Introduction

Pulmonary oedema is a major predictor of morbidity and mortality in patients with acute heart failure. Studies have shown that, compared with low cardiac output, pulmonary oedema has a greater impact on the readmissions and death of patients with acute heart failure [1]. How to accurately assess pulmonary oedema in acute heart failure patients has been a challenge. Previously, invasive examination included the right heart catheter and the Swan-Ganz floating catheter, both of which focused on the assessment of pulmonary oedema by measuring pulmonary capillary wedge pressure. However, because this is a technically invasive and complex operation with more complications, it has been used rarely in clinical work. In recent years, PiCCO (pulse indicator continuous cardiac output) through transpulmonary thermodilution with integrated pulse contour analysis can calculate extravascular lung water (extravascular lung water EVLW) accurately to assess pulmonary oedema, which had been confirmed by the lung gravity method, consequently, it has gradually started to replace the two catheter technologies [2, 3]. The previous study of Kitashiro et al. demonstrated that EVLW had good correlations with PCWP (r2 = 0.62, p < 0.05; r2 = 0.73, p < 0.05) during cardiac tamponade and ischaemia, respectively [4].

Lung ultrasound through B-lines, originating from water-thickened interlobular septa, has become a simple, semi-quantitative, non-invasive and bedside tool for evaluating pulmonary oedema. In recent years, lung ultrasound has increasingly attracted the attention of physicians. Our previous study showed B-lines were positively correlated with E/eʹ (r = 0.742, r = 0.52) and NT- proBNP (r = 0.678, r = 0.417), but were negatively correlated with EF (r =  − 0.365, r =  − 0.337) in the preserved ejection fraction heart failure group and reduced ejection fraction heart failure group [5]. However, the correlation between B-lines with EVLW is still unknown in acute heart failure (AHF). Regarding the prognostic value of B-lines, Coiro et al. reported B-lines ≥ 30 is a strong predictor of the primary endpoint (all-cause death or HF hospitalisation) at 3 months [6]. However, the role of B-lines in prognosis needs to be further explored in the long-term follow-up.

In this study, lung ultrasound was used to evaluate the accuracy of pulmonary oedema by comparing the B-lines with the extravascular lung water index (EVLWI), and according to the results of the 1-year follow-up, to explore the role of lung ultrasound in guiding the prognosis in acute heart failure patients.

Methods

Study patients

We included 124 ADHF patients who underwent transthoracic echocardiography, lung ultrasound, chest X ray and NT-proBNP within 24 h of hospitalization at the Fourth Medical Center of Chinese PLA General Hospital between February 2016 and February 2019. Out of the 124 patients, 11 patients underwent PiCCO monitoring (8.87%). We took a total of 26 PiCCO measurements under different clinical conditions, each measurement accompanied with a complete lung ultrasound and echocardiography examinations. Inclusion criteria were as follows: (1) age > 18 years; (2) moderate to severe heart failure (New York Heart Association functional class III, and IV) satisfying the guidelines of European Society of Cardiology [7]. Exclusion criteria were as follows: (1) pulmonary fibrosis, acute respiratory distress syndrome, interstitial pneumonia or pneumonitis; or (2) congenital heart and valve diseases. The study was approved by the Fourth Medical Center of Chinese PLA General Hospital Ethics Committee. All of the patients were informed in advance about the research content and signed an informed consent.

Echocardiography

Transthoracic echocardiography was performed on a Philips CX 50 (Phillips, Bothell, WA, USA) diagnostic bedside ultrasound machine using a 2D probe (S5-1, with a frequency of 1–5 MHz) within 24 h of hospitalization and before discharge. Referring to the recommendations for cardiac chamber quantification by echocardiography [8], left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), ventricular septal thickness, left atrial diameter, pulmonary arterial pressure (PAP), and inferior vena cava diameter (IVC) were measured. In the apical four-chamber view, the early diastolic fast-wave (E) was measured using pulsed-wave Doppler at the tip of the mitral valve leaflets, and Tissue Doppler was used to measure the mitral annulus diastolic early e 'wave velocity at the ventricular septum and left ventricle lateral wall; these were averaged to calculate the mean early velocity (e′). The ratio of early diastolic mitral inflow velocity to early diastolic velocity of the mitral annulus was calculated for E/e′.

Lung ultrasound

All patients underwent lung ultrasound to determine the presence of B-lines after immediate echocardiography within 24 h of hospitalization and before discharge. According to the recommendations for point-of-care lung ultrasound [9], we adopted the eight chest zones to analyse the anterior and lateral thorax, scanning from the parasternal line to the posterior axillary line between the second to the fourth intercostal spaces, with four zones in each hemi-thorax including the upper anterior, lower anterior chest areas, the upper lateral and basal lateral chest areas, respectively. Eight chest sites were scanned, the B-line score in each zone is from 0 to10, the counting method is shown in Table 1, and the number of B-lines in the eight zones is summed together for the total number of B-lines. According to the total number of ultrasound B-lines groups [10], B-lines < 15 was the mild pulmonary oedema group (33 cases), 15 ≤ B-lines < 30 was the moderate pulmonary oedema group (33 cases) and B-lines ≥ 30 was the severe pulmonary oedema group (58 cases). All lung ultrasound examinations were performed within 3–5 min by two operators who were blinded to the clinical details. Intra- and inter-observer variability was 6.2% and 7.8%, respectively, and the reproducibility was 96.2%. Three cases had unusable data because of obesity; we excluded the three cases. Lung ultrasound and corresponding E/e′ were showed in Fig. 1.

Table 1 B-line Score
Full size table
Fig. 1
figure 1

Lung ultrasound and corresponding E/eʹ. a In the apical four-chamber view, the early diastolic fast-wave (E) was measured using pulsed-wave Doppler at the tip of the mitral valve leaflets; b Tissue Doppler was used to measure the mitral annulus diastolic early e ’wave velocity at the ventricular septum and c left ventricle lateral wall; d B-lines in lung ultrasound

Full size image

PiCCO

The PiCCO monitoring system (PULSION Medical System, Munich, Germany) is a device for cardiac output (CO) measurement combined with cardiac preload volume and lung water monitoring. It computes the CO utilizing an arterial pulse contour analysis algorithm after calibration by means of a transpulmonary thermodilution method. A subclavian vein catheter and a right femoral artery catheter were placed and connected to the PiCCO System for monitoring [11]. When measuring, 15 ml of ice water (4 ℃) was injected rapidly from the central venous catheter with an injection time of less than 5 s, and the thermodilution curve was evaluated with arterial catheter inserted in the femoral artery. From the CO we can obtain the intrathoracic thermal volume and the intrathoracic blood volume; from the difference of these two parameters, we can obtain the value of EVLW and EVLWI. The measurement was repeated three times, and the average was recorded. The PiCCO System was used in 11 patients: every patient was measured separately at admission and before discharge, 4 patients were measured once more due to the worsening heart failure, so PiCCO was performed 26 times in total. After each PiCCO measurement, echocardiography and lung ultrasound examination will be performed at the same time within 1 h.

N-terminal pro brain natriuretic peptide analysis

Peripheral venous blood samples were obtained from each patient within 24 h of hospitalization and before discharge. NT-proBNP analysis was performed using the Elecsys 2010 analyser (Roche Diagnostics, Mannheim, Germany).

Statistical analysis

The SPSS 17.0 software package (IBM, Armonk, NY, USA) was used for statistical analysis. All data are expressed as the mean ± standard deviation (SD) for continuous data and as a ratio for categorical data. Group comparisons were performed using one-way analysis of variance (ANOVA), followed by the least significant difference (LSD) t-test. Spearman correlation analysis was used for correlation analysis. p < 0.05 was considered to be statistically significant. Univariable analyses and Multivariable analyses by cox regression models were performed to assess the association between each candidate variable and outcome, results were reported as hazard ratios (HR) and 95% confidence intervals (CI). Kaplan–Meier survival curves for HF re-hospitalization or death in patients with either B-lines ≥ 30 or B-lines < 30 assessed at admission.

Results

Patient characteristics

All 130 enrolled patients underwent lung ultrasound (3–5 min per patient), echocardiography, chest X ray and NT-proBNP within 24 h of hospitalization. Six patients were excluded because of the incomplete data (Fig. 2). Of the remaining 124 patients, 11 patients underwent PiCCO monitoring (8.87%) and made a total of 26 PiCCO measurements in different clinical conditions.

Fig. 2
figure 2

The flow chart of the study

Full size image

Baseline characteristics for this cohort, grouped by B-lines number, are presented in Table 2.Comparing the clinical data of the three groups, the NYHA grade, Rales ratio, level of NT-proBNP and chest X-ray of the pulmonary congestion ratio were higher in the severe group than in the mild and moderate groups. The usage of digoxin in the severe and moderate groups was higher than in the mild group.

Table 2 Baseline characteristics of the mild, moderate and severe groups
Full size table

Echocardiography measurements at admission

Comparing the echocardiography measurements of the three groups, the EF of the mild group was significantly higher than that of the moderate and severe groups. The diastolic function index of the severe group, such as E/A, pulmonary artery pressure and E/e′ were higher than that of the mild and moderate groups (Table 3).

Table 3 Echocardiography measurements of the mild, moderate and severe groups
Full size table

Correlation between EVLWI and B-lines, NT-proBNP, E/e′

The correlation between EVLWI and B-lines was the best (r = 0.95, p < 0.001), followed by NT-proBNP (r = 0.72, p < 0.001) and E/e′ (r = 0.62, p < 0.001) (Table 4, Fig. 3).

Table 4 Correlation between EVLWI and B-lines, NT-proBNP, E/e′
Full size table
Fig. 3
figure 3

Correlation between EVLWI and B-lines, NT-proBNP, E/eʹ. a Scatter plot of the correlation between EVLWI and B-lines; b Scatter plot of the correlation between EVLWI and NT-proBNP; c Scatter plot of the correlation between EVLWI and E/eʹ

Full size image

Comparison of B-lines, NT-proBNP and echocardiography parameters at admission and discharge

B-lines at discharge and NT-proBNP were significantly lower compared with at admission, EF at discharge was significantly higher than at admission. The left ventricular end systolic diameter, pulmonary artery pressure, E/e′ and inferior vena cava diameter were significantly lower than at admission (Table 5).

Table 5 Comparison of B-lines, NT-proBNP and echocardiography parameters at admission and discharge
Full size table

Follow up data: death or rehospitalization

In 1 year of follow-up, 21 cases of cardiovascular events occurred (15 cases were rehospitalized, 6 patients died). Multivariate cox regression analysis showed that age, E/e′ and B-lines ≥ 30 at admission (C-index of 75%) were the prognostic risk factors; EF at admission was the prognostic protective factor. Twelve-month event-free survival showed a significantly better outcome for those patients with < 30 B-lines at admission, whereas a worse outcome was observed in patients with ≥ 30 B-lines at admission (log rank χ2 9.794, p = 0.002) (Table 6, Fig. 4).

Table 6 Univariate and multivariate cox regression analysis
Full size table
Fig. 4
figure 4

Kaplan–Meier survival curves for HF rehospitalization or death in patients with either B-lines ≥ 30 or B-lines < 30

Full size image

Discussion

Our study showed that B-lines have a good correlation with EVLWI; the correlation of EVLWI with B-lines is better than NT-proBNP, E/e′. A multivariate cox regression analysis showed that age, E/e′ and B-lines ≥ 30 at admission (C-index of 75%) were risk factors for prognosis. 12-month event-free survival showed a significantly worse outcome was observed in patients with ≥ 30 B-lines at admission.

Although congestion is considered to be the crucial reason for hospital admission in patients with acute heart failure, a standardized protocol of congestion evaluation is still lacking. The clinical evaluation is often restricted to a simple physical examination including signs and symptoms, relying on a limited set of physical examination findings has met with low sensitivity and poor predictive value [12, 13]. Recently, a position paper by the ESC HF group suggested the use of a flow chart including either clinical, echocardiographic and lung ultrasound measurements to detect congestion more precisely [14]. Ultrasonography of the lungs using an echocardiographic probe is potentially useful way to assess pulmonary oedema.

When pulmonary oedema occurs, a layer of high resistance of the gas–liquid interface formed between a pulmonary lobular interval filled with liquid and the alveolar gas; the sound waves in this interface constantly repeated the reflection back and forth, producing a vertical laser beam of high echo bands, extending to the bottom of the screen without attenuation, thus forming a special comet tail sign, also known as the B-line in lung ultrasound. In 1994, Lichtenstein D found an association between a comet tail sign (B-line) and pulmonary interstitial syndrome [15]. In 2004, Jambrik et al. analysed the correlation between the number of pulmonary water B-lines and the extravascular pulmonary water line assessed by chest radiographs and concluded that the correlation was good [16]. Since then, the lung water B-line has been used as a semi-quantitative indicator to assess pulmonary oedema in patients with heart failure and has gradually gained attention.

Lung ultrasound was performed using different scanning regions method in different studies, such as scanning 28 regions, 12 regions, 8 regions, 6 regions or 2 regions [16,17,18], but the expert consensus document approved lung ultrasound in 2012 recommended the sonographic technique that ideally consisted of scanning eight regions in the evaluation of interstitial syndrome [19], so our study adopted the eight chest zones to quantify the number of B-lines. In our study, the correlation between EVLWI and B-lines was the best (r = 0.95), followed by NT-proBNP (r = 0.72) and E/e′ (r = 0.62). The results of this study are consistent with other findings. Hubert et al. reported the correlation between B-lines and LVEDP was higher than that observed for all echocardiographic parameters (r = 0.62 for B-lines vs. r = 0.50 for all right-or left-sided echocardiographic parameters) [11]. Agricola et al. selected 20 patients undergoing critical cardiac surgery and analysed the correlation between lung ultrasound and PiCCO. It was found that the "pulmonary comet score" was significantly correlated with EVLWI in PiCCO (r = 0.42, p = 0.001) [20]. Volpicelli et al. reported that critically ill ICU patients also showed a good correlation between B-lines and EVLW, with 81% sensitivity and specificity of 90% for predicting EVLWI [21]. However, the correlation between B-lines and EVLW in acute heart failure has not been reported. Recent studies were focused on the correlation between B-lines, NT-proBNP and E/e′ in heart failure patients. Miglioranza et al. reported that in patients with chronic heart failure in the outpatient clinic, the number of B-lines and NT- proBNP (r = 0.72, p < 0.0001) and E/e′ (r = 0.68, p < 0.0001) had good correlation [22]. Our previous study showed the correlation between B-lines and E/e′ was better, especially in the preserved ejection fraction heart failure group compared with reduced ejection fraction heart failure group [5]; similar findings have been reported by Palazzuoli et al. [23]. Moreover, Kobayashi et al. explored the association between these right-sided cardiac parameters and pulmonary congestion in acutely decompensated HF, and their study showed impairments in RV systolic function and RV–PA coupling were associated with a higher number of B-line, both on admission and at discharge [24].

Regarding the value of lung ultrasound in the management of heart failure, Girerd et al. emphasized the value of lung ultrasound for detecting congestion in heart failure patients [25]. In our study, B-lines at discharge were significantly lower compared with at admission, which implies that B-lines can have dynamic change after treatment. During 1 year of follow-up, 21 patients underwent cardiovascular events, including readmission in 15 patients and death in 6 patients. Multivariate analysis showed that age, E/e′ and B-lines ≥ 30 at admission (C-index of 75%) were risk factors for prognosis, and EF was the protective factor in the prognosis. This study showed that B-lines at admission were related to the prognosis, but B-lines before discharge were not associated with prognosis. Regarding the relationship between B-lines at admission or discharge and prognosis, different studies have different conclusions; there is no consistent conclusion yet. Frassi et al. reported that 290 patients who were hospitalized for dyspnoea or chest pain were followed for an average of 16 months (2.8–29.1) and that the prognosis was worse in patients with a higher number of B-lines at admission; there was a significant difference in the survival rate in patients with B-lines of 0 and B-lines > 30 (70% vs. 19%; p = 0.007) [26]. The study of Gargani et al. included 100 patients of dyspnea and/or clinical suspicion of AHF; the results showed B-lines > 15 before discharge (HR 11.74; 95% CI (1.30–106.16) was an independent predictor of events at 6 months [27]. Coiro et al. reported 110 acute HF patients; B-lines ≥ 45 early during HHF were most predictive of outcome (HR = 9.20, 1.82–46.61; p = 0.007) [28]. The value of B-lines threshold depends on a number of factors, including clinical status, timing scan, obesity and HF subtypes, so prior studies showed different B-lines threshold.

However, published studies were short-term prognosis for 3 or 6 months. In our study, 12-month event-free survival showed a significantly better outcome for those patients with < 30 B-lines at admission, whereas a worse outcome was observed in patients with ≥ 30 B-lines at admission (log rank χ2 9.794, p = 0.002). This result implies that the higher the number of B-lines, the worse the outcome.

In acute heart failure, some studies showed lung ultrasound could be used to guide therapy. Öhman et al. evaluated a rapid cardiothoracic ultrasound (CaTUS) protocol to guide therapy for acute heart failure; the treatment arm displayed better survival regarding the combined endpoint of 6-month all-cause death or acute heart failure re-hospitalization (log rank p = 0.017) [29]. Russell et al. are registering a pilot study which will inform future, larger trial design on lung ultrasound-driven therapy aimed at guiding treatment and improving outcomes in patients with acute heart failure [30]. Of late, the expert consensus document approved lung ultrasound was a useful tool for the assessment of patients with both acute and chronic heart failure; this consensus report will serve as a guide for investigators and clinicians and enhance the quality and transparency of lung ultrasound research in heart failure [19].

Limitations

There are several limitations to our study. First, this was a single-centre study and the number of patients was relatively small, especially of PiCCO patients. Second, B-line is still semi-quantitative method and the need for multiple intercostal collection of images and different zoning methods, different examiners, as well as the patient's body or body position changes, may have a certain impact on the results.

Conclusion

Lung water B-line has a good correlation with EVLWI; B-lines ≥ 30 at admission may be the prognostic risk factor. B-lines can be visualized using the conventional echocardiography probe, and it can illustrate the dynamic change of pulmonary oedema after treatment, so lung ultrasound is highly useful and convenient in the management of heart failure patients.