Ventricular assist devices for the failing univentricular circulation

Abstract

Introduction:
Improved survival following single ventricle palliation has led to a large population of patients with a Fontan circulation, many of whom will eventually develop Fontan failure. Many of these patients will require heart transplantation. However, more than half of these patients have Fontan failure despite preserved ventricular function. Increasing experience with ventricular assist devices (VAD) in children has paved the way for VAD support in those with failing univentricular circulation. Areas covered: The use of VADs to support the failing univentricular circulation is a relatively new concept. Most studies have focussed on supporting patients with the failing systemic ventricle. However, there are limited reports on VAD support of the pulmonary circulation in those patients with a failing Fontan circulation despite preserved ventricular function. Although the concept of implantation of a "mechanical right ventricle" is attractive, none of the current VADs have been designed to support the low-pressure pulmonary circulation. Novel devices, which use low-pressure, high-flow pumps, specifically designed to support the pulmonary circulation, are currently under development. However, at this stage none have been tested in vivo. Expert commentary: The failing univentricular circulation is one of the great challenges in the field of congenital heart disease. While current VADs are designed to support systemic circulation, many patients may require support of the pulmonary circulation in addition to systemic circulatory support or in isolation. A fully implantable VAD for support of the pulmonary circulation as destination therapy would be beneficial for patients with preserved systolic function, but must have a low energy requirement, negligible risk of stroke and low risk of device thrombosis and failure.

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Ventricular assist devices for the failing
univentricular circulation
Edward Buratto, William Y. Shi, Xin Tao Ye & Igor E. Konstantinov
To cite this article: Edward Buratto, William Y. Shi, Xin Tao Ye & Igor E. Konstantinov (2017)
Ventricular assist devices for the failing univentricular circulation, Expert Review of Medical
Devices, 14:6, 449-459, DOI: 10.1080/17434440.2017.1332523
To link to this article: http://dx.doi.org/10.1080/17434440.2017.1332523
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REVIEW
Ventricular assist devices for the failing univentricular circulation
Edward Buratto, William Y. Shi, Xin Tao Ye and Igor E. Konstantinov
Department of Cardiac Surgery, The Royal Children’s Hospital, Melbourne, Australia; Department of Paediatrics, The University of Melbourne,
Melbourne, Australia; Murdoch Children’s Research Institute, Melbourne, Australia
ABSTRACT
Introduction: Improved survival following single ventricle palliation has led to a large population of
patients with a univentricular circulation, many of whom develop heart failure. Increasing experience
with ventricular assist devices (VAD) in children has paved the way for VAD support in those with failing
univentricular circulation.
Areas covered: The use of VADs to support the failing univentricular circulation is a relatively new
concept. Most studies have focused on supporting patients with the failing systemic ventricle. There are
limited reports of VAD support of the pulmonary circulation in patients with Fontan failure despite
preserved ventricular function. None of the current VADs have been designed to support the pulmon-
ary circulation. Novel low-pressure, high-flow pumps, specifically designed to support the pulmonary
circulation, are under development.
Expert commentary: The failing univentricular circulation is one of the great challenges in the field of
congenital heart disease. While current VADs are designed to support the systemic circulation, many
patients require support of the pulmonary circulation. A fully implantable VAD for support of the
pulmonary circulation as destination therapy would be beneficial for patients with preserved systolic
function, but must have low energy requirements, negligible risk of stroke and low risk of device
thrombosis and failure.
ARTICLE HISTORY
Received 1 March 2017
Accepted 16 May 2017
KEYWORDS
Univentricular circulation;
Fontan failure; ventricular
assist devices; Fontan
circulation; single ventricle
palliation
1. Introduction
1.1. The univentricular circulation
The current standard of treatment for patients with a func-
tional single ventricle is multistage palliation, resulting in a
Fontan circulation [1,2]. The absence of a subpulmonary ven-
tricle results in elevated central venous pressure (CVP) that, in
turn, contributes to failure of the univentricular circulation
and, in particular, Fontan failure, despite preserved ventricular
function [1–3]. While improvements in surgical technique and
postoperative care have meant that early survival has
improved in recent years [4–8], it appears inevitable that
many univentricular circulations will eventually fail [1–3].
Heart transplantation in patients with a Fontan circulation is
technically challenging [9,10], but recent reports have demon-
strated improving results, comparable to other forms of con-
genital heart disease [11–13]. Nevertheless, there is limited
donor supply and substantial mortality while awaiting trans-
plantation [14]. Thus, ventricular assist devices (VADs) are an
emerging option for the management of the failing univen-
tricular circulation (Figure 1), both to reduce waiting list mor-
tality [14–16] and, potentially, as a destination therapy [2]. We
review the current status of VAD therapy in patients with
univentricular circulation and discuss the principles guiding
the application VAD technology in these patients.
1.2. Ventricular dysfunction in the univentricular
circulation
Systemic ventricular dysfunction may cause failure of the uni-
ventricular circulation at any stage of palliation. Ventricular fail-
ure in these patients tends to be multifactorial [17]. Firstly, the
single ventricle palliated with a systemic to pulmonary artery
shunt is subjected to excessive volume work and dilatation,
increasing stress on the growing ventricle [18]. The presence
of relatively poor cardiac output and low blood pressure con-
tributes to vasoconstriction, increased peripheral resistance and
hence increased afterload [18]. Secondly, multiple operations
with prolonged cross-clamp times cause ischemia–reperfusion
injury to the myocardium, contributing to long-term ventricular
dysfunction [17]. In fact, prolonged cross-clamp time during the
Fontan procedure has been associated with risk of Fontan fail-
ure [19]. Thirdly, the systemic ventricle may be of right ventri-
cular morphology and hence not developmentally suited to
withstand systemic ventricular pressures [3,20]. Finally, in asso-
ciation with the patient’s structural heart disease, there may be
genetic mutations affecting the myocardium itself [17]. Hence,
ventricular dysfunction in patients with univentricular circula-
tion is multifactorial and challenging to manage. The use of
VADs to support the failing systemic ventricle has emerged as a
new treatment option for these patients.
CONTACT Igor E. Konstantinov igor.konstantinov@rch.org.au The Royal Children’s Hospital, Flemington Road, Parkville, Melbourne, VIC 3052, Australia
EXPERT REVIEW OF MEDICAL DEVICES, 2017
VOL. 14, NO. 6, 449–459
https://doi.org/10.1080/17434440.2017.1332523
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2. VADs in the univentricular circulation
2.1. Current status of VADs
In adults, VADs have an established role in the treatment of
end-stage heart failure as a bridge-to-transplantation, destina-
tion therapy, or rarely, recovery [21]. Over an 8-year period,
the INTERMACS registry has documented the implantation of
over 15,000 VADs in North America, of which 60.9% were
implanted as bridge-to-transplantation and 38.2% as destina-
tion therapy [21]. Over this short period, there has been an
expansion of indications, refinement in technology and
implantation strategies, improvement in survival and reduc-
tion in complications [21–24]. One of the most important
advances has been the development of continuous flow
VADs, which are associated with lower rates of complications
and improved survival [21,25]. Recent experience from the
INTERMACS registry has demonstrated a 1-year survival of
80% for left ventricular assist devices (LVAD) and 50% for
biventricular assist devices (biVAD) [21].
In contrast, in the pediatric population, VAD therapy is
more challenging due to patient size as well as the complex
anatomy associated with congenital heart disease [26].
Nevertheless, there is evidence that the advent of VAD tech-
nology has reduced the risk of waiting list mortality in children
listed for heart transplantation [14–16] and improved survival
compared to extracorporeal membrane oxygenation (ECMO)
[26]. The only available VAD developed specifically for children
is the Berlin Heart EXCOR (BHE), a pulsatile paracorporeal
device, which is suitable for supporting children with a body
weight as low as 2.5 kg [26,27]. Due to the improved out-
comes associated with the use of continuous flow devices in
adults, they have been increasingly used in children [28]. So
far the smallest child supported with a continuous flow VAD
(HeartWare) was 3.7 years of age, with a body surface area
(BSA) of 0.6 m
2
, weighing 13.5 kg [29]. The relationship
between patient size and selection of VAD technology is
demonstrated in Figure 2.
The first report of the PediMACS registry, a multicenter
database including pediatric VAD implantations performed at
66 North American centers, included 200 durable VADs, of
which just over half (109/200, 54.5%) were continuous flow
devices [31]. Almost all patients below 20 kg of weight were
supported by the BHE, while more than 80% (105/130) of
patients over 20 kg of weight were supported with continuous
flow devices [31]. At 6-month follow-up, 58% of patients had
been transplanted, 28% were alive on VAD support and 14%
had died. Survival of patients with continuous flow devices
was significantly better than those with pulsatile flow devices;
however, these patients were significantly older and had
higher BSA [31]. Nevertheless, the PediMACS registry demon-
strated that the rate of device malfunction was much higher
with the pulsatile flow devices [32], and as such continuous
flow VADs appear to be the device of choice for children large
enough to accommodate them.
Historically, Matusuda et al. [33] described the first
attempts at supporting children with univentricular circulation
with VADs in 1988. However, these initial attempts were
unsuccessful. The modern era of VAD support of the failing
univentricular circulation began in 2005, with Frazier et al. [34]
implanting a HeartMate VAD in a patient with Fontan failure.
To date, the total reported experience with VAD in patients
with univentricular circulation is 53 patients, which is summar-
ized in Table 1.
2.2. VAD support following stage I palliation
The experience of VAD support of patients following stage I
palliation is limited. The largest report is from Weinstein et al.
[50], who supported nine patients following stage I palliation,
of whom only one survived to transplantation. Specifically,
they had no survivors when VAD was implanted for failure to
wean from bypass in the operating theater or for failure to
wean from ECMO. The only survivor was 17-months post stage
I palliation at the time of VAD implantation. The authors
suggested that ECMO should be the preferred strategy in
this scenario due to the poor outcomes with VADs. Pearce
et al. [43] reported a 15-month-old boy with double outlet
right ventricle, d-transposition of the great arteries and mitral
atresia with circulatory failure following pulmonary artery
banding. The patient was treated with construction of a cen-
tral shunt, ligation of the pulmonary trunk and implantation of
BHE, with inlet cannula in the right atrium and outflow into
Figure 1. Algorithm for selection of the appropriate configuration of ventricular assist devices in the univentricular circulation.
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the ascending aorta. The patient was supported for 7 weeks
and then transplanted.
Support of children following stage I palliation has most
commonly been performed for postoperative ventricular dys-
function. There are numerous factors which may contribute to
the poor outcomes in this group, including the physiology of
the shunt-dependent circulation, patient age and size, and the
fact that support was generally used as salvage, due to inabil-
ity to wean from bypass. Given the poor results reported thus
far, VADs do not seem to provide an advantage over ECMO in
this setting.
2.3. VAD support following bidirectional cavopulmonary
shunt (BCPS)
There have been several reports of VAD support in patients
following BCPS, which are summarized in Table 1.The
largest experience is from Weinstein et al. [50], who
reported 12 patients supported with BHE VADs following
BCPS, of whom 58.3% (7/12) survived to transplantation.
Niebler et al. [52] described four patients treated with BHE
following BCPS, of whom 75% (3/4) survived to transplan-
tation. They found that despite achieving high cardiac out-
put, patients continued to have an elevated CVP, which
they attributed to abnormal aortopulmonary and veno-
venous connections. To overcome this challenge, they
advocated selecting a larger chamber size than would
normally be used for the same sized patient with biven-
tricular physiology [52]. Brancaccio et al. [47]reportedtwo
cases of VAD support following BCPS, of whom 50% (1/2)
survived to transplantation. Of a further four individual
cases described in the literature, 25% (1/4) survived to
transplantation. While the overall experience with VADs
in the setting of BCPS is limited, it appears to be a feasible
strategy with just over half of patients surviving to
transplantation.
2.4. Strategies of VAD support for the failing Fontan
Patients with Fontan failure fall into one of two categories:
those with impaired ventricular function and those with
preserved ventricular function [2]. The choice of VAD strat-
egy needs to be tailored to the nature of the patient’s
physiology. In initial reports of VAD therapy in the Fontan
circulation, the devices were used much like a conventional
LVAD, with the inflow cannula in the dominant ventricle or
atrium, and the outflow cannula in the ascending aorta. This
is the strategy of choice for patients with ventricular dys-
function as the cause of Fontan failure. It has been sug-
gested that this strategy may also work for patients with
predominantly right-sided failure in order to ‘pull’blood
flow across the pulmonary vascular bed [2]. However, it
may be ineffective in the setting of high venous pressures
due to increased pulmonary resistance, and so ‘biventricular’
support has been described for patients with both ventri-
cular dysfunction and elevated venous and pulmonary pres-
sures [35,49,51]. Furthermore, there is a group of Fontan
patients who primarily have high venous pressure and pul-
monary resistance as the cause of their failure, despite
preserved ventricular function. In this group, the use of
Figure 2. The relationship between choice of ventricular assist device, patient age and size. The use of continuous flow devices becomes increasingly prevalent as
age increases. Reproduced from Rossano J, Villa C, Konstantinov I [30], with permission.
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Table 1. Reported experience of ventricular assist devices used to support failing univentricular circulation.
Author Year NDevice Age (years) Stage Preserved systolic function Duration of support (days) Outcome
Frazier [34] 2005 1 Heartmate IP LVAS 14 Fontan No 45 Transplantation
Nathan [35] 2006 1 BiVAD: Berlin Heart 4 Fontan Not reported 28 Transplantation
Newcomb [36] 2006 1 Thoratec 25 Fontan No 152 Transplantation
Calvaruso [37] 2007 1 Berlin Heart 10 Fontan No 7 Transplantation
Chu [38] 2007 1 Berlin Heart 4 BCPS No 10 Death
Pretre [39] 2008 1 RVAD Berlin Heart 27 Fontan Yes 395 Transplantation
Russo [40] 2008 1 Centrifugal pump 14 Fontan No >6 Transplantation
Cardarelli [41] 2009 1 Berlin Heart 1.5 Fontan No 183 Recovery
Irving [42] 2009 1 Berlin Heart 3 BCPS No 7 Transplantation
Pearce [43] 2009 1 Berlin Heart 1.3 PAB No 49 Transplantation
Meira [44] 2011 1 HeartWare 12 Fontan No 1 Transplantation
VanderPluym [45] 2011 1 Berlin Heart 3 Fontan Yes 174 Transplantation
Mackling [46] 2012 2 Berlin Heart 4 Fontan No 309 Death
4 BCPS No 270 Death
Brancaccio [47] 2013 2 Berlin Heart 2 BCPS No 2 Transplantation
Berlin Heart 4 BCPS No 166 Death
Sanders [48] 2014 1 Berlin Heart 16 Fontan No 2 Transplantation
Valeske [49] 2014 1 Berlin Heart BiVAD 19 Fontan No 23 Transplantation
Weinstein [50] 2014 26 Berlin Heart
LVAD = 24
BiVAD = 2
Stage 1 = 9 Not reported Median: Stage 1: transplantation in 1/9
Stage 2: transplantation in 7/12
Stage 3: transplantation in 3/5
Stage 2 = 12 52
Stage 3 = 5
Arnaoutakis [51] 2016 5 Heartware 18 Fontan Not reported Median: 60 (for survivors) Transplantation
TAH 14 Fontan Not reported Transplantation
Berlin heart 3 BCPS Not reported Death
Berlin Heart 5 Fontan Not reported Transplantation
Thoratec 23 Fontan Not reported Death
Niebler [52] 2016 4 Berlin Heart 0.6 –2.3 BCPS Not reported 9 –312 3 transplantations, 1 death
Total Experience 53 Stage 1 = 10 Stage 1: 2/10 (20%) transplanted
BCPS: 12/22 (55%) transplanted
Fontan: 16/21 (76%) transplanted
BCPS = 22
Fontan = 21
BCPS: bidirectional cavopulmonary shunt; LVAD: left ventricular assist device; BiVAD: biventricular assist device; PAB: pulmonary artery banding; RVAD: right ventricular assist device; TAH: total artificial heart.
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VADs to support the pulmonary circulation, so-called ‘cavo-
pulmonary support’, has been described [39]. These strate-
gies are demonstrated in Figures 3 and 4.
2.5. VADs to support the systemic ventricle
Inthemajorityofreportedcases, VADs have been used to support
the systemic ventricle in patients with univentricular physiology
[45–48,50–52], similarly to how an LVAD is used in the biventricu-
lar circulation (Figures 3(a) and 4(a)). In the majority of these cases,
BHE has been used (see Table 1), although there have also been
reports of Thoratec [36,51], HeartMate [34], and HeartWare [44].
The technique of VAD implantation to support the systemic ven-
tricle is similar to standard LVAD insertion; however, some specific
technical considerations have been described, particularly regard-
ing the positioning of the inlet cannula. Challenges include
adhesions due to previous surgery, coronary artery abnormalities,
presence of a prominent nondominant ventricle obscuring access
to the dominant ventricle, and cannula obstruction from ventri-
cular trabeculations and the subvalvular apparatus, especially
when the right ventricle is dominant [36,47,50,52]. Nevertheless,
in most reported cases, the inflow cannula has been placed in the
apex of the dominant left ventricle [36,37,41,42,48,50–52]orinthe
diaphragmatic surface of the dominant right ventricle [38,44,47].
Additional strategies have been described to deal with inlet can-
nula obstruction, such as resection of muscular bands and resec-
tion of the atrioventricular valves and their subvalvular apparatus
[34,52]. Placement of the inflow cannula in the pulmonary venous
atrium has been described as another strategy to avoid inlet
cannula obstruction [33,40,51].
Outcomes of VAD support of the systemic ventricle have been
reported in two small case series and a number of case reports
Figure 3. Configurations of Berlin Heart Excor VAD in the Fontan circulation. (a) supporting the systemic ventricle, (b) supporting the pulmonary circulation and (c)
supporting both.
Figure 4. Configurations of continuous flow VAD in the Fontan circulation. (a) supporting the systemic ventricle, (b) supporting the pulmonary circulation and (c)
supporting both.
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(Table 1). The largest report, from Weinstein et al. [50], includes
five patients with a Fontan circulation, of whom 60% (3/5) sur-
vived to transplantation. By comparison, 72% of children with
biventricular physiology from the same database survived to
transplantation. Arnatoukakis et al. [51]reportedfourpatients
with Fontan circulation who underwent VAD implantation, three
of whom (75%) survived to transplantation. Taken together, the
remaining case reports included 14 patients, of whom 78.6% (11/
14) survived to transplantation, 7.1% (1/14) were successfully
weaned and 14.3% died (2/14) [34,36,37,40,41,44–46,48]. These
results are similar to those reported for the overall population of
children supported with VAD in the PediMACS registry, which
demonstrated that at 6-month follow-up, 61% of patients had
been transplanted, 31% remained on VAD support, and 8% had
died prior to transplant [32]. These results are encouraging and
seem to be similar to the overall results reported for VAD support
in the pediatric population. However, it must be recognized that
data from case reports are particularly prone to publication bias
toward good results, and that none of these reports contains
significant long-term follow-up.
The complications observed during VAD support were similar
to those seen with VAD in children with biventricular circula-
tions, dominated by bleeding, neurological events, and infection
[32]. Weinstein et al. [50] reported an overall adverse event rate
of 73.1%, with respiratory failure (42.3%), bleeding (38.5%),
infection (23.1%), and neurologic dysfunction (15.4%) being
the most common complications. Furthermore, pump change
due to thrombus was required in 26.9% of patients. For compar-
ison, in the PediMACS database, the commonest adverse events
were device malfunction (39.5%), infection (39.0%), bleeding
(34.0%), and neurological dysfunction (26%) [32].
Despite the technical challenge of implanting VADs in
patients with a univentricular circulation, survival to transplanta-
tion is in the range of 60–80% across the small number of
published cases. Furthermore, the complication profile appears
to be similar to that reported for VADs in the general population
of children requiring ventricular support. The use of VAD ther-
apy as a bridge to transplantation for patients with a failing
univentricular circulation is emerging as a viable option.
2.6. ‘Biventricular’support in the univentricular
circulation
In patients with both ventricular dysfunction and raised venous
pressure and pulmonary resistance, supporting the systemic ven-
tricle may not be sufficient to achieve stable hemodynamics. In
these patients, it may be better to convert to ‘biventricular sup-
port,’with one pump supporting the systemic ventricle, and
another supporting the cavopulmonary circulation, much like a
conventional right ventricular assist device (RVAD) (Figures 3(c)
and 4(c)). There are few reports of biventricular support in the
setting of univentricular circulation, comprising three patients
with BiVADs and one patient with a total artificial heart (TAH).
Nathan et al. [35] reported BiVAD implantation in a 4-year-
old girl with a failing Fontan circulation. The child had plastic
bronchitis, pleural effusions, and a pulmonary vascular resis-
tance of 3.8 Wood units. Initially, a 30 mL BHE VAD was
implanted from the systemic ventricular apex to the ascending
aorta. However, as there was significant venous hypertension,
it was decided to place a 25 mL BHE as an RVAD. The cavo-
pulmonary anastomosis was taken down, the inflow cannula
was inserted into the lateral tunnel, and the outflow cannula
was inserted into the pulmonary arteries. This child underwent
transplantation after 28 days of support.
Valeske et al. [49] reported a 19-year-old male who had under-
gone Fontan with a total cavopulmonary connection (TCPC) and
presented in New York Heart Association (NYHA) class IV heart
failure with a severely dilated systemic ventricle. They implanted
two Berlin Heart pumps as a BiVAD. The RVAD drained both vena
cavae via the extracardiac conduit, with the outflow placed in the
pulmonary artery. The LVAD was placed between the left atrium
and the ascending aorta. The patient underwent successful
orthotopic heart transplantation after 23 days of support.
Arnaoutakis [51] reported a single case of TAH implantation
in a 14-year-old child with a failing Fontan circulation compli-
cated by renal failure and plastic bronchitis. They reported
recovery of end-organ function on TAH support and survival
to heart transplantation.
Although there is limited data on the use of BiVAD in
univentricular patients, there are promising results and this
strategy offers the potential to support patient with both a
failing systemic ventricle and high venous pressures, in whom
support of the systemic ventricle alone may not be sufficient.
2.7. Failure of Fontan circulation with preserved
ventricular function
Due to the lack of a sub-pulmonary ventricle, patients with a
Fontan circulation generally have a CVP of 10–15 mmHg, three
times greater than the normalphysiologicallevel[1](Figure 5).
Hence, these patients are prone to complications of elevated
venous pressures, including hepatic congestion and cirrhosis,
ascites, peripheral edema, and protein-losing enteropathy [18].
Due to the low flow across the pulmonary vasculature, there is
chronic under-filling of the systemic ventricle, which in combina-
tion with ventricular hypertrophy, contributes to diastolic dysfunc-
tion [3,18]. Additionally, the systemic ventricle may also fail due to
the factors described earlier: dilatation and overloading prior to
BPCS, increased afterload, repeated cardiac procedures, genetic
mutations, and right ventricular morphology. All of these factors
may contribute to Fontan failure, which although lacking a stan-
dardized definition, is generally said to be any of death, transplan-
tation, takedown, Fontan conversion, NYHA class III/IV symptoms,
protein-losing enteropathy, or plastic bronchitis [53]. Based on the
mechanism of Fontan failure, patients may be classified into two
groups: those with ventricular dysfunction and those with pre-
served ventricular function [3]. Importantly, more than half of
patients with Fontan failure have preserved ejection fraction [20].
The importance of understanding the mode of Fontan failure is
highlighted by the fact that those with preserved ejection fraction
have poorer survival after transplantation [54], demonstrating that
patients will respond differently to interventions depending on
their underlying mechanism of Fontan failure.
2.8. Isolated support of pulmonary circulation
As has been previously described, more than half of patients
with a failing Fontan have preserved function of their
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dominant ventricle, and thus effectively have ‘right-sided’fail-
ure [53]. These patients could be supported by a VAD placed
between the extracardiac conduit and the pulmonary arteries
(Figures 3(b) and 4(b)). There is only a single case report of
cavopulmonary support using a VAD in a patient with a uni-
ventricular circulation. Prêtre et al. [39] presented a 27-year-
old man who underwent Fontan conversion from an atriopul-
monary connection to extracardiac conduit and developed
severe cardiac failure 16 weeks later. The patient had normal
ventricular function but an elevated CVP of 33 mmHg. The
cavopulmonary anastomoses were taken down and the pul-
monary arteries repaired. The extracardiac conduit was
replaced with a larger graft and the superior vena cava (SVC)
and inferior vena cava (IVC) both anastomosed to it. The
inflow cannula of a 60 mL Berlin Heart was inserted into the
extracardiac conduit, while the outflow cannula was inserted
into the reconstructed pulmonary arteries. The patient’s clin-
ical condition improved substantially and he underwent car-
diac transplantation after 13 months of support. Given the
large proportion of Fontan patients with failure despite pre-
served ventricular function, this is a very promising strategy
and represents a ‘proof of concept’for the possibility of cavo-
pulmonary support for the treatment of Fontan failure.
However, the VADs currently available are designed for sup-
port of the systemic ventricle rather than the low-pressure
pulmonary circulation, and hence this strategy is currently
limited by the lack of appropriate pump technology.
3. Emerging technologies
While there have been encouraging results using VADs to support
the univentricular circulation, none of the devices currently avail-
able has been designed for this application. Given that more than
half of patients with Fontan failure effectively have ‘right-sided’
failure [53], with elevated venous pressures and pulmonary
resistance, much of the current research focuses on the develop-
ment of a ‘cavopulmonary assist device’. As previously discussed,
the major hemodynamic limitations of the Fontan circulation are
systemic venous hypertension, decreased pulmonary blood flow,
and under-filling of the systemic ventricle [55]. Based on the
hemodynamic complications observed with the Fontan circula-
tion, it has been postulated that the ideal hemodynamic effect of
the pump for cavopulmonary support is a small decrease in venous
pressure, with a small increase in pulmonary pressure and flow,
each of approximately 5 mmHg [55–57]. As such, the ideal pump
for cavopulmonary support differs markedly from currently avail-
able VAD technology. Current VADs are designed to generate a
high-pressure gradient at partial flow rates, and as a result have
significant energy requirements and generate significant negative
pressures at their inflow cannula [2,55]. A device for cavopulmon-
ary support, which is a low-pressure, high-volume pump providing
a pressure step up of only 5 mmHg, is likely to be sufficient for
supporting the Fontan circulation [55–57]. This should allow for
greater pump efficiency and improved battery life, potentially
allowing for a completely implantable design with a long-life
battery similar to pacemaker, or even transcutaneous charging
[2]. Finally, the ideal assist device would not obstruct the cavopul-
monary blood flow in the case of mechanical failure. Such devel-
opments would make destination therapy a viable option for
patients with Fontan failure.
Initial experimental research on cavopulmonary support of
the failing Fontan has utilized existing VAD technology in
animal models immediately after construction of the single-
stage TPCP. Several groups have shown that short-term sup-
port of the TCPC in an animal model is feasible, providing
adequate cardiac output and an increase in pulmonary arterial
(PA) pressures with stable or decreased venous pressures
compared to the biventricular circulation at baseline [55,57–
62]. However, venous collapse and hence circulatory obstruc-
tion, as well as entrainment of air through the Goretex graft,
Figure 5. Diagrammatic representation of the haemodynamics of (a) the normal biventricular compared to (b) the Fontan circulation compared to. Note the
elevated central venous pressure due to the lack of a subpulmonary ventricle to drive pulmonary blood flow. Reprinted from Jaquiss and Aziz [2] with permission
from Elsevier.
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have been observed due to the high negative pressures gen-
erated by these devices [58,59]. Furthermore, when placed in
the large caliber vessels of the TCPC, micro-axial pumps are
associated with recirculation of almost half of the pump flow,
as well as retrograde SVC flow, requiring higher pump speeds,
decreasing efficiency, and increasing the risk of hemolysis
[55,57,60].
To overcome the shortcomings of current generation VADs,
several groups are working on the development of novel
pumps specifically designed for cavopulmonary support.
Rodefeld’s group [63,64] have developed a design based on
the Von Kàrmàn impellar pump, which is implantable at the
junction of the TCPC, augmenting flow in all four directions,
directing outflow down both pulmonary arteries. Importantly
this is a low-power design, which provides a small step up in
pressure, replicating the role of the right ventricle.
Furthermore, even when stationary it improves efficiency of
the Fontan circulation by reducing turbulence, rather than
causing circulatory obstruction. This means that even in the
case of device failure it would still be of hemodynamic benefit,
which is an ideal situation. So far, however, only results of
computation modeling and in vitro experimentation have
been published.
Lacour-Gayet et al. [65] described the application of a novel
micro-axial flow pump in a modified in vitro mock-up of the
Fontan circulation. The extracardiac conduit in their model
had a Y-shaped configuration, with SVC and IVC inflow and
an outflow arm anastomosed to the pulmonary trunk. The
micro-axial pump was implanted in the outflow arm. Using
this strategy, recirculation and retrograde flow into the SVC
were minimized. In their model, CVP was reduced, PA pres-
sures were modestly increased, and cardiac output was
increased by up to 2L/min. However, they did observe collapse
of the vena cavae at pump speeds above 3000 rpm. This
design, however, has yet to be tested in vivo.
Throckmorton et al. [66] also described a novel, low-pres-
sure axial pump tested in vitro in a mock TCPC. The pump
demonstrated a pressure step up of 2–16 mmHg, without
evidence of cavitation. A further evolution of this pump is
designed to be percutaneously inserted in the IVC while pro-
viding the same hemodynamic benefits, and it has also been
tested in vitro [67]. Most recently, this group has published
work on refinements of axial flow pump design in order to
maximize efficiency for the specific application as cavopul-
monary support [68,69]. None of these designs has been
tested in vivo as of yet.
In vitro tests of existing VAD technology have provided
proof of concept for cavopulmonary support of the Fontan
circulation. However, these pumps have several limitations as
they are designed to support the systemic circulation. Novel
pumps designed specifically to address the requirement of
cavopulmonary support have shown promising results in
vitro, but have yet to be tested in vivo.
4. Conclusions
The failing Fontan circulation is one of the major challenges in
the field of congenital heart disease. There is a growing num-
ber of patients with a Fontan circulation and many, if not all,
will eventually experience failure of their Fontan circulation.
Results of VADs applied to failing univentricular circulation are
encouraging, and currently VAD support of the failing Fontan
as a bridge to transplantation is a viable strategy. However,
none of these devices have been designed to address the
majority of patients who have a Fontan circulation with pre-
dominantly ‘right-sided’failure. Novel devices designed to
support the low pressure, high flow cavopulmonary circulation
are under development, but have not yet been tested in vivo.
These devices offer hope of a fully implantable pump for
cavopulmonary support of the failing Fontan as destination
therapy.
5. Expert commentary
As the population of patients with a Fontan circulation surviv-
ing into adulthood continues to increase, clinicians will face
the clinical challenge represented by Fontan failure ever more
frequently. The current mainstay of therapy is heart transplan-
tation, but waiting times are long, donor supply is limited,
waiting list mortality is high, and we are often replacing the
heart in patients who have preserved systolic function.
Furthermore, heart transplantation substitutes one terminal
disease for another and does not offer these patients a chance
at normal life expectancy. The results of VAD use in patients
with a univentricular circulation are indeed encouraging, sug-
gesting that they are suitable for supporting patients with
Fontan failure who are deteriorating while awaiting transplan-
tation. However, the currently available technology is not well
suited to this application, being designed for support of the
systemic circulation, while more than half of all patients with
Fontan failure actually have preserved ventricular function.
Although the use of these devices to support the pulmonary
circulation has been reported, as they are designed for high
pressure environment, they are not optimized for this situa-
tion, unnecessarily increasing the risk of complications such as
pulmonary hypertension, venous collapse, obstruction of flows
and hemolysis.
We believe that a fully implantable low-pressure, high-
volume pump inserted into the Fontan pathway as cavopul-
monary support for use as destination therapy represents
thefutureofmanagingthefailingFontan.Thelowpower
requirements of this type of pump means that a long-life
battery, similar to that of a permanent pacemaker, should
be feasible, allowing intermittent replacement of a subcuta-
neous power supply. Alternatively, the advent of transcuta-
neous charging may eliminate the need for battery
replacement entirely. Allowing the device to become fully
implantable is a key to reducing the risk of infections. The
new pump designs are encouraging, especially that of
Rodefeld’sgroup[63,64], which promotes a complex flow
pattern from the IVC and SVC into both pulmonary arteries.
Most impressively, the pump improves Fontan efficiency
even when stationary, minimizing the risk posed by device
failure, and providing a unique opportunity to more easily
conduct weaning trials. This is a key feature for the totally
implantable device to be successful as destination therapy –
device failure must not result in circulatory obstruction. The
final major challenge which needs to be addressed is the
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risk of thrombogenicity, as the Fontan circulation is already
prone to thrombosis. However, devices such as Rodefeld’s
design, which improves blood streaming and reduces tur-
bulence at the TPCP, may go some way to mitigating this
risk.
As exciting as these technologies are, they remain a
long way from clinical practice, as none has yet been
tested even in animal models. Nevertheless, the growing
population of children and adults with a failing Fontan
circulation creates an urgent need for such devices,
which will no doubt expedite their development. A gen-
eration of children is relying on the community of cardiac
surgeons to provide them with a more certain future; a
fully implantable pump for cavopulmonary support
appears to be the way forward.
6. Five-year view
Given the promising results reported so far, in the next 5 years
we are likely to see increased use of current generation VADs
to support the failing Fontan circulation. It can be expected
that in the majority of cases these devices will be used as a
bridge to transplantation, as none of the devices are suitable
for destination therapy. Hence, heart transplantation will
remain the mainstay therapy for management of the failing
univentricular circulation, with VAD increasingly playing a
supporting role.
Testing of new-generation devices can be expected to
progress from the current in vitro experiments to animal test-
ing. It is possible, however, that toward the end of the next
5 years period we may see the first human trials of these novel
cardiopulmonary assist devices. While these developments are
exciting, the goal of a totally implantable cavopulmonary
support device as destination therapy appears to be more
than 5 years away from realization.
Key issues
●As the population of Fontan patients increases, Fontan fail-
ure will be an increasingly common problem.
●Current VADs are designed to support the systemic ventri-
cle. They are high-pressure pumps.
●VADs have promising results for the support of the failing
Fontan circulation as a bridge to transplantation.
●Most patients have ‘right sided failure’with preserved sys-
tolic function. These patients would benefit from a low
powered pump for cavopulmonary support.
●While novel low-pressure pumps for cavopulmonary sup-
port are under development, currently they remain at the
stage of in vitro testing.
●The goal is a totally implantable pump for cavopulmonary
support with prolonged battery life which can be used as
destination therapy.
Funding
This paper was not funded.
Declaration of interest
E. Buratto is a recipient of a Reg Worcester Scholarship from the Royal
Australasian College of Surgeons and a Post Graduate scholarship from the
National Health and Medical Research Council (APP1134340). The authors
have no other relevant affiliations or financial involvement with any organi-
zation or entity witha financial interest in or financial conflict with the subject
matter or materials discussed in the manuscript apart from those disclosed.
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