To conduct a randomized, unblinded clinical trial comparing the left ventricular assist device (LVAD) with maximum medical management in patients with end-stage heart failure who were not candidates for heart transplantation.

BACKGROUND:

Mortality rates for heart failure are high, with five year survival rates approximating 30 to 40 percent in patients with mild to moderate symptoms and 0 to 20 percent survival in patients with severe symptoms. The patient with class IV heart failure has a one year survival rate of only 40 to 50 percent. This is despite advances in medical therapy and the availability of ACE inhibitors. While cardiac transplantation is the most viable form of treatment for these patients, it is limited by complications of chronic immunosuppression, the development of graft coronary artery disease and the serious shortage of donor organs. As many as 16,500 patients per year may be suitable candidates for heart transplantation. The actual number of donor hearts procured over the past few years, however, has remained relatively constant at 2,000. Thus, there is a strong rationale for the therapeutic application of left ventricular assist devices (LVADs) as an alternative to cardiac transplantation.

With respect to LVAD efficacy, patients have been supported for periods as long as 344 days on the pneumatic system and 503 days with the electromechanical device. Experience with the TCI pneumatic system in 75 LVAD patients show improved one year survival after transplantation in the LVAD patients as opposed to patients who did not receive the LVAD despite the same selection criteria. Experience with the vented electric LVADs in bridge patients show a transplant and survival rate that is similar to the pneumatic device. LVADs have also been shown to have a favorable effect on circulatory hemodynamics and exercise capacity. Among 53 patients who survived the TCI LVAD procedure, 90 percent improved to New York Heart Association (NYHA) functional class I and 10 percent to functional class II.

With respect to safety, the principal adverse effects associated with the LVADs include bleeding, hemolysis, and organ dysfunction, thromboembolism, infection, right heart failure, and mechanical failure. Thromboembolic complications are low in the TCI device despite the lack of systemic anticoagulation. The overall mechanical failure rate is small, less than 1 percent in 26 patient years of use. The vented electric and pneumatic device experience to date indicates that the devices are similar with respect to adverse event rates. Thus, in 1997 there was a strong rationale for a randomized controlled trial that compared the benefits and cost of vented electric LVADs to medical treatment. The need to perform a randomized controlled study was further emphasized by the lack of rigorous data on survival, quality of life, and cost effectiveness comparing LVAD support with medical therapy.

DESIGN NARRATIVE:

Unblinded, randomized, multicenter. Patients were randomized to either the Thermo Cardiosystems, Inc. (TCI) vented electric (VE) LVAD or optimal medical therapy (OMM) and followed for at least two years. If randomized to LVAD therapy, patients received a LVAD implantation within 12 hours of randomization. If randomized to medical therapy, patients received optimal medical management including the use of digoxin, diuretics, and ACE (Angiotensin Converting Enzyme) inhibitors in maximally tolerated doses. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular mortality, exercise capacity (six-minute walk test) and health-related quality of life, adverse effects, and the relative cost-effectiveness of LVADs versus medical management. Recruitment ended in June, 2001.

Inclusion Criteria

1. Men and women with Class III and Class IV congestive heart failure
2. Between the ages of 18 and 72

Exclusion Criteria

1. Candidates for heart transplantation