A review of the current outlook of ventricular assist

devices
Mindy Harvey, Gannon Ray (Group 18)
Introduction
Heart failure is a physiological state caused by diminished cardiac output
and/or raised intracardiac pressures [1]. For several years, the occurrence
and pervasiveness of heart failure has increased in the United States. In
2010, it was estimated that in the United States alone that roughly 5.3
million people had heart failure [2]. Only three years later in 2016, the
estimate had risen to 5.7 million Americans with projections showing that in
2030 more than 8 million people will be affected [3]. Heart transplantation
persists to be the most efficacious surgical treatment for advanced heart
failure [1,3-7]. However, the limitation of heart donor availability has
prevented the application of this remedy for all cases of advanced heart
failure [7]. Less than 3000 organ donors are available worldwide per year
with approximately 2000 of those found in the United States [1,2,4].
Furthermore, patients over the age of 65 typically do not qualify for donor
hearts in spite of the fact that the frequency of heart failure is highest
among older patients [2]. Due to the lack of organ donors and those
rendered ineligible for transplantation due to age restrictions or
comorbidities, the need and interest for permanent mechanical circulatory
support assist devices has increased, resulting in intensive research over
recent decades. [2,4,5,8]. The desired mechanical circulatory response is
provided by ventricular assist devices (VADs). These devices may be utilized
to support a failing left or right ventricle or both, simultaneously [9].
Ventricular assist devices are being implemented as a bridge to myocardial
recovery, a bridge to candidacy or decision, bridge to heart transplantation,
or as a longer term destination therapy for patients in need of circulatory
support [1,2,4,6-9].
Background
Ventricular assist devices have significantly evolved in recent years. The
devices are generally classified by their characteristic outflow (pulsatile or
continuous) and operational characteristics [9]. Earlier models of the
devices focused on producing pulsatile outflow similar to that delivered by
the natural human heart [9]. The characteristic pulsatile flow was
accomplished by use of volume-displacement pumps. These pumps are
classified as the first generation of ventricular assist device models [7,9].
The devices incorporated pneumatically or electrically actuated diaphragms
or plates and were associated with inherently large tissue to blood
contacting surface area and multiple moving parts [9]. Due to the
imperative need for full mechanical circulatory support as a bridge to heart
implantation, the pulsatile heart pumps were aggressively developed in the
1990s [6,9]. Although the models increased the survival rate of patients in
heart failure, they were inherently prone to reliability and durability issues
as a result of their mode of operation [6,7,9]. The large amount of space
take-up also presented a high risk of infection, thrombus formation,
difficulty in positioning, and blood trauma [5,7,9]. The issues associated
with this type of pump led to a push for improved device design consisting
of continuous flow operation rather than pulsatile flow [9].
The development of continuous flow heart pumps gave rise to the second
and third generation of ventricular assist devices [6,7,8,9]. Continuous flow
devices operate by means of a rotating impeller housed within a small pump
chamber, without the need for directional valves [9]. The impeller may be
classified as axial, radial, or mixed flow based on the direction to which
blood enters and leaves the impeller [9]. The majority of second generation
rotary pumps are largely described as pumps with an axial blood flow path,
which have an internal rotor within the flow path that is suspended by
contact bearings [7]. Axial flow rotary pumps are relatively small, as
compared to first generation heart pumps, and can operate at speeds up to
15,000 rpm to deliver blood to the circulatory system [9]. This device
quickly replaced the previous first generation fill-to-empty devices after
demonstrating excellent clinical results [6,7]. The implantation of the pump
required the creation of an upper abdominal pocket and is connected to an
external percutaneous driveline and power source [6]. While the devices
showed improved capability of blood circulation, the extensive mechanical
contact levied a major contraindication for long-term use over five years [9].
This gave rise to the third generation of devices and most significant
advance in the field- the development and research of non-contact bearing
design within ventricular assist devices [6,9].
The third generation of devices have attempted to effectively eliminate
mechanical contact and wear by completely suspending the rotating
impeller using magnetic or hydrodynamic forces [7,9]. Impeller rotation is
achieved by magnetic coupling to the pump motor, resulting in a bearing-
less drive system [7,9]. The improved system removes frictional wear and
reduces heat generation that would normally be found in second generation
devices [7]. While there are exceptions, the majority of third generation
devices use a radial (centrifugal) blood flow path and can produce flows up
to 10 L/min [6,7]. A significant reduction in size of the design also allows for
intrapericardial placement and eliminates the need for a pump pocket in the
abdomen [6]. The improved design has greatly increased the device lifetime
to beyond ten years and shown to produce superior clinical results when
compared to its predecessors [9].
Ventricular Assist Devices: Then and Now
The notion of using ventricular assist devices began approximately 85 years
ago when Dr. Michael DeBakey developed the roller pump. This
advancement eventually led to the creation of the first heart and lung
bypass machine [3]. These advances continued towards the development of
single chamber pumps to provide cardiac support. Initially, these devices
were designed as bridge to transplant by generating additional blood flow in
parallel with the particular ventricle. Notably, the first successful
transplantation after VAD-implantation was performed in 1984 [8].
In the 1990s, Thoratec introduced the HeartMate I. This device began as
a pneumatically powered device (IP model) before evolving to the vented
electric VE and the subsequent XVE model. By switching to electric power,
the size of the percutaneous driveline was reduced as well as eliminated the
need for an external compressed air source. With this device, a cardiac
output of 10 L/min is achievable at a maximum heart rate of 120 BPM.
However, this performance comes at a cost. With the large size and weight
of this device it exhibits a restricted ability for intracorporeal implantation
for smaller patients. The HeartMate XVE was involved in the pivotal
Randomized Evaluation of Mechanical Assistance for the Treatment of
Congestive Heart Failure (REMATCH) trial. REMATCH demonstrated a
survival advantage for left ventricular assist device therapy over optimal
medical management for patients with advanced heart failure [7,9]. The
results of this trials led to approval of the HeartMate XVE for destination
therapy by the FDA in 2002 [6,9]. This trial also highlighted the device-
related complications associated with the first generation ventricular assist
devices. These disadvantages included the large size, noise emission,
infections of cannulas, and degradation of valves [3,7,9,8].
Thoratecs second generation ventricular assist device comes in the form of
the HeartMate II. The HeartMate II is an axial flow pump that provides up
to 10 L/min to left heart failure patients. The continuous pump is smaller
than its previous generation and is approximately the size of a D-Cell
battery. This titanium pump has an internal rotor within the blood flow path
that is suspended by contact bearings. Although the pump rotor is
suspended by blood-immersed contact bearings, it has been found to be a
durable and robust device. This device has demonstrated a five-year service
life. Since the initiation of clinical trials in July 2000, the FDA has approved
the device for bridge to transplant in 2008 and destination therapy in 2010
[6,9].
HeartWares HVAD is a third generation, small continuous-flow rotary
pump with a centrifugal, noncontact bearing design. The single rotating
impeller is completely suspended due to a combination of hydrodynamic and
passive magnetic forces created by a tapered thrust axial bearing. The
HVAD uses a wide-blade impeller design to maximize performance,
hemocompatibility, size minimization, long-term reliability, and overall
system efficiency. The device is the smallest and lightest of the radial flow
pumps with a flow capacity of up to 10 L/min. The device is small enough to
place within the ventricular cavity. In addition, the dual motor design
provides a level of redundancy [6,7,9]. In 2009, the HVAD received the
Conformit Europene (CE) mark and the Australian Therapeutic Goods
Administration approval in 2011. This pump has been evaluated in two FDA
trials: the ADVANCE Bridge to Transplant Trial and the ENDURANCE
Destination Therapy Trial. The HVAD received FDA approval for the bridge
to transplant indication in the United States in November 2012 [9]. The
ENDURANCE Destination Therapy Trial showed that 55% reached the
primary end point at 2 years. To affirm the positive results of the previous
trial, the follow-up EDURANCE Supplemental Trial is ongoing [10].
Outlook
Developments in ventricular assist device technology have significantly
enhanced the field of long-term mechanical circulatory support and
outcome of patients in heart failure, but there are certainly areas for
continued improvement [6,11]. Several significant limitations persist in the
arena of VADs, including invasive implantation methods, infections,
bleeding, and thromboembolic events [5,6]. As a result, research is ongoing
to develop devices to reduce and/or eliminate these effects. The longer
durability of devices based on simpler pump design with less mechanical
stress will continue to be engineered to further increase pump durability
and reliability [6]. Pump miniaturization also continues to progress to
produce devices that yield minimal surgical invasion and a smaller risk of
infection [6,11]. Other areas of research include automatic speed control,
pulsatility effects, and preventing backflow during surgical procedures [11].
Research is also being done to enhance not only the quantity of life, but the
quality of life in VAD patients. Several companies are working toward a
totally implantable system as the percutaneous driveline is a frequent
source of infection and discomfort [6,11]. In looking toward the future, the
number of patients that could benefit from VAD technology depends on a
number of factors, including patient selection, acceptance by the public and
medical community, and insurance providers [2,6]. Of these, patient
selection is key as the highest mortality rate after VAD implantation has
been observed in the sickest patient population [6]. Further steps toward
improving outcomes will involve the implantation of the VADs in less sick
populations [2]. These developments and research opportunities offer
exciting promise for the future of heart failure remediation and care.
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