Case 3 -

Ventricular Assist Device: The Good, the VAD and the Ugly Jagdish Butany Toronto General Hospital Toronto, ON, Canada

Virtual Slides as well as Still Images are displayed below.
For the fastest viewing of virtual slides, click:



under each thumbnail image below. You must have Aperio ImageScope installed on your PC.

If you do not already have Aperio ImageScope, Windows users with administrator privileges may download and install a free version in order to view USCAP Virtual Slides. Click the icon on the right to get your free copy:

Or, click on slide thumbnail images to view each slide
in a Web-based slide viewer, which is somewhat slower.

If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137.

At autopsy the heart weighed 560.0 grams. There was cardiomegaly, biventricular hypertrophy and dilatation and showed features of "status post open heart surgery, left ventricular assist device attachment". The ventricular assist device was attached to the inflow cannula in the left ventricular assist device (LVAD) - attached to the left ventricular apex, while the outflow cannula of the LVAD was attached to the proximal ascending aorta on its anterolateral aspect. The anterior surface of the heart was covered with small amounts of blood clot, between a half and three-quarter centimeters thick. The posterior surface of the heart showed a considerably larger amount of soft clot, up to 2.0 cm in thickness and distending the posterior part of the pericardial sac. Temporary pacer wires were attached to the anterior surface of the right ventricle and right atrium. Case 3 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 3 - Figure 1 - The left side of the heart has been opened and shows the atrium , mitral valve and the left ventricle. The LV apex shows the inflow cannula (A) of the LVAD in place . The LVAD pump has been disconnected. The outflow cannula (B) is also seen. The LV endomyocardium close to the cannula, shows an interesting lesion, which was sectioned. Case 3 - Figure 2 - A low power section from the H&E stained slide shows the interventricular septum. (Stain H&E, Original Magnification x2.5) Case 3 - Figure 3 - A higher magnification of the upper boxed area , from the slide #1. (Stain H&E, Original Magnification x 10.0, ) Case 3 - Figure 4 - A higher magnification of the upper boxed area from slide # 2. (Stain H&E, Original Magnification x 20.0) Case 3 - Figure 5 - A higher power image from the lower box from slide #2,showing the Right ventricular aspect of the IV septum. (Stain H&E, Original Magnification x2.5) The ventricles were dilated, significantly more so than the atria. Of the two sides, the left atrium and the left ventricle appeared more dilated and the anterior wall of the left ventricle appeared to "cave in", suggesting myocardial damage. The right heart showed mild dilatation, dilatation of the tricuspid valve annulus and mild to moderate dilatation of the right ventricle. The right ventricular wall thickness was 0.4 and 0.5 cm. No significant epicardial fat was seen, nor was any significant endocardial change noted. The trabeculae carnae and the papillary muscles appeared unremarkable as did the right ventricular outflow tract. The left ventricular myocardium felt soft and had a somewhat "redundant" appearance in the anteroseptal region, mainly at the apex, and with evidence of epicardial hemorrhage. This gave the myocardium a mottled appearance. On opening the left ventricle, it was dilated at least 3x normal and showed extensive endocardial fibrosis. The mitral valve and the papillary muscles, as well as the chordae tendinae, were grossly unremarkable. There was endocardial fibrosis in the posterobasal region, virtually the entire interventricular septum and the anteroseptal wall right up to the left ventricular apex. In fact, the interventricular septum was aneurysmal. The inflow cannula of the ventricular assist device, protruded over 2.5 cm into the chamber, about 0.9 cm from the interventricular septum, at the left ventricular apex. A nearly circular piece (25 cent size) of septal myocardium, appeared to prolapse into the VAD cannula orifice. (You were provided with a section of this prolapsing piece of septal myocardium). This transseptal (full thickness) piece of tissue had a diameter of 1.7 cm, a thickness of about 0.8 to 0.9 cm. Gentle probing showed that the probe passed fairly easily into the right ventricle, about 3.0 cm from the apex. The interventricular septum was up to 0.8 cm in thickness, in this region. Sections through this piece of tissue, especially the marginal areas, showed a gradual (saw-like) cut of the margins with thrombus of varying degrees of organization. In summary, this heart showed cardiomegaly, severe three vessel coronary artery disease, and evidence of extensive left ventricular infarction. The septum was extensively aneurysmal and it appeared that the aneurysmal septum had repeatedly been "sucked into" the inflow cannula and the friction against this gradually led to its getting cut and prolapsing into the inflow cannula. This part of the septal myocardium was fibrotic. The right ventricular side (subendocardial) of the interventricular septum, at this area, was not involved by fibrosis and it appeared to have been sliced through in one shot and this was likely the last event since it showed no evidence of thrombus, either acute or old. Heart failure (HF) is a common problem worldwide. By far the commonest cause of HF is coronary artery disease and its resultant ischemic heart disease. In the United States, over 5 million individuals with heart failure are under treatment at any one time, while half a million are added to this list each year. There are many treatments for heart failure, ranging from drugs, combinations of several drugs to treatment of the underlying cause, by interventions and devices: valve replacement / repair aneurysmectomy and valve replacement / repair coronary artery bypass grafts and aneurysmectomy heart transplantations ventricular assist devices Of all of these modes of therapy, heart transplantation is by far the most effective long-term solution. However, there is a significant paucity of organs for transplantation and roughly 50% of individuals die on the waiting list, that is succumb to their disease before they can get a heart transplant. Ventricular assist devices are now believed to be a good alternative to heart transplantation and can be of several types. Temporary or for short periods VAD for longer devices Ventricular Assist Devices are Classified Broadly As: Bridge to treatment Bridge to transplantation and Destination therapy, that is the individual is not fit for, or cannot get a transplant organ or graft organ at all. Under the category of temporary devices these devices may be divided again into two categories. These are for: Temporary devices: devices that will be in place between 1 day and 2 weeks - Bridge to treatment and transplantation Devices that can be in place for a few days to five years and Devices that are meant to be the last assistance devices that the individual receives, since they are otherwise not suitable for a heart transplantation. Temporary Devices: These are made of polyesters or plastics and an example of this is the ABIOMED device. These are large plastic tubes and contain three cuspid valves made of synthetic materials which are see-through plastics. So far, thrombosis and infection are common problems, though common is relative and complications are really not very frequent. We have not seen the cusps in these devices tear, at least at this time. Bridge to Transplantation: There are several devices available for these and these have been used for the longest times. These can be used for the left and right ventricles, individually or simultaneously. Destination Therapy: These devices are relatively new and of these the HeartMate 2 is the one in clinical trials, at this time. Complications: The major complications associated with these devices are those that you can imagine associated with any materials in which leads extend from inside the body cavity to the outside with exposed portions. Infection: Many microorganisms. Bleeding: Difficulties in maintaining the patient's coagulation status, lead to bleeding, related to the prosthesis. In a previous presentation (last year), Dr. Robert Padera talked about the pathology of ventricular assist devices and the roles of biofilms. I will not discuss the role of biofilms but will concentrate on the common long-term mode of failure of these devices. The most common feature in these devices is related to the presence of a prosthetic heart valve, usually a porcine bioprosthesis in the two arms of the device. Each LVAD therefore has two prosthetic valves in it, commonly porcine, stentless bioprosthesis. Post-implantation complications associated with these devices pertain to: The bioprostheses in the device. The changes in the cusps range from fibrosis and thickening of the cusps. Thickening and calcification of the cusps. "Uptake" of serum Changes in the Native Aortic Valve : Changing technology has led to the development of fully implantable, versatile, as well as the new continuous flow pumps, axial flow or centrifugal for left ventricular and total heart assist. The new thing in these devices is of course their use as studies based on the information acquired from the use of the ventricular assist devices, has led to conclusions that depress myocardial function, can sometimes recover for offloading for a period of time, specifically with the use of the ventricular assist device. Itself however has a significant incidence of complications. Device Failure: Bleeding complications. Thromboembolism Alterations in immunity Infections Some of These Support Systems are as Follows: Extracorporal life support devices: e.g. centrifugal pumps, ABIOMED BVS5000 Pyrocorporal systems: ThoraTec, suitable for support up to three months Implantable, pulsed systems: NovaCor, WorldHealth Corporation (Ottawa, Canada - now moved to Utah), TCI HeartMate, ThoraTec Corporation. All of these are devices indicated as bridge to recovery and now bridge to transplantation, as well as destination therapies for patients in end-stage heart failure. Fully implantable heart devices: NovaCor 2, Arrowline Heart AVS-2000, Arrow International, Heart Saver VAD and World Heart Corporation. Some total artificial hearts were developed many years ago. Some of these are still implanted in some centers, e.g. Jarvic 7, CardioWest. The use of ventricular assist devices got us a very significant impetuous with the results of a rematch trial (Randomized evaluation of mechanical assistance for the treatment of congestive heart failure). This demonstrated a significantly increased survival in non-heart transplant candidate patients with severe congestive heart failure, who were treated with a permanently implanted left ventricular assist device (Heart Mate) compared with the optimum medical treatment. Recovery of Myocardial Function after Ventricular Assist Device Placement: Reverse remodeling. In some cases, myocardial function appears to recover after a ventricular assist device placement. This recovery is significant enough that the device itself can be explanted and the need for heart transplantation avoided. The occurrence of this scenario is relatively low and by and large only antidotal reports are available. Examples of conditions in which VAD have been successfully explanted are: Post cardiotomy cardiogenic shock. Acute myocarditis Pre-infarct congestive heart failure. Rarely has this occurred in the setting of chronic heart failure with idiopathic dilated cardiomyopathy. Mechanisms of Myocardial Recovery after VAD: The VAD support leads to hemodynamic, neohormonal and inflammatory changes, as well as structural, cellular and molecular changes in patients with end-stage heart failure. Other mechanisms that may contribute to this have been described and include the activity of transcription factor nuclear factor Kappa B, a regulated gene involved in cellular proteins against apoptosis, its reversal during LVAD support. Lee et al (Reference 34) showed a decreased activation of MMPs after LVAD support along with increased un-------------- collagen, suggesting a diminished damage to the extracellular matrix. While Mann and Tegtmyer (Reference 34) suggests that remodeling may be facilitated by reorganization of the collagen network and not only by changes in the biology of the muscle fibers. On the other hand, Liden et al., found that in patients with severe advanced heart failure, there was no significant cardiac recovery following the use of the LVAD. Global Failure: Often in patients with congestive heart failure, it is not just the left or the right ventricles that are involved. The use of a LVAD decompresses the left heart, in the hope that the right ventricle will be able to cope with the increased venous return. However, many of these patients have high pulmonary vascular resistance and the right ventricles may not be able to cope with this. In these patients, right ventricular dysfunction ensues with high transfusion rate, increased length of hospital stay and high mortality. These patients should be given aggressive medical therapy and perhaps some of them will need an RVAD at the same time as the LVAD. Surgical Considerations: It is perhaps inappropriate to go into these here. I would advise the readers to look up the more recent surgical papers on the LVAD. Anesthetic Considerations: Anesthetists need to become more familiar with the indications, changes in anesthesia that the presence of a ventricular assist device leads to. These patients are prone to anticoagulation related problems, need the circulating blood volumes to be managed differently and the systemic vascular resistance to be monitored. Complications: A few years ago, the most common cause of death, while on long-term support with the VAD, was: Infection: The cause of death in about 41% of cases. Failure of the device: Up to 17% of cases. This is gradually decreasing. Bleeding and device malfunction along with infection were the major causes of device failure. Neurologic events: more than 4x higher than in the medial therapy group. Seventy-six percent of patients in the device group were free of serious neurologic events without systemic anticoagulation and have of the serious neurologic events occurring in this group were transient and non-embolic. Immunity and Malfunction: A few years ago, device malfunction was high with the Heart Mate device, lower with the NovaCor and results were few in regard to the other devices since they were relatively few in implantations. Today, the incidence of device malfunction has been decreasing. Most of these devices have porcine bioprosthesis. The closing pressures in the in-flow valve are considering higher than in the out flow valve, a situation similar to that in the native heart. In the native heart, the mitral valve fails more frequently than the aortic and in this instance the in-flow valve fails more significantly. The mode of failure is similar to that of bioprosthesis implanted in the heart. These porcine bioprosthesis face similar changes and the complications are comparable and include thrombosis, cusp calcification and cusp tears. As the duration of implantation increases, so do changes and porcine bioprosthesis failure. References: Collard E, van Dyck MJ, Jacquet LM. Ventricular Assist Devices. Current Opinion in Anaesthesiology. 2003. Vol. 16(1): 33-43 Shannon D, Hallinan W, Massey HT, Ackerman MH. Mechanical Circulatory Support Devices. 2006. Vol 17(4): 368-373 Gradaus R, Kerber S, Bocker D, et al. Therapeutic options and heart failure survival score predictability in an academic heart failure center: an analysis of 120 consecutive patients during a 1-year period. Eur J Heart Fail 2002; 4: 207-214. Cooley DA. Initial clinical experience with the Jarvik 2000 implantable axial-flow left ventricular assist system. Circ 2002; 105: 2808-2809. McGovern PC, Chambers S, Blumberg EA, et al. Successful explanation of a ventricular assist device following fulminant influenza type A-associated myocarditis. J. Heart Lung Transplant 2002; 21:290-293. Tisol WB, Mueller DK, Hoy FB et al. Reversible activation of nuclear factor-kappaB in human end-stage heart failure after left ventricular mechanical support. Cardiovasc Res 2002; 53: 124-130. Li YY, Feng Y, McTiernan CF, et al. Downregulation of matrix metalloproteinases and reduction in collagen damage in the failing human heart after support with left ventricular assist devices. Circ 2001; 104: 1147-1152 Barbone A, Holmes JW, Heerdt PM, et al. Comparison of right and left ventricular responses to left ventricular assist device support in patients with severe heart failure: a primary role of mechanical unloading underlying reverse remodeling. Circ 2001; 104: 670-675 Helman DN, Maybaum SW, Morales DLS, et al. Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable? Ann Thorac Surg 2000; 70: 1255- 1258. Kavarana MN, Pessin-Minsley MS, Urtecho J, et al. Right ventricular dysfunction and organ failure in left ventricular assist device recipients: a continuing problem. Ann Thorac Surg 2002; 73: 745 - 750. Rose EA, Gelijns AC, Moskowitz AJ, et al. Long-term left ventricular assistance for end-stage heart failure. N Engl J Med. 2001; 345: 1435 - 1443. Thom T, Haase N, Rosamond W et al. Heart Disease and Stroke Statistics - 2006 Update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circ 2006; 113: 85-151 Khan NA, Butany J, Zhou T, Ross HJ, Cusimano RJ, Rao V. Pathological findings in explanted porcine bioprostheses from ventricular assist devices. (In Press).