Asian Annals
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Daniel Loisance
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Loisance, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loisance, D.
Asian Cardiovasc Thorac Ann 2008;16:419-431
© 2008 Asia Publishing EXchange Ltd

REVIEW PAPER

Mechanical Circulatory Support: a Clinical Reality

Daniel Loisance, MD

National Academy of Medicine, Cardiovascular and Thoracic Surgery Service, Henri Mondor Hospital, Créteil Cedex, France

For reprint information contact: Daniel Loisance, MD, Tel: 33 1 4981 2551, Fax: 33 1 4981 2552, Email: daniel.loisance{at}wanadoo.fr, Hôpital Henri Mondor, Service de Chirurgie Thoracique et Cardiovasculaire, 51 Avenue du Maréchal de Lattre de Tassigny, 94010, Créteil Cedex, France.


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 
Mechanical circulatory support is becoming an alternative therapeutic option for patients in cardiogenic shock or advanced cardiac failure who cannot be improved by maximal medical therapy. More than 30 years of engineering development and clinical research have led to a level of efficacy and reliability of ventricular assist devices, which allows promotion of this approach for the most difficult patients. Uses include a gaining-time strategy as a bridge to cardiac transplantation or recovery of native cardiac function, as well as permanent support with the device. The large variety of devices permits every cardiac surgical unit, even those not used to cardiac transplantation, to propose this option to the patient. Recent experience with small silent implantable pumps suggests that the pioneering period of mechanical circulatory support is probably over, and the time has come for precise prospective trials to optimize both patient selection and the timing for utilization. In countries where cardiac transplantation has not developed, there is now an easily accessible technique for management of patients with cardiac failure.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 
Mechanical circulatory support of the failing heart was first documented in the early 19th century, but engineering and experimental research really started with the development of open heart surgery in the 1950s. The first clinical success was achieved by DeBakey1 in 1966 in a 37-year-old woman who had undergone surgery for mitral and aortic valve replacement and could not be weaned off cardiopulmonary bypass (CPB). She was supported by a left atrium-to-right axillary artery circuit equipped with a pulsatile pneumatically driven pump for 10 days. She was then successfully weaned and lived for many years. Kantrowitz and colleagues2 developed the concept of intraaortic balloon counterpulsation and first applied it to clinical cases in 1962. Kolff and Akutsu3 used dogs for the first total artificial heart in 1958, and the first human use occurred in Houston in 1969 in a 47-year-old man who could not be weaned from CPB.4 The pump was pneumatically driven and implanted after cardiectomy, but the patient died within 3 days. Clinical research on the total artificial heart began on December 2, 1982, when DeVries and colleagues5 implanted a Jarvik 7 total artificial heart in Dr Barney Clark, a 62-year-old dentist suffering from endstage dilated idiopathic cardiomyopathy, who survived for 112 days. During that period, it became obvious that the technology was less than optimal. The advantage of the procedure, survival, was clear but rapidly outweighed by a succession of major complications related to thromboembolism and infection. This case generated much enthusiasm in the media, and a lot of skepticism among engineers and cardiologists.

1982–2002 was an extremely productive period with 3 major strategies being evaluated: permanent implantation, sometimes called destination therapy; temporary implantation pending either transplantation ("bridge to transplantation") or recovery of native cardiac function and weaning from circulatory support ("bridge to recovery"). During this time, a variety of devices were designed, evaluated in animals, and tested in humans, meeting most of the indications for treatment of the whole spectrum of cardiac failure. Large retrospective studies on single-center experience or registries were published, showing the advantages and limitations of the various techniques.

Mechanical circulatory support entered a new era at the beginning of the 21st century when clinical use spread to most surgical centers familiar with cardiac transplantation. Throughout the USA and Europe, the number of patients treated by some kind of mechanical circulatory assistance is growing fast. There are probably several reasons for this. First, cardiac transplantation is reaching its limits and clearly no longer considered the only option for endstage cardiac failure. This is because of society’s ambiguous feelings towards organ donation and a shortage of cardiac grafts for emergencies. The problem of long-term immunosuppression may also account for the relative disillusionment with cardiac transplantation. Second, the REMATCH trial results have shown that 1-year survival of patients who are not transplant candidates is doubled by mechanical circulatory support.6 For the first time, a prospective study comparing medical treatment with a more aggressive approach has shown that endstage patients can live longer and with an improved quality of life. Third, several new less-invasive and more user-friendly systems have been introduced into clinical practice. Fourth, experience in excess of 20 years in pioneering centers, and better understanding of the selection of patients and devices in the various clinical presentations of cardiac failure, have clarified the indications for various systems of mechanical circulatory support. We have progressed to a point where it is possible to give a comprehensive overview of the role of mechanical circulatory support. There are 2 different scenarios: patients in cardiogenic shock, where decisions have to be made rapidly in a difficult emotional context as the treatment is lifesaving and the ultimate goal is survival; and those in profound advanced heart failure where prolonging life and improving its quality are the main concerns.


   THE EMERGENCY PATIENT
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 
There are various situations in which decisions have to be made rapidly, such as cardiogenic shock due to acute myocardial infarction or acute decompensation of chronic cardiomyopathy (idiopathic, viral, ischemic, or toxic), inability to wean from CPB or deterioration after cardiac surgery despite optimal medical and pharmacological management, and cardiac arrest in or out of hospital when the patient cannot be resuscitated by standard procedures. In these circumstances, the main concern is patient survival. The context is difficult because the patient’s medical history is usually unknown, and the underlying pathology may be not be clearly identified. Because of cardiogenic shock, major organ dysfunction progresses rapidly, with renal insufficiency, hepatic dysfunction, a large drop in coagulation factors, pulmonary dysfunction, and cerebral damage. In more dramatic situations, evaluation of this cerebral damage is a concern because there are few indices of the irreversibility of the situation. In addition, there is a whole-body reaction with massive activation of the inflammatory cascade, resulting in more organ dysfunction. The main objective is to break the vicious circle that will worsen the initial condition and precipitate irreversible organ dysfunction.

As soon as survival is guaranteed by the institution of mechanical assistance, the issue of the final intention of treatment is raised. The strategy can be to wait for full recovery of cardiac function either rapidly or after prolonged assistance, to wait for a suitable cardiac graft, or to use the system as a permanent implant. Each of these 3 approaches has solid theoretical grounds. The bridge to transplantation strategy is the consequence of problems linked to transplantation itself. It permits waiting in an acceptable condition for a suitable cardiac graft. It has been shown that when cardiac transplantation is performed after recovery of various organ functions, the outcome is similar to that of transplantation performed on a stable patient. The present cardiac graft shortage accounts for long waiting times on the transplant list. Progressive or abrupt decompensation of patients on the waiting list is frequent (approximately 20%) despite careful monitoring of cardiac condition and optimal medical therapy. In addition, there are many situations (acute myocarditis, acute myocardial infarction) in a previously healthy patient where cardiogenic shock occurs suddenly, and immediate cardiac transplantation is the only efficient therapy. The frontiers of this bridging to transplantation strategy must be flexible. For example, when the waiting time for transplantation becomes very long (several years), can we still talk of a bridging strategy? When a patient is developing immunization while on mechanical assistance, the intention of treatment is no longer a bridge to transplantation but permanent use of the assist device. When the patient shows signs of recovery on support, the bridge strategy becomes a recovery strategy.

The ideal technique of mechanical support in urgent situations has to allow rapid and easy implantation, with immediate return to normal circulation independently of the cardiac rhythm. It should not cause major blood damage and must leave open the option of a change in strategy: to permit recovery of native cardiac function, or support until cardiac transplantation. The various options and their results and limitations will be described.


   EXTRACORPOREAL CARDIOPULMONARY LIFE SUPPORT
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 
Extracorporeal circulation is the simplest approach, and it is available in every cardiac surgery unit. The connection is made, possibly percutaneously, using a long venous cannula in the femoral vein and arterial return to the femoral or iliac artery. Distal femoral perfusion prevents limb ischemia. The circuit includes a centrifugal pump, hollow-fiber membrane oxygenator, and arterial filter. These components may be used for 6–7 days, and more exceptionally up to 3–4 weeks. The system allows adequate peripheral perfusion in any cardiac condition, and control of shock. The main disadvantages are the lack of adequate left ventricular (LV) unloading, especially in cases of ventricular fibrillation, which does not permit recovery of native cardiac function, and the huge inflammatory response with its impact on the lungs and kidneys due to blood activation in the circulation.7 The major limitation is the impossibility of totally rehabilitating the patient. The advantages are easy access, rapidity of connection, and low cost. Consequently, extracorporeal circulation with membrane oxygenation may be the first-line procedure in urgent situations. It has been shown to be extremely efficient in cardiogenic shock caused by some forms of poisoning. Recently, it has been proposed as a triage method to optimize the use of costly ventricular assist devices (VADs). This bridge-to-bridge strategy avoids major investment in a patient unlikely to recover. A further step has been made in the use of extracorporeal cardiopulmonary life support in remote general hospitals to enable transfer of patients needing mechanical circulatory support to specialized centers.

CATHETER-BASED TECHNIQUES
There are 2 totally different catheter-based techniques: the intraaortic balloon pump (IABP) and the catheter pump. The IABP was first described by Kantrowitz and Moulopoulos2 in the early 1970s and has since been used extensively. Systolic balloon deflation reduces LV external work. Diastolic filling of the balloon improves coronary perfusion. The energetic balance of the left ventricle is improved, facilitating myocardial recovery. The main limitation is due to the relationship between the rise in diastolic aortic pressure and the initial mean aortic pressure: in low pressure conditions, diastolic augmentation is minimal. In other words, the benefit of an IABP is less than optimal in the more critical situations where real cardiac mechanical support is needed.8 The extent of diastolic augmentation is also related to aortic compliance, and it is not efficient in the extremely compliant aorta, as in infants or females, and most efficient in an old atherosclerotic aorta. Another limitation is in cardiac arrhythmia or arrest, because it works in synchronous mode. This explains why an IABP is most efficient in patients with isolated myocardial ischemia (evolving myocardial infarction, postoperative ischemic cardiac failure), and yet has no effect on aortic pressure and cardiac index. In cardiogenic shock, the main risk of an IABP is that it postpones the institution of real mechanical assistance that would really help the patient.

The most fascinating technique in mechanical circulatory support is probably the turbine placed at the tip of a catheter (Figure 1Go).9 It is implanted into the left ventricle via a retrograde transfemoral approach under fluoroscopic guidance. Blood is sucked out of the ventricle and delivered to the ascending aorta. The turbine is a rotary pump activated by a cable, which spins at up to 30,000 rpm. Surprisingly, blood trauma is less than might be expected but remains a concern for long-term application of the device. The main limitation is the maximum flow rate (rarely above 4 L·min–1), and the flow-pressure curve: flow is reduced in the case of elevated afterload. For industrial reasons, the first design, the Hemopump, which was quite promising, is no longer available. The Impella pump is still proposed for clinical use and progressively gaining acceptance in the medical community.10 There are 2 configurations: one for general use, in which a transfemoral approach delivers a 2.5 to 3 L·min–1 flow, and the other for use during cardiac surgery, implantation being via the ascending aorta, which delivers a higher flow (up to 4.5 to 5 L·min–1). The system can be used for up to 8 days without significant blood trauma. The best indications for the Impella pump are low cardiac output following cardiac surgery, high-risk procedures, such as percutaneous interventions on the left main trunk, or in patients with stenosis of the last patent coronary vessel.9 An interesting development is the right Impella. The catheter is surgically introduced into the right atrium, outflow being delivered into the pulmonary artery. The pump has been shown to be quite efficient in isolated right heart failure, such as after cardiac transplantation or mitral valve surgery. It allows recovery of right cardiac function. The Tandem heart is based on the same concept of a pump catheter. A long thin inflow cannula is placed via the femoral vein into the right atrium, and pushed into the left atrium through a septotomy. The pump is placed outside. Arterial return is directed into the abdominal aorta via a retrograde femoral approach. A recent version permits right ventricular decompression, with a bypass between the right atrium and the pulmonary artery.


Figure 1
View larger version (120K):
[in this window]
[in a new window]

  		Figure 1. The Impella intraventricular assist device which is positioned into the left ventricle through a retrograde approach.

 
The main advantage of these systems is the rapidity of institution of mechanical support without major surgery. The limitations are the rather low blood flow rate and the limited period of use (≤ 1 week). The nonocclusive character of the pump does not permit satisfactory unloading of the atrium or ventricle. As with the IAPB and extra corporeal circulation, the main deleterious effect of these techniques is that their primary use may postpone the institution of more efficacious mechanical circulatory support.


   VENTRICULAR ASSIST DEVICES
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 
The concept of the VAD is quite simple. Blood is drained from the atrium or ventricle to an artificial ventricle, and returned to the circulation via an arterial (pulmonary or aortic) connection. The most efficient drainage technique is direct ventricular cannulation after sternotomy, which permits full and stable ventricular unloading. The circuit is activated by a pump, such as a volume displacement or rotary pump. Various systems have been designed to prolong survival, using an extracorporeal or intracorporeal pump.

EXTRACORPOREAL DEVICES
Extracorporeal devices using positive displacement pumps or pulsatile pumps were used very early in the development of mechanical circulatory support. The first use was in San Francisco by the group of Hill and Farrar.11,12 At the start in the early 1980s, many systems were manufactured in the USA, Japan, and Europe. Today, 3 systems are still widely used: Excor, manufactured by Berlin Heart; Thoratec, by the Thoratec Corporation; and Toyoko, sold in Japan. These are based on the same concept: a collapsible polyurethane sac or a highly flexible membrane (Excor) divides the pump chamber into blood and air compartments, activated by compressed air. Two valves, either mechanical or polyurethane, give unidirectional blood flow. Flow is dependent on the volume of the sac and the rate of activation, and totally independent of cardiac function, preload, and afterload. Suction may be used to optimize filling of the artificial ventricle. Besides this independent mode, there is a possibility of synchronous pumping, triggered by ventricular contraction. The versatility of the system is one of its main advantages as support can be univentricular (left or right) or biventricular (Figure 2Go). Assistance can be total (extracorporeal artificial heart) or partial with the ventricle still ejecting part of the filling volume. The circuit can be very small for pediatric use or it can provide full assistance in adults with a large body surface. The pump is pneumatically driven in all systems. The driving system is an extracorporeal console (in hospital use) or a portable pneumatic compressor (out-of-hospital use). The system can be implanted via a sternotomy under CPB or using a less invasive approach via a left thoracotomy. The risk of adverse events is acceptable. Major complications due to device-related problems are rare. The most frequent events are related to anticoagulation, infection, or lack of recovery from the initial organ dysfunction. Anticoagulation protocols have been progressively improved to minimize the risk of bleeding or thrombus formation. The approach today is based on a multisystem evaluation, including monitoring of the coagulation cascade and evaluation of platelet function. Consequently, treatment includes antithrombotic and antiplatelet therapy. None of the many protocols in use around the world is fully satisfactory with a negligible risk of thrombus formation or bleeding.


Figure 2
View larger version (30K):
[in this window]
[in a new window]

  		Figure 2. The versatility of the extracorporeal ventricular assist devices: (left) biventricular support via an atrial connection, (right) left ventricular bypass.

 
In the past 20 years, paracorporeal mechanical support has been used most frequently as a bridge to transplantation. Approximately 5,000 cases have been reported to the Thoratec company, including 2,450 reports sufficient for data analysis (Figure 3Go).13 The age range of the patients was wide (5–73 years), as was their weight range, with a minimum of 17 kg. The Excor from Berlin Heart is the only system available for pediatric use. It provides the possibility of circulatory support in patients with a low body weight (as small as 2.8 kg), and clinical experience is consequently growing fast. A large variety of etiologies is observed, with a prevalence of ischemic and idiopathic cardiomyopathy, including acute myocardial infarction. Biventricular support is most frequently used (60%), and the rate is growing as more experience is acquired and because of better understanding of LV dysfunction.


Figure 3
View larger version (39K):
[in this window]
[in a new window]

  		Figure 3. The Thoratec extracorporeal ventricular assist device which is the most commonly used paracorporeal assist device.

 
In acute cardiac failure, optimal LV unloading permits the right ventricle to recover. This is due to the drop in pulmonary arterial pressure as a consequence of adequate LV unloading, and also to improved coronary perfusion, which results from the return to normal arterial pressure and cardiac output. Worldwide, transplantation survival rates are in the order of 70% at 1 year, and 50% at 10 years. Transplantation is performed (after a mean duration of assist of 90 days) when the patient’s condition has returned to normal and a suitable graft is available. This time on the device has been progressively increased throughout the past 20 years because of the increased donor shortage and also increased confidence in the technique. The main limitation of the method is the reduced quality of life due to the limited mobility of the patient who remains tethered to the external driver. The optimal timing of transplantation is dependent on many factors, including recovery of organ function, quality of general rehabilitation (usually 3–5 weeks), persistent risk of adverse events (hemorrhage, embolism, infection), and risk related to pericardial adhesions that make surgical reentry more hazardous as the duration of support increases. This latter is quite important as patients are fully anticoagulated and their platelet function is inhibited. Post-transplantation survival does not differ from that observed in primary cardiac transplantation.

As well as the pneumatically driven pumps, there are the rotary pumps. The most widely used is the centrifugal pump that is employed in standard CPB. The great advantage is wide availability, and the main limitation is its nonocclusive nature. The flow rate is related to the preload of the pump and to the afterload. Consequently, in most clinical situations, it is difficult to obtain adequate atrial decompression, which may account for persistent venous congestion. Another limitation is the short period of safe use of this pump (rarely more than 8 days). The best results obtained in clinical practice are in the order of 20% long-term survival. The weaning rate is much higher (50%), but mortality after weaning is high probably because of the persistence of major problems such as infection and renal insufficiency. Because of this, rotary pumps have not gained wide acceptance among surgeons.

INTRACORPOREAL DEVICES
The simplest approach is probably the implantable version of the Thoratec extracorporeal pump (Figure 4Go). Recently, Thoratec developed a new version of this well-proven technology in which the pump is encapsulated in a titanium housing.14,15 The smaller weight and volume and thinner 9-mm percutaneous lead, compared with the 20-mm drive line of the extracorporeal version, are not real innovations but technical refinements of the initial system. This device offers the patient more mobility in the post-hospitalization period and gives him a different perspective as he no longer sees the ventricle. The implantable VAD is quite appropriate when a prolonged bridge to transplantation can be foreseen, and it is the only system that permits biventricular implantable support. One of the major drawbacks is that deposits inside the pump and on the connectors are not visible, whereas extracorporeal ventricles are usually translucent.


Figure 4
View larger version (50K):
[in this window]
[in a new window]

  		Figure 4. The intracorporeal ventricular assist device is an optimized version of the extracorporeal ventricular assist device, encapsulated for implantation in the abdominal wall.

 
In the early 1960s, as most groups where struggling to develop an artificial heart, Portner and colleagues16 described the concept of an electromagnetically driven, fully implantable left ventricular assist system (LVAS) to be used as a permanent implant, as an alternative to cardiac transplantation and the total artificial heart (Figure 5Go). The concept was based on the assumption that return to normal LV function would permit the right ventricle to recover. As mentioned previously, this assumption turned out to be true. After almost 20 years of development, the Novacor LVAS was first used in Stanford as a bridge to transplantation on an intention-to-treat basis. The first European implantation was performed at the Henri Mondor Hospital.17 The surgical technique is not difficult, involving a connection between the apex of the left ventricle and the ascending aorta.18–20 A few tricks made the surgery safe and reproducible. For a few years, the ventricle was actuated by a large and heavy paracorporeal console. In 1993, an improved version, the wearable Novacor, was developed, and used for the first time in our institution. The real advantage of this concept was rapidly validated: an almost normal life was possible outside the hospital with an almost fully implantable LVAS. The controller and batteries, worn at the waist or on the shoulder, do not significantly worsen the patient’s quality of life. Thus the period on assist rapidly increased from 52 days on average in 1993 to 375 days in 2005.21 There are 152 patients who have lived for more than 1 year, and 7 implants have been in place more than 4 years. The final configuration of the Novacor LVAS, a fully implanted system, has never been manufactured. The idea was to implant the controller and the batteries at the same time as the pump itself. The initial design is very smart with a dual pusher plate pump that will activate a 70-mL stroke volume sac-type blood pump. Two porcine valve conduits permit connections the circulatory system. The design of the pump allows minimal blood activation. The main limitation of this LVAS was actually the conduits that were responsible for most of the thrombotic complications.22 Various changes have optimized the conduits (reduced size and length, improved compliance, more compatible material), reducing device-related thromboembolic events from 25%, despite anticoagulation, to less than 10%. The unique feature of the system is its reliability as the rate of dysfunction is extraordinarily low and the durability of the various improvements is remarkable. From the patient’s point of view, the noise generated by activation of the pump has a major negative impact on quality of life. More than 2,000 operations have been performed over the past 20 years, with comparable results in terms of transplantability to those observed with the paracorporeal device. Any new system will have to compare favorably with the Novacor LVAS.23


Figure 5
View larger version (73K):
[in this window]
[in a new window]

  		Figure 5. The Novacor LVAS which has been designed for a permanent use.

 
The HeartMate XVE LVAS, originally developed by Poirier at Thermo Cardiosystems, has been the leading product of the Thoratec Corporation for years (Figure 6Go). The pump was initially pneumatically driven, but an electrically powered pump was soon proposed. This pump is similar in size to the Novacor pump.24 The main difference is the blood-contacting surface which is rough and textured, consisting of titanium microspheres and a fibrillar textured structure, facilitating the growth of a pseudo-intima that is supposed to be less thrombogenic than a synthetic surface (Figure 7Go).25 Actually, the thromboembolism rate in clinical experience, which was expected to be significantly lower than with the Novacor LVAS despite the lack of anticoagulation, appeared to be quite significant in large series.26 The rate of cerebrovascular events in the REMATCH trial (a prospective evaluation of the HeartMate XVE in the treatment of endstage cardiac failure) was in the range of 30%.6 The various components of the system are less durable than those of the Novacor LVAS, and this has been one of the main limitations in the acquisition of clinical experience. In the REMATCH trial, one third of deaths were related to some kind of device failure. Optimists will argue that this leaves much scope for improvement. The general feeling about clinical experience with the Novacor and HeartMate is mixed. On one hand, both have been extremely efficient in prolonging life and improving its quality. Experience has clearly shown the role of conditions at the time of implantation in the final survival rate. The results are greatly improved by early implantation compared with implantation in patients with endstage heart failure. The expertise of the surgical and medical teams is also important, and the best results are achieved by the most experienced and active centers.27 This is due to protocol standardization, and procedural optimization has meant that the results of LVAS implantation at 2-year follow-up differ little from those obtained after cardiac transplantation. Despite these good results, the system has not gained wide acceptance because the method appears too invasive. This is probably true, for example, the need for an abdominal pocket for pump implantation, which is not a problem for the surgeon, actually leads to minor local problems that will eventually compromise the clinical outcome. Hematoma and local infection are the starting point of a cascade of events leading to an increased risk of thromboembolism or general sepsis. This probably explains why the more recent innovations in blood pumps (rotary pumps) are so easily accepted by the clinical community. A second reason for the lack of acceptance by cardiologists and patients is the noise generated by the pump. Surprisingly, the presence of the transcutaneous cable and need for a portable controller are not real issues.


Figure 6
View larger version (111K):
[in this window]
[in a new window]

  		Figure 6. The HeartMate LVAS allows the patient to be discharged home.

 

Figure 7
View larger version (136K):
[in this window]
[in a new window]

  		Figure 7. The textured surface of the ventricle reduces the risk of embolic complications.

 
Implantable rotary pumps are now used to activate the blood in implanted LVASs. In terms of mechanical efficiency, the rotary pump is the best. However, the use of rotary pumps to activate blood is difficult for many reasons, including design, manufacturing process, functional efficiency, and methods of control. The pump delivers a continuous flow, and for years there was a general belief that this continuous flow was less than optimal for long-term circulatory support. These observations probably account for the considerable delay in the growth of clinical experience. The main advantages of rotary pumps are that the energy source (electricity) is easy to store and transfer, and the extremely small size of the pump that has to deliver no more than 5 to 6 L·min–1. Implantation of a paraventricular rotary pump is therefore easy and, as seen previously, allows the design of a catheter-based intraventricular pump.

Several pump designs based on the concept of an axial flow pump are available today: the MicroMed DeBakey developed in Houston, the HeartMate II developed by the Thoratec Corporation, the Jarvik 2000 developed in New York, and the InCor developed at Berlin Heart Center (Figure 8Go).28–31 Each of these pumps is small and compact, silent, electromagnetically activated, and connected to extracorporeal components that include the controller and batteries. In most of these pumps, the rotor is maintained in the optimal position by bearings. In the InCor system, the rotor is suspended magnetically and there is no contact at all between the moving part and the stator, which theoretically prolongs the life of the system because there is no wear on the bearings. Most systems are connected to the ventricle in the same way as pulsatile devices. In the Jarvik 2000, the entry port of the pump is placed directly in the ventricular cavity, thus avoiding problems with the inflow cannula.


Figure 8
View larger version (33K):
[in this window]
[in a new window]

  		Figure 8. Axial flow pumps: the Jarvik 2000 which is implanted directly into the ventricle, the HeartMate II, and the InCor. The rotor of the Incor is suspended in a magnetic field.

 
The most interesting characteristic of the axial flow pump is the continuous nature of the flow. If the native ventricle is totally decompressed, aortic pressure will be pulseless. The clinical and biological consequences of pulseless organ perfusion appears to be surprisingly minimal in the patients supported so far with this type of continuous flow device. Nevertheless, more precise studies and a longer period of observation are required to reach a final opinion. In addition, it must also be said that quite frequently a persistent minimal transaortic valve ejection turns the continuous perfusion delivered by the pump into pulsatile aortic flow. One of the major limitations of the various systems proposed today is the lack of evidence about their durability. Theoretically, one may be concerned by the pump’s bearing and the fatigue of the material at the level of contact. However, the first clinical impression is that this durability appears satisfactory. Patients have now been living with the small pump for more than 3 years. In the meantime, problems with bearing-less pumps have been observed due to the instability of the permanent magnets. Recent developments (InCor) have reduced the impact of this technical issue.

It is interesting to note the huge interest of cardiologists in these new pumps. Is this because they are compact and silent, or because they are innovative in terms of hemodynamics? Recent experience clearly shows that cardiologists are now less reluctant to refer good patients in time, and because of early implantation in the course of chronic cardiac failure, the results with pulsatile pumps appear to be far better than before when there were frequent late implantations. More experience is needed to form a final opinion on this important issue, the cardiologist being the gatekeeper of the technique.

A second quite similar approach is based on suspended centrifugal pumps. Terumo is developing an original system where the rotor levitates in a magnetic field, so a long pump life can be expected (Figure 9Go). VentrAssist in Australia has also developed an original pump based on a hydrodynamic bearing. In both cases, clinical experience is still too limited to draw any conclusions. Both systems recently received approval for use from the European Commission, and studies are ongoing.


Figure 9
View larger version (64K):
[in this window]
[in a new window]

  		Figure 9. The Terumo pump is suspended in a magnetic field.

 
It is worth reiterating that the LVAS concept obviously works clinically, as RV function is acceptable. This means that early institution of the VAD is required, when return to strictly normal LV function can be achieved. This observation on the potential recovery of left ventricular function is important. Recovery from chronic LV dysfunction has also been observed over the past 5 years. A few anecdotal reports from Berlin and Houston have described reverse remodeling of the myocardium during prolonged LV bypass: the size of the cardiac silhouette is decreased, the size of the myocytes is normalized, and subcellular markers of cardiac insufficiency are improved. These observations have led to attempts at weaning after a long period of LV support. The success rate in these weaning attempts is variable, and is a function of the etiology of the underlying cardiomyopathy. The success rate can also be improved by an associated pharmacological approach.32 The administration of a beta agonist seems to improve the chances of ventricular recovery in patients who have responded favorably to a reverse remodeling therapy in the first weeks and months of support. Gene therapy or cell therapy might play a role in this recovery process. Time will tell whether such an approach can remove the need for artificial circulatory support that was intended initially to be permanent. This would have a huge impact on the overall management of endstage cardiac failure.

In the last 20 years, the total artificial heart has mostly been used in emergency patients. Such temporary use of artificial hearts has never been the ultimate goal of engineers and surgeons, but has provided a unique opportunity to evaluate the real benefit expected from permanent use. In addition, the surgical technique for implantation is quite aggressive and not suited to emergency patients with severe disease. Experience with this approach and its problems will be discussed later.


   THE CHRONIC PATIENT
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
CONCLUSION
 REFERENCES
 
Huge progress has been made in the treatment of cardiac failure through multidrug therapy based on beta-blocking agents, aldosterone inhibitors, angiotensin-converting enzyme inhibitors, and diuretics. Therapy is tailored to the individual patient, resulting in good compliance. Advances have also accrued in invasive therapy, such as resynchronization of the ventricles and implantable defibrillators, as well as in surgery. These developments mean that increasing numbers of patients are surviving to the stage of advanced heart failure. They live poorly and have limited physical activity between increasingly frequent periods of hospitalization. Discussion of mechanical assistance is now possible, even if the patient is not a cardiac transplant candidate because of age or comorbidities, because there are systems that prolong life and improve its quality now on the market. Mechanical assist systems should be minimally invasive, easy to implant, silent, and easy to control, because quality of life is an important goal in addition to survival. Obviously, the system has to be reliable and durable as the objective is to prolong life as much as possible. The silence of the pump, full implantation of all parts of the system, autoregulation of the system, and prolonged periods of full autonomy are important features of the ideal system. The total artificial heart and the implantable LVAS fulfill most of these characteristics.

Since the first clinical application of a total artificial heart in a human being as a permanent implant, various devices have been used throughout the world. Retrospectively, we can even say that every cardiac surgery center and every country that was seeking fame has been developing its own program. However, despite 25 years of engineering development and extensive clinical research, the therapeutic approach to cardiac failure based on the use of the artificial heart still cannot be considered reproducible and reliable. Most clinical experience has been acquired with the Jarvik 7, a pneumatically driven ventricle (Figure 10Go). Two ventricles (70 or 100 mL) are implanted orthotopically after excision of both ventricles between the atrioventricular annuli and the aorta and pulmonary arteries. They are activated by a compressor, placed paracorporeally. The first console, the Symbion driver, was replaced in the 1990s by the CardioWest console, and more recently, by a small wearable one. After a period of enthusiasm in the early 1980s, clinical use of the Jarvik was banned by the US Food and Drug Administration (FDA) because the risks of device-related events during short-term use as a bridge to transplantation were too great. In the meantime, use as a permanent implant was considered unacceptable for basic ethical reasons because of the poor quality of life of a patient with no or very limited mobility, and the size of the driving console, which is unacceptable on a long-term basis, even if the risk of device-related complications is minimized. The program was restarted a few years later by Syncardia CardioWest. In 2004, the CardioWest total artificial heart, which is almost identical to the Jarvik 7, was approved by the FDA as a bridging device to transplantation. Jack Copeland in Tucson played a major role in development of the system, and conducted good clinical research.33 He must be credited with standardization of the surgical protocol, a comprehensive anticoagulation protocol based on a multisystem monitoring approach, and for analysis of the clinical experience accumulated in a few centers in the USA and Europe. Since the early 1990s, more than 600 CardioWest total artificial hearts have been implanted worldwide, almost always as a bridge to transplantation. As usual in mechanical circulatory assistance, the rate of adverse events (infection, bleeding, thromboembolism) is acceptable and compares favorably with most other devices. This rather good experience in short-term use does not imply that the CardioWest is suitable for permanent use. Because it is pneumatically driven, the energy source has to remain paracorporeal. This can be miniaturized and the recent portable version of the driver is an advance, but it is still too big for definitive use and cannot be implanted. This probably explains why there are so few patients receiving a CardioWest system as definitive therapy.


Figure 10
View larger version (97K):
[in this window]
[in a new window]

  		Figure 10. The Jarvik 7/70 was the first artificial heat used as a permanent implant.

 
A second fascinating and more innovative approach is represented by the AbioCor pump, based on the concept of the Penn State electrical artificial heart, which has been developed by Abiomed in conjunction with the Texas Heart Institute and the University of Louisville (Figure 11Go).34 The first human implant was performed in July 2001, which marked the first use in humans of a totally implantable system comprising pumps, controller, and batteries. The device is extremely appealing. The 2 ventricles are placed orthotopically. The energy converter, a miniature centrifugal pump, is responsible for successive alternate filling and ejection of the ventricles. A balance chamber permits adjustment of right and left balance. The blood-contacting surfaces and the trileaflet valves are polyurethane fabric. The energy source is placed in the thorax and connected to a transcutaneous energy transfer coil that permits transcutaneous transfer of energy. The whole system may be connected to a bedside console or to external batteries. Full autonomy of the patient is limited by the need to recharge the implanted lithium batteries every few hours.


Figure 11
View larger version (99K):
[in this window]
[in a new window]

  		Figure 11. The design of the AbioCor is quite original; the septum moves, leading to alternate ejection of the right and left ventricles.

 
An FDA-controlled clinical study carried out from July 2001 included 14 patients enrolled in 4 centers. Most were older (51–79 years) and had many comorbidities, such as renal dysfunction, pulmonary hypertension, or previous cardiac surgery. Two patients died intraoperatively because of massive bleeding. Survival ranged from 53 to 512 days. The initial primary endpoint of improved survival at 90 days was reached, but the lack of long-term survivors (only 2 patients were discharged from hospital) and high rate of adverse events (thromboembolism and infection) account for the poor take-up rate of the technique by new centers. The company is presently developing a more compact version of the AbioCor. The FDA AbioCor clinical trial raised a lot of hope in the cardiological community. At the start, it was seen as a major breakthrough for at least 3 reasons: the quality of the patient selection, based on objective indices of severity of condition (only patients with a 30-day mortality of 70% were eligible); for the first time, a total artificial heart was proposed for clinical use, permitting full autonomy; and for the first time it was possible to study the real life of a patient with total circulatory support. On the other hand, the limitations of the strategy are obvious: surgery for implantation of components (pump + batteries + internal transcutaneous energy transfer coil) is actually quite aggressive, probably too aggressive for the very sick and often old patients who should not be kept waiting for transplantation; and the rate of device-related adverse events is far above the acceptable level. More technological refinements and clinical experience are needed before this approach can be used extensively. In addition, the system is far too big to be accommodated by the usual anatomy of patients.

The present limitations of an artificial heart provide solid reasons for preferring a less invasive approach such as the implantable LVAS. There are at least 3 reasons for recent enthusiasm for this approach. First, experience gained in emergency cases with the LVAS as a bridge to transplantation has shown that prolonged survival is possible with univentricular support. Second, the new compact and silent pump design allows simple surgical implantation and does not carry the risk of local complications of the pump pocket. Third, a quite unexpected improvement in cardiac function during long-term support opens up very attractive research and treatment options, with recovery of native cardiac function permitting explantation of the assist device and a prolonged life. The possibility of enhancing the natural potential for recovery of the failing myocardium by associated pharmacological support or cell therapy is currently exciting much interest among research and clinical cardiologists, and raising a lot of hope among patients.

The REMATCH trial, organized in the mid 1990s and performed in the late 1990s and first 2 years of the 21st century, is a landmark in the history of mechanical assistance. It prospectively compared patients treated medically with those supported by an implantable LVAS (Heartmate I XVE). The patients included were adults with profound cardiac failure who could not be transplanted for various reasons (age, comorbidities). The results showed improved survival after 1 year, and improved quality of life in the group selected for surgery. There was also a high risk of infection, thromboembolism, and device failure.35 The surgical community used this study to try to convince cardiologists that the technology was ready for wide application. However, considering the number of implants performed annually, it is clear that this study did not increase referrals, and the real change in attitude of cardiologists is due to the development of smaller pumps.

For the time being then, the only acceptable solution for permanent support is the LVAS approach. This means that cardiologists have to define clearly the category of chronic cardiac failure patients who are suitable for LVAS, and the optimal timing for elective implantation of the device. There are 300,000–500,000 patients with advanced heart failure in the USA; only about 2,000 have transplants.36 The gap between demand and the possibility of transplantation could be filled by more extensive use of assist devices. However, the number is not as large as it seems as many patients are very old (mean age of those with advanced heart failure is 74 years) and many have comorbidities that preclude major surgery. Finally, it is estimated that 8,000–10,000 patients might benefit from the currently available mechanical support techniques. These impressive numbers have prompted cardiologists to risk stratify advanced heart failure patients. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is presently working on a draft that should help in the decision process. Data collection will be complete as centers performing the implantation will not get reimbursement if they do not report to INTERMACS.37

The definition of clinical condition at the time of implantation is one of the most original features of the program. It does not consider only ejection fraction or peak oxygen consumption. There are 7 levels. Level 1 is the most dramatic one of rapidly evolving life-threatening hypotension despite rapidly escalating inotropic and pressor support ("crash and burn"). Level 2 describes patients who are dependent on intravenous inotropics and deteriorating ("sliding on inotropics"). Level 3 is patients with stable blood pressure, organ function, and nutrition, on continuous inotropic support but demonstrating repeated failure to wean because of recurrent hypotension and renal failure ("dependent stability"). Level 4 is patients who are stable but experience frequent relapses of fluid retention; the doses of diuretics fluctuate at high levels ("frequent flyers"). Level 5 defines patients who are living at home but walking from room to room with difficulty ("housebound"). Level 6 includes patients who have limited activity outside the house but fatigue after a few minutes of meaningful activity ("walking wounded"). Level 7 describes patients who are comfortable, without any episodes of recurrent decompensation. The presence of arrhythmia is a negative prognostic factor. In each of these groups, the prognosis is relatively clear (e.g., death within a few hours in level 1). In levels 1 to 4, rapid intervention such as implantation of a VAD is recommended. Prospective trials comparing medical and surgical therapies should be started in each of these cohorts. In every level of INTERMACS, the contraindications to aggressive therapy should be respected. These include technical obstacles to implantation and maintenance (cancer, active infection, severe LV dysfunction, mechanical valves, inadequate body surface area) as well as inability of the patient to understand and provide informed consent, and major psychiatric disorders. The preliminary results of INTERMACS were presented and discussed at a meeting of the International Society of Heart and Lung Transplantation in April 2007. The survival rate in the first 200+ patients in the previous year clearly showed a huge difference between level 1 and levels 2–4, with survival at 1 year of 70% in levels 2–4, a quite acceptable figure considering the severity of illness in this population.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
REFERENCES
 
After more than 25 years of continuous efforts by engineers and doctors, mechanical circulatory support is becoming a clinical reality. It has been shown to be the only therapeutic solution in terminally ill patients, as it gains time and makes cardiac transplantation possible. Recently, it has been demonstrated that patients with advanced heart failure are now surviving longer and under better conditions. More clinical research is needed to optimize the selection of ventricular assist device and timing of implantation.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 THE EMERGENCY PATIENT
 EXTRACORPOREAL CARDIOPULMONARY...
 VENTRICULAR ASSIST DEVICES
 THE CHRONIC PATIENT
 CONCLUSION
 REFERENCES
 

  1. DeBakey ME. Left ventricular bypass pump for cardiac assistance. Clinical experience. Am J Cardiol 1971;27:3–11.[Medline]

  2. Kantrowitz A, Tjonneland S, Freed PS, Phillips SJ, Butner AN, Sherman JL Jr. Initial clinical experience with intraaortic balloon pumping in cardiogenic shock. JAMA 1968;203:113–8.[Abstract/Free Full Text]

  3. Akutsu T, Mirkovitch V, Topaz SR, Kolff WJ. Silastic sac type of artifical heart and its use in calves. Trans Am Soc Artif Intern Organs 1963;9:281–5.[Medline]

  4. Cooley DA, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milam JD. Orthotopic cardiac prosthesis for two-staged cardiac replacement. Am J Cardiol 1969;24:723–30.[Medline]

  5. DeVries WC, Anderson JL, Joyce LD, Anderson FL, Hammond EH, Jarvik RK, et al. Clinical use of the total artificial heart. N Engl J Med 1984;310:273–8.[Abstract]

  6. Rose EA, Moskowitz AJ, Packer M, Sollano JA, Williams DL, Tierney AR, et al. The REMATCH trial: rationale, design, and end points. Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure. Ann Thorac Surg 1999;67:723–30.[Abstract/Free Full Text]

  7. Weber TR. Extending the uses of ECMO. Chest 2004;126:9–10.[Medline]

  8. Mundth ED, Buckley MJ, Daggett WM, McEnamy MT, Leinbach RC, Gold HD, et al. Intra-aortic ballon pump assistance and early surgery in cardiogenic shock. Adv Cardiol 1975;15:159–67.[Medline]

  9. Loisance D, Dubois-Rande JL, Deleuze P, Okude J, Rosenval O, Geschwind H. Prophylactic intraventricular pumping in high-risk coronary angioplasty. Lancet 1990;335:438–40.[Medline]

  10. Jurmann MJ, Siniawski H, Erb M, Drews T, Hetzer R. Initial experience with miniature axial flow ventricular assist devices for postcardiotomy heart failure. Ann Thorac Surg 2004;77:1642–7.[Abstract/Free Full Text]

  11. Hill JD, Farrar DJ, Hershon JJ, Compton PG, Avery GJ 2nd, Levin BS, et al. Use of a prosthetic ventricle as a bridge to cardiac transplantation for postinfarction cardiogenic shock. N Engl J Med 1986;314:626–8.[Medline]

  12. Farrar DJ, Hill JD, Pennington DG, McBride LR, Holman WL, Kormos RL, et al. Preoperative and postoperative comparison of patients with univentricular and biventricular support with the thoratec ventricular assist device as a bridge to cardiac transplantation. J Thorac Cardiovasc Surg 1997;113:202–9.[Abstract/Free Full Text]

  13. Farrar DJ, Holman WR, McBride LR, Kormos RL, Icenogle TB, Hendry PJ, et al. Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function. J Heart Lung Transplant 2002;21:516–21.[Medline]

  14. Farrar DJ, Buck KE, Coulter JH, Kupa EJ. Portable pneumatic biventricular driver for the Thoratec ventricular assist device. Asaio J 1997;43:M631–34.[Medline]

  15. Slaughter MS. Destination therapy: the future is arriving. Congest Heart Fail 2005;11:155–6.[Medline]

  16. Portner PM, Oyer PE, Jassawalla JS, Miller PJ, Chen H, LaForge DH, et al. An implantable permanent left ventricular assist system for man. Trans Am Soc Artif Intern Organs 1978;24:99–103.[Medline]

  17. Loisance D, Deleuze PH, Mazzucotelli JP, Abe Y, Le Besnerais P, Dubois-Randé JL. The initial experience with the wearable Baxter Novacor ventricular assist system. J Thorac Cardiovasc Surg 1994;108:176–7.[Free Full Text]

  18. Loisance DY, Deleuze PH, Mazzucotelli JP, Le Besnerais P, Dubois-Randé JL. Clinical implantation of the wearable Baxter Novacor ventricular assist system. Ann Thorac Surg 1994;58:551–4.[Abstract]

  19. Pennington DG, McBride LR, Swartz MT. Implantation technique for the Novacor left ventricular assist system. J Thorac Cardiovasc Surg 1994;108:604–8.[Abstract/Free Full Text]

  20. Vigano M, Martinelli L, Minzioni G, Rinaldi M, Pagani F. Modified method for Novacor left ventricular assist device implantation. Ann Thorac Surg 1996;61:247–9.[Abstract/Free Full Text]

  21. Wheeldon DR, LaForge DH, Lee J, Jansen PG, Jassawalla JS, Portner PM. Novacor left ventricular assist system long-term performance: comparison of clinical experience with demonstrated in vitro reliability. Asaio J 2002;48:546–51.[Medline]

  22. Houel R, Moczar M, Ginat M, Loisance D. Pseudointima in inflow and outflow conduits of a left ventricular assist system: possible role in clinical outcome. Asaio J 2001;47:275–81.[Medline]

  23. Lee J, Miller PJ, Chen H, Conley MG, Carpenter JL, Wihera JC, et al. Reliability model from the in vitro durability tests of a left ventricular assist system. Asaio J 1999;45:595–601.[Medline]

  24. Frazier OH, Benedict CR, Radovancevic B, Bick RJ, Capek P, Springer WE, et al. Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:675–82.[Abstract/Free Full Text]

  25. Spanier TB, Chen JM, Oz MC, Stern DM, Rose EA, Schmidt AM. Time-dependent cellular population of textured-surface left ventricular assist devices contributes to the development of a biphasic systemic procoagulant response. J Thorac Cardiovasc Surg 1999;118:404–13.[Abstract/Free Full Text]

  26. Oz MC, Argenziano M, Catanese KA, Gardocki MT, Goldstein DJ, Ashton RC, et al. Bridge experience with long-term implantable left ventricular assist devices. Are they an alternative to transplantation? Circulation 1997;95:1844–52.[Abstract/Free Full Text]

  27. Long JW. Advanced mechanical circulatory support with the HeartMate left ventricular assist device in the year 2000. Ann Thorac Surg 2001;71:S176–84.[Medline]

  28. Goldstein DJ. Worldwide experience with the MicroMed DeBakey Ventricular Assist Device as a bridge to transplantation. Circulation 2003;108(Suppl II):272–7.

  29. Griffith BP, Kormos RL, Borovetz HS, Litwak K, Antaki JF, Poirier VL, et al. HeartMate II left ventricular assist system: from concept to first clinical use. Ann Thorac Surg 2001;71:S116–20.[Medline]

  30. Westaby S, Banning AP, Jarvik R, Frazier OH, Pigott DW, Jin XY, et al. First permanent implant of the Jarvik 2000 Heart. Lancet 2000;356:900–03.[Medline]

  31. Potapov EV, Loebe M, Nasseri BA, Sinawski H, Koster A, Kuppe H, et al. Pulsatile flow in patients with a novel nonpulsatile implantable ventricular assist device. Circulation 2000;102(Suppl III):183–7.

  32. Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med 2006;355:1873–84.[Abstract/Free Full Text]

  33. Copeland JG, Smith RG, Arabia FA, Nolan PE, Sethi GK, Tsau PH, et al. Cardiac replacement with a total artificial heart as a bridge to transplantation. N Engl J Med 2004;351:859–67.[Abstract/Free Full Text]

  34. Dowling RD, Ghaly AS, Gray LA Jr. Creation of a diaphragm patch to facilitate placement of the AbioCor implantable replacement heart. Ann Thorac Surg 2004;77:1849–50.[Abstract/Free Full Text]

  35. Dowling RD, Park SJ, Pagani FD, Tector AJ, Naka Y, Icenogle TB, et al. HeartMate VE LVAS design enhancements and its impact on device reliability. Eur J Cardiothorac Surg 2004;25:958–63.[Abstract/Free Full Text]

  36. Adams KF Jr, Zannad F. Clinical definition and epidemiology of advanced heart failure. Am Heart J 1998;135:S204–15.[Medline]

  37. Stevenson LW, Rose EA. Left ventricular assist devices: bridges to transplantation, recovery, and destination for whom? Circulation 2003;108:3059–63.[Free Full Text]





This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Personal Folders
Right arrow Download to citation manager
Right arrow Author home page(s):
Daniel Loisance
Right arrow Permission Requests
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Loisance, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Loisance, D.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
ANN THORAC SURG ASIAN CARDIOVASC THORAC ANN EUR J CARDIOTHORAC SURG
J THORAC CARDIOVASC SURG ICVTS ALL CTSNet JOURNALS