STEVENSON AND KORMOS, ET AL., MECHANICAL CARDIAC SUPPORT
2000
JACC Vol. 37, No. 1, January 2001:340-70
I.
Current Status of Mechanical Cardiac Support
A
variety of devices are available to patients depending
on the indications for support.1
In Table
1, the
devices that have been used in more than 100 patients
in the U.S. are listed, along with the chief characteristics
that determine present use. Currently, specific device
use is governed by the FDA.
Devices
for circulatory support are currently used in three
broad categories: 1) acute CS with support <1 month;
2) more prolonged support from 30 days to >1 year; and
3) permanent support as an alternative to transplantation.2
The acute, short-term group includes patients who have
cardiac failure after cardiac operations, myocardial
infarction (MI) shock or acute cardiomyopathy due to
myocarditis or other causes, with a potential likelihood
of recovery. In the intermediate or long-term group
are those who are suitable for transplantation but deteriorate
before a heart becomes available and require mechanical
support prior to transplantation. A small percentage
of these patients with chronic HF regain ventricular
function and are able to have the devices removed without
requiring transplantation. The third group of patients
has irreversible cardiac failure that might require
circulatory support, but they are not good candidates
for cardiac transplantation. Therefore, if devices are
inserted, they must be considered permanent or “destination
therapy” and are currently investigational.
The
acute heart failure patients are still comprised primarily
of those requiring support after cardiac operations
and represent about 1.5% of the 400,000 patients who
undergo cardiac operations in the U.S. each year. Post-cardiotomy
patients may require support for a variety of problems,
often relating to the sequelae of perioperative MI,
valve disease or problems of myocardial preservation.
Several devices are available to support post-cardiotomy
shock patients. The simplest device is extracorporeal
membrane oxygenation (ECMO), a cardiopulmonary bypass
system with venoarterial cannulation placed either through
the femoral or intrathoracic vessels. These systems
are limited by their short-term usefulness of <1
week and by problems with bleeding and coagulation.
The systems have been improved recently by heparin coating
of the circuits, which may reduce the incidence of thromboembolism
as well as the bleeding caused by anticoagulation. However,
these systems do not always provide adequate LV decompression,
a primary determinant of recovery. Often the ECMO system,
the centrifugal or the Abiomed VADs are used as systems
for acute resuscitation to salvage severely ill patients,
who are subsequently determined to be transplant candidates
and are converted to a bridge to transplant device (Thoratec,
Cardiowest, Novacor and HeartMate), thus creating a
“bridge to a bridge.” Four centrifugal pumps
are currently available and provide the advantage of
biventricular support, but they also present problems
of anticoagulation.3
Two VADs, the Abiomed 4
and the Thoratec,5
offer the advantages of pulsatility, specially integrated
cannulas for a variety of cannulation options, and more
sophisticated control systems. The Thoratec VAD allows
for ambulation and management out of an ICU setting.
Currently, none of these systems allows for hospital
discharge of patients in the U.S. However, clinical
trials with a portable driver (Thoratec) are ongoing,
and the driver is approved for use in other countries.
Outcomes
of post-cardiotomy support are similar regardless of
the device employed 1
and relate primarily to age of recipient, timing of
insertion and degree of completed MI.3,4
Survival rates range from 20% to 40% with complications
of bleeding (25% to 45%), renal failure (20% to 30%),
multiorgan failure (20% to 25%), thromboembolism (4%
to 20%), neurological deficit (5% to 20%) and infections
(35% to 60%), of which only 5% to 10% are actually device
related. A small group of patients in the post-cardiotomy
group undergo support for a period of time without recovery
of cardiac function and become candidates for cardiac
transplantation. With the Thoratec VAD, the only device
approved for both post-cardiotomy support and bridge
to transplantation, there were 34 patients who underwent
bridge to transplantation after a recent cardiac operation.
Seventy-one percent were transplanted and 53% were actually
discharged from the hospital. By comparison, of 536
patients primarily implanted with Thoratec VADs as a
bridge to transplantation, 328 or 61% were transplanted,
and of those, 284 survived (87% of those transplanted),
with an overall survival rate of 53%. However, it is
important to note that in the post-cardiotomy group,
only 75% of those transplanted survived, while in the
primary VAD bridge-to-transplant group, 87% of those
transplanted survived.
Post-MI
support represents about 10% of all patients treated
with VADs. This application has not been widely employed,
because of the wide range of co-morbidities encountered
by such patients, many of whom succumb before surgery
can be performed. Of those implanted with VADs after
acute MI with CS, the majority have been considered
unsuitable for coronary revascularization. However,
the VAD in this population, either post-cardiotomy or
after failed medical management, may serve either as
a bridge to transplant or bridge to recovery, providing
an emerging potential application. Recent experiences
when LVADs were implanted within 14 days after acute
MI have shown a survival rate of 74% to transplantation
or explantation.6
This experience suggests that VAD implantation for post-MI
CS may be able to reduce the mortality of 65% to 80%
currently associated with medical management.
Acute
dilated cardiomyopathy has a variety of etiologies,
the most common of which is myocarditis.7
This has been an indication for LVAD implantation in
about 15% of all patients on VADs. The outcomes are
quite variable, but the potential for recovery is increased
in younger patients, patients who have had shorter periods
of heart failure and patients who have improved more
rapidly after LVAD implantation.8
Intermediate or long-term device support (30 days to
>1 year) has been employed largely for candidates for
cardiac transplantation whose condition deteriorates
before hearts become available. Of approximately 2,400
cardiac transplants performed in the U.S. in 1997, 15%
of those patients required circulatory support devices
to be bridged to transplantation. The types of devices
used to bridge patients include extracorporeal VADs,
implantable wearable LVADs and implantable biventricular
replacement devices. The most important evolution in
this group of patients has been the ability to discharge
them from the hospital with implantable wearable LVADs.
However, these LVADs do not provide for right ventricular
(RV) support. If severe right heart failure occurs,
another device must be implanted for the RV. Consequently,
patients with severe concomitant RV failure have usually
been implanted with extracorporeal VADs or implantable
biventricular replacement devices. Approximately 10%
to 15% of all patients implanted with wearable VADs
have required right heart support with another device.
Of
the more than 3,000 patients who have been implanted
with circulatory support devices as a bridge to transplantation,
approximately 60% to 70% actually received a transplant.
Of those who received a transplant, 85% to 90% survived
to be discharged from the hospital.9-11
Among those implanted as a bridge to transplantation,
approximately 5% recovered ventricular function and
survived without cardiac transplantation. Approximately
25% of patients from one series of more than 100 patients
implanted with VADs for bridge to transplantation recovered
ventricular function, and of those survivors, 14 retained
good cardiac function while the others later died or
required cardiac transplantation.8
During
the last year, at least 50% of patients receiving implantable
wearable LVADs have been able to be discharged from
the hospital, and patients have been supported from
periods of a few weeks to >4 years. Although patients
discharged from the hospital may require readmission
for problems of infection, anticoagulation or bleeding,
the cost of caring for these patients has been significantly
reduced by the out-of-hospital option. Currently, that
option is available only with the implantable wearable
LVADs and is not available with the extracorporeal LVADs
or the implantable biventricular replacement devices.
However, this option has potentially important economic
implications.
Complications
occurring during bridge to transplantation are well
documented in individual series, but unfortunately a
reliable common registry is not currently available
to determine outcomes. From individual series, it is
reported that bleeding requiring reoperation occurs
in 5% to 30%, infections occur in 40%, and device-related
infections occur in only 5% to 30%. Thromboembolism
has been reported in 5% to 25% of patients, with a stroke
rate of 2.7% to 25%. Elevated panel reactive antibodies
(PRA) may complicate the LVAD bridge to transplantation.
These are presumed to be due to anti-HLA antibodies
induced by blood products, cross-reactive antibodies
to the device itself or antiphospholipid antibodies
due to exposure to fibrin glue (topical bovine thrombin)
or perioperative blood transfusions. The consequent
elevation of PRAs cause “positive” donor-specific
crossmatches that may delay transplantation. In one
large series12
with the TCI HeartMate device, PRA elevation to greater
than 10% occurred in 66% of patients post-LVAD but persisted
in only 22% at the time of transplantation. However,
several patients required immunosuppressive therapy
and plasmapheresis to reduce the PRA.
The
final group of patients, who are not yet well defined,
are patients who have apparently irreversible cardiac
failure but are not good candidates for cardiac transplantation.
Enrollment is almost completed in the randomized, controlled
REMATCH trial, in which the TCI HeartMate vented electric
LVAD is compared with optimal medical therapy in patients
who are not candidates for cardiac transplantation.13
The FDA has recently given permission for Novacor to
begin a similar study of the permanent implantation
as “destination therapy” for patients with
severe cardiac failure who are not candidates for cardiac
transplantation. Unlike the REMATCH trial, the Novacor
study will not include a randomized control group. The
obvious impediments to the success of such long-term
device therapy are the risks of infection related to
externalized energy sources, the threat of thromboembolic
events and mechanical failure. Although we do not have
data from the current studies to address these questions,
it is apparent that the long-term result will depend
on solving these problems. If these trials can demonstrate
efficacy, it will be appropriate to consider this therapy
for similar patients among the 50,000 to 100,000 patients
in the U.S. who have been estimated to potentially benefit
from this technology.14
