Ventricular assist device

Pumps

The pumps used in VADs can be divided into two main categories – pulsatile pumps, that mimic the natural pulsing action of the heart, and continuous flow pumps. Pulsatile VADs use positive displacement pumps. In some pulsatile pumps (that use compressed air as the/a energy source), the volume occupied by blood varies during the pumping cycle. If the pump is contained inside the body then a vent tube to the outside air is required.

Continuous flow VADs are smaller and have proven to be more durable than pulsatile VADs. They normally use either a centrifugal pump or an axial flow pump. Both types have a central rotor containing permanent magnets. Controlled electric currents running through coils contained in the pump housing apply forces to the magnets, which in turn cause the rotors to spin. In the centrifugal pumps, the rotors are shaped to accelerate the blood circumferentially and thereby cause it to move toward the outer rim of the pump, whereas in the axial flow pumps the rotors are more or less cylindrical with blades that are helical, causing the blood to be accelerated in the direction of the rotor's axis.

An important issue with continuous flow pumps is the method used to suspend the rotor. Early versions used solid bearings; however, newer pumps, some of which are approved for use in the EU, use either magnetic levitation ("maglev") or hydrodynamic suspension. These pumps contain only one moving part (the rotor).

History

The first successful implantation of a left ventricular assist device was completed in 1966 by Dr. Michael E. DeBakey to a 37-year-old woman. A paracorporeal (external) circuit was able to provide mechanical support for 10 days after the surgery. The first successful long-term implantation of an artificial LVAD was conducted in 1988 by Dr. William F. Bernhard of Boston Children's Hospital Medical Center and Thermedics, Inc of Woburn, MA under a National Institutes of Health (NIH) research contract which developed Heart-mate, an electronically controlled assist device. This was funded by a three-year $6.2 million contract to Thermedics and Children's Hospital, Boston MA from the National Heart and Lung and Blood Institute, a program of the NIH. The early VADs emulated the heart by using a "pulsatile" action where blood is alternately sucked into the pump from the left ventricle then forced out into the aorta. Devices of this kind include the HeartMate IP LVAS, which was approved for use in the US by the Food and Drug Administration (FDA) in October 1994. These devices are commonly referred to as first generation VADs.

More recent work has concentrated on continuous flow pumps, which can be roughly categorized as either centrifugal pumps or axial flow impeller driven pumps. These pumps have the advantage of greater simplicity resulting in smaller size and greater reliability. These devices are referred to as second generation VADs. A side effect is that the user will not have a pulse, or that the pulse intensity will be seriously reduced.

Third generation VADs suspend the impeller in the pump using either hydrodynamic or electromagnetic suspension, thus removing the need for bearings and reducing the number of moving parts to one.

Another technology undergoing clinical trials is the use of trans cutaneous induction to power and control the device rather than using percutaneous cables. Apart from the obvious cosmetic advantage this reduces the risk of infection and the consequent need to take preventative action. A pulsatile pump using this technology has CE Mark approval and is in clinical trials for US FDA approval.

A very different approach in the early stages of development is the use of an inflatable cuff around the aorta. Inflating the cuff contracts the aorta and deflating the cuff allows the aorta to expand – in effect the aorta becomes a second left ventricle. A proposed refinement is to use the patient's skeletal muscle, driven by a pacemaker, to power this device which would make it truly self-contained. However a similar operation (cardiomyoplasty) was tried in the 1990s with disappointing results. In any case, it has substantial potential advantages in avoiding the need to operate on the heart itself and in avoiding any contact between blood and the device. This approach involves a return to a pulsatile flow.

Peter Houghton was the longest surviving recipient of a VAD for permanent use. He received an experimental Jarvik 2000 LVAD in June 2000. Since then, he completed a 91-mile charity walk, published two books, lectured widely, hiked in the Swiss Alps and the American West, flew in an ultra-light aircraft, and traveled extensively around the world. He died of acute renal failure in 2007 at the age of 69.

Recent developments

The majority of VADs on the market today are somewhat bulky. The smallest device approved by the FDA, the HeartMate II, weighs about 1 pound (0.45 kg) and measures 3 inches (7.6 cm). This has proven particularly important for women and children, for whom alternatives would have been too large.

One device gained CE Mark approval for use in the EU and began clinical trials in the US (VentrAssist). As of June 2007 these pumps had been implanted in over 100 patients. In 2009, Ventracor was placed into the hands of Administrators due to financial problems and was later that year liquidated. No other companies purchased the technology, so as a result the VentrAssist device was essentially defunct. Around 30–50 patients worldwide remain supported on VentrAssist devices as of January 2010.

The Heartware HVAD works similarly to the VentrAssist – albeit much smaller and not requiring an abdominal pocket to be implanted into. The device has obtained CE Mark in Europe, and FDA approval in the U.S. Recently, it was shown that the Heartware HVAD can be implanted through limited access without sternotomy.

In a small number of cases left ventricular assist devices, combined with drug therapy, have enabled the heart to recover sufficiently for the device to be able to be removed (explanted).

HeartMate II LVAD pivotal study

A series of studies involving the use of the HeartMate II LVAD have proven useful in establishing the viability and risks of using LVADs for bridge-to-transplantation and destination therapy.

HARPS

The Harefield Recovery Protocol Study (HARPS) is a clinical trial to evaluate whether advanced heart failure patients requiring VAD support can recover sufficient myocardial function to allow device removal (known as explantation). HARPS combines an LVAD (the HeartMate XVE) with conventional oral heart failure medications, followed by the novel β2 agonist clenbuterol. This opens the possibility that some advanced heart failure patients may forgo heart transplantation.

To date, 73% (11 of 15) of patients who underwent the combination therapy regimen demonstrated sufficient recovery to allow explantation and avoid heart transplantation; freedom from recurrent heart failure in surviving patients was 100% and 89% at one and four years after explantation, respectively; average ejection fraction was 64% at 59 months after explantation – all patients were NYHA Class I; and no significant adverse effects were reported with clenbuterol therapy.

REMATCH

The REMATCH (Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure) clinical trial began in May 1998 and ran through July 2001 in 20 cardiac transplant centers around the USA. The trial was designed to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. As a result of the clinical outcomes, the device received FDA approval for both indications, in 2001 and 2003, respectively.

The trial demonstrated an 81% improvement in two-year survival among patients receiving HeartMate XVE compared to optimal medical management. In addition, a destination therapy study following the REMATCH trial demonstrated an additional 17% improvement (61% vs. 52%) in one-year survival of patients that were implanted with a VAD (HeartMate XVE), with an implication for the appropriate selection of candidates and timing of VAD implantation.

A test carried out in 2001 by Dr. Eric A. Rose and REMATCH study group with patients with congestive heart failure that were ineligible for a transplant showed a survival at two years of 23% for those implanted with an LVAD compared with 8% for those who were treated with drugs. The two major complications of VAD implantation were infection and mechanical failure (see below).

According to a retrospective cohort study comparing patients treated with a left ventricular assist device versus inotrope therapy while awaiting heart transplantation, the group treated with LVAD had improved clinical and metabolic function at the time of transplant with better blood pressure, sodium, blood urea nitrogen, and creatinine. After transplant, 57.7% of the inotrope group had renal failure versus 16.6% in the LVAD group; 31.6% of the inotrope group had right heart failure versus 5.6% in the LVAD group; and event-free survival was 15.8% in the inotrope group versus 55.6% in the LVAD group.

Complications and side effects

Bleeding is the most common postoperative early complication after implantation or explantation of LVADs, necessitating reoperation in up to 60% of recipients. The implications of massive blood transfusions are great and include infection, pulmonary insufficiency, increased costs, right heart failure, allosensitization, and viral transmission, some of which can prove fatal or preclude transplantation. When bleeding occurs, it impacts the one year Kaplan-Meier mortality. In addition to complexity of the patient population and the complexity of these procedures contributing to bleeding, the devices themselves may contribute to the severe coagulopathy that can ensue when these devices are implanted.

Because the devices generally result in blood flowing over a non-biologic surface, predisposing the blood to clotting, there is need for anticoagulation measures. One device, the HeartMate XVE, is designed with a biologic surface derived from fibrin and does not require long term anticoagulation (except aspirin); unfortunately, this biologic surface may also predispose the patient to infection through selective reduction of certain types of leukocytes.

New VAD designs which are now approved for use in the European Community and are undergoing trials for FDA approval have all but eliminated mechanical failure.

VAD-related infection can be caused by a large number of different organisms:

Treatment of VAD-related infection is exceedingly difficult and many patients die of infection despite optimal treatment. Initial treatment should be with broad spectrum antibiotics, but every effort must be made to obtain appropriate samples for culture. A final decision regarding antibiotic therapy must be based on the results of microbiogical cultures.

Other problems include immunosuppression, clotting with resultant stroke, and bleeding secondary to anticoagulation. Some of the polyurethane components used in the devices cause the deletion of a subset of immune cells when blood comes in contact with them. This predisposes the patient to fungal and some viral infections necessitating appropriate prophylactic therapy.

Considering the multitude of risks and lifestyle modifications associated with ventricular assist device implant, it is important for prospective patients to be informed prior to decision making. In addition to physician consult, various Internet-based patient directed resources are available to assist in patient education.

List of implantable VAD devices

This is a partial list and may never be complete
Referenced additions are welcome