A have dovetailed with the availability of a plethora of

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1 Circulatory Support With a Centrifugal Pump Bridge to Cardiac Transplantation R. Morton Bolman 111, MD, James L. Cox, MD, William Marshall, MD, Nicholas Kouchoukos, MD, Thomas L. Spray, MD, Connie Cance, RN, Randall E. Genton, MD, and Jeffrey Saffitz, MD, PhD as a Department of Surgery, Division of Cardiothoracic Surgery; Department of Medicine, Division of Cardiology; and Department of Pathology, Washington University School of Medicine, St. Louis, Missouri Since January 1985, the Heart Transplant Program at Washington University Medical Center, St. Louis, has performed 89 heart transplantations in 86 patients. Twenty patients (23%) have required preoperative mechanical support of circulation or respiration prior to transplantation. The Bio-Medicus centrifugal pump (Bio- Pump) formed the basis of our circulatory support system during the period of this report. Nine patients were placed on the Bio-Pump with the intention of bridging them to transplantation. Six patients required left ventricular assistance; in 2, the device was inserted because they could not be weaned from cardiopulmonary bypass. Two patients required biventricular assistance, 1 because she could not be weaned from cardiopulmonary bypass at the end of a cardiac operation. Extracorporeal mem- brane oxygenation was necessary in 1 patient for right ventricular decompensation and cardiac arrest four hours after orthotopic cardiac transplantation. One of these 9 patients died on circulatory support, and in another, a complication developed that precluded transplantation. The remaining 7 patients (78%) underwent a successful transplant procedure after an average of 1.6 days of circulatory support (range, 0.5 to three days), and all are long-term survivors of transplantation. There has been 1 late death at 17 months from a cerebrovascular hemorrhage. In summary, the centrifugal pump provides excellent short-term circulatory support for individuals who would otherwise die before cardiac transplantation. (Ann Thorac Surg 1989;4i7:108-12) dvances in the efficacy of cardiac transplantation A have dovetailed with the availability of a plethora of biomechanical devices to allow the salvage of individuals who previously would have died. Stimulated by the advent of heart transplantation at Washington University in St. Louis, our group [1, 21 has had a large experience with circulatory support in attempting to salvage and maintain patients until a donor heart can be located. This report details our experience with the Bio-Medicus centrifugal pump (Bio-Pump; Bio-Medicus, Eden Prairie, Minn) in the support of such patients. Material and Methods Since January 1985, the Heart Transplant Program at Washington University School of Medicine, St. Louis, has performed 89 heart transplantations in 86 patients. Twenty of these individuals (23%) have required mechanical support of circulation or respiration. This report focuses on 9 individuals supported with the Bio-Pump for left ventricular or biventricular assistance or for extracorporeal membrane oxygenation (ECMO). The 9 patients ranged in age from 16 to 57 years with a mean of 42 years. The cardiac diagnoses are outlined in Table 1. Two thirds of the patients had ischemic heart disease. The condition Presented in part at the Circulatory Support Symposium of The Society of Thoracic Surgeons, St. Louis, MO, Feb 6 7, Address reprint requests to Dr Bolman, 3108 Queeny Tower, 4989 Barnes Hospital Plaza, St. Louis, MO of all patients had deteriorated to such a point that ventricular assistance or ECMO was required to sustain them until a donor heart became available (Table 2). Device Insertion The Bio-Console (model 520D) (Bio-Medicus) was used to provide circulatory support in the 9 patients. For left ventricular assistance, left atrial-aortic bypass was employed. A 36F right-angle cannula (Polystan A/S, Ballerup, Denmark) is inserted into the roof of the left atrium at its junction with the right superior pulmonary vein with the cannula tip directed to the middle of the left atrium as previously described [l]. Aortic cannulation is performed low in the ascending aorta with a standard aortic cannula. The cannulas are held in place with pursestring sutures and Rumel tourniquets. For right ventricular assistance, the venous cannula is inserted into the right atrium through a pursestring suture placed inferiorly in the right atrium in such a way that the tip of the right-angle cannula can be directed through the tricuspid valve. A standard arterial cannula is placed in the pulmonary artery. For biventricular assistance, cannulation is as described for left ventricular and right ventricular assistance in combination. To institute ECMO, right atrial-aortic bypass is used with cannulation as already described. In 7 patients in this series, the cannulas were brought out through the median sternotomy incision with the sternum left open and the skin closed. In 2 patients, the by The Society of Thoracic Surgeons /89/$3.50

2 Ann Thorac Surg 1989;47: BOLMAN ET AL 109 Table 1. Cardiac Diagnoses in Patients Supported as Bridge to Transplantation Cardiac Diagnosis Ischemic heart disease Aortic insufficiency Cardiomyopa thy Wolff-Parkinson-White syndrome with cardiomyopathy a Numbers in parentheses are percentages.. of Patients" chest could not be closed; a retractor was left in the sternum, and the cannulas were brought out in the midline. Heparin sodium is reversed in the operating theater with protamine sulfate to effect hemostasis. Once the patient is in the intensive care unit, and when mediastinal drainage is acceptably low, a continuous heparin infusion is instituted to achieve an activated clotting time between 150 and 200 seconds for individuals on left ventricular, right ventricular, or biventricular support, and between 250 and 400 seconds for individuals on ECMO. Patients are maintained on broad-spectrum antibacterial therapy during the period of circulatory support. To assess adequacy of neurological function, all patients were allowed to awaken from anesthesia; several had sustained one or more cardiac arrests before the institution of circulatory support. Renal and hepatic function and infection status were also carefully surveyed. Attempts at weaning from circulatory support confirmed in each instance that the native heart showed no signs of recovery. Thus, all patients had to meet conventional criteria for transplantation before we could initiate a search for a donor organ. Trmsplantation At the time of orthotopic transplantation, attempts were made to remove the aortic cannulation sites with the diseased native heart to limit foci of infection. Orthotopic transplantation otherwise proceeded in routine fashion. Especially meticulous wound care was administered, including copious irrigation with antibiotic solution at the time of transplantation. Immunosuppression consisted of triple therapy with cyclosporine, azathioprine, and prednisone. Perioperative antibiotic prophylaxis consisted of vancomycin for 48 hours and cephalosporin until all invasive lines were removed. Specific infectious complications were treated according to the organism identified. All patients received Mycostatin (nystatin) orally and by nasal inhalation for the first 3 months, and were maintained on trimethoprim sulfamethoxazole prophylaxis indefinitely. Patients seronegative for cytomegalovirus before transplantation received exclusively cytomegalovirus-negative blood and blood products. All patients received cytomegalovirus hyperimmune globulin (R. Conti, University of Minnesota) 1 week and 1 month after transplantation. Table 2. Summary of Data on Patients Given Circulatory Support zoith Bio-Medicus Bio-Pimp Circulatory Patient., Support CPB for Flow Rate" Age (yr) Cardiac Diagnosis (days) Insertion (Limin) Outcome Perioperative MI during repeat CABG Failure to be weaned from CPB after third AVR Perioperative MI, cardiac arrest after CABG RV failure, cardiac arrest after OHT Failure to be weaned from CPB after WPW procedure Perioperative MI, cardiac arrest after CABG LVAD (3) LVAD (2) LVAD (0.5) LVAD (1.5) LVAD (1) ECMO (1.5) BVAD (4) LVAD (1) BVAD (1.5) Average days 3.2 '' Data are given as a range with mean in parentheses AVR = aortic valve replacement; BVAD = biventricular assist device; CABG = coronary artery bypass grafting; CPB = cardiopulmonary bypass; CVA = cerebrovascular accident; ECMO = extracorporeal membrane oxygenator; LVAD = left ventricular assist device; MI = myocardial infarction; OHT = orthotopic heart transplantation; RV = right ventricular; WPW = Wolff-Parkinson-White. 2.CL5.0 (3.5) (2.3) (2.0) (4.0) (3.0) (4.0) (4.0) (2.0) (4.0) OHT; died at 17 mo CVA on device Died on device

3 110 BOLMAN ET AL Ann Thorac Surg 1989;47:10%12 Results Left Ventricular Assistance Six patients required left ventricular assistance. Three had experienced massive acute myocardial infarction and were in cardiogenic shock. One patient sustained a perioperative infarction during reoperative coronary artery bypass grafting and could not be weaned from bypass. Another patient could not be weaned from cardiopulmonary bypass after his third aortic valve replacement. One patient sustained a large perioperative myocardial infarction and cardiac arrest several hours after coronary artery bypass grafting. In three instances, the Bio-Pump left ventricular assist device (LVAD) was inserted without the use of cardiopulmonary bypass. Each of these patients had sustained massive myocardial infarction and were in cardiogenic shock. The device was inserted utilizing a 36F right-angle cannula placed in the roof of the left atrium just posterior to the interatrial groove with routine aortic cannulation as previously described [l]. One patient, the first in our series, was a 44-year-old man who sustained a massive myocardial infarction and, when transferred to our hospital, was in cardiogenic shock and on an intraaortic balloon pump. The LVAD was placed, but because of substantial biventricular failure, it did not provide adequate support. The patient died before additional measures could be instituted. The other 5 patients supported with an LVAD were adequately resuscitated on the device and determined to be suitable candidates for cardiac transplantation. All 5 underwent a successful transplant procedure within 12 hours to three days, and are long-term survivors of transplantation. One individual died of an intracerebral hemorrhage 17 months after transplantation. Biven t ricular Ass is tance Two patients were supported with biventricular devices. One patient sustained a large perioperative myocardial infarction and cardiac arrest shortly after coronary artery bypass grafting. The patient was supported for 36 hours, and then a successful transplant procedure was performed. This patient is a long-term survivor of cardiac transplantation. The other patient was a 16-year-old girl undergoing surgical correction of Wolff-Parkinson-White syndrome who could not be weaned from cardiopulmonary bypass. She had an underlying cardiomyopathy in addition to Wolff-Parkinson-White syndrome, and was placed on biventricular support with Bio-Pumps. On the fourth postoperative day, she sustained a cerebrovascular accident and was declared brain dead. Thus, 1 of 2 patients supported with biventricular devices was deemed a suitable candidate for transplantation and underwent transplantation successfully. Extracorporeal Membrane Oxygenation One patient, a 32-year-old man, required support with an extracorporeal membrane oxygenator. He had undergone a routine orthotopic transplantation for cardiomyopathy several hours earlier. Acute right ventricular failure and cardiac arrest developed several hours after the transplant > TIME AFTER TRANSPLANT (mo) Fig I. Survival of 7 patients supported with the Bio-Pump prior to transplan tation. procedure. The patient was taken to the operating room with his chest open and internal massage being performed. Extracorporeal membrane oxygenation was instituted without the use of cardiopulmonary bypass. Thirtysix hours later, a second donor heart was located and transplantation was performed. The patient is a long-term survivor of transplantation, although he has mild neurological residua attributed to the prolonged cardiac arrest. Transplantation and Long-Term Outcome Seven of these 9 desperately ill patients were deemed suitable candidates for cardiac transplantation while being maintained with various degrees of circulatory support. All 7 underwent a successful transplantation and were long-term survivors. One patient resumed use of alcohol postoperatively and was not able to be rehabilitated. He died 17 months after transplantation of alcohol-related pancreatitis and a cerebrovascular accident. The other 6 patients (86%) are alive, and have been rehabilitated to their premorbid level of activity. Actuarial survival in this group is 100% at 3, 6, and 12 months and 71'% at 24 months (Fig 1). Complications Table 3 lists the complications that occurred in these patients supported with the Bio-Pump as a bridge to transplantation. There were seven events in 9 patients, a complication rate of 78%. In 2 patients the complications proved fatal. One p3- tient died of inadequate circulatory support. He was on an LVAD and died of biventricular failure before other measures could be instituted. He was the first patient in our circulatory support experience. In the other patient, massive cerebral edema, uncal herniation, and brain death occurred while she was on the device, and support was discontinued. Two individuals sustained neurological damage as a result of cardiac arrest before the institution of circulatory support. Enterobacter septicemia developed in 1 patient after transplantation. Severe adult respiratory distress syndrome developed in another patient, who was given left ventricular assistance. Superficial wound dehiscence subsequently occurred in the same patient; it responded to conservative measures and healed without incident.

4 Ann Thorac Surg 1989;4710%12 BOLMAN ET AL 111 Table 3. Complications in Patients Supported as Bridge to Transplantation Complication Before transplantation Death on device Cerebrovascular accident Before device insertion After device insertion After transplantation. of Patients Sepsis 1(11) Adult respiratory distress syndrome 1(11) Superficial wound dehiscence 1(11) Total 7 (78) * Numbers in parentheses are percentages The overall incidence of complications in this group is quite high. Fortunately, in the posttransplant setting, none of these complications proved fatal. Rejection Of the 7 patients bridged to transplantation, only 3 had any evidence of rejection during the first 3 months after transplantation. This is an incidence of 0.42 episodes per patient in the first 3 months, which is comparable to the incidence of rejection observed in our total patient experience [l, 21. Comment In appropriately selected individuals, heart transplantation has been demonstrated to be effective for increasing longevity and improving the quality of life. Many patients who are candidates for transplantation die while on the waiting list because of the current and ongoing shortage of available donors. In addition, some patients sustain severe myocardial damage as a result of a myocardial infarction or during attempted surgical repair of a cardiac lesion. Replacement of the heart becomes the only option for survival in these individuals. In the past, these patients would have died without the benefit of heart replacement-and many still do. In a few, however, as represented in this series, a catastrophic illness develops in a setting where facilities for mechanical bridging and heart transplantation are present. The ventricular assist device has found increasing application in the support of patients with cardiogenic shock. Hill and associates [3] reported its use as a bridge to heart transplantation in a patient with postinfarction cardiogenic shock. The centrifugal pump enjoys widespread use in cardiac surgery and recently has been applied as a ventricular assist device for patients unable to be maintained in a conventional fashion. As reported previously, we [l] have devised a technique of cannulating the roof of the left atrium that provides satisfactory left atrial decompression when the device is used as an LVAD. The centrifugal pump has been used in this series in a variety of circumstances. Two patients were in cardiogenic shock after massive myocardial infarction and could not be supported despite use of an intraaortic balloon pump and mechanical ventilation. Two other patients required the Bio-Pump in the operating room because they could not be weaned from cardiopulmonary bypass after cardiac surgical procedures. In 2 patients the pump was necessary for support following cardiac arrest in the wake of attempted coronary revascularization. The Bio- Pump, with the cannulation technique described, provides excellent short-term support of either the left or right ventricle. In addition, in 3 patients in our series, the LVAD was able to be inserted without the use of cardiopulmonary bypass. This obviates the bleeding problems attending full heparinization. We have found that maintaining the activated clotting time in the range of 150 to 200 seconds performs the dual purpose of preventing thrombus formation in the pump head and keeping the cannulas and cannulation sites free from thrombus and an associated cerebrovascular accident. Extracorporeal membrane oxygenation was a lifesaving maneuver in the 1 patient in whom it was used in this series. The device was inserted following cardiac arrest several hours after a seemingly routine orthotopic transplantation. Right ventricular decompensation developed, rapidly eventuating in cardiac arrest and necessitating ECMO. Generally, ECMO is poorly tolerated in the adult population; we were fortunate to find a donor for this individual in the window of time available. Extracorporeal membrane oxygenation was instituted without the need for cardiopulmonary bypass in this patient, and this limited postoperative bleeding complications. Clearly, another option for this type of patient would be the total artificial heart (41. Some interesting points have emerged from this small group of patients. The majority of patients requiring bridging had ischemic heart disease as the basis of their cardiac decompensation. As we [ 11 previously reported, after successful transplantation, patients bridged in this manner experience a slightly higher rate of infection in the first 3 postoperative months. The infections have been predominantly bacterial and may be related to the prolonged instrumentation attending the use of these devices. Mediastinitis did not develop in any patient in our series, regardless of whether bridging was required. This is gratifying and surprising in view of the multiple trips to the operating room that some of these patients required. The generally low rates of infection with the use of triple therapy in heart transplantation have been reported by our group [5]. Clearly, this played a role in the low rate of infection in these patients. In addition, there have been no fatal infections in this group of patients who required preoperative circulatory support. As mentioned, allograft rejection has occurred with approximately equal frequency in patients with and without bridging procedures. The 2 deaths that took place during ventricular assistance were instructive. One patient, a 16-year-old girl, was on biventricular support for failure to be weaned

5 112 BOLMAN ET AL Ann Thorac Surg 19~9;47: from bypass after surgical correction of Wolff-Parkinson- White syndrome. Massive cerebral edema with brain stem herniation occurred. The generalized edema in patients on the Bio-Pump can be problematic, as in this young girl, and may be related to the absence of pulsatile flow. The other patient, a 44-year-old man with a massive myocardial infarction, died in cardiogenic shock despite an LVAD. Undoubtedly he had right ventricular failure as well, but died before additional support could be instituted. Many patients require support of both ventricles, as pointed out by Pennington and associates [6]. With the advent of pneumatic orthotopic devices, as well as extracorporeal devices and electrically driven implantable devices, one must raise the question as to the role of the centrifugal pump in circulatory support. As demonstrated by this small group of patients, short-term support is excellent with the centrifugal pump and bridging can be successful provided a donor is found in a short time. Clearly, donor availability is a critical limitation to transplantation in general and to the implementation of assist devices in particular. Anecdotal reports of longer-term support (up to 31 days) with the Bio-Pump (Golding LR, Frazier OH; unpublished observations) encourage further development of the application of the Bio-Pump in bridging to transplantation. Golding and Frazier have utilized ventricular cannulation and have completely closed the sternum, thus making early mobilization of patients possible. This suggests that the Bio-Pump can provide longer-term support than has been appreciated. netheless, in most hands the device has proved useful for only a few days at most. This limits the opportunity for the native heart to recover in the postcardiotomy setting and may force a premature decision as to transplant candidacy. The pneumatic extracorporeal assist device (Thoratec Laboratories Corp, Berkeley, Calif) has yielded excellent results as a bridge to transplantation [7]. However, only 1 patient has been successfully bridged in the postcardiotomy setting. This suggests that the ideal candidate for bridging is the patient who is already on a transplant waiting list whose condition deteriorates before a donor heart can be found and who can be taken into the operating room and have a device implanted as a primary procedure. This individual has the best opportunity for long-term support if necessary, without the attending infectious complications. The patient requiring ventricular assistance because of failure to be weaned from bypass at the time of a cardiac procedure is a less favorable candidate for a number of reasons. First, such patients are generally entirely unknown to the transplant service before a seemingly routine cardiac surgical procedure and therefore cannot be evaluated in a meaningful fashion. Second, devices inserted in the postcardiotomy setting of necessity are associated with a higher risk of both bleeding and infec- tion than would otherwise be the case. This greatly compromises the chances of a successful transplant procedure in such an individual. For these reasons, we believe the centrifugal pump should retain an important role in circulatory support. In patients on the transplant waiting list whose condition deteriorates prior to the availability of a donor heart,, assist devices such as the pneumatic extracorporeal or the implantable electrically driven pumps are preferable in that they clearly provide safer long-term support. Recent isolated experiences suggest, however, that the Bio-Pump with certain modifications can also provide longer-term support. In the postcardiotomy setting, we must remain circumspect about individuals in whom any devices are inserted, as the overall results are quite dismal. Enough data have accumulated to allow us to take a realistic view of the unlikely possibility of successfully accomplishing transplantation in a patient in the postcardiotomy setting given the donor organ shortages. In this circumstance, we think that the centrifugal pump is the most logical choice for support because of its ease of insertion, reliability, general availability, and low cost. As our experience with this device increases, we will be able to support patients for longer periods. In summary, in a small group of patients, the Bio-Pump centrifugal device provided excellent short-term support as a bridge to transplantation. This has been true in two settings: after a myocardial infarction and after cardiotomy. The device is readily available, inexpensive, and reliable. It is easy to insert and to monitor, and increasing experience will enhance confidence in its ability to extend the period of safe circulatory support. References 1. Bolman R, Spray T, Cox J, et al. Heart transplantation in patients requiring preoperative mechanical support J Heart Transplant 1987;6: Bolman RM 111, Cance C, Spray T, et al. The changing face of cardiac transplantation: the Washington University program, Ann Thorac Surg 1988;45: Hill JD, Farrar DJ, Hershon JJ, et al. Use of a prosthetic ventricle as a bridge to cardiac transplantation for postinfarction cardiogenic shock. N Engl J Med 1986;314: Griffith BP, Hardesty RL, Kormos RL, et al. Temporary use of the Jarvik-7 total artificial heart before transplantation. N Engl J Med 1987;316: Andreone PA, Olivari MT, Elick B, et al. Reduction of infectious complications following cardiac transplantation. J Heart Transplant 1986;5: Pennington DG, Merjavy JP, Swartz MT, et al. The importance of biventricular failure in patients with postoperative cardiogenic shock. Ann Thorac Surg 1985;39: Farrar DJ, Hill JD, Gray LA, Pennington DG, et al. Heterotopic prosthetic ventricles as a bridge to cardiac transplantation: a multicenter study in 29 patients. N Engl J Med 1988;318: