The Quest for Permanent Ventricular Assistance: The Role of Aortic Counterpulsation

Need For Permanent Lvad The treatment of CHF due to left ventricular dysfunction has evolved dramatically in the past several decades.1,2 Advances in medical treatments have helped patients in all stages of heart failure, even those with NYHA IV symptoms.3,4 However, for an expanding group of patients, non-pharmacologic circulatory assistance is the only option. Currently, transplantation is the best option for these patients, but it is limited by a shortage of donors and by the complications of immuno-suppression and chronic allograft vasculopathy.5 These statistics have focused attention on mechanical circulatory assist devices for permanent use. Investigators have utilized mechanical energy in three ways to improve circulation. The first is direct augmentation of the heart, demonstrated by concepts such as dynamic cardiomyoplasty,6 the Abiobooster (Abiomed Corp, Danvers, MA), Heart Booster7 and Direct Mechanical Ventricular Actuation (DMVA).8 Cardiomyoplasty has not shown to be effective in advanced stages of heart failure, due to operative mortality, the length of time needed to train the latissimus dorsi muscle, chronic muscle fatigue, and only marginal efficacy in improving myocardial function. The Abiobooster and DMVA wrap around and squeeze the heart.9 These devices are still under development. The second method of augmenting circulation is pumping blood from the left atrium/ventricle to the aorta with enough force to maintain systemic blood pressure. The HeartMate/Thoratec10 (Thoratec Inc., Pleasanton, CA) and Novacor11 (WorldHeart Corp., Ottawa, Canada) devices follow this principle and are FDA approved for ventricular assistance as bridges to transplantation. Using results from the REMATCH study, the HeartMate became the first device approved for permanent implantation.12 The Novacor (INTREPID trial), and the AbioCor total artificial heart (Abiomed Corp, Danvers, MA)13 are also undergoing trials for permanent implantation. These devices are electrically driven. They all have valves and deliver blood in a pulsatile fashion. Another group of devices pump blood in a non-pulsatile fashion using axial flow or centrifugal technology. All these devices are “obligatory”, meaning that they cannot be stopped even for a short period of time without dire consequences for the patient, such as thromboembolic events or VAD regurgitation. The third method of mechanical assistance consists of supplying energy to portions of the vascular system in order to decrease the workload of the heart and increase cardiac output. This approach, referred to as diastolic augmentation,14 increases myocardial blood flow, increases diastolic blood pressure and decreases the systemic resistance applied to the heart during systole. The original work regarding diastolic augmentation originated in the laboratories of Charles Wiggers in 1953. Coronary flow was measured using an optical monometer. Dr. Kantrowitz, working in Wiggers laboratory, discovered that altering the position of the aortic pulse could improve coronary blood flow. The first thought for translating the concept of diastolic augmentation into a surgical procedure was to wrap the hemidiaphragm around the distal portion of the thoracic aorta and stimulate it during each diastole. In all experiments in this group, diastolic pressure increased significantly as compared with control studies. However, this required long term permanent pacing of the diaphragm, which was unavailable technology at that time. As an alternative to the use of autologous muscle, Dr. Adrian Kantrowitz and colleagues began to investigate use of a mechanical prosthesis as an auxiliary ventricle (MAV) in a series of studies. Other investigators were also focusing on counterpulsation as a method of cardiac assistance. Two groups working in Boston - Dwight Harken and Armand Lefemine,15 and Ralph Deterling and Harry Soroff,16 with their colleagues developed systems in which cannulae where placed in one or both femoral arteries and blood was withdrawn during systole and reinserted during diastole. The amount of blood that could be moved in the short time available was only 5 to 10 m. This limitation, combined with the fact that the blood was being withdrawn and infused at the femoral arteries, far away from the aortic valve, obviated the possibility of achieving significant benefit. Moulopoulous et al.17 experimented with an intraaortic balloon pump, as did Clauss et al.18 These were precursors of the now ubiquitous IABP but were limited by large drivelines required for shuttling of air and by the size of the balloons. A diastolic leg compression method of reproducing the effects of arterioarterial pumping without entering the arterial tree was studied by Dennis et al.,19 Osborn et al.,20 and Birtwell et al.21 The legs were compressed suddenly during diastole and released suddenly during systole. This technology is used at the current time for treatment of CHF and cardiac ischemia. Yukihiko Nosè demonstrated that the closer the MAV is to the hearts, the more effective the circulatory assistance.22 By the mid 1960s, after further experimental work by Yukihiko Nosè, Franz Gradel, and Martin Schamaun23 with a valveless, pneumatic, ellipsoidal left ventricular assist pump, they shifted to a U-shape device, which bridged the aortic arch24 (Figure 1). These U-shaped devices were made in the AVCO-Everrett Research Laboratory (Massachusetts), directed by Arthur Kantrowitz. This LVAD was extremely powerful, because the pump inlet was placed within centimeters of the aortic valve and had a stroke volume that far exceeded that of the left ventricle. The first patient (February 1966), a 33-year-old man, died of an uncontrollable tachycardia < 24 h after the operation. The second implantation, in a 63-year-old woman, took place in May 1966. There was dramatic confirmation of the hemodynamic effectiveness of the assist device in alleviating fulminant left ventricular failure. However, in spite of the marked clinical improvement that diastolic augmentation brought about, the patient suffered a stroke 12 days after implantation, and she died soon afterward. Autopsy disclosed a thrombus in the long efferent limb of the auxiliary ventricle.23 To avoid the limb problem, the LVAD was completely redesigned with the goal of fitting the device within the wall of the descending aorta.Figure 1.: The U-shaped, first-Generation mechanical auxiliary Ventricle and its power supply.After the patient experience with the U-shaped LVAD, in which it was possible to quickly return central venous, left ventricular, end-diastolic pressures and cardiac output to normal ranges, investigators felt that it would be relatively easy to achieve a LVAD that was intended for temporary use. Applying lessons learned from previous attempts at diastolic augmentation using an intraaortic balloon pump,17,18 members of the Kantrowitz laboratory decided to try to make a temporary device that would be useful in treating patients in medically refractory acute heart failure. During 1966, they designed and fabricated animal balloon pumps in the laboratory. They quickly learned the advantage of using helium as the driving gas. Helium, which has 1/20th the density of carbon dioxide, could be moved much more rapidly and achieve more precise diastolic augmentation than had been accomplished previously. Secondly, they became aware of the negative effect of a completely occlusive balloon. In 1968, they published the experiences in five patients, of whom three recovered.25 These were patients in clearly defined medically refractory cardiogenic shock after myocardial infarction, whose chances of death in those days were very close to 100%. The use of counterpulsation for circulatory assistance leading to improvement in myocardial function was established and led to further refinement. The technology evolved and at the current time, the most common method to augment diastolic pressure is the IABP.26 It is the most frequently used mechanical assist device in the world (>100,000 uses annually, personal communication Datascope Corp). The most common use has been for treatment of cardiogenic shock,27 primarily ischemic, but for other causes as well, such as postcardiotomy, myocarditis, transplant rejection, and as a bridge to transplantation.28 Increasing coronary blood flow and decreasing myocardial work give the heart an opportunity to recover. It is even used in chronic heart failure to recover patients from a decompensated state of CHF by decompressing the heart and bringing the myocytes to a better portion of the Starling Curve.29 Once the IABP is removed, the beneficial effects can be long- lasting.28 After the temporary IABP was designed, the focus turned toward a permanent aortic-wall LVAD. Laboratory findings corroborated earlier evidence of the hemodynamic capability of this type of left ventricular assistance. When this device satisfied criteria for use in human subjects, the first implant was performed in September 1971. The patient was a 64-year-old man who survived 96 days.30 The LVAD returned left ventricular end-diastolic pressure, pulmonary capillary wedge pressure and cardiac output to normal values. And, from having been bedridden, the patient improved to the point where he could walk several hundred yards in the hospital. This patient was discharged from the hospital with his implanted pump deactivated and untethered to any external apparatus. While at home on an intermittent pumping regimen, he was able to take walks in the neighborhood for the first time in 2 years. In fact, he can be considered the first successful “destination therapy” patient. Initial clinical implants were encouraging but eventually failed due to thromboembolic episodes and driveline infections. Research then focused on improving the blood interface surface and the transcutaneous exit site. These changes have lead to the current generation device, the Kantrowitz CardioVAD (KCV). The KCV consists of three components: a blood pump, a percutaneous access device and drive consoles (Figure 2). The blood pump consists of an inflatable bladder mounted on an oblong rigid plastic shell. Valves are not required as backward circulatory flow is inhibited by the native aortic valve. The bladder provides about 50 cc of stroke volume, which is designed to approximate that of a normal heart. This pump is installed in the descending aorta and works in series with the patient’s left ventricle (Figure 3 and Figure 4). This pump 1. increases the diastolic blood pressure and flow; 2. decreases the afterload for the left ventricle; 3. increases the coronary blood flow; 4. increases the mean arterial pressure; and 5. decreases the workload of the left ventricle.Figure 2.: Components of the Kantrowitz CardioVAD (KCV): a) Blood pump; b) Percutaneous access device (PAD); and c) External Drive Unit (EDU).Figure 3.: Cardiovad – descending aorta: Balloon ONFigure 4.: Cardiovad – descending aorta: Balloon OFFTo address potential problems with infection, the PAD was developed to allow for connection of the internal blood pump to the external console. This allows pneumatic and electrical signals to pass between the drive unit and the blood pump. The PAD consists of a dacron covered 8 cm diameter disk that rests on the abdominal fascia. A stem made of polycarbonate traverses the epidermal layer. To promote maximal biocompatibility, the polycarbonate is coated with autologous fibroblasts. Fibroblasts are obtained from a skin biopsy 2 weeks prior to implantation. They are cultured and allowed to proliferate. After proper seeding, these fibroblasts effectively line the surface of the polycarbonate and healing occurs between the layer of fibroblasts and the patient’s granulation tissue. This biological interface prevents downward growth of the epidermal layer, which can lead to marsupialization and creation of infection prone sinuses.31,32 The final component is the external drive unit. These units house the pneumatic compressor and microprocessor to actuate the blood pump. They are connected to the PAD via a flexible and removable driveline. The microprocessor automatically analyzes the electrical signal from the heart and triggers the KCV during diastole. The KCV can detect alterations in rhythm and trigger the pump accordingly. The compressor shuttles pressurized room air between the console and pump. There is no need for helium as the tube that connects the device to the balloon pump is large enough to allow rapid transitions. This unit is available in three configurations. The suitcase model can be powered by AC current and has a battery backup. It weighs around 70 pounds and can be moved around with moderate difficulty. The other configurations are based around two 2.5 pound rectangular units the size of paperback books. One unit contains rechargeable batteries that are removable and charged through an independent charging base. The other unit contains the microprocessor that senses the EKG from the epicardial electrodes and automatically triggers the pump to inflate during diastole. The units can be separated and carried around as a vest. This configuration is preferred during ambulation. For limited ambulation, patients are offered the attaché case configuration in which the units are put together in a case that is well sound insulated. Most of the patients primarily utilize the vest unit except when sleeping. Clinical Experience The initial feasibility trial was designed to test the safety of the device at one and three months.33 The enrolled eight patients were non-transplant candidates who had end stage cardiomyopathy. They had minimal exercise capacity and two were bedridden. The criteria for entry into the trial were consistent with other mechanical assist device trials such as REMATCH trial – in fact, four of the patients had either refused entry into or were deemed too sick to be candidates for the REMATCH trial. All patients who had Cardiovad implantation were in severe cardiac failure and had no other treatments options available to them. The 7 male and 1 female patients averaged 70.1 years of age (range 53 to 74). Six patients had ischemic cardiomyopathy, and five had previous CABG surgery. One patient had valvular cardiomyopathy and had previously received a mechanical aortic valve (St. Jude Medical, St. Paul, MN). All patients were NYHA class IV, and dependent on intravenous inotropic therapy. The ejection fraction (mean + sd) was 16 + 5% (range 9–24%). The mean weight loss during the year prior to KCV implantation was 31 + 12 lbs. The first patient expired in the operating room from technical problems arising from left atrial to femoral bypass. The implantation was aborted in another patient due to severe pleural adhesions that did not allow mobilization of the lung. By using partial CPB, all subsequent 6 patients have been able to be extubated within 48 hours and have survived to the first endpoint (30 days). The mean CPB time was 157 minutes (range 120–196). The average crossclamp time was 62 minutes and decreased by half from the first to the last patient. For the 6 patients surviving the operative procedure, there were no re-operations for bleeding and mean chest tube blood loss was only 450cc. All patients were extubated within 48 hours. One patient who was ventilator dependent prior to implantation due to pneumonia required re-intubation 4 days later and received a tracheostomy. The other 5 patients were ambulatory and dischargeable. All patients were on aspirin, and only one required anti-coagulation for his prosthetic aortic valve. Hemodynamic and laboratory data before implantation and at 30 days are summarized. The reductions in serum creatinine, RA and PCWP, as well as increase in CI, were statistically significant when compared with baseline values. Although the QOL parameters and the 6-minute walk improved, the differences were not significant (Table 1).Table 1: Hemodynamics & Laboratory Values Before And 30 Days After ImplantationBleeding was minimal and subsequently, right heart failure was not a problem. Injury to the spinal arteries, a potential for paraplegia, could be a possible concern. However, compared to aneurysm repair, the intercostal arteries are not disrupted. During KCV implantation, they are temporarily occluded with Fogarty catheters to prevent obscuring the surgical field. After KCV implantation, the arteries are allowed to perfuse normally. This study demonstrated the ability to implant the KCV safely. In addition, there is reversal of the heart failure syndrome with improved hemodynamics. There was no deleterious effect of the KCV on red blood cells, platelet number, liver function or coagulation parameters. None of the patients received anti-coagulation for the KCV (one patient was placed on coumadin for a prosthetic mechanical aortic valve) and there were no thromboembolic events. The KCV has also shown the ability to be used intermittently without any adverse events. Although the patients required KCV assistance for the majority of the time, the device could be disconnected to allow for increased patient comfort. This allows them to shower or perform other activities of daily life without being tethered to any device. This non-obligatory feature simplifies outpatient management and reduces the impact of device failure in the field. The device is also very easy to use and has only a patient controlled on/off switch. There were several device related problems that required KCV The driveline in the earlier patients of which was discovered to from that into the PAD and became by the of compressed This was by the PAD connection The patient had an the PAD due to a of the The connection has been to prevent this in the One patient had increased of the PAD to the abdominal fascia. This led to infection the The PAD stem has been made to patients with this Two patients had in the pump. This was due to by fitting a flexible pump within a short The pump has been redesigned and is not rigid and is by 3 it can any of the aorta without The of the device is the and is in the of the feasibility of the trial. aortic counterpulsation is used for the management of cardiogenic By the of several permanent aortic counterpulsation is close to a clinical The initial clinical experience with permanent aortic counterpulsation has demonstrated that it can be implanted with very and It is a non-obligatory device that has several other There is no need for anti-coagulation and no valves or internal that could and force VAD The control is as the device is by the electrical of the native heart. it is it can be turned on/off at by the patient without the of thromboembolic events. The are that it provides only It increases cardiac output by on the afterload of the patient. It native heart to function and cannot be placed in patients with severe or with native valvular However, the of obtained to the heart failure improve dysfunction and The KCV is designed for in NYHA class IV patients before there is severe failure or of any myocardial It would not be an acute device or one in which IABP pumping not improve hemodynamics. The KCV can be considered to a and have a in improving the length and of life in patients with end stage heart failure. By treating advanced CHF the KCV the of patients cardiac with transplantation or a total artificial of The of

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