The Journal of Heart and Lung Transplantation
Volume 29, Issue 12 , Pages 1321-1329, December 2010

Aortic valve pathophysiology during left ventricular assist device support

  • Ranjit John, MD

      Affiliations

    • Division of Cardiothoracic Surgery, Department of Surgery, University of Minnesota, Minneapolis, Minnesota
    • Corresponding Author InformationReprint requests: Ranjit John, MD, Division of Cardiothoracic Surgery, University of Minnesota Minneapolis, MN 55455. Telephone: 612-626-3664. Fax: 612-625-1683
    • ,
  • Katie Mantz, BS

      Affiliations

    • Department of Biomedical Engineering, University of Minnesota, Minneapolis, Minnesota
    • ,
  • Peter Eckman, MD

      Affiliations

    • Department of Medicine, University of Minnesota, Minneapolis, Minnesota
    • ,
  • Alan Rose, MD

      Affiliations

    • Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
    • ,
  • Karen May-Newman, PhD

      Affiliations

    • Bioengineering Program, Department of Mechanical Engineering, San Diego State University, San Diego

published online 02 August 2010.

Article Outline

The increased applicability and excellent results with left ventricular assist devices (LVADs) have revolutionized the available treatment options for patients with advanced heart failure. Pre-existing valve abnormalities are common in this population, and subsequent development of valve abnormalities after LVAD placement is also often noted. Although native mitral and tricuspid valve disease is more common in heart failure patients before LVAD placement, aortic valves are much more likely to generate abnormal pathophysiology in the LVAD patient during as well as after LVAD placement. The aim of this comprehensive review is to review aortic valve function in LVAD patients and highlight the consideration of pre-existing valve disease on patient treatment at the time of LVAD implant. The basis for structural changes leading to valve pathophysiology during and after LVAD placement will be described, providing a basis for improved clinical understanding and new strategies to prevent these conditions.

Keywords: heart failure, ventricular assist device, aortic valve

 

Heart transplant remains the gold standard treatment of patients with end-stage heart failure, yet the shortage of adequate donors has led to the effective use of left ventricular assist devices (LVADs) in such patients.1, 2, 3 Success with LVADs as bridge-to-transplant therapy has now led to their successful use as an alternative altogether to transplants, that is, as destination therapy.4

It is well recognized that coexisting heart valve disease might complicate the placement and efficient functioning of LVADs. However, significantly abnormal valve pathophysiology can also occur after LVAD placement and can seriously interfere with its benefits.5 Native mitral and tricuspid valve disease is certainly more common in the heart failure patients who are most likely to undergo LVAD placement. Nonetheless, aortic valves are much more likely to undergo structural changes and lead to abnormal pathophysiology in the LVAD patient, both during as well as after LVAD placement. This article will provide a background on aortic valve function in LVAD patients and highlight the consideration of pre-existing valve disease on patient treatment at the time of LVAD implant. The basis for structural changes leading to valve pathophysiology during LVAD will be described, providing a basis for improved clinical understanding and new strategies. The development of aortic valve disease in LVAD patients is a consequence of the altered biomechanics of the cardiovascular system, which can be affected by the LVAD-host integration. The current clinical strategy for LVAD patients must be constantly reassessed in light of recent findings.

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Methods 

The PubMed databases were used to perform an extensive search of the English language literature published between 1980 and 2008 using the keywords “ventricular assist devices” and “aortic valve.” Additional studies were identified from references cited in publications found using the search terms as well as in relevant published review articles.

Management of aortic valve pathophysiology at the time of LVAD placement 

Altered aortic valve biomechanics in LVAD patients 

The biomechanics of the aortic valve are clearly altered in patients with LVADs.5, 6, 7 The LVAD diverts blood from the LV directly into the aorta, increases cardiac output, and decreases LV pressure. LVADs decrease the load on the ventricle and reduce wall stress, which encourages reverse remodeling and results in a reduced ventricular cavity size. Another consequence of the decrease in LV pressure is an increase in the pressure difference between the aortic root and the LV, also known as the transvalvular pressure (TVP) of the aortic valve.5, 6 The valve opens when the TVP is near zero and closes under pressure load. The TVP is increased in both magnitude and duration in LVAD patients, which effectively results in a prolonged diastolic period for the aortic valve (Figure 1).

  • View full-size image.
  • Figure 1. 

    Transvalvular pressure for three different blood flow paths through the heart: normal (no LVAD), series, and parallel. The time series were obtained by subtracting the left ventricular pressure from the aortic pressure for several cardiac cycles.

During periods of high LVAD support, blood flow occurs entirely through the LVAD, the aortic valve is continuously closed, and the heart operates in series with the pump. With sufficient intrinsic contraction, the 2 pumps operate in parallel (Figure 2). Even under parallel flow conditions, the aortic valve does not open fully, exhibiting a reduced opening area and duration (Figure 3). Thus, the LVAD shifts the pressure load away from the mitral valve and LV to the aortic valve, which is not designed for this loading. The valve no longer cycles between open and closed states, but instead, the tissue is stretched to its maximum continuously, without cyclic relaxation. This mechanical condition likely stresses the valve tissue and leads to deterioration and remodeling.

  • View full-size image.
  • Figure 2. 

    (A) When the aortic valve does not open, the left ventricle (LV) functions in series with the LV assist device (LVAD). (B) If the heart pumps strongly enough to open the valve, the ventricle is operating in parallel with the LVAD. LA, left atrium; RA, right atrium; RV, right ventricle.

Influence of anatomic and fluid mechanics of the human aorta on aortic valve pathophysiology in LVAD patients 

The anatomic and fluid mechanics of the aortic root have been the subject of study for centuries, with a particular focus on the interplay between the valve and the region of the aorta immediately adjacent, known as the sinuses of Valsalva.8 The aortic valve leaflets, the aortic root, and sinus walls function together as an integrated system that participates in stress sharing while controlling blood flow from the heart to the rest of the body. The aortic sinus geometry and material properties are important in this mechanism, as the sinuses expand with pressure to increase the volume in that region by 20% to 35%.9, 10, 11 The cyclic distension of the aortic sinuses is critical for normal valve biomechanics, which depends on both the distensibility of the sinus tissue as well as the pressure cycle in the aortic root.12 Both the vortex formation and the pulsatility of pressure are important for optimal aortic root-valve function.

VAD implantation dramatically changes the fluid dynamics of the aortic root. When the aortic valve opens, the amount of forward flow is greatly reduced as is the leaflet opening. The formation of vortices is disrupted by the retrograde flow from the VAD, which contributes to early valve closure and shortened systole. When the valve is closed, as in many VAD patients, flow in the aortic root occurs due to retrograde flow from the VAD outflow conduit, which is often several centimeters away. The retrograde flow may follow a fluid trajectory that “washes out” the bulbous geometry of the aortic root and prevents thrombus formation. Two of the 3 sinuses are drained by coronary arteries, which promotes blood flow in the aortic root, but the third noncoronary sinus is at risk for thrombus formation due to stagnation of the blood in that location.

Another difference in the VAD-assisted heart is the propagation of pressure pulsatility from the LV to the aorta and blood. In the normal heart, the aorta sees a systolic to diastolic pressure change of about 40 mm Hg when the LV changes 90 to 100 mm Hg. When the VAD is providing a low level of support, the aortic pressure variation is reduced to 10 to 30 mm Hg after a reduction in LV pressure variation to 50 to 60 mm Hg. The higher levels of VAD support further decrease the pulsatility of pressure in the aorta, as does a closed aortic valve. The decrease in pulsatility in the aortic root does not mimic the normal physiology and may contribute further to the abnormal aortic valve biomechanics that has been linked to aortic valve insufficiency in a significant fraction of VAD patients.6, 7 Further, the established relationship between aortic root dilatation and aortic incompetence (AI) may suggest that the presence of aortic dilatation in a LVAD patient (even without pre-existing AI), may favor the development of subsequent AI.13

Changes in the exterior of the aortic root, such as the presence of an aortic graft anastomosis or even spraying the exterior with adhesives, may also increase the stress loading on the leaflets as a result of loss of sinus compliance. This may potentially alter the normal degenerative process of the aortic valve leaflets.14

Pre-existing aortic stenosis 

Pre-existing aortic stenosis (AS) does not adversely affect the normal functioning of an LVAD because LVAD patients are not dependent on significant antegrade flow through the aortic valve for cardiac output. However, if the LVAD is placed with the possibility of LV recovery, then a stenotic aortic valve should be replaced with a tissue valve, preferably at the time of LVAD placement (note that this situation is extremely rare). Only in such circumstances should replacing a severely stenotic aortic valve be considered; otherwise, pre-existing AS should be left alone.

Pre-existing aortic incompetence 

The aortic valve is constantly exposed to high TVP from the LVAD. As a result, pre-existing AI tends to worsen over time in LVAD patients, resulting in a circulatory loop, with blood returning from the outflow graft back to the LVAD through the incompetent aortic valve. This causes ineffective recirculation that substantially increases the pump work and decreases systemic perfusion.

With the potential for AI to worsen with LVAD support, we recommend that AI be corrected during LVAD implantation. Intraoperative transesophageal echocardiography (TEE) is the ideal way to diagnose and quantify the degree of AI, although the degree might be underestimated with reduced afterload when the patient is under general anesthesia.

The various options mentioned in the literature to treat AI before LVAD placement have included medical care (afterload reduction medications such as hydralazine and diuretics), closure of the native valve (with sutures), valve replacement with a bioprosthetic valve, or patch closure of the aortic/LV outflow tract.15, 16, 17, 18, 19, 20 The optimal method of treating AI remains unclear, but due to significant shortcomings in other approaches outlined below, we recommend strong consideration be given to suture closure of the native aortic valve.

We believe that medical care alone is inappropriate given the tendency for AI to worsen over time, thus resulting in worsening heart failure with pulmonary hypertension. Until recently, the best technique to treat AI at the time of LVAD placement was thought to be replacing the native valve with a bioprosthetic valve. However, numerous reports of fusion of the leaflets of the bioprosthetic valve, with or without concomitant thrombus formation, have significantly reduced enthusiasm for that technique.19, 20, 21 Feldman et al19 reported 2 patients in whom a bioprosthetic valve implanted at the time of LVAD placement resulted in fusion of the leaflets of the valve. Rose et al21 also reported 2 patients with existing bioprosthetic aortic valves who developed total LV outflow tract obstruction due to subaortic thrombosis.

In theory, use of a bioprosthetic valve may be preferable to aortic valve closure in patients receiving a continuous-flow LVAD with significant AI. If a continuous-flow LVAD developed mechanical failure or completely occluded because of thrombus, cardiac output would be dependent on a functioning aortic valve. However, with recent data showing a significant increase in operative mortality in patients undergoing concomitant aortic valve procedures at the time of HeartMate (HM) II (Thoratec, Pleasanton, CA) placement, our enthusiasm to perform a concomitant aortic valve replacement is significantly dampened.22 Rather, we recommend (as we later discuss) doing what appears to be a shorter and easily reproducible procedure of oversewing the incompetent aortic valve with a purse string suture.

We believe that the increased mortality reported in the prior study may be related to the increased ischemic time required for aortic valve replacement with its subsequent deleterious effects on right ventricular function. Thus, the fear of bioprosthetic valve leaflet closure (with thrombosis) and the lengthy time required for valve implantation make this option less appealing than previously thought. Moreover, bioprosthetic aortic valve fusion and stenosis have been reported with both porcine and pericardial valves: closure was reported as early as 2 months after implantation.23 Bioprosthetic valve implantation with LVAD placement may also carry a higher risk of thrombus formation in the early postoperative period when the native LV is typically too weak to eject against the pressure generated by the LVAD. The alternative of mechanical aortic valve implantation is contraindicated in LVAD patients with aortic incompetence, given the high risk of thrombus formation and embolization with intermittent opening of the leaflets.6

Thus, in patients requiring LVAD support as bridge-to-transplant therapy, the commonly used strategy has been to oversew the incompetent aortic valve with a continuous suture, with or without pledgets. Small single-center series have shown that the single-suture technique provides a durable result for at least 1 year.16 With this technique, the aortic valve is still able to open during cardiac ejection, allowing for some washing of the aortic outflow tract and diminishing the risk of thrombus formation. However, direct closure of the valve by oversewing the edges of all 3 leaflets can also be done if there are concerns regarding the durability of this repair. At this time, the effect of central aortic valve closure on long-term aortic valve function as well as durability of the repair with continuous-flow devices remains to be determined, especially with regard to the long-term durability that has been demonstrated with these devices.24, 25

Prosthetic aortic valves 

As noted above, there is a significant risk of functional closure of a bioprosthetic valve in a patient on LVAD support as a fibrosis or endothelialization.19, 20, 21 Thus, in the patient with a pre-existing bioprosthetic valve receiving an LVAD, we recommend that the pump speed be slightly reduced to allow intermittent opening of the valve as long as adequate cardiac output and support can be maintained to avoid valve closure.

The most common strategy to deal with a mechanical aortic valve in LVAD patients is to close the aortic valve with a synthetic patch (either Dacron [Du Pont, Wilmington, DE] or Hemashield [Boston Scientific, Wayne, NJ]).26, 27, 28 Placing this patch through the same aortotomy used for LVAD outflow graft placement is technically challenging because of sub-optimal visualization of the sewing ring of the mechanical valve. A separate aortotomy may be necessary, usually at the site of the previous aortotomy (the one used for the initial valve replacement). We recommend using continuous 4-0 Prolene (Ethicon, Somerville, NJ) sutures to fix the patch to the sewing ring of the mechanical valve.

Other techniques have also been reported.29, 30 One alternative strategy is to replace the mechanical aortic valve with a bioprosthetic valve, but again, several reports of fusion of the leaflets of the bioprosthetic valve in LVAD patients as well as the technical difficulty of performing a redo valve replacement diminish enthusiasm for this approach.19, 20, 21, 22, 23 Recent trials involving continuous-flow LVADs, such as the HMII,, maintain in their inclusion criteria the need to replace a mechanical aortic valve with a bioprosthetic one.24

Management of aortic valve pathophysiology after LVAD placement 

Aortic valve fusion and stenosis 

Structural remodeling such as aortic valve fusion has been observed in a large percentage of VAD patients, leading to functional problems such as AS and AI in some cases. Aortic commissural fusion is a remodeling process in which fibrous tissue is deposited at the commissures of the coapted leaflets, adhering them together, and preventing complete opening. Fusion can occur in 1, 2, or all 3 of the cusps and usually covers a total of several millimeters of commissural length summed over all leaflets.

After the initial observation at the University of Minnesota,31 others have also reported the development of aortic valve fusion and stenosis with the HM XVE (Thoratec Corp) LVAD.32, 33, 34, 35, 36 The effective unloading of the LV by pulsatile pumps like the HM XVE often favors closure of the aortic valve by fusion. Stasis of blood on the ventricular aspect of the permanently immobilized aortic valve cusps (more particularly in the commissural region) favors the development of thrombus. Organization of such thrombus can lead to commissural fusion and acquired AS (Figure 4). The severity of AS will depend on the number and the extent of aortic valve commissural fusion. Fusion of a single commissure is the most common form of aortic valve fusion in LVAD patients.

Connelly et al32 identified some degree of commissural fusion in 51.5% of patients on LVAD support. In that series, 76.5% of the cases of aortic valve fusion involved only 1 commissure; in all these cases, the right coronary cusp was involved. Histopathologic examination of areas of fusion revealed loose fibrous tissue between commissures (Figure 5). Rose et al31 identified aortic valve commissural fusion in 4 of 6 patients on LVAD support. Interestingly, they found an organizing thrombus at the site of commissural fusion in 1 patient31 and postulated that the organization of such a thrombus leads to commissural fusion. Thrombi are unlikely to form on the aortic (outflow) aspect of the aortic valve or in the sinuses of Valsalva, given frequent washing by the jet of blood from the LVAD outflow graft. Further, Rose et al31 did not find any correlation between the duration of LVAD support and commissural fusion. But Connelly et al32 reported a trend between the duration of LVAD support and the length of commissural fusion.

Baradarian et al36 examined 31 patients receiving LVAD support with implanted pneumatic (IP) or vented electric (VE) HM versions. At the time of LVAD explantation, 7 patients had some degree of aortic valve fusion (5 in their native aortic valves; 2 in porcine bioprostheses). Of the 5 native aortic valves, 4 had varying degrees of fusion of all 3 cusps, and 1 had fusion of 2 cusps.

In the only published observation of aortic valve fusion with the Novacor LVAD (WorldHeart, Oakland, CA), Nishimura et al37 showed that after nearly 3 years, severe aortic valve fibrous fusion occurred between all commissures. Fusion occurred despite the patients' strict anticoagulation regimen with Coumadin (Bristol-Myers Squibb, Princeton, NJ) and aspirin, a regimen required with the Novacor LVAD. The HM VE LVAD requires minimal or no anti-coagulation; however, the newer continuous-flow LVADs that are currently predominant all require anti-coagulation. (What effect anti-coagulation will have on aortic valve fusion in LVAD patients is unknown.) A recent study by Mudd et al38 found evidence of commissural fusion in 8 of 9 patients with continuous-flow LVADs, which was correlated with decreased valve opening and an increasing prevalence of AI.

AS in patients on LVAD support can easily be distinguished from senile calcific AS, which does not produce commissural fusion and shows cuspal calcification. Chronic rheumatic AS also shows commissural fusion, but the valve cusps are diffusely thickened and fibrosed and may show inflammation. Moreover, mitral valve disease invariably precedes aortic valve involvement with rheumatic fever. The fusion tissue deposits along the commissures from the annular edges towards the free edge, often for several millimeters. This fusion reduces the opening area of the valves, producing a stenosis. In aortic stenosis associated with LVAD-induced commissural fusion, the aortic valve leaflets appear normal, apart from the commissural fusion.

Biochemical and biomechanical basis for aortic valve fusion 

Remodeling is defined as changes in the geometry, structure, and mechanical properties that occur as the environmental conditions of the tissue system change. Biochemical and biomechanical stimuli can both induce remodeling in tissues, which in turn affects the morphology and mechanical behavior of the stimulated tissue by altering the structure-function relation.39, 40, 41

Stress is an important biomechanical signal for remodeling in a variety of tissues. In arteries, wall thickness increases in response to increased blood pressure, which effectively lowers the increased aortic wall stress to normal levels.42, 43 In valve tissue, increased stress has been associated with calcification (bioprosthetic leaflets), growth (tissue engineering), and pathologic remodeling, each of which is highly dependent on the direction and magnitude of mechanical stress and strain.44, 45, 46 When closed, the valve leaflets stretch in opposition to high transvalvular pressure. The leaflets relax as they open, reducing the stretch and stress in the leaflets and allowing nutrient flow to the tissue. In the series flow condition, the leaflets are subjected to the high transvalvular pressure continuously, rather than intermittently, which provides a stimulus for collagen production and remodeling.46

A recent study further identified increased expression of proteolytic enzymes such as matrix metalloproteinases (MMPs) and cathepsin S and K after high levels (15% to 20%) of circumferential stretch in the leaflets.47 In addition, the leaflets undergo continuous contact of coaptation areas, which exposes endothelial cells to prolonged contact which may influence adhesion.48 The production of extracellular matrix reflects a stimulus of cardiac fibroblasts, likely in response to mechanical stretch, which is highly dependent on the magnitude and direction of the stretch field49, 50 and involves the up-regulation of growth factors and integrins as cell-signaling mediators.51

These previous studies indicate that aortic valve fusion is likely a remodeling response to an increase in stress and strain in the valve, which occurs primarily due to the increase in TVP during VAD use. Aortic valve fusion is one example of pathologic remodeling of the tissue, and there are probably other remodeling responses to the VAD-altered loading conditions that have not yet been revealed.

Aortic incompetence 

Although the development of aortic valve fusion resulting in stenosis has been extensively reported, the contributions of altered flow patterns that result in clinically significant AI are less well described.

The shear stress distribution on the walls of the aorta is greatly altered after LVAD implantation. Because the LVAD outflow conduit is much narrower than the aorta, the velocity through the conduit needed to maintain an adequate flow rate is much higher than what is normally seen in the aorta. This increase in velocity can change the flow profile throughout the aorta as well as create areas of very high shear stress.52 In an animal model of non-pulsatile support, Nishimura et al53 described thinning of the aortic medial layer, decreased smooth muscle cells, and an increase in the number of inactive (atrophic) smooth muscle cells. Westaby et al54 reported the development of abnormal aortic wall morphology in patients supported by continuous-flow circulatory support (Jarvik 2000 LVAD, Jarvik Heart Inc, New York, NY). They observed significant reductions in aortic wall medial thickness, a decreased number of smooth muscle cells, and a decrease in the medial layer elastin content. A further observation was that the process of atrophy in these patients appeared to progress with time. These findings provide histologic evidence of some degree of aortic dilatation in response to the increased shear stress provided by the LVAD flow. It remains unknown at this time whether these changes have any effect on the development of clinically significant AI.

The 4 main potential clinical implications of aortic valve fusion and stenosis during LVAD support are:

1. Impaired LVAD function. One detrimental effect is the need for increased levels of LVAD support and output, which can lead to pre-mature LVAD failure. Letsou et al33 found that fusion led to AI in some LVAD patients. Increased LVAD flow is necessary to compensate for the AI.33 The resulting increased cardiac output demands on the LVAD can cause increases in the mechanical demands of the LVAD system (specifically on the valves, bearings, and pivot mechanisms), thus leading to premature LVAD failure or replacement. This phenomenon is mainly a concern with pulsatile devices, which have several wearable parts and are of limited durability. In addition, in the event of LV remodeling and myocardial recovery (uncommon, but not impossible), clinical manifestations of fusion include a lack of tolerance to exercise late after LVAD placement, along with decreased parallel flow and possible subendocardial ischemia.

2. Thromboembolism. The closing of the aortic valve after LVAD implantation creates a thrombogenic environment as a result of a relatively low-flow state acting as a source of emboli. Systemic embolization can also occur, including cerebrovascular accidents, during intermittent opening of the aortic valve. The formation of a thrombus usually precedes and even forms the basis for the development of fusion.

3. Ventricular recovery. Severe aortic valve fusion is not a serious problem in patients destined for a heart transplant, but it clearly is of great concern in bridge-to-recovery patients. The effect, if any, of fusion on LV recovery during LVAD support is unknown. It is possible, although unlikely, that a higher than expected degree of aortic valve fusion in LVAD patients may be responsible for a rather low rate of LV recovery, leading to LVAD explantation.55, 56 If myocardial recovery occurs with concomitant valve fusion (a rare phenomenon), the aortic valve must be replaced at the time of LVAD explantation.

4. LVAD-related infections. Although infections remain a constant obstacle to the long-term success of LVAD patients, their association with aortic valve fusion is rare. Thrombus adjacent to the aortic valve (secondary to stasis from fusion) has only been reported rarely, but it may predispose to bloodstream-based infections as a result of seeding of the thrombus. Bardarian et al36 described a patient with aortic valve fusion who had Enterobacter cloacae isolated from the thrombus on the LV side of the valve.36

Effect of LVAD type on aortic valve pathophysiology 

The study by Connelly et al32 found that commissural fusion was significantly more common in patients on a VE LVAD (76%) than those on an IP LVAD (8%). The IP HM LVAD is no longer used, but it is still worth noting that the difference in fusion prevalence in IP vs VE LVAD users can be attributed to the different operation of the 2 models. The VE model captures the entire cardiac output during normal operation, meaning that the native aortic valve frequently does not open. The IP model must be vented every 24 hours, during which the pump does not operate and the native LV function takes over. During this venting period, the native aortic valve opens; this motion may be enough to inhibit valve fusion. Connelly et al concluded that the detrimental fusion effects could be decreased by stopping the pump for short periods, slowing the rate periodically, or carefully controlling systemic blood pressure.

Tuzun et al57 examined the use of a newer-generation Jarvik 2000 LVAD in a calf model. They evaluated whether the newer axial continuous-flow pumps, coupled with an intermittent low-speed controller, had a positive effect on aortic valve opening. Allowing intermittent opening alleviated hemostagnation around the aortic valve and prevented complications associated with blood stasis, such as thrombosis and leaflet fusion. They achieved these favorable results by slowing the pump speed every 10 seconds/min (operating it in the intermittent low-speed mode).

In the only clinical study reported in patients supported with continuous-flow technology, Mudd et al38 reported a rather high incidence of aortic valve fusion. Although significant AI did not develop in any of the patients in their series, the higher likelihood of longer-term support with these devices does raise potentially significant implications for such patients What remains unknown is whether reducing the pumps speeds in continuous flow LVADs (while not compromising cardiac output) could favorably influence aortic valve function and prevent fusion.

More recently, an increased incidence of native aortic valve or root thrombosis has been reported in patients on continuous-flow LVADs.58 This has been particularly problematic in patients for whom the LVAD outflow conduit was attached to the distal aorta. But it is possible that if continuous-flow LVADs are maintained on a relatively high pump speed, the aortic valve will remain in a closed position and predispose to thrombus formation because of blood stasis.

Prevention of aortic valve fusion and stenosis 

Preventing the development of aortic valve fusion in LVAD patients would be beneficial. At our institution, we usually adjust the fixed-rate speed of the current continuous-flow LVADs to maximize LV decompression, to improve cardiac output, and to simultaneously allow for at least a 1:3 ratio of aortic valve opening. We believe this adjustment may have a favorable effect on reducing the incidence of aortic valve fusion and thereby a favorable effect on the prevention of thromboembolism, although no clear data are available to confirm this.25, 59 LV decompression is important, irrespective of the type of LVAD, but it is also important to allow for intermittent opening of the aortic valve. Currently, the only way to ensure intermittent opening of the aortic valve is to perform serial echocardiograms and alter the pump speed accordingly.

It also remains to be seen what effect anti-coagulation will have on reducing the incidence of thrombus adjacent to the aortic valve, irrespective of the frequency of aortic valve opening. It is possible that if continuous-flow LVADs are maintained on a relatively high pump speed, then the aortic valve will remain in a closed position, predisposing to thrombus formation because of stasis. Early post-operatively, when the likelihood of native LV function and ejection through the aortic valve is low, it is especially critical to keep the speed of continuous-flow LVADs relatively low to optimize flow through the aortic valve. With improved LV function after the initial 24 to 48 hours, the speed can be gradually increased to optimize LVAD output.

In conclusion, abnormal aortic valve pathophysiology is very prevalent in LVAD patients who have an increased incidence of “acquired” aortic valve disease that can adversely affect outcomes. This is a problem in a significant fraction of the VAD population. There are deleterious consequences for patients who develop aortic disease and who do not receive a transplant. For instance, parallel flow will be limited by a stenotic valve, reducing the range of cardiac output and exercise capacity. In these patients, who will either have the LVAD as a bridge-to-recovery or as a permanent implant, a method for timely diagnosis and treatment of aortic valve disease is imperative.

With the increasing use of long-term LVADs (especially as destination therapy) and with an increasing emphasis on the potential of LV recovery, a greater understanding of the pathophysiologic changes in aortic valves and of measures to prevent those changes is imperative. Close attention to the information provided by echocardiographic evaluation of aortic valves remains a high priority in the patient undergoing LVAD implantation.60, 61 In addition, echocardiographic follow-up in patients on LVAD support must focus on aortic valve function. Our recommendations to deal with both native and prosthetic aortic valves are summarized in Figure 6. The goals of these strategies are to optimize native aortic valve function, to minimize the occurrence of abnormalities in LVAD patients, and to provide low-risk strategies to manage prosthetic aortic valves in LVAD patients. What remains unknown at this time is what strategy (likely echocardiographic follow-up) should be considered in patients receiving continuous-flow devices to prevent aortic valve fusion. Further, a better understanding of the disturbances in the coagulation pathways in LVAD patients is needed and may allow potentially beneficial changes in the strategies to deal with both native and prosthetic valves in LVAD patients.

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Disclosure statement 

The authors thank Mary E. Knatterud, PhD, for editorial assistance.

Ranjit John has a research grant from Thoratec, Inc. None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

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PII: S1053-2498(10)00367-0

doi:10.1016/j.healun.2010.06.006

The Journal of Heart and Lung Transplantation
Volume 29, Issue 12 , Pages 1321-1329, December 2010

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