Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation.

BACKGROUND: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. METHODS: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. RESULTS: The VE LVAS-treated and non-VE LVAS-treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L x min(-1) x m(-2). Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS-related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS-treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS-treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). CONCLUSION: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation.

Investigations with an implantable, electrically actuated ventricular assist device.

A permanent, implantable, circulatory support system for patients with irreversible cardiomyopathy is gradually becoming a reality. Progress has been achieved toward formation of a stable, nonthrombogenic, blood-prosthesis interface, and an electrically actuated ventricular assist device has reached an advanced stage of fabrication. The two most important components of the system, an electromechanical energy converter and a contiguous, pusher-plate, blood pump (stroke volume 85 ml) were employed in these studies. The energy converter consisted of a 50 volt, low-speed, brushless, torque motor and a mechanism to convert rotary motion into a pulsatile output. An electronic controller and variable-volume compliance chamber were not evaluated. Left ventricular bypass experiments were conducted in 13 calves for periods of 30 to 149 days. Preoperatively, four devices were inoculated with bovine, fetal fibroblasts to accelerate formation of a collagenous lining, and nine nonseeded pumps served as controls. The collagen-lined devices functioned for longer periods of time with unrestricted blood flow and no thromboembolic complications when compared to the control devices. Additional studies are contemplated employing a complete VAD system prior to undertaking preclinical trials.

Development and evaluation of electrically actuated abdominal left ventricular assist systems for long-term use.

A long-term, totally implantable, electrically actuated, abdominally positioned left ventricular assist system (ALVAS) is being developed, characterized in vitro, and evaluated in vivo for utilization in patients with end-stage cardiac failure refractory to conventional therapeutic techniques. The first two major subsystems of the ALVAS (the pusher-plate blood pump and electrical-mechanical energy converters) have been integrated and are undergoing in vitro characterization and long-term in vivo evaluations in calves. Duration of these studies has exceeded 6 months. System performance in terms of hemodynamic effectiveness, mechanical reliability, and biocompatibility has been excellent and no untoward effects have been observed. Long-term effectiveness of the ALVAS remains to be established in continuing experiments, with a 2 year period of clinical use as an ultimate goal.

HeartMate II left ventricular assist system: from concept to first clinical use.

The HeartMate II left ventricular assist device (LVAD) (ThermoCardiosystems, Inc, Woburn, MA) has evolved from 1991 when a partnership was struck between the McGowan Center of the University of Pittsburgh and Nimbus Company. Early iterations were conceptually based on axial-flow mini-pumps (Hemopump) and began with purge bearings. As the project developed, so did the understanding of new bearings, computational fluid design and flow visualization, and speed control algorithms. The acquisition of Nimbus by ThermoCardiosystems, Inc (TCI) sped developments of cannulas, controller, and power/monitor units. The system has been successfully tested in more than 40 calves since 1997 and the first human implant occurred in July 2000. Multicenter safety and feasibility trials are planned for Europe and soon thereafter a trial will be started in the United States to test 6-month survival in end-stage heart failure.

Transition from cardiopulmonary bypass to the HeartMate left ventricular assist device.

BACKGROUND: Safe transition from cardiopulmonary bypass to the HeartMate left ventricular assist device without periods of low output, air emboli, or injury to the right ventricle is vital to its successful implantation. A right atrial-to-left ventricular shunt has been developed to purge quickly and completely all air from the system and prevent its reentry, as well as to assist the right ventricle during the transition from cardiopulmonary bypass to the HeartMate. METHODS: From January 1994 through July 1996, we used an extracorporeal membrane oxygenation right atrial-to-left ventricular shunt during 17 HeartMate implantations in 16 patients. The shunt consists of the existing right atrial two-stage cannula, the bypass circuit, and a separate aortic line that fills the left ventricle using a 21F cannula in the lateral ventricular wall. Air is monitored in the heart and aorta using transesophageal echocardiography. RESULTS: Ten of the 16 patients are living and 8 have undergone transplantation. Two patients are still using the device and are awaiting transplantation. None of the patients have experienced postoperative neurologic events suggestive of air emboli. CONCLUSIONS: The extracorporeal membrane oxygenation right atrial-to-left ventricular shunt is simple and inexpensive to construct. It provides for a smoother and safer transition from cardiopulmonary bypass to the HeartMate left ventricular assist device.

Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device.

The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty-five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thromboembolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No device-related thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients (p greater than 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage cardiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

Mechanical cardiac assistance and replacement.

This article aims not to review the limited and difficult to compare clinical results with mechanical cardiac assist devices. Instead, a practical classification and analysis of these devices is presented, which will afford the clinician insights about when, how, and why to use specific mechanical support.

The heartmate left ventricular assist system: worldwide clinical results.

To date 482 patients have been treated with TCI's HeartMate left ventricular assist system (LVAS) at 70 clinical centers worldwide. Of those, 433 patients have undergone treatment with the HeartMate IP (implantable pneumatic) LVAS, while 49 patients were treated with the HeartMate VE (vented electric) LVAS. Currently 65 patients are on the HeartMate LVAS: 51 on the pneumatic version and 14 on the electric version. Of the 482 patients, 64% were transplanted after being supported for an average duration of 72 days (range 1-503 days) to arrive at a cumulative experience of greater than 100 patient years. Neural incidents occurred in 19% of the patients as a result of a variety of complications, including but not limited to air emboli, seizures, drug reactions, as well as thromboembolic complications whether device-related or not. Device-related complications remain quite low at the 2-3% range with minimal or no anticoagulant therapy. Fourteen patients on the electric version have been discharged to live at home for periods ranging from 1 to 7 months. Patients while being supported have successfully gone back to work or to school.

HeartMate VE LVAS design enhancements and its impact on device reliability.

OBJECTIVE: The HeartMate VE left ventricular assist system (LVAS) has supported more than 2300 patients and has been shown to be effective for bridge to cardiac transplantation and has demonstrated improved outcomes in survival as a destination therapy. Improvements in device durability are needed as bridge to transplant times increase and as we move into the era of LVAD as destination therapy. The purpose of this study is to determine if design enhancements to the HeartMate LVAS have improved device reliability and durability. METHODS: A retrospective analysis of serious mechanical failures was performed in 1865 devices (1458 VE, 407 XVE). The analysis of data included devices used to support patients from September 1998 for bridge to transplantation and destination therapy. Serious mechanical failures were defined as inflow valve dysfunction, percutaneous lead breaks, diaphragm fractures or punctures, bearing failures, outflow graft erosion and pump disconnects. RESULTS: Median device duration for the VE was 97 days (max 1206 days), and 85 days (max 517 days) for the XVE. A total of 134 serious mechanical failures occurred and included inflow valve dysfunction (5.3% VE, 2.4% XVE) (P = 0.853) percutaneous lead breaks (1.9% VE, 0% XVE) (P < 0.001) diaphragm fractures (0.1% VE, 0% XVE) (P = 0.134) outflow graft erosion (0.2% VE, 0% XVE) (P = 0.1096), pump disconnects (0.1% VE, 0% XVE) (P = 0.1336) and bearing failures (0.6% VE, 0.2% XVE) (P = 0.5538). Of the XVEs 97% were free of serious mechanical failures at 6 months and 82% at 1 year compared to 92 and 73% for the VE, respectively. The 6-month difference between the devices was statistically significant (P = 0.0063) and there was no statistically significant difference at 1 year (P = 0.1492). CONCLUSIONS: Preliminary experience with the HeartMate XVE LVAS demonstrated a significant reduction in percutaneous lead breaks. Early trends indicate positive impact of recent design modifications on XVE performance. These design modifications may improve device durability and reliability, which is crucial as we enter the era of LVADs as an alternative to medical therapy.

The quest for a solution. We must continue. We must push forward. The 16th Hastings Lecture.

The development of an artificial heart and heart assist devices has been ongoing for several decades. Great progress has been achieved leading to the safe and effective support of patients with end stage cardiac disease. Although patients can now live at home with a high quality of life, much work is left to be done. With the majority of technical problems behind us, we must now overcome the economic, regulatory, and acceptance barriers. We must continue, we must push forward to make these systems available for our fellow human beings.

Use of a left ventricular assist device in an outpatient setting.

The vented electric Heartmate LVAD (VE-LVAD) (Thermo Cardiosystems, Inc., Woburn, MA) is a reliable, fully portable system that allows selected patients with end-stage cardiomyopathy to undergo outpatient treatment while waiting for heart transplantation. This implantable, pusher-plate LVAD is actuated by an electric motor located within the pump housing. The patient wears external batteries and a system controller, which power and control the LVAD motor through a percutaneous lead. Since May 1991, four men have been supported with the VE-LVAD. They ranged in age from 33 to 50 years (mean, 44.3 years); two had idiopathic cardiomyopathy, and two had ischemic cardiomyopathy. Of the four patients, three underwent support of 196, 219, and 504 days; support in the fourth patient is ongoing at more than 90 days. All four patients were fully rehabilitated to New York Heart Association Class I status. Because they were well and fully mobile, the protocol was amended to allow these patients to leave the hospital in a four phase program that begins with 16 hr day passes and leads to hospital discharge. When patients leave the hospital, they are accompanied by trained family members or friends. The patients who have participated in the program have performed routine activities, attended social events, and spent the night at home. The VE-LVAD system seems safe and appropriate for the outpatient setting in selected patients. Patients have been able to manage the system without assistance from medical or engineering personnel. This initial positive experience with outpatient LVAD treatment demonstrates the potential for providing long-term cardiac support with this type of implantable technology.

Clinical responses to ventricular assistance versus transplantation in a series of bridge to transplant patients.

Hemodynamic and peripheral organ responses to ventricular assistance were compared with transplantation in a cohort of patients bridged with the HeartMate 1000 IP left ventricular assist device (LVAD) (Thermo Cardiosystems Inc., Woburn, MA). The study population included 27 patients that were supported an average of 102 days (range, 15-324 days). Two hepatic (total bilirubin and serum glutamic oxaloacetic transaminase [SGOT]) and two renal (creatinine and blood urea nitrogen [BUN]) parameters were measured: 1) before LVAD insertion, 2) 30 and 60 days during ventricular assistance, 3) before transplantation while still on the VAD, and 4) 30 and 60 days after transplantation. Total bilirubin values were significantly greater just before LVAD implant (2.3 mg/dl) than before transplantation (0.7 mg/dl). Although there was no difference after 30 days of either treatment, the total bilirubin values were greater at 60 days after transplantation (1.1 mg/dl) than at an equivalent time on the LVAD (0.6 mg/dl). The SGOT values were also significantly reduced before transplantation. No differences at 30 and 60 days after either procedure were noticed. Creatinine and BUN values were greater before LVAD implant (1.7 and 37 mg/dl) than before transplantation (1.2 and 19 mg/dl). The creatinine values were also greater after transplantation at 30 and 60 days (2.0 and 1.6 mg/dl) than at comparable intervals after LVAD implantation (1.0 and 1.2 mg/dl), presumably as a result of the use of immunosuppressive drugs. End organ function was markedly improved while on the device, enhancing the physiologic status of the patients before transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

HeartMate III: pump design for a centrifugal LVAD with a magnetically levitated rotor.

A long-term, compact left ventricular assist device (LVAD), the HeartMate III, has been designed and fabricated, featuring a centrifugal pump with a magnetically levitated rotor. The pump has been optimized by in vitro testing to achieve a design point of 7 L/min against 135 mm Hg at high hydrodynamic efficiency (30%) and to be capable of up to 10 L/min under such a load. Furthermore, the pump has demonstrated no mechanical failures, low hemolysis (4-10 mg/dl plasma free Hb), and low thrombogenicity during six (40, 27, 59, 42, 27, and 49-day) in vivo bovine studies.

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

LVADs--a new era in patient care.

Clearly, a challenge exists in treating end stage congestive heart failure patients. Drug therapy is not effective and too few donor hearts prevent transplantation from being the therapy of choice. The only alternative that is developing is the use of LVAD technology. Patients can benefit with an improved quality of life as well as increased longevity. Physicians can benefit by providing their patients with an effective alternative with the potential of reversing the disease process. Costs are significant; however they are comparable in comparison to other treatment arms. With increased use, costs will reduce as the result of developing the efficient use of this technology.

Worldwide experience with the TCI HeartMate system: issues and future perspective.

Until 1997, 993 patients have been treated with TCls HeartMate left-ventricular assist system (LVAS) at 122 clinical centers worldwide. Of those, 753 patients have undergone treatment with the HeartMate IP (implantable pneumatic) LVAS, while 240 patients were treated with the HeartMate VE (vented electric) LVAS. Currently, 121 patients are on the HeartMate LVAS: 62 on the pneumatic version and 59 on the electric version. Of the 993 patients, 59% were either transplanted or had the pump removed after recovery after being supported for an average duration of 92 days (range 1 - 727 days) to arrive at a cumulative experience of greater than 228 patient years. Device-related thromboembolic complications remain quite low at the 2-4% range with minimal or no anticoagulation therapy. Fifty-four patients on the electric version have been discharged to live at home for periods ranging from 1 to 15 months. Patients while being supported have successfully gone back to work or to school.

Can we develop a permanent pulsatile rotary blood pump? Yes, we can.

Active U.S. participation in the development of artificial heart technology began in 1966 with the award of six contracts. Since that beginning, and continuing to this day, we have been asking the same question, "Can we develop a system to take the place of the natural heart?" There are four formidable barriers that must be overcome before success can be achieved: technological development (Can the system perform as designed?); economic challenges (Can we finance the development?); regulatory hurdles (Can we get it approved for general use?); and acceptance (Will it be used, and will society accept it for what it is?). After 30 years, all but the last barrier has been overcome.