Victor L. Poirier

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.

Improved mortality and rehabilitation of transplant candidates treated with a long-term implantable left ventricular assist system

ObjectiveThis nonrandomized study using concurrent controls was performed to determine whether the HeartMate implantable pneumatic (IP) left ventricular assist system (LVAS) could provide sufficient hemodynamic support to allow rehabilitation of severely debilitated transplant candidates and to evaluate whether such support reduced mortality before and after transplantation. MethodsOutcomes of 75 LVAS patients were compared with outcomes of 33 control patients (not treated with an LVAS) at 17 centers in the United States. All patients were transplant candidates who met the following hemodynamic criteria: pulmonary capillary wedge pressure ≥ 20 mm Hg with a systolic blood pressure ≤ 80 mm Hg or a cardiac index ≤ 2.0 L/minute/m2. In addition, none of the patients met predetermined exclusion criteria. ResultsMore LVAS patients than control patients survived to transplantation: 53 (71%) versus 12 (36%) (p = 0.001); and more LVAS patients were alive at 1 year: 48 (91%) versus 8 (67%) (p = 0.0001). The time to transplantation was longer in the group supported with the LVAS (average, 76 days; range, <1–344 days) than in the control group (average, 12 days; range, 1–72 days). In the LVAS group, the average pump index (2.77 L/minute/m2) throughout support was 50% greater than the corresponding cardiac index (1.86 L/minute/m2) at implantation (p = 0.0001). In addition, 58% of LVAS patients with renal dysfunction survived, compared with 16% of the control patients (p < 0.001). ConclusionsThe LVAS provided adequate hemodynamic support and was effective in rehabilitating patients based on improved renal, hepatic, and physical capacity assessments over time. In the LVAS

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.

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.

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)

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.

Bethesda conference: conference for the design of clinical trials to study circulatory support devices for chronic heart failure 1 2

James M. Anderson, MD Eugene H. Blackstone, MD Harvey S. Boroevetz, PhD Arthur Ciarkowski, MD Jack G. Copeland III, MD Maria Rosa Costanzo-Nordin, MD Kurt Daase, MD Mary Amanda Dew, PhD Michael J. Domanski, MD Benjamin H. Eidleman, MD Roger W. Evans, PhD David J. Farrar, PhD O. H. Frazier, MD Bartley P. Griffith, MD Charles-Julien Hahn, MD J. Donald Hill, MD Sharon Hunt, MD Kay Kendell, RN Robert L. Kormos, MD Howard R. Levin, MD Donna M. Mancini, MD Patrick M. McCarthy, MD Dennis McNamara, MD Fr Kevin O’Rourke, PhD Lisa Parker, PhD D. Glenn Pennington, MD Victor L. Poirier, PhD Peer M. Portner, PhD Eric A. Rose, MD Wolf Sapirstein, MD Eleanor Schron, MD Rhona Shanker, MD Ramiah Subramanian, MD John Wallwork, MD Lynne Warner Stevenson, MD

Transition from cardiopulmonary bypass to the HeartMate left ventricular assist device

BACKGROUNDnSafe 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.nnnMETHODSnFrom 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.nnnRESULTSnTen 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.nnnCONCLUSIONSnThe 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.

Portable Electric Systems for Long-Term Use

A long-term ventricular assist system has been designed for either air or electric actuation. Portability and simplicity have been the dominant design goals for this system throughout its 17-year development cycle. The system is designed for the ultimate use as an alternative to transplant and thus is configured to provide the patient freedom from external control consoles. Patients are to be discharged from the hospital to an active social life. The system configured for air operation has been evaluated in 84 patients to date, while the electric version has been evaluated in 4 patients. Both systems have proven to be safe and to provide the necessary blood flow and pressure required by the patient. In the bridge to transplant category, 63% of the patients have been supported to transplant with 88% either discharged or awaiting discharge. With the exception of one patient, there have been no reported device-related thromboembolic complications leading to stroke. These results were obtained in patients anticoagulated with only aspirin and Persantine. Heparin or Coumadin are not used in these patients unless indicated for other medical reasons. The lack of thromboembolic complications is significant in considering the duration of support, with the longest pneumatic patient at 324 days and the longest electric patient at 328 days and continuing. Average duration of support is approximately 3 months, with a total of over 14 patients years of experience.