Design Rationale and Preclinical Evaluation of the HeartMate 3 Left Ventricular Assist System for Hemocompatibility

Bourque, Kevin; Cotter, Christopher J.; Dague, Charles; Harjes, Daniel I.; Dur, Onur; Duhamel, Julien; Spink, Kaitlyn; Walsh, Kelly S.; Burke, E.A.

doi:10.1097/mat.0000000000000388

Cited by 162 publications

(144 citation statements)

References 19 publications

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“…Although there are many published reports about the HVAD and the HMII, quantitative hemolysis data are limited. Bourque et al performed an in vitro experimental study to compare the hemolysis level of the HMII and the HMIII using bovine blood . Based on their report, the NIH value of the HMII is estimated to be 0.0098 g/100 L at 5 L/min against 100 mm Hg pressure head, while the HMIII produced a much lower level of hemolysis (NIH ~ 0.0035 g/100 L).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

et al. 2019

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In vitro hemolysis testing remains one of the most important performance measures to judge the hemocompatibility of a left ventricular assist device (LVAD). Clinically relevant operating conditions and appropriate testing blood are essential to infer in vitro data for potential clinical use. This in vitro study was carried out to evaluate and compare the hemolytic performance of a newly developed magnetically levitated (maglev) LVAD (CH‐VAD) with two clinically used LVADs (HVAD and HeartMate II (HMII)) using fresh human blood. A small volume (~300 mL) in vitro circulating flow loop was constructed with a LVAD generated flow of 4.5 L/min at the nominal or reported clinical operating speed for each LVAD. The blood was circulated in the loop for 4 hours with samples drawn at baseline and hourly. Plasma‐free hemoglobin (PFH) concentrations in the hourly blood samples were determined with spectrophotometry. Normalized index of hemolysis (NIH) was calculated to compare the hemolytic performance of the CH‐VAD and the two reference LVADs. Platelet activation was measured with flow cytometry. The experimental test for each device was repeated at least 7 times. The data from this study showed that all the three LVADs generated very low hemolysis (NIH <0.01 g/100 L). The CH‐VAD was found to have a significantly lower NIH value (0.00135 ± 0.00032 g/100 L) compared to the HVAD (0.00525 ± 0.00183 g/100 L) and the HMII (0.00583 ± 0.00182 g/100 L). No statistically significant difference in device‐generated hemolysis was found between the HVAD and the HMII. The level of platelet activation induced by the CH‐VAD is significantly lower than those by the HVAD and the HMII. The data suggest that the shear‐induced hemolysis and platelet activation of the CH‐VAD are acceptable relative to the two LVADs currently in clinical use.

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Section: Discussionmentioning

confidence: 99%

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

et al. 2019

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“…5 These engineering attributes, in vitro, are associated with reduced shear stress and absence of hemolysis or thrombosis in comparison with contemporary devices. 11 A proposed explanation for reduced hemocompatibility-related complications with the HM3 include the absence of observed hemolysis, which is directly correlated with the impact of the LVAS on blood element destruction and the effects on high-molecular-weight multimers of von Willebrand factor. These clinical biomarkers are also known to reflect effects of the continuous-flow circulatory interface and potentially herald hemocompatibility-related adverse outcomes.…”

Section: Discussionmentioning

confidence: 99%

Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months

et al. 2017

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BACKGROUND:The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibilityrelated clinical adverse events (HRAEs) between the 2 LVAS. METHODS:We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. RESULTS:In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/ patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065). CONCLUSIONS:In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. CLINICAL TRIAL REGISTRATION: 2004H emocompatibility-related adverse events (HRAEs) are the Achilles heel of the interaction between a left ventricular assist system (LVAS) and its biological circulatory interface.1 The constellation of device-related hemolysis, pump thrombosis leading to malfunction, neurological events (predominantly stroke and bleeding), and nonsurgical bleeding (particularly gastrointestinal bleeding) are the principal concerns that influence outcomes in mechanical circulatory support. These frequent complications are noted to occur with all contemporary centrifugal and axial continuous-flow devices, the HeartWare ...

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“…The increased hemolysis associated with HMII is expected given the higher mechanical shear stress (25,26) compared to EXCOR that generates low shear stress force necessary to achieve the similar differential pressure across the pump and flow. The increased hemolysis associated with HMII is expected given the higher mechanical shear stress (25,26) compared to EXCOR that generates low shear stress force necessary to achieve the similar differential pressure across the pump and flow.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study

Chan¹,

Diab

Moody³

et al. 2018

Artificial Organs

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Development of pediatric ventricular assist devices (VADs) has significantly lagged behind that of adult devices. This frustrating reality is reflected by the fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric-specific device in the USA. An alternative option is an off-label use of adult continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes patient-device size mismatch in small children. We sought to conduct in vitro hemocompatibility testing in a pediatric flow condition, with a specific aim to provide benchmark values for future pediatric device development. Given the aforementioned fact that both pulsatile and continuous-flow devices are being used in the pediatric population, we opted to test both types of devices in the present study. The EXCOR and HMII blood pumps were tested using bovine blood under constant hemodynamic conditions (flow rate, Q = 2.5 ± 0.25L/min; differential pressure across the pump, ΔP = 68 ± 5mm Hg). Hemolysis was measured by Harboe assay. There was a steady increase in plasma free hemoglobin during in vitro testing, with a statistically significant difference between 5 and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree of an increase in plasma free hemoglobin was more significant with HMII (P < 0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 ± 0.0026g/100 L and 0.085 ± 0.0119g/100 L, respectively. There was also a steady increase in platelet activation detected by CAPP2A antibody using flow cytometry, with a statistically significant difference between 5 and 360 min for both devices (P < 0.05). The degree of an increase in platelet activation was similar between the two devices (P = 0.218). High molecular weight von Willebrand factor (HMW vWF) multimer degradation measured by immunoblotting was evident for both devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from all three time points (120, 240, and 360 min) were significantly different from the baseline (5 min), whereas only 360 min samples had a significant difference from the baseline with the HMII. In conclusion, we have observed similarities and differences in hemocompatibility profiles between the EXCOR and HMII, both of which are commonly used in the pediatric population. We anticipate the benchmark values in the present study will facilitate future pediatric VAD development.

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Design Rationale and Preclinical Evaluation of the HeartMate 3 Left Ventricular Assist System for Hemocompatibility

Cited by 162 publications

References 19 publications

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

Evaluation of in vitro hemolysis and platelet activation of a newly developed maglev LVAD and two clinically used LVADs with human blood

Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months

In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric Flow Conditions: A Benchmark Study

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