Journal of Cardiac Failure Vol. 18 No.

3 2012

Differentiation of Cardiac and Noncardiac Dyspnea Using

Bioelectrical Impedance Vector Analysis (BIVA)
ANTONIO PICCOLI, MD, DSc,1 MARTA CODOGNOTTO, MD,1 VITO CIANCI, MD,2 GIANNA VETTORE, MD,2
MARTINA ZANINOTTO, PhD,3 MARIO PLEBANI, MD,3 ALAN MAISEL, MDFACC,4 AND W. FRANK PEACOCK, MD5

Padova, Italy; San Diego, California; and Cleveland, Ohio

ABSTRACT
Background: There is no gold standard for the differential diagnosis of acute dyspnea despite the useful-
ness of N-terminal proeB-type natriuretic peptide (NT-proBNP) and lung ultrasound. No study has eval-
uated the contribution of bioelectrical impedance vector analysis (BIVA) in discriminating between
cardiac and noncardiac dyspnea. We sought to determine whether a relationship exists between ultrasound
detection of lung congestion, NT-proBNP, and BIVA in patients with acute dyspnea.
Methods and Results: Eligible patients were between 50 and 95 years, with an estimated glomerular fil-
tration rate of $30 mL min
1 1.73 m
2, who presented to an emergency department with dyspnea. Dysp-
nea was classified by reviewers blinded to BIVA as cardiac or noncardiac based on physical examination,
electrocardiogram, chest X-ray, NT-proBNP, and B-lines of lung congestion on ultrasound. Overall, 315
patients were enrolled (median age 77 years, 48% male). An adjudicated diagnosis of cardiac dyspnea was
established in 169 (54%). Using BIVA, vector positions below
1 SD of the Z-score of reactance were
associated with peripheral congestion (c2 5 115; P ! .001). BIVA measures were reasonably accurate
in discriminating cardiac and noncardiac dyspnea (69% sensitivity, 79% specificity, 80% area under the
receiver operating characteristic curve).
Conclusions: In patients presenting with acute dyspnea, the combination of BIVA and lung ultrasound
may provide a rapid noninvasive method to determine the cause of dyspnea. (J Cardiac Fail
2012;18:226e232)
Key Words: Congestion, heart failure, lung ultrasound, NT-proBNP.

Acute dyspnea is a common cause of emergency depart-
ment (ED) admission. Although tools to assist in accurate
diagnosis include natriuretic peptides (NPs) and lung ultra-
sound (LUS), the differential diagnosis can be challenging.
The interpretation of elevated N-terminal proeB-type natri-
uretic peptide (NT-proBNP) can be confounded by the pres-
ence of renal injury and obesity, therefore more objective
From the 1Department of Medicine, University of Padova, Padova,
Italy; 2Department of Emergency, University of Padova, Padova, Italy;
3
Department of Laboratory Medicine, University of Padova, Padova,
Italy; 4University of Californi and San Diego Veterans Affairs Medical
Center, San Diego, California and 5Department of Emergency Medicine,
Cleveland Clinic, Cleveland, Ohio.
Manuscript received March 24, 2011; revised manuscript received Octo-
ber 28, 2011; revised manuscript accepted November 9, 2011.
Reprint requests: Prof. Antonio Piccoli, Department of Medicine, Poli-
clinico IV piano, Via Giustiniani, 2, I-35128 Padova, Italy. Tel: þ39-335-
8256780; Fax: þ39-049-8212151. E-mail: apiccoli@unipd.it
See page 232 for disclosure information.
1071-9164/$ - see front matter
Ó 2012 Elsevier Inc. All rights reserved.
doi:10.1016/j.cardfail.2011.11.001
measures of volume overload are needed. In the setting of
elevated NT-proBNP, thoracic ultrasound can detect pulmo-
nary fluid and thereby aid in diagnosis. The presence of so-
nographic artifacts, known as B-lines, suggests thickened
interstitia of interlobular septa or fluid-filled alveoli. LUS
has been shown to have greater diagnostic accuracy in dif-
ferentiating the causes of acute dyspnea in emergency set-
tings compared with the traditional methods. Its major
advantages are the absence of ionizing radiation, speed,
and insensitivity to the patient’s breath-hold limitations or
agitation. It also allows distinction between solid and fluid
lesions (consolidation vs effusion) and provides dynamic
information of moving structures in real time.1e3
A newer technology, bioelectrical impedance vector
analysis (BIVA) evaluates hydration status.4 Body imped-
ance is a combination of resistance (R) (ie, the opposition
to flow of an alternating current through intra- and extracel-
lular ionic solutions) and reactance (Xc) (ie, the capacita-
tive component of tissue interfaces, cell membranes, and
organelles).4e6 With BIVA, the impedance measurements
of R and Xc are normalized by the subject’s height (H)

226
 BIVA in Cardiac Dyspnea  Piccoli et al 227

and then expressed graphically (Fig. 1) as R/H and Xc/H on
the x and y axes, respectively.4,7e9
Body impedance is 90% determined by soft tissues of
limbs, so peripheral congestion is specifically detected.6,7
Only 10% is generated by the trunk, owing to its large
cross-sectional area and heterogeneity of tissues and mate-
rials. Therefore the presence of pleural effusions, fluid in
the lung, ascites, etc. does not contribute to the measured
impedance. Whole-body bioimpedance and LUS provide
complementary information: Bioimpedance cannot detect
lung fluid status, and LUS (acoustic impedance) cannot de-
tect peripheral congestion.
Using the R versus Xc graph allows the presentation of
impedance vectors, the terminus of which may be presented
in relation to ellipses of the 50th, 75th, and 95th percentiles
of vectors derived from a normal population (Fig. 1). Vec-
tors that project into the upper poles of the ellipses indicate
decreased tissue fluid volume according to
1,
2, and
3
dehydration ranks, and conversely vectors that terminate in
the lower poles are associated with increased tissue fluid
volume according to þ1, þ2, and þ3 fluid accumulation
ranks. The lower pole of the 75% ellipse has been identified
as a threshold for apparent edema in renal patients, with
100% sensitivity and 92% specificity. Edema is not usually
detectable until the interstitial fluid volume has risen to
about 30% above normal (4 to 5 kg of body weight).10
BIVA can detect increased fluid volume before pitting
edema is present, ie, when rank is þ1.4,5 Vectors falling
in the left halves of ellipses indicate more soft tissue
mass (eg, obese and athletic subjects) compared to vectors
falling in the right halves (which suggest lean and malnour-
ished subjects).4,11e16
The purpose of the present study was to determine if
there is an association between ultrasound detected lung
congestion, NT-proBNP, and BIVA in patients presenting
with acute dyspnea.
Materials and Methods
Experimental Design
This was a prospective observational cross-sectional study of pa-
tients presenting to the ED of Padua University Hospital with acute
dyspnea. The study was approved by the local Ethics Committee.
Caucasian ED patients with a chief complaint of dyspnea were el-
igible for inclusion if they were between 50 and 95 years of age, had
a body mass index (BMI) between 15 and 40 kg/m2 and estimated
glomerular filtration rate (eGFR) $30 mL min
1 1.73 m
2 (calcu-
lated according to the National Kidney Foundation’s Kidney
Disease Outcomes Quality Initiative recommendations17).
Patients were excluded if they were unconscious, seizing, had
a presentation secondary to trauma, acute coronary syndrome,
ascites, edema secondary to vein disorders, lymphedema, or
hypoalbuminemia.
In the ED, after obtaining informed consent, we recorded the clin-
ical history and physical examination. Blood samples were taken for
the routine laboratory determinations. NT-proBNP was determined
using the PBNP method (Dade-Behring, Newark, New Jersey) with
results available in 1 hour. Electrocardiogram (ECG), chest X-ray,
and LUS were also performed. The ultrasound examination con-
sisted of bilateral scanning of the anterior and lateral chest wall, per-
formed on the patient in a supine or near-supine position by 1
operator. A MyLab50 machine (Esaote, Genova, Italy), equipped
with a convex 3.5-MHz probe, was used. According to Volpicelli
et al, an examination for lung interstitial syndrome (which includes
cardiogenic pulmonary congestion but cannot differentiate other
conditions) is considered to be positive if $2 positive scans per

Fig. 1. In bioelectrical impedance vector analysis, the intersubject variability of the impedance vector is represented with the bivariate nor-
mal distribution, ie, a graph with elliptical probability regions (50%, 75%, and 95% tolerance ellipses) on the R-Xc plane normalized by
height (R/H, and Xc/H, in Ohm/m). Vector position on the R-Xc graph is interpreted and ranked following 2 directions: 1) Vector displace-
ments parallel to the major axis of tolerance ellipses indicate progressive changes in soft tissue hydration; and 2) vectors lying on the left
side above the major axis or on the right side below the major axis of tolerance ellipses indicate more or less soft tissues, respectively. R,
resistance; Xc, reactance; H, height.
228 Journal of Cardiac Failure Vol. 18 No. 3 March 2012
side are observed when the examination is performed on 8 chest
areas (2 anterior and 2 lateral per side). Each scan is considered
to be positive when $3 close B-lines is visualized (maximum dis-
tance between adjacent B-lines of 7 mm).2,3
BIVA measurements were obtained with standard tetrapolar
bioelectrical impedance electrodes at a frequency of 50 kHz using
a phase-sensitive analyzer (BIA-101; Akern-RJL Systems,
Florence, Italy) as described elsewhere.8 The 2 vector components
R and Xc were recorded and divided by the subject’s height.4
BIVA results were blinded to the clinician caring for the patient.
All BIVA measurements were performed by 1 operator.
Sex-specific reference intervals were available for the Italian
healthy population as 50%, 75%, and 95% tolerance ellipses on
the R-Xc graph.11 The values of R and Xc in Ohm/m were trans-
formed into bivariate Z-scores using the mean and the SD of the
sex-specific reference healthy population: Z(R) 5 (R/H
mean
R/H)/SD (ie, [R/H
371.9]/49 if female and [R/H
298.6]/
43.2 if male) and Z(Xc) 5 (Xc/H
mean Xc/H)/SD (ie, [Xc/H

34.4]/7.7, if female and [Xc/H
30.8]/7.2, if male), thus defin-
ing one set of tolerance ellipses (50%, 75%,, and 95%) indepen-
dent of sex.12 Individual vectors were plotted on the Z-score
graph. Mean vectors of groups were represented as point vectors
with their 95% confidence ellipse on the same Z(R)-Z(Xc)
plane.12
After medical evaluation and stabilization in the ED, the gold
standard diagnosis of cardiac or noncardiac dyspnea was made
by physicians using all of the clinical data, including physical ex-
amination, ECG, chest X-ray, NT-proBNP, and LUS, but blinded
to BIVA results. European Society of Cardiology criteria were
used for an HF diagnosis, which is based on the following opera-
tional definition: ‘‘The patient has symptoms typical of heart fail-
ure (breathlessness at rest or on exercise, fatigue, tiredness, ankle
swelling) and signs typical of heart failure (tachycardia, tachipnea,
pulmonary rales, pleural effusion, raised jugular venous pressure,
peripheral edema, hepatomegaly) and objective evidence of
a structural or functional abnormality of the heart at rest (cardio-
megaly, third heart sound, cardiac murmurs, abnormality on the
echocardiogram, raised natriuretic peptide concentration).’’18
Assuming that peripheral congestion is specifically detected by
BIVA and lung congestion by LUS, we defined ‘‘peripheral con-
gestion without lung congestion’’ as the condition in which a pa-
tient had a negative LUS and an impedance vector below
1 SD
of Z(Xc) (wet BIVA pattern), ‘‘lung congestion without peripheral
congestion’’ as a positive LUS and a BIVA vector that exceeded

1 SD of Z(Xc) (dry BIVA pattern), and ‘‘lung and peripheral
congestion’’ as occurring when a patient had a positive LUS and
a BIVA vector below the
1 SD of Z(Xc).
Statistical Analysis
In BIVA plots, the reference intervals for an individual subject
are represented by 50%, 75%, and 95% tolerance ellipses derived
from a healthy population. The bivariate confidence intervals of
mean vectors are represented by 95% confidence ellipses derived
from the study population (more flat and elongated with higher
correlation). Separate 95% confidence ellipses indicated a statisti-
cally significant difference between mean vector positions on the
ReXc plane (P ! .05, which is equivalent to a significant Hotel-
ling T2 test, ie, a significant difference in R, Xc, or both compo-
nents).4,12 Ellipses were plotted with BIVA software (Piccoli A
and Pastori G, Department of Medical and Surgical Sciences, Uni-
versity of Padova, Italy, 2002).
The receiver operating characteristic (ROC) curve analysis on
Z-scores and the calculation of common statistical tests were per-
formed with the SPSS statistical package (v 18; Chicago, Illinois).
Results of NT-proBNP (log-normal distribution) are reported as
geometric means.
Results
Characteristics of patients are reported in Table 1. Mean
age was 77 years and 48% were male. Of 315 patients, 169
(54%) received a gold standard diagnosis of cardiac dysp-
nea due to acute HF. Noncardiac dyspnea was diagnosed
in 146 patients (46%), due to decompensated chronic
obstructive pulmonary disease (58%; n 5 85), asthma
(30%; n 5 44), anxiety (10%; n 5 15), or pneumonia
(3%; n 5 4). Dyspnea category, NT-proBNP, LUS, BIVA
results, and final clinical state are depicted in Figure 2. In
the cardiac dyspnea group, the concentrations of troponin-
I and NT-proBNP were higher and the impedance vector
components Z(R) and Z(Xc) were significantly decreased.
Group Mean Vectors
In Figure 3, mean Z-scores vectors are depicted as point vec-
tors with their 95% confidence ellipse with coordinates in SD
units. Separate confidence ellipses indicate a significant differ-
ence in mean vector position.4,12 As shown in Figure 1, the
mean vector of the group with noncardiac dyspnea (group a)
was close to 0 SD of both components [Z(R) 5
0.38;
Z(Xc) 5
0.37 SD], indicating a normal body hydration
with impedance close to the mean value of the healthy popula-
tion.11,12 In the cardiac dyspnea group without edema on
physical examination (group b in Figure 3), the mean vector
was displaced along the major axis and close to the lower
pole of the 50% tolerance ellipse [Z(R) 5
0.92; Z(Xc) 5

0.86 SD] and was consistent with a mild peripheral conges-
tion. Peripheral congestion with pitting edema on physical
examination was detected by BIVA (Fig. 1). The mean
vector from the cardiac dyspnea and pitting edema group
(65 out of 169 patients, 38%) (group c in Fig. 3) was close
to the lower pole of the 95% tolerance ellipse [Z(R) 5

2.48; Z(Xc) 5
1.80 SD], indicating peripheral edema.
Individual Vectors
Most vectors from patients with noncardiac dyspnea lay
above
1 SD of Z(Xc) (79% specificity), and the majority
with cardiac dyspnea were below this cutpoint (69% sensi-
tivity). The optimal cutoff for differentiating cardiac and
noncardiac dyspnea as identified by ROC curve analysis
was a vector that terminated below
1 SD of Z(Xc) (sensi-
tivity 69%, specificity 79%, area under the ROC curve 80%).
Lung and Peripheral Congestion
NT-proBNP mean levels were used to aid in interpreting
BIVA results, based on the principle that the greater the NT-
proBNP, the higher the likelihood of a HF diagnosis. Using
this standard, there was a weak significant inverse correla-
tion between the vector terminus and log NT-proBNP
 BIVA in Cardiac Dyspnea  Piccoli et al 229

Table 1. Characteristics of Patients by Dyspnea Group

Noncardiac (n 5 146) Cardiac (n 5 169)
Mean SE Mean SE t* P Value
Age. y 74.7 0.85 79.0 0.69
4.0 !.01
BMI, kg/m2 25.8 0.38 26.3 0.33
1.0 ns
Creatinine, mmol/L 96.0 2.92 111.6 2.8
3.8 !.01
eGFR, mL min
1 1.73 m
2 70.3 2.26 57.6 1.84 4.4 !.01
Troponin-I, mg/L 0.04 0.01 1.11 0.45
2.2 .03
NT-proBNP, ng/Ly 407.4 0.06 3236.0 0.04
12.6 !.01
Z(R)
0.4 0.11
1.5 0.10 7.0 !.01
Z(Xc)
0.3 0.07
1.2 0.06 9.7 !.01

BMI, body mass index; eGFR, estimated glomerular filtration rate; NT-proBNP, n-terminal proeB-type natriuretic peptide.
*Student t test for unpaired data.
y
The mean values of NT-proBNP are geometric means.

(r 5
0.4; r2 5 16%; P ! .001). This was consistent with
our finding that patients with a physical examination of
‘‘edema with pulmonary congestion’’ had an NT-proBNP
3 times higher than ‘‘edematous patients without lung con-
gestion’’ (3,890 vs 1,318 ng/L; P 5 .005).
Figure 2 demonstrates the combined classification of the
315 patients by clinical diagnosis, LUS, BIVA, and NT-
proBNP. Among the 146 patients with a gold standard di-
agnosis of noncardiac dyspnea, 95% had a negative LUS.
Of these, 78% had vectors exceeding the
1 SD of
Z(Xc) and were consistent with a non-HF state (BIVA
dry). Representing the ‘‘no congestion’’ cohort (ie, neither
lung nor peripheral), this group had the lowest NT-proBNP
concentration (419 ng/L). A minority (30/139, 22%) of
patients with a negative LUS had a BIVA consistent with
increased fluid volume. In this group, the increase in
NT-proBNP (815 ng/L) was twofold higher than the ‘‘no
congestion’’ group, suggesting that BIVA may contribute
to the evaluation of volume status above and beyond that
of LUS alone.
Cardiac Dyspnea Group
The majority (91%) of 169 patients with a gold standard
diagnosis of cardiac dyspnea also had a positive LUS and
the highest NT-proBNP levels (4,501 and 4,217 ng/L). Of

BIVA dry NT-proBNP

No congestion
78% 419 ng/L
LUS -
95%

BIVA wet 815 ng/L Peripheral congestion

Non-cardiac 22% without lung congestion
N = 146,46%
BIVA dry
100%
993 ng/L

LUS +
5%
BIVA wet
Acute dyspnea 0%
N = 315 BIVA dry
899 ng/L No congestion
43%

LUS -
9%
BIVA wet Peripheral congestion
1809 ng/L without lung congestion
57%
Cardiac
N = 169,54% BIVA dry
4217 ng/L Lung congestion without
29% peripheral congestion

LUS +
91%

BIVA wet
4501 ng/L Lung and peripheral congestion
71%

Fig. 2. Probability tree reporting the conditional distributions by type of dyspnea, lung ultrasound (LUS), and bioelectrical impedance vec-
tor analysis (BIVA) pattern. Geometric means of N-terminal proeB-type natriuretic peptide (NT-proBNP) and patterns of congestion are
reported on leaves.
230 Journal of Cardiac Failure Vol. 18 No. 3 March 2012
Z(Xc)
4
3
2 95%
75%
1
50%
0
-4 -3 -2 -1 0 1 2 3
a Z(R)
-1
b normohydration suggests that patients with HF and clini-
-2
c causing dyspnea. In patients with dyspnea and a negative
-3
-4
Fig. 3. Mean impedance vectors with their 95% confidence ellip-
ses plotted on the 3 tolerance ellipses (50%, 75%, 95%): a) mean
vector of patients with noncardiac dyspnea; b) mean vector of pa-
tients with cardiac dyspnea without pitting edema; and c) mean
vector of patients with cardiac dyspnea with pitting edema.
patients with ‘‘lung and peripheral congestion,’’ 71% had
a vector that was below
1 SD of Z(Xc) (BIVA wet). Of
patients with ‘‘lung congestion without peripheral conges-
tion’’ 29% had a positive LUS and a BIVA vector exceeding

1 SD of Z(Xc) of the normal population. However, the
vectors of most of these patients exceeded
1 SD of
Z(Xc), because lung congestion is not detected by BIVA.
Despite a gold standard diagnosis of cardiac dyspnea, 9%
of LUS examinations were negative. Of these patients, 57%
had a BIVA measurement below
1 SD of Z(Xc), with an
NT-proBNP that was 2 times increased versus the ‘‘no con-
gestion’’ BIVA patients (from 899 to 1,809 ng/L). Overall,
peripheral congestion as determined by BIVA, without ul-
trasound evidence of pulmonary congestion was associated
with an increased NT-proBNP level 2.3 times that of pa-
tients without peripheral congestion (1,072 vs 457 ng/L;
P 5 .007).
Renal Dysfunction
We found that there was a weak, inverse, linear correla-
tion (r 5
0.45; P 5 .001) between log NT-proBNP and
eGFR which accounted for less than 20% of the NT-
proBNP variability. As reported in Table 1, patients with
a gold standard diagnosis of cardiac dyspnea had 12 mL/
min/1.73 m2 eGFR less than patients with noncardiac
dyspnea. The difference is statistically significant but not
relevant for the explanation of the higher NT-proBNP con-
centrations in patients with cardiac dyspnea. Furthermore,
the differences in eGFR between patients with a wet versus
dry BIVA pattern were not statistically significant in both
cardiac and noncardiac dyspnea. In patients with ‘‘periph-
eral congestion without pulmonary congestion,’’ the eGFR
was the same as in patients without peripheral congestion
(67.1 vs 67.6 mL min
1 1.73 m
2). Patients with a physical
examination of edema and with pulmonary congestion had
an eGFR similar to that of edematous patients without lung
congestion (61 vs 64 mL min
1 1.73 m
2).
Discussion
BIVA provided a threshold for discrimination between
4
cardiac and noncardiac dyspnea with 69% sensitivity and
79% specificity. Using a BIVA threshold of 1 SD below
cally apparent normovolemia may have an excess of fluid
LUS, the mean NT-proBNP level was twofold higher in
patients with peripheral congestion compared with those
without peripheral congestion (wet vs dry BIVA pattern).
Therefore, peripheral congestion without lung congestion
may result in heart overload with increased (wet) NT-
proBNP. When the LUS was positive, the NT-proBNP
reached the maximal concentration in either BIVA pattern.
Both BIVA and LUS can be performed at the bedside and
results are available almost immediately, which has the po-
tential to improve ED decision making regarding therapeu-
tic intervention and disposition.
It is well established that HF patients present with a vari-
ety of clinical manifestations. Though some may present
with only lung congestion or only peripheral congestion,
others may manifest both peripheral and lung congestion.18
It is recommended that patients presenting to emergency
services with dyspnea should undergo a history, physical
examination, chest X-ray, ECG, and blood sampling for
NP and renal function measurements.19
In the present analysis, we evaluated the association be-
tween BIVA and LUS as compared to a gold standard diag-
nosis. LUS has been validated in the general ED population
(not only dyspneic patients) for lung interstitial syndrome,
which includes cardiac pulmonary congestion.2 Obviously,
LUS cannot detect peripheral congestion. BIVA operates as
a stand-alone procedure using soft tissue electrical pro-
perties and is independent of body weight.5,7 BIVA is
potentially superior to conventional BIA that is based on re-
gression equations that include body weight. Indeed, con-
ventional BIA may yield inaccurate volume estimates
when tissue hydration exceeds 73%, owing to the weight
of trunk fluid added to the body weight.7,20
LUS for the detection of lung congestion was positive in
91% of patients with cardiac dyspnea and negative in 95%
of patients with noncardiac dyspnea. Our findings were
similar to those recently reported in the literature. Prosen
et al found 100% sensitivity and 94% specificity of LUS
in discriminating between cardiac versus noncardiac dysp-
nea in a prehospital setting.23 LUS was performed in 1 min-
ute on the arrival of the patient. Because in a number of our
patients LUS has been performed after some delay due to

stabilization, some LUS examination could have led to
false negative results, as suggested in the literature.2 Dysp-
nea without pulmonary congestion could also have been
caused by low-flow hemodynamic states. In 57% of these
patients, a wet BIVA pattern was found, suggesting periph-
eral congestion without lung congestion. This result can be
interpreted as a false positive result of the wet BIVA pattern
in relation to negative LUS or as a true positive result in
relation to cardiac dyspnea. NT-proBNP concentration in
patients with negative LUS and dry BIVA pattern (‘‘no con-
gestion’’) was lowest among patients with cardiac dyspnea.
When LUS was positive, the NT-proBNP was at the highest
concentration regardless of peripheral congestion (either
dry or wet BIVA pattern).
Interestingly, 22% of patients with noncardiac dyspnea
without lung congestion (negative ultrasound) had a periph-
eral congestion as diagnosed by BIVA (ie, a wet BIVA pat-
tern; Fig. 2). In these patients, NT-proBNP concentration
was about double than in patients without peripheral con-
gestion. Because there is no gold standard diagnostic test
for cardiac dyspnea, our results can be interpreted as either
that the wet BIVA pattern was a false positive or, con-
versely, that it indicated ‘‘peripheral congestion without
lung congestion’’ and was causal for NT-proBNP release.
In these dyspneic patients, treatment with diuretics would
be reasonable if not contraindicated by the clinical status.
Unfortunately, we cannot comment on an interpretation of
the BIVA pattern in the 5% of patients with a positive
LUS and noncardiac dyspnea, owing to insufficient sample
size (Fig. 2).
Latent Peripheral Congestion
Peripheral congestion with pitting edema is easy to iden-
tify. Peripheral congestion without pitting edema is difficult
to establish, because edema is not usually detectable until
the interstitial fluid volume has risen to w30% above nor-
mal (4e5 kg of body weight).10
Fluid accumulation and removal in hemodialysis patients
is a good model for validation of BIVA in peripheral con-
gestion.15,16,21 The reference method is the ultrafiltration
volume that is measured every 30 minutes with a bed scale.
Changes in ultrafiltration are mapped to changes in imped-
ance vector position. In a clinical validation study in hemo-
dialysis patients free from edema (1,116 patients), we
previously demonstrated that after ultrafiltration (mean 3
L), impedance vectors migrate from lower to upper poles
of the reference tolerance ellipses according to a wet-dry
cycle of impedance that is associated with a wet-dry body
weight cycle. BIVA is not suitable to detect pulmonary con-
gestion due to heterogeneity of soft tissue in the trunk and
to the wide cross-sectional area of the trunk (see introduc-
tory section).
Peripheral congestion with pitting edema on physical ex-
amination was detected by BIVA (Fig. 1). The mean vector
from the cardiac dyspnea and pitting edema group (group c
in Fig. 3) was close to the lower pole of the 95% tolerance
BIVA in Cardiac Dyspnea  Piccoli et al 231
ellipse, indicating peripheral edema. This is also consistent
with the BIVA pattern observed in patients with nephrotic
syndrome, edematous peritoneal dialysis patients and those
with New York Heart Association functional classes III and
IV HF.4,13,21,22 This suggests that BIVA may have a role for
detecting latent peripheral congestion and for monitoring
fluid removal in congested patients.
Optivolemic Status
It is established that prognosis improves in patients who
are able to lower their NT-proBNP levels after treatment of
congestion.19 Conceptually, the NP level of a patient is
composed of 2 components, that of a baseline optivolemic
(‘‘dry’’) NP level and that occurring from acute pressure or
a volume overload (‘‘wet’’) NP level.19 At an acute presen-
tation to the ED, the contribution of wet and dry compo-
nents of NP is frequently unknown. Our findings of
elevated NP being associated with a wet BIVA pattern
suggest that there may be clinical value in considering
the results of these tests in combination. Furthermore, we
hypothesize that a decrease in NT-proBNP from wet to
dry levels is associated with a vector migration from wet
to dry BIVA pattern with disappearance of B-lines in
LUS. Because LUS and BIVA carry different information,
we propose that the definition of the optivolemic status
may be considered when there is a dry BIVA pattern
together with a negative LUS. In these conditions we docu-
mented the lowest NT-proBNP concentrations.
BIVA Threshold for Cardiac Dyspnea
Others have suggested that the BIVA threshold for car-
diac dyspnea Z(Xc) 5
1 SD lies just on the lower pole
of the 50% tolerance ellipse, where the fluid volume and
central venous pressure begin to increase.14 This indicates
that patients with cardiac dyspnea cannot tolerate a still-
normal fluid volume. In contrast, patients without HF (eg,
renal patients) with vectors between the lower poles of
50% and 75% tolerance ellipses (Fig. 1; þ1 rank) are
asymptomatic and their modest fluid volume increase is
not clinically detectable.10,15,21,22 They develop pitting
edema as soon as their vectors migrate below the lower
pole of the 75% ellipse (þ2 rank or more, 100% sensitivity,
and 92% specificity).4,13,14,22
A study on treatment of congestive HF patients with a di-
uretic load documented an impedance vector displacement
similar to that observed in fluid removal with hemodialy-
sis.20 Therefore, BIVA can be properly used for detecting
latent peripheral congestion and for monitoring fluid re-
moval from congested patients. Segmental bioimpedance
measurements of the trunk have been proposed to detect
lung congestion. Although there was a correlation with
whole-body impedance, we cast doubts about the useful-
ness of impedance measurements from the trunk, where
very low values, particularly of the Xc component (3e6
Ohm with SD 2e3 Ohm), are meaningless owing to a small
signal-to-noise ratio.24
232 Journal of Cardiac Failure Vol. 18 No. 3 March 2012
Study Limitations
In this study, we did not evaluate the consequences of in-
terventions. Therefore, additional studies are needed to es-
tablish whether adequacy of fluid removal with diuretics or
ultrafiltration can be achieved by bringing the BIVA vector
above the ‘‘wet’’ threshold. Also, because physicians were
blinded to the BIVA data, we cannot speculate on the con-
sequence of outcomes from interventions based solely on
BIVA and ultrasound results. Furthermore, using NT-
proBNP level in the adjudication may have presented biases
in any of the analyses that incorporated NT-proBNP. Next,
although a noninvasive strategy with minimal direct costs is
likely to be cost-effective, we did not evaluate the financial
implications of this strategy in our protocol. Finally, our
gold standard diagnosis was defined by clinical impression
rather than an external adjudication committee. Additional
studies using long-term end points may provide objective
outcome data for these diagnostic modalities.
Conclusion
In the present study, immediately available BIVA results
provided a threshold for discrimination between cardiac
and noncardiac dyspnea with 69% sensitivity and 79%
specificity. Using a BIVA threshold of 1 SD below normo-
hydration suggests that patients with HF and clinically ap-
parent normovolemia may have an excess of fluid causing
dyspnea. When LUS was negative, the mean NT-proBNP
level was twofold higher in patients with peripheral conges-
tion than in those without peripheral congestion (wet com-
pared to dry BIVA pattern). Finally, peripheral congestion
without lung congestion may result in heart overload with
increased (wet) NT-proBNP release. The optimal evalua-
tion of a dyspneic patient may include the search for pe-
ripheral congestion by BIVA and lung congestion by LUS.
Disclosures
None.
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