Multiple Device Exchanges and Recurrent Thrombosis
After a primary device exchange for any indication, seven patients required at least one additional exchange (refer to Figure 3 for flowchart of device exchanges by indication and procedure). Overall, three patients had primary and secondary exchanges for device thrombosis and thus had recurrent thrombosis at the time of their secondary exchange (second thrombus indicated by arrows and dashed lines in Figure 3B). In addition, two patients had second and third device exchange for thrombosis, so the recurrent thrombosis occurred at their third device exchange (second thrombus indicated in Figure 3C).
Of the 18 patients who had at least one exchange for device thrombosis (14 during a primary exchange and 4 for a secondary exchange), five (31%) had at least one recurrence. The rate of re-thrombosis was 0.43 events per patient-year for patients whose first thrombosed device was exchanged by sternotomy, and 0.33 events per patient-year for those whose first thrombosed device was exchanged subcostally. The second device thrombosis was exchanged with a subcostal incision in two patients and a sternotomy in the other three (Figure 4).
All of the patients who required multiple exchanges were male, and there were no significant differences in the patients who had recurrent device thrombosis versus first time device thrombosis (Table 3). Furthermore, the average INR between the initial implant and first device exchange for all patients who had a primary exchange for device thrombosis was 1.93 ± 0.56 for patients who did not have recurrent thrombosis, and 1.94 ± 0.77 for patients who re-thrombosed (p = 0.97). In addition, for the patients who re-thrombosed, the average INR between the first and second thrombus was 2.07 ± 0.58. Although two of the patients who had a device thrombosis (at any time) did have hematological disorders, neither of them had recurrent thrombosis. The first patient was a 73 year-old male with idiopathic thrombocytopenic purpura (ITP) who had a primary sternotomy exchange for device thrombosis, who died 16 months post device exchange without any further device thromboses. The second patient was a 43 year-old female who also had a primary sternotomy exchange for device thrombosis, and died in the first month after exchange because of multiorgan failure.
Outcomes After Primary Device Exchange
After a primary device exchange, the possible outcomes were transplantation, re-exchange, death, or continued support. The 1 year survival was 62.5% for the sternotomy exchanges and 100% for the subcostal exchanges (p = 0.02; Figure 5), censored for re-exchange and transplantation. At 30 days post device exchange, the actuarial survival was 83.3% and 100% for the sternotomy and subcostal cohorts, respectively (p = 0.09). In the sternotomy cohort (5 bridge to transplant [BTT]/7 destination therapy (DT)), four patients were re-exchanged, one was transplanted, one remains on HM II support, and six died. Four of these patients died within 1 year of sternotomy device exchange, two died because of postoperative multiorgan failure, one because of an infection (bacteremia), and one because of battery removal while intoxicated. The other two patients died at 16 months and 3 years post device exchange because of multiorgan failure and sudden death at home, respectively. In contrast, none of the patients who received a subcostal exchange (11 BTT/5 DT) have died at the time of this writing. Seven (44%) were successfully transplanted with a median time to transplantation of 4.5 months (IQR = 2.1, 8.9), four (25%) were re-exchanged, and five (31%) remain on HM II support (for a mean time of 21.63 ± 7.64 months).
A total of 10 patients received a transplant, eight after the first device exchange, two after a second exchange, and one after a third exchange. The median follow-up time posttransplant is 13.23 months, ranging from 6.66 to 49.85 months. The 1 year freedom from death posttransplant was 87.5%, with one death at 9 days after transplant. This patient was successfully transplanted after a subcostal primary device exchange for device thrombosis, and died posttransplant because of a massive intraoperative ischemic stroke. The intraoperative TEE showed a large columnar thrombus that slowly migrated from the ascending aorta down to the descending aorta, which was suggestive of the migration of a thrombus that had existed inside of the outflow graft. Our current protocol includes screening patients with (suspected) left ventricular assist device (LVAD) thrombosis with CT angiogram to assess the outflow graft.
We examined long-term outcomes of HM II recipients requiring device exchange, as well as the risk for recurrent device thrombosis in this population. Our principal finding is that the long-term outcomes after a primary subcostal device exchange, with a 1 year survival of 100% in 16 subjects, are excellent and possibly superior to those achieved with full sternotomy. Furthermore, although the precise etiology of recurrent device thrombosis remains elusive, the frequency of 31% in this series is of great concern and warrants particularly careful monitoring.
The HM II is the only currently approved device for destination therapy in the United States and has an excellent overall performance record with a nearly 65% 2 year survival in patients otherwise highly unlikely to survive at all.7, 8 However, the recently reported significant increase in the rate of device thrombosis has raised concerns regarding the overall benefit of its use.1 Historically, device thrombosis has been an infrequently observed event diagnosis of which required substantial hemolysis (plasma free hemoglobin > 40, lactate dehydrogenase > 1,000) as well as overt device malfunction.7 More recently, many centers, including our own, use surveillance LDH screening and echocardiography to detect device thrombosis early.9 Whether the recently reported “spike” in device thrombosis is a true increase or the result of enhanced screening and “preemptive” device exchange remains subject of intense discussion in the LVAD community at the time of this writing. Furthermore, device exchange is a clinical endpoint equivalent to major stroke or death in prior as well as ongoing mechanical circulatory support trials (ENDURANCE).10, 11 Therefore, development of a successful management approach for device thrombosis and understanding of its impact on overall outcomes are necessary.
Although device exchange is costly and has historically been associated with major morbidity and possibly mortality, our data support the use of an early subcostal device exchange as a favorable solution to device thrombosis. Although the difference in survival between sternotomy and subcostal approach in our experience at first glance is striking (and similar to those previously reported by Moazami et al.),12 a report of 45 primary continuous flow device exchanges performed by sternotomy by Stulak et al. with 95% actuarial survival rate at 1 year and 77% at 18 months underscores that the sternotomy approach might also yield outstanding results.13 Therefore, the outcome differences we report may be because of selection bias, as patients with a suspicion of inflow cannula or outflow graft thrombosis will undergo device exchange via sternotomy. With that said, we believe that shorter operative and bypass times would ultimately translate into better outcomes in a head-to-head comparison, and that the substantially less invasive nature of subcostal exchange prohibits randomized study. Furthermore, although subcostal exchange is less traumatic, we do not feel that this resulted in a lower threshold for surgical intervention in either cohort. Although the introduction of subcostal exchange may lead to more widespread adoption of early device exchange algorithms, our indication for device exchange has been unchanged for several years. As described in one of our earlier publications, we routinely proceed to device exchange once device thrombosis is suspected based on LDH elevation as well as positive ramp study, and end-organ dysfunction has ensued.9, 14 This algorithm has been used regardless of the surgical technique that was used, and as such we do not believe this could have biased our results.
The risk of recurrent thrombosis caused by surgical and mechanical factors must also be considered. One concern inherent in the use of subcostal exchange (i.e., a simple “motor replacement”) is the chance of missing a thrombus when the outflow graft and inflow cannula are not removed.10 However, we did not detect a difference in recurrent thrombosis rate between subcostal (i.e., motor exchange only) and sternotomy approach (with replacement of inflow cannula and outflow graft). Of note, multiple steps are taken in the operating room to reduce the chance of missing a thrombus. After motor removal, the inlet stator is inspected for clot to confirm the clinical diagnosis of device thrombosis. Clot is most commonly found in this location. Second, brisk back-bleed should be expected from an uncompromised inflow conduit and outflow graft. Absence of clot in conjunction with poor back bleeding would dictate conversion to sternotomy with replacement of inflow cannula and outflow graft. Furthermore, an abbreviated ramp test with intraoperative TEE is sometimes performed after the exchange to ensure that the left ventricle (LV) decompresses with increased speed.9
Although multiple papers have commented on the relative safety of device exchange, none have highlighted a high rate of recurrent thrombosis. In our series, 31% of patients with device thrombosis developed a second thrombosis despite strict monitoring of anticoagulation; none of these patients had a known hematological disorder. This is much higher than the previously reported rate of multiple exchanges of 8.3% by Moazami et al., in which only six of the 72 patients required multiple device exchanges (note: this is for all indications).12
Although the recurrent thrombosis cohort is not large enough to warrant any definitive conclusions, it is clear that this issue requires further investigation of potentially contributing clinical, surgical, and manufacturing factors. Since the five patients who experienced recurrent device thrombosis required a total of 17 devices, it is apparent that this phenomenon has considerable financial and clinical implications.
As with any retrospective analysis with relatively small cohort sizes, this investigation has its limitations. For example, it must be noted that the subcostal and sternotomy exchanges were used in different eras, so that familiarity and understanding of device exchanges were higher when the subcostal exchanges began. Also, the high rate of re-exchange as compared to prior analyses must be evaluated in the context of increased vigilance for the detection of device thrombosis. Lastly, it is acknowledged that the direct comparison of surgical technique to long-term outcomes is not perfect, and that many clinical confounding factors likely exist.
In conclusion, this study shows excellent long-term outcomes after subcostal device exchange, as well as the significant risk of re-thrombosis after device exchange, irrespective of operative approach. The subcostal exchange is without question less traumatic and costly than a sternotomy exchange with lower, if any, blood transfusion requirements, shorter time to extubation, and shorter ICU stay.3 Lastly, patients can be successfully exchanged multiple times, although recurrent device thrombosis may render multiple device exchanges a costly and ultimately futile effort despite excellent technical results. This finding further underscores the urgent need to study the etiology of device thrombosis.
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3. Ota T, Yerebakan H, Akashi H, et al. Continuous-flow left ventricular assist device exchange: clinical outcomes. J Heart Lung Transplant. 2014;33:65–70
4. Gregoric ID, Bruckner BA, Jacob L, et al. Clinical experience with sternotomy versus subcostal approach for exchange of the HeartMate XVE to the HeartMate II ventricular assist device. Ann Thorac Surg. 2008;85:1646–1649
5. Uriel N, Pak SW, Jorde UP, et al. Acquired von Willebrand syndrome after continuous-flow mechanical device support contributes to a high prevalence of bleeding during long-term support and at the time of transplantation. J Am Coll Cardiol. 2010;56:1207–1213
6. Slaughter MS, Naka Y, John R, et al. Post-operative heparin may not be required for transitioning patients with a HeartMate II left ventricular assist system to long-term warfarin therapy. J Heart Lung Transplant. 2010;29:616–624
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9. Uriel N, Morrison KA, Garan AR, et al. Development of a novel echocardiography ramp test for speed optimization and diagnosis of device thrombosis in continuous-flow left ventricular assist devices: the Columbia ramp study. J Am Coll Cardiol. 2012;60:1764–1775
10. Pagani F, Rogers J. A Clinical Trial to Evaluate the HeartWare® Ventricular Assist System (ENDURANCE). 2010 http://clinicaltrials.gov
. Unique identified: NCT01166347.
11. 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
12. Moazami N, Milano CA, John R, et al.HeartMate II Investigators. Pump replacement for left ventricular assist device failure can be done safely and is associated with low mortality. Ann Thorac Surg. 2013;95:500–505
13. 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;95:1262–1267 discussion 1267
14. Uriel N, Han J, Morrison KA, et al. Device thrombosis in HeartMate II continuous-flow left ventricular assist devices: A multifactorial phenomenon. J Heart Lung Transplant. 2014;33:51–59
CF-LVAD; Exchange; LVAD; Malfunction; Subcostal; Sternotomy; ThrombosisCopyright © 2015 by the American Society for Artificial Internal Organs