Ex vivo assessment of erythrocyte tolerance to the HeartWare ventricular assist device operated in three discrete configurations

Abstract

Despite technological advances in ventricular assist devices (VADs) to treat end‐stage heart failure, hemocompatibility remains a constant concern, with supraphysiological shear stresses an unavoidable reality with clinical use. Given that impeller rotational speed is related to the instantaneous shear within the pump housing, it is plausible that the modulation of pump speed may regulate peak mechanical shear stresses and thus ameliorate blood damage. The present study investigated the hemocompatibility of the HeartWare HVAD in three configurations typical of clinical applications: standard systemic support left VAD (LVAD), pediatric support LVAD, and pulmonary support right VAD (RVAD) conditions. Two ex vivo mock circulation blood loops were constructed using explanted HVADs, in which pump speed and external loop resistance were manipulated to reflect the flow rates and differential pressures reported in configurations for standard adult LVAD (at 3150 rev⸱min−1), pediatric LVAD (at 2400 rev⸱min−1), and adult RVAD (at 1900 rev⸱min−1). Using bovine blood, the mock circulation blood loops were tested at 37°C over a period of 6 hours (consistent with ASTM F1841‐97) and compared with static control. Hemocompatibility assessments were conducted for each test condition, examining hematology, hemolysis (absolute and normalized index), osmotic fragility, and blood viscosity. Regardless of configuration, continuous exposure of blood to the VAD over the 6‐hour period significantly altered hematological and rheological blood parameters, and induced increased hemolysis when compared with a static control sample. Comparison of the three operational VAD configurations identified that the adult LVAD condition—associated with the highest pump speed, flow rate, and differential pressure across the pump—resulted in increased normalized hemolysis index (NIH; 0.07) when compared with the lower pump speed “off‐label” counterparts (NIH of 0.04 in pediatric LVAD and 0.01 in adult RVAD configurations). After normalizing blood residence times between configurations, pump speed was identified as the primary determinant of accumulated blood damage; plausibly, blood damage could be limited by restricting pump speed to the minimum required to support matched cardiac output, but not beyond.

Accelerated Hemocompatibility Testing of Rotary Blood Pumps

“…Thus, in a chronological sense, our results are in agreement with those of Woelke et al ., 6,7 although our data extend these observations; our congruence of results from the three loops were achieved despite differences in the two most extreme conditions varying by 240 ml and 192 minutes (Figure 2B). The mean NIH observed in the present study ranged 4.2–4.9 mg·100 L c1 , which is mildly lower than prior reports of 5.3, 10 6.8, 11 and 7 12 mg·100 L −1 ; our hypothesis is that our venesection technique, and rapid use of blood following collection may explain, at least in part, this observation. Nevertheless, it is encouraging that the tight range of NIH values in the present study, despite the substantially different loop volumes, provides confidence in further evaluation of smaller blood test loops for accelerated hemolysis assessment.…”

Hemolysis Testing In Vitro: A Review of Challenges and Potential Improvements

“…Of these publications, only primary sources of experimental hemolysis were included (n = 9). 6,[27][28][29][30][31][32][33][34] As a common comparative measure for reproducibility, the absolute coefficient of variation (CV) was calculated, which is the ratio of the standard deviation to the mean value of a series of measurements. The CV was calculated separately for all reported test conditions, totaling 31 collected measurement series with an average of 51 ± 30%.…”

Red Blood Cell Mechanical Fragility as a Potential Predictor of Long-Term Hemolysis from Ventricular Assist Devices

“…The pivotal MOMENTUM 3 study reported a significantly improved net hemocompatibility score for HM3 as compared to HM2, with such improvement linked to the absence of observed hemolysis 48 . The HVAD system, which was reported to induce hemolysis compared to static sample 49 , also showed less induced hemolysis when compared to HM2 50 . Other work, however, reported elevated shear stress and shear rate in the aortic arch with the HVAD when compared to both HMII and HM3 51 .…”