Left ventricular assist devices (LVADs) are increasingly being used to manage advanced heart failure. In patients who receive an LVAD as a bridge to transplantation or as destination therapy, potential complications include hemolysis, pump thrombosis, and pump failure. We report the successful use of direct thrombolytic therapy for recurrent hemolysis and thrombosis-related pump failure in a patient with the HVAD (HeartWare, Inc., Framingham, MA), a third-generation, centrifugal flow pump. To our knowledge, direct thrombolytic therapy has been used to treat failure of a third-generation device in only one previous case.1
A 49-year-old man with nonischemic cardiomyopathy received a HeartWare ventricular assist device (HVAD) as a bridge to transplantation. A year later, he developed hemolysis, and recurrent alarms indicated abnormally high pump power levels, so the device was exchanged for another HVAD. Intraoperative assessment showed thrombus near the inflow cannula of the explanted device. The thrombus had not been seen on imaging studies.
Nine months after the second HVAD was implanted, the patient again had hemolysis, as evidenced by increasing plasma lactate dehydrogenase levels, free hemoglobin, and anemia at outpatient follow-up examination. Six weeks later, he was readmitted to the hospital for the evaluation of high power alarms. He started to show signs of heart failure (fatigue and dyspnea on mild exertion), but his condition was hemodynamically stable. Although his resting pump speed was 2,400 rpm at home, the resting pump speed was later adjusted upward multiple times to improve his heart failure symptoms. Eventually, the resting pump speed was increased to 3,500 rpm. Although device thrombosis was suspected, noncontrast computed tomography of the chest did not show any thrombus or kinking of the outflow cannula. Transthoracic and transesophageal echocardiograms were equivocal because of shadowing and artifacts related to the inflow cannula. No donor heart was available for transplantation, and a repeat LVAD exchange procedure was considered too risky, given the patient’s history. One week after being hospitalized, he was referred for direct thrombolytic therapy that was performed in the catheterization laboratory.
To cross the aortic valve, a 5F pigtail catheter was inserted into the left ventricle via the femoral artery. This was done without a guidewire, to prevent wire-device entanglement. No heparin was given, as the prothrombin time and international normalized ratio (INR) were already within the therapeutic range of 2.5–3 because of oral anticoagulant treatment with warfarin. This INR goal was used because he had a history of thrombosis in his first pump. Alteplase, a recombinant tissue plasminogen activator (rt-PA) enzyme with a half-life of 35 minutes, was infused through the inflow cannula at 1 mg/min for 20 minutes, resulting in a total dose of 20 mg. The pump speed was increased to 4,000 rpm to allow maximal rt-PA perfusion through the device. Hemodynamic values and pump parameters are shown in Tables 1 and 2, respectively. The infusion was stopped once a significant reduction in pump power and a significant improvement in hemodynamic values were observed. No cardiopulmonary support system or other adjunct was used during thrombolytic therapy. The patient tolerated the procedure well without any bleeding or neurologic complications. After treatment, his hemolysis resolved, renal function returned to normal, and clinical status markedly improved. Improved pump mechanics were also documented. Ten days after undergoing thrombolysis, the patient was discharged home. Two months later, he had a heart transplant.
An improved quality of life has been documented in patients undergoing LVAD support as destination therapy, bridge to transplantation, or bridge to recovery.2,3 However, thrombosis4 and anemia5 are potential complications of prolonged mechanical circulatory support, and both these conditions are associated with adverse outcomes.
Pump-related thrombosis usually results in intravascular hemolysis, which occurs when wall shear stress and turbulent flow lead to accelerated flow and interaction of the blood with artificial surfaces.6 Evaluation of free hemoglobin and lactate dehydrogenase released from hemolyzed blood cells can characterize the extent of hemolysis.6 When thrombosis occurs, it may not be evident on the basis of hemodynamic compromise or clinical deterioration. However, increases in pump power and hemolysis may be clues to the correct diagnosis. Our experience has shown that device thrombosis can present as increased hemolysis even before power spikes become evident on the device monitor.
The risk of hemolysis and thrombosis varies, depending on the type of pump involved. Continuous flow pumps offer better survival and entail fewer device-related complications than do pulsatile LVADs.7 Moreover, the risk of hemolysis is lower with centrifugal LVADs than with either axial flow or pulsatile pumps.6 In the HVAD, the hydrodynamic thrust bearings work by establishing a “cushion” of blood between the impeller and the pump housing. Once power is applied to the device and the impeller begins to rotate, there are no points of mechanical contact within the pump, so it is essentially a “wearless” system. The elimination of mechanical bearings is expected to result in long-term device reliability and a reduced risk of physical damage to blood cells as they pass through the pump. However, additional factors may play a significant role in the mechanism of hemolysis in centrifugal LVADs.6 For instance, early in the initial clinical trial of the HVAD, manufacture-related variability in the thrust bearings was implicated in two cases of thrombus formation that necessitated device replacement; the manufacturing process was modified, and the complication did not recur.8 The true risk of pump thrombosis associated with intracorporeal centrifugal LVADs is unknown because these devices are still undergoing clinical investigation.1 In a recent multicenter, nonrandomized study of the HVAD in 50 patients, thrombosis and pump failure occurred in four patients (8%), who required a device exchange.8 These pump exchanges occurred at 3, 71, 97, and 560 days postimplantation.
Although pump replacement is a definitive treatment for pump thrombosis, device exchange is limited by the prohibitive risk of repeat surgery. The only other definitive treatment is immediate heart transplantation, which is limited by the scarcity of donor organs. Minimally invasive strategies, including anticoagulant, thrombolytic, and direct thrombolytic therapy, have been used with varying success. Delgado et al. 9 were the first to report on the use of direct thrombolytic therapy in LVAD patients; the two patients who underwent this therapy had a Jarvik 2000 pump (Jarvik Heart, Inc., New York, New York), a second-generation axial flow LVAD. To our knowledge, the present case is only the second in which direct thrombolytic therapy has been used to treat failure of a third-generation device.1
The glycoprotein IIb/IIIa inhibitor tirofiban has been described as an alternative thrombolytic agent for pump thrombosis.10 It is unclear whether direct administration of thrombolytic therapy has an advantage over peripheral administration. In eight patients with the MicroMed DeBakey VAD (MicroMed, Inc., Houston, Texas), Rothenburger et al. 11 treated pump thrombosis successfully by administering rt-PA peripherally and encountered no major bleeding complications. However, the therapy was given for a longer period of time (4 days continuously), epistaxis was common, and two patients required multiple treatments with rt-PA. In comparison, direct thrombolytic therapy involves shorter administration times and lower doses of rt-PA but requires that the patient undergo a minimally invasive procedure in the catheterization laboratory.4 In our case, the goal of maximal perfusion was the reason why we chose to perform direct injection of rt-PA.1,9
Pump-related thrombosis is a life-threatening complication that may manifest as hemolysis and abnormally high LVAD power consumption. The paradigm for treating this complication is not well established, especially in patients who are not heart transplant candidates or who have a high surgical risk. On the basis of our experience in the present case, we believe that direct thrombolytic therapy should be considered a feasible option in these patients.
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2. Lietz K, Long JW, Kfoury AG, et al. Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: Implications for patient selection. Circulation. 2007;116:497–505
3. Miller LW, Pagani FD, Russell SD, et al.HeartMate II Clinical Investigators. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–896
4. Rothenburger M, Schmid C, Huelksen G, Loeher A, Scheld HH. Thrombolytic therapy due to thrombus formation associated with left ventricular assist devices. J Heart Lung Transplant. 2005;24:2305
5. Vrtovec B, Radovancevic R, Delgado RM, et al. Significance of anaemia in patients with advanced heart failure receiving long-term mechanical circulatory support. Eur J Heart Fail. 2009;11:1000–1004
6. Heilmann C, Geisen U, Benk C, et al. Haemolysis in patients with ventricular assist devices: Major differences between systems. Eur J Cardiothorac Surg. 2009;36:580–584
7. Slaughter MS, Rogers JG, Milano CA, et al.HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device. N Engl J Med. 2009;361:2241–2251
8. Strueber M, O’Driscoll G, Jansz P, Khaghani A, Levy WC, Wieselthaler GMHeartWare Investigators. . Multicenter evaluation of an intrapericardial left ventricular assist system. J Am Coll Cardiol. 2011;57:1375–1382
9. Delgado R 3rd, Frazier OH, Myers TJ, et al. Direct thrombolytic therapy for intraventricular thrombosis in patients with the Jarvik 2000 left ventricular assist device. J Heart Lung Transplant. 2005;24:231–233
10. Thomas MD, Wood C, Lovett M, Dembo L, O’Driscoll G. Successful treatment of rotary pump thrombus with the glycoprotein IIb/IIIa inhibitor tirofiban. J Heart Lung Transplant. 2008;27:925–927
11. Rothenburger M, Wilhelm MJ, Hammel D, et al. Treatment of thrombus formation associated with the MicroMed DeBakey VAD using recombinant tissue plasminogen activator. Circulation. 2002;106(12 suppl 1):I189–I192
Keywords:Copyright © 2013 by the American Society for Artificial Internal Organs
left ventricular assist device; centrifugal flow; hemolysis; thrombosis; thrombolysis