VE LVAS for End-Stage Heart Failure

HeartMate Vented Electric Left Ventricular Assist System (VE LVAS): A New Option for Patients with End-Stage Heart Failure

Traditionally, patients with end-stage congestive heart failure (CHF) who were not transplant candidates, due to age, presence of insulin dependent diabetes mellitus (IDDM) with end-organ damage, chronic renal failure (CRF), or any other major co-morbidities, were treated primarily with pharmacologic therapy (including digoxin, angiotensin-converting enzyme (ACE) inhibitors, diuretics and inotropes). Many consider pharmacologic therapy to be only palliative because it has demonstrated only short-term improvements in survival for patients in moderate to severe heart failure.^1,2

On November 6, 2002 the Food and Drug Administration (FDA) approved the HeartMate Vented Electric Left Ventricular Assist System (LVAS) for use in patients with chronic end-stage heart failure who are ineligible for cardiac transplantation. This expanded indication, also known as Destination Therapy, was based upon the results of a landmark clinical trial, the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH).³

Device Description

The device used in the REMATCH study was the HeartMate VE LVAS which consists of an implanted blood pump (Figure 1), System Controller and external power supply components. The blood pump, is a pusher-plate type device with a stroke volume of up to 83 ml, generating a maximum of 10 liters of blood flow per minute at a beat rate up to 120 beats per minute.^4,5

The pump consists of a rigid titanium housing divided into two halves by a flexible polyurethane diaphragm. One half functions as the blood chamber, while the opposite half serves as a chamber for the electric motor. This motor chamber is connected to the external control and power components via a percutaneous tube. Displacement of the diaphragm by rotation of the electric motor results in the pumping of blood.^4,5

Power supply to the device can be provided by a pair of wearable, rechargeable batteries, or via connection to a dedicated power supply device called a Power Base Unit (PBU). An additional portable, back-up power source, the Emergency Power Pack (EPP), can be used in periods of extended power outage. In the event that electric motor actuation is disrupted, the LVAD may also be actuated by delivery of a pneumatic pulses through the percutaneous tube via the Hand Pump or a standard HeartMate Implantable Pneumatic Drive Console.^4,5

The System Controller is a microprocessor-based unit that initiates motor actuation, monitors and reports on system function, and serves as the primary interface with the system. The controller provides two modes of operation, either Fixed or Auto. The rate range for both modes is 50-120 beats per minute. In the Fixed Mode, the pump ejects at a pre-set beat rate per minute. In the Auto Mode the pump is responsive to physiologic demand and the pump’s beat rate will speed up or slow down based on preload to the LVAD.^4,5

The LVAD pump cycle works asynchronous to the electrical conduction of the native heart. The LVAS pump cycle is based on preload and filling pressures. The pump fills (diastole) passively from the left ventricle via a unidirectional porcine valve. When pump pressure exceeds left ventricular (LV) pressure, the inflow valve closes; then there is a short period of isovolumic pressurization within the pump. When pump pressure exceeds the pressure in the patient’s ascending aorta, the outflow valve opens and the pump ejects (systole).⁶

The blood pump’s unique design features textured blood contacting surfaces. These surfaces promote a thin, adherent coagulum that organizes into a biological matrix. The result is a low propensity for thrombus formation, requiring only low-level anticoagulation with anti-platelets drugs post-operatively.⁴

Rematch

The investigator-initiated REMATCH trial was conducted at 21 clinical sites and was a cooperative agreement among Thoratec Corporation, the National Institutes of Health (NIH), and Columbia University. Eligible patients were adults with chronic end-stage heart failure and contraindications to transplantation.³

Study Objectives

The primary objective of the study was to determine the effect of the HeartMate VE LVAS on all-cause mortality in patients with end-stage chronic heart failure who were receiving optimal medical management and were not candidates for cardiac transplantation.⁷ Adverse events and the incidence of device malfunction and failure were also documented in the LVAS patients.⁸

A number of secondary objectives were evaluated during the REMATCH study, including a comparison of functional status, serious adverse events, quality of life, days alive, days out of hospital, and symptoms of depression.^8,9

Study Hypothesis

Study hypothesis included a 33% reduction in the 2-year mortality rate of patients supported with the HeartMate LVAS compared to those patients treated with optimal medical management (OMM).^7,8

Results

A total of 129 patients (68 device and 61 controls) were enrolled, from May 15, 1998 to June 27, 2001, at 21 clinical sites. The patients had a median age of 69 years (range 34 to 84 years). The majority of patients (74%) had ischemic etiology of heart failure. Most patients were in New York Heart Association (NYHA) functional class IV (98%), and 70% were receiving IV inotropic support at baseline. The median baseline left ventricular ejection fraction (LVEF) was 18% (range 4 to 25%) and VO2 max was 9.5 ml/kg/min (range 3.9 to 13.9).⁹

Survival

The REMATCH study demonstrated that implantation of the VE LVAS was associated with a 48% relative reduction in the risk of death from any cause during the two year follow-up period and a 27% absolute reduction in one-year mortality. The Kaplan-Meier analysis showed significantly reduced mortality in the LVAS group.^7,9 The Kaplan-Meier estimates of survival (Figure 2) at one year were 52 percent in the device group and 25 percent in the OMM group (P=0.002), and at 2 years were 23 percent and 8 percent respectively (P=0.003).⁹

Quality of Life

The LVAS groups quality of life (QOL) was significantly improved as evidenced by the Minnesota Living with Heart Failure (MLWHF) score, the Beck Depression Inventory score and SF36 physical function scores. The functional status, as measured by the NYHA class was significantly improved in the LVAS patients as compared to the OMM patients. Within one month the LVAS patients had statistically improved functional status, which was maintained through month 12. After month 12 the sample sizes were too small for accurate analysis. Additionally, LVAS patients had reduced depressive symptoms to within normal range, below that of clinical depression, a phenomenon which was not seen in the OMM group. The only negative QOL impact was the issue of short-term post-operative pain, which is an obvious result of surgery for device implantation.⁹

Time Spent In and Out of Hospital

Median time spent in and out of the hospital was dramatically different in the two groups. The median survival of the LVAD group was 408 days compared to 150 days in the OMM group. LVAD patients enjoyed almost a full year of days out of the hospital during a two-year observation period, compared to OMM patients who enjoyed approximately 100 days out of the hospital.⁹

Discussion

The REMATCH trial demonstrates that long-term support with the HeartMate LVAS resulted in substantial improvement in survival and quality of life in patient with severe heart failure who were not candidates for cardiac transplantation.⁹

The HeartMate VE LVAS as a bridge to cardiac transplantation is currently approved for payment under Medicare DRG 525. Most private insurers pay for this indication as well.

On March 12, 2003 a Medicare Coverage Advisory Committee (MCAC) voted that the quality of the evidence was adequate to draw conclusions about the net health outcomes in Medicare beneficiaries comparable to patients enrolled in the REMATCH trial. Additionally, the Technology Evaluation Center (TEC) of Blue Cross and Blue Shield (BCBS) issued a positive assessment and also announced that the HeartMate VE LVAS as Destination Therapy improves net health outcomes.¹¹

Conclusions

Years of clinical experience and data have led to the use of LVADs for longer term support, in outpatients settings, and now as Destination Therapy. The REMATCH trial demonstrated that long-term support with the VE LVAS resulted in substantial survival in patients with severe end-stage heart failure who were not candidates for cardiac transplantation. FDA approval of the VE LVAS for non-transplant candidates represents a historic change in the world of medicine by expanding how LVADs can be used across different patient populations. Further, it provides a valuable new tool for doctors and a new treatment option for end-stage heart failure patients. The XVE has also recently been FDA approved for destination therapy as well.