Investigational Device Exemption Trial Research Articles

Prospective, randomized, multicenter Food and Drug Administration investigational device exemption study of lumbar total disc replacement with the CHARITÉ artificial disc versus lumbar fusion: Five-year follow-up

Background context The CHARITÉ artificial disc, a lumbar spinal arthroplasty device, was approved by the United States Food and Drug Administration in 2004 based on two-year safety and effectiveness data from a multicenter, prospective, randomized investigational device exemption (IDE) study. No long-term, randomized, prospective study on the CHARITÉ disc or any other artificial disc has been published to date. Purpose The purpose of this study was to compare the safety and effectiveness at the five-year follow-up time point of lumbar total disc replacement using the CHARITÉ artificial disc (DePuy Spine, Raynham, MA) with that of anterior lumbar interbody fusion (ALIF) with BAK cages and iliac crest autograft, for the treatment of single-level degenerative disc disease from L4 to S1, unresponsive to nonoperative treatment. Study design/setting Randomized controlled trial—five-year follow-up. Patient sample Ninety CHARITÉ patients and 43 BAK patients. Outcome measures Self-reported measures: visual analog scale (VAS); validated Oswestry disability index (ODI version 1.0); Short-Form 36 Questionnaire, and patient satisfaction. Physiologic measures: radiographic range of motion, disc height, and segmental translation. Functional measures: work status. Methods Of the 375 subjects enrolled in the CHARITÉ IDE trial, 277 were eligible for the five-year study and 160 patients thereof completed the five-year follow-up. The completers included 133 randomized patients. Overall success was defined as improvement≥15 pts in ODI vs. baseline, no device failure, absence of major complications, and maintenance or improvement of neurological status. Additional clinical outcomes included an ODI questionnaire as well as VAS, SF-36, and patient satisfaction surveys. Work status was tracked for all patients. Safety assessments included occurrence and severity of adverse events and device failures. Radiographic analyses such as index- and adjacent-level range of motion, segmental translation, disc height, and longitudinal ossification were also carried out. Results Overall success was 57.8% in the CHARITÉ group vs. 51.2% in the BAK group (Blackwelder's test: p=0.0359, Δ=0.10). In addition, mean changes from baseline for ODI (CHARITÉ: −24.0 pts vs. BAK: −27.5 pts), VAS pain scores (CHARITÉ: −38.7 vs. BAK: −40.0), and SF-36 questionnaires (SF-36 Physical Component Scores [PCS]: CHARITÉ: 12.6 pts vs. BAK: 12.3 pts) were similar across groups. In patient satisfaction surveys, 78% of CHARITÉ patients were satisfied vs. 72% of BAK patients. A total of 65.6% patients in the CHARITÉ group vs. 46.5% patients in the BAK group were employed full-time. This difference was statistically significant (p=0.0403). Long-term disability was recorded for 8.0% of CHARITÉ patients and 20.9% of BAK patients, a difference that was also statistically significant (p=0.0441). Additional index-level surgery was performed in 7.7% of CHARITÉ patients and 16.3% of BAK patients. Radiographic findings included operative and adjacent-level range of motion (ROM), intervertebral disc height and segmental translation. At the five-year follow-up, the mean ROM at the index level was 6.0° for CHARITÉ patients and 1.0° for BAK patients. Changes in disc height were also similar for both CHARITÉ and BAK patients (0.7 mm for both groups, p=0.9827). Segmental translation was 0.4 and 0.8 mm in patients implanted with CHARITÉ at L4–L5 vs. L5–S1, respectively, and 0.1 mm in BAK patients. Conclusions The results of this five-year, prospective, randomized multicenter study are consistent with the two-year reports of noninferiority of CHARITÉ artificial disc vs. ALIF with BAK and iliac crest autograft. No statistical differences were found in clinical outcomes between groups. In addition, CHARITÉ patients reached a statistically greater rate of part- and full-time employment and a statistically lower rate of long-term disability, compared with BAK patients. Radiographically, the ROMs at index- and adjacent levels were not statistically different from those observed at two-years postsurgery.

Results and Lessons Learned from a United States Hip Resurfacing Investigational Device Exemption Trial

Improvements in metal-on-metal bearings have made hybrid hip surface replacement a potential alternative for the young active patient with end-stage hip disease. Possible advantages include greater hip joint stability, bone preservation, and decreased osteolysis. In this study, we compared the clinical and radiographic results of a new resurfacing device with those in a historical group of standard total hip arthroplasties. In 2001, the Cormet 2000 Hip Resurfacing Investigational Device Exemption study was initiated at twelve centers. A total of 337 patients treated with unilateral hip surface replacement with the Cormet device were enrolled in that study. These patients were compared with 266 patients in a previous study who had undergone unilateral total hip arthroplasty with ceramic bearing surfaces. Clinical and radiographic results were compared at similar time intervals. A newly recommended performance standard, the composite clinical success score, was used to assess non-inferiority of the hip resurfacing compared with the total hip arthroplasty used in the historical comparison population. At the time of follow-up, at a minimum of two years, the Harris hip scores were comparable between the resurfacing and total hip arthroplasty groups. Statistical evaluation of the composite clinical success scores confirmed the non-inferiority hypothesis. Revision was required in twenty-four patients in the resurfacing group and five patients in the total hip arthroplasty group. The most common cause of revision following resurfacing was failure of the femoral component (fracture of the femoral neck or loosening of the femoral component). Careful review of this study population revealed several important criteria for successful introduction of this resurfacing device into the United States. These include careful patient selection based on clinical and radiographic parameters and attention to various surgical details of implantation. These findings can be used to focus the training process for surgeons who wish to add implantation of this device to their surgical armamentarium. Such efforts should help to ensure safe and effective introduction of this new technology.

Patient selection for lumbar arthroplasty and arthrodesis: the effect of revision surgery in a controlled, multicenter, randomized study

Patient selection is perhaps the most important factor in successful lumbar surgery. In this study, the authors analyzed the clinical outcomes of patients enrolled in the CHARITE investigational device exemption (IDE) trial who underwent revision surgery after primary total disc replacement with CHARITE or an anterior lumbar interbody fusion (ALIF) with placement of a BAK cage and iliac crest autograft. This revision surgery was either a supplemental posterior lumbar fixation or a 360 degrees fusion. Statistical analysis was conducted to compare clinical success in patients who underwent revision surgery with those who did not. The patients enrolled in the CHARITE IDE study were divided into 6 groups according to treatment and repeated operation status, and their Oswestry Disability Index (ODI) and visual analog scale (VAS) scores at the 2-year follow-up and at baseline were compared. The patients had received the following treatments by group: A) ALIF without reoperation; B) ALIF with conversion to 360 degrees fusion; C) arthroplasty (randomized) without repeated operation; D) arthroplasty with supplemental posterior lumbar fixation; E) arthroplasty (nonrandomized) without repeated operation; and F) arthroplasty (nonrandomized) with supplemental posterior lumbar fixation. Outcome scores in the groups of patients who required revision surgeries (Groups B, D, and F; 23 patients) were compared with the groups that did not require revision surgery (Groups A, C, and E; 299 patients). Patients who required revision surgery had a significantly lower level of clinical improvement than those who did not. The mean change in ODI score was -53.0% in Groups A, C, and E, but just -12.7% in Groups B, D, and F (p < 0.0001). The mean change in VAS score was -59.1% in Groups A, C, and E, compared to -23.4% in Groups B, D, and F (p < 0.0001). No significant differences were identified in analyzing absolute change in scores and the percentage change. A comparison of outcomes in patients who had undergone arthroplasty without reoperation (Groups C and E) with all patients who had undergone revision surgery (Groups B, D, and F) demonstrated similar results (p < 0.0001). The 7.1% of patients who underwent a secondary stabilization procedure had poor clinical improvement. This finding may indicate that if the alternative treatment had been the initial treatment, these patients would not have benefited, and further implies a 7.1% rate of imprecision in preoperative evaluation.

Artificial Disc Versus Fusion

A total of 115 patients were randomized in a 1:1 ratio to a Bryan artificial disc replacement (56) or an anterior cervical fusion with allograft and a plate (59). The purpose of this study is to examine the functional outcome and radiographic results of this prospective, randomized trial to determine the role of the Bryan artificial cervical disc replacement for patients with 1-level cervical disc disease. Artificial cervical disc replacement has become an option for cervical radiculopathy. Previous studies have evaluated the efficacy of this alternative without the scientific rigor of a concurrent control population. This study is a pooled data set from 3 centers involved in the U.S. FDA Investigational Device Exemption trial evaluating the Bryan artificial cervical disc. The purpose of this study is to examine the functional outcome and radiographic results of this prospective, randomized trial to determine the role of the Bryan artificial cervical disc replacement for patients with 1-level cervical disc disease; 12-month follow-up is available for 110 patients and 24 month follow-up complete for 99 patients. There are 30 males and 26 females in the Bryan group and 32 males and 27 females in the fusion group. The average age was 43 years (Bryan) and 46 years (fusion). Disability and pain were assessed using the Neck Disability Index (NDI) and the Visual Analog Scale (VAS) of the neck and of the arm pain. SF-36 outcome measures were obtained including the physical component as well as the mental component scores. Range of motion was determined by independent radiologic assessment of flexion-extension radiographs. We report a prospective, randomized study comparing the functional outcome of cervical disc replacement to an anterior cervical fusion with results of 99 patients at 2 years. Prospective data were collected before surgery and at 6 weeks, 3, 6, 12, and 24 months after surgery. The average operative time for the control group was 1.1 hours and the Bryan Group 1.7 hours. Average blood loss was 49 mL (control) and 64 mL (Bryan). Average hospital stay was 0.6 days (control) and 0.9 days (Bryan). The mean NDI before surgery was not statistically different between groups: 47 (Bryan) and 49 (control). Twelve-month follow-up NDI is 10 (Bryan) and 18 (control) (P = 0.013). At 2-year follow-up, NDI for the Bryan group is 11 and the control group is 20 (P = 0.005). The mean arm pain VAS before surgery was 70 (Bryan) and 71 (control). At 1-year follow-up, Bryan arm pain VAS was 12 and control 23 (P = 0.031). At 2-year follow-up, the average arm pain VAS for the Bryan group was 14 and control 28 (P = 0.014). The mean neck pain VAS before surgery was 72 (Bryan) and 73 (control). One-year follow-up scores were 17 (Bryan) and 28 (control) (P = 0.05). At 2 years: 16 (Bryan) and 32 (control) (P = 0.005). SF-36 scores: Physical component--Before surgery Bryan 34 and control 32. At 24 months: Bryan 51 and control 46 (P = 0.009). More motion was retained after surgery in the disc replacement group than the plated group at the index level (P < 0.006 at 3, 6, 12, and 24 months). The disc replacement group retained an average of 7.9 degrees of flexion-extension at 24 months. In contrast, the average range of motion in the fusion group was 0.6 degrees at 24 months. There were 6 additional operations in this series: 4 in the control group and 2 in the investigational group. There were no intraoperative complications, no vascular or neurologic complications, no spontaneous fusions, and no device failures or explantations in the Bryan cohort. The Bryan artificial disc replacement compares favorably to anterior cervical discectomy and fusion for the treatment of patients with 1-level cervical disc disease. At the 2-year follow-up, there are statistically significant differences between the groups with improvements in the NDI, the neck pain and arm pain VAS scores, and the SF-36 physical component score in the Bryan disc population.

Comparison of LionHeart LVAD-Implanted Calves Based on Renal Infarctions

Calves implanted with the LionHeart left ventricular assist device during the Food and Drug Administration Investigational Device Exemption (IDE) trial had fewer renal infarctions than calves implanted after this trial (post-IDE). Since a decrease in renal infarctions indicates a favorable outcome, we compared nine IDE with 16 post-IDE implantations. Renal infarct severity was graded (0 to 4) on the basis of necropsy reports, histopathology reports, and photographs. Implants were compared for duration of support, anticoagulation, device flow, percent fill, device rate, free plasma hemoglobin, fibrinogen, platelet count, nonsteroidal anti-inflammatory drug use, inlet cannula shape, and outlet graft-to-graft anastomosis technique. IDE calves had lower renal pathology scores (1.8 vs. 2.8, p = 0.03), mean device percent fill (88.5% vs. 94.0%, p = 1 x 10), and median free plasma hemoglobin (2.6 vs. 4.4 mg/dL, p = 0.01). IDE animals also had a higher mean device rate (108 vs. 98 bpm, p = 0.04), received low-molecular-weight dextran in the early postoperative period, began oral warfarin earlier, had straighter inlet cannulae, and had factory-sewn outlet graft-to-graft anastomoses. Duration of support did not predict severity of renal infarction, and there were no differences in device flow, international normalized ratio, platelet count, or nonsteroidal anti-inflammatory drug use. These results could assist future implantations.

Development of Stabilimax NZ From Biomechanical Principles

Background Traditionally, spinal degeneration and injury have been associated with abnormal intervertebral motion; thus, treatment for lowback pain has centered on prevention of motion through spinal fusion. Although the rate of successful spinal fusions is improving, complications such as adjacent-level syndrome emphasize the need to develop alternatives for treating spinal degeneration. In an effort to improve the clinical outcomes associated with such treatment, we hypothesized that spinal stabilization and a consequent reduction in symptoms is achievable without the harsh restrictions to spinal motion imposed by fusion. This idea was based on the principle of the neutral zone and the neutral zone hypothesis of back pain. Development Performance requirements for a novel device were determined through a series of biomechanical experiments. From these data, the Stabilimax NZ was developed to provide stabilization to a degenerated or surgically destabilized spine while maintaining the maximum possible total range of motion. Applied Spine Technologies Inc has tested 70 bilateral assemblies of the final design of the Stabilimax NZ, and all exceeded the biomechanical, static, fatigue, wear, and histological requirements necessary to initiate clinical investigation. Discussion The Stabilimax NZ device has been systematically designed and tested under protocols developed by Applied Spine Technologies in conjunction with Panjabi, Patwardhan, and Goel. The device decreased the neutral zone in destabilized spines while maintaining substantial range of motion. Clinical Relevance Development testing has been submitted to the US Food and Drug Administration and permission obtained to initiate an investigational device exemption trial to clinically investigate the efficacy of the Stabilimax NZ device.

Development of Stabilimax NZ From Biomechanical Principles.

BackgroundTraditionally, spinal degeneration and injury have been associated with abnormal intervertebral motion; thus, treatment for lowback pain has centered on prevention of motion through spinal fusion. Although the rate of successful spinal fusions is improving, complications such as adjacent-level syndrome emphasize the need to develop alternatives for treating spinal degeneration. In an effort to improve the clinical outcomes associated with such treatment, we hypothesized that spinal stabilization and a consequent reduction in symptoms is achievable without the harsh restrictions to spinal motion imposed by fusion. This idea was based on the principle of the neutral zone and the neutral zone hypothesis of back pain.DevelopmentPerformance requirements for a novel device were determined through a series of biomechanical experiments. From these data, the Stabilimax NZ was developed to provide stabilization to a degenerated or surgically destabilized spine while maintaining the maximum possible total range of motion. Applied Spine Technologies Inc has tested 70 bilateral assemblies of the final design of the Stabilimax NZ, and all exceeded the biomechanical, static, fatigue, wear, and histological requirements necessary to initiate clinical investigation.DiscussionThe Stabilimax NZ device has been systematically designed and tested under protocols developed by Applied Spine Technologies in conjunction with Panjabi, Patwardhan, and Goel. The device decreased the neutral zone in destabilized spines while maintaining substantial range of motion.Clinical RelevanceDevelopment testing has been submitted to the US Food and Drug Administration and permission obtained to initiate an investigational device exemption trial to clinically investigate the efficacy of the Stabilimax NZ device.

44 POSTER Regulating hypoxia-driven VEGF by inhibiting IGF-1 signaling in childhood cancer cells

The CHARITÉ artificial disc, a lumbar spinal arthroplasty device, was approved by the United States Food and Drug Administration in 2004 based on two-year safety and effectiveness data from a multicenter, prospective, randomized investigational device exemption (IDE) study. No long-term, randomized, prospective study on the CHARITÉ disc or any other artificial disc has been published to date.The purpose of this study was to compare the safety and effectiveness at the five-year follow-up time point of lumbar total disc replacement using the CHARITÉ artificial disc (DePuy Spine, Raynham, MA) with that of anterior lumbar interbody fusion (ALIF) with BAK cages and iliac crest autograft, for the treatment of single-level degenerative disc disease from L4 to S1, unresponsive to nonoperative treatment.Randomized controlled trial—five-year follow-up.Ninety CHARITÉ patients and 43 BAK patients.Self-reported measures: visual analog scale (VAS); validated Oswestry disability index (ODI version 1.0); Short-Form 36 Questionnaire, and patient satisfaction. Physiologic measures: radiographic range of motion, disc height, and segmental translation. Functional measures: work status.Of the 375 subjects enrolled in the CHARITÉ IDE trial, 277 were eligible for the five-year study and 160 patients thereof completed the five-year follow-up. The completers included 133 randomized patients. Overall success was defined as improvement≥15 pts in ODI vs. baseline, no device failure, absence of major complications, and maintenance or improvement of neurological status. Additional clinical outcomes included an ODI questionnaire as well as VAS, SF-36, and patient satisfaction surveys. Work status was tracked for all patients. Safety assessments included occurrence and severity of adverse events and device failures. Radiographic analyses such as index- and adjacent-level range of motion, segmental translation, disc height, and longitudinal ossification were also carried out.Overall success was 57.8% in the CHARITÉ group vs. 51.2% in the BAK group (Blackwelder's test: p=0.0359, Δ=0.10). In addition, mean changes from baseline for ODI (CHARITÉ: −24.0 pts vs. BAK: −27.5 pts), VAS pain scores (CHARITÉ: −38.7 vs. BAK: −40.0), and SF-36 questionnaires (SF-36 Physical Component Scores [PCS]: CHARITÉ: 12.6 pts vs. BAK: 12.3 pts) were similar across groups. In patient satisfaction surveys, 78% of CHARITÉ patients were satisfied vs. 72% of BAK patients. A total of 65.6% patients in the CHARITÉ group vs. 46.5% patients in the BAK group were employed full-time. This difference was statistically significant (p=0.0403). Long-term disability was recorded for 8.0% of CHARITÉ patients and 20.9% of BAK patients, a difference that was also statistically significant (p=0.0441). Additional index-level surgery was performed in 7.7% of CHARITÉ patients and 16.3% of BAK patients.Radiographic findings included operative and adjacent-level range of motion (ROM), intervertebral disc height and segmental translation. At the five-year follow-up, the mean ROM at the index level was 6.0° for CHARITÉ patients and 1.0° for BAK patients. Changes in disc height were also similar for both CHARITÉ and BAK patients (0.7 mm for both groups, p=0.9827). Segmental translation was 0.4 and 0.8 mm in patients implanted with CHARITÉ at L4–L5 vs. L5–S1, respectively, and 0.1 mm in BAK patients.The results of this five-year, prospective, randomized multicenter study are consistent with the two-year reports of noninferiority of CHARITÉ artificial disc vs. ALIF with BAK and iliac crest autograft. No statistical differences were found in clinical outcomes between groups. In addition, CHARITÉ patients reached a statistically greater rate of part- and full-time employment and a statistically lower rate of long-term disability, compared with BAK patients. Radiographically, the ROMs at index- and adjacent levels were not statistically different from those observed at two-years postsurgery.

Disc Prosthesis for Lumbar Degenerative Disease and Axial Instability—ProDisc

The Prodisc-L artificial disc replacement is a useful tool in the treatment of discogenic pain syndrome. The semi-constrained design allows for near anatomic motion while diminishing shear forces on the facets. The surgical technique is reproducible and allows for a minimally invasive safe approach. The sixteen year European experience has been excellent. Under the stringent criteria set forth by the United States Food and Drug Administration investigational device exemption trial, early reports of the Prodisc-L have shown at least equivalence to circumferential fusion with important short term benefits.

Algorithm for the diagnosis and treatment of endoleaks

Background: Endoluminal grafting of abdominal aortic aneurysms (AAA) has shown promising early results. However, endoleaks present a new and challenging obstacle to successful aneurysm exclusion. We report our experience with primary, persistent endoleaks and provide an algorithm for their diagnosis and management. Methods: Over a 19-month period, 73 patients underwent endoluminal repair of their AAAs using a modular bifurcated endograft as part of a US FDA Investigational Device Exemption trial. Spiral computed tomography (CT) scanning was performed prior to discharge after repair to evaluate for complete aneurysm exclusion. If no endoleak was present on that initial CT scan, color-flow duplex scanning was performed at 1 month, with repeat CT scanning at 6 months and 1 year. If the initial CT scan revealed the presence of an endoleak, repeat CT scanning was performed at 2 weeks, 1 month, and 3 months, or until the endoleak resolved. Any patient with an endoleak that persisted beyond 3 months underwent angiographic evaluation to localize the source of the leak. Results: At 1 month, 62 patients (85%) had successful aneurysm exclusion. The remaining 11 patients (15%) had primary endoleaks, 8 (11%) of which persisted beyond 3 months, prompting angiographic evaluation. In 2 patients the endoleak was related to a graft-graft or graft-arterial junction. One was from the endograft terminus in the common iliac artery and was successfully embolized, along with its outflow lumbar artery. The other required placement of an additional endograft component across a leaking graft-graft junction to successfully exclude the aneurysm. The remaining six endoleaks were due to collateral flow through the aneurysm sac. In 4 cases this was lumbar to lumbar flow fed by hypogastric artery collaterals to the inflow lumbar artery. In the remaining 2 patients the endoleak was found to be due to flow between a lumbar and inferior mesenteric artery. Resolution of the endoleak by coil embolization of the feeding hypogastric artery branch in 1 patient was unsuccessful due to rapid recruitment of another hypogastric branch. Two of the six collateral flow endoleaks have resolved spontaneously without treatment, while the remaining cases have been followed up without evidence of aneurysm expansion. Conclusion: Systematic postoperative surveillance facilitates proper diagnosis and treatment of endoleaks. This involves serial CT scans to detect the presence of endoleaks, followed by angiography to determine their etiology and guide treatment, if clinically indicated.

A Prospective Study of 342 Patients Using Transpedicular Fixation Instrumentation for Lumbosacral Spine Arthrodesis

The objective of this research was to determine the efficacy and safety of an experimental instrumentation device designed for transpedicular spinal fixation by evaluating fusion rates and clinical pain and function scores; to determine complication rates associated with the device; and to compare the obtained data with that previously published in the literature. Four hundred forty-two consecutive patients were enrolled in this 4-year, Food and Drug Administration-monitored investigational device exemption trial to undergo surgery for implantation of the device. Eighteen surgeons at 11 nationwide medical centers performed the operations and subsequent evaluations. The study population was derived from three diagnostic categories: degenerative disc disease, multioperated back, and vertebral fracture. The data source consisted of radiographs, clinical examination, and structured forms and questionnaires. Patients were evaluated preoperatively, intraoperatively, and postoperatively at 3, 6, 12, and 24 months. By the 24-month postoperative interval, attrition had reduced the study population to 342 patients, among whom bony fusion was obtained in 91.5%. Pain scores demonstrated a statistically significant improvement in clinical outcome. Intraoperative complications occurred in 21.9% of patients. Of the 442 study patients, 2.9% experienced device-related complications. Moreover, a total of 2,304 screws and bolts were implanted in this patient population. Of these, 0.39% were reported to have fractured. Among the 342 study patients observed during 24 months, the breakage rate of device components (bolt or screw) was 2.63%. These data compare favorably to existing reports of spinal arthrodesis effected with other types of instrumentation and without device implantation. In a 4-year trial, the experimental transpedicular fixation instrumentation produced successful spinal fusion in the majority of our study population, with acceptable complication rates.

Ventricular assist devices as a bridge to cardiac transplantation. A prelude to destination therapy.

Ventricular assist devices (VADs) have been used for temporary circulatory support pending transplantation or recovery of the native heart. Outcome in 38 patients treated at the authors' institution with VADs pending transplantation was analyzed to provide information relevant to the future use of VADs as permanent implants. Thoratec (Thoratec Laboratories, Pleasanton, CA) or HeartMate (Thermo Cardiosystems, Woburn, MA) VADs were used in all cases. Patients were considered for VAD placement if they were candidates for cardiac transplantation and fulfilled the criteria for the Food and Drug Administration investigational Device Exemption trials. The following adverse events were included in the analysis; death during VAD support, device malfunction, bleeding, neurologic events, support-related events that preclude transplantation, and device-related infections. Patient survival and complication rates were quantified using the Kaplan-Meier method, competing risk analysis, and hazard functions. Nineteen patients had transplantation. Three patients had VAD removal after cardiac recovery and 16 died without transplantation. The duration of VAD support ranged from 0 to 279 days. The hazard function for death during VAD support had an early phase that lasted for 2 weeks after VAD placement, and early death was related to the preimplant condition of the patient. Device-related infections were noted in 11 patients. Seven of these patients had transplantation after clearing the infection, whereas four died without transplantation. Neurologic events occurred in seven patients. There were no device malfunctions that led to patient death. The absence of fatal device malfunctions suggests that longer term support with current VAD designs is feasible. Appropriate patient selection, infection control, and avoidance of thromboembolic neurologic complications will be crucial to the success of permanent VAD use.