- Email: [email protected]
Successful experience in bridging patients to heart transplantation with the MicroMed Debakey ventricular assist device
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Successful Experience in Bridging Patients to Heart Transplantation With the MicroMed DeBakey Ventricular Assist Device Ettore Vitali, MD, Marco Lanfranconi, MD, Elena Ribera, MD, Giuseppe Bruschi, MD, Tiziano Colombo, MD, Maria Frigerio, MD, and Claudio Russo, MD Departments of Cardiac Surgery and Cardiology “A. De Gasperis,” Niguarda Ca’ Granda Hospital, Milan, Italy
Background. Pulsatile left ventricular assist devices are used with increasing frequency to bridge patients with end-stage heart failure to heart transplantation (HTx). Implantation of pulsatile devices is a cumbersome surgical procedure that is associated with major complications, such as bleeding, thromboembolism, and infection. Recently, a continuous axial flow left ventricular assist device (DeBakey ventricular assist device) has been introduced with the goal of reducing the incidence of major complications. Methods. We reviewed our experience with 11 patients who received a DeBakey ventricular assist device axial flow pump for bridge to HTx from April 2000 through November 2001. Results. Two patients (18.2%) died of multiple-organ failure while on left ventricular assist device support. Bleeding requiring thoracotomy occurred in 2 patients (18.2%). One patient had a minor neurologic event, and
one patient developed left ventricular assist device thrombosis, which was successfully treated without pump exchange. Renal failure developed in 1 patient and hepatic dysfunction in 2 patients. There were no instances of right heart failure. No device, pocket, or drive-line infections occurred. Nine patients (9 of 11, 81.8%) had HTx within 51 ⴞ 49 days (range, 11 to 141 days) after left ventricular assist device implant. One patient died 29 days after HTx because of acute rejection. Conclusions. The continuous axial flow DeBakey ventricular assist device had reliable features, including a high rate of bridge to HTx. This device had low complication and system failure rates. We consider the DeBakey ventricular assist device a favorable alternative to pulsatile heart assist devices as a bridge to HTx.
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lar assist devices (LVAD), the nonpulsatile axial-flow pump, have been introduced and tested [6]. The main characteristics of these devices are their small size and absence of compliance chamber and prosthetic valves. These features are expected to result in a lower complication rate than the pulsatile pumps. The DeBakey ventricular assist device (VAD) is such a device. We describe our clinical experience with 11 patients who were supported with the DeBakey VAD (MicroMed Technology, Inc. Houston, TX) axial flow pump as a bridge to HTx. This study was retrospective, observational, and nonrandomized.
etween 1989 and 1998, the number of patients awaiting heart transplantation (HTx) tripled, and between 1995 and 1998 the number of registrants for this procedure increased by 21% [1]. Furthermore, because of a shortage of suitable donors, in recent years, the waiting time for HTx has increased to a point that up to 30% of patients die while on the transplant waiting list [2]. Mechanical ventricular assist devices as a bridge to HTx can increase the survival rate of these patients. Consequently, bridge to HTx by using pulsatile ventricular assist devices has become a standard in clinical practice. During the past 3 decades, technical improvements as well as development of small, wearable, and mechanically reliable circulatory assist pumps have encouraged their clinical application and have demonstrated their effectiveness, resulting in reduced morbidity and mortality rates among patients waiting for an HTx [3, 4]. The implantable pulsatile pumps, however, are large devices, and their implantation has been associated with major complications, such as bleeding, thromboembolism, and infection [5]. Recently, a new generation of left ventricuAccepted for publication Oct 17, 2002. Address reprint requests to Dr Vitali, Department of Cardiac Surgery “A. De Gasperis,” Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy; e-mail: [email protected].
© 2003 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
(Ann Thorac Surg 2003;75:1200 – 4) © 2003 by The Society of Thoracic Surgeons
Material and Methods Between November 1985 and December 2001, 618 patients underwent HTx at “A. De Gasperis” Cardiac Surgery Department in Milan. Since March 1988, 109 patients were supported with a mechanical circulatory assist device in the form of left, right, or biventricular assist pumps. Mechanical circulatory assistance as a bridge to HTx was used in 64 patients and as an alternative therapy to HTx in 1 patient. Among the former group, between April 2000 and November 2001, 53 patients had received an LVAD, including 11 patients (8 0003-4975/03/$30.00 PII S0003-4975(02)04660-X
VITALI ET AL SUCCESSFUL EXPERIENCE WITH DEBAKEY VAD
Table 1. Patient Characteristics Before Implant Characteristic
Mean ⫾ SD
Age (years) Body surface area (m2) Aortic pressure (mm Hg) Pulmonary artery pressure (mm Hg) Right atrial pressure (mm Hg) Pulmonary capillary wedge pressure (mm Hg) Cardiac index (L/min/m2) Pulmonary vascular resistance (WU) Serum creatinine (mg/dL) Total bilirubin (mg/dL) Aspartate aminotransferase (U/L) Alanine aminotransferase (U/L)
41 ⫾ 14 1.67 ⫾ 1.14 75 ⫾ 6.3 31.5 ⫾ 11.5 18.8 ⫾ 3.1 25.7 ⫾ 9.8 1.58 ⫾ 0.52 5.36 ⫾ 2.4 1.15 ⫾ 0.21 1.97 ⫾ 1.2 74.37 ⫾ 77.34 25.82 ⫾ 57.19
SD ⫽ standard deviation.
males, 3 females, ages 12 to 57 years) who were assisted with the continuous axial flow DeBakey VAD pump and are the subject of this review. All patients had a sudden or gradual deterioration of heart function requiring a change in their waiting list priority to status I for HTx. The causes of heart failure were idiopathic dilated cardiomyopathy in 7 patients (63.6%), ischemic heart disease in 3 (27.3%), and dilated cardiomyopathy with specific myopathy and normal dystrophine in 1 patient (9.1%). At the time of device implantation all patients were in sinus rhythm. The clinical characteristics of the 11 study patients are detailed in Table 1. The inclusion criteria for enrollment and use of an assist device were left atrial pressure or wedge pressure of at least 18 mm Hg and cardiac index less than or equal to 2 L · min⫺1 · m⫺2 or systolic pressure less than 90 mm Hg while on therapy with intraaortic balloon pump and vasopressor agent (dopamine ⱖ 10 g · kg⫺1 · min⫺1, dobutamine ⱖ 7.5 g · kg⫺1 · min⫺1, epinephrine ⱖ 0.02 g · kg⫺1 · min⫺1, isoproterenol ⱖ 0.5 g · kg⫺1 · min⫺1, or milrinone ⱖ 0.5 g · kg⫺1 · min⫺1). All patients provided written informed consent for device implantation, and the study was approved by the Institutional Review Committee.
MicroMed DeBakey Ventricular Assist Device This device consists of three subsystems—a miniaturized titanium axial flow pump, an external controller, and a clinical data acquisition system. The device is electromagnetically actuated, miniaturized, and fully implantable. A titanium inflow cannula connects the pump to the apex of the left ventricle, and a Vascutek Gelweave vascular graft (outflow conduit) connects the pump to the ascending aorta. An ultrasonic flow probe is placed around the outflow conduit. Together with the flow probe’s wiring, the pump motor cable is exteriorized above the right iliac crest and is attached to the VAD external controller system. The pump is 30.5 mm in diameter, 76.2 mm long, and weighs 93 g. It is designed to achieve 5 L/min of blood flow against 100 mm Hg pressure, with a motor speed of 10,000 rpm and a power input of 10 W. The control
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system is completely external and consists of a smart controller and two batteries. The controller displays pump variables and provides audible and visual alarms. The clinical data acquisition system records and displays pump data (pump flow, pump speed, power consumption, and current signals) and can be used to modify the pump speed. Adjustments of the pump speed can be made only when it is connected to the clinical data acquisition system. For optimal mobilization of the patient and freedom of movement, the electrical power is delivered by one of the two 12-V batteries. Each battery lasts 6 to 8 hours. The entire system weighs 2.5 kg [7].
Implant Procedures For pump implantation, a median sternotomy incision is done, which extends a few centimeters below the xiphoid process. A small abdominal wall pocket is created below the rectus muscle sheath. The size and configuration of the pocket is determined by using a mock pump model. Standard ascending aorta and two-stage (right atrial and inferior vena cava) cannulations are done, and cardiopulmonary bypass is initiated. The left ventricular apex is elevated, and a suitable insertion site for the LVAD inflow cannula is selected. After aortic cross-clamp and infusion of cold blood cardioplegia, an apical fixation ring is sewn to the apex of the left ventricle. A round-bladed device is inserted into the left ventricle to extract an apical core. A visual and digital exploration of the ventricle is performed to ensure absence of any potential obstructions to the device’s inflow cannula. The LVAD inflow cannula is inserted into the left ventricular apex and is sewn to the apical fixation ring. Similar to implantation of other LVAD systems, the inflow cannula is inserted during cardioplegic arrest. In our experience with first-generation pulsatile LVADs, we used the beating heart technique. Now, however, we prefer to insert the inflow cannula on an arrested heart because it allows for more accurate suturing. The aortic cross-clamp is then removed. A trocar is used to create a tunnel from the abdominal wall pocket, across the midline subcutaneously, and through the skin at a convenient location above the right iliac crest. The MicroMed DeBakey VAD is placed into the small abdominal pocket, and an appropriate length of the outflow graft is selected. We place the graft under the right sternal border without kinking or overstretching and pass it into the mediastinum to reach the ascending aorta. Before and after completion of the anastomosis to the aorta, the air is removed from the system carefully. The LVAD is started with a speed of 7,500 rpm as the patient is progressively weaned from cardiopulmonary bypass. By using inotropic support and nitric oxide to support the right heart function, the pump speed is adjusted to maintain a cardiac index of 2.0 to 2.5 L/m2 per minute and a mixed venous-oxygen saturation greater than 60% as indicated by a Swan-Ganz catheter. A few hours postoperatively the pump speed is gradually increased to obtain mixed venous-oxygen saturations of greater than 70%. After 48 to 72 hours, the pump speed is set between 9,000 and 11,000 rpm. The location of the
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inflow cannula and the function of both ventricles are examined by echocardiography. The right ventricle in particular is assessed for adequate preload and for its systolic function. To avoid adhesions and to facilitate surgical reentry at the time of transplantation, the pericardial closure and wrapping of the VAD and the outflow cannula is done with a Gore-Tex membrane (W.L. Gore & Assoc, Flagstaff, AZ) as previously described [8].
Anticoagulation Anticoagulation treatment is based on the protocol proposed by the group at the “La Pitie´ –Salpetrie`re” Hospital in Paris [9, 10] and is the same protocol that we use for all patients receiving an LVAD. In brief, the regimen is as follows: during the first 24 hours postoperatively, the patients receive no anticoagulation. Thereafter, intravenous heparin therapy is started according to thromboelastography (TEG) modified with heparinase and Activated Partial Thromboplastin Time (APTT) (1.5 to 2 times normal value). Long-term anticoagulation consists of sodium warfarin (dosage according to international normalized ratio of prothrombin time 2.5 to 3.5 times normal value) and enoxaparine (2,000 to 4,000 IU/day) whenever requested. Low-molecular-weight-heparin, which antagonizes the activated coagulation Factor X and prevents formation of thrombin, is added to sodium warfarin when TEG reveals suboptimal anticoagulation even if the international normalized ratio of prothrombin time values are optimal. This abnormal phenomenon is due to the presence of thrombin in microdoses, which pose a potential risk for thrombosis. This protocol is very careful with regard to platelet activity by including dypiridamol (800 mg/day intravenously intraoperatively and thereafter 800 mg/day orally) and aspirin (100 mg daily). When thrombocytosis or platelet-related hypercoagulability is discovered, ticlopidine (250 mg/day) is added to the regimen. Pentoxifylline (400 mg/day intravenously initially and thereafter 800 mg/day orally) is used to further improve hemorheology. The efficacy of this anticoagulation treatment is monitored by TEG (daily in the acute phase, then weekly when the patients are moved to a regular ward, and later on whenever it is necessary). TEG is the only test that dynamically studies the formation and characteristics of blood clot. It examines all phases of coagulation, including platelet activity and presence of fibrinolysis. We use TEG data coupled with the blood tests required by this protocol to check the final result of pharmacologic interventions regarding anticoagulation and to evaluate whether any drugs must be added or removed, as well as to calibrate the drug dosages. This anticoagulation protocol requires several blood tests, including TEG and the necessity of taking multiple drugs. Monitoring is frequent in the early phases after the implant, including blood tests twice a day and TEG once a day. As the patients move to the regular ward care, monitoring is less frequent and is further decreased when the tests show a stabilized anticoagulation effect. As the patients recover, blood and TEG tests are done
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once a week and during the follow-up examinations; TEG is tested every 3 or 4 weeks on an out-patient basis. During the chronic phase, the frequency of monitoring of this protocol is comparable to that of patients with prosthetic cardiac valves or atrial fibrillation. It is important to note that this pharmacologic regimen has been well tolerated and has been associated with a satisfactory patient compliance rate.
Results All patients survived the LVAD implantation procedure. Weaning from extracorporeal circulation was facilitated in all patients with the use of inotropic drugs (eg, dopamine, epinephrine, phosphodiesterase-III inhibitors) and nitric oxide. Intraoperatively by echocardiography, the position of the inflow cannula was assessed. The cannula tip stayed in a neutral position within the left ventricle. It was not oriented towards the septum or the free lateral wall, and its position allowed proper drainage of blood and did not require repositioning of the cannula. Furthermore, repeated echocardiographic survery showed that the left ventricle was properly drained without rightward shift of the septum. After postoperative stabilization, the pump speed was set between 9,000 and 11,000 rpm to allow for optimal cardiac output and to achieve a satisfactory physical activity tolerance [11]. Further adjustments of pump speed were uncommon because, in chronic stages, the pump flow was optimized mainly by adjusting the patient’s fluid balance. Arterial blood pressure was measured invasively in the perioperative period; pump flow changes due to pump speed adjustment were not compared with arterial pressure changes. The mean duration of MicroMed DeBakey VAD support was 51 ⫾ 49 days (range 11 days to 4.7 months), and the cumulative time of support was 16.66 months. Two patients (18.2%) died while on LVAD support due to multiple-organ system failure after 13 and 44 days of circulatory assistance. All other patients recovered rapidly from the operation and were discharged from the intensive care unit to ward care where they performed regular physical training. These patients were able to perform their normal daily activities. As each patient gained confidence with the MicroMed Debakey VAD they were taught to manage the device themselves. In this initial experience, the patients assisted with the DeBakey VAD were not discharged home. Our policy was to keep the patients in the hospital to observe their clinical progress and to analyze the device function on a daily basis. Furthermore, most of these patients resided too far away from our hospital, which prevented their early dismissal per our hospital policy [12]. Eight of the nine transplanted patients (88.9%) were discharged home. One patient died of graft failure due to acute rejection 29 days after HTx. Nine patients (81.8%) underwent HTx between 11 and 141 days after LVAD implant. At the time of HTx, minimal adhesions and bleeding from the pump nesting site facilitated the removal of DeBakey VAD pump,
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Table 2. Index of Organ Function Before Cardiac Transplant Variable Serum creatinine (mg/dL) Total bilirubin (mg/dL) Aspartate aminotransferase (U/L) Alanine aminotransferase (U/L) Lactate dehydrogenase (U/L) Plasma free hemoglobin (mg/L)
Mean ⫾ SD 0.81 ⫾ 0.38 1.17 ⫾ 0.56 31.25 ⫾ 17 22 ⫾ 11.45 817 ⫾ 595 48 ⫾ 7
SD ⫽ standard deviation.
level was persistently elevated in 1 patient during continuos veno-venous hemofiltration and normalized after cessation of this treatment. Lactate dehydrogenase levels also increased in a few patients during the period of cardiac assist, as in another report [11]. The increase in lactate dehydrogenase level was not related to the increase in plasma fHb. The mean level of plasma fHb and lactate dehydrogenase was slightly above normal at termination of circulatory assistance. However, plasma fHb peaks and the elevation of lactate dehydrogenase was not associated with decrease in blood hemoglobin level or need for blood transfusion. Indices of end-organ function and hemolysis at the time of termination of cardiac assistance (before HTx) for all patients are shown in Table 2.
Comment Clinical experience has shown compatibility of nonpulsatile blood flow with adequate end-organ perfusion for periods of up to several months [7]. The continuous flow axial DeBakey VAD recently was introduced into clinical practice as a bridge to HTx [15]. It has demonstrated adequate circulatory support in patients with end-stage heart failure. Our study confirms other reports and shows that this device is safe and effective [7, 15–17]. This study was retrospective and nonrandomized. In selecting patients for implanting the MicroMed DeBakey VAD as a bridge to HTx, we considered factors related to the device characteristics and to the patients’ probability of getting a suitable donor heart in an adequate time after device implantation. For these reasons we selected to implant the MicroMed DeBakey VAD in patients who had a high probability of receiving a suitable donor heart in an adequate time interval. Consequently, we did not implant this device in patients with a large body surface area, (ie, ⬎ 2 m2), which could be a possible bias in patient selection for implantation of this device and represents another limitation of this study. Other indications for device implantation, such as the preoperative end-organ function (especially liver and kidneys), followed the criteria used for all patients that needed an LVAD. The patients who are suitable for LVAD implantation were strictly monitored by a team of surgeons and cardiologists; if optimized medical therapy (oral and intravenous) was not sufficient to maintain cardiac function to satisfy tissue perfusion and led to progressive end-organ damage, we proceeded with de-
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making the operation easier and faster than removal of bulky pulsatile LVAD pumps. Major bleeding episodes (blood loss of more than 1500 mL in 24 hours requiring surgical hemostasis in the mediastinum) occurred in 2 patients (2 of 11, 18.2%). One patient (9.1%) had a minor neurologic event (slight aphasia lasting less than 30 minutes), 101 days after LVAD insertion. Contrast-enhanced computed tomographic scan showed a small area of hypodensity compatible with ischemic damage in the left frontal region. None of the LVAD patients experienced any septic episodes (defined as body temperature above 38.5°C, white blood cell count over 12,000 g/dL, positive blood cultures, or low systemic vascular resistance). None of the patients showed signs of inflammation or infection at the exit site of the transcutaneous cables. Renal failure (defined as the need for hemodialysis or continuos venovenous hemofiltration) occurred in 1 patient (9.1%) with multiple-organ system failure. Liver failure (defined as aspartate aminotransferase or alanine aminotransferase levels or both at least twofold above normal values, and pathologic total bilirubin levels) occurred in 2 patients (18.2%). None of the patients had severe right ventricular failure (defined as cardiac index less than 2 L · min⫺1 · m⫺2 despite a central venous pressure of 18 to 22 mm Hg and maximal pharmacologic support with inotropic drugs and vasodilators) requiring right ventricular assistance [13]. One patient, on the 112th day of support, had possible thrombosis of the DeBakey VAD pump despite a normal anticoagulation profile. This complication was suspected because of an increase in current and power registered by the controller with a decrease in pump flow rate. Emergency transthoracic echocardiogram and contrastenhanced computed tomographic scan showed no endoventricular thrombus image. There was no turbulent flow on the anastomosis between the outflow graft and the ascending aorta, and no obstruction or kinking of the outflow graft beyond the flow probe. Before proceeding to pump replacement, upon recommendation of the manufacturer’s technical support staff, we performed endoventricular thrombolysis, by direct delivery of recombinant tissue plasminogen activator into the left ventricle, as we have previously reported [14]. After 20 minutes, power and current values began to diminish, flow rate increased, and the clinical status began to improve. After 3 hours, current and power values reached normal ranges, with flow rate normalization (4.5 L/min) and complete hemodynamic recovery. Neither major nor minor neurologic events were observed. In the following days, the pump function was appropriate, and on postoperative day 142, the patient had a successful cardiac transplantation. Indices of hemolysis, indicated by plasma free hemoglobin (fHb) and lactate dehydrogenase levels, showed episodes of slight hemolysis. Isolated transient peaks of fHb were detected in a few patients, similar to a report by Wieselthaler and colleagues [11]. The plasma fHb peaks were not related to clinical or mechanical events. The
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vice implantation within 12 to 24 hours. Our policy was to implant LVAD before serious end-organ dysfunction occurred. In the case of emergency implants in which the patient has advanced end-organ dysfunction, our policy is to implant a paracorporeal device. In our experience, the MicroMed DeBakey VAD is an effective device as a bridge to HTx with a high success rate (9 of 11, 81.8%). These results are due to improvement in end-organ function achieved by multiple factors, including the function of the DeBakey VAD and strict adherence to our anticoagulation protocol. Therefore, a low rate of adverse events, such as bleeding, thromboembolism, and infection, was encountered in this study and by others [11]. Since we started using LVADs, we adopted the anticoagulation protocol of “La Pitie´ ” hospital [9, 10]. We attribute the low incidence of bleeding complications in this study mainly to the careful application and monitoring of this protocol, which has a multiple-system approach to the determinants of the coagulation cascade. The DeBakey VAD compared with pulsatile LVADs appears to influence contact activation and to promote platelet damage [18]. The anticoagulation protocol adopted in this study is very attentive to platelet activity and preservation, which could have positively influenced the results. Other reasons, such as the absence of artificial valves, compliance chamber, and the type of flow characteristics of this device, also could have played an important role in reducing the incidence of thromboembolic events. Because of its small size, the DeBakey VAD requires a small nesting site and needs limited surgical dissection, which could explain the low rate of infection and bleeding after device removal. Inflammation or infection at the motor cable exit site was not observed in our patients. This finding was probably related to both the small diameter and flexibility of the percutaneous cable and to the lack of pump motion due to nonpulsatile flow. In conclusion, the continuous axial flow MicroMed DeBakey VAD as a bridge to heart transplantation showed good hemodynamic performance and low incidence of major complications and achieved a high rate of conversion to HTx. Additional experiences with a larger number of patients and with longer duration of assist should further define the role of this device in the area of mechanical circulatory assistance not only as bridge to transplant but possibly for destination therapy. The authors thank Dr Hooshang Bolooki for language editing.
References 1. Date Highlights UNOS Scientific Registry Annual Report, 1999. UNOS website: www.unos.org.
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2. Harper AM, Rosendale JD. The UNOS OPTN waiting list and donor registry: 1988 –1996. In: Cecka JM, Teraski PI, eds. Clinical transplants. Los Angeles: UCLA Tissue Typing Laboratory, 1996:69 –99. 3. Frazier OH, Rose EA, McCarthy PM, et al. Improved mortality and rehabilitation of transplant candidates treated with a long term implantable left ventricular assist system. Ann Surg 1995;222:327–38. 4. McCarthy PM, Smerida NO, Vargo RL, et al. One hundred patients with the HeartMate left ventricular assist device: evolving concepts and technology. J Thorac Cardiovasc Surg 1999;115:904 –12. 5. Sun BC, Catanese KA, Spanier TB, et al. 100 long-term implantable left ventricular assist devices. The Columbia Presbyterian interim experience. Ann Thorac Surg 1999;68: 688 –94. 6. Noon GP, Morlry D, Irwin S, Benkowski R. Development and clinical application of the MicroMed DeBakey LVAD. Curr Opin Cardiol 2000;15:166 –71. 7. Noon GP, Morley DL, Irwin S, et al. Clinical experience with the MicroMed DeBakey ventricular assist device. Ann Throac Surg 2001;71:133–8. 8. Vitali E, Russo C, Colombo T, Lanfranconi M, Bruschi G. Modified pericardial closure technique in patients with ventricular assist device. Ann Thorac Surg 2000;69:1278 –9. 9. Bellon JL, Szefner J, Cabrol C. Coagulation et coeur artificiel. Paris: Masson, 1989. 10. Szefner J, Cabrol C. Control and treatment of hemostasis in patients with a total artificial heart: the experience of La Pite´ . In: Pifarre´ R, ed. Anticoagulation, hemostasis, and blood preservation in cardiovascular surgery. Philadelphia: Hanley and Belfus Inc., 1993:237–64. 11. Wieselthaler GM, Schima H, Lassnigg AM, et al. Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial flow pump: a single center report. Ann Thorac Surg 2001;71:139 –43. 12. Fey O, El-Banayosys A, Arosuglu L, Posival H, Ko¨ rfer R. Out of hospital experience in patients with implantable mechanical circulatory support: present and future trends. Eur J Cardiothorac Surg 1997;11:S51–3. 13. Chen JM, Rose EA. Management of perioperative right-side circulatory failure. In: Goldstein DJ, Oz MC, eds. Cardiac assist device. Armonk, NJ: Futura Publishing Company, 2000:83–101. 14. Russo C, De Biase AM, Bruschi G, Agati S, Vitali E. Successful intraventricular thrombolysis during ventricular assist device support. Ann Thorac Surg 2002;73:1628 –9. 15. Wieselthaler GM, Schima H, Hiesmayr M, et al. First clinical experience with the DeBakey LVAD continuous-axial-flow pump for bridge to transplantation. Circulation 2000;101: 356 –9. 16. Lanfranconi M, Russo C, Ribera E, et al. Assistenza monoventricolare sinistra con pompa a flusso continuo DeBakey LVAD: prima esperienza clinica italiana. Italian Heart J 2001;2 Suppl:653–8. 17. Wilhelm MJ, Hammel D, Schmid C, et al. Clinical experience with nine patients supported by continuous flow DeBakey LVAD. J Heart Lung Transplant 2001;20:201. 18. Kostner A, Loebe M, Hansen R, et al. Alterations in coagulation after implantation of a pulsatile Novacor LVAD and the axial flow Micromed DeBakey LVAD. Ann Thorac Surg 2000;70:533–7.
Successful Experience in Bridging Patients to Heart Transplantation With the MicroMed DeBakey Ventricular Assist Device Ettore Vitali, MD, Marco Lanfranconi, MD, Elena Ribera, MD, Giuseppe Bruschi, MD, Tiziano Colombo, MD, Maria Frigerio, MD, and Claudio Russo, MD Departments of Cardiac Surgery and Cardiology “A. De Gasperis,” Niguarda Ca’ Granda Hospital, Milan, Italy
Background. Pulsatile left ventricular assist devices are used with increasing frequency to bridge patients with end-stage heart failure to heart transplantation (HTx). Implantation of pulsatile devices is a cumbersome surgical procedure that is associated with major complications, such as bleeding, thromboembolism, and infection. Recently, a continuous axial flow left ventricular assist device (DeBakey ventricular assist device) has been introduced with the goal of reducing the incidence of major complications. Methods. We reviewed our experience with 11 patients who received a DeBakey ventricular assist device axial flow pump for bridge to HTx from April 2000 through November 2001. Results. Two patients (18.2%) died of multiple-organ failure while on left ventricular assist device support. Bleeding requiring thoracotomy occurred in 2 patients (18.2%). One patient had a minor neurologic event, and
one patient developed left ventricular assist device thrombosis, which was successfully treated without pump exchange. Renal failure developed in 1 patient and hepatic dysfunction in 2 patients. There were no instances of right heart failure. No device, pocket, or drive-line infections occurred. Nine patients (9 of 11, 81.8%) had HTx within 51 ⴞ 49 days (range, 11 to 141 days) after left ventricular assist device implant. One patient died 29 days after HTx because of acute rejection. Conclusions. The continuous axial flow DeBakey ventricular assist device had reliable features, including a high rate of bridge to HTx. This device had low complication and system failure rates. We consider the DeBakey ventricular assist device a favorable alternative to pulsatile heart assist devices as a bridge to HTx.
B
lar assist devices (LVAD), the nonpulsatile axial-flow pump, have been introduced and tested [6]. The main characteristics of these devices are their small size and absence of compliance chamber and prosthetic valves. These features are expected to result in a lower complication rate than the pulsatile pumps. The DeBakey ventricular assist device (VAD) is such a device. We describe our clinical experience with 11 patients who were supported with the DeBakey VAD (MicroMed Technology, Inc. Houston, TX) axial flow pump as a bridge to HTx. This study was retrospective, observational, and nonrandomized.
etween 1989 and 1998, the number of patients awaiting heart transplantation (HTx) tripled, and between 1995 and 1998 the number of registrants for this procedure increased by 21% [1]. Furthermore, because of a shortage of suitable donors, in recent years, the waiting time for HTx has increased to a point that up to 30% of patients die while on the transplant waiting list [2]. Mechanical ventricular assist devices as a bridge to HTx can increase the survival rate of these patients. Consequently, bridge to HTx by using pulsatile ventricular assist devices has become a standard in clinical practice. During the past 3 decades, technical improvements as well as development of small, wearable, and mechanically reliable circulatory assist pumps have encouraged their clinical application and have demonstrated their effectiveness, resulting in reduced morbidity and mortality rates among patients waiting for an HTx [3, 4]. The implantable pulsatile pumps, however, are large devices, and their implantation has been associated with major complications, such as bleeding, thromboembolism, and infection [5]. Recently, a new generation of left ventricuAccepted for publication Oct 17, 2002. Address reprint requests to Dr Vitali, Department of Cardiac Surgery “A. De Gasperis,” Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore, 3, 20162 Milan, Italy; e-mail: [email protected].
© 2003 by The Society of Thoracic Surgeons Published by Elsevier Science Inc
(Ann Thorac Surg 2003;75:1200 – 4) © 2003 by The Society of Thoracic Surgeons
Material and Methods Between November 1985 and December 2001, 618 patients underwent HTx at “A. De Gasperis” Cardiac Surgery Department in Milan. Since March 1988, 109 patients were supported with a mechanical circulatory assist device in the form of left, right, or biventricular assist pumps. Mechanical circulatory assistance as a bridge to HTx was used in 64 patients and as an alternative therapy to HTx in 1 patient. Among the former group, between April 2000 and November 2001, 53 patients had received an LVAD, including 11 patients (8 0003-4975/03/$30.00 PII S0003-4975(02)04660-X
VITALI ET AL SUCCESSFUL EXPERIENCE WITH DEBAKEY VAD
Table 1. Patient Characteristics Before Implant Characteristic
Mean ⫾ SD
Age (years) Body surface area (m2) Aortic pressure (mm Hg) Pulmonary artery pressure (mm Hg) Right atrial pressure (mm Hg) Pulmonary capillary wedge pressure (mm Hg) Cardiac index (L/min/m2) Pulmonary vascular resistance (WU) Serum creatinine (mg/dL) Total bilirubin (mg/dL) Aspartate aminotransferase (U/L) Alanine aminotransferase (U/L)
41 ⫾ 14 1.67 ⫾ 1.14 75 ⫾ 6.3 31.5 ⫾ 11.5 18.8 ⫾ 3.1 25.7 ⫾ 9.8 1.58 ⫾ 0.52 5.36 ⫾ 2.4 1.15 ⫾ 0.21 1.97 ⫾ 1.2 74.37 ⫾ 77.34 25.82 ⫾ 57.19
SD ⫽ standard deviation.
males, 3 females, ages 12 to 57 years) who were assisted with the continuous axial flow DeBakey VAD pump and are the subject of this review. All patients had a sudden or gradual deterioration of heart function requiring a change in their waiting list priority to status I for HTx. The causes of heart failure were idiopathic dilated cardiomyopathy in 7 patients (63.6%), ischemic heart disease in 3 (27.3%), and dilated cardiomyopathy with specific myopathy and normal dystrophine in 1 patient (9.1%). At the time of device implantation all patients were in sinus rhythm. The clinical characteristics of the 11 study patients are detailed in Table 1. The inclusion criteria for enrollment and use of an assist device were left atrial pressure or wedge pressure of at least 18 mm Hg and cardiac index less than or equal to 2 L · min⫺1 · m⫺2 or systolic pressure less than 90 mm Hg while on therapy with intraaortic balloon pump and vasopressor agent (dopamine ⱖ 10 g · kg⫺1 · min⫺1, dobutamine ⱖ 7.5 g · kg⫺1 · min⫺1, epinephrine ⱖ 0.02 g · kg⫺1 · min⫺1, isoproterenol ⱖ 0.5 g · kg⫺1 · min⫺1, or milrinone ⱖ 0.5 g · kg⫺1 · min⫺1). All patients provided written informed consent for device implantation, and the study was approved by the Institutional Review Committee.
MicroMed DeBakey Ventricular Assist Device This device consists of three subsystems—a miniaturized titanium axial flow pump, an external controller, and a clinical data acquisition system. The device is electromagnetically actuated, miniaturized, and fully implantable. A titanium inflow cannula connects the pump to the apex of the left ventricle, and a Vascutek Gelweave vascular graft (outflow conduit) connects the pump to the ascending aorta. An ultrasonic flow probe is placed around the outflow conduit. Together with the flow probe’s wiring, the pump motor cable is exteriorized above the right iliac crest and is attached to the VAD external controller system. The pump is 30.5 mm in diameter, 76.2 mm long, and weighs 93 g. It is designed to achieve 5 L/min of blood flow against 100 mm Hg pressure, with a motor speed of 10,000 rpm and a power input of 10 W. The control
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system is completely external and consists of a smart controller and two batteries. The controller displays pump variables and provides audible and visual alarms. The clinical data acquisition system records and displays pump data (pump flow, pump speed, power consumption, and current signals) and can be used to modify the pump speed. Adjustments of the pump speed can be made only when it is connected to the clinical data acquisition system. For optimal mobilization of the patient and freedom of movement, the electrical power is delivered by one of the two 12-V batteries. Each battery lasts 6 to 8 hours. The entire system weighs 2.5 kg [7].
Implant Procedures For pump implantation, a median sternotomy incision is done, which extends a few centimeters below the xiphoid process. A small abdominal wall pocket is created below the rectus muscle sheath. The size and configuration of the pocket is determined by using a mock pump model. Standard ascending aorta and two-stage (right atrial and inferior vena cava) cannulations are done, and cardiopulmonary bypass is initiated. The left ventricular apex is elevated, and a suitable insertion site for the LVAD inflow cannula is selected. After aortic cross-clamp and infusion of cold blood cardioplegia, an apical fixation ring is sewn to the apex of the left ventricle. A round-bladed device is inserted into the left ventricle to extract an apical core. A visual and digital exploration of the ventricle is performed to ensure absence of any potential obstructions to the device’s inflow cannula. The LVAD inflow cannula is inserted into the left ventricular apex and is sewn to the apical fixation ring. Similar to implantation of other LVAD systems, the inflow cannula is inserted during cardioplegic arrest. In our experience with first-generation pulsatile LVADs, we used the beating heart technique. Now, however, we prefer to insert the inflow cannula on an arrested heart because it allows for more accurate suturing. The aortic cross-clamp is then removed. A trocar is used to create a tunnel from the abdominal wall pocket, across the midline subcutaneously, and through the skin at a convenient location above the right iliac crest. The MicroMed DeBakey VAD is placed into the small abdominal pocket, and an appropriate length of the outflow graft is selected. We place the graft under the right sternal border without kinking or overstretching and pass it into the mediastinum to reach the ascending aorta. Before and after completion of the anastomosis to the aorta, the air is removed from the system carefully. The LVAD is started with a speed of 7,500 rpm as the patient is progressively weaned from cardiopulmonary bypass. By using inotropic support and nitric oxide to support the right heart function, the pump speed is adjusted to maintain a cardiac index of 2.0 to 2.5 L/m2 per minute and a mixed venous-oxygen saturation greater than 60% as indicated by a Swan-Ganz catheter. A few hours postoperatively the pump speed is gradually increased to obtain mixed venous-oxygen saturations of greater than 70%. After 48 to 72 hours, the pump speed is set between 9,000 and 11,000 rpm. The location of the
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inflow cannula and the function of both ventricles are examined by echocardiography. The right ventricle in particular is assessed for adequate preload and for its systolic function. To avoid adhesions and to facilitate surgical reentry at the time of transplantation, the pericardial closure and wrapping of the VAD and the outflow cannula is done with a Gore-Tex membrane (W.L. Gore & Assoc, Flagstaff, AZ) as previously described [8].
Anticoagulation Anticoagulation treatment is based on the protocol proposed by the group at the “La Pitie´ –Salpetrie`re” Hospital in Paris [9, 10] and is the same protocol that we use for all patients receiving an LVAD. In brief, the regimen is as follows: during the first 24 hours postoperatively, the patients receive no anticoagulation. Thereafter, intravenous heparin therapy is started according to thromboelastography (TEG) modified with heparinase and Activated Partial Thromboplastin Time (APTT) (1.5 to 2 times normal value). Long-term anticoagulation consists of sodium warfarin (dosage according to international normalized ratio of prothrombin time 2.5 to 3.5 times normal value) and enoxaparine (2,000 to 4,000 IU/day) whenever requested. Low-molecular-weight-heparin, which antagonizes the activated coagulation Factor X and prevents formation of thrombin, is added to sodium warfarin when TEG reveals suboptimal anticoagulation even if the international normalized ratio of prothrombin time values are optimal. This abnormal phenomenon is due to the presence of thrombin in microdoses, which pose a potential risk for thrombosis. This protocol is very careful with regard to platelet activity by including dypiridamol (800 mg/day intravenously intraoperatively and thereafter 800 mg/day orally) and aspirin (100 mg daily). When thrombocytosis or platelet-related hypercoagulability is discovered, ticlopidine (250 mg/day) is added to the regimen. Pentoxifylline (400 mg/day intravenously initially and thereafter 800 mg/day orally) is used to further improve hemorheology. The efficacy of this anticoagulation treatment is monitored by TEG (daily in the acute phase, then weekly when the patients are moved to a regular ward, and later on whenever it is necessary). TEG is the only test that dynamically studies the formation and characteristics of blood clot. It examines all phases of coagulation, including platelet activity and presence of fibrinolysis. We use TEG data coupled with the blood tests required by this protocol to check the final result of pharmacologic interventions regarding anticoagulation and to evaluate whether any drugs must be added or removed, as well as to calibrate the drug dosages. This anticoagulation protocol requires several blood tests, including TEG and the necessity of taking multiple drugs. Monitoring is frequent in the early phases after the implant, including blood tests twice a day and TEG once a day. As the patients move to the regular ward care, monitoring is less frequent and is further decreased when the tests show a stabilized anticoagulation effect. As the patients recover, blood and TEG tests are done
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once a week and during the follow-up examinations; TEG is tested every 3 or 4 weeks on an out-patient basis. During the chronic phase, the frequency of monitoring of this protocol is comparable to that of patients with prosthetic cardiac valves or atrial fibrillation. It is important to note that this pharmacologic regimen has been well tolerated and has been associated with a satisfactory patient compliance rate.
Results All patients survived the LVAD implantation procedure. Weaning from extracorporeal circulation was facilitated in all patients with the use of inotropic drugs (eg, dopamine, epinephrine, phosphodiesterase-III inhibitors) and nitric oxide. Intraoperatively by echocardiography, the position of the inflow cannula was assessed. The cannula tip stayed in a neutral position within the left ventricle. It was not oriented towards the septum or the free lateral wall, and its position allowed proper drainage of blood and did not require repositioning of the cannula. Furthermore, repeated echocardiographic survery showed that the left ventricle was properly drained without rightward shift of the septum. After postoperative stabilization, the pump speed was set between 9,000 and 11,000 rpm to allow for optimal cardiac output and to achieve a satisfactory physical activity tolerance [11]. Further adjustments of pump speed were uncommon because, in chronic stages, the pump flow was optimized mainly by adjusting the patient’s fluid balance. Arterial blood pressure was measured invasively in the perioperative period; pump flow changes due to pump speed adjustment were not compared with arterial pressure changes. The mean duration of MicroMed DeBakey VAD support was 51 ⫾ 49 days (range 11 days to 4.7 months), and the cumulative time of support was 16.66 months. Two patients (18.2%) died while on LVAD support due to multiple-organ system failure after 13 and 44 days of circulatory assistance. All other patients recovered rapidly from the operation and were discharged from the intensive care unit to ward care where they performed regular physical training. These patients were able to perform their normal daily activities. As each patient gained confidence with the MicroMed Debakey VAD they were taught to manage the device themselves. In this initial experience, the patients assisted with the DeBakey VAD were not discharged home. Our policy was to keep the patients in the hospital to observe their clinical progress and to analyze the device function on a daily basis. Furthermore, most of these patients resided too far away from our hospital, which prevented their early dismissal per our hospital policy [12]. Eight of the nine transplanted patients (88.9%) were discharged home. One patient died of graft failure due to acute rejection 29 days after HTx. Nine patients (81.8%) underwent HTx between 11 and 141 days after LVAD implant. At the time of HTx, minimal adhesions and bleeding from the pump nesting site facilitated the removal of DeBakey VAD pump,
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Table 2. Index of Organ Function Before Cardiac Transplant Variable Serum creatinine (mg/dL) Total bilirubin (mg/dL) Aspartate aminotransferase (U/L) Alanine aminotransferase (U/L) Lactate dehydrogenase (U/L) Plasma free hemoglobin (mg/L)
Mean ⫾ SD 0.81 ⫾ 0.38 1.17 ⫾ 0.56 31.25 ⫾ 17 22 ⫾ 11.45 817 ⫾ 595 48 ⫾ 7
SD ⫽ standard deviation.
level was persistently elevated in 1 patient during continuos veno-venous hemofiltration and normalized after cessation of this treatment. Lactate dehydrogenase levels also increased in a few patients during the period of cardiac assist, as in another report [11]. The increase in lactate dehydrogenase level was not related to the increase in plasma fHb. The mean level of plasma fHb and lactate dehydrogenase was slightly above normal at termination of circulatory assistance. However, plasma fHb peaks and the elevation of lactate dehydrogenase was not associated with decrease in blood hemoglobin level or need for blood transfusion. Indices of end-organ function and hemolysis at the time of termination of cardiac assistance (before HTx) for all patients are shown in Table 2.
Comment Clinical experience has shown compatibility of nonpulsatile blood flow with adequate end-organ perfusion for periods of up to several months [7]. The continuous flow axial DeBakey VAD recently was introduced into clinical practice as a bridge to HTx [15]. It has demonstrated adequate circulatory support in patients with end-stage heart failure. Our study confirms other reports and shows that this device is safe and effective [7, 15–17]. This study was retrospective and nonrandomized. In selecting patients for implanting the MicroMed DeBakey VAD as a bridge to HTx, we considered factors related to the device characteristics and to the patients’ probability of getting a suitable donor heart in an adequate time after device implantation. For these reasons we selected to implant the MicroMed DeBakey VAD in patients who had a high probability of receiving a suitable donor heart in an adequate time interval. Consequently, we did not implant this device in patients with a large body surface area, (ie, ⬎ 2 m2), which could be a possible bias in patient selection for implantation of this device and represents another limitation of this study. Other indications for device implantation, such as the preoperative end-organ function (especially liver and kidneys), followed the criteria used for all patients that needed an LVAD. The patients who are suitable for LVAD implantation were strictly monitored by a team of surgeons and cardiologists; if optimized medical therapy (oral and intravenous) was not sufficient to maintain cardiac function to satisfy tissue perfusion and led to progressive end-organ damage, we proceeded with de-
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making the operation easier and faster than removal of bulky pulsatile LVAD pumps. Major bleeding episodes (blood loss of more than 1500 mL in 24 hours requiring surgical hemostasis in the mediastinum) occurred in 2 patients (2 of 11, 18.2%). One patient (9.1%) had a minor neurologic event (slight aphasia lasting less than 30 minutes), 101 days after LVAD insertion. Contrast-enhanced computed tomographic scan showed a small area of hypodensity compatible with ischemic damage in the left frontal region. None of the LVAD patients experienced any septic episodes (defined as body temperature above 38.5°C, white blood cell count over 12,000 g/dL, positive blood cultures, or low systemic vascular resistance). None of the patients showed signs of inflammation or infection at the exit site of the transcutaneous cables. Renal failure (defined as the need for hemodialysis or continuos venovenous hemofiltration) occurred in 1 patient (9.1%) with multiple-organ system failure. Liver failure (defined as aspartate aminotransferase or alanine aminotransferase levels or both at least twofold above normal values, and pathologic total bilirubin levels) occurred in 2 patients (18.2%). None of the patients had severe right ventricular failure (defined as cardiac index less than 2 L · min⫺1 · m⫺2 despite a central venous pressure of 18 to 22 mm Hg and maximal pharmacologic support with inotropic drugs and vasodilators) requiring right ventricular assistance [13]. One patient, on the 112th day of support, had possible thrombosis of the DeBakey VAD pump despite a normal anticoagulation profile. This complication was suspected because of an increase in current and power registered by the controller with a decrease in pump flow rate. Emergency transthoracic echocardiogram and contrastenhanced computed tomographic scan showed no endoventricular thrombus image. There was no turbulent flow on the anastomosis between the outflow graft and the ascending aorta, and no obstruction or kinking of the outflow graft beyond the flow probe. Before proceeding to pump replacement, upon recommendation of the manufacturer’s technical support staff, we performed endoventricular thrombolysis, by direct delivery of recombinant tissue plasminogen activator into the left ventricle, as we have previously reported [14]. After 20 minutes, power and current values began to diminish, flow rate increased, and the clinical status began to improve. After 3 hours, current and power values reached normal ranges, with flow rate normalization (4.5 L/min) and complete hemodynamic recovery. Neither major nor minor neurologic events were observed. In the following days, the pump function was appropriate, and on postoperative day 142, the patient had a successful cardiac transplantation. Indices of hemolysis, indicated by plasma free hemoglobin (fHb) and lactate dehydrogenase levels, showed episodes of slight hemolysis. Isolated transient peaks of fHb were detected in a few patients, similar to a report by Wieselthaler and colleagues [11]. The plasma fHb peaks were not related to clinical or mechanical events. The
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vice implantation within 12 to 24 hours. Our policy was to implant LVAD before serious end-organ dysfunction occurred. In the case of emergency implants in which the patient has advanced end-organ dysfunction, our policy is to implant a paracorporeal device. In our experience, the MicroMed DeBakey VAD is an effective device as a bridge to HTx with a high success rate (9 of 11, 81.8%). These results are due to improvement in end-organ function achieved by multiple factors, including the function of the DeBakey VAD and strict adherence to our anticoagulation protocol. Therefore, a low rate of adverse events, such as bleeding, thromboembolism, and infection, was encountered in this study and by others [11]. Since we started using LVADs, we adopted the anticoagulation protocol of “La Pitie´ ” hospital [9, 10]. We attribute the low incidence of bleeding complications in this study mainly to the careful application and monitoring of this protocol, which has a multiple-system approach to the determinants of the coagulation cascade. The DeBakey VAD compared with pulsatile LVADs appears to influence contact activation and to promote platelet damage [18]. The anticoagulation protocol adopted in this study is very attentive to platelet activity and preservation, which could have positively influenced the results. Other reasons, such as the absence of artificial valves, compliance chamber, and the type of flow characteristics of this device, also could have played an important role in reducing the incidence of thromboembolic events. Because of its small size, the DeBakey VAD requires a small nesting site and needs limited surgical dissection, which could explain the low rate of infection and bleeding after device removal. Inflammation or infection at the motor cable exit site was not observed in our patients. This finding was probably related to both the small diameter and flexibility of the percutaneous cable and to the lack of pump motion due to nonpulsatile flow. In conclusion, the continuous axial flow MicroMed DeBakey VAD as a bridge to heart transplantation showed good hemodynamic performance and low incidence of major complications and achieved a high rate of conversion to HTx. Additional experiences with a larger number of patients and with longer duration of assist should further define the role of this device in the area of mechanical circulatory assistance not only as bridge to transplant but possibly for destination therapy. The authors thank Dr Hooshang Bolooki for language editing.
References 1. Date Highlights UNOS Scientific Registry Annual Report, 1999. UNOS website: www.unos.org.
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2. Harper AM, Rosendale JD. The UNOS OPTN waiting list and donor registry: 1988 –1996. In: Cecka JM, Teraski PI, eds. Clinical transplants. Los Angeles: UCLA Tissue Typing Laboratory, 1996:69 –99. 3. Frazier OH, Rose EA, McCarthy PM, et al. Improved mortality and rehabilitation of transplant candidates treated with a long term implantable left ventricular assist system. Ann Surg 1995;222:327–38. 4. McCarthy PM, Smerida NO, Vargo RL, et al. One hundred patients with the HeartMate left ventricular assist device: evolving concepts and technology. J Thorac Cardiovasc Surg 1999;115:904 –12. 5. Sun BC, Catanese KA, Spanier TB, et al. 100 long-term implantable left ventricular assist devices. The Columbia Presbyterian interim experience. Ann Thorac Surg 1999;68: 688 –94. 6. Noon GP, Morlry D, Irwin S, Benkowski R. Development and clinical application of the MicroMed DeBakey LVAD. Curr Opin Cardiol 2000;15:166 –71. 7. Noon GP, Morley DL, Irwin S, et al. Clinical experience with the MicroMed DeBakey ventricular assist device. Ann Throac Surg 2001;71:133–8. 8. Vitali E, Russo C, Colombo T, Lanfranconi M, Bruschi G. Modified pericardial closure technique in patients with ventricular assist device. Ann Thorac Surg 2000;69:1278 –9. 9. Bellon JL, Szefner J, Cabrol C. Coagulation et coeur artificiel. Paris: Masson, 1989. 10. Szefner J, Cabrol C. Control and treatment of hemostasis in patients with a total artificial heart: the experience of La Pite´ . In: Pifarre´ R, ed. Anticoagulation, hemostasis, and blood preservation in cardiovascular surgery. Philadelphia: Hanley and Belfus Inc., 1993:237–64. 11. Wieselthaler GM, Schima H, Lassnigg AM, et al. Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial flow pump: a single center report. Ann Thorac Surg 2001;71:139 –43. 12. Fey O, El-Banayosys A, Arosuglu L, Posival H, Ko¨ rfer R. Out of hospital experience in patients with implantable mechanical circulatory support: present and future trends. Eur J Cardiothorac Surg 1997;11:S51–3. 13. Chen JM, Rose EA. Management of perioperative right-side circulatory failure. In: Goldstein DJ, Oz MC, eds. Cardiac assist device. Armonk, NJ: Futura Publishing Company, 2000:83–101. 14. Russo C, De Biase AM, Bruschi G, Agati S, Vitali E. Successful intraventricular thrombolysis during ventricular assist device support. Ann Thorac Surg 2002;73:1628 –9. 15. Wieselthaler GM, Schima H, Hiesmayr M, et al. First clinical experience with the DeBakey LVAD continuous-axial-flow pump for bridge to transplantation. Circulation 2000;101: 356 –9. 16. Lanfranconi M, Russo C, Ribera E, et al. Assistenza monoventricolare sinistra con pompa a flusso continuo DeBakey LVAD: prima esperienza clinica italiana. Italian Heart J 2001;2 Suppl:653–8. 17. Wilhelm MJ, Hammel D, Schmid C, et al. Clinical experience with nine patients supported by continuous flow DeBakey LVAD. J Heart Lung Transplant 2001;20:201. 18. Kostner A, Loebe M, Hansen R, et al. Alterations in coagulation after implantation of a pulsatile Novacor LVAD and the axial flow Micromed DeBakey LVAD. Ann Thorac Surg 2000;70:533–7.