Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial

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1 FEATURED ARTICLES Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial Georg M. Wieselthaler, MD, a Gerry O=Driscoll, MD, b Paul Jansz, MD, c Asghar Khaghani, MD, d and Martin Strueber, MD, e for the HVAD Clinical Investigators From the a Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria; b Royal Perth Hospital, Perth, Australia; c St. Vincent=s Hospital, Darlinghurst, New South Wales, Australia; d Harefield Hospital, Harefield, United Kingdom; and e Division of Thoracic and Cardiovascular Surgery, Hannover Medical Center, Hannover, Germany. KEYWORDS: HeartWare HVAD; continuous flow LVAD; bridge to transplant; clinical trial BACKGROUND: Third-generation rotary blood pumps have magnetically levitated rotors that eliminate mechanical wear over the years. Together with their potential for miniaturization, these pumps seem suitable for long-term support of patients with a wide range of body surface areas (BSA). Recently, the novel HVAD pump (HeartWare Inc, Framingham, MA), a miniaturized centrifugal pump with a hydrodynamic, magnetically levitated rotor, became ready for clinical application. METHODS: In a multi-institutional trial in Europe and Australia, 23 patients (mean age, years) in end-stage heart failure were enrolled in 5 centers. The primary end point of the bridge-totransplant study was survival to heart transplant or survival to 180 days on the device, whichever occurred first. Follow-up data at 1 year are presented. The small size of the device allows for intrapericardial placement of the pump. RESULTS: Implant procedures were generally fast and uneventful. Mean duration of support was days (range, days), and mean blood flow provided by the pump was liters/min. At the 180-day end point, 2 patients had undergone successful transplant at 157 and 175 days, 2 patients died while on the device, and 19 patients continued pump support for more than 180 days. Actuarial survival after 6 months was 91% and was 86% at the 1-year follow-up. CONCLUSIONS: The design of the HVAD pump enables a quick and less invasive implantation. The results to date demonstrate satisfactory long-term survival with excellent quality of life in this cohort of 23 patients of the initial multi-institutional Conformité Européene (CE) mark trial. J Heart Lung Transplant 2010;29: International Society for Heart and Lung Transplantation. All rights reserved. Reprint requests: Georg M. Wieselthaler, MD, Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna General Hospital, Waehringer Guertel 18-20, A-1090 Vienna, Austria. Telephone: Fax: address: georg.wieselthaler@meduniwien.ac.at /$ -see front matter 2010 International Society for Heart and Lung Transplantation. All rights reserved. doi: /j.healun Cardiac transplantation is still considered the gold standard for the treatment of end-stage heart failure. However, due to an insufficient number of donor organs and growing waiting lists for cardiac transplantation, the use of mechanical assist devices (blood pumps) for bridge to transplant has become an established therapeutic option. Moreover, mechanical blood pumps have proven to be superior to optimized medical treatment in patients with a contraindication for transplant. 1 Volume displacement pumps, mimicking the pulsatility of the natural heart, were widely and successfully used in the past to support the failing heart, but the limitations of these devices in size, energy consumption, and reliability led to the introduction of the new generation of smaller,

2 Wieselthaler et al. Initial Experience With the HVAD Pump 1219 (HeartWare Inc, Framingham, MA), with a hydromagnetically levitated rotor, was introduced into the clinical arena in 2006, and this report summarizes the results collected from the first patients in an international, multiinstitutional trial to obtain Conformité Européene (CE)- mark approval. Material and methods HVAD pump Figure 1 The HVAD pump. (Photo and permission for print provided by HeartWare Inc.) more efficient, and more reliable continuous-flow rotary pumps. In several international clinical trials, the application of these new miniaturized rotary pumps showed significantly improved clinical results, with reduction in pumprelated morbidity and improvement not only in length of survival but also in quality of life. 2,3 The replacement of mechanical bearings with magnetically levitated rotor systems eliminated mechanical wear in third-generation rotary pumps and therefore improved expected long-term device durability. Active magnetic bearings in rotary pumps need complex control, whereas passive magnetic bearings in combination with hydrodynamic bearings simplify rotor control and facilitate miniaturization of these pumps. The novel HVAD pump The HVAD pump is a miniaturized centrifugal blood pump with a displaced volume of only 50 ml, a maximum external diameter of 53 mm, and a weight of 140 grams (Figure 1). A short inflow cannula integrated into the pump housing is placed in the apex of the left ventricle, and a 10-mm pre-clotted vascular graft connects as an outflow conduit from the pump to the ascending aorta. This configuration allows intrapericardial placement, thereby avoiding abdominal surgery and pump pockets. A thin and flexible driveline connects the pump through the skin to the external controller and power sources. Durability has been designed into the HVAD pump with a passive, wearless impeller suspension system and with redundant motor stators and drive circuitry. The impeller suspension system uses a stack of 3 passive magnets in the impeller and a similar stack within the center post. These 2 magnet stacks repel each other to provide radial stiffness and a magnetic axial pre-load force to keep the impeller up against the front face of the housing. The magnetic axial force is resisted by the hydrodynamic forces created on the thrust-bearing surfaces on each of the impeller blades (Figure 2). The result is a more stable, wearless Figure 2 Cross-section view of the HVAD pump. (Photo and permission for print provided by HeartWare Inc.)

3 1220 The Journal of Heart and Lung Transplantation, Vol 29, No 11, November 2010 impeller suspension system that does not require the large and complex sensors of active magnetic suspended impellers. The dual motor stators concept was designed for highpower efficiency and improved safety. With independent cabling and drive circuitry, the device can seamlessly transition into single stator mode in the unlikely event of damage to the driveline. The driveline cable is a composite design that uses 6-stranded, silver-core cables, 3 for each motor, encased within a silicone lumen and sheathed within a polyurethane casing. The stranded cables are made from a chrome cobalt alloy that exhibits excellent fatigue resistance compared with the traditional copper wire typically used in pump driveline cables. The result is a highly durable and fatigue-resistant driveline cable. Study design and patients The purpose of this study was to evaluate the safety and efficacy of the HVAD pump in patients with refractory, end-stage heart failure as a bridge to transplantation. All patients were New York Heart Association (NYHA) class IV with optimized medical treatment and were receiving intravenous inotropic agents (detailed inclusion and exclusion criteria are listed in Appendix A) comparable to the study group of the Randomized Evaluation of Mechanical Assistance in Treatment of Chronic Heart Failure (REMATCH) trial. 1 This multicenter, prospective, non-randomized, singlearm feasibility study enrolled 23 patients between March 2006 and November 2007 at 3 European and 2 Australian centers (Appendix B). The primary end point was survival to heart transplant or survival to 180 days on the device, whichever occurred first. However, each patient was monitored beyond this study end point for the full period of pump support. For this initial report, all patients completed a follow-up period of 365 days, except those who received an allograft, were weaned for recovery, or died within the first year. All patients were monitored for pump flow, selected laboratory parameters, adverse events, and device malfunctions throughout the interval of device support. The study was conducted according to the Declaration of Helsinki, International Conference on Harmonization (ICH) E6-Good Clinical Practice Guidelines, and International Organization for Standardization (ISO) The clinical protocol was approved by the competent authority of each country and the Ethics Committee at each participating center. Written informed consent was obtained from each patient. Adverse events (AE) were defined according to the accepted Interagency Registry for Mechanically Assisted Circulatory Support criteria. 4 Device implantation and anticoagulation Device implantation was performed through a standard sternotomy using normothermic cardiopulmonary bypass (CPB) with beating heart. 5 The sewing ring was attached epicardially to the left ventricular (LV) apex, and the inflow cannula was inserted through the sewing ring into the LV. The outflow graft was cut to length and sewn to the ascending aorta using an end-to-side anastomosis. The percutaneous lead was tunneled to exit in the right upper quadrant. After de-airing was completed, the clamp on the outflow graft was removed and HVAD pump speed was adjusted to accomplish full flow. Pharmacologic support and volume were adjusted to provide appropriate right heart function for successful weaning from CPB. Study protocol allowed standard post-operative care and individual anti-coagulation regimens according to each center s previous device experience. General guidelines included intravenous unfractionated heparin once chest tube drainage was 50 ml/hour to maintain an activated partial thromboplastin time of 50 to 60 seconds, and acetylsalicylic acid (80 to 160 mg/day) was started 48 to 72 hours after HVAD pump implant. Warfarin replaced heparin once the patient was stable, chest tubes had been removed, and gastrointestinal function had returned. Warfarin was adjusted to achieve an international normalized ratio (INR) of 2.5 to 3.0. Statistical analysis Patient data were collected by study coordinators in each center and forwarded to the data analysis center of the sponsor. All results for continuous biochemical and hemodynamic variables are expressed as mean standard deviation. Adverse events are presented as the number of patients who had the event as well as event rates per patient-year. Survival analysis for patients was performed with the Kaplan-Meier method, with censoring for heart transplant or cardiac recovery. Results Between March 2006 and December 2007, 20 men and 3 women with a mean age of years (range, years) who met the study entry criteria were enrolled into the clinical evaluation trial of the HVAD pump. Baseline hemodynamic data are provided in Table 1, and pre-operative risk factors are listed in Table 2. Body surface areas varied widely, with a mean of 1.98 m 2 (range, m 2 ), and the mean body mass index was 27.6 kg/m 2 (range, kg/m 2 ). Idiopathic cardiomyopathy was the etiology of heart failure in 61% of the patients, 30% had ischemic heart disease, and 9% had viral cardiomyopathy and myocarditis. Implant procedures were fast and uncomplicated, and all pumps were placed intrapericardially. The mean CPB time was 67 minutes (range, minutes), strongly dependent on natural right ventricular function as the trigger for the LVAD flow. Within the 1-year follow-up, the mean duration of support was days and total support was 19.2 patient years. However, 14 patients (61%) went on to be supported longer than 1 year.

4 Wieselthaler et al. Initial Experience With the HVAD Pump 1221 Table 1 Preoperative Hemodynamic Parameters Variable Mean SD Median Range Cardiac index, liters/min/m LVEF, % LVEDD, mm Blood pressure, mm Hg Systolic Diastolic Mean PCWP, mm Hg PAP, mm Hg Systolic Mean Diastolic CVP, mm Hg CVP, central venous pressure; LVEED, left ventricular end diastolic diameter; LVEF, left ventricular ejection fraction; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; SD, standard deviation. Overall survival was 91% at 180 days and 86% at 365 days (Figure 3). During the first 180 days, 2 patients underwent successful transplant. Two others died of septicemia and consecutive multiorgan failure (MOF) at 7 and 81 days, respectively. Between 180 and 365 days, 3 additional patients received an allograft, and 1 patient recovered left ventricular function and was successfully weaned from pump support. One patient with ischemic cardiomyopathy died after an uneventful postoperative course at 203 days due to an intracranial hemorrhage. One year after implantation of the HVAD pump, 20 of the 23 patients were alive, 14 patients were still receiving device support, 1 patient was successfully weaned from the device, and 5 patients had undergone a successful transplant between 157 and 355 days (mean, 269 days) after implant. For the entire cohort, renal, hepatic, and hematologic laboratory parameters improved during support (Table 3). Adverse events The most common AE within a 1-year follow-up period was infection, which occurred on 16 occasions in 11 patients Table 2 Factor Pre-operative Risk Factors No. or mean SD (range) Moderate-severe RV dysfunction 9 Previous sternotomy 5 Pacemaker and/or ICD 16 Previous myocardial infarction 6 Diabetes 4 Coronary angioplasty 6 Cardiac hospitalizations within last (0 15) 6 mon ICD, implantable cardioverter defibrillator; RV, right ventricular; SD, standard deviation. (Table 4). Sepsis developed in 3 patients (1 fungal, 2 bacterial). None of the septic episodes were related to the device. Eight local driveline exit site infections developed in 6 patients. The exit site infections appeared rather late, between 102 and 364 days (mean, 238 days) post-operatively. With the exception of 1 surgical débridement, all of the exit sites were successfully treated with a combination of anti-biotics (oral and intravenous) and with local dressing changes. None of the driveline infections progressed into ascending driveline infections. There were 11 bleeding events in 7 patients, with 1 patient accumulating 7 events, because of a perforating intravenous catheter. These included 3 repeat explorations for immediate post-operative bleeding, 3 gastrointestinal bleeds, 2 severe nose bleeds, and 3 additional bleeding episodes that required transfusions. In 6 of the first 13 patients, thrombus formation within the pump was suspected due to a manufacturing defect in the impeller. Thrombolytic therapy was instituted in all patients. 6 Reversal of all symptoms was achieved in 4 patients, whereas the remaining 2 patients were refractory to therapy, resulting in device exchange (replaced with HVAD pump). Both patients had an uneventful clinical course thereafter. No neurologic events occurred in the patients as a result of pump thrombus or hemolysis. This issue has not recurred since revised manufacturing and monitoring techniques were implemented (see Discussion). Two patients had cerebrovascular accidents. One patient with heparin-induced thrombocytopenia had systemic arterial thrombi, and femoral artery thrombosis developed, as well as a stroke, which left him with some residual loss of peripheral vision in 1 eye. This was the first study patient whose heart fully recovered and could be weaned from the HVAD pump. The second patient sustained a stroke at 203 days (INR 2.8) and died of an intracranial hemorrhage. This translates into a linearized stroke rate of 0.10 events per patient-year. Post-implant right heart failure developed in 1 patient that was severe enough to require a right ventricular assist

5 1222 The Journal of Heart and Lung Transplantation, Vol 29, No 11, November 2010 Figure 3 The 12-month outcome of the multi-institutional HVAD trial. device (RVAD). The patient s right heart recovered sufficiently to have the RVAD removed. Unfortunately, the patient died of sepsis on post-operative Day 81. There were 3 deaths at 13, 81, and 203 days after device implant. Twenty-one of the 23 patients were discharged home. There were 9 post-implant readmissions for complications, or 0.47 readmissions per patient-year of support. In contrast to this, within the year before device implant, the same group of patients was admitted to the hospital for the treatment of end-stage heart failure times per patientyear (range, 1 15 admissions/patient). Discussion In November 1998, when the first miniaturized axial-flow pumps were implanted in humans, 7 no one could have anticipated that the evolving technology of rotary blood pumps would replace the displacement pumps used for the previous 20 years. Rotary pumps seemed to provide striking advantages in terms of potential for miniaturization of pumps and controller units, elimination of noise, reduction of driveline diameters, and the need for compliance chambers. However, there was uncertainty regarding the long- Table 3 Laboratory Values at Baseline and at 6 and 12 Months for the Entire Cohort Laboratory values Pre-operative Median (range) 3 months Median (range) 6 months Median (range) Blood urea nitrogen, mg/dl 27.4 (7 73) 19.7 ( ) 20.7 (9 68) Creatinine, mg/dl 1.2 ( ) 1.1 ( ) 1.2 ( ) LDH, IU/liter 256 ( ) 281 ( ) 277 ( ) ALT, IU/liter 24 (8 106) 30 (10 92) 34.6 (12 102) AST, IU/liter 26 (14 52) 23.1 (12 48) 28.5 (18 51) Total bilirubin, mg/dl 1.2 ( ) 0.8 ( ) 0.8 ( ) Hemoglobin, mg/dl 12.0 ( ) 12.5 (9 14.1) 12.9 ( ) Plasma-free Hgb, mg/dl 1.8 ( ) 7.1 (1.2 15) 7 (0.8 11) INR 1.5 ( ) 2.7 (1.1 4) 2.8 ( ) Platelet count, 10 3 / l 242 ( ) 269 ( ) 223 ( ) APTT, sec 39.5 (23 84) 46.6 (28 49) 49.1 (31 56) ALT, serum alanine aminotransferase; APTT, activated partial thromboplastin time; AST, serum aspartate aminotransferase; Hgb, hemoglobin; INR, international normalized ratio; LDH, lactate dehydrogenase.

6 Wieselthaler et al. Initial Experience With the HVAD Pump 1223 Table 4 Adverse Events in the 23 Study Patients a Adverse event 90 days days days Total AE/patient-year Infection Sepsis Exit site infection Local, not device-related Bleeding Requiring surgery Gastrointestinal Requiring 2 units PRC Cardiac arrhythmias Hemolysis Pleural effusion Respiratory Reintubated Tracheostomy Pneumonia Device replacement b Renal dysfunction Hepatic dysfunction Right heart failure Cerebrovascular accident Embolic/thrombotic Hemorrhagic AE, adverse event; PRC, packed red blood cells. Follow-up equals 19.2 patient/years. a Adverse events defined using Interagency Registry for Mechanically Assisted Circulatory Support definitions. b Replacements due to manufacturing issue. term effects of the non-physiologic, non-pulsatile flow patterns produced by the continuous-flow pumps. With the increasing use of implanted rotary blood pumps, extensive clinical experience has been gained during the last 10 years. 8,9 The expanded use of the axial-flow pump technology with the DeBakey (MicroMed Technology, Houston, TX), 10 Jarvik 2000 (Jarvik Heart Inc, New York, NY), 11 and HeartMate II (Thoratec, Pleasanton, CA) 12 pumps has provided evidence that patients can tolerate low-pulsatile flow patterns over long periods of time and that the postulated negative effects of long-term continuous flow perfusion were not observed. 13 The clinical experience with the continuous-flow pumps during the past decade has led to better patient selection and the standardization of care, which is contributing to better outcomes. 14 The growing incidence of end-stage heart failure worldwide and limited transplant numbers due to lack of suitable donors has created a significant need for an alternative treatment option. Mechanical blood pumps with long-lasting durability could be such an alternative. Magnetically levitated rotor systems are demonstrating high durability because the rotor, the only moving part, does not touch the housing and therefore has no mechanical wear. The HVAD pump, with its hydromagnetic, frictionless bearing system, fulfills these criteria for durability. This first report on the clinical use in a bridge to transplant trial of the HVAD pump shows promising results. The 91% survival rate at 180 days in these first 23 patients compares favorably with published results from other VAD clinical trials, thus demonstrating the efficacy of this new technology. 2 The long durations of support and small percentage of patients who receive a transplant speak to the minimal availability of donor hearts at the participating centers in Europe and Australia. The average time to transplant was 269 days, there were no urgent transplants, and the earliest transplant was at 157 days. Several of the first patients were beyond 600 days of support at the time this report was written, and further updates will be provided in a final clinical trial report with extended patient numbers. Suspected pump thrombus formations occurred in 6 of the first 13 patients. Because of the level of thrombotic activity seen in these early implants, an interim retrospective analysis of the explanted pump impellers and the pump manufacturing techniques was conducted and revealed a small variation in the dimensions of the thrust bearing on the front surface of the impeller. These investigations provided information that led to a change in the impeller manufacturing process and tighter specifications for the thrust bearing dimensions. There were no recurrences of this issue after the revised manufacturing and monitoring techniques were implemented. The small pump size, integrated inflow cannula, and the unique sewing ring support a simplified implant procedure that accommodates a large range of body surface areas and chest cavity and heart sizes. The abrogation of a surgically created pump pocket simplified the surgical procedure and

7 1224 The Journal of Heart and Lung Transplantation, Vol 29, No 11, November 2010 reduced associated post-operative complications. Furthermore, no pericardial or intrathoracic infections were observed in any of the patients during the entire study period. The patients conditions improved after pump implantation, and 21 of the 23 patients were discharged home from the hospital. Patients physical improvement was also evidenced by normalization of vital laboratory parameters, and from baseline to 3 and 6 months, renal and hepatic function improved during HVAD pump support (Table 7). The HVAD pump showed excellent long-term blood compatibility, as evidenced by low levels of plasma free hemoglobin and lactate dehydrogenase. Full cardiac support was achieved with very low power consumption by the device. Estimated mean HVAD pump flow was liters/min, with a mean power consumption of W at a mean rotational speed of rpm. This reflects positively on the duration of the battery power supply, especially in combination with the small controller and battery size and low weight of the HeartWare System compared with other implantable rotary pumps. All together, this further impacts positively on the quality of life of patients while on pump support. The limitations of this study were the small number of patients enrolled and the non-randomized study design. The clinical data of these initial 23 patients were used to obtain CE-mark approval. A continuation of this study at the same centers has been performed, but data analysis is not finished at this point. In conclusion, the efficacy and safety of the novel HVAD blood pump in a multi-institutional clinical trial as a bridge to transplant was evaluated. Initial experience with this device demonstrates intrapericardial placement is feasible and that survival is high when compared with studies for other available VADs. The results in this initial study show that excellent hemodynamic support and physical recovery can be achieved with this new technology for at least 1 year. Disclosure statement G. M. Wieselthaler is member of the Medical Advisory Board of HeartWare Inc, and his institution participates in technical research that is funded by a grant from HeartWare Inc. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. Appendix A Inclusion and Exclusion Criteria for Study Participantion Inclusion criteria 1. Age 18 and 75 years 2. Patient listed for cardiac transplant or patient eligible for cardiac transplant listing as determined by the institution s multidisciplinary cardiac transplant team. 3. Patient meets United Network for Organ Sharing status 1A or 1B listing criteria. 4. Left ventricular assist device implant is planned as a bridge to transplant. 5. Signed informed consent form. Exclusion criteria 1. Body surface area 1.2 m Existence of any ongoing mechanical circulatory support other than an intra-aortic balloon pump. 3. Prior cardiac transplant within 12 months. 4. History of confirmed, untreated aortic aneurysm 5 cm. 5. Cardiothoracic surgery within 30 days of enrollment. 6. Myocardial infarction within 14 days of enrollment. 7. On ventilator support for 72 hours. 8. Pulmonary embolus within 2 weeks of enrollment as documented by computed tomography scan or nuclear scan. 9. Symptomatic peripheral vascular disease manifested by rest pain or skin ulceration. 10. History of cerebrovascular disease documented by a prior documented stroke within 90 days or a 80% extracranial stenosis. 11. Aortic regurgitation grade 1 as determined by echocardiogram. 12. Patient with a mechanical valve. 13. Severe right ventricular failure as defined by the anticipated need for right ventricular assist device support or extracorporeal membrane oxygenation at the time of left ventricular assist device implantation or right atrial pressure 20 mm Hg on multiple inotropic agents. 14. Active, uncontrolled infection. 15. Uncorrected thrombocytopenia or generalized coagulopathy (eg, platelet count 125,000, international normalized ratio 1.6, or partial thromboplastin time 2.5 times control in the absence of anticoagulation therapy). 16. Serum creatinine 3.5 mg/dl within 24 hours of study enrollment or requires dialysis (does not include use of ultrafiltration for fluid removal). 17. Liver enzyme levels (aspartate aminotransferase [serum glutamic oxaloacetic transaminase], alanine aminotransferase [serum glutamate pyruvate transaminase], or lactate dehydrogenase) 3 times upper limit of normal or a total bilirubin 3 mg/dl within 24 hours of study enrollment, or biopsy-proven liver cirrhosis or portal hypertension. 18. Participation in any investigational device study. 19. Severe illness, other than heart disease, which would exclude cardiac transplantation. 20. Pregnancy. 21. Patient unwilling to comply with the study requirements. 22. Concomitant cardiac procedure planned at the time of implant with the exception of patent foramen ovale closure.

8 Wieselthaler et al. Initial Experience With the HVAD Pump 1225 Appendix B Participating Centers and Number of HVAD Implants Performed Implant center Medical University of Vienna, Austria 7 Medical Center Hannover, Germany 6 Royal Perth Hospital, Australia 4 St. Vincent=s Hospital, Sydney, Australia 4 Harefield Hospital, United Kingdom 2 Total 23 References Implants 1. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term mechanical left ventricular assistance for end-stage heart failure. N Engl J Med 2001; 345: Miller LW, Pagani FD, Russell SD, et al. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med 2007; 357: Esmore D, Kaye D, Spratt P, et al. A prospective, multicenter trial of the VentrAssist left ventricular assist device for bridge to transplant: safety and efficacy. J Heart Lung Transplant 2008;27: Kirklin JK, Naftel DC, Stevenson LW, et al. INTERMACS database for durable devices for circulatory support: first annual report. J Heart Lung Transplant 2008;27: Wieselthaler GM, Zimpfer D, Rajek AM, et al. Simplified implant technique for the novel HeartWare HVAD. JTCVS (submitted). 6. Thomas MD, Wood C, Lovett M, et al. Successful treatment of rotary pump thrombus with the glycoprotein IIb/IIIa inhibitor tirofiban. J Heart Lung Transplant 2008;27: Wieselthaler GM, Schima H, Hiesmayr M, et al. First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantation. Circulation 2000;101: Wieselthaler GM, Schima H, Lassnigg AM, et al. Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial pump: a single center report. Ann Thorac Surg 2001;71(3 suppl):s Kirklin JK, Naftel DC, Kormos RL, et al. Second INTERMACS annual report: more than 1,000 primary left ventricular assist device implants. J Heart Lung Transplant 2010;29: Goldstein DJ. Worldwide experience with the MicroMed DeBakey Ventricular Assist Device as a bridge to transplantation. Circulation 2003;108(suppl 1):II Frazier OH, Myers TJ, Westaby S, et al. Clinical experience with an implantable, intracardiac, continuous flow circulatory support device: physiologic implications and their relationship to patient selection. Ann Thorac Surg 2004;77: Strüber M, Sander K, Lahpor J, et al. HeartMate II left ventricular assist device; early European experience. Eur J Cardiothorac Surg 2008;34: Thalmann M, Schima H, Wieselthaler G, et al. Physiology of continuous blood flow in recipients of rotary cardiac assist devices. J Heart Lung Transplant 2005;24: Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant 2010;29(4 suppl):s1-39.