JACC: HEART FAILURE VOL. 9, NO.

9, 2021

ª 2021 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

Lung Ultrasound–Guided Emergency

Department Management of Acute
Heart Failure (BLUSHED-AHF)
A Randomized Controlled Pilot Trial

Peter S. Pang, MD,a Frances M. Russell, MD,a Robert Ehrman, MD, MS,b Rob Ferre, MD,a Luna Gargani, MD, PHD,c
Phillip D. Levy, MD, MPH,b Vicki Noble, MD,d Kathleen A. Lane, MS,e Xiaochun Li, PHD,e Sean P. Collins, MD, MSf

ABSTRACT

OBJECTIVES The goal of this study was to determine whether a 6-hour lung ultrasound (LUS)-guided strategy-of-care
improves pulmonary congestion over usual management in the emergency department (ED) setting. A secondary goal
was to explore whether early targeted intervention leads to improved outcomes.

BACKGROUND Targeting pulmonary congestion in acute heart failure remains a key goal of care. LUS B-lines are a
semi-quantitative assessment of pulmonary congestion. Whether B-lines decrease in patients with acute heart failure by
targeting therapy is not well known.

METHODS A multicenter, single-blind, ED-based, pilot trial randomized 130 patients to receive a 6-hour LUS-guided
treatment strategy versus structured usual care. Patients were followed up throughout hospitalization and 90 days’
postdischarge. B-lines #15 at 6 h was the primary outcome, and days alive and out of hospital (DAOOH) at 30 days was
the main exploratory outcome.

RESULTS No significant difference in the proportion of patients with B-lines #15 at 6 hours (25.0% LUS vs 27.5% usual
care; P ¼ 0.83) or the number of B-lines at 6 hours (35.4  26.8 LUS vs 34.3  26.2 usual care; P ¼ 0.82) was observed
between groups. There were also no differences in DAOOH (21.3  6.6 LUS vs 21.3  7.1 usual care; P ¼ 0.99). However, a
significantly greater reduction in the number of B-lines was observed in LUS-guided patients compared with those
receiving usual structured care during the first 48 hours (P ¼ 0.04).

CONCLUSIONS In this pilot trial, ED use of LUS to target pulmonary congestion conferred no benefit compared with usual
care in reducing the number of B-lines at 6 hours or in 30 days DAOOH. However, LUS-guided patients had faster resolution
of congestion during the initial 48 hours. (B-lines Lung Ultrasound–Guided ED Management of Acute Heart Failure Pilot
Trial; NCT03136198) (J Am Coll Cardiol HF 2021;9:638–648) © 2021 by the American College of Cardiology Foundation.

D espite
outcomes,
decades of
patients
efforts
with
failure (AHF) experience poor in-hospital
and postdischarge morbidity (1,2). No initial man-
to
acute
improve
heart
no guideline recommendations receive the highest
grade (3–5). Similarly, well-defined, robust, repro-
ducible endpoints of therapy identifying patients
for safe and early hospital discharge remain
agement strategy definitively improves outcomes; elusive (4).

From the aDepartment of Emergency Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA; bDepartment
of Emergency Medicine, Wayne State School of Medicine, Detroit, Michigan, USA; cInstitute of Clinical Physiology, National
Research Council, Pisa, Italy; dDepartment of Emergency Medicine, Case Western Reserve University, Cleveland, Ohio, USA;
e
Department of Biostatistics, Indiana University School of Medicine, Indianapolis, Indiana, USA; and the fDepartment of Emer-
gency Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Barry Greenberg, MD, has served as the Guest Editor for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.

Manuscript received February 11, 2021; revised manuscript received May 14, 2021, accepted May 14, 2021.

ISSN 2213-1779/$36.00 https://doi.org/10.1016/j.jchf.2021.05.008

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JACC: HEART FAILURE VOL. 9, NO. 9, 2021
SEPTEMBER 2021:638–648
Symptoms related to pulmonary congestion drive
patients to seek acute care. Reducing these symptoms
is a primary goal of treatment (6,7). However, many
patients who feel better leave the hospital with pul-
monary congestion, placing them at risk
postdischarge events. Traditional methods of quan-
tifying such residual congestion, including physical
examination, body weight, and urine output, lack
both sensitivity and inter-rater reliability (8,9). These
are unreliable measures of response to therapy,
especially across different physicians.
Lung ultrasound (LUS) is an objective method to
quantify pulmonary congestion via measurement of
extravascular lung water signals, known as B-lines
(10,11). Both easy to learn and perform, B-lines augment
or outperform radiographs, natriuretic peptides, and
physical examination as a marker for congestion
(9,12–14). B-lines are also associated with prognosis (15),
even after adjusting for N-terminal pro–B-type natri-
uretic peptide levels (16). Importantly, as intravascular
volume is removed, B-lines decrease (17).
Preliminary data suggest that B-lines may be used
as an objective measure of response to therapy in
patients with AHF. In a recent single-blind, controlled
trial of 123 patients managed in the outpatient
setting, a significant improvement in the composite
outcome of urgent visits, hospitalizations for wors-
ening HF, and death from any cause in the LUS-
guided group was observed; however, this improve-
ment was driven solely by decreased urgent visits
(18,19).
Despite preliminary signals, whether B-lines are a
potential target for acute management remains a
knowledge gap. The BLUSHED-AHF
Ultrasound–Guided Emergency Department Manage-
ment of Acute Heart Failure) study was a randomized
controlled, single-blind trial, designed to test the
following hypothesis: LUS-guided treatment will
result in less congestion (defined by LUS B-lines #15)
than treatment with structured usual care 6 hours
after start of AHF treatment in the emergency
department (ED).
SEE PAGE 649
METHODS
A detailed design and rationale paper has previously
been published (20). Briefly, BLUSHED-AHF was a
multicenter, prospective, single-blind, randomized
controlled, strategy-of-care pilot trial enrolling pa-
tients from 5 EDs in the United States. Only adult
patients (aged $21 years), with a history of HF,
shortness of breath, and having at least one sign or
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Pang et al. 639
BLUSHED-AHF
radiographic evidence of AHF were eligible. ABBREVIATIONS
Patients were required to have >15 B-lines AND ACRONYMS
(with B-lines present in both hemithoraces)
AHF = acute heart failure
to be included. Patients were excluded if
DAOOH = days alive and out of
for they had an estimated glomerular filtration
hospital
2
rate <45 mL/min/173 m ; were in shock; had
ED = emergency department
a systolic blood pressure <100 or
LUS = lung ultrasound
>175 mm Hg; were intubated; were on
pressors or inotropes; had an acute coronary syn-
drome, anemia requiring transfusion, known inter-
stitial lung disease, or end-stage HF; or were
pregnant. After written informed consent was
obtained, patients were randomized 1:1 to receive
LUS-guided strategy-of-care or structured usual care.
This study was approved by the institutional review
boards at all study sites and was registered on
clinicaltrials.gov (NCT03136198).
Patients in the structured usual care arm under-
went management guided solely by clinical re-
assessment. Clinical care teams were blinded to the
B-line score. Figure 1 presents the treatment
algorithm.
Although a structured treatment protocol was
suggested, care teams could override study recom-
mendations per clinical judgment. Patients in the
LUS-guided arm underwent treatment per protocol
until a decrease in B-lines on LUS to #15 or 6 hours
elapsed from enrollment.
STUDY PROCEDURES. L U S a s s e s s m e n t s . All pa-
tients underwent a baseline LUS assessment (T0). The
next assessment occurred 2–4 hours after randomi-
zation (T2). The final re-assessment (T6) occurred
2-4 hours after the first re-assessment (T2), or
(Lung
immediately before ED disposition. If a patient was
admitted to the hospital or an observation unit before
the 6-h treatment period, the second re-assessment
(T6) could occur at this location.
In addition to LUS assessments, patients also un-
derwent clinical assessments at each of the 3 time
points. After the 6-hour treatment period, per proto-
col, patients continued to undergo LUS assessments
daily throughout hospitalization (up to 7 days or
discharge, whatever came first) to characterize the
trajectory of congestion as measured by LUS. There
were no protocol stipulations to share results of
hospital stay LUS results.
F o l l o w - u p . Patients had additional data collection
performed at 30 and 90 days’ postrandomization.
Both follow-up visits were by telephone only (unless
hospitalized) to assess vital status, unscheduled
health care visits, and rehospitalization. Given that
the 90-day outcomes were exploratory, they are not
reported.
640 Pang et al. JACC: HEART FAILURE VOL. 9, NO. 9, 2021

BLUSHED-AHF SEPTEMBER 2021:638–648

F I G U R E 1 Study Treatment Algorithm

Recommended management for both lung ultrasound (LUS)-guided and usual structured care arms. Reprinted from Heart & Lung, Vol 48, Design and Rationale of the
BLUSHED-AHF (B-lines lung ultrasound guided emergency department management of acute heart failure) pilot trial, 2019, with permission from Elsevier.
IV ¼ intravenous; NIV ¼ noninvasive ventilation; T2 ¼ second assessment 2-4 h after baseline; T6 ¼ final assessment within 2-4 h after T2.

Ultrasound machine s e t t i n g s . As previously images and accuracy of B-line counting by

described (20), LUS examinations were performed by
using Zonare ZS3 or Z One Pro (Mindray) or SonoSite
MTurbo (FUJIFilm SonoSite) ultrasound machines
with a curvilinear transducer. Settings were stan-
dardized across all sites as part of the study-specific
LUS training (20,21): depth of 18 cm, clip length 6 s,
and tissue harmonics and multi-beam former turned
off.
I m a g e a c q u i s i t i o n . A standard 8-zone image acqui-
sition approach was used (22,23). Probes were trans-
versely oriented, with the probe indicator facing the
patient’s right side and the probe face placed within
the rib space parallel to adjacent ribs. All patients
were scanned in a semi-upright position, with the
head of the bed at 45  . Sonographers who were in-
dependent of the care team completed LUS assess-
ments. Sonographers were required to complete
standardized LUS training sessions before imaging
study patients. These sessions included didactics,
proctored independent scanning, and review of
expert sonographers to determine proficiency.
Proficiency was deemed when the sonographer
submitted $25 LUS examinations and reached an
intraclass correlation for interpretation with an
expert of >0.7 (20).
Q u a n t i f y i n g B - l i n e s . The total B-line count was
determined by summing the number of B-lines
counted within each of 8 possible zones. The range
of B-line counts for each zone was 0 to 20. With-
in each zone, discrete B-lines were counted indi-
vidually. For zones with wide, fused, or coalescing
B-lines, B-line counts were determined by multi-
plying the percentage of the intercostal space filled
with confluent B-lines by 20 (ie, fused B-lines
occupying 60% of the scanned intercostal
space ¼ 14 B-lines).
In addition to the sonographer counting the num-
ber of B-lines, an independent imaging core labora-
tory, composed of 2 blinded expert LUS sonographers,
reviewed all images. For this primary analysis, scores

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JACC: HEART FAILURE VOL. 9, NO. 9, 2021 Pang et al. 641
SEPTEMBER 2021:638–648 BLUSHED-AHF

F I G U R E 2 Blushed Consort Diagram

Flow of patients through each predefined study time point. BLUSHED-AHF ¼ Lung Ultrasound–Guided Emergency Department Management
of Acute Heart Failure; ED ¼ emergency department; LUS ¼ lung ultrasound; T2 ¼ second assessment 2-4 h after baseline; T6 ¼ final
assessment within 2-4 h after T2.

generated by research teams, not the core imaging
laboratory, were used. Given that the study premise
was predicated on the ease of LUS acquisition and
training, “at the bedside” research team scores were
used.
Ancillary t e s t i n g . All laboratory results, chest
radiograph, and an electrocardiogram were per-
formed as part of usual care.
STATISTICAL ANALYSIS. P r i m a r y e n d p o i n t . The
primary endpoint was the number of patients
with #15 B-lines on LUS at 6 hours after enrollment.
Only LUS with $2 sections from the left lung and $2
sections from the right lung were counted. Previous
pilot research identified 15 B-lines as a prognostic
threshold for worse outcomes when assessed before
hospital discharge; however, a 28-zone scoring
method was used (15). Because this was a pilot trial,
multiple exploratory endpoints were also assessed.
However, an a priori primary exploratory hypothesis
was stipulated: LUS-guided patients will have
more days alive and out of hospital (DAOOH)
at 30 days.
S a f e t y o u t c o m e s . Adverse events were collected
from time of informed consent through 7 days after
end of study treatment. Patients were followed up
through 90 days for both safety and efficacy,
capturing death, rehospitalization, and ED visits. An
independent data safety and monitoring board met
throughout the duration of the study.
P o w e r . With 59 patients in each of the 2 study arms,
there was 81% power to detect an effect size of 2 (ie,
25% in the usual care arm will have #15 B-lines vs
50% in the LUS-guided strategy), where the type I
error rate was set at 0.05 (2-sided). A 10% dropout
rate was assumed.
A n a l y s e s . Two preplanned analyses are presented:
an intention-to-treat analysis and a per-protocol
analysis on selected outcomes, including 6-hour B-
lines and 30-day DAOOH. The per-protocol analysis
excluded patients with major protocol violations,
such as not receiving all 3 LUS assessments or dis-
charged from the ED. Patients who did not receive
medication treatment per protocol were included,
however.
Comparisons of binary endpoints (B-lines #15),
number of B-lines at all intervals, 30-day DAOOH,
baseline comorbidities, baseline medications (in
particular, guideline-recommended therapies), in-
hospital medications, baseline renal function, serum
sodium, natriuretic peptide levels, troponin levels,

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642 Pang et al. JACC: HEART FAILURE VOL. 9, NO. 9, 2021

BLUSHED-AHF SEPTEMBER 2021:638–648

T A B L E 1 Baseline Characteristics

Usual Structured Care (n ¼ 64) LUS Guided (n ¼ 66) P Value

Study site 64 66 0.929

Detroit 17 (26.6) 15 (22.7)
Indianapolis site 1 14 (21.9) 13 (19.7)
Indianapolis site 2 5 (7.8) 6 (9.1)
Nashville 28 (43.8) 32 (48.5)
Male 64 46 (71.9) 66 47 (71.2) 1.000
Age at consent, y 64 66.2  12.2 66 63.8  15.9 0.336
Race 63 65 1.000
Black or African American 34 (54.0) 35 (53.8)
White or Caucasian 29 (46.0) 30 (46.2)
Ethnicity 64 66 0.854
Hispanic or Latino 1 (1.6) 2 (3.0)
Not Hispanic or Latino 61 (95.3) 63 (95.5)
Refused or unknown 2 (3.1) 1 (1.5)
Any ED visit or hospitalization in the past 6 mo 64 41 (64.1) 63 45 (71.4) 0.449
Health insurance 62 55 (88.7) 65 58 (89.2) 1.000
Myocardial infarction 64 22 (36.7) 65 27 (41.50.9) 0.588
Percutaneous transluminal coronary angioplasty 64 16 (25.0) 66 17 (25.8) 1.000
Coronary artery bypass graft 64 16 (25.0) 65 16 (24.6) 1.000
Hypertension 64 58 (90.6) 66 60 (90.9) 1.000
Hyperlipidemia 64 34 (53.1) 64 44 (68.8) 0.103
Diabetes 64 28 (43.8) 66 31 (47.0) 0.728
Insulin-dependent diabetes 27 13 (48.1) 30 17 (56.7) 0.600
Chronic kidney disease 63 19 (30.2) 65 25 (38.5) 0.356
Depression history 64 14 (21.9) 65 20 (30.8) 0.318
Asthma or COPD 64 28 (43.8) 66 29 (43.9) 1.000
Pacemaker 64 8 (12.5) 66 16 (24.2) 0.114
Implantable cardioverter-defibrillator 64 16 (25.0) 66 12 (18.2) 0.397
Systolic BP at screening, mm Hg 63 138.6  22.9 66 140.7  24.5 0.615
Diastolic BP at screening, mm Hg 63 82.4  18.8 66 88.6  19.7 0.069
Body mass index, kg/m2 64 32.2  10.7 65 31.2  8.9 0.580
Ejection fraction, % 52 38.8  16.8 57 41.3  15.9 0.428
Ejection fraction #40% 52 31 (59.6) 57 30 (52.6) 0.563

Values are n, n (%), or mean  SD.

COPD ¼ chronic obstructive pulmonary disease; BP ¼ blood pressure; ED ¼ emergency department; LUS ¼ lung ultrasound.

hemoconcentration, physical examination findings, Per-protocol analysis included analysis of covari-

baseline blood pressure, and hospital discharge
medications were performed between the treatment
groups by using Fisher exact tests and Student’s
t-tests, as appropriate.
An analysis of the trajectory of B-lines throughout
hospitalization was also performed. Due to skewness
in the sum of LUS scores, data were transformed for
trend modeling by taking the log of the B-line
score þ1 (1 was added to account for patients with 0 B-
lines). We used random effects models on the log-
transformed outcome, with treatment group, time,
an interaction between the two, and site as cova-
riates. Subject ID was the random effect. Two models
were run; one included data from baseline until 48 h
later, and the second model included data from
baseline until day 7.
ance models on 30-day DAOOH according to treat-
ment group, adjusting for site, 6-hour B-line number,
or B-lines #15.
Unless stated otherwise, 2-sided P values <0.05
were considered statistically significant. All analyses
were performed by using SAS release 9.4 (SAS Insti-
tute, Inc).
RESULTS
A total of 130 patients were enrolled across 4 sites,
from July of 2017 to March of 2019. One patient
withdrew consent and was excluded from the primary
analysis (Figure 2).
Overall, the 2 groups were well matched at
baseline (Table 1). The mean age was 66 years in

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JACC: HEART FAILURE VOL. 9, NO. 9, 2021 Pang et al. 643
SEPTEMBER 2021:638–648 BLUSHED-AHF

the usual care arm and 64 years in the LUS-guided

T A B L E 2 Baseline Laboratory Test Results
arm (72% of patients were male). No differences
were observed regarding race or ethnicity, with Usual Structured Care (n ¼ 64) LUS Guided (n ¼ 66) P Value

>50% of patients Black or African American. The Sodium (mEq/L) 64 138.5  3.6 66 138.1  6.8 0.619
Potassium (mmol/L) 64 4.1  0.6 66 4.1  0.6 0.935
presence of recent hospitalizations, insurance sta-
Carbon dioxide (mEq/L) 64 29.3  17.6 66 27.4  13.9 0.495
tus, and medical history were similar, as were
BUN (mmol/L) 64 21.5  8.5 66 20.6  8.3 0.551
initial blood pressure, natriuretic peptide and Creatinine (mmol/L) 64 1.2  0.3 66 1.2  0.3 0.281
troponin levels, and other laboratory markers Glucose (mmol/L) 63 140.2  78.4 66 129.9  64.0 0.413
(Tables 1 and 2). BNP (pg/mL) 59 1,404.7  1,145.1 61 1,449.6  1,198.5 0.834
The total number of B-lines per patient at baseline NT-proBNP (pg/mL) 4 7,814.8  3,424.6 2 6,810.5  4,719.9 0.775
were also similar (49.3  28.3 usual structured care Albumin (g/dL) 16 3.6  1.5 19 3.7  0.5 0.844
Troponin-I (ng/mL) 53 0.09  0.15 57 0.14  0.51 0.490
arm vs 47.5  25.7 LUS-guided arm; P ¼ 0.70) (Tables 3
Hemoglobin (g/dL) 64 12.1  1.9 66 12.0  2.1 0.775
and 4, Supplemental Table 1).
Hematocrit (%) 64 37.4  5.5 66 37.3  6.2 0.984
PRIMARY ENDPOINT. After the 6-hour treatment
period, the number of patients with B-lines #15 was Values are n or mean  SD.
BNP ¼ B-type natriuretic peptide; BUN ¼ blood urea nitrogen; LUS ¼ lung ultrasound; NT-proBNP ¼ N-ter-
14 (27.5%) in the usual care arm and 14 (25.0%) in the minal pro–B-type natriuretic peptide.
LUS-guided arm (P ¼ 0.83). The total number of
B-lines per patient at 6 hours was also similar
(35.4  26.8 vs 34.3  26.2; P ¼ 0.82) (Tables 3 and 4).
DAOOH AT 30 DAYS AND HOSPITAL LENGTH OF usual care arm (39.6  31.1; P ¼ 0.051). Numerically,
STAY. No differences were observed between treat- LUS-guided patients had fewer B-lines throughout
ment arms regarding DAOOH at 30 days (21.3  7.1 hospitalization (Central Illustration). A significantly
usual care vs 21.3  6.6 LUS arm; P ¼ 0.99). No dif- greater reduction in the number of B-lines was
ferences in length of stay were observed (5.7  5.4 observed in the LUS- guided arm than in the usual
usual care vs 4.7  4.0 LUS arm; P ¼ 0.26). care arm during the first 48 hours (P ¼ 0.04),
suggesting that LUS-guided patients had faster
TREATMENT DURING THE FIRST 6 HOURS. Table 5 resolution of congestion. By discharge, this difference
highlights medications given during the 6-hour in B-line reduction between the 2 arms was no longer
study period. One hundred percent of patients in significant (P ¼ 0.56).
the LUS arm received initial diuretic therapy versus Supplemental Table 2 describes treatment during
92% in the structured usual care arm (P ¼ 0.03), ac- hospitalization. There was a numeric trend towards
counting for both oral and intravenous therapy. less medication given, doses, and amount in the LUS-
However, there were significant group differences in
terms of when patients received therapy. Notably,
more patients in the usual structured care arm
received only an initial dose of diuretics, but more T A B L E 3 LUS Results: Patients With B-Lines #15

patients in the LUS-guided arm received an additional Usual Structured Care (n ¼ 64) LUS Guided (n ¼ 66) P Value
dose during a re-assessment (P ¼ 0.02). The total Day 1 screening 64 1 (1.6) 66 0 (0.0) 0.492
intravenous dose, however, was not significantly Day 1 T2 60 11 (18.3) 65 18 (27.7) 0.289
different (P ¼ 0.23). Day 1 T6 51 14 (27.5) 56 14 (25.0) 0.828
Despite a mean initial SBP of 140 mm Hg, few pa- Day 2 58 14 (24.1) 64 21 (32.8) 0.322

tients in either arm received vasodilator therapy Day 3 49 19 (38.8) 56 21 (37.5) 1.000
Day 4 36 12 (33.3) 46 19 (41.3) 0.499
within the 6-hour study time period. Although nearly
Day 5 25 9 (36.0) 28 13 (46.4) 0.578
twofold more patients received nitroglycerin in the
Day 6 21 13 (61.9) 22 9 (40.9) 0.227
LUS-guided arm, this did not reach statistical signifi-
Day 7 17 8 (47.1) 15 7 (46.7) 1.000
cance (n ¼ 9 [14.5%] usual care arm vs n ¼ 17 [26.6%] Discharge day if #7 d 33 15 (45.5) 39 19 (48.7) 0.817
LUS-guided arm; P ¼ 0.12). Discharge day if #7 d or day 7 48 22 (45.8) 54 26 (48.1) 0.845
if longer hospital stay
LUS AND TREATMENT DURING HOSPITALIZATION. Tables 3
and 4 show B-line scores throughout hospitalization. Values are n or n (%).
LUS ¼ lung ultrasound; T2 ¼ second assessment 2-4 h after baseline; T6 ¼ final assessment within 2-4 h after
By day 2, patients in the LUS-guided arm had reduced T2.
B-lines (29.7  22.7) compared with the structured

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644 Pang et al. JACC: HEART FAILURE VOL. 9, NO. 9, 2021

BLUSHED-AHF SEPTEMBER 2021:638–648

was related to the intervention itself, according to

T A B L E 4 LUS Results: Total B-Line Count
investigator review of individual events.
Usual Structured Care (n ¼ 64) LUS Guided (n ¼ 66) P Value

Day 1 screening 64 49.3  28.3 66 47.5  25.7 0.700 DISCUSSION

Day 1 T2 60 42.0  29.9 65 36.0  26.6 0.241
Day 1 T6 51 35.4  26.8 56 34.3  26.2 0.821 In this randomized controlled, pilot trial testing LUS-
Day 2 58 39.6  31.1 64 29.7  22.7 0.051
guided versus usual structured care to alleviate pul-
Day 3 49 31.5  31.0 56 28.0  24.5 0.524
monary congestion within the first 6 hours of ED
Day 4 36 35.6  32.1 46 26.7  23.2 0.167
management, no significant differences in B-lines
Day 6 21 27.4  36.1 22 24.3  21.5 0.736
Day 7 17 38.4  39.5 15 26.0  23.1 0.281 were observed between groups. There were also no
Discharge day if #7 d 33 26.5  27.8 39 20.8  18.4 0.322 differences in DAOOH within 30 days, the main
Discharge day if #7 d or day 7 48 29.6  31.0 54 22.2  19.8 0.162 exploratory endpoint. However, early numeric
if longer hospital stay
improvement in pulmonary congestion in LUS-guided
Values are n or mean  SD.
patients was observed by day 2, which just missed
LUS ¼ lung ultrasound. statistical significance (P ¼ 0.051). A significant
time  treatment interaction was also observed
through day 2, showing faster and greater resolution
of B-lines in the LUS-guided arm. Although protocol-
guided arm compared with the usual structured care driven treatment stopped at 6 hours, repeat dosing
arm except at the time of discharge. during this interval was more common in the LUS-
PER-PROTOCOL ANALYSIS. There were no signifi- guided arm. This suggests that protocol-driven ther-
cant differences between groups (n ¼ 54 LUS arm vs apy might facilitate a more rapid reduction in
n ¼ 48 usual structured care arm) by per-protocol congestion. This also may explain our finding of an
analysis for either the number of B-lines at 6 hours early but attenuated separation in congestion reduc-
(P ¼ 0.64) or 30-day DAOOH (P ¼ 0.58). Furthermore, tion with LUS-guided treatment.
there were no significant group differences in 30-day Signs and symptoms of congestion drive patients
DAOOH after adjusting for site or 6-hour B-line with AHF to seek care (24–28). How to best assess,
number or B-lines #15 (P ¼ 0.58 in all models). grade, and manage congestion is not well established,

SAFETY. Five serious adverse events occurred: 3 in

however (27,29). The absence of robust, reliable

the intervention arm and 2 in the control arm. methods to measure congestion is one reason why it

Regarding nonserious adverse events, 20 occurred in is not well assessed (27,30). LUS improves diagnostic

the control arm and 10 in the intervention arm. None
T A B L E 5 Medications During First 6 H
Usual Structured Care LUS Guided
(n ¼ 64)
Furosemide given? 62 57 (91.9) 64
Number of Furosemide oral doses 2 3
1 2 (100.0)
Number of Furosemide intravenous doses 57 63
1 38 (66.7)
2 16 (28.1)
3 3 (5.3)
4 0 (0.0)
Total intravenous dose of Furosemide, mg 57 76.1  55.9 63
Total oral dose of Furosemide, mg 2 130.0  155.6 3 53.3  23.1
Nitroglycerine given 62 9 (14.5) 64
Noninvasive ventilation 62 8 (12.9) 64
Inotropes or vasopressors given 62 1 (1.6) 64
Values are n, n (%), or mean  SD.
LUS ¼ lung ultrasound; NR ¼ not reported.
accuracy and is highly reproducible (9,31–37). Intra-
observer and interobserver variability of B-line cap-
ture and summary have been reported as low as 5.1%
and 7.4%, respectively (33). In a meta-analysis, LUS
was the best test to affirm the diagnosis of AHF, more
than natriuretic peptide (likelihood ratio positive for
the diagnosis of AHF by LUS was 7.4 [95% CI: 4.2-12.8]
(n ¼ 66) P Value
and likelihood ratio negative was 0.16 [95% CI: 0.05-
64 (100.0) 0.026
NR 0.51]) (9).
3 (100.0) Importantly, B-lines are a dynamic marker of
0.021 prognosis. In patients undergoing dialysis, B-lines
26 (41.3) decrease markedly postdialysis (17). In patients with
32 (50.8) AHF, B-lines decrease throughout hospitalization
4 (6.3)
(15,38). However, persistence of B-lines predischarge
1 (1.6)
identifies patients at higher risk for worse outcomes
87.3  46.3 0.234
0.612
(15,39). B-lines even outperformed B-type natriuretic
17 (26.6) 0.124 peptide as a prognostic marker (38). Finally, serial
7 (10.9) 0.788 measurement of B-lines is both easy to learn and
1 (1.6) 1.000 perform (31,32,40–42). LUS is low cost and does
not involve radiation. A systematic review (43)
supports our findings: B-lines decrease as a result of
treatment during hospitalization. However, the lack

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JACC: HEART FAILURE VOL. 9, NO. 9, 2021 Pang et al. 645
SEPTEMBER 2021:638–648 BLUSHED-AHF

C ENTR AL I LL U STRA T I O N Comparison of Sum of B-Lines Throughout Hospitalization

Primary Endpoint
Usual Structured Care (n = 64) LUS Guided (n = 66)
N n (%) N n (%) P Value
LUS ≤15 at 6 h 51 14 (27.5%) 56 14 (25.0%) 0.828

Total B-Lines Counts Throughout Hospitalization

150
+
+
125 + +
+
+
+
Sum of 8 LUS Scores

+ + +
+
+
75

50

25
15
0
rg r
0

Da On e
6

Di y 7

ha /o
T

rg
T

y
y

e
sc nd
y ly
Da
Da

Da
1,

Da

Da
1,

Da

ha
1,
y

Di 7 a
y

sc
Da
Da

Da

LUS Guided Usual Structured Care

Usual Structured Care LUS Guided

(n = 64) (n = 66)
Day/Time N Mean ± SD N Mean ± SD P Value
Day 1 Screening 64 49.3 ± 28.3 66 47.5 ± 25.7 0.700
Day 1 T2 60 42.0 ± 29.9 65 36.0 ± 26.6 0.241
Day 1 T6 51 35.4 ± 26.8 56 34.3 ± 26.2 0.821
Day 2 58 39.6 ± 31.1 64 29.7 ± 22.7 0.051
Day 3 49 31.5 ± 31.0 56 28.0 ± 24.5 0.524
Day 4 36 35.6 ± 32.1 46 26.7 ± 23.2 0.167
Day 5 25 30.8 ± 32.3 28 20.8 ± 16.8 0.175
Day 6 21 27.4 ± 36.1 22 24.3 ± 21.5 0.736
Day 7 17 38.4 ± 39.5 15 26.0 ± 23.1 0.281
Discharge day if ≤7
33 26.5 ± 27.8 39 20.8 ± 18.4 0.322
days
Discharge day if ≤7
days or day 7 if longer 48 29.6 ± 31.0 54 22.2 ± 19.8 0.162
hospital stay

Pang, P.S. et al. J Am Coll Cardiol HF. 2021;9(9):638–648.

The primary endpoint of B-lines #15 at 6 h was not achieved. Despite only 6 h of protocolized therapy, lung ultrasound (LUS)-guided arm
patients had less evidence of pulmonary congestion consistently throughout hospitalization. T0 ¼ All patients under a baseline assessment;
T2 ¼ second assessment 2-4 h after baseline; T6 ¼ final assessment within 2-4 h after T2.

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646 Pang et al.
BLUSHED-AHF
of randomized trial data and overall small number of
patients studied limits the strength of evidence sup-
porting use of B-lines as a target.
Several randomized control trials outside of the
acute setting have been reported. Rivas-Lasarte et al.
(18) reported a significant reduction in urgent HF
visits in patients managed with LUS versus usual
therapy alone. Araiza-Garaygordobil et al
showed a decrease in urgent HF visits but no change
in re-hospitalizations for HF. Another study by
Marini et al. (45) found a significant decrease in HF
hospitalization as well as N-terminal pro–B-type
natriuretic peptide level in LUS-guided patients. It
remains unknown whether LUS-guided therapy im-
proves outcomes if used as a target throughout
hospitalization. Our findings suggest that additional
studies using LUS-guided therapy throughout hos-
pitalization may be of benefit but this requires
further study.
STUDY LIMITATIONS. As a pilot trial, the ED phase of
management was targeted to test proof of concept,
with a priori acknowledgement that a longer time-
frame may be needed to show the potential effects of
a LUS-guided strategy-of-care. Although we exam-
ined hospital-based outcomes, these are exploratory
and should be viewed as hypothesis-generating only.
Adherence to protocol is another limitation. Many
patients did not receive all 3 LUS assessments,
contributing to many patients not receiving timely
therapy. LUS assessments were missed for the
following reasons: to avoid interference with ongoing
patient care, patients had left the ED for other diag-
nostic tests, or patients had left the ED for admission
to the hospital. Whether this would have changed the
primary outcome is unknown. Lack of blinding may
also have introduced bias into either treatment arm.
Our effect size of 2 was informed by preliminary work
on a small number of patients and may have
contributed to the neutral results. In terms of gener-
alizability, our average age of approximately 65 years
is considerably younger than that of the registries and
also 4 to 7 years younger than the average age of the
other AHF trials (46–48). However, the median age in
ASCEND-HF (Acute Study of Clinical Effectiveness of
Nesiritide in Decompensated Heart Failure), the
largest AHF trial conducted to date, was 67 years (49).
We enrolled approximately 1.5 patients per month per
site; this is lower than the presentation rate for a busy
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JACC: HEART FAILURE VOL. 9, NO. 9, 2021
SEPTEMBER 2021:638–648
ED but a considerably higher rate of enrollment than
other AHF clinical trials (50,51).
CONCLUSIONS. In this pilot trial, targeting pulmo-
nary congestion caused by AHF in the ED with LUS
did not show any significant decrease in pulmonary
congestion within 6 h compared with usual standard
care. However, we did observe a consistent numeric
(44) reduction in pulmonary congestion, as measured by
B-lines, in the intervention group during hospitali-
zation, suggesting that future work targeting B-line
reduction throughout hospitalization is warranted.
ACKNOWLEDGMENT The authors are grateful to
Chris O’Connor for his mentorship and role as senior
mentor for this study.
FUNDING SUPPORT AND AUTHOR DISCLOSURES
Research reported in this publication was supported by the National
Heart, Lung, and Blood Institute of the National Institutes of Health
under Award Number R34HL136986. The content is solely the re-
sponsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. Dr Pang has
received research funding from the Agency for Healthcare Research
and Quality (AHRQ), the American Heart Association, BMS, Beckman
Coulter, Ortho Diagnostics, and Roche over the last year. Roche pro-
vided in-kind support for biomarker analysis for this trial. Dr Ehrman
has received research funding from GE Healthcare, CNA Diagnostics,
and Blue Cross/Blue Shield of Michigan over the last year. Dr Russell
has received research funding from GE Healthcare over the last year.
Dr Collins has received research funding from the National Institutes
of Health, the Patient-Centered Outcomes Research Institute, the
Department of Defense, AHRQ, and Beckman Coulter; and consulting
with Boehringer Ingelheim, Ortho Clinical, and Bristol Myers Squibb
over the last year. Dr Levy has received research funding from the
National Institutes of Health, the Patient-Centered Outcomes
Research Institute, AHRQ, the Michigan Health Endowment Fund,
Delta Dental, and Michigan Department of Health and Human Ser-
vices, Cardiosounds, Edwards Lifesciences, Novartis, Pfizer, Siemens,
and Beckman Coulter; and consulting with Baim Institute, Car-
dionomics, Ortho Clinical, Roche, Quidel, and the Michigan Public
Health Institute over the last year. Dr Ferre has received consulting
with Vave Healthcare, Inc; and course director for 3rd Rock Ultra-
sound, LLC over the last year. Dr Gargani has received research
funding from the Italian Ministry of Health and Regione Toscana; and
consultancy honoraria from GE Healthcare, Philips Healthcare, and
Caption Health over the last year. All other authors have reported that
they have no relationships relevant to the contents of this paper to
disclose.
ADDRESS FOR CORRESPONDENCE: Dr Peter S. Pang,
Department of Emergency Medicine, Indiana Uni-
versity School of Medicine, 720 Eskenazi Avenue,
FOB 3rd Floor, Indianapolis, Indiana 46202, USA.
E-mail: ppang@iu.edu.
JACC: HEART FAILURE VOL. 9, NO. 9, 2021 Pang et al. 647
SEPTEMBER 2021:638–648 BLUSHED-AHF

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE: Patients TRANSLATIONAL OUTLOOK: LUS is an easy to learn,

with AHF continue to have poor postdischarge outcomes.
Failure to adequately decongest is a major contributor.
Despite well-established traditional assessments of
congestion, their objective performance in terms of
accuracy and reliability is poor, especially among non-
cardiovascular experts. LUS is a novel method to assess
pulmonary congestion, especially when combined with
traditional methods. In the ED setting, we did not show
any differences in LUS B-line scores after 6 hours of tar-
geted guided management. However, we did see a signal
at 48 hours, suggesting that early and aggressive man-
agement leads to a more rapid resolution of pulmonary
congestion when measured by LUS.
easy to perform, noninvasive assessment of pulmonary
congestion in patients with AHF. It is a relatively well-
supported diagnostic aid and prognostic marker: those
with persistent B-lines on LUS have worse outcomes.
Whether B-lines are a viable target for therapy during
hospitalization is not well known. This preliminary study
did not show any difference in B-lines with guided ther-
apy in the first 6 hours in the ED. However, a signal was
observed during hospitalization: LUS-guided patients had
less congestion. Further studies should account for the
entire hospitalization period when testing LUS-guided
decongestion management versus usual care.

REFERENCES

1. Metra M, Teerlink JR. Heart failure. Lancet.
2017;390(10106):1981–1995.
2. Chioncel O, Collins SP, Ambrosy AP, et al.
Improving postdischarge outcomes in acute heart
failure. Am J Ther. 2018;25(4):e475–e486.
3. van der Meer P, Gaggin HK, Dec GW. ACC/AHA
versus ESC guidelines on heart failure: JACC
Guideline Comparison. J Am Coll Cardiol.
2019;73(21):2756–2768.
4. Ponikowski P, Voors AA, Anker SD, et al. 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 Cardiol-
ogy (ESC) developed with the special contribution
of the Heart Failure Association (HFA) of the ESC.
Eur Heart J. 2016;37(27):2129–2200.
5. Yancy CW, Jessup M, Bozkurt B, et al. 2017
ACC/AHA/HFSA focused update of the 2013 ACCF/
AHA guideline for the management of heart fail-
ure: a report of the American College of Cardiol-
ogy/American Heart Association Task Force on
Clinical Practice Guidelines and the Heart Failure
Society of America. J Am Coll Cardiol. 2017;70(6):
776–803.
6. Collins SP, Liu D, Jenkins CA, et al. Effect of a
self-care intervention on 90-day outcomes in pa-
tients with acute heart failure discharged from the
emergency department: a randomized clinical
trial. JAMA Cardiol. 2021;6(2):200–208.
7. Greene SJ, Mentz RJ, Limkakeng AT, et al.
Comparison of dyspnea measurement instruments
in acute heart failure: the DYSPNEA-AHF Pilot
Study. J Card Fail. 2021;27(5):607–609.
8. Wang CS, FitzGerald JM, Schulzer M, Mak E,
Ayas NT. Does this dyspneic patient in the emer-
gency department have congestive heart failure?
JAMA. 2005;294(15):1944–1956.
9. Martindale JL, Wakai A, Collins SP, et al. Diag-
nosing acute heart failure in the emergency
department: a systematic review and meta-anal-
ysis. Acad Emerg Med. 2016;23(3):223–242.
10. Gargani L. Lung ultrasound: a new tool for the
cardiologist. Cardiovasc Ultrasound. 2011;9:6.
11. Platz E, Jhund PS, Girerd N, et al. Expert
consensus document: reporting checklist for
quantification of pulmonary congestion by lung
ultrasound in heart failure. Eur J Heart Fail.
2019;21(7):844–851.
12. Pivetta E, Goffi A, Nazerian P, et al. Lung ul-
trasound integrated with clinical assessment for
the diagnosis of acute decompensated heart fail-
ure in the emergency department: a randomized
controlled trial. Eur J Heart Fail. 2019;21(6):
754–766.
13. Swamy V, Brainin P, Biering-Sorensen T,
Platz E. Ability of non-physicians to perform and
interpret lung ultrasound: a systematic review. Eur
J Cardiovasc Nurs. 2019;18(6):474–483.
14. Laursen CB, Sloth E, Lassen AT, et al. Point-of-
care ultrasonography in patients admitted with
respiratory symptoms: a single-blind, randomised
controlled trial. Lancet Respir Med. 2014;2(8):
638–646.
15. Gargani L, Pang PS, Frassi F, et al. Persistent
pulmonary congestion before discharge predicts
rehospitalization in heart failure: a lung ultrasound
study. Cardiovasc Ultrasound. 2015;13(1):40.
16. Platz E, Campbell RT, Claggett B, et al. Lung
ultrasound in acute heart failure: prevalence of
pulmonary congestion and short- and long-term
outcomes. J Am Coll Cardiol HF. 2019;7(10):
849–858.
17. Noble VE, Murray AF, Capp R, Sylvia-
Reardon MH, Steele DJR, Liteplo A. Ultrasound
assessment for extravascular lung water in pa-
tients undergoing hemodialysis. Time course for
resolution. Chest. 2009;135(6):1433–1439.
18. Rivas-Lasarte M, Alvarez-Garcia J, Fernandez-
Martinez J, et al. Lung ultrasound-guided
treatment in ambulatory patients with heart fail-
ure: a randomized controlled clinical trial (LUS-HF
study). Eur J Heart Fail. 2019;21(12):1605–1613.
19. Gargani L, Ferre RM, Pang PS. B-lines in heart
failure: will comets guide us? Eur J Heart Fail.
2019;21(12):1616–1618.
20. Russell FM, Ehrman RR, Ferre R, et al. Design
and rationale of the B-lines lung ultrasound
guided emergency department management of
acute heart failure (BLUSHED-AHF) pilot trial.
Heart Lung. 2019;48(3):186–192.
21. Russell FM, Ferre R, Ehrman RR, et al. What are
the minimum requirements to establish profi-
ciency in lung ultrasound training for quantifying
B-lines? ESC Heart Fail. 2020;7(5):2941–2947.
22. Gargani L, Volpicelli G. How I do it: lung ul-
trasound. Cardiovasc Ultrasound. 2014;12:25.
23. 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.
24. Mozaffarian D, Benjamin EJ, Go AS, et al.
Heart disease and stroke statistics—2015 update: a
report from the American Heart Association. Cir-
culation. 2015;131(4):e29–e322.
25. Yancy CW, Jessup M, Bozkurt B, et al. 2013
ACCF/AHA guideline for the management of heart
failure: a report of the American College of Car-
diology Foundation/American Heart Association
Task Force on Practice Guidelines. J Am Coll Car-
diol. 2013;62(16):e147–e239.
26. Gheorghiade M, Filippatos G, De Luca L,
Burnett J. Congestion in acute heart failure syn-
dromes: an essential target of evaluation and
treatment. Am J Med. 2006;119 Suppl 1:S3–S10.
27. Gheorghiade M, Follath F, Ponikowski P, et al.
Assessing and grading congestion in acute heart
failure: a scientific statement from the Acute
Heart Failure Committee of the Heart Failure As-
sociation of the European Society of Cardiology

Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en septiembre 13, 2021. Para
uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
648 Pang et al.
BLUSHED-AHF
and endorsed by the European Society of Intensive
Care Medicine. Eur J Heart Fail. 2010;12(5):
423–433.
28. O’Connor CM, Stough WG, Gallup DS,
Hasselblad V, Gheorghiade M. Demographics,
clinical characteristics, and outcomes of patients
hospitalized for decompensated heart failure: ob-
servations from the IMPACT-HF registry. J Card
Fail. 2005;11(3):200–205.
29. Mentz RJ, Kjeldsen K, Rossi GP, et al. Decon-
gestion in acute heart failure. Eur J Heart Fail.
2014;16(5):471–482.
30. Stevenson LW, Perloff JK. The limited reliability
of physical signs for estimating hemodynamics in
chronic heart failure. JAMA. 1989;261(6):884–888.
31. Martindale JL, Noble VE, Liteplo A. Diagnosing
pulmonary edema: lung ultrasound versus chest
radiography. Eur J Emerg Med. 2013;20(5):
356–360.
32. Bedetti G, Gargani L, Corbisiero A, Frassi F,
Poggianti E, Mottola G. Evaluation of ultrasound
lung comets by hand-held echocardiography.
Cardiovasc Ultrasound. 2006;4:34.
33. Jambrik Z, Monti S, Coppola V, et al. Useful-
ness of ultrasound lung comets as a nonradiologic
sign of extravascular lung water. Am J Cardiol.
2004;93(10):1265–1270.
34. Mallamaci F, Benedetto FA, Tripepi R, et al.
Detection of pulmonary congestion by chest ul-
trasound in dialysis patients. J Am Coll Cardiol Img.
2010;3(6):586–594.
35. Basso F, Milan Manani S, Cruz DN, et al.
Comparison and reproducibility of techniques for
fluid status assessment in chronic hemodialysis
patients. Cardiorenal Med. 2013;3(2):104–112.
36. Pivetta E, Goffi A, Lupia E, et al. Lung
ultrasound-implemented diagnosis of acute
decompensated heart failure in the ED: a SIMEU
multicenter study. Chest. 2015;148(1):202–210.
Descargado para Anonymous User (n/a) en National Autonomous University of Mexico de ClinicalKey.es por Elsevier en septiembre 13, 2021. Para
uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2021. Elsevier Inc. Todos los derechos reservados.
37. Gullett J, Donnelly JP, Sinert R, et al. Interob-
server agreement in the evaluation of B-lines
using bedside ultrasound. J Crit Care. 2015;30(6):
1395–1399.
38. Coiro S, Rossignol P, Ambrosio G, et al. Prog-
nostic value of residual pulmonary congestion at
discharge assessed by lung ultrasound imaging
in heart failure. Eur J Heart Fail. 2015;17(11):
1172–1181.
39. Cogliati C, Casazza G, Ceriani E, et al. Lung
ultrasound and short-term prognosis in heart
failure patients. Int J Cardiol. 2016;218:104–108.
40. Cibinel GA, Casoli G, Elia F, et al. Diag-
nostic accuracy and reproducibility of pleural
and lung ultrasound in discriminating cardio-
genic causes of acute dyspnea in the emer-
gency department. Intern Emerg Med.
2012;7(1):65–70.
41. Noble VE, 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. BMC
Medical Educ. 2009;9:3.
42. Baker K, Soong L, Harding T, et al. Sensitivity,
specificity and diagnostic accuracy of novices
integrating lung ultrasound into the care of
breathless older patients. Australas J Ultrasound
Med. 2015;18(4):143–145.
43. Platz E, Merz AA, Jhund PS, Vazir A,
Campbell R, McMurray JJ. Dynamic changes and
prognostic value of pulmonary congestion by lung
ultrasound in acute and chronic heart failure: a
systematic review. Eur J Heart Fail. 2017;19(9):
1154–1163.
44. Araiza-Garaygordobil D, Gopar-Nieto R, Mar-
tinez-Amezcua P, et al. A randomized controlled
trial of lung ultrasound-guided therapy in heart
failure (CLUSTER-HF study). Am Heart J.
2020;227:31–39.
JACC: HEART FAILURE VOL. 9, NO. 9, 2021
SEPTEMBER 2021:638–648
45. Marini C, Fragasso G, Italia L, et al. Lung
ultrasound-guided therapy reduces acute decom-
pensation events in chronic heart failure. Heart
(British Cardiac Society). 2020;106(24):
1934–1939.
46. Pang PS, Butler J, Collins SP, et al. Biased
ligand of the angiotensin II type 1 receptor in pa-
tients with acute heart failure: a randomized,
double-blind, placebo-controlled, phase IIB, dose
ranging trial (BLAST-AHF). Eur Heart J.
2017;38(30):2364–2373.
47. Metra M, Teerlink JR, Cotter G, et al. Effects of
serelaxin in patients with acute heart failure.
N Engl J Med. 2019;381(8):716–726.
48. Mebazaa A, Pang PS, Tavares M, et al. The
impact of early standard therapy on dyspnoea in
patients with acute heart failure: the URGENT-
dyspnoea study. Eur Heart J. 2010;31(7):832–841.
49. O’Connor CM, Starling RC, Hernandez AF,
et al. Effect of nesiritide in patients with acute
decompensated heart failure. N Engl J Med.
2011;365(1):32–43.
50. Metra M, Davison BA, Gimpelewicz C, et al.
Site enrollment rate, outcomes, and study drug
effects in a multicenter trial. Results from RELAX-
AHF. Int J Cardiol. 2018;253:91–96.
51. Greene SJ, Hernandez AF, Sun JL, et al. Influ-
ence of clinical trial site enrollment on patient
characteristics, protocol completion, and end
points: insights from the ASCEND-HF Trial (Acute
Study of Clinical Effectiveness of Nesiritide in
Decompensated Heart Failure). Circ Heart Fail.
2016;9(9):e002986.
KEY WORDS acute heart failure, B-lines,
congestion, lung ultrasound
A PPE NDI X For supplemental tables, please
see the online version of this paper.