Left Ventricular Assist Device Thrombosis Research Articles

Left Ventricular Assist Device Inflow Cannula Angle and Thrombosis Risk.

As heart failure prevalence continues to increase in the setting of a static donor supply, left ventricular assist device (LVAD) therapy for end-stage heart failure continues to grow. Anecdotal evidence suggests that malalignment of the LVAD inflow cannula may increase thrombosis risk, but this effect has not been explored mechanistically or quantified statistically. Our objective is to elucidate the impact of surgical angulation of the inflow cannula on thrombogenicity. Unsteady computational fluid dynamics is used in conjunction with computational modeling and virtual surgery to model flow through the left ventricle for 5 different inflow cannula angulations. We use a holistic approach to evaluate thrombogenicity: platelet-based (Lagrangian) metrics to evaluate the platelet mechanical environment, combined with flow-based (Eulerian) metrics to investigate intraventricular hemodynamics. The thrombogenic potential of each LVAD inflow cannula angulation is quantitatively evaluated based on platelet shear stress history and residence time. Intraventricular hemodynamics are strongly influenced by LVAD inflow cannula angulation. Platelet behavior indicates elevated thrombogenic potential for certain inflow cannula angles, potentially leading to platelet activation. Our analysis demonstrates that the optimal range of inflow angulation is within 0±7° of the left ventricular apical axis. Angulation of the inflow cannula >7° from the apical axis (axis connecting mitral valve and ventricular apex) leads to markedly unfavorable hemodynamics as determined by computational fluid dynamics. Computational hemodynamic simulations incorporating Lagrangian and Eulerian metrics are a powerful tool for studying optimization of LVAD implantation strategies, with the long-term potential of improving outcomes.

Treatment of Left Ventricular Assist Device Thrombosis: Single-Center Experience.

Heart failure is the one of the biggest health problem in the world. Because of limited donors for heart transplant procedures, the ventricular assist device has become a solution for heart failure therapy. With the increase in number of ventricular assist devices, the incidence of complications has also increased. One of the most important life-threatening complications is ventricular assist device thrombosis. Medical therapy and changes in the ventricular assist device are the main therapy methods for ventricular assist device thrombosis. In this study, we showed our clinical experience with treatment of ventricular assist device thrombosis.

Novel use of low-dose thalidomide in refractory gastrointestinal bleeding in left ventricular assist device patients.

Gastrointestinal bleeding (GIB) is a complication reported in patients post left ventricular assist device (LVAD) implantation that is associated with high mortality rates. Thalidomide is an anti-angiogenic compound that may offer a potential option for management of refractory LVAD-related GIB. A single-center, retrospective review was conducted from January 2009 to October 2016 at a tertiary cardiology center. It included LVAD patients initiated on thalidomide for refractory GIB. All patients (n = 11) were started on thalidomide 50 mg nocte and there was resolution of GIB in all patients except one (90.9%) during initial thalidomide treatment.The median duration of thalidomide therapy was 98 days (interquartile range: 34-215). The dose of thalidomide was reduced for 2 patients due to adverse effects. Thalidomide therapy was discontinued in 6 patients due to cessation of GIB (n = 4) and adverse effects (n = 2). Reported adverse effects included LVAD thrombosis (n = 2), somnolence (n = 1), neuropathy (n = 1), constipation (n = 1), and transaminitis (n = 1).Recurrent GIB occurred in 4 patients (45.4%) post-discontinuation of thalidomide therapy, which led to the re-initiation of therapy. Thalidomide appears to be a safe and effective option for management of refractory LVAD-related GIB. Monitoring for recurrent GIB should be performed closely following cessation of thalidomide therapy.

Clinical and In Vitro Evidence That Subclinical Hemolysis Contributes to LVAD Thrombosis

Recent data suggest that hemolysis contributes to left ventricular assist device (LVAD) thrombosis, but the mechanism is unknown. In a clinical study, we measured plasma free hemoglobin (pfHgb) and the incidence of LVAD thrombosis. In an in vitro study, we examined biophysical relationships between shear stress, pfHgb and von Willebrand factor (vWF) metabolism toward understanding mechanisms of LVAD thrombosis. In the clinical study, blood samples were obtained from continuous-flow LVAD patients (n= 30). Plasma free hemoglobin was measured via enzyme-linked immunosorbent assay. Plasma lactate dehydrogenase (LDH) was measured with a fluorimetric assay. In the in vitro study, to investigate mechanism, human plasma (n= 10)was exposed to LVAD-like shear stress (175 dyne/cm2) with and without free hemoglobin (30 mg/dL). ADAMTS-13 (the vWF protease) activity was quantified with Förster resonance energy transfer. vWF size was quantified withimmunoblotting. vWF clotting function was quantified with an enzyme-linked immunosorbent assay. In the clinical study, LVAD support caused subclinical hemolysis. In all patients, LDH increased significantly from 213 ± 9 U/L to 366 ± 31 U/L at 10 days of support (p < 0.0001) and remained significantly elevated at 280 ± 18 U/L at 1 month of support (p < 0.01). In 21 patients that did not develop LVAD thrombosis, pfHgb increased early but decreased over time (pre-LVAD: 5.2 ± 0.8 mg/dL; 1week: 19.8 ± 4.4 mg/dL, p < 0.01; 3 months: 9.3 ± 2.2 mg/dL, p= 0.07). In 9 patients that developed LVAD thrombosis, pfHgb was significantly elevated versus patients without thrombosis before (p < 0.001) and after 3 months (p < 0.05) of support (pre-LVAD: 20.2 ± 6.3 mg/dL; 1 week: 17.3 ± 3.7 mg/dL; 3 months: 21.5 ± 7.8 mg/dL). Similarly, after 3 months, patients that did not develop LVAD thrombosis had an LDH of 271 ± 28 U/L, whereas patients that later developed LVAD thrombosis had a significantly higher LDH of 625 ± 210 U/L (p= 0.02). In the in vitro study, shear stress degraded vWF similarly to an LVAD. Free hemoglobin inhibited ADAMTS-13 activity during shear stress (633 ± 27 ng/mL to 565 ± 24 ng/mL; p < 0.001). vWF was thereby protected from degradation, 4 vWF fragments decreased significantly (p ≤ 0.05), and vWF clotting function increased (1.15 ± 0.09 U/mL to 1.29 ± 0.09 U/mL, p= 0.06). These are the first data to demonstrate mechanistic relationships between subclinical hemolysis and a procoagulant state during continuous-flow LVAD support. Patients with high pfHgb and LDH were more likely to develop LVAD thrombosis. In vitro experiments demonstrated that free hemoglobin inhibited ADAMTS-13, protected vWF from degradation, increased vWF clotting function, and created a procoagulant state. As such, pfHgb may be a clinical target to prevent LVAD thrombosis.

Medical Management of Pump-Related Thrombosis in Patients with Continuous-Flow Left Ventricular Assist Devices: A Systematic Review and Meta-Analysis.

Pump thrombosis is a dreaded complication of left ventricular assist devices (LVADs). We completed a systematic review to evaluate the efficacy and complications associated with medical management of LVAD thrombosis. Databases were searched using the terms "vad*" or "ventricular assist device" or "heart assist device" and "thrombus" or "thrombosis" or "thromboembolism." Of 2,383 manuscripts, 49 articles met the inclusion criteria. The risk of partial or no resolution of LVAD thrombosis did not significantly differ between thrombolytic and nonthrombolytic regimens (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.20-1.16). When response to therapy was evaluated based on pump type, there were no significant differences in how patients with a HeartMate II or HeartWare ventricular assist device responded to thrombolytic or nonthrombolytic treatment. Pooled risk of major bleeding in the thrombolytic group was 29% (95% CI, 0.17-0.44) and 12% (95% CI, 0.01-0.57) in the nonthrombolytic group. Odds of death did not differ between thrombolytic and nonthrombolytic regimens (OR, 1.28; 95% CI, 0.42-3.89). Although thrombolytic and nonthrombolytic treatment similarly resolved LVAD thrombosis, major hemorrhage may be increased with the use of thrombolysis. Randomized clinical trials comparing thrombolytic and nonthrombolytic treatment of LVAD thrombosis are needed to establish the most effective and safe option for patients who are not surgical candidates.

First results of HeartWare left ventricular assist device implantation with tunnelling of the outflow graft through the transverse sinus.

The number of left ventricular assist device (LVAD) implants for the treatment of advanced heart failure is increasing tremendously. The main therapeutic goal of this operation is to provide a bridge to transplant for patients awaiting a donor heart. In 2011, we developed a novel, minimally invasive surgical technique for LVAD implantation. To avoid possible outflow graft injuries during redo sternotomies as well as to provide a more physiological outflow towards the aortic arch, a further modification of this approach was made with outflow graft tunnelling through the transverse sinus. More than 500 LVADs were implanted at Hannover Medical School between 2008 and 2015. From September 2012 to December 2015, we used this novel technique in 17 consecutive bridge-to-transplant patients and analysed their clinical outcomes retrospectively. Baseline characteristics were obtained for all patients, and outcome data were collected from a review of electronic medical records. Subsequently, we compared the results of a data analysis of a group of 86 patients with a minimally invasive left thoracotomy LVAD implantation with the results from patients in a control group receiving a conventional outflow graft placement between May 2009 and January 2015. Our data demonstrate that the outcomes and adverse events of the operated group were comparable to those of the control group. Three patients of the study group died within the first year (3 of 17, 18%); survival to 3 years was 84%. The adverse events were similar in both groups. The study group had 3 ischaemic strokes (18%) and 1 LVAD thrombosis (6%). Five patients had LVAD thrombosis (5 of 86, 6%) and 6 in the control group had ischaemic strokes (6 of 86, 7%). The average in-hospital stay was 35.4 days for the study group and 27.4 days for the control group. Three patients from the study group and 5 from the control group had cardiac transplants. The average time until cannulation and start of extracorporeal circulation was 56 min in the study group and 96 min in the control group. Re-thoracotomy was necessary in 2 patients from the control group, whereas none was necessary in the study group. LVAD implantation with outflow graft tunnelling through the transverse sinus is an innovative technique to prevent outflow graft damage in case of cardiac resternotomy. The results of this study show that there are no significant differences in pump speed or flow, adverse events or patient outcomes compared with the standard implant techniques. The theoretical benefits of this novel technique are the reduced risk in redo cases and the physiological direction of blood flow. Consequently, this procedure might be particularly suitable for younger patients who received an LVAD as a bridge-to-transplant option.

The Use of Eptifibatide Alone or in Combination With Heparin or Argatroban for Suspected Thrombosis in Patients With Left Ventricular Assist Devices.

Pump thrombosis and hemolysis in patients with left ventricular assist devices (LVADs) are associated with significant morbidity and mortality. Intensification of anticoagulation has been suggested as potential therapy, with mixed results. The aim of this study is to assess the safety and efficacy of adding eptifibatide with or without an anticoagulation agent in managing patients with LVAD presenting with hemolysis and suspected pump thrombosis. This retrospective single center study included all patients who presented with their first episode of suspected pump thrombosis and were treated with eptifibatide with or without an anticoagulant between March 1, 2011 and July 30, 2015. A total of 27 patients (23 HeartMate II, 4 HeartWare) were identified. The average age was 55 years (range 19-75) and time from implant to event averaged 513 days (range 35-1760). The average lactate dehydrogenase on presentation was 1111 and 63% of patients had power elevations. The average international normalized ratio (INR) on admission was 2.4, with INR of ≥2 in 21/27 patients. All patients received eptifibatide: 10 received eptifibatide only, 9 received eptifibatide and argatroban, and 8 received eptifibatide and heparin. Warfarin was continued in 25/27 patients. Overall, 21 patients (77.8%) were successfully treated medically, 5 (18.5%) underwent pump exchange, and 1 (3.7%) died. There were no differences in outcomes or complications between the three treatment groups. Despite initial success, 12/21 patients developed repeat episodes of hemolysis at 1 year. The 1-year survival in the patients treated medically was 90% and surgically was 60%. Our experience indicates that medical therapy for hemolysis and suspected LVAD thrombosis with warfarin and eptifibatide alone or in combination with argatroban or heparin appears safe and may be effective, although the episodes of recurrent hemolysis after medical management remain high.

(128) - Device Exchange Is Superior to Medical Therapy for Treating Continuous-Flow Left Ventricular Assist Device Thrombosis

(128) - Device Exchange Is Superior to Medical Therapy for Treating Continuous-Flow Left Ventricular Assist Device Thrombosis

Role of contrast CT for the diagnosis and the prognosis of suspected LVAD thrombosis.

There is an urgent need for further studies evaluating the role of imaging modalities in the management of left ventricular assist device (LVAD) thrombosis. This study reviews the role of computed tomography (CT) in the diagnosis of suspected LVAD thrombosis. All contrast chest CTs performed in patients with suspected LVAD thrombosis at the University of Minnesota between January 2008 and April 2014 were reviewed. Significant CT findings were identified, operative notes were reviewed, and patient outcomes were reported. A total of 32 contrast chest CT examinations were performed in 24 patients with suspected LVAD thrombosis. LVAD thrombus was identified on CT in two patients (one in the outflow graft and one in the inflow cannula), and complications were found in two patients (one with inflow cannula malposition and one with outflow graft stenosis at aortic anastomosis site). Thirteen patients (67%) underwent LVAD explantation for clinically presumed LVAD thrombosis (LVAD exchange in seven, orthotopic heart transplant in six). LVAD thrombus was confirmed at the time of surgery in eight patients (62%; six in the motor, two in the outflow graft). CT has a low sensitivity but high specificity for detecting LVAD thrombus. The sensitivity is higher, but still modest for the detection of thrombus in the outflow cannula.

LVAD Outflow Graft Angle and Thrombosis Risk.

This study quantifies thrombogenic potential (TP) of a wide range of left ventricular assist device (LVAD) outflow graft anastomosis angles through state-of-the-art techniques: 3D imaged-based patient-specific models created via virtual surgery and unsteady computational fluid dynamics with Lagrangian particle tracking. This study aims at clarifying the influence of a single parameter (outflow graft angle) on the thrombogenesis associated with flow patterns in the aortic root after LVAD implantation. This is an important and poorly-understood aspect of LVAD therapy, because several studies have shown strong inter and intrapatient thrombogenic variability and current LVAD implantation strategies do not incorporate outflow graft angle optimization. Accurate platelet-level investigation, enabled by statistical treatment of outliers in Lagrangian particle tracking, demonstrates a strong influence of outflow graft anastomoses angle on thrombogenicity (platelet residence times and activation state characterized by shear stress accumulation) with significantly reduced TP for acutely-angled anastomosed outflow grafts. The methodology presented in this study provides a device-neutral platform for conducting comprehensive thrombogenicity evaluation of LVAD surgical configurations, empowering optimal patient-focused surgical strategies for long-term treatment and care for advanced heart failure patients.

Post-Operative Anticoagulation and the Incidence of Left Ventricular Assist Device Thrombosis

IntroductionAnticoagulation is critical for patients with durable left ventricular assist devices (LVADs) in order to protect against life threatening thromboembolic events. An increase in the incidence of pump thrombosis between 2009 and 2014 prompted examination of our anticoagulation practices following device implants. As the majority of pump thromboses occurred within six months of implant, we hypothesized that anticoagulation strategies employed immediately after implant might play a role. We describe the initial post-operative anticoagulation management of 105 patients implanted with a Heart Mate II (HM II) LVAD by a single surgeon at our academic center. Although patients with more severe clinical compromise were more likely to be bridged, we found no difference in overall pump thrombosis incidence based on the use of a post-operative parenteral anticoagulation bridge compared to unopposed warfarin.MethodsWe performed a retrospective review of 105 patients undergoing primary implant of a HM II LVAD at our center from 2009 through 2014 with follow up through May 31, 2015. Data included demographics, clinical status at time of implant, intra-operative practices, and initial post-operative anticoagulation management. A parenteral bridge was defined as initiation of a parenteral anticoagulant prior to achieving an INR ≥2.0. A parenteral bridge was further defined as early if initiated within ≤3 days of device implant and therapeutic if a goal PTT was achieved during each of the first 0-24, 24-48, and 48-72 hours of the bridge duration. A parenteral bridge was considered sub-therapeutic if at least one but not all PTT measurements were at goal and non-therapeutic if no PTT measurements were at goal. Unopposed warfarin was defined as initiation to reach a therapeutic INR without the use of parenteral anticoagulants. Pump thrombosis was defined as detection within the device, inflow cannula, or outflow conduit at the time of pump replacement, pump explantation, heart transplantation, or autopsy. Pump thrombosis within 186 days of implant was defined as early. Fisher’s exact test and the Wilcoxon rank-sum test were used to compare categorical and continuous variables between groups. Cumulative incidence of pump thrombosis was compared using the Gray test with reimplantation, explantation, transplantation, or death as a competing risk.ResultsAmong 105 HM II implants, 73 (70%) were treated with any parenteral bridge, 50 (48%) with an early bridge, and 29 (28%) with an early therapeutic bridge. Median time to bridge initiation was 3 days (range 1 to 7) and median bridge duration was 6 days (range 1 to 45). A total of 32 patients (30%) received unopposed warfarin. Time to warfarin initiation and therapeutic INR were shorter in patients who received unopposed warfarin compared to a parenteral bridge, with median values of 1 vs. 2 days and 5 vs. 8 days, respectively (p<0.001 for both). Patients who received a parenteral bridge had more severe preoperative clinical compromise (p=0.039) and longer intensive care unit length of stay (p=0.005).Pump thrombosis occurred in 25 patients (24%) and 14 (13%) were early. Hypertension was the only clinical variable that differed by group (p=0.012) and was more prevalent in patients with pump thrombosis.Cumulative incidence analyses showed no significant difference in the incidence of pump thrombosis between patients who did and did not receive a parenteral bridge (p = 0.25), an early parenteral bridge (p=0.37), or a therapeutic parenteral bridge (p=0.87) (Figure 1). At 6 months the cumulative incidence (95% confidence interval) of pump thrombosis was 7.9% (2.0, 19.3) for those who received a therapeutic bridge and 16.4% (8.7, 26.3) for those who did not. At 24 months these values were 22.7% (9.4, 39.5) and 24.3% (14.6, 35.3), respectively.Among patients who did not receive a parenteral bridge, there was no difference in the time to initiation of warfarin (p=0.23) or therapeutic INR (p=0.13) according to the outcome of pump thrombosis.ConclusionsPost-operative parenteral bridging was more common than initiation of unopposed warfarin. Indices of more severe clinical compromise were associated with the use of a parenteral bridge. Our data suggest that post-implant bridging does not affect overall incidence of LVAD thrombosis. Further analysis will be performed to determine if parenteral bridging prevents early pump thrombosis. [Display omitted] DisclosuresConnors:Thoratec (St Jude's): Other: Consultant; Bristoml Meyer Squibb: Consultancy, Other: Scientific Ad Boards/Consultant; Boehringer Ingelheim: Consultancy, Other: Scientifc Ad Boards.

Left Ventricular Assist Device Thrombosis Is Associated With an Increase in the Systolic-to-Diastolic Velocity Ratio Measured at the Inflow and Outflow Cannulae

To determine whether the ratio of peak systolic-to-nadir diastolic velocity (S/D ratio) measured using Doppler at the left ventricular assist device (LVAD) inflow and outflow cannulae is associated with pump thrombosis and to determine whether there is an absolute decrease in the diastolic cannula velocities in LVAD thrombosis. Retrospective chart review. University hospital. Patients who underwent LVAD exchange. None. Transesophageal echocardiograms were reviewed from all patients with the HeartMate II device (Thoratec Corporation, Pleasanton, CA) over a 6-year period and who underwent LVAD exchange for pump thrombosis. The following 3 time points were evaluated: (1) initial LVAD placement (prethrombosis), (2) thrombosis, and (3) exchanged LVAD placement (postthrombosis). Systolic and diastolic flow velocities were examined using pulse-wave spectral Doppler at the inflow and outflow cannulae, and the S/D ratio for each was determined. Statistical analysis was performed with SAS, version 9.4 (SAS Institute, Cary, NC), using 2-tailed tests and alpha = 0.05. Thirteen patients were included in the study. Significant differences were observed in S/D ratios among the 3 phases at both the inflow (p = 0.0234) and outflow (p = 0.0047) cannulae. Pairwise tests of the inflow cannulae showed that the mean S/D ratio at the time of thrombosis (mean ± standard deviation [SD], 4.29 ± 1.74) was significantly greater than the prethrombosis ratio (2.49 ± 0.65; p = 0.0069). Among outflow measurements, the mean S/D ratio at thrombosis (3.94 ± 1.34) was significantly higher than both the prethrombosis (2.63 ± 0.56; p = 0.0025) and postthrombosis (2.74 ± 0.83) (p = 0.0093) ratios. Decreases in diastolic velocities were not statistically significant at the inflow cannula. At the outflow cannula, there was a significant difference in diastolic velocity among the phases (p = 0.0233). Specifically, the postthrombosis diastolic measurements (41.50 ± 9.94) were significantly higher than both the prethrombosis (26.85 ± 10.13; p = 0.0140) and thrombosis (26.7 ± 15.35; p = 0.0151) values. An increased S/D ratio measured with Doppler at the LVAD inflow and outflow cannulas may be associated with pump thrombosis. Decreased diastolic cannula velocities were not observed in LVAD thrombosis.

Operating in the Dark

The benefits of left ventricular assist device (LVAD) therapy in advanced heart failure are clear—device implantation can prolong patient survival, enhance functionality, and improve quality of life.1 Since US Food and Drug Administration approval of the first continuous-flow LVAD in 2008, utilization has grown rapidly, and now, >2500 devices are placed annually.1 Given the current epidemic of heart failure, this volume may only be scratching the surface. Current estimates suggest that there are upwards of 250 000 to 300 000 potential LVAD candidates in the United States alone.2 Despite technological and design advances, broader application of LVAD therapy remains limited in part by its relatively high rate of adverse events (AEs). Six-month freedom from rehospitalization is only 40%, whereas 70% of patients will experience an AE within the first year of support.1 See Article by Levin et al In this issue of Circulation : Heart Failure , Levin et al retrospectively described hemolytic events of HeartMate II (St. Jude Medical, Pleasanton, CA) patients at 2 large academic medical centers. Specifically, they compared outcomes for patients with hemolysis managed with surgical versus medical therapy, to determine the most effective strategy.3 Their findings were humbling. One-year freedom from stroke or death was 87.5% and 49.5% in the surgical and medical cohorts, respectively. Resolution of primary hemolysis without stroke, death, or recurrent hemolysis was only 44% in patients treated with medical therapy, compared to 63% in patients treated operatively. Even more sobering is the realization that the surgical cohort first failed medical therapy, and thus, the true treatment response to medical therapy alone was a paltry 29%. In summary, the principal finding was that for patients meeting the author’s definition of hemolysis, a surgical strategy (after failed medical intervention) resulted in less death or stroke than a medical strategy alone, …

(652) - LVAD Support Increases Plasma Iron Species: Implications for a Pathophysiologic Relationship between LVAD-Associated Hemolysis and Thrombosis

Emerging evidence suggests a relationship between left ventricular assist device (LVAD)-associated hemolysis and LVAD thrombosis. Plasma iron species such as free hemoglobin, hemin, and free iron (Fe2+, Fe3+), which are produced during hemolysis, generate oxidative stress and may promote thrombogenesis. As a preliminary study to guide in vitro mechanistic investigations into contributors to LVAD thrombosis, we examined plasma iron species in patients during LVAD support. Patients undergoing continuous-flow LVAD support were studied (n=23). Whole blood was obtained prior to LVAD implantation and after one week of LVAD support. Lactate dehydrogenase (LDH) was measured as a marker of hemolysis. Free hemoglobin, hemin, Fe2+, and Fe3+ were measured as plasma iron species. Paired Student’s t-tests were performed between pre-LVAD and post-LVAD samples. LVAD support increased LDH (pre-LVAD 245±20 units/L vs. post-LVAD 333±36 units/L, p=0.07), plasma free hemoglobin (pre-LVAD 46±6 mg/dL vs. post-LVAD 67±9 mg/dL, p=0.01), hemin (pre-LVAD 0.26±0.06 μg/dL vs. post-LVAD 4.8±2.3 μg/dL, p=0.06), Fe2+ (pre-LVAD 173±17 μg/dL vs. post-LVAD 220±27 μg/dL, p=0.02), and Fe3+ (pre-LVAD 29±7 μg/dL vs. post-LVAD 51±9 μg/dL, p=0.03). LVAD support significantly increased plasma levels of free hemoglobin, hemin, Fe2+, and Fe3+. Elevated plasma iron species during LVAD support may contribute to the pathophysiology of LVAD thrombosis. These data are guiding in vitro studies to determine whether the relationship between LVAD-associated hemolysis and thrombosis is causal or associative.

(683) - A Single Center Experience of Device Exchange for Continuous Flow Left Ventricular Assist Device Thrombosis

(683) - A Single Center Experience of Device Exchange for Continuous Flow Left Ventricular Assist Device Thrombosis

(189) - Prospective Evaluation of Urine Dipstick for Detection of Significant Hemolysis in Outpatients on CF-LVAD Support

Purpose: The mechanism of left ventricular assist device (LVAD) thrombosis initiation and propagation is unknown. Correctly identifying the thrombi components could aid in directing therapy for patients with suspected LVAD thrombosis. Methods: H&E staining was used for histologic analysis of thrombi removed from HeartMate II (HMII) devices explanted at the University of Louisville. Immunohistochemistry identified platelets and neutrophils using antibodies against CD42b (glycoprotein Ib) and myeloperoxidase, respectively. Age of fibrin was assessed by Martius, Scarlet, Blue staining. Results: 28 thrombi from 17 LVADs were analyzed. Four pumps only had an inlet bearing thrombus, 3 pumps only had a rotor vein thrombus, and 2 pumps only contained an outlet bearing thrombus. Seven pumps had clots in multiple locations. In total, 72% of the thrombi (20/28) were either located around the inlet bearing (9), the rotor veins (5), or the outlet bearing (6). The laminated fibrin rings of the inlet stator thrombi were 150 -2618 microns thick. The inner rings had crosshatched fibrin followed by dense fibrin rings (Figure). Outer rings had mixed fibrin with less organized structure. Rings with higher densities of platelets and neutrophils were more commonly seen in the outer rings of rotor thrombi (Figure). Outlet bearing thrombi varied histologically, but most were similar to the rotor and inlet thrombi with increased areas of nuclear material. Three thrombi from the inlet conduit and three from outlet elbow were similarly structured and composed of loose meshwork with white blood cells and areas of layered fibrin. Platelets were present in dense areas. Conclusion: The fibrin density varied in clots formed in different parts of the HMII. Fibrin of different ages in the inlet bearing thrombi suggests development over time and reinforces the necessity of anticoagulation. The increased frequency of platelets in the outer rings of the inlet bearing thrombi would support further investigation into their role in thrombus propagation.

Continuous-Flow Left Ventricular Assist Device Thrombosis: A Solvable Problem.

Continuous-Flow Left Ventricular Assist Device Thrombosis: A Solvable Problem.

Incidence, Management, and Outcome of Suspected Continuous-Flow Left Ventricular Assist Device Thrombosis.

Left ventricular assist device (LVAD) thrombosis is associated with high morbidity and mortality because of device malfunction, embolic events, and hemolysis. There remains uncertainty as to whether immediate device exchange versus an initial trial of anticoagulant and antiplatelet therapy is most appropriate in hemodynamically stable patients. We conducted a retrospective analysis of all LVAD implantations at a single center between January 2009 and June 2013 with follow-up through December 2013. Suspected LVAD thrombosis occurred in 20% of patients (N = 25) over a median follow-up of 275 days. Medical therapy led to resolution of hemolysis, and discharge to home, in 15 of 25 (60%) cases; however, this strategy was associated with intracranial hemorrhage in 4 patients and readmission with recurrent thrombosis in 10 patients. The 30 day, 6 month, and 1 year freedom from suspected LVAD thrombosis was 96.5, 85.9, and 80.3% in HeartMate II devices and 100, 92.9, and 87.1% in HeartWare ventricular assist devices, respectively (p = 0.11). Although medical treatment with intravenous heparin, antiplatelet agents, antithrombotic agents, or thrombolytic therapy can lead to initial resolution of hemolysis, the risks of recurrence after transition to warfarin and adverse events are high.

Mechanical circulatory support: balancing bleeding and clotting in high-risk patients.

Mechanical circulatory support (MCS) provides a bridge to heart transplant in children and adults with life-threatening heart failure and sustains patients ineligible for transplant. Extracorporeal membrane oxygenation (ECMO) provides temporary support for patients in cardiac or pulmonary failure through external gas exchange and continuous flow of blood. Because the median time to heart transplant exceeds event-free time on ECMO, pulsatile left ventricular assist devices (LVADs) are used to support infants and children. Continuous flow LVADs are preferred in adolescents and adults due to increased pump durability and improved overall survival. The shear stress created by the mechanical pumps cause changes in the hematologic system; acquired von Willebrand syndrome occurs in almost all patients treated with MCS. Despite the improvements in survival, major bleeding occurs in one-third of patients with a LVAD and ischemic stroke and LVAD thrombosis can affect 12% of adults and 29% of children. An antithrombotic strategy to mitigate LVAD bleeding and thrombotic complications has been tested in a randomized trial in children, but intensity of antithrombotic therapy in adults varies widely. Consensus guidelines for antithrombotic therapy during ECMO were created due to significant differences in management across centers. Because of the high risk for both bleeding and thrombotic complications, experts in hemostasis can significantly impact care of patients requiring mechanical circulatory support and are a necessary part of the management team.

Abstract 18412: Lactate Dehydrogenase Trends Predict Left Ventricular Assist Device Thrombosis

Introduction: Recent analyses have demonstrated an increasing risk of HeartMate II (HMII) left ventricular assist device (LVAD) thrombosis than previously reported. Elevation of serum lactate dehydrogenase (LDH), a biomarker of hemolysis secondary to thrombosis, parallels the overall pattern of HMII thrombosis. Hypotheses: We hypothesized that longitudinal trends of LDH could predict HMII thrombosis. Methods: From 10/2004 through 9/2014, 350 HMII devices were implanted in 323 patients at a single center. Of these, patients on 339 devices had at least 1 postop LDH value through 9/2014 (7,996 total measurements). A 2-step joint model combining longitudinal biomarker data and pump thrombosis events was generated to assess the impact of changing LDH on the risk of thrombosis. Device-specific LDH values were first estimated using Multivariate Boosted Trees to reduce measurement error and produce unbiased regression estimates. Estimated LDH values were then used as a time-varying covariate function in a multiphase hazard model to analyze time to thrombosis. Results: Thirty-five HMII pumps (10%) had either confirmed (18 HMIIs) or suspected (17 HMIIs) thrombosis, with 15 (43%) occurring within 3 months of implant. LDH was associated with pump thrombosis occurring both early and late after implant (P&lt;.0001 for both phases). The model demonstrated increased probability of HMII thrombosis as LDH trended upward, with steep changes in thrombosis probability paralleling similar trajectories in LDH. Two individual patient probaliities are graphed in the figure. Conclusions: Longitudinal trends in surveillance LDH for patients on HMII support is useful for dynamic prediction of pump thrombosis, both early after implant and late. Incorporating upward and downward trends in LDH provides a dynamically updated model of LVAD thrombosis risk that may eventually be a tool for LVAD clinical management.