Drakos, Stavros G.

Kfoury, Abdallah G.

Li, Dean Y.

Selzman, Craig H.

Stehlik, Josef

Wever-Pinzon, Omar

Elsevier - Publisher Connector 

JACC Vol. 62, No. 23, 2013 Correspondence
December 10, 2013:2255–9
2257Letters to the EditorLeft Ventricular Assist Devices
in Chronic Heart Failure
More Questions Than Answers?We welcome the paper by Drakos et al. (1), who investigated the
longitudinal effects of continuous-ﬂow left ventricular assist device
(LVAD) unloading on cardiac structure and function. The authors
concluded that younger patients and those with earlier LVAD
implantation since onset of heart failure achieved the largest struc-
tural improvements and the most favorable functional recovery (1).
Nonetheless, the report raises more questions than those it purports
to address.
First, neither the paper nor the supplementary material describes
which devices were actually used as LVADs. As each device has its
own unique characteristics and risk–beneﬁt proﬁle that may
translate on the individual response to cardiac unloading (2), we
recommend that the authors provide comparative data testing
whether any speciﬁc device was associated with better or worse
results than the others.
Second, it is well established that several pathophysiological
mechanisms interplay in a complex, yet hitherto incompletely
determined, fashion with the beneﬁts of LVAD. Speciﬁcally,
important mediators in the recovery of cardiac function after LVAD
implantation should include proapoptotic genes such as caspases;
microribonucleic acid; tumor necrosis factor-a, with its essential
regulation of maladaptive cardiac remodeling; and insulin-like
growth factor-1 (3,4). Furthermore, the demonstration that car-
diomyocytes are not terminally differentiated cells with the capacity
to re-enter the cell cycle even in LVAD models strongly suggests
that they might also be involved in determining which patients do
or do not respond favorably to LVAD therapy in routine clinical
practice (5–7).
However, no comprehensive and uniﬁed appraisal of the afore-
mentioned pathophysiological mechanisms has been performed
before in a suitably large cohort of subjects treated with LVAD
support. We thus believe that it is crucial to further investigate
the cluster of metabolic, neuroendocrine, and molecular markers
and chemokines for a “full biomolecular proﬁle” of patients
receiving LVAD (8), which is expected to provide a more precise
diagnostic and prognostic tool to guide the choice and timing
of LVAD implantation as well as to monitor the impact of LVAD
on cardiac remodeling and recovery well after its deployment.
Indeed, the precise characterization and modulation of molecular
pathways and resident stem cells would allow the optimization of
left ventricular response aiming for a more satisfactory cardiac
recovery.*Antonino G. M. Marullo, MD, PhD
Mariangela Peruzzi, MD, PhD
Elena Cavarretta, MD, PhD
Giuseppe Biondi-Zoccai, MD
Giacomo Frati, MD*Department of Medical-Surgical Science and Biotechnologies
Faculty of Pharmacy and Medicine
University of Rome “La Sapienza”
Corso della Repubblica 79
04100 Latina
Italy
E-mail: antoninomarullo@hotmail.com
http://dx.doi.org/10.1016/j.jacc.2013.06.060
REFERENCES
1. Drakos SG, Wever-Pinzon O, Selzman CH, et al., for the UCAR (Utah
Cardiac Recovery Program) Investigators. Magnitude and time course of
changes induced by continuous-ﬂow left ventricular assist device
unloading in chronic heart failure: insights into cardiac recovery. J Am
Coll Cardiol 2013;61:1985–94.
2. Lim KM, Constantino J, Gurev V, Zhu R, Shim EB, Trayanova NA.
Comparison of the effects of continuous and pulsatile left ventricular-
assist devices on ventricular unloading using a cardiac electromechanics
model. J Physiol Sci 2012;62:11–9.
3. Carnevale D, Cifelli G, Mascio G, et al. Placental growth factor regulates
cardiac inﬂammation through the tissue inhibitor of metalloproteinases-
3/tumor necrosis factor-a-converting enzyme axis: crucial role for adap-
tive cardiac remodeling during cardiac pressure overload. Circulation
2011;124:1337–50.
4. Ramani R, McTiernan CF. A micro-ribonucleic acid signature associ-
ated with recovery from assist device support in 2 groups of patients with
severe heart failure. J Am Coll Cardiol 2011;58:2270–8.
5. BergmannO, Bhardwaj RD, Bernard S, et al. Evidence for cardiomyocyte
renewal in humans. Science 2009;324:98–102.
6. Kajstura J, Gurusamy N, Ogórek B, et al. Myocyte turnover in the aging
human heart. Circ Res 2010;107:1374–86.
7. Wohlschlaeger J, Levkau B, Brockhoff G, et al. Hemodynamic support
by left ventricular assist devices reduces cardiomyocyte DNA content in
the failing human heart. Circulation 2010;121:989–96.
8. Soppa GK, Barton PJ, Terracciano CM, Yacoub MH. Left ventricular
assist device-induced molecular changes in the failing myocardium. Curr
Opin Cardiol 2008;23:206–18.ReplyLeft Ventricular Assist Devices
in Chronic Heart Failure
More Questions Than Answers?
We appreciate the interest that Dr. Marullo and colleagues have
taken in our study (1). Previous data on left ventricular assist device
(LVAD)-induced myocardial recovery have suggested that the
patient’s age and duration of heart failure history may be associated
with successful recovery (2,3). In our study, patients who achieved
a meaningful functional and structural myocardial recovery were
younger (median age 48 years) and had a shorter duration of heart
failure symptoms (median 1 year), agreeing with such observations.
Comparative studies between pulsatile and continuous ﬂow devices
have shown differences in the degree of left ventricular (LV)
unloading, hemodynamic proﬁle, and their potential to induce
myocardial recovery, as we have recently summarized (4). However,
such hemodynamic disparities are not apparent among different
types of the continuous-ﬂow LVAD (5), which was the type of
device evaluated in our study. The assist devices implanted in our
study included 57 (71%) HeartMate II (Thoratec, Pleasanton,
California), 10 (13%) HVAD (HeartWare International,
Correspondence JACC Vol. 62, No. 23, 2013
December 10, 2013:2255–9
2258Framingham, Massachusetts), 6 (7%) Jarvik 2000 (Jarvik Heart,
New York, New York), 5 (6%) VentrAssist (Ventracor Ltd,
Chatswood, NSW, Australia), and 2 (3%) Levacor (WorldHeart,
Salt Lake City, Utah) LVADs. There were no signiﬁcant differ-
ences in the degree of LV unloading, speciﬁcally right atrial pres-
sure (p ¼ 0.76), mean pulmonary artery pressure (p ¼ 0.20),
pulmonary vascular resistance (p ¼ 0.40), pulmonary capillary
wedge pressure (p ¼ 0.33), and cardiac index (p ¼ 0.26), among
the various types of devices (overall p value was obtained by
Kruskal-Wallis test). Similarly, when examining the distribution of
patients who achieved an LV ejection fraction 40%, we found no
signiﬁcant difference between individual device types (p ¼ 0.12).
We agree that diverse and complex pathophysiological mecha-
nisms might be responsible for the structural and functional
beneﬁts observed with LVAD unloading. We have recently
summarized information from various groups, including our own,
that examined the effects of LVAD unloading on calcium cycling,
contractile function, metabolism and bioenergetics, beta-adrenergic
signaling, cytokines, cytoskeletal proteins, ﬁbrosis, myocyte
hypertrophy, and gene expression (4). However, due to the limited
data correlating structure and function, it is difﬁcult to discern
between structural, cellular, and molecular changes that uniformly
occur in LVAD patients regardless of possible myocardial recovery
and changes that occur exclusively in patients with LVAD-induced
myocardial functional recovery. Therefore, large-scale, translational
studies comprehensively evaluating and correlating functional and
clinical outcomes with cellular, structural, molecular, and other
biological outcomes are urgently needed to identify the clinical and
biological signatures of LVAD-induced myocardial recovery that
will further improve our prognostic capacity and allow for the
identiﬁcation of new therapeutic strategies to augment myocardial
recovery and regeneration.Omar Wever-Pinzon, MD
Abdallah G. Kfoury, MD
Craig H. Selzman, MD
Dean Y. Li, MD, PhD
Josef Stehlik, MD
*Stavros G. Drakos, MD, PhD
*Heart Failure Program (Division of Cardiology) &
Molecular Medicine Program (Eccles Institute of Human Genetics)
University of Utah
15 North 2030 East
Room 4420
Salt Lake City, Utah 84112
E-mail: stavros.drakos@hsc.utah.edu
http://dx.doi.org/10.1016/j.jacc.2013.08.713
REFERENCES
1. Drakos SG, Wever-Pinzon O, Selzman CH, et al. Magnitude and time
course of changes induced by continuous-ﬂow left ventricular assist
device unloading in chronic heart failure: insights into cardiac recovery.
J Am Coll Cardiol 2013;61:1985–94.
2. Dandel M, Weng Y, Siniawski H, et al. Pre-explant stability of
unloading-promoted cardiac improvement predicts outcome after
weaning from ventricular assist devices. Circulation 2012;126 Suppl 1:
S9–19.
3. Goldstein DJ, Maybaum S, Macgillivray TE, et al. Young patients with
nonischemic cardiomyopathy have higher likelihood of left ventricular recovery
during left ventricular assist device support. J Card Fail 2012;18:392–5.4. Drakos SG, Kfoury AG, Stehlik J, et al. Bridge to recovery: under-
standing the disconnect between clinical and biological outcomes.
Circulation 2012;126:230–41.
5. Pauwaa S, Bhat G, Tatooles AJ, et al. How effective are continuous ﬂow
left ventricular assist devices in lowering high pulmonary artery pressures
in heart transplant candidates? Cardiol J 2012;19:153–8.Management of
Tricuspid Regurgitation by
Caval Valve Implantation
From Technical Feasibility to
Evaluation of Efﬁcacy
We congratulate Laule et al. (1) for the ﬁrst reported use of the
29-mm Edwards Sapien XT balloon-expandable valve (Edwards
Lifesciences, Irvine, California) for transcatheter venous implan-
tation to treat tricuspid regurgitation (TR). However, when we
ﬁrst investigated and clinically applied the concept of caval valve
implantation (CAVI) as a management option for severe TR, we
observed major hemodynamic and anatomic limitations that should
be considered when selecting patients for this approach (2–6). First,
CAVI does not address TR itself but the regurgitation of blood
into the caval veins. Because this condition is present only in a
subgroup of patients with severe, often long-standing TR and right
ventricular (RV) enlargement, hemodynamic proof of caval regur-
gitation is essential before valve implantation. Second, CAVI in-
creases RV afterload by exclusion of backward regurgitation. Thus,
this novel approach should be reserved for patients with preserved
RV systolic function and without elevated pulmonary vascular
resistance. In the aforementioned patient group, there is consid-
erable variation in the anatomic diameter of the inferior vena
cava (IVC), which may reach up to 45 mm. The diameter of the
IVC usually exceeds the suitable range for implantation of current,
commercially available devices. Therefore, these patients require
speciﬁcally designed, potentially individualized devices, which are
currently not commercially available. In the series presented by
Laule et al, the IVC diameter was within the range to allow im-
plantation of 29-mm balloon-expandable devices, whichdfrom
our experiencedcontradicts “hemodynamically” severe TR.
Further issues in the article by Laule et al. (1) deserve clariﬁca-
tion. First, the clinical beneﬁt observed in these patients, particu-
larly the reduction of edema and ascites, is frequently affected by
the improved medical therapy and close clinical follow-up they
are given. In the data presented, there is no obvious change in
echocardiographic parameters to substantiate clinical improvement.
Improved RV function as stated in the text is not supported by
the data presented and is unlikely for the aforementioned reasons.
Lack of documentation of pressure-derived parameters such as
RV end-diastolic pressure and mean right atrial pressure further
complicates the justiﬁcation of procedure-related clinical improve-
ment. Second, the authors unfortunately did not present imaging
studies or invasive hemodynamic data demonstrating function of
both valves. Considering the overall status of the patients, we
consider this information essential to actually support the hemody-
namic and clinical beneﬁt in these patients.


Reply Left Ventricular Assist Devices in Chronic Heart Failure: More Questions Than Answers?

file:///data/core-remote/dit/data/elsevier/pdf/4df/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMDczNTEwOTcxMzAzOTgyeA==.pdf

Reply Left Ventricular Assist Devices in Chronic Heart Failure: More Questions Than Answers?

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector