The objective of this health technology policy assessment was to determine the effectiveness and cost-effectiveness of using implantable ventricular assist devices in the treatment of end-stage heart failure.
Heart failure is a complex syndrome that impairs the ability of the heart to maintain adequate blood circulation, resulting in multiorgan abnormalities and, eventually, death. In the period of 1994 to 1997, 38,702 individuals in Ontario had a first hospital admission for heart failure. Despite reported improvement in survival, the five-year mortality rate for heart failure is about 50%.
For patients with end-stage heart failure that does not respond to medical therapy, surgical treatment or traditional circulatory assist devices, heart transplantation (in appropriate patients) is the only treatment that provides significant patient benefit.
Heart Transplant in Ontario
With a shortage in the supply of donor hearts, patients are waiting longer for a heart transplant and may die before a donor heart is available. From 1999 to 2003, 55 to 74 people received a heart transplant in Ontario each year. Another 12 to 21 people died while waiting for a suitable donor heart. Of these, 1 to 5 deaths occurred in people under 18 years old. The rate-limiting factor in heart transplant is the supply of donor hearts. Without an increase in available donor hearts, attempts at prolonging the life of some patients on the transplant wait list could have a harmful effect on other patients that are being pushed down the waiting list (knock on effect).
Ventricular assist devices [VADs] have been developed to provide circulatory assistance to patients with end-stage heart failure. These are small pumps that usually assist the damaged left ventricle [LVADs] and may be situated within the body (intracorporeal] or outside the body [extracorporeal). Some of these devices were designed for use in the right ventricle [RVAD] or both ventricles (bi-ventricular).
LVADs have been mainly used as a “bridge-to-transplant” for patients on a transplant waiting list. As well, they have been used as a “bridge-to-recovery” in acute heart failure, but this experience is limited. There has been an increasing interest in using LVAD as a permanent (destination) therapy.
Review of LVAD by the Medical Advisory Secretariat
The Medical Advisory Secretariat’s review included a descriptive synthesis of findings from five systematic reviews and 60 reports published between January 2000 and December 2003. Additional information was obtained through consultation and by searching the websites of Health Canada, the United Network of Organ Sharing, Organ Donation Ontario, and LVAD manufacturers.
Summary of Findings
Safety and Effectiveness
Previous HTAs and current Level 3 evidence from prospective non-randomized controlled studies showed that when compared to optimal medical therapy, LVAD support significantly improved the pre-transplant survival rates of heart transplant candidates waiting for a suitable donor heart (71% for LVAD and 36% for medical therapy). Pre-transplant survival rates reported ranged from 58% to 90% (median 74%). Improved transplant rates were also reported for people who received pre-transplant LVAD support (e.g. 67% for LVAD vs 33% for medical therapy). Reported transplant rates for LVAD patients ranged from 39% to 90% (median 71%).
Patient’s age greater than 60 years and pre-existing conditions of respiratory failure associated with septicemia, ventilation, and right heart failure were independent risk factors for mortality after the LVAD implantation.
LVAD support was shown to improve the New York Heart Association [NYHA)] functional classification and quality of life of patients waiting for heart transplant. LVAD also enabled approximately 41% - 49% of patients to be discharged from hospitals and wait for a heart transplant at home. However, over 50% of the discharged patients required re-hospitalization due to adverse events.
Post-transplant survival rates for LVAD-bridged patients were similar to or better than the survival rates of patients bridged by medical therapy.
LVAD support has been associated with serious adverse events, including infection (median 53%, range 6%–72%), bleeding (8.6%–48%, median 35%), thromboembolism (5%–37%), neurologic disorders (7%–28%), right ventricular failure (11%–26%), organ dysfunction (5%–50%) and hemolysis (6%–20%). Bleeding tends to occur in the first few post-implant days and is rare thereafter. It is fatal in 2%–7% of patients. Infection and thromboembolism occurred throughout the duration of the implant, though their frequency tended to diminish with time. Device malfunction has been identified as one of the major complications. Fatalities directly attributable to the devices were about 1% in short-term LVAD use. However, mechanical failure was the second most frequent cause of death in patients on prolonged LVAD support. Malfunctions were mainly associated with the external components, and often could be replaced by backed up components.
LVAD has been used as a bridge-to-recovery in patients suffering from acute cardiogenic shock due to cardiomyopathy, myocarditis or cardiotomy. The survival rates were reported to be lower than in bridge-to-transplant (median 26%). Some of the bridge-to-recovery patients (14%–75%) required a heart transplant or remained on prolonged LVAD support. According to an expert in the field, experience with LVAD as a bridge-to-recovery technology has been more favourable in Germany than in North America, where it is not regarded as a major indication since evidence for its effectiveness in this setting is limited.
LVAD has also been explored as a destination therapy. A small, randomized, controlled trial (level 2 evidence) showed that LVAD significantly increased the 1-year survival rate of patients with end-stage heart failure but were not eligible for a heart transplant (51% LVAD vs 25% for medical therapy). However, improved survival was associated with adverse events 2.35 times higher than medically treated patients and a higher hospital re-admission rate. The 2-year survival rate on LVAD decreased to 23%, although it was still significantly better compared to patients on medical therapy (8%). The leading causes of deaths were sepsis (41%) and device failure (17%).
The FDA has given conditional approval for the permanent use of HeartMate SNAP VE LVAS in patients with end-stage heart failure who are not eligible for heart transplantation, although the long-term effect of this application is not known.
In Canada, four LVAD systems have been licensed for bridge-to-transplant only. The use of LVAD support raises ethical issues because of the implications of potential explantation that could be perceived as a withdrawal of life support.
Potential Impact on the Transplant Waiting List
With the shortage of donor hearts for adults, LVAD support probably would not increase the number of patients who receive a heart transplant. If LVAD supported candidates are prioritized for urgent heart transplant, there will be a knock on effect as other transplant candidates without LVAD support would be pushed down, resulting in longer wait, deterioration in health status and die before a suitable donor heart becomes available.
Under the current policy for allocating donor hearts in Ontario, patients on LVAD support would be downgraded to Status 3 with a lower priority to receive a transplant. This would likely result in an expansion of the transplant waiting list with an increasing number of patients on prolonged LVAD support, which is not consistent with the indication of LVAD use approved by Health Canada.
There is indication in the United Kingdom that LVAD support in conjunction with an urgent transplant listing in the pediatric population may decrease the number of deaths on the waiting list without a harmful knock-on effect on other transplant candidates.
LVAD support as a bridge-to-transplant has been shown to improve the survival rate, functional status and quality of life of patients on the heart transplant waiting list. However, due to the shortage of donor hearts and the current heart transplant algorithm, LVAD support for transplant candidates of all age groups would likely result in an expansion of the waiting list and prolonged use of LVAD with significant budget implications but without increasing the number of heart transplants. Limited level 4 evidence showed that LVAD support in children yielded survival rates comparable to those in the adult population. The introduction of LVAD in the pediatric population would be more cost-effective and might not have a negative effect on the transplant waiting list.