnea due to AHFS (369.5 ± 246.3 vs. 622.0 ± 505.3 pg/ml; p = 0.277). The ability of BNP to differentiate AHFS from pulmonary disease was assessed by ROC analysis. The area under the ROC curve for differentiating AHFS from pulmonary disease with BNP was 0.750 (95% confidence interval: 0.698 to 0.804). A BNP value of 663.2 pg/ml had a sensitivity of 37.0%, specificity of 97.2%, negative predictive value of 50.7%, and positive predictive value of 95.2% for differentiating AHFS from pulmonary disease.
Lung-cardiac-inferior vena cava (LCI) integrated ultrasound
Plasma BNP, lung ultrasound alone or combined with BNP, cardiac findings, and the LCI integrated ultrasound for diagnosis of AHFS
BNP ≥100 pg/ml
Lung ultrasound alone
Both Lung ultrasound and BNP (≥100 pg/ml)
Reduced EF (LVEF <40%)
MR or TR ≥ moderate
IVC collapsibility <50%
Both preserved EF and MR ≥ moderate
Both reduced EF and either MR or TR ≥ moderate
Lung-cardiac-inferior vena cava (LCI) integrated ultrasound
The present study demonstrated that rapid evaluation by lung-cardiac-inferior vena cava (LCI) integrated ultrasound has a higher diagnostic accuracy for differentiating acute dyspnea due to AHFS from pulmonary acute dyspnea (including COPD/asthma, pulmonary fibrosis, and ARDS) compared with lung ultrasound either alone or in combination with plasma BNP assay. These findings suggest that LCI integrated ultrasound has become a fundamental tool for diagnostic evaluation of patients with acute dyspnea and selection of early treatment in the emergency setting.
Rapid and accurate diagnosis and management can be lifesaving for patients with acute dyspnea. However, making a differential diagnosis and selecting early treatment for patients with acute dyspnea in the ED is a clinical challenge that requires complex decision-making in order to achieve hemodynamic balance, improve functional capacity, and decrease mortality and the length of hospital stay. Methods for evaluation of emergency patients with possible AHFS include the history, physical examination, chest radiography, 12-lead electrocardiography, and measurement of BNP or N-terminal pro-BNP[5–10]. Among these methods, chest radiography is a cornerstone in the diagnostic evaluation of acute dyspnea. Although chest radiography serves a vital role in the evaluation of patients with acute dyspnea, including the identification of various causes, the lack of radiographic signs of congestion does not exclude AHFS[2, 41]. Recently, BNP and N-terminal pro-BNP have been studied extensively and are frequently used in clinical practice. However, some recent randomized trials on the use of BNP to aid in diagnosis or serial BNP levels to dictate therapy in the acute setting found no improvement of diagnostic accuracy or important clinical outcomes because age, sex, and renal dysfunction have an impact on natriuretic peptide levels and need to be considered when test results are interpreted[42, 43]. Also, patients with a history of decompensated HF can have chronically elevated BNP or N-terminal pro-BNP levels, making the test inconclusive. In addition, it was reported that BNP does not reliably distinguish ARDS from AHFS. In our study, the BNP level of patients with a history of heart failure who had dyspnea due to pulmonary disease or ARDS showed no significant difference compared to that of patients with acute dyspnea due to AHFS, a finding that is in agreement with prior reports[42, 43]. Therefore, among patients with acute dyspnea (including those with a history of heart failure and those with ARDS), the baseline BNP level alone could have various limitations for making a differential diagnosis in the emergency setting, and further research is needed to address this issue.
B-lines assessed by lung ultrasound have been proposed as an easy alternative diagnostic tool for monitoring pulmonary congestion in AHFS patients. Recently, it was reported that B-lines alone or B-lines combined with N-terminal pro-BNP show a high diagnostic accuracy for differentiating AHFS-related acute dyspnea from that due to COPD/asthma in the ED[3, 41]. However, it is impossible to differentiate AHFS from bilateral pneumonia, pulmonary fibrosis, or ARDS by lung ultrasound alone, because although B-lines are a very sensitive sign of cardiogenic pulmonary edema, this sign is not specific. However, in the present study, the lung ultrasound in two patients with pure right-sided heart failure, which was not in association with left-sided heart failure, showed a false negative, suggesting that B-lines may not be sensitive for pure right-sided heart failure. Recently, Gargani has suggested that addition of lung ultrasound to echocardiography provides additive information about pulmonary involvement. Furthermore, Kimura et al. has reported the usefulness of cardiopulmonary-limited ultrasound examination consisting of only 4 ultrasound views, such as LV systolic dysfunction, left atrial enlargement, IVC, and B-lines, for the diagnostic accuracy and prognostic information, although they did not evaluate a diagnostic accuracy for differentiating acute dyspnea due to AHFS from that caused be primary pulmonary disease. On the basis of these available reports and our findings, it is suggested that LCI integrated ultrasound assists with the rapid and accurate diagnosis and treatment of acute dyspnea in the emergency setting.
Our study had several limitations. First, this was a single-center investigation of a small patient population. Second, assessment of diastolic dysfunction and quantitative analysis of valvular heart disease could not be done with the hand-held ultrasound device employed in this study. Therefore, complete evaluation of acute dyspnea in patients requires comprehensive standard echocardiography after LCI ultrasound evaluation. Third, we could not evaluate the extravascular lung water in AHFS patients because we did not examine the number of B-lines. Therefore, further prospective investigation to evaluate the extravascular lung water by a hand-held device for patients with acute dyspnea in the emergency setting is needed. Fourth, training is needed to interpret the findings of LCI ultrasound.
In conclusion, our study demonstrated that rapid evaluation by lung-cardiac-IVC (LCI) integrated ultrasound has a higher accuracy for differentiating AHFS-related acute dyspnea from pulmonary-related acute dyspnea compared with lung ultrasound alone or lung ultrasound combined with BNP. These findings suggest that LCI integrated ultrasound is a useful tool to expedite the evaluation of patients with acute dyspnea before initiating treatment in the ED. However, further research will be needed to provide more insight into the impact of LCI integrated ultrasound using a portable ultrasound device on diagnosis and decision making in the ED.
Acute heart failure syndromes
Lung-cardiac-inferior vena cava
Inferior vena cava
We express our appreciation to Katsunori Shimada, PhD (Statz Institute, Inc., Tokyo, Japan) for expert statistical assistance.
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