www.elsevier.com/locate/ppedcard

Progress in Pediatric Cardio

Ventricular assist devices for children

J. Timothy Baldwin a,*, Brian W. Duncan b

a The Division of Heart and Vascular Diseases, The National Heart, Lung, and Blood Institute. Two Rockledge Centre, Room 9150,

6701 Rockledge Drive, Bethesda, MD 20892-7940, USAb The Departments of Pediatric and Congenital Heart Surgery and Biomedical Engineering, The Cleveland Clinic Foundation, USA

Abstract

Infants and children may experience such severe heart failure that circulatory support is required as a bridge to recovery,

transplantation, or until other surgical intervention can be performed. While older children may be supported by devices designed for use

in adults, historically, options for pediatric circulatory support have been limited to extracorporeal membrane oxygenators (ECMO), short-

term centrifugal pump-based ventricular assist devices (VADs), and paracorporeal VADs. However, these devices present substantial risk

for adverse events in the pediatric population. To address the need for improved circulatory support devices for the youngest pediatric

patients, new devices specifically targeted to this vulnerable population are being developed. These include implantable rotary blood

pumps, compact cardiopulmonary assist systems, and extracorporeal pulsatile and rotary pumps for acute and chronic support. Several

devices are expected to be available for clinical evaluation soon. These devices will hopefully provide solutions for challenges that are

unique to pediatric circulatory support, such as the anticipated growing population of failing single ventricle patients who have previously

undergone a Fontan procedure.

D 2005 Elsevier Ireland Ltd. All rights reserved.

Keywords: Heart failure; Ventricular assistance; Cardiomyopathy; Pediatric and congenital heart disease

1. Introduction

Ventricular assist devices (VADs) are now reaching

relatively high levels of success for treating heart failure in

adults, as demonstrated by the growing bridge to transplant

experience which now numbers in the thousands of cases [1–

7]. The superiority of VADs over optimal medical therapy as

a treatment for late-stage congestive heart failure was

demonstrated in the landmark REMATCH trial. The trial

also provided clinical evidence for FDA approval of the

HeartMate VE VAD as a permanent ‘‘destination’’ therapy

[8–10]. Other VADs, including newer-generation rotary

devices, are currently undergoing clinical trials to achieve

similar approval [11,12]. In contrast, technological advances

in pediatric mechanical circulatory support have lagged well

behind. While the patient numbers are much smaller, the

potential in recovered patient-years is great considering that,

when given adequate support, the likelihood of long-term

1058-9813/$ - see front matter D 2005 Elsevier Ireland Ltd. All rights reserved.

doi:10.1016/j.ppedcard.2005.11.005

* Corresponding author. Tel.: +1 301 435 0498; fax: +1 301 480 1335.

E-mail address: baldwint@nhlbi.nih.gov (J. Timothy Baldwin).

recovery is very high [13,14]. Today, the most common

approach to pediatric mechanical circulatory support is

extracorporeal membrane oxygenation (ECMO) [15–19].

This can be attributed to both a lack of alternative pediatric

assist devices and the extensive pediatric experience utilizing

ECMO for the treatment of respiratory failure. Despite its

widespread use, ECMO restricts patient mobility, presents

significant risks for adverse events such as bleeding,

thromboembolic events, and infection, and, as such, is only

adequate for short-term support.

The use of VADs for pediatric circulatory support has

been shown to result in significantly fewer long-term

complications compared to ECMO support [13,14]. Essen-

tially all pediatric VAD experience in the United States is

limited to a single centrifugal pump-based system. While a

greater number of alternatives are available worldwide, most

are pulsatile, paracorporeal devices, that are not fully

implantable for the majority of children [20–24]. Clearly,

the limited options for mechanical support of the failing

circulation continues to be one of the major issues in

pediatric cardiology and cardiac surgery.

logy 21 (2006) 173 – 184

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184174

2. Challenges in pediatric mechanical circulatory

support

2.1. General considerations

The most obvious consideration in the design and

development of circulatory support systems for children is

patient size. The ideal device for pediatric mechanical

circulatory support should be capable of providing support

across a large range of patient sizes—from newborns to

young adults. Existing paracorporeal systems require major

skin penetrations, which commonly result in substantial risk

for infection. Beyond implications for the pump itself,

however, size considerations exist for all aspects of device

design for children including cannulas, energy sources, and

control mechanisms. In addition to challenges relating to the

size of the pediatric patient, the diverse anatomic variations

routinely encountered in congenital heart disease make

universal application of a single pump design impossible.

Specifically, abnormalities of the systemic and pulmonary

venous anatomy affect design of pump inflow while

abnormalities of the great arteries impact on the design of

pump outflow. Abnormalities of visceroatrial situs, such as

situs inversus, and abnormalities of the location of the

cardiac apex, such as dextrocardia and heterotaxy, may

make institution of support difficult for many existing pump

designs.

Circulatory support devices for children should take into

account other physiologic considerations unique to pediat-

rics. Children, especially newborns, are more prone to

complications related to anticoagulation and are vulnerable

to the infections commonly associated with mechanical

circulatory support [15]. Newborns often manifest an

exaggerated systemic inflammatory response after cardio-

pulmonary bypass that may evolve into multi-system organ

failure during prolonged ECMO or VAD support. Also, a

large percentage of children who require a VAD need urgent

institution of support to treat cardiac arrest following cardiac

surgery or in the setting of acute myocarditis [15,25–27]. To

address these issues, pediatric circulatory support devices

should require only minimal or no anticoagulation, mini-

mize the risk of infection, trauma to blood elements, and

systemic inflammation, and allow rapid deployment to

improve outcomes [25,28,29].

Despite these challenges, mechanical circulatory support

has become an important option for treatment of pediatric

cardiac disease. In the acute setting, even the most severe

cases of postcardiotomy circulatory failure and various

medical conditions such as myocarditis and cardiomyopathy

can be managed with mechanical circulatory support if

medical management fails [15–18,22–56]. For isolated

postcardiotomy failure, the availability of mechanical

circulatory support has often provided the ‘‘safety net’’ that

has allowed increasingly complex surgical procedures to be

developed for children with the most severe forms of

congenital heart disease. In addition to the use of

mechanical circulatory support in the acute setting, there

exists an expanding patient population with congenital heart

disease that may benefit from chronic mechanical circula-

tory support. One such important patient category to be

discussed below includes children who possess single

ventricle physiology who have undergone the series of

palliative operations referred to as the ‘‘Fontan pathway’’

that physiologically septates the pulmonary and systemic

circulations. The great majority of children are now

surviving after the Fontan procedure who would have

otherwise died during childhood. Having survived through

childhood, but possessing palliated circulatory physiology,

many of these patients may develop the need for implant-

able circulatory support devices as a bridge to transplanta-

tion or as destination therapy in the future.

2.2. Mechanical support of the failing single ventricle

Due to increasingly successful early management, the

population of patients with palliated single ventricle

physiology who develop failure of the systemic ventricle

will undoubtedly continue to increase. The need for

mechanical circulatory support for this patient population

is expected to increase in parallel as a bridge to

transplantation and perhaps eventually as destination

therapy. There are a limited number of reports describing

the use of ECMO and VADs primarily for short-term

circulatory support for these patients, while very little

experience exists for chronic support of the failing single

ventricle [19,57,58]. This will be a particularly challenging

patient population to support with a number of unique

issues. For example, these patients often exhibit anatomic

abnormalities of the great arteries and veins, which may

make cannulation difficult. Most of these patients encoun-

tered beyond early childhood have undergone multiple

operations predisposing them to complications that occur

in any reoperative cardiac surgical patient. Finally, many

of these patients suffer from complications resulting from

venous hypertension in the splanchnic circulation such as

cirrhosis, ascites and protein losing enteropathy. Therefore,

many of these patients will have ongoing issues related to

infection, malnutrition and postoperative bleeding at the

time of device implantation, or be predisposed to their

development postoperatively.

Perhaps the greatest challenge will be to understand and

appropriately manage the underlying physiology of patients

with single ventricles while supported using devices

designed for patients with two ventricles. In the vast

majority of cases, effective support of failing Fontan

circulation can be achieved with apical cannulation of the

systemic ventricle for drainage with reinfusion via the aorta

as is performed for left ventricular assistance in two

ventricle physiology. Left-sided support would reduce the

filling pressure of the single ventricle, which would result in

decreased pressure in the Fontan (pulmonary) circuit. This

would undoubtedly provide substantial reduction in system-

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184 175

ic venous hypertension thereby improving pulmonary and

systemic hemodynamics with assistance of the left-side

circulation alone.

Significant improvement would be expected even in

cases where complications of systemic hypertension in the

splanchnic circulation predominate, such as isolated protein

losing enteropathy. Placing a pump directly in the Fontan

pathway would probably usually be less useful and would

provide a number of additional challenges. This approach

would be limited to settings in which pulmonary vascular

resistance was elevated due to recurrent pulmonary emboli

or pulmonary parenchymal disease, with preserved single

ventricle function. Even in these cases great care in

management would be required if, for example, a single

axial flow pump was placed in the inferior vena cava limb of

the Fontan circuit to avoid dangerous elevations of systemic

venous pressure in the superior vena cava and remainder of

the pulmonary circuit. In addition, increased filling of the

systemic ventricle due to increased pulmonary flow might

unmask subclinical dysfunction of the single ventricle.

Regardless of the side of the circulation supported,

mechanical support instituted for systemic venous hyper-

tension due to a failing single ventricle might be able to be

effectively achieved with relatively low flows and minimal

energy requirements. Perhaps only intermittent use would

be required. For example, support applied only during sleep

might effectively reverse complications related to systemic

venous hypertension if regurgitation through the device was

limited during periods when device flow was not occurring.

The exact details of mechanical circulatory support systems

for the failing Fontan circulation remain largely speculative

at the moment, but represent another potentially exciting

application of mechanical circulatory support of congenital

heart disease.

3. Special topics in pediatric mechanical circulatory

support

3.1. Use of rapid resuscitation ECMO in the treatment of

cardiorespiratory arrest

Cardiac arrest is a common indication for ECMO,

accounting for nearly 25% of all indications for mechan-

ical circulatory support of pediatric patients [15]. Several

groups have developed systems that allow the expeditious

institution of ECMO after cardiac arrest that is refractory

to conventional cardiopulmonary resuscitation [25,28,29].

One system that has been described utilizes a modified

ECMO circuit, an organized team of personnel to perform

cannulation, and a streamlined priming process [25]. The

‘‘rapid resuscitation’’ ECMO circuit is maintained vacuum

and CO2-primed in the intensive care unit and is portable

with a battery power supply allowing it to be quickly

utilized in any location throughout the hospital. If standard

CPR is unsuccessful within 10 min, the circuit is moved to

the patient’s bedside and crystalloid priming is initiated

while cannulation is proceeding. If cannulation is com-

pleted prior to the availability of blood products, ECMO

flow is initiated with a crystalloid-primed circuit and blood

products are added when available. In the original

description of this system, 11 pediatric cardiac patients

who had suffered cardiorespiratory arrest were resuscitated

with this rapid resuscitation approach [25]. The median

duration of CPR for these 11 patients was 55 min (range

15–103 min) compared to a median duration of CPR of 90

min (range 45–200 min) for seven historical controls

resuscitated with conventional means prior to the utiliza-

tion of the rapid resuscitation system. All but one of the 11

rapid resuscitation patients were weaned from ECMO with

seven patients (64%) surviving to hospital discharge

compared to two survivors (29%) of the seven historical

controls.

Jacobs and coworkers reported a rapid resuscitation

system based on a circuit that employs a hollow-fiber

oxygenator and a centrifugal pump [29]. This system is fully

portable with a priming volume of 250 ml and is heparin-

bonded throughout. The use of the centrifugal pump

eliminates the need for gravity drainage, which results in

shorter tubing lengths and greater portability. A major

advantage of this system is the extremely short set-up time

which enables crystalloid priming to be completed in as

little as 5 min. Using this system, the duration of CPR was

only 12 min prior to the institution of ECMO.

These reports support the concept that pediatric cardiac

patients who suffer cardiac arrest often deserve an aggres-

sive approach with prompt institution of ECMO if

conventional resuscitative measures fail. Rapid institution

of circulatory support with modified ECMO systems can be

life saving with preservation of end-organ function in these

patients.

3.2. Support for hypoplastic left heart syndrome and other

single ventricle forms

In a report of a single center’s pediatric mechanical

circulatory support experience through 1996, only 2% of all

cases were children with hypoplastic left heart syndrome

[15]. A subsequent report from 2001 demonstrated that

perioperative support of the Norwood procedure was the

single largest diagnostic category (28%) for all pediatric

cardiac cases who required circulatory support [59]. This

difference over a 5-year period is representative of trends

reported by other institutions. While previously considered

to be a relative contraindication, patients who possess

hypoplastic left heart syndrome and other forms of single

ventricle physiology are now considered to be candidates

for mechanical circulatory support. In fact, several reports

have emphasized the importance of having an active ECMO

program available at pediatric cardiac centers to provide the

full complement of treatment options for these complex

patients [57,59,60].

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184176

Pizarro and Aharon described survival rates of 50% and

64%, respectively, for infants who required mechanical

circulatory support after the Norwood procedure [59,60].

While conventional ECMO may be used in these patients,

Darling and co-authors reported 80% survival utilizing a

circuit configured without an oxygenator to support patients

after the Norwood procedure [57].

3.3. Mechanical circulatory support for acute, fulminant

myocarditis

The survival rate for children who require mechanical

circulatory support for myocarditis is relatively good in

most reports [33,34,61–65]. A recent multi-institutional

review of 15 patients with viral myocarditis supported by

ECMO (12 patients) or VADs (3 patients) demonstrated an

overall survival rate of 80% [27]. Nine of 15 patients were

weaned from support with seven survivors (78%) while the

remaining six patients were successfully bridged to

transplantation with five survivors (83%). An especially

important finding was that all non-transplanted survivors

are currently alive with normal ventricular function. Two

recent reports further emphasize the likelihood of recovery

in these patients with survival rates of 73% and 100%; no

patient in either series required transplantation and all

survivors demonstrated normal ventricular function

[66,67]. Historically, it was believed that a significant

percentage of children with acute myocarditis would

develop dilated cardiomyopathy with the ultimate need

for cardiac transplantation. These studies suggest that

children with acute, fulminant myocarditis have an overall

favorable outcome and a significant degree of disease

reversibility if successfully supported during the acute

phase of illness.

The reasons for better long-term outcomes and a

decreased incidence of progression to dilated cardiomyop-

athy in patients most severely affected by myocarditis

remains unexplained. However, mechanical circulatory

support may contribute to the improved long-term outcomes

in these children. It is reasonable to speculate that

normalization of ventricular geometry and function by the

early institution of support may help to prevent progression

to dilated cardiomyopathy.

Based on these results, the optimal approach for children

presenting with acute fulminant myocarditis may be to

provide mechanical circulatory support, even if required for

prolonged periods, in anticipation of eventual ventricular

recovery. Previous reports have demonstrated the feasibility

of this approach with full return of ventricular function in

children and young adults with myocarditis after weeks or

months of mechanical support [23,54,68,69]. Prolonged

mechanical circulatory support in a larger number of

pediatric patients with fulminant myocarditis may reveal

that extended MCS in children restores native ventricular

function, thereby obviating the need for transplantation in

virtually all of these children.

4. Existing pediatric circulatory support devices

The circulatory support devices currently available for

clinical use to support the circulation in pediatric patients

are described below.

4.1. ECMO

Reports of single center’s experience usually find that

conditions of complex cyanotic heart disease with either

excess pulmonary blood flow (such as transposition of the

great arteries) or decreased pulmonary blood flow (such as

tetralogy of Fallot) constitute the majority of cases requiring

ECMO for pediatric cardiac support [15,49,70]. The most

common scenarios for support usually occur in children

after cardiac surgery, namely, failure to wean from

cardiopulmonary bypass and cardiogenic shock or cardiac

arrest occurring in the intensive care unit postoperatively

[33,38,45,48,50,51,55,70–75]. However, refractory medical

conditions also occur in children that require mechanical

circulatory support including hypoxia and pulmonary

hypertension, along with diseases of the myocardium

including metabolic cardiomyopathy and myocarditis

[24,27,34,54,76,77]. Conditions that were historically felt

to represent contraindications for ECMO are now often

successfully supported. For example, patients with shunted

single ventricle physiology, including patients with hypo-

plastic left heart syndrome, were often denied ECMO in the

past due to difficulties in achieving balance between the

pulmonary and systemic circulations during support. Due to

improvements in management, ECMO and VADs are

currently felt to be necessary adjuncts to the successful

surgical approach to these patients [15,55,57,60,70,78].

Since its inception, ECMO has served as the predominant

form of support for children. Due to the presence of an

oxygenator in the circuit, ECMO is most useful in providing

support when heart disease is accompanied by hypoxia and

pulmonary hypertension. ECMO is also capable of provid-

ing bi-ventricular support and may be instituted via

cannulation of peripheral vessels. However, much of the

predominance of ECMO in pediatric mechanical circulatory

support is due simply to device availability and familiarity;

pediatric centers have historically greater experience with

ECMO due to its widespread use in the treatment of

pediatric respiratory failure. However, due to the complexity

of the ECMO circuit, substantial morbidity, if not mortality,

is incurred with this type of support compared to the

relatively simpler VAD circuit. In the acute setting,

increased tubing lengths and the presence of an oxygenator

damage blood elements and increase activation of the

inflammatory cascade [15–18,23,24,29,41,54]. The pres-

ence of an oxygenator and other complexities of the ECMO

circuit such as the ‘‘bladder box’’ require higher levels of

anticoagulation, which makes hemorrhagic complications

more common especially when support is required in the

immediate postoperative period. In a recent report, in-

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184 177

hospital neurologic complications due to both intracranial

hemorrhage and embolic events were three times more

likely in children supported with ECMO compared with

those supported with VADs [15,17,41]. Neurologic morbid-

ity persisted in these children with significantly more

ECMO supported children demonstrating neurologic im-

pairment during long-term follow-up [13,14].

Another important difference between devices is the

impact on recovery of ventricular function during support.

Experimental studies have demonstrated increased ventric-

ular wall stress during ECMO support while VADs provide

better ventricular unloading leading to decreased wall stress

[79,80]. ECMO may also contribute to ongoing myocardial

damage during support by providing desaturated blood flow

to the coronary arteries. With most cannula configurations

employed for venoarterial ECMO, oxygenated blood from

the arterial cannula fails to reach the coronary arteries with

coronary arterial blood flow provided by the left ventricle

only if there is any appreciable ventricular ejection [81–83].

If there is significant pulmonary parenchymal disease or

mechanical ventilation is withheld during ECMO support,

hypoxic blood returning to the left ventricle may provide the

sole source of coronary perfusion with deleterious effects on

ventricular function and recovery [84]. Desaturated coro-

nary artery blood flow may go unnoticed because peripheral

arterial blood gases will be fully saturated and may not

reflect the oxygen level in the aortic root. Finally, and

perhaps most importantly, ECMO provides only short-term

support, requires intensive nursing management, and is not

suitable for ambulatory support. ECMO support is invari-

ably limited to days to a few weeks; after this time period,

multi-system organ failure invariably ensues, probably due

to chronic activation of the inflammatory cascade that

occurs during ECMO support [15,18,19,41].

4.2. Centrifugal pump VAD

Centrifugal pump systems, such as the Bio-Pump

(Medtronic Bio-Medicus, Minneapolis, MN), are the most

commonly used form of VAD support for children. Such

VADs provide non-pulsatile flow by a constrained vortex

design that is both pre-load and after-load sensitive. The

centrifugal VAD circuit employs short tubing lengths to

connect the pump to the venous and aortic cannulas, which

reduces priming volumes compared to ECMO and makes

the system easy to maintain [15,29,85]. Heparin require-

ments as well as trauma to blood elements may be reduced

with Bio-Pump-based VAD circuits owing to the absence of

an oxygenator or venous reservoir. Despite its simplicity and

proven track record, the chief limitation for the Bio-Pump

VAD, like ECMO, is its unsuitability for prolonged support.

Thuys reported excellent results using the Bio-Pump to

support infants and children weighing 6 kg or less [86].

Utilizing this system, the authors supported 34 children with

median age of 60 days (range 2–258 days) and weight of

3.7 kg (range 1.9–5.98 kg). Of 34 supported, 63% were

successfully weaned from VAD support and 31% of this

difficult patient population survived to hospital discharge.

Other reports have described the utility of centrifugal VAD

to support the entire spectrum of pediatric cardiac disease

[31,42,46,47,87–89].

4.3. Adult systems used for pediatric support-Heartmate,

Thoratec and the ABIOMED BVS 5000

Several groups have successfully provided mechanical

circulatory support for older children utilizing systems

designed primarily for adult applications [31,44,90,91].

Helman described the use of the Heartmate VAD (Thoratec

Corp., Pleasanton, CA) in 12 adolescent patients, the

majority of whom had idiopathic dilated cardiomyopathy

[44]. The relatively older age of these patients (range 11–20

years) and larger size (body surface area range 1.4–2.2 m2)

allowed the use of this device. As in the adult experience,

the majority of children supported by the vented electric

model were discharged home with resumption of normal

activities.

A number of reports exist describing experience with the

Thoratec VAD (Thoratec Corp., Pleasanton, CA) in children

[90–93]. In Reinhartz’s review, 101 pediatric patients

[median age 13.7 years (range 7–17 years), median weight

54 kg (17–110 kg), median body surface area 1.5 m2 (range

0.7–2.2 m2)] had undergone support with the Thoratec VAD

worldwide with 66% survival to hospital discharge [93].

Ashton and co-workers employed the ABIOMED BVS

5000 (ABIOMED, Inc., Danvers, MA) in four older

children [31]. The ABIOMED device was used to provide

temporary circulatory support for patients with a body

surface area greater than 1.2 m2 with flows greater than 2 L/

min. A particular limitation to more widespread pediatric

application of devices designed primarily for adults can be

attributed to low pump rates during support for all but the

largest children limiting pump wash-out leading to increased

thromboembolic risk [22,31].

4.4. Pulsatile pediatric VADs-MEDOS HIA VAD and the

Berlin Heart

The MEDOS HIA VAD (MEDOS Medizintechnik AG,

Stolberg, Germany) and the Berlin Heart VAD (Berlin Heart

AG, Berlin, Germany) are paracorporeal pulsatile VAD

systems. Because the systems are available in a variety of

pump sizes (10–80 ml), they are suitable for the entire age

range of pediatric patients including neonates [21,94]. Both

are paracorporeal systems that employ pneumatically

driven, flexible blood sac pumps, to provide pulsatile flow.

Inlet and outlet valves are tri-leaflet and constructed from

polyurethane in the smallest versions.

Both the MEDOS and Berlin Heart systems are superior

to ECMO in providing moderate to long-term support and

preserve the options of bridging to transplantation or

recovery for children. Also unlike ECMO, both of these

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184178

systems allow extubation and ambulation during support

with the same salutary effects provided by similar systems

designed for adults. Several series have been published

describing use of the MEDOS system for pediatric support

[20,23,61,93]. Reinhartz reported 64 children supported

with the MEDOS HIAVAD, 44% of whom were supported

with the smallest pump sizes with an overall survival of

38% for patients with available follow-up [93]. A number of

reports exist detailing results with the Berlin Heart VAD in

children [21,22,24,53,54,95–98]. The Berlin Heart VAD

appears to have fewer bleeding complications compared to

ECMO with decreased blood product utilization during

support [97]. A recent report noted improving results for

infant support in the latest cohort of patients with survival

rates now approaching those achieved in adults [98]. The

worldwide experience with the Berlin Heart VAD in

pediatric patients now exceeds one hundred patients (Dr.

Peter Goettel, Berlin Heart AG, Berlin, Germany, personal

communication). In the United States, because device

availability is restricted to emergency use, only 25 implants

have been performed.

4.5. The MicroMed DeBakey VAD child

The DeBakey VAD Child (MicroMed Technology, Inc.,

Houston, TX) was granted Humanitarian Device Exemption

(HDE) status by the Food and Drug Administration and

became available for use in 2004 [99]. This pediatric device

employs the same axial-flow pump used in the adult version

with design modifications aimed at reducing the lateral

space requirements for device implantation. These design

modifications include a shortened inflow cannula with a

more acute angle for the inflow tubing, a shortened plastic

outflow graft protector and reduced size of the flow probe

on the outflow graft. Under the current HDE, the VAD Child

is used to provide temporary left ventricular support as a

bridge to cardiac transplantation for children from 5 to 16

years of age with a BSA >0.7 m2 and <1.5 m2 and is

designed to be fully implantable in this size range.

Although the clinical experience is still limited, this

device has been used successfully in a number of children

since its introduction.

5. Pediatric circulatory support devices under

development

The clear need for better means to chronically support the

circulation in infants and children with congenital and

acquired heart disease resulting in severe heart failure has

stimulated recent efforts to develop these much needed

devices. The development of these devices is being funded

by government agencies, industry, and institutions. The

National Heart, Lung, and Blood Institute currently supports

the development of pediatric circulatory support devices

through its Pediatric Circulatory Support Contract Program

and various grants. The program and the devices being

developed through NHLBI support are described below.

Other devices under development intended specifically for

pediatric circulatory support are also described.

5.1. NHLBI pediatric circulatory support program

On March 30, 2004, five 5-year contracts totaling

$22,399,727 were awarded by the NHLBI to provide a

comprehensive program for the development of a family of

novel pediatric circulatory support devices. The types of

devices intended to be developed under the program

included left and right VADs, ECMO systems, and other

novel bioengineered systems for children ranging in weight

from 2 to 25 kg. The devices funded by the program are

described below.

5.1.1. The PediaFlow (University of Pittsburgh; Carnegie

Mellon University; Children’s Hospital of Pittsburgh;

LaunchPoint, LLC; and World Heart Corporation)

The PediaFlow VAD is an implantable, magnetically

suspended mixed-flow turbodynamic blood pump being

developed to provide up to 6 months of circulatory support

to patients from 3 to 15 kg in body weight who have

congenital or acquired heart disease. Anticoagulation

therapy while on the device is intended to be limited to

anti-platelet medications. The targeted flow rate range of the

devices is from 0.3 to 1.5 L/min. It is being designed to have

a maximum weight of 30 g, a maximum volume of 5 ml, a

maximum priming volume of 0.5 ml, and to require only a

single percutaneous lead for energy transmission. The

PediaFlow VAD’s ‘‘smart’’ sensor-based controller will

continuously monitor the performance of the PediaFlow

device and support either continuous or pulsatile flow

modes. The device’s cannulae will be designed to be

suitable for both left and right ventricle cannulation (NHLBI

Contract HHSN268200448192C).

5.1.2. pCAS (Ension, Inc.; University of Louisville; Seare

Biomatrix Systems; Fluent, Inc.)

The pediatric Cardiopulmonary Assist System, or

pCAS, is a compact, paracorporeal rotary flow device

capable of simultaneously pumping blood and providing

oxygenation. The device rotor is fabricated from layers of

microporous hollow fibers through which gas exchange

occurs. These fibers will have a custom coating to both

increase fiber life and minimize requirements for systemic

anticoagulation.

The paracorporeal design of the pCAS system affords

modularity, allowing a separate device for each target

patient population, and the possibility of device exchange

during the support period. Such modularity also permits

the patient to be ‘‘upgraded’’ from the neonatal-sized

device to the child-sized device as growth or support needs

change. In addition to steady flow, the pCAS system will

include an option to deliver pulsatile flow at the higher

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184 179

heart rates of the intended patient population. (NHLBI

Contract HHSN268200448189C).

5.1.3. Infant- and Child-size Jarvik 2000 (Jarvik Heart,

Inc.; University of Maryland Medical Center; Mississippi

State University; Whalen Biomedical, Inc.)

Jarvik Heart is developing child- and infant-sized versions

of the Jarvik 2000\ that will provide full or partial circulatory

support for more than 6 months. The 35 g, 10 ml child-size

model is intended for 15–25 kg children and the 12 g, 4 ml

infant-size model is intended for 3–15 kg children. Through

device design and using various creative surgical techniques,

these small pediatric Jarvik 2000 models should be implant-

able in any of the normal heart’s four chambers in order to

provide chronic mechanical left, right, or biventricular

support (NHLBI Contract HHSN268200448190C).

5.1.4. Penn State PVADs (Penn State University;

Minnetronix, Inc.)

The Penn State Pediatric Ventricular Assist Device

(PVAD), is a pulsatile, pneumatically actuated blood pump

based on the design principles of the adult-sized Pierce–

Donachy VAD. The device is intended to be used for left,

right, or biventricular support for up to 6 months and is

being developed in two sizes. The smaller infant-size device

has a 12 ml dynamic stroke volume size for infants ranging

in weight from 5 to 15 kg. The larger child-size device has a

25 ml stroke volume size for children 15–35 kg. The target

flow rate ranges of the infant and child-size devices are 0.5–

1.3 and 1.3–3.3 L/min, respectively. The device is intended

primarily for paracorporeal placement but will also be

implantable for bridge-to-transplant applications (NHLBI

Contract HHSN268200448191C).

Fig. 1. The intravascular PediPump deployed as a BVAD (A) and the extravascu

Cleveland Clinic Foundation, 2005, used with permission.

5.1.5. PediPump (The Children’s Hospital at the Cleveland

Clinic; The Department of Biomedical Engineering, The

Cleveland Clinic Foundation; Foster-Miller Technologies,

Inc.)

The PediPump is a mixed-flow VAD with a rotating

assembly consisting of an impeller in the front, front and rear

radial magnetic bearings and a motor rotor magnet in its

center. Blood enters axially at the inlet and is turned to exit the

pump at an intermediate angle through the pump’s outside

diameter. Titanium shells seal all potentially corrodible

components from blood and tissue. The initial PediPump

prototype measures approximately 7�75 mmwith a priming

volume of 0.6 ml, imparting less than 10% of the physical

displacement of currently available axial flow pumps.

The PediPump’s deployment will be based on patient

size: for larger children (>15 kg), the small size of the

PediPump may allow completely intravascular implantation

(Fig. 1A). For smaller children (<15 kg), extravascular,

intracorporeal implantation may be performed using stan-

dard cannulation strategies employed for existing axial flow

pumps with inflow and outlet cannulas configured as needed

(Fig. 1). The same basic pump is anticipated for use as a

right ventricular assist device (RVAD), left ventricular assist

device (LVAD), or a biventricular assist device. (NHLBI

Contract HHSN268200448188C).

5.2. Other NHLBI-supported research

5.2.1. Pediatric pVAD (CardiacAssist)

CardiacAssist, Inc., is assessing the feasibility of

modifying its TandemHeart\ PTVA\ (Percutaneous Trans-

septal Ventricular Assist) System, developed for adults, for

pediatric patients. The device, which will be placed on the

lar, intracorporeal PediPump deployed as a BVAD (B). Copyright by The

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184180

outside of the body, is expected to deliver up to 50% of the

normal cardiac output in infants and children with heart

disease or heart defects. To accommodate pediatric patients

who weigh between 3.5 and 50 kg, six different cannulas are

planned for development (Supported by Grant R44

HL078077).

5.2.2. CardioFlowPQ (Ension)

Ension is developing the CardioFlow PQ blood pump

system to provide pulsatile flows in neonatal and pediatric

patients. The device, which is based on the porous pump

rotor concept being used in the pCAS devices described

previously, is being designed to more effectively entrain

blood to generate effective pulse pressures at the requisite

high beat-rates than other commercially available pulsatile

pumps. (Supported by Grant R44 HL059810).

5.2.3. Miniature MagLev VAD (Levitronix)

Levitronix is currently developing two pediatric devices,

the Levitronix Short-Term and Long-Term Pediatric VADs,

based on bearingless motor technology. The Short-Term

Pediatric VAD (Fig. 2A) is intended to provide circulatory

support for up to 14 days. The system includes a

polycarbonate pump with a 14 ml priming volume capable

of generating up to 3.0 LPM flow at a speed of 5500 rpm

against a pressure drop of 300 mm Hg. Actuation is

accomplished by magnetically levitating and rotating a

freely suspended impeller. The Long-Term pediatric VAD

(Fig. 2B) is based on the same bearingless motor technol-

ogy. The system includes a titanium pump with a 7.5 ml

priming volume capable of generating up to 6.0 LPM flow

at a speed of 9000 rpm against a pressure drop of 200 mm

© 2005 Levitronix LLC

© 2005 Levitronix LLC

© 2005 Levitronix LLC

A

B

Fig. 2. The Levitronix pediatric short-term pump (A) and long-term pump

and motor (B). Copyright by Levitronix LLC, 2005, used with permission.

Hg. The intended duration of use is for up to 6 months

(Supported by Grant R44 HL074628).

5.2.4. Toddler VAD (Pittsburgh/Carnegie-Mellon

University)

The overall goal of this project is to develop a safe,

reliable, and biocompatible VAD for toddlers/small children

between 15 and 35 kg. The ‘‘Toddler VAD’’ (TVAD), shown

in Fig. 3, will utilize a mixed-flow pump design with hybrid

magnetic and blood-lubricated bearings, optimized to

minimize blood trauma and thrombosis. The device will be

fully implantable, and capable of providing extended support

for up to 3 months (Supported by Grant R41 HL077028).

5.2.5. Fetal Perfusion System (Ension, Inc.)

Approximately 0.8% of children are born with congenital

heart defects that are detectable within the first trimester. If

these defects could be corrected in utero, outcomes may be

improved by eliminating the need for multiple, complex

surgeries after birth. In response, Ension has begun

development of a fetal cardiac bypass circuit enabling

correction of certain congenital heart defects before birth

(Fig. 4). The circuit consists of a specialized miniature

centrifugal pump and a miniature oxygenator—both specif-

ically designed for the unique aspects of fetal bypass. This

modular system will have an ultra-low priming volume and

will provide pulsatile flow and gas transfer, if required

(Supported by Grant R43 HL079737).

5.3. Other devices

The Circulite Micro-VAD (Aachen, Germany) is a small

implantable axial flow VAD designed to produce flows up

to 3 LPM. The device, which has blood immersed hybrid

bearings, a priming volume of 1.5 ml, a diameter of 12 mm,

and a length of 50 mm. No signs of hemolysis or emboli

were found following short-term (four weeks) animal

studies of the device. Longer-term animal studies are being

planned to further demonstrate safety [100].

A miniature centrifugal rotary VAD known as the

TinyPump is being developed in Japan by investigators at

Tokyo Medical and Dental University, Okayama University

in Okayama, and Ekisaikai Hospital in Nogoya [101]. The

device has a height of 20 mm, a diameter of 49 mm, and a

priming volume of 5 ml. In vitro tests reveal that the device

can generate up to 4 LPM and an index of hemolysis similar

to that of the Bio-Pump. Successful acute animal studies of

the device have been completed and efforts are continuing

to assess the pump_s performance at low flow rates in

chronic animal studies.

6. Future directions and summary

Each of the pediatric devices under development targets

features to address the needs of pediatric patients needing

Fig. 3. The Toddler VAD shown with a cut-away view of the mixed-flow pump. Copyright by Carnegie Mellon University, 2005, and University of Pittsburgh,

2004, used with permission.

J. Timothy Baldwin, B.W. Duncan / Progress in Pediatric Cardiology 21 (2006) 173–184 181

circulatory support, such as size, expected duration of support,

intention of therapy as a bridge or to aid recovery, and type of

heart disease. Together, these devices are expected to help

provide the missing options for the vulnerable, small pediatric

patients who are currently limited to short-term extracorporeal

VADs and cumbersome conventional ECMO. However,

substantial work must be completed before these devices are

ready for clinical use.Clinical evaluations for the devices being

developed under the NHLBI Pediatric Circulatory Support

Program are expected to begin at or before the conclusion of

Fig. 4. The ension fetal perfusion system.

the development program in 2009. The other devices under

development are expected to be ready for clinical use at various

times with the earliest expected to be ready for clinical trials

within a few years.

Acknowledgements

The authors would like to thank James Antaki, Ph.D.

(Carnegie Mellon University), Mark Gartner (Ension, Inc.),

Kurt Dasse, Ph.D. (Levitronix, Inc.), and David Wang, Ph.D.

(CardiacAssist, Inc.) for their contributions and Tracey Hoke,

M.D., Sc.M. (NHLBI) for her contributions as co-Project

Officer for NHLBI’s Pediatric Circulatory Support Program.

Conflicts of Interest: Dr. Baldwin is an employee of NHLBI

and a Project Officer for NHLBI’s Pediatric Circulatory

Support Program and administrator for numerous grants to

develop pediatric circulatory support devices. Dr. Duncan is

the PI for the contract awarded to The Cleveland Clinic and is

a member of the Advisory Board for the DeBakey VAD

Child, a product of MicroMed Technologies, Inc.

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