Thromboresistance Comparison of the HeartMate II Ventricular Assist Device With the Device Thrombogenicity Emulation-Optimized HeartAssist 5 VAD

The number of patients suffering from cardiovascular diseases grows annually, and approximately 2% of the United States population (∼5.7 × 106) are diagnosed with congestive heart failure (CHF) with a projected 25% of increase in their number by 2030 [1]. Mechanical circulatory support (MCS) devices, such as total artificial hearts (TAHs) or ventricular assist devices (VADs) were introduced as a bridge-to-transplant (BTT) to sustain eligible patients while waiting for available heart transplants [2,3]. Owing to insufficient amount of eligible organs for heart transplant annually [4], the Food and Drug Administration (FDA) approved the use of one of the more hemodynamically and mechanically robust VADs, the Thoratec HeartMate II VAD (HMII; Thoratec Corp., Pleasanton, CA), for destination therapy in 2010 [5,6]. Prior to the HeartMate II, various VADs were developed and introduced to the market broadly under the following two categories: pulsatile-flow (i.e., the first generation pulsatile VADs) and continuous-flow (i.e., the second generation axial VADs and the third generation centrifugal VADs) [7,8]. Due to their relatively simpler mechanics, the continuous-flow VADs provide higher durability and require smaller implantation volume than the pulsatile-flow VADs. In the continuous-flow VADs, the blood is constantly propelled out from the apex of the left ventricle by a turbine, and returned to the ascending aorta. In order to generate physiological cardiac outputs, those continuous-flow VADs operate at very high impeller speeds (7000 to 12,000 RPM), which generates unusually high shear stress levels in some locations like the impeller-shroud gaps and regions of elevated residence time in the rear (inlet) and front (outlet) hubs. These high stress accumulation regions may potentially cause damage to the blood cells flowing through the device (e.g., hemolysis of RBCs and activation of platelets has been reported) [9,10], which may lead to various post-implant complications, such as flow-induced platelet activation, aggregation, and subsequent thromboembolic complications or complete device obstruction/malfunction due to thrombus formation [11–14]. Due to these post-implant complications, device recipients are mandated to life-long antiplatelet and anticoagulation regimens, which lead to secondary complications such as heparin-induced thrombocytopenia or several bleeding incidents [15–18]. In order to reduce or eliminate the administration of the antiplatelet or anticoagulation regimens, modifying the geometrical features of the VADs implicated in higher stress accumulation by applying the device thrombogenicity emulation (DTE) methodology in order to reduce the device thrombogenic potential has shown to be a very promising approach, and is briefly described below [11,19,20]. Our group had successfully optimized the thrombogenic performance of an axial continuous-flow VADs, the modern MicroMed DeBakey VAD (DeBakey; MicroMed Cardiovascular, Inc., Houston, TX). The optimized version of the device called MicroMed HeartAssist 5 VAD (HA5; MicroMed Cardiovascular, Inc., Houston, TX) shows an order of magnitude reduction in flow-induced thrombogenicity in vitro [11] and markedly improved benefit over Aspirin or Dipyridamole addition in vitro [20]. The DTE methodology interfaces numerical (in silico) flow simulations with in vitro experiments performed in a hemodynamic shearing device (HSD), which replicates stress-time data extracted from problematic regions of the device, to perform iterative optimization of the device thrombogenic potential [11,19,21]. This in silico/in vitro methodology can potentially reduce the research and development costs of developing thromboresistant mechanical circulatory support (MCS) devices by reducing the need for costly in vivo experimentation prior to the device approval by the FDA. As mentioned previously, the HMII is currently the only FDA approved continuous-flow VAD for both BTT and DT—it has been widely implanted worldwide [2,3,5,6]. However, HMII recipients still require long-term/life-long anticoagulation or antiplatelet regimens, yet not eliminating post-implant bleeding or thrombotic complications [17,22,23]. For instance, in approximately 6% of HMII recipients' device thrombosis was reported which lead to replacement of the implanted device with associated morbidities [12–14,24]. Given this high incidence of thrombotic complications rates, it is judicious to compare this FDA-approved VAD (HMII) currently in clinical use with a similar device which thrombogenicity has been optimized such as the HA5 VAD [11]. The weight of HMII is approximately 3-fold that of HA5 (i.e., 281 g compared to 92 g, respectively), with approximately 2.3-fold larger external volume (i.e., approximately 117,628 mm3 and 50,187 mm3 of HMII and HA5, respectively) (Figs. 1(a)i and (b)ii for HMII and HA5, respectively). Due to the smaller dimension and lighter weight, the HA5 offers significant benefits of implanting the HA5 in the pericardial space while the HMII has to be implanted below the diaphragm. Due to the design differences of the interior components between these two VADs, the HA5 has slightly larger fluid volume capacity than the HMII (5.55 ml and 5.80 ml of fluid in the HMII and HA5, respectively, from the inlet tip of the flow straightener to the exit tip of the diffuser (Figs. 1(a)ii and (b)ii for HMII and HA5, respectively)). This implies that the HA5 may consume less energy and operate at a lower impeller speed—to generate identical cardiac output (CO) as compared to the HMII. Fig. 1 Illustrations of the exterior and interior features of (a) HMII and (b) HA5 and (c) Flow-loop for the in vitro experiments. The exterior features of HMII (a)i and HA5 (b)i; the length of the VADs are 71 mm and 81 mm, and the maximum diameter ...