I tion (OCT) has been related to advances in myocardial

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1 The Pierce-Donachy Ventricular Assist Device as a Bridge to Cardiac Transplantation Laman A. Gray, Jr, MD, Brian L. Ganzel, MD, Constantine Mavroudis, MD, and A. David Slater, MD Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Louisville School of Medicine, and the Jewish Hospital Heart and Lung Institute, Louisville, Kentucky The Pierce-Donachy ventricular assist device WAD) was used as an attempted bridge to orthotopic cardiac transplantation in 12 patients aged 13 to 55 years. (4 patients), dilated (4 patients), acute viral (1 patient), postpartum (1 patient), and hypertrophic cardiomyopathy (1 patient), along with a failed transplant (1 patient), were the causative factors of end-stage cardiomyopathy in these patients. All patients were candidates for orthotopic cardiac transplantation but sustained refractory cardiogenic shock (cardiac index < 2 L/min/mz). Left VADs were placed in all patients; 7 also required right VADs. Four patients died of hemorrhagic complications less than 24 hours after VAD insertion. Ventricular assist device stabilization was successful in 8 patients and support ranged from eight hours to 64 days. Seven patients successfully underwent orthotopic cardiac transplantation. One died postoperatively of hemorrhagic complications, 6 were discharged from the hospital, and 1 patient died at 3 months of cytomegalovirus infection. Five patients are long-term survivors. The Pierce- Donachy VAD is an effective means for supporting critically ill patients with end-stage cardiomyopathy and cardiogenic shock before orthotopic cardiac transplantation. is related to hemorrhagic, rather than infectious or thromboembolic, complications. Patients successfully stabilized with the VAD can undergo orthotopic cardiac transplantation with acceptable mortality and morbidity rates. (Ann Thoruc Surg ) mproved survival with orthotopic cardiac transplanta- I tion (OCT) has been related to advances in myocardial preservation and more effective antirejection medication. This has led to a proliferation of cardiac transplantation programs and has resulted in a shrinking donor pool, causing increased pressure on the available recipients. Heterotopic ventricular assist devices (VADs) have helped to support the circulation in hemodynamically unstable patients who have deteriorated into cardiogenic shock [l-41. This paper reviews our experience with the Pierce- Donachy VAD (Thoratec, Berkeley, CA) in critically ill patients who underwent VAD insertion as a bridge to OCT and recommends guidelines for VAD application. Material and Methods The Pierce-Donachy prosthetic ventricle is a pericorporeal pneumonic sac-type VAD placed in the heterotopic position that can maintain partial or complete circulatory support. The blood sac is made of segmented polyurethane and is enclosed in a rigid acrylic housing. Lowprofile mechanical valves are used as inlet and outlet valves. Pumping action is generated by a pneumatic driver that periodically compresses the blood sac, emptying the prosthetic ventricle. The pump has a stroke Presented at the Thirty-fifth Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 10-12, Address reprint requests to Dr Gray, Department of Surgery, University of Louisville, Louisville, KY volume of 65 ml and is capable of maintaining a cardiac output of up to 5.5 L/min. The drive console can pump at a fixed rate or in a synchronous or fill to empty mode. The fill to empty mode has a variable rate, fixed stroke volume capacity. When the blood pump is full, a signal is sent to the drive console and the unit ejects blood from the blood sac. If the preload changes, the pump will fill faster or slower, changing the ejection rate. In the fill to empty mode, the drive console is autoregulatory. Rate and percentage of systole can be controlled by the console. The percentage of systole is the percentage of time the device is in systole versus diastole, which controls the filling and emptying time of the device. It is important to maintain complete filling of the blood sac to ensure that no blood clots can form within this part of the device. The left VAD is connected to the heart by placing an outflow cannula into the ascending aorta. The inflow cannula may be placed in the left atrial appendage or left ventricular apex, or through the interatrial groove into the left atrium. The cannulas are then tunneled through the skin below the costal margin, and the device is placed on the abdomen external to the chest. A right VAD can be placed by connecting the outflow cannula to the pulmonary artery and the inflow cannula to the right atrium. Again, the cannulas are tunneled through the skin and the device is placed external to the thoracic cavity on the abdomen (Fig 1). The device can be placed while the patient is on cardiopulmonary bypass, cannulating through either the aortic arch or the femoral artery. If the by The Society of Thoracic Surgeons /89/ $3.50

2 Ann Thorac Surg GRAYETAL 223 Fig 1. Pierce-Donachy biventricular assist. Left ventricular assist device inflow from the interatrial groove and outflow to the ascending aorta (Ao). Right ventricular assist device inflow from the right atrium (RA), outflow to the pulmonary artery (PA). (IVC = inferror vena cava; LA = left atrium; RV = right ventricle.) patient s condition remains stable, the device can be inserted without the aid of cardiopulmonary bypass by using the interatrial groove approach. A complete description of the insertion technique for the VAD is presented elsewhere [5]. From May 1985 to June 1988, 12 patients (Table 1) who were candidates for cardiac transplantation deteriorated hemodynamically before donor hearts were procured. Eight patients were listed with the United Network for Organ Sharing as priority organ recipients, and 4 patients were admitted in critical condition and underwent immediate operation. These patients were placed on a Pierce- Donachy VAD as a bridge to cardiac transplantation. There were 10 male and 2 female patients with an age range of 13 to 55 years and a weight range of 44 to 111 kg. All patients had been accepted as candidates for cardiac transplantation before VAD placement, and none had VAD placement after cardiotomy. Before insertion of the VAD, the average ejection fraction was 12.5%, mean cardiac index was 1.4 L/m2, mean systolic arterial pressure was 75 mm Hg, and mean wedge pressure was 32 mm Hg (Fig 2). All patients had maximal inotropic support to maintain adequate tissue perfusion before insertion Of the VADs. Three patients were intubated before entering the surgical suite, and 5 had had a previous cardiac arrest. All patients except 1 were neurologically normal before induction of anesthesia. The obtunded patient was taken to Table 1. Clinical Characteristics and Outcome for Patients Being Bridged to Transplantation ThorateciPierce-Donachy VAD Patient Cannulation Duration No. Cardiomyopathy L-VAD R-VAD (h) Outcome Complications Cause of 1 2 Acute viral endocarditis LA-A0 LA-A Renal failure (reversible) Bleeding, respiratory failure Shock lung, brain 3 Hypertrophic LA-A Hemolysis, renal failure 4 5 LA-A0 LA-A (reversible) Bleeding, intraoperative Bleeding, biventricular Pulmonary hypertension Bleeding around failure cannula Postpartum None None None 10 IAG-A , Bleeding, shock lung Infection, respiratory Bleeding, died 4h Sepsis Failed transplantation IAG-A0 IAG-A , failure, bleeding Bleeding B 1 e e d i n g Bleeding Cytomegalovirus sepsis, died 3 mo IAG-A0 = interatrial groove to aorta; LA-A0 = left atrium to aorta; L-VAD = left ventricular assist device; = left ventricle to aorta; = right atrium to pulmonary artery; R-VAD = right ventricular assist device; = transplantation; VAD = ventricular assist device.

3 224 GRAYETAL Ann Thorac Surg TOTAL PATIENTS :I- TRANSPLANTED lo -- OPERATIVE DEATH / 1 a -- DISCHARGED FROM HOSPITAL l6 20 \ 6 -- DEATH AT 3 MO FROM , CMV INFECTION I LONG-TERM CI AoP PCW EJ SURVIVORS Fig 2. Hemodynamic findings in patients before ventricular assist 5 device insertion: cardiac index (CI) (Llm ), systolic aortic pressure Fig 3. Patients undergoing implantation of the Pierce-Donachy ven- (Ad ) (mm Hg), mean PUlmOnarY Capillary wedge Pressure (pew) tricular assist device as a bridge to transplantation. (CMV = cyto- (mm Hg), and ejection fraction (EJ)(%). megalovirus.) the operating room during cardiopulmonary resuscitation. A left VAD was inserted in all patients, and 7 also required simultaneous right VADs. Ten patients were placed on cardiopulmonary bypass, 6 through the ascending aorta and 4 through the femoral artery, before the VADs were inserted. Two patients who had the VAD placed through the interatrial groove were not placed on cardiopulmonary bypass. The VAD outflow cannulas were placed in the ascending aorta in all patients. The left ventricular inflow cannulas were inserted through the left atrial appendage in 5 patients, through the left ventricular apex in 4 patients, and through the interatrial groove in 3 patients. After the left VAD was inserted, an attempt was made to wean the patients from cardiopulmonary bypass. The right VAD was inserted in 7 patients who could not be weaned from cardiopulmonary bypass due to right ventricular dilatation, elevated right atrial pressures (greater than 20 mm Hg), and inadequate filling of the left VAD. In all patients, the direct left atrial pressure was monitored through a pressure transducer. Intravenous heparin therapy was delayed until mediastinal chest drainage was reduced to approximately 25 ml/h. Results Twelve patients in cardiogenic shock underwent VAD placement as a bridge to cardiac transplantation. One intraoperative occurred due to uncontrollable bleeding in a reoperative patient who received a left VAD only. Three early s occurred at 15 and 18 hours and 2.6 days; all of these patients had biventricular assist devices and none received a transplant. After the VADs were inserted and the patients had stabilized, 7 patients underwent cardiac transplantation (Fig 3). Three patients had biventricular assist devices and 4 had left VADs. One patient who received a left VAD died of consumption coagulopathy 8.5 hours after transplantation. Another patient died of a cytomegalovirus infection 3 months after transplantation. The remaining 5 patients are alive and well 1 to 4 years after transplantation. All the early s after insertion of the VAD were associated with excessive amounts of blood loss. Techni- cal complications related to cannulation caused one of the s. In 3 other patients, uncontrolled consumption coagulopathy developed, which did not respond to medical or surgical interventions. Nonsurgical bleeding is very common after insertion of VADs. It is most important to reverse the heparin fully with titrated doses of protamine, monitoring the activated clotting times. Complete coagulation surveys, including platelet counts, prothrombin times, partial thromboplastid times, fibrinogen levels, and split fibrin products, should be performed frequently. If any of the values are abnormal, they must be corrected immediately before the patient leaves the operating room. Patients with large perioperative bleeding problems have statistically less chance of survival because bleeding rather than thromboembolism is a greater postoperative risk to life (Fig 4). Anticoagulation therapy is reserved until mediastinal chest tube drainage is reduced to approximately 25 ml/h. At this time, intravenous heparin therapy is started to maintain the activated clotting time I so ALIVE EXPIRED Fig 4. Mean blood loss in milliliters for first 24 hours after insertion of ventricular assist devices. Seven patients are alive and 5 are dead. (p < 0.05, patients who lived versus those who died.)

4 Ann Thorac Surg GRAYETAL EXPIRED Fig 5. Mean cardiac index while on ventricular assist in liters per minute per square meter. L/MIN/M MJ GW WM JT JM KT GR JF AW PJ TP BH between 1 and 2 times control. This regimen ensures minimal likelihood of cerebrovascular embolus while the threat of uncontrolled bleeding is also decreased. A moderate amount of hemolysis occurred in the 3 long-term patients who were VAD dependent for 21, 32, and 64 days, respectively. The plasma free hemoglobin range was from 15 to 125 mg/dl while patients were on VADs, compared with a normal range of 0 to 5 mg/dl. These patients required approximately 1 U of blood every 3 to 4 days to maintain a stable hemoglobin level. The remaining 7 patients were not on the VAD long enough for any clinically significant hemolysis to be detected. Two technical problems were related to cannulation. In 1 patient who weighed 117 kg, the inflow cannula placed to the left atrial appendage was too short for the patient s size and caused leakage around the cannula site. This resulted in excessive blood loss, consumption coagulopathy, and. In a second patient, the cannula was placed too deeply into the left atrium through the intraatrial groove and resulted in obstruction to the inflow of the cannula. This patient required reoperation; the cannula was withdrawn approximately 1 cm, and flow was reestablished. No difference was related to the inflow to the VADs whether the cannula was placed through the left atrium or through the left ventricle. Placing the inflow cannula either in the left ventricular apex or through the intraatrial groove rather than the left atrial appendage allowed the sternum to be closed, followed by extubation of the stabilized patient. This was a major advantage. Although no technical problems were encountered in placing the cannula through the left ventricular apex, it is a more difficult procedure than placing the cannula through the intraatrial groove. A patient with recent infarction is contraindicated for use of the left ventricular approach. The sutures may not hold adequately in these patients, resulting in bleeding at the suture line. Two patients who had intraatrial groove inflow cannulas and whose sternums were closed were able to be extubated approximately 1 week after insertion of biventricular assist devices. These patients were able to get out of bed, sit in a chair, and eat full liquid diets. Unfortunately, both patients later became infected and required reintubation; 1 subsequently underwent transplantation and the other died of generalized sepsis. All patients maintained normal hemodynamics while on the VAD, with an average cardiac output of 4 to 4.5 L/min. This was true whether a left VAD or biventricular assist device was inserted (Fig 5). In all 12 patients requiring circulatory support, a left VAD was inserted first. Inotropic support, dobutamine or dopamine at a dose of 10 mg/kg, was always required to wean a patient with a left VAD from cardiopulmonary bypass and usually was required, although at decreasing doses, throughout the entire VAD support period. If administration of inotropic agents was discontinued, right ventricular failure frequently followed. A decision to insert the right VAD was made only after attempted weaning with the left VAD in place. To fill a left VAD adequately, mean left atrial pressure of approximately 15 mm Hg was required. If the right heart was unable to generate adequate filling pressures for a left VAD, or the right atrial pressure increased above a mean of 20 mm Hg, or the right ventricle became distended and contracted poorly, a right VAD was immediately inserted. A right VAD was also inserted in 2 patients who had severe preoperative ventricular arrhythmias. Both patients developed refractory ventricular fibrillation after placement of the VADs before transplantation. Patients who have been placed on biventricular assist devices also require inotropic support during the initial postoperative period because of low peripheral vascular resistance. Moderate doses of epinephrine or norepinephrine (5 to 15 &kg) are required to maintain adequate perfusion. Inotropic support can usually be tapered within 48 hours of VAD implantation; patients can then remain support free. Left atrial pressures were usually maintained at 15 mm Hg to fill the left VAD adequately with appropriate fluid replacement. Pulmonary edema was easily controlled by diuresis and, in patients with biventricular support, by increasing cardiac output of the left VAD slightly over that of the right VAD. Right atrial pressures were usually maintained at a mean of 12 mm Hg in patients on biventricular assistance. These patients

5 226 GRAYETAL Ann Thorac Surg showed no evidence of any peripheral edema whether they had left VADs or biventricular assist devices. Renal failure developed in 2 patients before the VADs were inserted. Both received biventricular assist devices, and 1 patient required hemodialysis while on the VAD for 5 days. The patient continued with hemodialysis after transplantation but eventually regained normal kidney function. The other patient had improvement of renal function while on the biventricular assist device; function returned to normal after cardiac transplantation. No patient without preexisting renal failure had deterioration of renal function while on a VAD. Creatinine levels remained between 1.2 and 2.5 mg/dl with blood urea nitrogen ranging from 15 to 50 mg/dl. There were three infections after VAD placement. One was a non-vad-related, successfully treated Legionnaires disease at seven days after implantation. This patient later underwent transplantation and is a long-term survivor. Another patient sustained subclavian line sepsis. The Swan-Ganz catheter became entangled in the VAD cannula and was difficult to remove. Once the catheter was removed, the patient responded to treatment and underwent eventual OCT. However, this patient died of cytomegalovirus sepsis 3 months after transplantation and after discharge. The last patient developed generalized sepsis from an unknown source before transplantation. Besides pneumonia, the most common source of sepsis is through invasive monitoring lines. Therefore, our protocol now includes changing of all central lines every four days. Swan-Ganz catheters are removed permanently as soon as the patient is hemodynamically stable, which usually occurs within the first seven days after insertion. Whenever a temperature is elevated in patients after VAD placement, we obtain a complete fever workup with blood cultures. Patients receive antibiotics throughout the entire VAD support; initial treatment consists of cephalosporins but is changed appropriately according to any positive cultures. No infections in the mediastinum or around the cannula tracts developed in these patients. There were two neurological deficits in long-term patients on biventricular assist devices. One patient who was infected sustained embolization and a thalamic infarct was documented by computed tomographic scan approximately 35 days after VAD insertion. The patient s sepsis was treated successfully; he subsequently regained normal neurological function and underwent transplantation 64 days after VAD implantation. A second patient, who was also septic, developed a left lower extremity weakness at 19 days after implantation. The patient subsequently died of sepsis 33 days after implantation, and for his last four days was neurologically unresponsive. Both of these patients were on full heparinization at the times of their strokes. We stress that both of these patients were infected at the time of their neurological event. After the VADs were inserted and the patients were stabilized, 7 patients underwent cardiac transplantation. Three were on biventricular assist devices and 4 were on left VADs. One patient, who received a left VAD, died of consumptive coagulopathy 8.5 hours after transplantation. Another patient died of a cytomegalovirus infection 3 months after transplantation. The remaining 5 patients are alive and well 1 to 4 years after transplantation. They are all in functional class I. Comment Improved results with OCT have resulted in proliferating cardiac transplant programs, increased pressure on the donor pool, and more patients deteriorating to pretransplantation cardiogenic shock [6]. We used the Pierce- Donachy VAD to intervene with these critically ill patients as a bridge to OCT. Of the 12 patients who underwent primary VAD placement as a bridge to transplantation, 7 had OCT within one to 64 days. The 5 survivors are alive and well 1 to 4 years postoperatively. These results compare favorably with results of other investigators [24, 7, 81. Patient selection after VAD placement but before OCT played a major role in eventual survival as all patients but 1 were hemodynamically, hematologically, and neurologically stable before transplantation. This led to a more efficient use of the available donor hearts with a greater chance for success. Substantial morbidity is associated with VAD placement and includes bleeding, hemolysis, infection, stroke, and mechanical dysfunction [2, 91. Clearly, the most important immediate problem is bleeding. Pennock and associates [l] and Farrar and co-workers [2] both reported severe bleeding with VAD placement in postcardiotomy and primary bridge to transplantation patients. Our experience mirrored these reports and showed that patients who have had previous median sternotomy and those who require extensive adhesiolysis are at great risk for severe postoperative bleeding. Two operative s occurred under such conditions. Ongoing long-term hemolysis by plasma free hemoglobin studies was observed in 3 patients who were VAD dependent for 21, 32, and 64 days, respectively. Other investigators [2, 10, 111 have not encountered this problem, presumably due to the shortterm use of the VAD in their patients. All our long-term (>21 days) VAD patients had hemolysis and some required blood transfusions. After hemodynamic and hematological stabilization, infection looms as the most serious impediment to successful OCT. Pennock and other researchers have emphasized the importance of avoiding sepsis in patients being bridged to transplantation [2, 81. We have avoided cannula tract infections and mediastinal sepsis by local antiseptic wound care and continuing intravenous antimicrobial therapy. Swan-Ganz catheters are removed as soon as practical, and all central catheters are changed every 4 to 5 days. Clearly, the longer VAD patients must wait for OCT, the greater the risk for infection and. Clinical cerebrovascular thromboembolic complications occurred in 2 septic patients. One patient had complete resolution and subsequent successful OCT; the other died of post-vad sepsis before OCT. Neurological events such as these have been reported by other investigators [2, 81 and remain a constant threat. In the immediate postoperative period, however, bleeding rather than thromboembolytic complications is the greater risk to life. Consequently, intravenous heparin anticoagulation therapy was

6 Ann Thorac Surg GRAY ETAL 227 delayed until bleeding was controlled. This regimen helped to minimize early bleeding complications and late cerebrovascular thromboembolic events. Guidelines for VAD placement have been reviewed by other investigators [l-3, 121 and merit discussion. All patients with the degree of cardiogenic shock we describe require a left VAD. The decision to place the right VAD in addition to the left VAD is based on the hemodynamic data recorded during the attempted separation from cardiopulmonary bypass. Severe ventricular arrhythmias, increasing right atrial pressures (>20 mm Hg), and poorly contractile right ventricles unable to maintain left atrial pressures greater than 15 mm Hg are all indications to insert the right VAD. Pierce, Pennington, Zumbro, and their associates [3, 7, 91 have all emphasized the importance of right ventricular failure in this group of critically ill patients. Patients who have been placed on VADs require inotropic support to be weaned from cardiopulmonary bypass. Patients with left VADs usually require dopamine or dobutamine (5 to 10 pg/kg) to provide adequate right ventricular output. Administration of these inotropic agents is usually maintained at low doses throughout the VAD period. Those patients who require biventricular assist devices also require initial inotropic support, usually epinephrine or norepinephrine (5-10 pglkg), because of low peripheral vascular resistance. Within a few hours after the patient is weaned from cardiopulmonary bypass, the peripheral vascular resistance usually begins to increase and inotropic support can be tapered off. Our patients achieved hemodynamic stability easily on VADs with excellent perfusion, which is similar to the findings of Pierce, Pennington, Pae, and their co-workers [ Cardiac output ranged from 4 to 5 L/min with normal systemic pressures. Left atrial pressures were usually maintained at 15 mm Hg to ensure adequate filling of the left VAD with appropriate fluid replacement. Right atrial pressures were maintained at about 12 mm Hg. There was no evidence of any peripheral edema or venous congestion. Pulmonary edema was easily controlled by appropriate diuresis or by increasing left ventricular output slightly over right ventricular output. The guidelines for OCT after VAD placement are critical to the economic and moral use of the available and shrinking donor pool. We believe that all patients should be hemodynamically, hematologically, and neurologically stabilized before OCT. One of our patients never had post-vad, pretransplantation control of a consumption coagulopathy. He underwent OCT shortly after VAD placement but the coagulopathy never resolved and he died of uncontrollable hemorrhage. Clearly, this patient would have profited from more time to stabilize, whereas another patient may have benefited from the donor heart. The dilemma of concomitant post-vad, pretransplantation organ failure requires careful evaluation. Potentially reversible organ failure is not a contraindication to OCT, as we had 1 patient who required renal dialysis while on VAD support but had successful OCT with return to normal renal function. However, one must use careful and prudent judgment in evaluating these critically ill patients realistically before OCT. The long-term survival of these patients should reflect the survival rates of non-vad OCT patients. Optimal stabilization of VAD patients before transplantation (2, 7, 8, 121 will ensure an efficient use of donor hearts with acceptable mortality and morbidity rates. Our 5 surviving patients are in class I and are indistinguishable from other transplant patients. References 1. Pennock JL, Pierce WS, Wisman CG, et al. Survival and complications following ventricular assist pumping for cardiogenic shock. Ann Surg 1983;198: Farrar DJ, Hill JD, Gray LA Jr, et al. Heterotopic prosthetic ventricles as a bridge to cardiac transplantation. N Engl J Med 1988;318: Zumbro GL, Kitchens WR, Shearer G, et al. Mechanical assistance for cardiogenic shock following cardiac surgery, myocardial infarction, and cardiac transplantation. Ann Thorac Surg 1987;44: Carpentier A, Perier P, Brugger JP, et al. Heterotopic artificial heart as bridge to cardiac transplantation [Letter]. Lancet 1986;2: Ganzel BL, Gray LA Jr, Slater AD, Mavroudis C. Surgical techniques for the implantation of heterotopic prosthetic ventricles. Ann Thorac Surg 1989; Slater AD, Klein JB, Gray LA Jr. Clinical orthotopic cardiac transplantation. Am J Surg 1987;153: Pennington DG, Codd JE, Marjavy JP, et al. The expanded use of ventricular bypass systems for severe cardiac failure and as a bridge to cardiac transplantation. J Heart Transplant 1984;lll: Pennock JL, Pierce WS, Campbell DB, et al. Mechanical support of the circulation followed by cardiac transplantation. J Thorac Cardiovasc Surg 1986;92:99P Pierce WS, Parr GVS, Myers JL, et al. Ventricular-assist pumping in patients with cardiogenic shock after cardiac operations. N Engl J Med 1981;305: Pennington DG, Samuels LD, Williams G, et al. Experience with the Pierce-Donachy ventricular assist device in postcardiotomy patients with cardiogenic shock. World J Surg 1985;9: Pae WE Jr, Pierce WS, Pennick JL, et al. Long-term results of ventricular assist pumping in postcardiotomy cardiogenic shock. J Thorac Cardiovasc Surg 1987;93: 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;314:626-8.