Download Jarvik 2000 Heart

Jarvik 2000 Heart
Potential for Bridge to Myocyte Recovery
Stephen Westaby, MS, FRCS; Takahiro Katsumata, MD, PhD; Remi Houel, MD; Rhys Evans, MD;
David Pigott, MD; O.H. Frazier, MD; Robert Jarvik, MD
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Background—Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We
sought to validate the use of a new intracardiac axial flow impeller pump for this purpose.
Methods and Results—The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability,
biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants
with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed
in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow,
and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible.
Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and
safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption
occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no
thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial
endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or
vascular graft.
Conclusions—The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical
circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge
to transplantation or long-term support. (Circulation. 1998;98:1568-1574.)
Key Words: heart failure n myocytes n Jarvik 2000 n heart-assist device
W
hile the incidence of heart failure continues to rise,
both medical and surgical treatment options remain
limited.1,2 The radical solution, cardiac transplantation, is
constrained by donor availability.3 The left ventricular reduction (Batista) operation remains controversial, and dynamic
cardiomyoplasty seems ineffective.4 – 6 There is room for a
new approach.
Recent experience from mechanical bridge to transplantation has provided compelling evidence for myocyte recovery
after prolonged left ventricular unloading.7,8 Myocyte morphology and metabolism may return to normal in dilated
cardiomyopathy, and recovery appears sustainable particularly after myocarditis.9 This has encouraged some centers to
pursue mechanical bridge to myocyte recovery as an alternative to cardiac transplantation for selected patients.10 –13 In this
context the scope of existing left ventricular assist devices
(LVADs) is limited by size, noise, and driveline problems,
including infection, which restrict their use predominantly to
adult males. Conducting an uneventful LVAD removal while
preserving the native heart is difficult. In contrast, the
emerging axial flow impeller pumps are compact and silent
with the potential for ease of extraction.14 Their mechanical
function allows the process of weaning from the device. We
have tested the feasibility of a mechanical device in this
context using the Jarvik 2000 Heart. We assessed the relationships between pump flow, cardiac physiology, and the
risk of hemolysis and also tested removal of the device with
survival. An approach to avoid driveline infection using an
innovative new percutaneous system is under study.15
Methods
Jarvik 2000 Heart
The Jarvik 2000 Heart is a compact axial flow impeller pump with
an outflow Dacron graft for anastomosis to the descending thoracic
aorta (Figure 1). The pump is inserted through a sewing cuff into the
apex of the left ventricle. The adult model measures 2.5 cm in
diameter by 5.5 cm in length. The weight is 85 g with a displacement
volume of 25 mL. The pediatric device measures 1.4 cm in diameter
by 5 cm in length; the weight is 18 g, and the displacement volume
is 5 mL. The pump rotor contains the permanent magnet of a
brushless direct current motor and mounts the impeller blades. A
titanium shell accommodates the rotor and suspends it at each end by
tiny, blood-immersed ceramic bearings. The adult pump functions at
speeds of 8000 to 12 000 rpm, providing blood flow up to 8 L/min.
The smaller pediatric version pumps up to 3 L/min. Noise is
imperceptible.
Received January 21, 1998; revision received April 21, 1998; accepted May 14, 1998.
Guest editor for this article was Eric A. Rose, MD, Columbia-Presbyterian Medical Center, New York, NY.
From the Oxford Heart Centre (S.W., T.K., R.H., R.E., D.P.), Oxford, UK; the Texas Heart Institute (O.H.F.), Houston, Tex, and Jarvik Heart, Inc
(R.J.), New York, NY.
Correspondence to Stephen Westaby, MS, FRCS, Oxford Heart Centre, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK.
© 1998 American Heart Association, Inc.
1568
Westaby et al
October 13, 1998
1569
a carbon or titanium pedestal was tunneled in a zigzag fashion to the
occipital region of the skull.
The periosteum of the skull was elevated, and the external table of
the occiput was excavated to recess the power cable beneath the
pedestal. The pedestal was then secured with bone screws to the
outer table of the skull, providing complete immobility in relation to
the skin.
With the electrical system in place thoracotomy was performed
and the Jarvik 2000 pump was implanted. The Dacron graft was first
anastomosed end to side to the descending thoracic aorta. The pump
was then inserted through a cuff sewn to the apex of the left
ventricle. This was achieved by excising apical left ventricular
muscle with a cork bore while the heart supported the circulation.
Cardiopulmonary bypass was not required.
The percutaneous power cable was then connected to the external
controller and battery or direct current main power supply.
Intraoperative Hemodynamic Studies
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In the last 6 animals implanted with the definitive adult human
model, an electromagnetic flow probe was placed around the graft to
record flow during detailed hemodynamic studies.
Carotid arterial pressure, pulmonary wedge pressure, and graft
flow were measured before and after insertion of the pump, then
serially with escalating pump flow to the maximum speed tolerated
before collapse of the left atrium. Measurements were made in
triplicate and the average used to plot flow curves. The flow probe
was removed before the chest was closed.
Recovery
Figure 1. Jarvik 2000 pump implanted into the left ventricular
apex (reproduced with permission of Mosby-Year Book, Inc).
In the Oxford system, percutaneous power is delivered from
external batteries via a controller unit. Internal electrical wires are
brought via the left pleural cavity to the apex of the chest and then
subcutaneously across the neck to the base of the skull, where a
percutaneous titanium pedestal transmits fine electrical wires
through the skin of the scalp.14
Animal Experiments
Between July 1995 and August 1997, 27 adult and 3 pediatric
pumps were implanted into Welsh mule sheep weighing between
70 and 90 kg.
All animal data were prospectively entered into a database to
record device-related morbidity and mortality, non– device-related
morbidity and mortality, pump function (driving speed and energy
consumption), and autopsy findings.
Blood samples were collected serially to determine hematological
and biochemical indices, prothrombin times, and markers of
hemolysis.
The surgical procedures and postoperative care were undertaken
humanely by licensed personnel in compliance with UK Home
Office guidelines.
Operation
The sheep were anesthetized with thiopentone and then intubated and
ventilated with halothane in oxygen. A thermodilution pulmonary
arterial catheter and arterial cannula were introduced into the left
internal jugular vein and the left common carotid artery, respectively.
The animals were positioned for left thoracotomy. Before entering
the left pleural cavity, the power cable and percutaneous pedestal
were tunneled under the scapula toward the midline. In the first 20
animals, the electrical wires were brought out through the skin of the
middle of the shoulder. In the last 10 animals, the power cable with
At the end of the procedure a single chest drain was inserted, the
chest closed, and the muscle relaxant reversed. The sheep were
extubated after 30 to 60 minutes of spontaneous respiration with
documentation of satisfactory blood gases and acid base balance.
A vest was placed around the thorax to carry the controller and
connect with the overhead electrical power line. The animals were
then allowed to mobilize, drink, feed, and roam around the sheep
pen. Blood from uncrossmatched donor sheep was used to correct
hypovolemia or anemia. Indwelling carotid arterial and jugular
venous lines were left in situ in all animals for 48 hours. These
were used to monitor arterial and venous pressure and to
determine the rate of pump flow that abolished left ventricular
ejection through the aortic valve. At this stage, all systemic blood
flow was through the pump and was nonpulsatile. This flow rate
was maintained, and the animals were observed for adverse
neurological or renal effects of nonpulsatile flow. Neurological
status was determined after recovery from anesthetic by observing
behavior, mobility, and balance. Renal function was assessed by
measurements of blood urea and creatinine; hydration was maintained by intravenous fluid administration.
After removal of the indwelling lines, blood samples were
obtained by direct puncture of the internal jugular vein. Pump speed
and power requirements were measured and recorded twice daily.
Auscultation was used to check the tone of the device.
Aspirin 300 mg/d and warfarin in doses escalating to 25 mg/d
were prescribed, but because of the sheep’s rumen, it proved
impossible to achieve an International Normalized Ratio .1.5:1.
Elective Device Removal
To simulate the bridge to myocardial recovery strategy, permission
was obtained from the Home Office to perform 3 elective device
explants with survival. Animals chosen for elective explant had
suffered irreparable power interruption, and the pumps were removed at 25, 198, and 211 days postoperatively. The animals were
anesthetized and positioned for left thoracotomy; the medial one
third of the healed thoracotomy wound was reopened. The apex of
the heart was located by sharp dissection through dense adhesions,
and the vascular graft was ligated and transected. The device was
then removed by cutting the ligatures in the cuff and directly
oversewing the apical window. No circulatory support or antidys-
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Jarvik 2000 Heart
TABLE 1.
Complications
Events
No. of Sheep
Device-related
Pump failure (fractured bearing)
1
Thrombosis
0
Anticoagualtion-related hemorrhage
3
Endocarditis
2
Driveline infection
2
Malhealing of the wound
5
Non–device related
Hemorrhage
4
Respiratory infection
2
Sepsis
2
Interrupted power delivery
15
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rhythmic therapy was used. The thoracotomy was then closed
without a drain, and the sheep were allowed to recover.
Autopsy Studies
After death or elective euthanasia, the device was removed from the
left ventricle, photographed, and disassembled, in a search for
thrombus formation. The bearings and moving parts were checked
for wear. The heart, lungs, brain, kidneys, and liver were examined
for macroscopic evidence of thromboembolism. Slices of brain,
heart, and kidney were examined histologically. The percutaneous
pedestal and surrounding tissues were closely inspected for signs of
infection.
Statistic Analysis
All results for continuous variables are expressed as mean6SD.
Student’s paired or unpaired t test or Mann-Whitney U test, if
appropriate, was used to compare continuous variables between 2
subgroups. A P value of ,0.05 was considered indicative of
statistical significance.
Results
excessively heparinized pending attempted anticoagulation
with warfarin. Two sheep in whom arterial cannulae were
kept for several days contracted bacterial endocarditis. These
animals had a persistent febrile illness from the first postoperative week and eventually developed pneumonia or sepsis.
One died and the other one was euthanized, at 42 and 74 days
respectively.
Driveline infection (n52) and impaired healing of cable
exit site (n55) occurred in sheep with a mobile percutaneous
power cable at the shoulder. In contrast, all 10 animals with
skull-mounted pedestals were free from infection or healing
problems.
Three sheep died suddenly at 13, 17, and 22 days, respectively, of delayed aortic rupture, not at the anastomosis but at
the site of side-clamp application. This problem was addressed by obtaining younger sheep instead of elderly ewes
discarded from breeding stock. One died of peritoneal bleeding after rumen puncture for the treatment of acute bloat.
Bloat occurred when a general anesthetic was administered to
correct a subcutaneous power-line disconnection due to
head-butting by the sheep. Two animals who developed
perihoof abscess were euthanized.
Nine animals experienced 15 incidents of electrical driveline breakage. This was inevitable given the humane, unrestricted environment required by the Home Office. Power
cables were chewed by sheep in neighboring pens, and the
percutaneous carbon pedestal was shattered by head-butting.
Whenever possible, power was reestablished by electrical
repair (usually several hours after disruption).
In 1 animal, the pump stopped because of a fractured
bearing. The pump was later removed surgically, and the
animal recovered. The bearing design was modified to
provide greater strength; scanning electron microscope
screening of all bearings was instituted to ensure that no
cracks were present at implant. No further bearing fractures
have occurred.
Mortality and Morbidity
During the learning curve, 3 deaths occurred in the perioperative period as a result of ventricular arrhythmia caused by
suturing or coring the heart. This complication was eliminated by infusing the antidysrhythmic agent bretylium 30
minutes (rather than immediately) before apical coring. An
additional 4 deaths occurred within 24 hours of the operation
from inhalation and respiratory failure or intrapleural bleeding (aorta or internal mammary artery).
One animal developed acute mitral insufficiency during
ventricular coring and was euthanized immediately. Autopsy
showed a severed strut chord stuck in the inflow of the
device. These events each occurred during our first 15
implants, reflecting the learning curve and our inexperience
with the animal model.
Twenty-two animals survived between 3 and 198 days
(mean 52612 days) with a functioning device. All complications are annotated in Table 1.
Three sheep died of secondary hemorrhage from the aorta
between the third and fifth postoperative days. They had
initially made an uneventful postoperative recovery, but
severe hypertension and bleeding were noted at the time of
arterial line removal from neck. All 3 were found to be
Performance of the Jarvik 2000 Heart
In 27 animals with the adult device, pump speeds were set
and maintained between 10 000 and 12 000 rpm, and pulse
width–modulated speed control at 14 V (DC power) was
used. This pump speed corresponds with an in vitro flow of 5
to 6 L per minute. Natural ventricular contraction provided a
differential pressure load on the pump, and the torque load on
the motor varied with pulse pressure. The mean energy
consumption was 6.361.1 W (n525) during intraoperative
measurement (baseline*), 5.860.9 W (n59; P50.09*) at day
30, 6.261.2 W (n56; P50.71*) at day 60, and 6.961.0 W
(n53) at day 90.
The 3 pediatric devices, which provided blood flow of 1 to
2 L/min, required 5 to 8 W at a continuous speed of 12 000
rpm and were operated at 8 to 9 V (DC).
Intraoperative Hemodynamic Studies
Introduction of the space-occupying (25-mL) device into the
small, restrictive left ventricle of the sheep (with the vascular
graft clamped) caused significant elevation of the pulmonary
wedge pressure (8.060.6 mm Hg before implantation to
14.063.8 mm Hg after pump insertion, P50.02). Before the
Westaby et al
October 13, 1998
1571
Effects of Nonpulsatile Flow
With relatively simple neurological observation and measurements of urea and creatinine, we could detect no adverse
sequelae from nonpulsatile flow. The animals’ behavior was
normal with early restoration of feeding and drinking. There
were no problems with balance after recovery from the
anesthetic drugs. Renal function remained normal
throughout.
Hemolysis
Figure 2. Systemic arterial pressure and pump speed. As pump
speed increased, mean arterial pressure progressively rose and
pulse pressure diminished.
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pump was switched on (clamp off the graft) there was
bidirectional (to and fro) flow in the vascular graft but a mean
negative (descending aorta to left ventricle) flow of 0.960.4
L/min corresponding to 21% of the total cardiac output
(4.360.5 L/min). With “functional aortic regurgitation,” the
pulmonary wedge pressure rose from 14.063.8 to
25.066.9 mm Hg (P50.01), with a corresponding decrease
in overall cardiac output from 5.160.7 to 4.360.5 L/min
(P50.01). Despite preexisting elevation of the left atrial
pressure, this change in hemodynamics was well tolerated by
the animals.
As the nonpulsatile pump flow increased, the aortic pulse
pressure fell progressively from 2564 (pump off) to
1164 mm Hg at 10 000 rpm (P50.06) (Figure 2). At 10 000
rpm, the pump captured all blood flow through the mitral
valve so that the aortic valve remained in the closed position
with the left ventricle fully unloaded. Systemic vascular
resistance averaged 11906170 dyne z s/cm.5 As the pump
speed and flow rate increased further, the mean arterial
pressure rose progressively, and at 12 000 rpm the cardiac
output was augmented by 33% (1.960.5 L/min) over preimplantation values (Figure 3). At speeds exceeding 15 000
rpm, the left atrium became concave or collapsed, depending
on the blood volume. Transfusion lessened this effect and
allowed higher pump speeds and cardiac output.
Table 2 shows indices of hemolysis preoperatively and at 1,
4, 8, 12, and 28 weeks.
Elevations of lactate dehydrogenase from 4876108 to
9786226 U/L (P50.0001) at 1 week after operation probably
resulted from uncrossmatched blood transfusion, drug administration, or resolution of intrathoracic hematoma after operation. Elevated levels of mean plasma-free hemoglobin from
11.568.7 to 14.267.7 mg/dL at 1 week were not statistically
significant (P50.55), nor were decreased hemoglobin levels
(from 13.261.8 to 10.561.8 g/dL; P50.14). Creatinine
levels remained within the control range.
Elective Explants
All 3 animals recovered rapidly after limited thoracotomy and
device removal to simulate bridge to left ventricular recovery.
None required blood transfusion.
Autopsy Studies
There was no left ventricular endothelial overgrowth or
intracavity thrombus formation. The most common findings
were of pulmonary atelectasis and pleural effusion (n512).
Four animals had diffuse consolidation in the left lung.
Histological examination showed chronic inflammatory
changes with active bacterial infection.
Pump infection (endocarditis) was observed in 2 animals, 1
of which had excavating driveline sepsis. Both had a mass of
vegetations around the inflow cage, which partially obstructed the pump head. One had extensive involvement of
intracardiac structures, with mitral chordal fusion and septic
embolism of the kidneys.
Figure 3. Cardiac output and pump speed. At
10 000 rpm the pump captured all transmitral
blood flow and the aortic valve remained
closed. Cardiac output was determined by thermodilution. Flow through the vascular graft
(conduit) was obtained by electromagnetic flowmeter. *P,0.05.
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Jarvik 2000 Heart
TABLE 2.
Indices of Hemolysis
Before Operation
(n530)
1 week
(n519)
4 weeks
(n511)
8 weeks
(n57)
12 weeks
(n54)
28 weeks
(n51)
Hb (g/dL)
13.2 (1.8)
10.5 (1.8)
11.4 (1.8)
10.0 (1.7)
10.4 (2.1)
11.1
Pl-Hb (mg/dL)
11.5 (8.7)
14.2 (7.7)
6.4 (2.9)
8.2 (6.0)
7.9 (3.4)
5.0
LDH (U/L)
487 (108)
978 (226)
701 (102)
527 (119)
519 (187)
642
Cr (mmol/L)
110 (11)
88 (8)
101 (14)
106 (20)
88 (14)
89
Data presented are mean6SD.
Cr indicates serum creatinine; Hb, hemoglobin; LDH, lactate dehydrogenase; and Pl-Hb, plasma-free hemoglobin.
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No abnormalities were detected in the brain or liver in any
animal. In extensive (5-mm) histological sections of the
kidneys from 10 noninfected animals that survived for .30
days, we found no evidence of thromboembolism, infarction,
or infection.
In the 11 animals that survived .1 month with a functioning device, a tiny undetachable black ring torus (,1 mm) of
heat-coagulated protein, fibrin, and degenerated platelets was
found on the bearing supporting each end of the rotor (Figure
4). This did not restrict the rotation of the impeller or obstruct
the inflow of the device. There was no increase in size of this
nodule with time. There were no histological changes in the
myocardium around the device that might suggest dissemination of heat into the tissues.
Apart from those with endocarditis, all pumps were remarkably free from thrombus formation even when disconnected from power for prolonged periods. After the device
was removed, examination of the bearings showed no perceptible wear. One of the pumps electively explanted 5
months after losing power was free from thrombus with a
completely clean vascular graft and no anticoagulation. In
sheep in which devices stopped and were restarted several
hours later, there were no detectable emboli or clinical events
to suggest embolism.
hours or days without achieving anticoagulation, and still no
thrombus occurred in the pump. Our findings are supported
by the absence of thrombus formation or embolism in the
animal experiments by Kaplon et al17 (sheep at the ColumbiaPresbyterian Medical Center, New York, NY) and Macris et
al18 (calves at the Texas Heart Institute). Collectively, these
studies and the most recent work at the Texas Heart Institute
have demonstrated mechanical reliability, remarkably little
hemolysis, and freedom from thrombosis for up to 8 months
after implantation. The tiny microtorus of coagulated protein
on the bearings was not detachable, did not interfere with the
moving parts, and is probably caused by local heat during
high-speed flow.
It is now clear that moribund heart-failure patients fitted
with an LVAD can improve to NYHA class I status and
Discussion
In contrast to the electric pusher-plate LVADs, the compact
Jarvik 2000 Heart is silent, easily implantable, and unobtrusive. The intraventricular position conveys distinct advantages. The device is practically encapsulated by the native
myocardium, and, theoretically, infections around the device
may be less likely. There is no inflow graft at risk for
thrombus formation, there are no valves, and the device can
be used in patients of all sizes. Energy requirements are less
than those of pusher-plate pumps, and the infection-resistant
percutaneous electric cable has the advantages of simplicity
and reliability. None of the animals with a skull-mounted
carbon or titanium pedestal had driveline infection or impaired healing.15 A similar skull-mounted pedestal used for
cochlear stimulation has functioned in humans for almost 20
years without causing infection.16
The critical feature of the Jarvik 2000 design is a high-flow
stream of blood that continuously washes the tiny bearings
and prevents thrombus formation. Given the failure to
achieve anticoagulation in normal sheep, the absence of
thrombosis together with minimal hemolysis generates optimism for use in humans. In the electively explanted devices
(with sheep survival), the pumps had been off for several
Figure 4. Autopsy findings 70 days after implantation with a
continuously functioning device. A, Left ventricular cavity and
pump inflow were free from thrombus. B, A clean outflow and
conduit. The Dacron vascular prosthesis was endothelialized
along its length.
Westaby et al
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return to the community. Pilot studies in the United States,
Germany, and the United Kingdom show that well-motivated
LVAD patients with family support can live at home and
work while they wait for a transplant.19 The success of early
LVAD programs provided a powerful argument for the use of
the electric HeartMate (Thermo Cardio Systems) and Novacor (Baxter Edwards) devices as alternatives to cardiac
transplantation.20,21 Unlike the supply of donor hearts, the
availability of LVADs is limited only by the industrial
capacity for production and the costs.
Many patients between the ages of 60 and 75 given
conventional medical treatment have an expected mortality of
'40% per year. This is a large and rapidly growing population that is in need of an alternative. Given the incontrovertible shortage of transplant donors, the prospect of permanent
mechanical circulatory assistance or circulatory support as a
therapeutic option is compelling.
For widespread use, an LVAD must be easily worn,
portable, silent, and not noticeable by the patient. The
abilities to alter flow according to demand and to wean
slowly before removal are also great advantages. For bridge
to myocyte recovery, the device must be mechanically
reliable for at least 12 months and be easy to remove. Our
elective explants of the Jarvik 2000 Heart proved relatively
simple through a limited left thoracotomy without cardiopulmonary bypass; they were followed by rapid recovery of the
animals. We found no adverse sequelae from capturing all
transmitral blood flow with a continuous-flow device. The
animals behaved normally, and many recovered uneventfully
from a major surgical procedure with predominantly pulseless flow. The effects of a temporary lack of pulsatility in the
circulation need to be explored further in humans through
neurohormonal studies. Our original intention for long-term
carotid arterial monitoring to study pulseless flow was abandoned when 2 animals developed endocarditis. For patients
with considerably larger hearts, the intent is to partially
offload the left ventricle allowing concomitant pulsatile
ejection through the outflow tract. There is also the potential
for biventricular support using the smaller pediatric device in
the right ventricle with balanced flow.
Evidence to support the “keep your own heart” (myocyte
recovery) strategy continues to accumulate, although most
reports are anecdotal and without detailed physiological
studies. In contrast to the modest pharmacological reductions
in ventricular filling pressure and volume, mechanical blood
pumps have the capacity to completely offload the left
ventricle while the patient remains active. After mechanical
bridge to transplantation, the hearts of patients with end-stage
idiopathic cardiomyopathy reverted to a normal size and
weight. In many patients, indices of left ventricular function
approach normal values by the time a donor organ becomes
available. Levin and colleagues7 studied the end-diastolic
pressure-volume relationships in excised hearts from transplant recipients with idiopathic dilated cardiomyopathy. They
compared cardiac function between those who had received
intensive medical management alone versus mechanical circulatory support. Prolonged LVAD use greatly reduced the
left ventricular end-diastolic dimensions and pressure-volume
relationships. Left ventricular mass was reduced substantially
October 13, 1998
1573
in the LVAD group. The authors concluded that severe left
ventricular dilatation in idiopathic cardiomyopathy could be
substantially reversed by mechanical offloading.
Frazier and colleagues8 took tissue samples from the core
of the left ventricular apex removed at the time of LVAD
implantation and compared them with myocardium from the
explanted heart at transplantation. Histological studies
showed a marked reduction in the extent of myocytolysis,
whereas deranged calcium uptake and binding rates in the
sarcoplasmic reticulum were found to have normalized.
These features were associated with clinical and radiological
improvements together with reduction of plasma norepinephrine levels to near normal. Changes in intracellular calcium
concentration have been linked with apoptosis in tumor cells
as well as in the heart failure myocyte. Calcium channel
blockers have been shown to delay apoptosis; recent studies
on the response of myocytes to stress factors suggests an
association of apoptosis with the progression of cardiomyopathy.22 Transient myocardial pressure overload induces the
expression of proto-oncogenes, which leads to compensatory
hypertrophy of myocytes. It is possible that left ventricular
unloading with an LVAD would reverse this process.
Westaby and colleagues10 performed detailed echocardiographic studies of left ventricular function in patients
with end-stage dilated cardiomyopathy not listed for cardiac transplant and treated with a permanent LVAD. With
the LVAD briefly switched off, a progressive increase in
myocardial contractility was observed, beginning as early
as 4 weeks postoperatively.
Müller and colleagues,23 in Berlin, committed 17 dilated
cardiomyopathy patients to the bridge to myocyte recovery
strategy using pusher-plate LVADs. Five had significant
recovery and were weaned from mechanical support at
between 160 and 794 days. Six died during mechanical
support, and 4 were received a transplant. Two remained on
the device. Disappearance of the autoantibody against the
b1-adrenergic receptor was used to time device removal, and
left ventricular recovery was sustained. At the same center, 2
infants with acute viral myocarditis and ejection fraction
,15% underwent cardiopulmonary resuscitation and then
implantation of the extracorporeal “Berlin” left and right
ventricular assist devices. They were successfully weaned at
25 and 31 days, with sustained ejection fractions of 55% and
65%, respectively, thus avoiding transplantation. These infants now have normal left ventricular function.
The potential costs for the bridge to myocyte recovery
strategy need not be excessive. Gelijns and colleagues,24 from
the Columbia-Presbyterian Hospital, reported similar costs
for long-term outpatient treatment with the HeartMate vented
electric LVAD as for cardiac transplantation. Ultimately,
long-term mechanical cardiac assistance may prove to be less
expensive than cardiac transplantation or the intensive medical treatment of patients in NYHA classes III and IV.
A structured clinical program of mechanical bridge to
myocyte recovery requires a user-friendly blood pump and
pharmacological or genetic strategies to sustain recovery.
Some of these prerequisites are now in place. The remainder
will emerge with human experience.
1574
Jarvik 2000 Heart
Acknowledgments
Financial support was provided by the TI Group p1c UK.
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Jarvik 2000 Heart: Potential for Bridge to Myocyte Recovery
Stephen Westaby, Takahiro Katsumata, Remi Houel, Rhys Evans, David Pigott, O. H. Frazier
and Robert Jarvik
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Circulation. 1998;98:1568-1574
doi: 10.1161/01.CIR.98.15.1568
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