The incidence of aortic valve thrombosis after left ventricular assist device (LVAD) implantation is unknown, but this complication is thought to be rare; available literature includes only case reports. In one report, four patients with HeartMate II LVADs (Thoratec Corporation, Pleasanton, CA) developed thrombosis on the noncoronary cusp of the aortic valve despite anticoagulation.1 Known risk factors include constant aortic valve closure, leaflet fusion, stasis in the noncoronary sinus,1 tilting disk prosthetic valves, outflow grafts anastomosed to the descending thoracic aorta,2 and hypercoagulable states. Treatment is aimed at dissolving the clot with medical therapy or surgically excising it.
A 45-year-old woman with a history of nonischemic cardiomyopathy underwent implantation of a HeartMate II LVAD as a bridge to cardiac transplantation. The patient had previously developed deep vein thrombosis after a period of immobilization after radiofrequency catheter ablation for ventricular tachycardia. She had been taking warfarin until her current admission. Heparin was initiated as a bridge to warfarin after LVAD implantation (partial thromboplastin time goal of 50–70 seconds). Follow-up transthoracic echocardiography performed 1 week later showed that the aortic valve remained closed at all assessed speeds and revealed an ill-defined echodensity in the noncoronary cusp of the aortic valve, possibly representing a laminated thrombus. Transesophageal echocardiography (TEE) confirmed the presence of a well-organized thrombus in the noncoronary cusp (diameter, 1.2 cm; Figure 1). A hypercoagulable evaluation showed that she was heterozygous for the R506q mutation. Repeat TEE while the patient was on heparin showed a minimal decrease in thrombus size. The patient had no neurologic deficits and no evidence of distal embolization.
Heparin was discontinued, bivalirudin was started as a constant intravenous infusion (0.15 mg/kg/hr for creatinine clearance >60 ml/min with no bolus), and the thrombus size was closely monitored. A repeat TEE 4 days later showed that the clot was less than half its original size, and 12 days after the initiation of bivalirudin, the clot could no longer be seen on TEE. Warfarin was then initiated, and bivalirudin was discontinued when the international normalized ratio was within therapeutic range. The patient was discharged home in stable condition on warfarin, aspirin, and dipyridamole. She remained complication free over a follow-up period of 24 months.
We describe the case of a patient with a previously undiagnosed factor V Leiden mutation who developed a thrombus on the noncoronary cusp of the aortic valve after a short period of interrupted anticoagulation for LVAD implantation.
Factor V Leiden thrombophilia is characterized by a poor anticoagulation response to activated protein C and an increased risk of venous thromboembolism; however, the association of this mutation with arterial thrombosis is less clear, but available literature about patients undergoing coronary artery bypass surgery suggests that there may be an increased risk.3 Studies have shown that early postoperative anticoagulation or even anticoagulation continued throughout cardiac surgery is safe and might reduce the incidence of perioperative thromboembolic events.4
Available treatment options include anticoagulation,5 increased LVAD speed to keep the aortic valve closed, thrombolytics,6 direct thrombin inhibitors, surgical removal of the thrombus, and emergent heart transplantation.
Unfractionated heparin has been shown to accelerate the inactivation of plasminogen activator inhibitory type 1, which allows the activity of endogenous tissue plasminogen activator to predominate, thereby promoting fibrinolysis.5 However, in our patient, the thrombus size remained the same despite therapeutic doses of heparin. Thrombolytic therapy, though effective, can be challenging in patients who have undergone recent major surgery because of the risk of bleeding. Our patient had high panel reactive antibodies, which made listing her for emergent heart transplantation impractical.
Bivalirudin is a reversible, bivalent, direct thrombin inhibitor that binds to thrombin at both the active site and the fibrinogen-binding site, causing its inhibition regardless of whether the thrombin is free or bound to fibrin. In comparison with heparin, bivalirudin decreases platelet adhesion and has a lower immunogenic potential and a shorter half-life (approximately 25 minutes). Clinical trials have also shown that bivalirudin is associated with a lower rate of major bleeding than heparin.7 He et al. 8 studied the effects of different thrombin inhibitors on fibrin formation using a physiologically relevant system and found that bivalirudin increases the fibrin network porosity, thus facilitating fibrinolysis.
Despite technological advances in the design and size of nonpulsatile LVADs, implanted patients remain at risk for life-threatening thromboembolism. The described case shows successful treatment of an aortic valve thrombus with bivalirudin in a patient for whom treatment with unfractionated heparin had failed; the successful bivalirudin therapy prevented the need for more invasive therapy. Bivalirudin has several theoretical advantages over unfractionated heparin and has been proven superior to it for several clinical indications. Although our patient was hypercoagulable with factor V Leiden mutation, current data suggest that the advantage of bivalirudin over unfractionated heparin is not limited to patients with coagulation disorders. Bivalirudin therapy may be useful in LVAD patients who develop a thrombus despite anticoagulation with unfractionated heparin, whether the thrombus forms on the aortic valve, on the distal arteries, on the pump, or on the inflow or outflow tract. Additional studies will be required to clarify the role of bivalirudin in thrombus resolution in patients with nonpulsatile LVADs.
The authors thank James Philpot for graphics assistance and Chrissie Worth, MA, ELS, and Diana Kirkland for editorial assistance.
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