Chandrashekhar, Y.

Eckman, Peter

Vakil, Kairav

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J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 6 4 , N O . 1 2 , 2 0 1 4
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P U B L I S H E D B Y E L S E V I E R I N C . h t t p : / / d x . d o i . o r g / 1 0 . 1 0 1 6 / j . j a c c . 2 0 1 4 . 0 7 . 9 4 2EDITORIAL COMMENTEchocardiographic Identiﬁcation of
Elevated Filling Pressures in
LVAD Patients*
Y. Chandrashekhar, MD,yz Peter Eckman, MD,y Kairav Vakil, MDyz*Ed
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Yogi Berra (1)SEE PAGE 1231M echanical circulatory support systems,such as continuous-ﬂow left ventricularassist devices (CF-LVADs), are being
increasingly used as destination therapy or bridge to
heart transplantation in patients with end-stage heart
failure. The rate of implantation has nearly doubled
since 2010, with >5,000 devices placed in the last
2 years in the United States alone (2). Despite
survival improvement with these devices, the clinical
course of the patient is punctuated by a number of
adverse events, including residual heart failure,
which frequently warrants additional investigations.
Inadequate left ventricular (LV) unloading, often
as a consequence of suboptimal left ventricular assist
device (LVAD) parameters or comorbidities, is central
to the worsening symptoms; some of these events can
be treated with simple but effective options (e.g.,
optimize the device settings, use diuretics). However,
other causes, such as right ventricular (RV) failure,
can present with heart failure–like symptoms (edema,
elevated jugular venous pressure, and shortness of
breath on exercise), in which such treatment may be
less effective and, in certain situations, even harmful.
An accurate estimate of LV ﬁlling pressures, a good
surrogate of LV unloading, would be invaluable initorials published in the Journal of the American College of Cardiology
ect the views of the authors and do not necessarily represent the
s of JACC or the American College of Cardiology.
m the yDepartment of Medicine, Division of Cardiovascular Medicine,
versity of Minnesota, Minneapolis, Minnesota; and the zVA Medical
ter, Minneapolis, Minnesota. Dr. Eckman has received grant support
honoraria from Thoratec and HeartWare. All other authors have
orted that they have no relationships relevant to the contents of this
er to disclose.this scenario. Current guidelines support the use of
right heart catheterization (RHC) (3) to aid clinical
management in such settings to optimize LVAD
parameters in these patients. However, invasive
hemodynamic assessment is uncomfortable and
carries a small but deﬁnite procedural risk in anti-
coagulated patients. Although deﬁnite data are
lacking, it is estimated that thousands of RHCs are
performed each year in the LVAD population, with
some patients needing many such procedures over
their lifetime. The ability to gauge ﬁlling pressures
noninvasively would therefore be of great advantage.In this issue of the Journal, Estep et al. (4) validate,
for the ﬁrst time, the reliability of echocardiography
in estimating LV ﬁlling pressures obtained through
catheterization in 50 prospectively enrolled patients
with CF-LVADs (40 in the derivation cohort and 10 in
the validation cohort) who underwent clinically
indicated RHC. Multiple echocardiographic indices
were compared with simultaneous invasive RHC
measurements. There were 2 major ﬁndings. First,
noninvasive measurements of pressures (right atrial
[RA] and pulmonary artery) correlated well with
invasive ones, which has been shown before but in
smaller studies. RV stroke volume and pulmonary
vascular resistance, however, showed only modest
correlation. Second, the authors devised an echo
algorithm combining the E/A ratio (ratio of mitral
valve peak early [E] and late [A] diastolic velocities)
with 3 other echocardiographic parameters and found
a 90% accuracy in differentiating between “high”
versus “not high” LV ﬁlling pressures. This is a
good ﬁrst step to a complex, fairly common problem.
This algorithm, if validated elsewhere, will be useful
in clinical practice if it can avoid RHC in some
patients.
J A C C V O L . 6 4 , N O . 1 2 , 2 0 1 4 Chandrashekhar et al.
S E P T E M B E R 2 3 , 2 0 1 4 : 1 2 4 2 – 4 Echo and LVAD Filling Pressures
1243Unfortunately, although left atrial (LA) pressure is
a strong predictor of symptoms, and a major prog-
nostic factor for outcome (5), very limited data are
available on how well one can noninvasively assess
LA pressures in LVAD patients. A number of echo
parameters currently are being used to gauge the
adequacy of ﬁlling pressures and LV unloading in
CF-LVAD patients. Although intuitively useful, many
of these have not been rigorously validated at the
current time. Given the controversy regarding the use
of the E/e’ ratio (mitral inﬂow early diastolic ﬁlling
peak velocity/early diastolic mitral annular velocity)
in deﬁning LA pressure in patients with advanced
heart failure (6,7), we need to thoroughly validate
noninvasive measures of LA pressure in the setting
of a CF-LVADs. A comprehensive method to identify
and quantitate LA pressure under different patho-
physiological conditions might be critical.
Currently, RHC is the primary method to estimate
RA and LA pressures in CF-LVAD patients presenting
with symptoms of suboptimal LV unloading (class IB).
Given the importance of accurate assessment of pul-
monary vascular resistance, there will continue to be
a role for invasive hemodynamic evaluation in
CF-LVAD patients, particularly those who are candi-
dates for heart transplantation (3). Physical exami-
nation is a disappearing skill, and there are few
objective data to show that it accurately predicts LA
pressure in most patients supported with an LVAD.
Noninvasive methods are attractive, and some echo
parameters may be useful, but the severe paucity of
data in this space is reﬂected in the fact that 2 recent
major reviews addressing the role of echocardio-
graphy in LVAD patients did not mention any strong
studies supporting noninvasive prediction of LA
pressure (8,9). The few available studies with any
validation using invasive hemodynamic measure-
ments have been very small (<10 to 15 patients),
were often a small part of another study, and
mainly limited to correlative conclusions rather than
providing absolute cutoff values.
Do we need to estimate LA pressure itself or can
another surrogate substitute for it in decision
making? Some studies have incorporated serial
changes between RV and LV end-diastolic sizes post-
LVAD and on follow-up, in evaluating for optimal
unloading and thereby indirectly assess ﬁlling pres-
sures. LV diastolic size decreases post-LVAD implan-
tation due to decompression, but chronic support can
be associated with an increase in LV size even while
not adversely affecting symptoms (10). Nevertheless,
ramp studies have used LV size as one useful
endpoint to optimize LV unloading (11). Interestingly,
this ramp protocol did not use any direct measure ofLV ﬁlling pressures. Others have used septal position
in decision-making strategies for optimally unloading
of the left ventricle. However, the relation between
chamber pressures is complicated. LVAD consistently
unloads the left ventricle with a reduction in LA
pressure but has variable effects on RA pressure that
can remain unchanged, decrease (if severe pulmonary
arterial hypertension and RV failure is improved), or
even increase from better venous return (12). Simi-
larly, interventricular septum shifts while represent-
ing LV unloading might also be inﬂuenced by RV
dysfunction and tricuspid regurgitation, further
complicating its ability to predict therapeutic changes
(9). Topilsky et al. (5) showed reasonable correlation
(r ¼ 0.74) between echo estimates of LA pressure
(on the basis of position of interatrial septal posi-
tion) and RHC-measured wedge pressure in 8 sub-
jects. This ﬁnding was replicated in the study by
Estep et al. (4) but was not found to be useful to
incorporate in the algorithm. Finally, the pattern of
LV ﬁlling has been used with modest correlation to
ﬁlling pressures in some studies. These features did
not seem to add to predicting LA pressure with good
speciﬁcity in the present study. The role of brain
natriuretic peptide (BNP) in predicting LA pressure
has been inadequately studied in LVAD patients.
Paradoxically, higher BNP levels predicted fewer
readmissions in 1 large study (13), and BNP levels
correlate only modestly with wedge pressures in
CF-LVAD patients (14). We therefore have few direct
measures of LA pressure in CF-LVAD patients, and the
index presented in the present study by Estep et al. (4)
is a good start.
The strengths of the study by Estep et al. (4) are
obvious: the importance of the problem they address;
the number of patients from a single center studied
prospectively with comprehensive simultaneous
echo and RHC measurements; and a validation
cohort, albeit small. The authors also showed that
although individual echo components may correlate
well with elevated pulmonary capillary wedge
pressure, none of them is clinically useful by them-
selves, lacking good positive and negative pre-
dictive values. The E/e’ ratio, a good marker of ﬁlling
pressure in patients with heart failure, did not
differ very signiﬁcantly between CF-LVAD patients
with and without high LA pressure. A composite
of multiple variables seemed to provide the best
estimate.
The limitations of this study (4) are the highly
selected patient population with mainly normal
or only mildly reduced RV systolic function. Appli-
cability may be limited in patients with atrial ﬁbril-
lation, RV failure, and/or previous mitral valve
Chandrashekhar et al. J A C C V O L . 6 4 , N O . 1 2 , 2 0 1 4
Echo and LVAD Filling Pressures S E P T E M B E R 2 3 , 2 0 1 4 : 1 2 4 2 – 4
1244surgeries. In the group that was short of breath, one
could argue that dyspnea alone would have predicted
a high ﬁlling pressure in a large proportion of them.
The algorithm identiﬁed elevated wedge pressures
with reasonable accuracy (w90%), but the index was
feasible in only three-fourths of the population.
Future real-world studies involving multiple centers
should address this issue. The algorithm also needs to
be validated in other devices (e.g., HeartWare HVAD
[HeartWare Inc., Framingham, Massachusetts) and
other pump speeds.
It is gratifying that, within the aforementioned
limitations, we can noninvasively estimate LV ﬁlling
pressures with decent accuracy in patients with
CF-LVADs. A subset of CF-LVAD patients who will
beneﬁt from this echocardiographic assessment may
be spared from an invasive RHC. The next step shouldbe to demonstrate that this echocardiographic index
is actionable and sensitive to changes in ﬁlling pres-
sures. Finally, it remains to be seen whether making
clinical decisions on the basis of “echo data” alone
can improve outcomes without needing RHC in
patients with residual heart failure. This would
greatly increase the utility of this algorithm. In the
end, the goal is to produce better strategies for
improving patient symptoms and longevity by opti-
mally unloading the heart, while minimizing risks
from unnecessary diagnostic testing.
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
Y. Chandrashekhar, Division of Cardiology (111c),
University of Minnesota/Veterans Affairs Medical
Center, 1 Veterans Drive, Minneapolis, Minne-
sota 55417. E-mail: shekh003@umn.edu.RE F E RENCE S1. Brainy quote. Available at: http://www.
brainyquote.com/quotes/quotes/y/yogiberra3
91900.html. Accessed July 24, 2014.
2. INTERMACS Interagency Registry for Mechani-
cally Assisted Circulatory Support. Quarterly
statistical report. 2014 1st quarter. Available at:
https://www.uab.edu/medicine/intermacs/statistical-
summaries. Accessed July 20, 2014.
3. Feldman D, Pamboukian SV, Teuteberg JJ, et al.
The 2013 International Society for Heart and Lung
Transplantation Guidelines for Mechanical Circu-
latory Support: executive summary. J Heart and
Lung Transpl 2013;32:157–87.
4. Estep JD, Vivo RP, Krim SR, et al. Echocardio-
graphicevaluationofhemodynamics inpatientswith
systolic heart failure supported by a continuous-
ﬂow LVAD. J Am Coll Cardiol 2014;64:1231–41.
5. Topilsky Y, Hasin T, Oh JK, et al. Echocardio-
graphic variables after left ventricular assist device
implantation associated with adverse outcome.
Circ Cardiovasc Imaging 2011;4:648–61.
6. Mullens W, Borowski AG, Curtin RJ, Thomas JD,
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10. Maybaum S, Mancini D, Xydas S, et al., for
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KEY WORDS CF-LVAD, echocardiography,
heart failure, LA pressure


Echocardiographic Identification of Elevated Filling Pressures in LVAD Patients∗ 

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Echocardiographic Identification of Elevated Filling Pressures in LVAD Patients∗

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