All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- November 6, 1999 - Mechanical heart support devices are called ventricular assist devices (VADs). There are 3 types of VADs - intra-aortic balloon pump (IABP), nonpulsatile devices, and pulsatile devices. Nonpulsatile VADs are external pump-driven devices that were designed for short-term support. Pulsatile VADs are air or electric powered and are the most advanced type of VAD device. Pulsatile VADs have gained widespread acceptance as medium- and long-term bridges to heart transplant. Pulsatile VADs, whether external or implantable, can be used for longer periods of time than nonpulsatile devices. Pulsatile VADs are described below: External VADs: Abiomed BVS 5000 by ABIOMED Inc - The ABIOMED BVS 5000 is FDA approved for acute viral myocarditis and right heart assist. Thoratec VAD by Thoratec Laboratories, Inc - The Thoratec VAD is used for short or long-term support. It has FDA approval for bridge to transplant. Implantable VADs: Novacor Left Ventricular Assist System by Baxter Healthcare - The Novacor is an electrical pump powered by a battery pack. The Novacor has FDA approval only for left ventricular support as bridge to transplant. Thermo-Cardiosystems Heartmate (TCI Heartmate) by Thermo- Cardiosystems. The TCI Heartmate is available as a pneumatically or electrically driven pump. It has FDA approval for left ventricular support as bridge to transplant. Total Artificial Heart: CardioWest Total Artificial Heart by CardioWest Technologies AbioCor by ABIOMED, Inc. LionHeart LVD LVAS 2000 by Arrow International, Inc. Although designed as a temporary support of the patient in acute heart failure, VAD benefits have been most dramatic in patients with *chronic* heart failure. Dr. James Young from the Cleveland Clinic opened the conference. In an overview of the development of such devices, Dr. Young described 4 reasons for using them: 1) bridge to heart transplant: support until donor heart is available 2) bridge to recovery: heart recovers and there is no need for transplant 3) bridge to bridge: use of a short-term device and later replacement with a longer-term device 4) destination therapy: permanent device as an alternative to transplant. What patients will benefit most from these therapies? Which device is most appropriate? When is the best time to start therapy? What is the best management of patients with these devices? According to Dr. Mehmet Oz, even though about half of CHF patients die so suddenly they would not benefit from device therapy, it is possible that many of the remaining half could. Dr. Oz presented outcomes of a referral network established in the New York City area. Heart surgery centers in the New York area were encouraged to refer patients as early as possible to the hub of this network, Columbia- Presbyterian Medical Center, for early management and LVAD implant. Findings of 37 patients were reported. Twenty-one patients (57%) received LVADs, 10 patients (27%) recovered without mechanical support, and 6 patients (16%) died. In the device group, 67% had an intra-aortic balloon pump and 43% had an external VAD. The treatments resulted in a 68% survival rate compared with a predicted 20% discharge rate for patients with shock after heart surgery. Dr. Oz concluded that regional networks centered around bridge to transplant centers with LVAD implant capability might significantly improve survival of patients with CHF after heart surgery. Dr. Oz also reported on an analysis of 100 long-term LVADs at Columbia-Presbyterian. One hundred LVADs were implanted in 95 patients over 7 years. The overall survival rate was 75% and the transplant rate was 70%, indicating that some patients recovered enough heart function to avoid transplant. Dr. Nicholas Smedira from the Cleveland Clinic, described his center's experience of implanting 200 LVADs (Novacor and TCI Heartmate). He detailed their lessons learned about device malfunction and failure since treatment of their first 100 patients. Infection and blood clots/stroke were the main problems seen. About 25% of the patients needed later surgery for bleeding after implant. Dr. Smedira identified 3 goals for continuing VAD development: 1) improved mechanical reliability and durability 2) decreased potential for clots 3) elimination of through-the-skins lines so that devices are completely implanted, eliminating a main source of infection. Dr. Jack Copeland was next. Factors that weigh heavily on patient survival include making the best match between each patient and type of device, timing of intervention, and best management after implant. No one device is suitable for all patients. For example, Novacor had the highest rate of neurologic events, but proved best for patients with small body size. Cardiowest, on the other hand, was best suited for larger patients. Patients implanted with the total artificial heart had the highest rate of survival before transplant, and patients who were treated with a Thoratec did not survive as long after transplant. However, Dr. Copeland said that Thoratecs were implanted in the most deteriorated patients in the study. Discussion then centered on the need for a national database for comparing devices. In addition to the call for more head-to-head comparisons of various devices, other areas of needed research were said to be: neurohumoral responses to heart failure, recovery of heart function, and complications associated with long-term device use such as infection, clot/stroke, and high blood pressure. Baxtor's Dr. Peer Portner described results of 1000 patients treated at multiple centers with the Novacor over the last 15 years. The Novacor is a wearable system and may be used either as a permanent or temporary device. Most of these patients (94%) were bridged to transplant for heart failure due to nonischemic cardiomyopathy. The average length of device use was 7 months. The longest implant time was 1110 days. Early complications included postinsertion bleeding, right heart failure, kidney failure, and liver failure. Neurologic problems and infection were the main complications seen later in treatment. Dr. Portner discussed the benefits of early hospital discharge of patients with LVADs waiting for transplant. Not only is it less costly but quality of life is better. Dr. Kormos also addressed quality of life. He reported on a survey of 35 LVAD patients, interviewed at 2 and 3 months after implant. Patients reported better functionality (97%), agreed to a device for a relative (97%), and had a more positive outlook on life (89%). Patient concerns included infection (45%), sleep problems related to the driveline (40%), device malfunction (37%), and device noise (33%). Dr. William Holman discussed frequently occurring infections in VAD patients. Infection is the problem with extended LVAD use. Dr. Holman estimated that 40-50% of bridge to transplant patients experience infection. Potential types of infection identified were: 1) bloodstream infections 2) pump endocarditis 3) infection of internal components such as valves 4) pocket infection 5) external surface infections not involving device drive lines 6) drive line infections which occur where materials pass through the skin The adhesive properties of some bacteria and fungi allow them to stick to the surfaces of the device, forming a "biofilm" which serves as a barrier to host defenses and antibiotics, and allows cells to reproduce. Eventually bacteria are ejected from the biofilm and cause sepsis and immune reactions. Dr. Holman discussed ways to diagnose, prevent and treat device-related infections. Blood clots/stroke remain a problem with VADs. Dr. William Wagner said that given the extent of biomaterial surface area implanted, the complex flow environment, and long periods of support, these are expected problems in VAD patients. Dr. Talia Spanier discussed neurohumoral issues arising from VAD use. According to Dr. Spanier, a series of events transforms the VAD from a machine into an organ that inflames the immune system. Cells that live on the VAD surface create an inflammatory environment that causes T and B cell reaction in some patients. Efforts to prevent this are use of Aprotinin to prevent clots, aspirin and steroids as anti-inflammatory agents, and cyclosporine, immunoglobulins and cyclophosphamide to weaken the immune system. Recently, hypertension (high blood pressure) has been reported in VAD patients. Dr. Srinivas Murali reported on an analysis of 75 patients to measure hypertension in CHF patients on temporary VAD support. The incidence of hypertension in patients with a Novacor (electric VAD support) was compared to that seen in patients with a Thoratec (pneumatic VAD support). Hypertension was 80% in the Novacor group, 38% in the Thoratec LVAD group, and 60% in the Thoratec BiVAD group). The death rate between patients with high blood pressure and those without was compared. In normal pressure patients, the death rate was 10% fro Novacor and 8% for Thoratec. The death rate in hypertensive patients was 13% for Novacor and 21% for Thoratec. Hypertensive patients were twice as likely to have an adverse neurological event. Drs Guillermo Torre, Kenneth Margulies, Donna Mancini and Douglas Mann discussed using LVADs as a way to recover heart function in heart failure patients. Tumor necrosis factor alpha (TNF) is an inflammatory cytokine produced by heart cells in patients with advanced heart failure. TNF is thought to be partly responsible for the heart remodeling that makes CHF patients worse, and to have negative inotropic effects. Evidence for heart function and neurohumoral improvement after prolonged LVAD use include: 1) less heart stiffness 2) normalization of neurohormone levels, including TNF-alpha, norepinephrine, renin, and atrial natriuretic peptide (ANP) 3) decrease in cell volume, size 4) increased contractility and relaxation Dr. Joannes Mueller reported differences in patients who recovered vs those who did not in patients followed for over 4 years. Of 107 patients, 24 were weaned and 14 had lasting recovery from 5 months to 5 years. Length of heart failure before implant, time from implant to device removal, and left ventricular size and ejection fraction before implant were factors in recovery. Dr. Douglas Mann cautioned that normalization of heart structure does not necessarily mean that heart function is normalized. Even though partial recovery rates may be as high as 50%, only a few patients achieve enough recovery to allow device removal. The ultimate goal of VAD research is to develop an implantable system for long-term use outside the hospital setting. In the next 10 years, it is likely that VADs will be used as a permanent treatment for some CHF patients. Updates on devices in development were also described. The reduced pulsatile systems included the Magnetic Bearing Action Flow Pump, the Heartmate II VAD, a third-generation rotary pump, and the DeBakey VAD. The pulsatile systems in development are the Lion Heart LVAS, HeartSaver VAD, and Abiomed AbioCor Implantable Replacement Heart. LionHeart LVD LVAS - Dr. Walter Pae Jr described the Lion Heart LVD LVAS by Arrow International, Inc. It is being designed as a permanent implant. Development began in 1994 and to date, 23 in vivo and 20 in vitro studies have been completed. The Lion Heart LVD LVAS is fully implantable with an across-the-skin energy transmission so there are no wires piercing the skin. The cardiac output control is fully automatic at flow rates from 3-7 liters per minute. The battery power pack, weighing almost 8 pounds has a 6-hour capacity and recharges rapidly. The first human was implanted with this device in late October of 1998 in Germany. Pending FDA approval, a clinical trial of Lion Heart LVD LVAS in the USA is expected to begin in early 2000. HeartSaver VAD - Dr. Tofy Mussivand reported the latest information on the HeartSaver VAD, a totally implantable, pulsatile VAD. The HeartSaver VAD is remotely powered by means of acroos-the-skin energy transfer monitored and controlled by a telemetry system. Preclinical studies have been completed. Abiomed AbioCor Implantable Replacement Heart - Progress of the AbioCor Replacement Heart by Abiomed, Inc was described by Dr. Robert Dowling. The AbioCor is fully implantable with no wires piercing the skin, and has 2 pumping chambers and trileaflet valves. It consists of an electrically driven centrifugal pump that provides continuous, one directional hydraulic fluid motion. A second electrical motor alternatively drives the left and right pumping chambers to produce alternate right and left "contraction." Animal studies began on this device at the Texas Heart Institute in 1991. The AbioCor has been implanted into 18 calves - 16 have had a normal recovery. Clinical trials are expected to begin by 2001. Title: Mechanical Cardiac Support and Replacement: Evolving Strategies for Congestive Heart Failure Authors: Peggy Keen, Susan L. Smith Source: International Society for Heart and Lung Transplantation Second Annual Fall Education Meeting