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Ventricular Assist Device Thrombosis: Past, Present, and Future Chapter | 29 425

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FIGURE 29.3 Factors contributing to pump thrombosis by grouping: pump-related, patient-related, and management-related. HTN, hyper-

tension; INR, international normalized ratio; RPM, revolutions per minute; RVF, right-ventricular failure. Permission needed Blitz A. Pump thrombosisda

riddle wrapped in a mystery inside an enigma. Ann Cardiothorac Surg 2014;3(5):450e71.

thrombosis alone, but rather composite data of thromboembolic events (pump thrombosis, ischemic stroke, etc.) There is debate in the literature questioning if AF is a meaningful risk factor. Stulak et al. in 2013 [24] reported that patients with preoperative AF had more thromboembolic events compared with patients without preoperative AF (1 year, 62% vs. 79%; 2 years, 46% vs. 72%; 3 and 4 years, 42% vs. 62%, respectively; P < .001). A more recent study by Xuereb et al. [25] showed no difference in thromboembolic events, though it should be noted this was a single-center study with fewer patients than the previously mentioned study. Despite this ongoing debate, elevated risk of pump thrombosis associated with AF seems to be a reasonable assumption. Some centers perform left-atrial appendage ligation at the time of LVAD implantation, although this is not a widespread approach.

Infection and sepsis are risk factors for pump thrombosis, as they have multiple effects on coagulation [26]. Sepsis is an inﬂammatory state that may increase the rate of thrombus formation [27]. For this reason, it has been proposed that anticoagulation be intensiﬁed during periods of sepsis and infection.

Medication noncompliance is a direct cause of pump thrombosis. Hackmann et al. [28] reported that 2-year actuarial freedom from device malfunction was signiﬁcantly higher (83%) in compliant patients versus those who were noncompliant (63%) (P < .03), making this a priority assessment in the preselection process for LVAD candidacy.

Hypercoagulable states present an interesting challenge. Many of these are tested for preimplantation to avoid future complications. These include factor V Leiden mutation, antiphospholipid antibodies, protein S deﬁciency, and glucose-6phosphate dehydrogenase deﬁciency [29,30]. Despite a thorough evaluation for preexisting hypercoagulable states, some hypercoagulable states may present de novo after LVAD implantation. A common offender is heparin-induced thrombocytopenia (HIT), which may occur postoperatively in up to 5% of all cardiac surgeries [31]. HIT may occur in up to 11% in patients receiving mechanical circulatory support [32]. HIT presents two unique challenges in that the platelet count precipitously drops at the same time as thrombus is forming. Another recognized cause of acquired hypercoagulable state is the diagnosis of malignancy after LVAD implantation, an outcome that is almost impossible to predict preimplantation.

Management-related complications are of multiple etiologies. The most common is poor management of warfarin anticoagulation. Warfarin is a notoriously challenging medication to adjust, which requires frequent lab analysis and is inconvenient to the patient, and can also be affected by patient-related factors, such as dietary indiscretion. Poor anticoagulation control (proportion of time spent in therapeutic range <50%; hazard ratio 3.36, 95% CI 1.17e9 .66; P ¼ .025) was associated with an increased risk of thromboembolism [33]. Furthermore, target international normalized ratios (INRs) are frequently lowered after a clinically signiﬁcant gastrointestinal (GI) bleeding event; as GI bleeding occurs in up to 30% of LVAD patients, this becomes a very common and complex problem. It has been suggested that patients experiencing GI

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bleeding show a 7.4-fold increase in thromboembolic events, such as pump thrombosis or stroke, presumably related to the temporary discontinuation of or reduction in warfarin dose and target INR [34]. Novel anticoagulants are not supported for use in this cohort.

Using low-speed settings to help prevent GI bleeding and/or aortic insufﬁciency can also raise the risk of pump thrombosis. Lower speeds allow pulsatility of arterial ﬂow, as evident by radial artery palpation and aortic valve excursion on echocardiography. At this writing, there are no national guidelines that recommend the frequency with which the aortic valve should open during CF LVAD support. As CF LVADs have been associated with GI arteriovenous malformations (AVMs) [35], some institutions advocate for lower LVAD speeds, allowing for frequent aortic valve opening to increase pulsatile blood ﬂow. The theory behind this is that increased pulsatility returns circulation to its inherent form and may prevent AVMs; however, data are lacking for broad support. Unfortunately, lower VAD revolutions per minute seem to be accompanied by a higher incidence of pump thrombosis, perhaps as lowering the pump speed increases the likelihood of areas of stasis within the device and decreases the washout of heat.

Suboptimal hypertension management may also contribute to pump thrombosis. Elevated blood pressure causes elevated afterload and leads to decreased blood ﬂow through all types of ventricular assist devices [15]. As blood ﬂows through the device, the heat created by the device does not wash out as efﬁciently, leading to elevated temperatures and platelet activation as described previously. The HeartWare device is particularly sensitive to afterload reduction as it relates to forward ﬂow and pump thrombosis.

As the INTERMACS registry is overwhelmingly populated with HeartMate II devices, a separate analysis by Najjar et al. was conducted to evaluate the risk factors for thromboembolic events in the HeartWare devices [12]. The events and the characteristics that confer signiﬁcant risk are listed below:

l being on aspirin (ASA) at doses at or below 81 mg/d; l having an INR <2; l having a less ill patient proﬁle of INTERMACS 3e7; l having a mean arterial pressure (MAP) >90.

The presence of any of these risk factors doubled the risk of a pump thrombosis event. It has been hypothesized that the increased MAP decreases ﬂow through the pump, causing less heat dissipation in the pump [14]. With respect to an INTERMACS proﬁle of 3e7, it is not yet apparent why this may be a risk factor for pump thrombosis in the HeartWare device.

MANAGEMENT AND MITIGATION OF RISK FACTORS AND PREVENTION OF PUMP THROMBOSIS

As mentioned previously, in the early experience of CF LVADs, initial pump thrombosis rates were quite low. In contrast to the topic of this chapter, in the years prior to 2012 much of the focus was on the management of bleeding complications. After anticoagulation protocols were relaxed across the community, rates of pump thrombosis were noted to elevate, as described earlier [36]. Given the signiﬁcant mortality and morbidity associated with pump thrombosis events, contemporaneous anticoagulation and antiplatelet protocols have been reinstated in most programs. As noted before, rates of pump thrombosis have fallen but not returned to 2010 levels, despite the widespread resumption of contemporaneous anti coagulation regimens [11]. This probably speaks to the multifactorial nature of pump thrombosis.

The PREVENT trial comprises the most syst ematic regimen of pump thrombosis prevention as of this writing [37].It was conducted at 24 centers across the United States, comprising a total of 300 patients. It was designed in response to the

8.4% 3-month pump thrombosis rate reported by Starling et al. [9]. The trial was an effort to adjust the totality of the aforementioned risk factors, and an effort to modify all of them concurrently to reduce pump thrombosis rates signiﬁcantly. The PREVENT trial recommendations are noted in Fig. 29.4.

The PREVENT trial tracked the incidence of pump thrombosis at 3 months as its primary end point. Secondary end points included 6-month pump thrombosis analysis as well as predeﬁned adverse events and level of adheren ce to the trial’s recommendations over the 6-month study period. Full adherence to implant techniques, heparin bridging, and pump speeds 9000 rpm resulted in a signiﬁcantly lower risk of pump thrombosis (1.9% vs. 8.9%; P < .01) and lower composite risk of suspected thrombosis, hemolysis, and ischemic stroke (5.7% vs. 17.7%; P < .01) at 6 months. When the study group was taken as a whole, including sites that did not fully adhere to the study recommendations, end-point analysis showed a conﬁrmed pump thrombosis rate of 2.9% at 3 months and 4.8% at 6 months. This is the most comprehensive prospective analysis on preventing early pump thrombosis as of this writing.

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FIGURE 29.4 Overview of PREVENT recommendations. HMII, HeartMate II; INR, international normalized ratio; LMWH, low-molecular-weight

heparin; LVAD, left-ventricular assist device; MAP, mean arterial pressure; PTT, partial thromboplastin time. Need permission Maltais S, Kilic A, Nathan

S, Keebler M, Emani S, Ransom J, et al. PREVENtion of HeartMate II Pump Thrombosis Through Clinical Management: the PREVENT multi-center study. J Heart Lung Transplant 2017;36(1):1e12. https://doi.org/10.1016/j.healun.2016.10.001.

With regard to longer-term thrombosis prevention, the goals become less clear. The mainstay of prevention is anticoagulant and antithrombotic management. The International Society of Heart and Lung Transplantation (ISHLT) guidelines give a class I level of evidence C recommendation for the use of aspirin (81e325 mg daily) in addition to warfarin in patients with mechanical circulatory support devices (MCSDs). They also give a class I level of evidence B recommendation that patients with MCSD should receive anticoagulation with warfarin to maintain an INR within a range as speciﬁed by each device manufacturer [38].

The most recent meta-analysis of antithrombotic therapy for prevention of pump thrombosis is a prime example of the lack of consensus in the literature surrounding this topic [39]. It showed major variations in antithrombotic treatment between studies and institutions, ranging from the use of dual antiplatelet agents to the exclusion of any antiplatelet agents. There seemed to be no trend toward what antiplatelet strategy prevents pump thrombosis. The literature is plagued with single-center studies comprising signiﬁcantly different populations, and this meta-analysis was unable to extract a useful signal from which to inform about the use of antiplatelet treatment. The best available guidance is based on expert opinion from the ISHLT guidelines on antithrombotic treatment options.

The same meta-analysis by Baumann Kreuziger et al. also failed to show any distinct signal in the use of chronic warfarin in LVAD patients [39]. Again, this was due to the widely differing institutional protocols, bleeding events leading to deescalation of warfarin dosing, and differences in study deﬁnitions of pump thrombosis and bleeding events. The best evidence for thrombosis prevention was reveal ed in one study, which found that subtherapeutic INR levels were reported in 31% of patients prior to a hemolytic event or thrombosis [40]. Because of this lack of certainty, antithrombotic and anticoagulant regimens vary signiﬁcantly by institution and are more dependent on institutional preference and experience than on scientiﬁc data.

PUMP THROMBOSIS PRESENTATION

Generally, pump thrombosis is initially categorized by the time of presentation after device implantation, with early being deﬁned as immediately postimplantation to 3 months and late being deﬁned as greater than 3 months postimplantation.

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FIGURE 29.5 International Society of Heart and Lung Transplantation diagnostic algorithm for left-ventricular assist device thrombosis and

treatment. INR, international normalized ratio. Need to ask for permission Goldstein DJ, John R, Salerno C, Silvestry S, Moazami N, Horstmanshof D, et al. Algorithm for the diagnosis and management of suspected pump thrombus. J Heart Lung Transplant 2013;32(7):667e70. https://doi.org/10.1016/j.

healun.2013.05.002.

Each presen tation period has different diagnosis and treatment strategies. Early presentations vary signiﬁcantly, and have no characteristic pattern. Common among them is persistent power elevations. If power elevations occur after the postoperative period an extensive workup should be initiated (Fig. 29.5).

Patients with late pump thrombosis typically present in four different ways. The ﬁrst is the patient with asymptomatic sustained power elevations. This is deﬁned as power greater than 10 W or power greater than 2 W above baseline for greater than 24 h. Typically, anticoagulation is optimized and markers of hemolysis are measured along with lactate dehydrogenase (LDH). If any of these markers are elevated, the patient is generally admitted to the hospital for intensiﬁcation of anticoagulation with a heparin infusion and further investigation.

The second type of presentation is an isolated elevation of LDH. This should prompt an urgent evaluation of intravascular hemolysis. Should intravascular hemolysis be present, then the patient should be considered for admission to the hospital and treatment with intravenous heparin or bivalirudin. It should be noted that sustained power elevations and isolated elevations of LDH are relatively late ﬁndings of pump thrombosis. They should be treated urgently with prompt evaluation, diagnosis, and treatment.

Occasionally, patients will present with clinical signs of hemolysis and/or symptoms of acute heart failure (including hemodynamic shock). This should prompt immediate admission to the hospital for diagnostic workup and acute therapy. Finally, some patients will present with obvious pump thrombosis with red alarm alerts and/or pump stoppage. Many of these patients will require emergent pump exchange without further diagnostic test ing.

DIAGNOSIS OF PUMP THROMBOSIS

A multidisciplinary and multiinstitutional ISHLT group devised an algorithm based on the best evidence for the diagnosis and management of pump thrombosis [26].

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The ﬁrst and most frequent sign of pump thrombosis is elevated pump power. This is used as a ﬁrst signal for pump thrombosis and has been proposed as a diagnostic tool. This has not proven to be of great utility. Steffen et al. tracked 203 HeartMate II patients between 2008 and 2012 and found 42 adverse events. Of the 42 adverse events, 8 were preceded by power elevations: three patients had power elevations before hemolysis, three had elevations before their transient ischemic attack or embolic stroke, none had an elevation before peripheral thromboembolism, and two had power elevations before conﬁrmed pump thrombosis [41]. Power elevations are probably best used as a sign of potential pump thrombosis leading to further investigation.

The ﬁrst truly useful diagnostic tool is measurem ent of serum LDH and plasma free hemoglobin (pfHgb). It should be noted that serum haptoglobin is often undetectable in patients with normally functioning LVADs because of chronic lowlevel hemolysis induced by these devices. INTERMACS deﬁnes signiﬁcant hemolysis as pfHgb >40 mg/dL with clinical signs and symptoms. The more contemporary deﬁnition of hemolysis also includes elevations of LDH >2.5 times the upper limit of normal, or an overall value >600 IU/L. Most centers use both laboratory values to assess for possible pump thrombosis. Recent debate in the literature suggests that serum LDH is the most sensitive and speciﬁc marker of current or impending pump thrombosis [42]. Shah et al. analyzed outcomes of 241 CF LVAD patients at their institution and created receiver operating characteristic curves for pfHgb and LDH. The area under the curve for LDH as a marker of device thrombosis was 0.94  0.01, which was signiﬁcantly higher than the 0.79  0.01 calculated for pfHgb (P < .001) [43]. The mechanism of this is probably due to the accelerated removal of pfHgb in the absence of haptoglobin, whereas LDH takes much longer to be eliminated from the bloodstream [44], meaning that the “signal” from pfHgb is detectable for a shorter period following mechanical hemolysis than the “signal” from LDH. Despite this debate, both levels are useful for diagnosing pump thrombosis and are widely used.

Echocardiography is used as a further tool to detect pump thrombosis. Echocardiography can be used to directly visualize thrombus in and adjacent to the inﬂow and outﬂow cannulas, but there are frequent technical limitations that prevent the direct visualization of thrombus (limited acoustic windows, presence of thrombus inside of an echodense structure, etc.). Uriel et al. described a novel echocardiographic ramp test for the diagnosis of device thrombosis [45]. Their group lowered HeartMate II pump speeds to 8000 rpm and measured the baseline left-ventricular end diastolic dimension (LVEDD) and pulsatility index (PI). They subsequently increased the pump revolutions per minute to 12,000 using increments of 400 rpm per step. They found that patients without thrombosis would have signiﬁcant decreases in LVEDD and PI with revolutions per minute increases, whereas the patients with surgically conﬁrmed pump thrombosis had no decrease in LVEDD or PI. This testing protocol has subsequently become a commonly utilized diagnostic tool.

Computed X-ray tomography with angiography (CTA) is also a useful tool in the diagnosis of suspected pump thrombosis. Tran and Nijjar examined the course of 24 patients with suspected LVAD thrombosis who underwent CTA

[46]. For the detection of any surgically conﬁrmed LVAD thrombosis, CTA had a sensitivity of 13% and a speciﬁcity of

100%. Most LVAD thrombosis occurs in the pump motor. Although these thrombi go undetected by CTA, this imaging tool provides an excellent detection of inﬂow or outﬂow graft thrombosis, with a sensitivity and speciﬁcity of 85% and 100%, respectively. Despite its limitations, CTA is still a very useful tool in the diagnosis of pump thrombosis (Fig. 29.6).

Conﬁ

rmation of pump thrombosis is provided only by visualization of the thrombus at the time of LVAD explantation (Fig. 29.7AeC), placing great importance on the preceding evaluation techniques. Successful management of pump thrombosis starts with heightened clinical awareness and early diagnosis, with a collaborative approach using the tools and testing described.

TREATMENT OF PUMP THROMBOSIS

Pump thrombosis is a dreaded complication after LVAD implantation because of the lack of safe and highly efﬁcacious medical treatment. Multiple series of case reports have been performed on treatment with tissue plasminogen activator (tPA) and GP IIb/IIIa inhibitors. Most reports have revealed low success rates and elevated mortality directly related to the treatments. Starling et al. reported a mortality of patients who did not undergo transplant or pump exchange of 48.2% at 6 months [9]. Speciﬁc details of these patients were not provided and it is presumed that this patient population may have been signiﬁcantly sicker than the population who went on to have device exchange and/or heart transplantation. Starling went on to note that mortality at 6 months among patients treated with device replacement or transplantation was similar to mortality among patients who did not have device thrombosis.

Köksel et al. published their case series of treating pump thrombosis with tPA. Of 10 patients treated, 4 died of intracranial hemorrhage and 1 died of ischemic cerebrovascular accident [47]. Tellor et al. examined the use of eptiﬁbatide for the treatment of pump thrombosis. They published a success rate of 22.7%, a bleeding event rate of 64.7%, and a death rate of 41.2% [48]. These data are from a mix of HeartMate II and HeartWare devices.

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(A) (B)

FIGURE 29.6 Normal imaging characteristics of left-ventricular assist device (LVAD) on computed tomography (CT). (A) Contrast-enhanced CT

maximal intensity projection (MIP) image showing different components of the LVAD. The motor, and the adjoining parts of the inﬂow and outﬂow cannulas, are not well visualized due to a beam hardening metal artifact. (B and C) Contrast-enhanced CT MIP coronal and axial images showing homogeneous contrast opaciﬁcation of the outﬂow cannula. The proximal outﬂow cannula has a bend protector, with a normal space in between. This space can erroneously be interpreted as circumferential thrombus. (D) Contrast-enhanced CT MIP image of inﬂow cannula showing homogeneous contrast opaciﬁcation of the proximal portion, with near midline position. The distal portion is not visualized due to a beam hardening artifact. Need permission

Tran BC, Nijjar PS. Role of contrast CT for the diagnosis and the prognosis of suspected LVAD thrombosis. J Card Surg 2017;32(2):162e5. https://doi.

org/10.1111/jocs.13094.

In HeartWare devices the outcomes of medical therapy seem to be similar to those of the HeartMate II. Stulak et al. reports medical treatment was successful in 14 of 29 episodes (48%). Complications of medical treatment included hemorrhagic stroke in six patients (21%), need for urgent device exchange/transplant in six (21%), and death in three (10%). Surgical treatment was successful in all seven patients (100%). No signiﬁcant early complications or early deaths occurred after device exchange [49].

Given the low success rate and high morbidity and mortality rate of available medical therapies, ﬁrst-line treatment of pump thrombosis is device exchange or transplantation. Stulak et al. reported a low early mortality of 3.5% after pump replacement. Furthermore, the actuarial 1-year survival and freedom from repeated device exchange after the ﬁrst exchange were 89% and 79%, respectively [50]. Moazami et al. reported on the overall safety of pump replacement for all causes, including infection and percutaneous lead damage, with an early mortality of 6.5% and a 1-year mortality of 30% [51]. Patients were likely to feel similarly well after device replacement compared with patients not requiring a device replacement as measured by a visual analog scale [10].

There are some downsides to surgical intervention. First, the probability of recurrent thrombosis is progressively higher after each pump exchange, and the thrombosis event confers an increased risk of morbidity and death [52]. Patients also experienced more stroke and more device infection after device exchange compared with patients maintained on their ﬁrst device [10]. The third, and most obvious, downside is the need for anothe r highly invasive surgical procedure, which includes a prolonged recovery and reconditioning time.

(B)

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Ventricular Assist Device Thrombosis: Past, Present, and Future Chapter | 29 431

(A)

(C)

FIGURE 29.7 (A) Explanted HeartMate II left-ventricular assist device with suspected thrombosis. (B) Thrombus found on rotor and outlet bearing cup.

Although surgical outcomes are reported to be vastly superior compared with those described in the medical treatment studies, there is one important caveat; the patient must be healthy enough to survive a second cardiac surgery. It is likely that patient selection bias plays a powerful role in all these studies, and that the healthy patients end up with device exchange while the sick patients end up with medical therapy. Furthermore, there is an important role of medical therapy in patients supported as BTT as suspected pump thrombosis with active treatment elevates a patient’s position on the transplant list to 1A. Therefore, choices between medical or surgical therapy can be quite complex and do not lend well to a generalized algorithm. Choices for treatment are probably best made on a highly individualized basis, employing consideration of the patient riskebeneﬁt proﬁle and the treatment options available.

CURRENT AND FUTURE DIRECTIONS

The HeartMate III LVAD is a fully magnetically levitated centrifugal-ﬂow pump that is under investigation as of this writing. It is designed to address many issues of the previous generation of LVADs, including pump thrombosis [53]. The magnetically levitated pump rotor decreases local heat formation and lacks a bearing that is a common site of pump thrombosis on the HeartMate II. The levitated rotor also provides large pump gaps to decrease shear stress on the blood components. The inlet cannula and rotor are a single unit, much like the HeartWare device, eliminating much of the cannula length from the HeartMate II design, which is a common site of pump thrombosis. There is an independent pulsatility offered with brief cycles of increased rotation speed.

Though the HeartMate III device is still in the investigational phase via the CE Mark and MOMEN TUM 3 trials, early results have been encouraging. MOMENTUM 3 has 294 patients, of which 152 have been assigned to the centrifugal-ﬂow pump and 142 to the axial-ﬂow pump (HeartMate II). At 6 months, only one patient in the HeartMate III group underwent reoperation to replace or remove the pump, compared with the HeartMate II group, which had a total of 18 pump thromboses in 14 patients. There were no reported cases of suspected or conﬁrmed pump thrombosis in the HeartMate III

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group [54]. While not statistically signiﬁcant, the HeartMate III group had fewer strokes in tota l (7.9% vs. 10.9%, P ¼ .39), yet more disabling strokes (6% vs. 3.6%, P ¼ .36) compared with the HeartMate II group. As the latest data as of this writing cover only 6 months on device therapy, further follow-up data will be required to assess for the potential of late complications from the HeartMate III.

The CE Mark trial has longer follow-up, but signiﬁcantly fewer patients (n ¼ 50). In their 1-year analysis [55], they reported zero episodes of pump thrombosis with one event of outﬂow graft thrombosis. Schmitto et al. have reported 2-year outcomes at the most recent annual meeting of ISHLT in April of 2017; in follow -up to date, there has yet to be an episode of pump thrombosis [56].

SUMMARY

LVAD thrombosis is a complicated, multifaceted problem that ranges from molecular derangements to device-speciﬁc pathologic interactions and patient-speciﬁc etiologies. It is a problem that must be approached in a multidisciplinary fashion from many different perspectives to prevent thrombosis from occurring. Although ongoing device redesigns, such as the HeartMate III, and studies such as the PREVENT trial are excellent steps in the direction toward lowering the incidence of pump thrombosis, more work needs to be done in the areas of prevention, detection, and treatment.

REFERENCES

[1] Englert III JA, Davis JA, Krim SR. Mechanical circulatory support for the failing heart: continuous-ﬂow left ventricular assist devices. Ochsner J

2016;16(3):263e9.

[2] Sheikh FH, Russell SD. HeartMate

1586/erd.10.77.

[3] Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Long-term use of a left ventricular assist device for end-stage

heart failure. N Engl J Med 2001;345(20):1435e43.

[4] Miller LW, Pagani FD, Russell SD, John R, Boyle AJ, Aaronson KD, et al. Use of a continuous-ﬂow device in patients awaiting heart trans-

plantation. N Engl J Med 2007;357(9):885e96.

[5] Slaughter MS, Rogers JG, Milano CA, Russell SD, Conte JV, Feldman D, et al. Advanced heart failure treated with continuous-ﬂow left ventricular

assist device. N Engl J Med 2009;361(23):2241e51.

[6] Tuncer ON, Kemaloglu C, Erbasan O, Gölbas¸ı I, Türkay C, Bayezid ö. Outcomes and readmissions after continuous ﬂow left ventricular assist

device: Heartmate II versus heartware ventricular assist device. Transplant Proc 2016;48(6):2157e61. https://doi.org/10.1016/j.transproceed.2016.

03.056.

[7] University of Alabama at Birmingham. INTERMACS quarterly stastical report 2016 Q3. Birmingham, AL: University of Alabama at Birmingham;

2016. Retrieved from: https://www.uab.edu/medicine/intermacs/images/Federal_Quarterly_Report/Federal_Partners_Report_2016_Q3.pdf.

[8] Pagani FD, Miller LW, Russell SD, Aaronson KD, John R, Boyle AJ, Frazier OH. Extended mechanical circulatory support with a continuous-ﬂow

rotary left ventricular assist device. J Am Coll Cardiol 2009;54(4):312e21. https://doi.org/10.1016/j.jacc.2009.03.055.

[9] Starling RC, Moazami N, Silvestry SC, Ewald G, Rogers JG, Milano CA, et al. Unexpected abrupt increase in left ventricular assist device

thrombosis. N Engl J Med 2014;370(1):33e40. https://doi.org/10.1056/NEJMoa1313385.

[10] Kirklin JK, Naftel DC, Kormos RL, Pagani FD, Myers SL, Stevenson LW, et al. Interagency Registry for Mechanically Assisted Circulatory Support

(INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device. J Heart Lung Transplant 2014;33(1):12e22. https://

doi.org/10.1016/j.healun.2013.11.001.

[11] Kirklin JK, Naftel DC, Pagani FD, Kormos RL, Myers S, Acker MA, et al. Pump thrombosis in the Thoratec HeartMate II device: an update analysis

of the INTERMACS Registry. J Heart Lung Transplant 2015;34(12):1515e26. https://doi.org/10.1016/j.healun.2015.10.024.

[12] Najjar SS, Slaughter MS, Pagani FD, Starling RC, McGee EC, Eckman P, et al. An analysis of pump thrombus events in patients in the HeartWare

ADVANCE bridge to transplant and continued access protocol trial. J Heart Lung Transplant 2014;33(1):23e34. https://doi.org/10.1016/j.healun.

2013.12.001.

[13] Rogers JG, Pagani FD, Tatooles AJ, Bhat G, Slaughter MS, Birks EJ, et al. Intrapericardial left ventricular assist device for advanced heart failure.

N Engl J Med 2017;376(5):451e60. https://doi.org/10.1056/NEJMoa1602954. [14] Blitz A. Pump thrombosisda riddle wrapped in a mystery inside an enigma. Ann Cardiothorac Surg 2014;3(5):450e71. [15] Kapur NK, Vest AR, Cook J, Kiernan MS. Pump thrombosis: a limitation of contemporary left ventricular assist devices. Curr Probl Cardiol

2015;40(12):511e40. https://doi.org/10.1016/j.cpcardiol.2015.03.004. [16] Tchouta LN, Bonde PN. The quest for nonthrombotic surface modiﬁcations to achieve hemocompatibility of implantable devices. Am Soc Artif

Intern Organs J 2015;61(6):623e34. https://doi.org/10.1097/MAT.0000000000000283 [17] Hamilton KF, Schmidt VI, Mager I, Schmitz-Rode T, Steinseifer U. Consequences arising from elevated surface temperatures on human blood:

thoughts and progress. Artif Organs 2010;34(9):783e7. https://doi.org/10.1111/j.1525-1594.2010.01089.x. [18] Saeed O, Maybaum S, Alessandro DD, Goldstein DJ, Patel SR. Aortic valve opening and thrombotic events with continuous-ﬂow left ventricular

assist devices. J Heart Lung Transplant 2014;33(1):109e12. https://doi.org/10.1016/j.healun.2013.07.008.

II continuous-ﬂow left ventricular assist system. Expet Rev Med Dev 2011;8(1):11e21. https://doi.org/10.

Ventricular Assist Device Thrombosis: Past, Present, and Future Chapter | 29 433

https://t.me/med1917

[19] Valerio L, Tran PL, Sheriff J, Brengle W, Ghosh R, Chiu W-C, et al. Aspirin has limited ability to modulate shear-mediated platelet activation

associated with elevated shear stress of ventricular assist devices. Thromb Res 2016;140:110e7. https://doi.org/10.1016/j.thromres.2016.01.026.

[20] Sheriff J, Tran PL, Hutchinson M, DeCook T, Slepian MJ, Bluestein D, Jesty J. The platelet hammer: in vitro platelet activation under repetitive

hypershear. In: Engineering in medicine and biology society (EMBC), 2015 37th annual international conference of the IEEE. IEEE; 2015. p. 262e5. Retrieved from: http://ieeexplore.ieee.org/abstract/document/7318350/.

[21] de Biasi AR, Manning KB, Salemi A. Science for surgeons: understanding pump thrombogenesis in continuous-ﬂow left ventricular assist devices.

J Thorac Cardiovasc Surg 2015;149(3):667e73. https://doi.org/10.1016/j.jtcvs.2014.11.041.

[22] Taghavi S, Ward C, Jayarajan SN, Gaughan J, Wilson LM, Mangi AA. Surgical technique inﬂuences HeartMate II left ventricular assist device

thrombosis. Ann Thorac Surg 2013;96(4):1259e65. https://doi.org/10.1016/j.athoracsur.2013.05.081.

[23] Uriel N, Han J, Morrison KA, Nahumi N, Yuzefpolskaya M, Garan AR, et al. Device thrombosis in HeartMate II continuous-ﬂow left ventricular

assist devices: a multifactorial phenomenon. J Heart Lung Transplant 2014;33(1):51e9. https://doi.org/10.1016/j.healun.2013.10.005.

[24] Stulak JM, Deo S, Schirger J, Aaronson KD, Park SJ, Joyce LD, et al. Preoperative atrial ﬁbrillation increases risk of thromboembolic events after

left ventricular assist device implantation. Ann Thorac Surg 2013;96(6):2161e7. https://doi.org/10.1016/j.athoracsur.2013.07.004.

[25] Xuereb L, Go PH, Kaur B, Akrawe S, Nemeh HW, Borgi J, et al. Impact of preoperative atrial ﬁbrillation on postoperative thromboembolic events

after left ventricular assist device implantation. Ann Thorac Surg 2016;102(5):1543e9. https://doi.org/10.1016/j.athoracsur.2016.04.025.

[26] Goldstein DJ, John R, Salerno C, Silvestry S, Moazami N, Horstmanshof D, et al. Algorithm for the diagnosis and management of suspected pump

thrombus. J Heart Lung Transplant 2013;32(7):667e70. https://doi.org/10.1016/j.healun.2013.05.002.

[27] Lipinska-Gediga M. Coagulopathy in sepsis d a new look at an old problem. Anestezjol Intensywna Ter 2016;48(5):352e9. https://doi.org/10.

5603/AIT.a2016.0051.

[28] Hackmann A, Lockard K, Allen C, Kunz N, Jackson K, Bhama J, et al. Post discharge non-compliance increases risk of left ventricular assist device

(LVAD) malfunction but does not affect survival. J Heart Lung Transplant 2013;32(4):S176. https://doi.org/10.1016/j.healun.2013.01.422.

[29] Mehra MR, Stewart GC, Uber PA. The vexing problem of thrombosis in long-term mechanical circulatory support. J Heart Lung Transplant

2014;33(1):1e11. https://doi.org/10.1016/j.healun.2013.12.002.

[30] Alhosaini H, Jensen BC, Chang PP, Sheridan BC, Katz JN. A novel link between G6PD deﬁciency and hemolysis in patients with continuous-ﬂow

left ventricular assist devices. J Heart Lung Transplant 2014;33(1):116e7. https://doi.org/10.1016/j.healun.2013.10.028.

[31] Welp H, Ellger B, Scherer M, Lanckohr C, Martens S, Gottschalk A. Heparin-induced thrombocytopenia during extracorporeal membrane

oxygenation. J Cardiothorac Vasc Anesth 2014;28(2):342e4. https://doi.org/10.1053/j.jvca.2012.10.014.

[32] Schenk S, El-Banayosy A, Prohaska W, Arusoglu L, Morshuis M, Koester-Eiserfunke W, et al. Heparin-induced thrombocytopenia in patients

receiving mechanical circulatory support. J Thorac Cardiovasc Surg 2006;131(6). 1373e1381.e4, https://doi.org/10.1016/j.jtcvs.2006.01.048.

[33] Boehme AK, Pamboukian SV, George JF, Dillon C, Levitan EB, Grifﬁ

assist device. Am Soc Artif Intern Organs J 2015;61(6):640e7. https://doi.org/10.1097/MAT.0000000000000284.

[34] Stulak JM, Lee D, Haft JW, Romano MA, Cowger JA, Park SJ, et al. Gastrointestinal bleeding and subsequent risk of thromboembolic events during

support with a left ventricular assist device. J Heart Lung Transplant 2014;33(1):60e4. https://doi.org/10.1016/j.healun.2013.07.020.

[35] Demirozu ZT, Radovancevic R, Hochman LF, Gregoric ID, Letsou GV, Kar B, et al. Arteriovenous malformation and gastrointestinal bleeding in

patients with the HeartMate II left ventricular assist device. J Heart Lung Transplant 2011. https://doi.org/10.1016/j.healun.2011.03.008. [36] Stulak JM, Maltais S. A different perspective on thrombosis and the HeartMate II. N Engl J Med Boston 2014;370(15):1467e8. [37] Maltais S, Kilic A, Nathan S, Keebler M, Emani S, Ransom J, et al. PREVENtion of HeartMate II pump thrombosis through clinical management:

the prevent multi-center study. J Heart Lung Transplant 2017;36(1):1e12. https://doi.org/10.1016/j.healun.2016.10.001. [38] Feldman D, Pamboukian SV, Teuteberg JJ, Birks E, Lietz K, Moore SA, et al. The 2013 international society for heart and Lung transplantation

guidelines for mechanical circulatory support: executive summary. J Heart Lung Transplant 2013;32(2):157e87. https://doi.org/10.1016/j.healun.

2012.09.013.

[39] Baumann Kreuziger LM, Kim B, Wieselthaler GM. Antithrombotic therapy for left ventricular assist devices in adults: a systematic review.

J Thromb Haemostasis 2015;13(6):946e55. https://doi.org/10.1111/jth.12948. [40] Frazier OH, Gemmato C, Myers TJ, Gregoric ID, Radovancevic B, Loyalka P, Kar B. Initial clinical experience with the HeartMateÒ II axial-ﬂow

left ventricular assist device. Tex Heart Inst J 2007;34(3):275. [41] Steffen RJ, Soltesz EG, Miracle K, Lee S, Mountis M, Moazami N. Incidence of increases in pump power use and associated clinical outcomes with

an axial continuous-ﬂow ventricular assist device. J Heart Lung Transplant 2014;33(1):105e6. [42] Cowger JA, Romano MA, Shah P, Shah N, Mehta V, Haft JW, et al. Hemolysis: a harbinger of adverse outcome after left ventricular assist device

implant. J Heart Lung Transplant 2014;33(1):35e43. https://doi.org/10.1016/j.healun.2013.08.021. [43] Shah P, Mehta VM, Cowger JA, Aaronson KD, Pagani FD. Diagnosis of hemolysis and device thrombosis with lactate dehydrogenase during left

ventricular assist device support. J Heart Lung Transplant 2014;33(1):102e4. https://doi.org/10.1016/j.healun.2013.07.013. [44] Dale J, Myhre E, Rasmussen K. Elimination of hemoglobin and lactate dehydrogenase from plasma in normals and patients with intravascular

hemolysis. Scand J Clin Lab Investig 1972;29(4):389e95. [45] Uriel N, Morrison KA, Garan AR, Kato TS, Yuzefpolskaya M, Latif F, et al. Development of a novel echocardiography ramp test for speed

optimization and diagnosis of device thrombosis in continuous-ﬂow left ventricular assist devices. J Am Coll Cardiol 2012;60(18):1764e75. https://

doi.org/10.1016/j.jacc.2012.07.052.

[46] Tran BC, Nijjar PS. Role of contrast CT for the diagnosis and the prognosis of suspected LVAD thrombosis. J Card Surg 2017;32(2):162e5. https://

doi.org/10.1111/jocs.13094.

n R, et al. Predictors of thromboembolic events in patients with ventricular

434 Cardiovascular Thrombus

https://t.me/med1917

[47] Köksel U, Erbasan O, Bayezid ö, Kemaloglu C, Özçobanoglu S, Gölbas¸ı I, Türkay C. Thrombosis in continuous ﬂow left ventricular assist

devices: our cl inical experience with medical and surgical management. Transplant Proc 2016;48(6):2162e7. https://doi.org/10.1016/j.

transproceed.2016.04.025.

[48] Tellor BR, Smith JR, Prasad SM, Joseph SM, Silvestry SC. The use of eptiﬁbatide for suspected pump thrombus or thrombosis in patients with left

ventricular assist devices. J Heart Lung Transplant 2014;33(1):94e101. https://doi.org/10.1016/j.healun.2013.11.002.

[49] Stulak JM, Dunlay SM, Sharma S, Haglund NA, Davis MB, Cowger J, et al. Treatment of device thrombus in the HeartWare HVAD: success and

outcomes depend signiﬁcantly on the initial treatment strategy. J Heart Lung Transplant 2015;34(12):1535e41. https://doi.org/10.1016/j.healun.

2015.10.020.

[50] Stulak JM, Cowger J, Haft JW, Romano MA, Aaronson KD, Pagani FD. Device exchange after primary left ventricular assist device implantation:

indications and outcomes. Ann Thorac Surg 2013;95(4):1262e8. https://doi.org/10.1016/j.athoracsur.2012.08.031.

[51] Moazami N, Milano CA, John R, Sun B, Adamson RM, Pagani FD, et al. Pump replacement for left ventricular assist device failure can be done

safely and is associated with low mortality. Ann Thorac Surg 2013;95(2):500e5. https://doi.org/10.1016/j.athoracsur.2012.09.011.

[52] Stewart GC, Givertz MM, Mehra MR. Pump thrombosis redux. J Heart Lung Transplant 2015;34(12):1511e4. https://doi.org/10.1016/j.healun.

2015.10.038.

[53] Schmitto JD, Hanke JS, Rojas SV, Avsar M, Haverich A. First implantation in man of a new magnetically levitated left ventricular assist device

(HeartMate III). J Heart Lung Transplant 2015;34(6):858e60. https://doi.org/10.1016/j.healun.2015.03.001.

[54] Mehra MR, Naka Y, Uriel N, Goldstein DJ, Cleveland JC, Colombo PC, et al. A fully magnetically levitated circulatory pump for advanced heart

failure. N Engl J Med 2017;376(5):440e50. https://doi.org/10.1056/NEJMoa1610426.

[55] Krabatsch T, Netuka I, Schmitto JD, Zimpfer D, Garbade J, Rao V, et al. Heartmate 3 fully magnetically levitated left ventricular assist device for the

treatment of advanced heart failure e1 year results from the Ce mark trial. J Cardiothorac Surg 2017;12(1). https://doi.org/10.1186/s13019-017-

0587-3.

[56] Schmitto JD, Pya Y, Zimpfer D, Krabatsch T, Garbade J, Rao V, et al. (151) - HeartMate 3 fully magnetically levitated left ventricular assist device

for the treatment of advanced heart failure - CE mark study 2-year results. J Heart Lung Transplant 2017;36(4, Suppl.):S66. https://doi.org/10.1016/j.

healun.2017.01.162.