(Circulation. 1997;95:2340-2343.)
© 1997 American Heart Association, Inc.
Articles |
Deep Thoughts on Tin Men
Fact, Fallacy, and Future of Mechanical Circulatory Support
Cardio Technologies, Inc (H.R.L.), and the Department of Medicine, Columbia-Presbyterian Medical Center (M.L.W.), New York, NY.
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Introduction |
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Since the first artificial heart implant in 1969, physicians have expressed both ardent enthusiasm and serious doubt regarding the potential of mechanical devices to replace the failing human heart.1 The recent funding of the REMATCH trial by the US NIH may best illustrate the renewed interest in mechanical circulatory support. This trial is a milestone in the development of mechanical support because it will be the first large, controlled trial of the effect of LVAD support on survival when used as a permanent alternative to medical therapy.
In large part, the basis for this renewed optimism in mechanical circulatory support has been the impressive success of the LVAD in its "bridge-to-transplant" role of providing hemodynamic support until a donor heart is available.2 A recent study showed that 72% of patients supported with a LVAD survived for 60 days after heart transplantation, compared with 33% of patients who received medical therapy alone.3 A more limited but still impressive experience with long-term LVAD therapy has been obtained among patients now successfully supported for 1 year; a handful of patients have been supported for almost 2 years. Furthermore, patients supported with LVADs are in general better transplant candidates, because they experience a significant improvement in vital organ function during support.4
In this issue of Circulation, Jaski et al5 report their experience with the improvements in exercise capacity that can be achieved with LVAD support. Their study illustrates the need for a better understanding of the underlying physiology of LVAD support before a more widespread clinical application of LVADs is implemented as a permanent alternative to other therapies. While LVADs are one of the most commonly used methods of mechanical cardiac assistance, the range of cardiac replacement therapies clinically available or in the research phase is substantially broader.
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The Spectrum of Cardiac Replacement Therapy |
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TopIntroductionThe Spectrum of Cardiac...The FutureReferences |
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Cardiac replacement therapy encompasses the biological, biomechanical, and mechanical therapies that can substitute in part or whole for the function of the native heart. Note that while these treatments are currently used for patients with end-stage heart failure, future success of some therapies may lead to their use in earlier stages of heart failure, as a result of a marked increase in the potential patient population.
Biological Therapy
The first practical implementation of cardiac replacement therapy was the development of heart transplantation as a viable alternative to medical therapy. Although the first human heart transplant was performed by Dr C. Barnard in 1969, it was not until the development of cyclosporine and its widespread use in the early 1980s that acceptable mortality and morbidity rates were realized. Currently, cardiac transplantation is associated with 95% perioperative, 85% 1-year and 65% 5-year survival rates.6 Although these operations are successful, a flattening of the donor supply limits the number of heart transplants performed nationwide to 
2500 per year, or 5% of the potential recipients.7 Because of this, 30% of patients awaiting transplantation die before they receive a donor heart.8 While issues such as rejection are not currently major causes of mortality, the inability to develop therapies for other complications, primarily accelerated graft atherosclerosis, has led physicians to explore other potential therapies.
Other biological options, including xenotransplantation and humanizing the hearts of other animal species, have been proposed and in some cases even attempted.9 There are not enough data at this point to either support or deny the eventual clinical usefulness of such options. However, some investigators have raised questions separate from the uniqueness of the immunosuppression required for these transplants. It has been suggested that the prevention of transmission of animal-borne diseases, called zoonoses, may be more of a challenge than actual development of the procedures.
Biomechanical Therapy
Another potential cardiac replacement therapy is the use of a patient's own skeletal muscle to assist the failing heart. Termed cardiomyoplasty, this technique wraps a patient's latissimus dorsi muscle around the heart and stimulates it in synchrony with the heart by use of a modified pacemaker.10 This concept is very attractive because it would not require the use of immunosuppressive drugs or an external power source. However, several factors, such as the need for prolonged conditioning of the muscle and the adverse effect of the procedure on ventricular loading in larger hearts, may limit its overall clinical potential.11 12 13 In previous trials, although subjective benefits were seen in some patients, a significant overall clinical benefit was not shown. In addition, some investigators have noted other complications, such as muscle necrosis, arrhythmias, and sudden death.
It is clear that a large percentage of the population that requires cardiac replacement therapy currently has no viable alternative to medical therapy. The question remains: Can mechanical cardiac assistance fill this void?
Mechanical Cardiac Assistance
A large number of devices represents the spectrum of mechanical replacement therapy. These devices can be arbitrarily broken down into categories based on the intended length of use. These categories are short-term/acute use (hours to days), intermediate-term use (
29 days), and long-term/permanent use (>30 days).
Short-term/Acute Use Devices
The IABP has been used in multiple roles ranging from postcardiotomy shock to as a bridge to transplant.14 The increased waiting period for donor hearts has limited the usefulness of this technology in the bridge situation. Centrifugal pumps were introduced in the late 1970s for use in cardiopulmonary bypass. Their use as a cardiac assist device was a logical extension of this primary function. Unfortunately, several complications are associated with these longer durations of support, including bleeding, renal dysfunction, infection, and thromboembolism.15 ECMO, or the use of a centrifugal pump in concert with an oxygenator, provides both respiratory and hemodynamic support. Poor survival rates in the adult population, a limited duration of support, and complication rates have caused ECMO to be used only rarely except in the pediatric population.15
Intermediate-term Devices
Other devices, such as the Thoratec and the Abiomed BVS systems, are external devices that not only can be LVADs but also right ventricular assist devices (RVADs). These devices have been used successfully in the bridge-to-transplant situation and for temporary hemodynamic support in postcardiotomy shock.16 17 However, these systems are subject to the same complications (bleeding, thromboembolism, etc) as the short-term devices.
Long-term/Permanent Devices
The prototypical permanent cardiac assist device is the TAH. The TAH program sponsored by the NIH in the 1960s led to the development of the first clinically useful devices. While overall clinical use has been limited, two TAHs are still being used in a bridge-to-transplant role. Two additional TAHs are being developed under an NIH contract for permanent use. However, TAH support has been associated with a significant risk of complications, such as stroke and mediastinitis, though use of the newer designs may reduce these events.
Early clinical results with the TAH were at best mixed, although recent data show some improvement. However, the TAH may play an important role in patients who are at a high risk to develop right heart failure after LVAD placement or who are in need of a repeat heart transplant. Despite its potential benefits, it is unlikely that we will see widespread use of a TAH in the next decade.
The most common long-term devices currently in use are the HeartMate (Thermo CardioSystems, Inc) and the Novacor (Baxter) LVADs.18 19 The HeartMate device is unique among mechanical devices in that it does not require systemic anticoagulation to prevent thromboembolic events.20 These devices are generally implanted in an intraperitoneal or extraperitoneal position. The device is connected by cannulas between the apex of the left ventricle and the base of the aorta. Blood fills the device from the left ventricle. A pneumatic or electrically powered mechanism compresses the blood in the device, producing forward blood flow, which is directed by a pair of unidirectional mechanical valves. Power is supplied through the skin by use of an external drive line.
Since the inception of this type of LVAD, many hurdles have been overcome. Originally, blood clots formed on device surfaces, creating a source of embolism. This problem was alleviated by texturing the surfaces of the device instead of making it perfectly smooth. A rough surface encourages epithelialization, which forms a natural physiological surface of endothelial cells. This endothelial cell layer then protects against thrombogenesis. These devices are no longer responsible for significant hemolysis, and the rate of infection has been significantly reduced. Initial problems of power requirements have been addressed so that patients who use electrically powered LVADs today are equipped with external, rechargeable batteries that are carried on a belt and provide power for 6 to 8 hours. Although many of the original technological problems have been worked out, clinical use of LVADs still has limitations.
Although extensive studies have been done, clinicians are still unable to predict which patients are the best candidates for LVAD placement. However, a number of absolute contraindications to LVAD implantation are known. These include technical issues, such as small body surface area, as well as physiological problems, including significant aortic valve regurgitation, previous neurological, pulmonary, liver, or renal failure, or other factors that would preclude a patient from being a candidate for heart transplantation. In the impending REMATCH trial, some of these contraindications, such as previous malignancy, may not be an absolute contraindication but are weighed in relation to the expected survival of the patient and the likelihood that the LVAD would function appropriately for longer than this period.
In this issue of Circulation, Jaski et al5 extend the findings of previous investigators21 22 on a factor crucial to the success of long-term LVAD support: its ability to improve exercise capacity. Exercise capacity is a major determinant of the quality of life possible in permanent LVAD recipients. Previous investigators have shown that most patients who were NYHA class IV improve to class I before operation during mechanical circulatory support.23 This subjective improvement is associated with a 59% increase in cardiac output from before to 2 months after operation, a benefit that was documented to last for the duration of LVAD support. Similar increases in blood pressure and end-organ function were also noted.
Jaski et al provide important information about the mechanics of exercise response in patients with LVADs. While the patients were in the supine position, there was an increase in LVAD output of a modest degree, which results largely from the increase in pumping frequency of the LVAD. Pump stroke volume changed little. The native heart appeared to contribute little to output in the resting state as an independent parallel pump. During exercise in the supine position, there was modest but distinct stroke output of the heart. Thus, increased venous return to the assisted heart was met by an increase in pump frequency and a stroke output of the left ventricle at a normal exercise heart rate. A profound decrease in pulmonary saturation during the supine exercise from 66% to 38% was present. This fact raises the possibility of a very significant constraining force on cardiac output while in this position.
When the patients were in the upright position, oxygen consumption increased to a much greater degree, and LVAD output did not increase much more in the upright than the supine position. Thus, the heart must have augmented its output much more in the upright than the supine position. These data strongly suggest a profound constraining effect on cardiac filling in the supine position. The similar right and left ventricular filling pressures also support this idea. Echocardiograms taken with the patients in the supine position showed a decrease in right ventricular size or change in septal position. This may also reflect the constrained left ventricle compressing the right ventricle. In the upright position, there must be significant relief from this constraint, since oxygen consumption and presumably cardiac output increase strikingly more. It will be of great interest to have further documentation of use of the upright exercise position on the size and function of the cardiac chambers under these circumstances. Certainly, striking augmentation of native cardiac function in the upright position would portend well for the short- and long-term benefits of insertion of an LVAD.
Clearly, we lack important information about the overall ability of patients to recover from the heart failure state. It is even possible that the deleterious effects of advanced heart failure on such areas as skeletal muscle and autonomic system function are not significantly reversible. The future success of circulatory assist devices will depend on proof that these devices are safe, clinically useful, and economically viable. Initial data from the "physiological laboratory" of patients undergoing LVAD support as a bridge to transplant provided the crucial information that made the concept of permanent cardiac assistance feasible. Data from studies such as the REMATCH trial will change permanent cardiac assistance from concept to reality.
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The Future |
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TopIntroductionThe Spectrum of Cardiac...The FutureReferences |
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Perhaps the most important mode of LVAD support is not its use as a permanent alternative to transplantation but its use as a bridge to recovery of native cardiac function. Recent studies23 have suggested that reverse remodeling of the heart can occur in patients who have undergone prolonged loading of the left ventricle by LVAD support. Other investigations have shown normalization of hypertrophy and fiber orientation under similar conditions.24 25 Nevertheless, it is a long journey from restoration of normal cardiac geometry to significant reversal of the systemic biochemical and mechanical alterations seen in the heart failure state. Only with the increased use of mechanical assist devices and the careful study of their physiologies can the promise of these devices as important additions to the armamentarium for the treatment of patients with chronic congestive heart failure be realized. Maybe then we can give the Tin Man a good heart.
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Selected Abbreviations and Acronyms |
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Footnotes |
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Reprint requests to Howard R. Levin, MD, Chief Scientific Officer, Cardio Technologies, Inc, 3960 Broadway, New York, NY 10032.
Dr Levin is a stockholder in Cardio Technologies, Inc, a startup medical device manufacturer of cardiac assist devices.
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References |
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TopIntroductionThe Spectrum of Cardiac...The FutureReferences |
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