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Ann Thorac Surg 2000;70:1270-1274
© 2000 The Society of Thoracic Surgeons

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Original articles: cardiovascular

Partial aortic valve fusion induced by left ventricular assist device

^a Department of Laboratory Medicine and Pathology, University of Minnesota and Fairview-University Medical Center, Minneapolis, Minnesota, USA
^b Division of Cardiovascular and Thoracic Surgery, University of Minnesota and Fairview-University Medical Center, Minneapolis, Minnesota, USA
^c Division of Cardiology, University of Minnesota and Fairview-University Medical Center, Minneapolis, Minnesota, USA

Address reprint requests to Dr Rose, Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, MMC 76, Mayo Building, 420 Delaware St SE, Minneapolis, MN 55455
e-mail: rosex031{at}tc.umn.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment Addendum References

 
Background. Left ventricular assist devices (LVADs) may be used (1) as a bridging device to cardiac transplantation, (2) for permanent replacement of left ventricular function, and (3) as a bridge to recovery of ventricular function, for example, in recoverable myocardial disease. In this third group of patients, it is important that the LVAD does not produce changes in the heart that will have a deleterious effect on cardiac function once the device is removed. Furthermore, if the LVAD fails, survival depends on optimal function of the diseased heart.

Methods. All hearts with LVADs encountered as surgical specimens following heart transplantation or at autopsy at the Fairview-University of Minnesota Medical Center during the 5-month period August 1998 to January 1999 were examined for native valvular heart disease. The nature and extent of commissural fusion was noted and measured. Light microscopy was performed on any valve lesions.

Results. Four of 6 patients with HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) LVADs showed evidence of commissural fusion (acquired aortic stenosis). In 1 patient, this condition was caused by an organizing thrombus uniting a 14-mm length of the commissural region of the right coronary and noncoronary cusps of the aortic valve. Fibrous commissural fusion due to totally organized thrombus in the other 3 patients affected one aortic commissure (2 patients, 2 mm and 4 mm, respectively) and two commissures (1 patient, 2 mm and 5 mm). Partial cuspal fusion in each case was due to permanent closure of the native aortic valve induced by the LVAD’s operating in its automatic setting. Mean length of commissural fusion was 5.4 mm (range, 2 to 14 mm; standard deviation [SD] = ±5.0 mm). Mean duration of implantation of the six LVADs was 180.3 days (range, 26 to 689 days; SD = ±253.8 days). The LVADs of the 3 patients with fibrous fusion of the commissures had been implanted for an average of 252.3 days (range, 26 to 689 days; SD = ±378.2 days).

Conclusions. Normal function of the LVAD produces permanent closure of the native aortic valve. Stasis on the ventricular aspect of the aortic valve, combined with a low level of anticoagulation, favors thrombosis at this site. Thrombus organization leads to aortic stenosis of variable severity. This previously unsuspected complication was not detected clinically in any of our patients. Aortic stenosis may hold serious implications for patients in whom the LVAD acts as a bridge to recovery or in those in whom the LVAD fails. Prevention may be achieved by intermittently reducing LVAD pumping action. A built-in venting cycle would be of value in long-term implants. Thrombi on the aortic valve may also predispose patients to infective endocarditis, because bloodstream infection is common in patients with LVADs.

	Introduction

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The left ventricular assist device (LVAD) has proved to be an effective bridge to transplantation [1–5]. It has recently been shown that the use of a LVAD has allowed some patients with dilated cardiomyopathy to recover sufficient native myocardial function to allow the pump to be removed [6, 7]. The University of Minnesota is one of the sites at which a clinical trial of LVAD (HeartMate; Thermo Cardiosystems, Inc, Woburn, MA) as an alternative to medical therapy for patients who are not transplant candidates is currently under way. Disadvantages of current mechanical devices [5, 8] include the following: a variable propensity for thromboembolic complications necessitating systemic anticoagulation (and its attendant complications), infection of the transcutaneous connec-tions, and possible device malfunction. A low thromboembolic risk without anticoagulation using advanced-design LVADs has been reported [9]. Nevertheless, although procoagulant and fibrinolytic pathways are apparently balanced in such patients, the presence of the LVAD leads to significant thrombin generation and corresponding fibrinolysis. This underscores the potential for the development of bleeding or thrombosis in clinically relevant settings [10].

The purpose of this communication is to draw attention to the possible development of aortic valve stenosis in recipients of LVADs and to suggest a means of preventing this potentially serious complication.

	Material and methods

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During the period January 1995 to January 1999, 26 HeartMate LVADs have been implanted at the Fairview-University Medical Center. All patients with implants received one aspirin daily for anticoagulation, and the LVAD pump was vented once per nursing shift. Left ventricular function stayed depressed in most patients on echo assessment. The native aortic valve stayed closed during the automatic pumping mode. All hearts bearing a HeartMate LVAD, including hearts explanted at cardiac transplantation and those encountered at autopsy in the Department of Laboratory Medicine and Pathology at Fairview-University of Minnesota Medical Center during the period August 1998 to January 1999, were examined for evidence of valvular heart disease. Careful note was made of any valvular alterations. The length and nature of commissural fusion was recorded. The valves were photographed, and histologic sections were made of any valvular lesions encountered. The commissures were sectioned horizontally to include the aortic wall as well as both cusps. All valvular tissue was processed by routine paraffin embedding. Sections were stained by hematoxylin and eosin and by Verhoeff’s elastic stain with a van Gieson counterstain.

	Results

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We encountered six hearts with an implanted HeartMate LVAD; three were explanted recipient hearts following cardiac transplantation, and three were autopsy hearts. Five out of the six HeartMate LVADs (those in hearts 1, 2, 3, 4, and 6) were pneumatically powered (model 1000 IP devices), and one heart (heart 5) had the HeartMate VE (vented electrical) model. Clinicopathologic data are given in Table 1 and Figures 1, 2, and 3.

View larger version (86K): [in this window] [in a new window]   Fig 1. Heart 1. (A) Organizing fibrin thrombus unites anterior aspect of commissure between right coronary cusp (RCC; left) and noncoronary cusp (NCC; right). (B) Aortic aspect of the aortic valve shown in (A) showing the fusing commissure between RCC (left) and NCC (right). A portion of the left ventricular assist device outflow anastomosis in the aorta distal to the aortic valve is present (top). (C) Organizing intercuspal fibrin-platelet thrombus (left) and portion of RCC (right); artifactual disruption has occurred during sectioning. (Hematoxylin and eosin; x70.)

View larger version (48K): [in this window] [in a new window]   Fig 2. Heart 3. (A) Fibrous fusion of commissure between left coronary cusp and noncoronary cusp (next to forceps). The fusion between the right coronary and left coronary cusps was disrupted before photography. (B) Histologic section of fused portion of left coronary and noncoronary cusps. The original valve cusps appear dark red, and the intervening area of fusion appears paler and represents less dense, more recently formed collagen, probably due to organization of an intercuspal fibrin deposit. (Elastic van Gieson stain; x20.)

View larger version (128K): [in this window] [in a new window]   Fig 3. Heart 5. Macroscopic appearance of healed, fibrous commissural fusion between left coronary cusp (right, held by forceps) and noncoronary (left) cusp of aortic valve.

No correlation was found between the duration of LVAD implantation and the generation of aortic valve thrombosis and commissural fusion. Mean duration of implantation of the six LVADs was 180.3 days (range, 26 to 689 days; SD = ±253.8 days). The LVADs in the 3 patients with firm, fibrous union of the affected commissures had been implanted for 252.3 days (range, 26 to 689 days; SD = ±378.2 days).

Patient 1, whose device had been implanted for the second longest period (152 days) showed a greater (14 mm) extent of cuspal apposition by an organizing intercuspal thrombus that had been deposited on the ventricular aspect of the left coronary and noncoronary cusps (Fig 1). Patient 3 was a woman with dilated cardiomyopathy whose LVAD had been implanted for 689 days. Her myocardial function had improved in the interim, and the patient had been discharged from hospital, but the LVAD had to be removed because of drive-line sepsis. A month later the patient suddenly collapsed at home, was partially resuscitated, and died shortly thereafter. Autopsy revealed fusion of two commissures of her aortic valve (Fig 2). Because the valvular complication had been unsuspected, the echocardiogram performed just before removal of the LVAD had not specifically visualized the aortic valvular commissures, nor had it measured aortic valve gradients. Patient 5, whose device had been implanted for the shortest period (26 days), showed healed, fibrous fusion of a single commissure (Fig 3).

	Comment

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A recent comprehensive review of implantable LVADs [11] lists only the following as possible complications of LVADs: (1) the most common early complications are bleeding, right-sided heart failure, air embolism, and progressive multisystem organ failure; and (2) the most common late complications are infection, thromboembolism, and device failure. Although the review discusses hemodynamic features of the blood flow in LVAD recipients with various valvular lesions, no mention is made of any valvular complications in the native heart resulting from the LVAD. It was recommended that patients with preexisting mitral stenosis or aortic regurgitation may require correction of the valvulopathy before implantation of a LVAD [11]. As far as we are aware, there has been no previous report describing aortic valve pathology induced by a LVAD.

The development of aortic stenosis will have a less deleterious effect in patients scheduled for biological cardiac transplantation, but it holds potentially serious implications for the following populations: (1) patients in whom the LVAD is aimed to serve as a "bridge to recovery" [6], and (2) patients whose device fails. Muller and colleagues [6] have described 5 patients with idiopathic dilated cardiomyopathy treated with long-term LVAD therapy who were successfully weaned from mechanical support.

The wearable electrical devices currently available have external backup mechanisms to continue temporary support [11, 12]. If the backup mechanism should not be available or fail, the native heart must provide systemic support until the device can be repaired. Under such circumstances, the presence of significant aortic stenosis could have highly unfavorable effects on the function of a diseased left ventricle that has not been called upon to support the full circulation for many months or years.

When set in the automatic mode, the HeartMate LVAD automatically ejects when it reaches 90% of filling capacity. This keeps the left ventricle "unloaded," and the aortic valve remains permanently closed [13]. Stasis of blood on the ventricular aspect of the permanently immobilized aortic valve cusps (more particularly in the commissural region), combined with low anticoagulation, favors development of thrombi in this region. Increased thrombin generation in patients with LVAD acts as an additional factor favoring thrombosis. Thrombi are unlikely to form on the aortic aspect of the aortic valve or in the sinuses of Valsalva, which are washed by blood pumped in from the LVAD. The native aortic valve will only open when pressure in the left ventricle exceeds that in the ascending aorta, as happens, for example, during the regular cycle of venting the pneumatically powered drive line or during exercise. With exercise (a rare event in patients with LVADs), increased preload results in a more forceful left ventricular contraction and in Doppler evidence of significant flow across the native aortic valve [14, 15].

Organization of such thrombus leads to commissural fusion and acquired aortic stenosis. The severity of the latter will depend on the number and extent of the aortic valvular commissural fusions. Fusion of a single commissure leads to an acquired bicuspid aortic valve (as seen in heart 1 and, to a lesser extent, in heart 5). Fusion of two commissures was observed in heart 3. Fusion of all three commissures, which was not observed in this study, may also be predicted to occur.

The aortic valvular stenosis resulting from the LVAD is easily distinguishable from senile calcific aortic stenosis, which does not produce commissural fusion and shows cuspal calcification [16]. Chronic rheumatic aortic stenosis shows commissural fusion, but the valve cusps are diffusely thickened, fibrosed, and vascularized and may show inflammation. The mitral valve is also usually affected in patients with rheumatic aortic stenosis. In aortic stenosis associated with LVAD-induced commissural fusion, the aortic leaflets appear normal apart from the commissural fusion.

Infection is common in patients with implanted LVADs. In the series reported by McCarthy and colleagues [17], 55% of patients had bloodstream infection during LVAD support. The presence of thrombus on the aortic valve may predispose to infective endocarditis, the pathogenesis of which involves infection of a preexisting bland valvular thrombus.

In future clinical examination of patients with LVADs, we shall be paying particular attention to the native aortic valve. In theory, thrombi on the aortic valve cusps and partial commissural fusion may be prevented by allowing intermittent opening of the aortic valve by left ventricular systole, induced by periodic venting of the LVAD. A built-in pump-venting cycle would be of value in long-term implants.

	Addendum

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Subsequent to the submission of this manuscript, we have encountered 3 additional patients with partial aortic valve commissural fusion associated with the presence of a LVAD. The heart of 1 of these patients, who had a LVAD for 165 days, is illustrated in Figure 4.

View larger version (100K): [in this window] [in a new window]   Fig 4. (A) Healed, fibrous commissural fusion of two aortic valve cusps in an additional patient not discussed in the article, whose LVAD had been implanted for 165 days (see Addendum). (B) Transverse section of fused commissure. (Elastic van Gieson stain; x20.)

	References

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