Left Ventricular Assist Device Thrombosis Research Articles

Left ventricular dimension decrement index early after axial flow assist device implantation: A novel risk marker for late pump thrombosis

It is increasingly recognized that pump thrombosis most likely represents the end stage of a complex interaction between the patient-pump interface. We hypothesized that early patient/pump mismatch, as manifested by suboptimal left ventricular (LV) unloading early after left ventricular assist device (LVAD) implantation, may be a harbinger of increased risk for later LVAD thrombosis. In 64 patients (59 ± 11 years old, 78% men, 44% destination therapy) discharged alive without thrombosis or other device malfunction after first HeartMate II LVAD implantation (between January 2011 and June 2014), LV dimensions in end diastole (LVIDd) and end systole (LVIDs) were compared between pre-implant and optimal set speed pre-discharge echocardiography. LV dimension decrement indices (pre-implant dimension - optimal set speed dimension ÷ pre-implant dimension × 100) for LVIDd [LVIDdDI] and LVIDs [LVIDsDI] were calculated. The incidence of pump thrombosis was 0.06 per patient year (n = 18, median time 8 [interquartile range 2, 17] months). Baseline characteristics including pre-operative LVIDd and LVIDs were similar between LVAD thrombosis and no thrombosis groups. After ventricular assist device implantation, set speed and other ramp parameters did not differ between groups. However, LVIDdDI (19 ± 13% vs 25 ± 11%, p = 0.04) and LVIDsDI (16 ± 16% vs 27 ± 13%, p = 0.008) were significantly lower in patients with later pump thrombosis. A cutoff value of ≤15% using receiver operating characteristic curve analysis was 83% sensitive for LVIDdDI and LVIDsDI for predicting pump thrombosis. Patients with LVIDdDI of >15% vs ≤15% were significantly more likely to be free of pump thrombosis over a median follow-up period of 15 (interquartile range 9, 26) months (log-rank test, p = 0.045). LV dimension decrement index at optimized speed setting on pre-discharge echocardiography is associated with LVAD thrombosis.

Clinical Characteristics of Patients with Suspected Left Ventricular Assist Device Thrombosis Who Respond to Intensified Anticoagulation

Clinical Characteristics of Patients with Suspected Left Ventricular Assist Device Thrombosis Who Respond to Intensified Anticoagulation

Continuous-Flow Left Ventricular Assist Device Thrombosis: A Danger Foreseen is a Danger Avoided.

Left ventricular assist devices (LVAD) are an increasingly implemented therapeutic intervention for patients with end-stage heart failure. A growing body of evidence, however, has shown an elevated risk of device thrombosis, a major complication jeopardizing the patient’s post-implantation survival. To date, multiple causative factors for LVAD thrombosis have been identified, such as internal shear stress, device material, infection, and inadequate anticoagulation.Understanding the mechanisms leading to LVAD thrombosis will not only enable device optimization, but also allow for better patient handling, hence improving post-implantation outcome. In this review we highlight the most commonly identified factors leading to LVAD thrombosis and discuss their mechanisms.

Medication management for left ventricular assist device thrombosis.

Current strategies for prevention and treatment of "pump thrombosis" associated with the use of left ventricular assist devices (LVADs) are discussed. LVADs provide morbidity, mortality, and quality-of-life benefits in patients with advanced heart failure. Since continuous-flow LVADs came into wide use, there have been increased reports of pump thrombosis (clot formation in the LVAD system that can lead to pump dysfunction and clinical complications). Anticoagulation and antiplatelet therapies are important for preventing pump thrombosis, although the optimal antithrombotic regimen remains unclear. International Normalized Ratio goals should be determined according to specific device characteristics and patient risk factors. Medication therapy for pump thrombosis provides a less invasive option than surgical pump exchange or heart transplantation but is associated with high risks of bleeding events, recurrent pump thrombosis, and mortality. Decisions regarding medical versus surgical management should be based on clinical status and surgical candidacy. Management of pump thrombosis may include intensified i.v. anticoagulation, i.v. or intraventricular thrombolytics, or glycoprotein IIb/IIIa inhibitors. Optimization and close monitoring of anticoagulation and antiplatelet therapy can help reduce the risk of pump thrombosis. Intensive clinical and laboratory monitoring are important in identifying signs and symptoms of LVAD thrombosis. Medical management of LVAD thrombosis can be considered an early treatment strategy before thrombi become too large and unresponsive to pharmacotherapies, but antithrombotic medications carry a high risk of bleeding complications and should be used judiciously. More definitive treatment with pump exchange or heart transplantation in appropriate candidates may be required.

(320) - Contributing Factors to the Successful Medical Management of Suspected Left Ventricular Assist Device Thrombosis

(320) - Contributing Factors to the Successful Medical Management of Suspected Left Ventricular Assist Device Thrombosis

HEMOLYSIS: PREDICTORS OF RISK FACTORS POST LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION

Hemolysis continues to be a challenge in patients supported by left ventricular assist devices (LVADs) and can occasionally lead to LVAD thrombosis and the necessity for surgical exchange. We investigated possible risk factors for hemolysis. This retrospective study included 227 patients implanted

Management of anticoagulation and antiplatelet therapy in patients with left ventricular assist devices.

Left ventricular assist devices (LVADs) have increased the survival of patients with advanced heart failure fourfold. Despite these advances, significant bleeding and thrombotic complications occur. Hemorrhage requiring surgery has been reported in up to 30% of adults and 50% of children after LVAD placement. LVAD thrombosis and embolic stroke lead to significant long-term morbidity. Adults are treated with antithrombotic therapy to prevent thrombotic complications, but the amount and intensity of treatment differs between institutions. The goal international normalized ratio for warfarin therapy varies from 1.5 to 3.0. Some physicians manage adult LVAD patients without antiplatelet medication, whereas other adults are treated with aspirin as a single agent or combined with dipyridamole. In contrast, physicians typically manage children with LVADs using the Edmonton Anticoagulation and Platelet Inhibition Protocol, a detailed algorithm for anticoagulation and antiplatelet treatment modified based on thromboelastography results. LVAD implantation causes consumption of coagulation proteins, activation of fibrinolysis, and loss of high molecular weight von Willebrand protein multimers. How these changes in the coagulation system influence the risk of hemorrhage and initiation of thrombosis is unknown. Prospective, controlled studies are needed to determine the antithrombotic regimen that most effectively balances bleeding and thrombosis in LVAD patients.

Abstract 19810: A Significant Decrease in Early Confirmed Left Ventricular Assist Device Pump Thrombosis: Recent Observations from a Large Multi-Institutional Experience

Introduction: Recent reports have documented an abrupt increase in 3-month confirmed HeartMate II left ventricular assist device (LVAD) thrombosis beginning in 2011 without a plateau observed to date. Because very little data exist from multi-institutional efforts, we report our experience. Methods: From January 2004 to December 2013, 516 pt underwent HeartMate II LVAD implant at three institutions (University of Michigan (n=254), Mayo Clinic Rochester (n=205), and Vanderbilt Heart and Vascular Institute (n=57)). Median age at implant was 60 yr (range, 18-82) and 428 (83%) were male. Confirmed pump thrombosis at 3 months was defined as thrombus found in the blood-contacting surfaces of the pump at the time of urgent transplant, device exchange or autopsy. Pt without at least 3 months of follow-up were excluded. Results: Confirmed pump thrombosis occurred in 9 pt within 3 months post implant. The incidence was greatest in the year 2012 (5.3%). Following this peak, the incidence of 3-month confirmed pump thrombosis decreased significantly to 2.9% (Figure). Significant differences in preoperative characteristics between patients with pump thrombosis and without thrombosis included female sex (36% vs. 16%, p=0.01), bridge to transplant (77% vs. 54%, p=0.03), atrial fibrillation (55% vs. 32%, p=0.04), and preop platelet count (231,000 vs. 172,000, p<0.001). Follow-up was available in all for a total of 857 patient years of support. At a median follow-up of 1.2 years (max., 9.8 years), a similar proportion of patients were alive (73% vs. 74%, p=0.9). Conclusions: We report a recent decrease in early, confirmed HeartMate II LVAD thrombosis to historically observed levels, which is disparate to recent reports. While we identified several differences in clinical characteristics between patient groups, the issue of pump thrombosis is complex and multifactorial. Most importantly, our findings demonstrate the need for more granular analyses from collaborative efforts.

Outcomes with Medical Management of Continuous Flow Left Ventricular Assist Device(CF-LVAD) Thrombosis

Outcomes with Medical Management of Continuous Flow Left Ventricular Assist Device(CF-LVAD) Thrombosis

Hematologic markers better predict left ventricular assist device thrombosis than echocardiographic or pump parameters.

Left ventricular assist device (LVAD) thrombosis is a life-threatening complication that remains a major clinical problem. Consensus diagnostic criteria do not exist. We investigated whether hematologic, echocardiographic, or pump parameters reliably change during LVAD thrombosis. A retrospective analysis of 20 consecutive cases of continuous-flow LVAD thrombosis (Thoratec HeartMate II n = 16, HeartWare HVAD n = 4) was performed. Hematologic markers (lactate dehydrogenase, plasma-free hemoglobin, hemoglobin, creatinine), echocardiographic parameters (left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity), and pump characteristics (speed, power, estimated flow, pulsatility index) were analyzed with one-way repeated measures ANOVA with Tukey post-test or paired Student t-tests. Lactate dehydrogenase and plasma-free hemoglobin were significantly (p < 0.05) elevated at admission for LVAD thrombosis. Hemoglobin and creatinine were not significantly different at admission but changed significantly after admission. Left ventricular end-systolic and end-diastolic diameter, mitral regurgitation, aortic insufficiency, inflow-cannula velocity, LVAD speed, power consumption, estimated flow, and pulsatility index were not significantly different at admission for LVAD thrombosis. Hematological markers of hemolysis, but not echocardiographic or pump parameters, reliably changed during LVAD thrombosis. Markers of hemolysis are the best early predictors of LVAD thrombosis.

(655) - Continuous Flow Left Ventricular Assist Device Thrombosis: Presentation, Management and Outcomes

(655) - Continuous Flow Left Ventricular Assist Device Thrombosis: Presentation, Management and Outcomes

Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

BackgroundWe observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study.MethodsWe obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis.ResultsA total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis.ConclusionsThe rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Thrombolytic Therapy for Thrombosis of Continuous Flow Ventricular Assist Devices

BackgroundDespite chronic systemic anticoagulation, advanced heart failure patients treated with a continuous-flow left ventricular assist device (LVAD) remain at risk for pump thrombosis. Pump thrombosis may initially be suspected in the setting of clinical and biochemical evidence for intravascular hemolysis, putatively related to shear stress on red blood cells propelled through a partially occluded pump. Limited data exist to guide management in these patients. Methods and ResultsWe present a series of 8 LVAD patients who presented with intravascular hemolysis secondary to pump thrombosis who were treated with intraventricular thrombolytic therapy. In 3 patients, thrombolytic therapy led to complete and lasting resolution of hemolysis, suggesting successful dissolution of pump thrombus. In the remaining 5 patients, thrombolytic therapy ultimately failed to halt or reverse pump thrombosis and hemolysis: 1 patient required emergent pump exchange, 2 patients progressed to cardiogenic shock and died, 1 patient suffered a debilitating stroke after which care was withdrawn, and 1 patient underwent cardiac transplantation. ConclusionsIn the setting of LVAD thrombosis, thrombolytic therapy is an alternate treatment strategy in a subset of patients. Candidacy for this alternate procedure must carefully weigh the risks of complications, including hemorrhage and thromboembolism.

Diagnosis, Nonsurgical Management, and Prevention of LVAD Thrombosis

Left ventricular assist device (LVAD) thrombosis is a life-threatening complication. Multiple case reports describe successful nonsurgical management with thrombolytics, aggressive antiplatelet therapy, or percutaneous catheter-directed thrombectomy. However, consensus management of LVAD thrombosis has not been established and guidelines are urgently needed. In order to raise awareness of nonsurgical treatment options, we review the current strategies for the clinical diagnosis, management, and prevention of LVAD thrombosis.

Role of Echocardiography in Patients With Intravascular Hemolysis Due to Suspected Continuous-Flow LVAD Thrombosis

This study sought to characterize the echocardiographic findings of patients presenting with intravascular hemolysis (IVH) due to suspected continuous-flow left ventricular assist device (LVAD) pump thrombosis. LVAD patients who develop pump thrombosis often present with IVH. Echocardiography may be able to detect device dysfunction in this setting. Continuous-flow LVAD patients presenting with IVH due to suspected pump thrombosis were identified. Patients underwent echocardiography with cannula Doppler flow velocity interrogation. Findings were compared with baseline and follow-up studies, and with 49 stable LVAD control patients. Of 145 patients, 14 (10%) had IVH due to suspected pump thrombosis. The mean age was 55 ± 15 years, 93% were men, and 50% received LVAD as destination therapy. Mean duration between implantation and IVH was 231 ± 218 days. Eleven (79%) patients presented with hemoglobinuria, 9 (64%) with jaundice, and 5 (36%) with acute heart failure. Reduced cannula diastolic flow velocity and increased systolic/diastolic (S/D) flow velocity ratio were the only echocardiographic parameters significantly different from controls (outflow cannula 0.3 ± 0.2 m/s vs. 0.8 ± 0.3 m/s, p = 0.03, and 5.9 ± 2.8 vs. 1.7 ± 0.7, p < 0.01, respectively), and were worse for IVH patients with acute heart failure compared with those without (outflow cannula 0.2 ± 0.1 m/s vs. 0.5 ± 0.2 m/s, p = 0.04, and 7.2 ± 3.3 vs. 5.3 ± 2.0, p = 0.02, respectively). Outflow cannula diastolic flow velocity and S/D flow velocity ratio changed significantly from baseline (p = 0.01 and p < 0.01, respectively) in IVH patients, whereas systolic flow velocity did not change (p = 0.59). Odds ratios for outflow cannula diastolic flow velocity and S/D flow velocity ratio for predicting IVH were 0.60 (95% confidence interval [CI]: 0.51 to 0.73), p = 0.02, and 2.45 (95% CI: 2.37 to 2.52) p < 0.01, respectively. Corresponding inflow cannula values were similarly significant. Pump thrombosis was confirmed in 7 (50%) patients after LVAD retrieval. Reduced cannula diastolic flow velocity and increased S/D flow velocity ratio identified continuous-flow LVAD dysfunction in patients with IVH due to suspected pump thrombosis better than other echocardiographic parameters.

Device Exchange and Thrombolytic Therapy for Left Ventricular Assist Device Thrombosis

Optimal management strategies for continuous-flow LVAD thrombosis (LVAD-T) have not been determined. We describe our experience with 11 pts managed for LVAD-T receiving device exchange and/or thrombolytic therapy (TPA).

Novel Thrombosis Risk Index as Predictor of Left Ventricular Assist Device Thrombosis

Left ventricular assist devices (LVADs) are an effective therapy for patients with advanced heart failure, increasing patient survival and quality of life. Left ventricular assist devices are associated with the risks of bleeding and thrombosis. We used lactate dehydrogenase (LDH) and brain natriuretic peptide (BNP) as biomarkers for developing a thrombosis risk index. Data from a single center was retrospectively queried between January 1, 2008, and 10/15, 2011, to identify LVAD patients and related complications. Of 75 consecutive patients implanted with an LVAD, nine had device thrombosis. Analysis of the relationship among international normalized ratio (INR), BNP, LDH, and device thrombosis was performed. Of nine patients with thrombosis, seven had at least 30% of INR readings below 1.5 and two had at least 22% below the therapeutic range from the time of LVAD implant to date of thrombosis. Timeline variability in INR, BNP, and LDH were used to calculate thrombosis risk index (TRI). The TRI retrospectively was able to accurately predict patients with impending device thrombosis. Indexed rise in BNP and LDH in LVAD patients may be useful to identify early device dysfunction and possible future thrombosis. Fibrinogen and D-dimer assays are currently being evaluated in these patients for their possible inclusion and added value to the TRI.

Treatment of Left Ventricular Assist Device Thrombosis With Extended Catheter-Directed Intraventricular Thrombolytic Therapy

Continuous flow left ventricular assist devices (LVAD) are used in patients with advanced heart failure, either as bridge to transplant or as destination therapy.1 Because current generation continuous flow LVADs activate the coagulation system, anticoagulant therapy with warfarin is recommended to minimize the risk of device thrombosis.2 Occasionally, however, device thrombosis may still occur, which may necessitate surgical LVAD exchange. Because of the relatively high morbidity and mortality associated with a surgical LVAD exchange, alternative methods to abort LVAD thromboses short of surgical intervention would be attractive. Recently, resolution of device thrombosis with catheter-directed intraventricular administration of a single bolus dose of fibrinolytic therapy has been reported.3,4 Here, we report the successful resolution of 2 consecutive cases of LVAD thrombosis using continuous catheter-directed intraventricular administration of fibrinolytics for an extended period in patients who did not respond to the initial bolus dose of fibrinolytics without resorting to surgical LVAD exchange. A 45-year-old man with HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD as destination therapy for dilated cardiomyopathy presented with dark red urine 11 months after device implantation. Further evaluation revealed a subtherapeutic international normalized ratio (INR) (1.4), markedly elevated serum lactate dehydrogenase (LDH; 4010 U/L), low serum haptoglobin (<20 mg/dL), mild hyperbilirubinemia (1.2 mg/dL), and elevated plasma-free hemoglobin (15.4 mg/dL), consistent with hemolysis. Review of logged waveform files revealed no power …

Is Intermittent Hemodialysis Safe in Patients with a Continuous Flow Left Ventricular Assist Device?

Purpose Dialysis centers are wary of performing intermittent hemodialysis (HD) on patients with continuous flow (CF) left ventricular assist devices (LVAD) because of the potential for volume flux related complications and Doppler probe dependent blood pressure monitoring. We report the conduct of HD in patients with LVAD (Heart Mate II), identify events requiring modification of or termination of HD and their management. Methods and Materials We abstracted clinical data from dialysis session on all patients who underwent intermittent HD following placement of LVAD at our institution. Results From June 2009 to October 2012, 139 patients received LVAD at our institution, 10 (7%) required intermittent HD post-operatively. Mean age was 53±14yrs, 90% were male. A total of 281 HD sessions were administered amounting to 1,025 hours of HD. Mean systolic blood pressure monitored with Doppler was 97±18mmHg. Dialysis durations averaged 218±18 mins, mean blood flow rate was 334±38 cc/min and 2.6±1.1 L was ultrafiltrated during each HD session. Only 15 (5.3%) HD sessions were interrupted or terminated in 6 patients, due to symptomatic hypotension 6, asymptomatic hypotension 3, ventricular tachycardia terminated with AICD 1, HD machine malfunction 2, low phosphorus 2 and abdominal cramps 1. Volume expansion was necessary on 3 occasions in 2 patients both of whom were transferred to intensive care unit for sepsis. Low flow LVAD alarms were registered during 2 of the symptomatic hypotension episodes. No serious adverse effect i.e. MI, LVAD thrombosis or stroke was observed. Conclusions Intermittent HD with standard blood flow and ultrafiltration rates were well tolerate in patients with CF LVAD. Hypotension, LVAD dysfunction or serious adverse effects requiring termination of HD were infrequent. Reason for terminating HD Frequency (%) Symptomatic Hypotension 6 (2) Aymptomatic Hypotension 3 (1) HD machine malfunction 2 (0.7) Low phosphorus 2 (0.7) Abdominal cramps 1 (0.36) Ventricular tachycardia 1 (0.36) Total 15 (5.3)

Epitifibatide in the Treatment of Continuous Flow Left Ventricular Assist Device Thrombosis: A Case Series

Purpose Continuous flow left ventricular assist device (cfLVAD) thrombosis remains one of the most difficult complications to diagnose and treat. There is limited evidence for anticoagulation strategies after failure of heparin/warfarin. We present a single-center case series of suspected cfLVAD thrombosis treated with eptifibatide (EPT) after failing conventional therapy. Methods and Materials We reviewed all cfLVAD implants (n=83) from 1/2010 to present. Diagnostic evidence of cfLVAD thrombosis evaluated included 1) echo evidence of thrombosis, 2) evidence of hemolysis, and 3) changes in cfLVAD parameters. Successful treatment was defined as discharge from hospital and freedom from 30-day readmission without treatment with an alternative anticoagulant, cfLVAD explant/exchange, or heart transplant. Results Eleven patients (16 infusions) were treated with EPT. The majority were male (73%) with a mean age of 46 (21-67) years. All patients were on warfarin and an antiplatelet regimen. The mean time from cfLVAD implant to thrombosis was 201 (5-856) days. Most patients presented with evidence of hemolysis and changes in cfLVAD parameters. Fifty percent of patients were successfully treated with EPT infused for an average of 71 (22-119) hours. Blood transfusions occurred in 6/16 EPT infusions and minor bleeding occurred in 2/16 EPT infusions. Conclusions This review failed to identify a single surrogate marker of cfLVAD thrombosis that may predict response to EPT. For patients with suspected thrombosis failing standard anticoagulation the use of EPT appears safe and effective. This approach warrants further study. Baseline characteristics and outcome after EPT treatment Patient cfLVAD generation Echo evidence of thrombosis Peak LDH (U/L) Δ in cfLVAD parameters EPT success A-1 2nd + 939 + + A-2 2nd − -- + + B 2nd − 3065 + + C-1 2nd − 860 + − C-2 2nd + -- + + D-1 2nd + 5666 + − D-2 2nd − 815 + − E 2nd − 766 + + F 3rd − 4860 + − G 3rd − 1751 + + H 2nd + 889 + − I-1 2nd + 1035 + − I-2 2nd − 900 + − J 2nd − 1018 + + K-1 2nd − 3714 − + K-2 2nd − 1014 − −