Reducing regional flow stasis and improving intraventricular hemodynamics with a tipless inflow cannula design: An in vitro flow visualization study using the EVAHEART LVAD.

Due to the high stroke rate of left ventricular assist device (LVAD) patients, reduction of thrombus has emerged as an important target for LVAD support. Left ventricular blood flow patterns with areas of flow stasis and recirculation are associated with platelet aggregation, which is worsened by exposure to high shear stress. Previous reports of intraventricular thrombus in LVAD patients have identified the outside of the LVAD inflow cannula as a nidus for LV thrombus formation. Previous studies of LVAD inflow cannula design have shown a region of low blood velocity and pulsatility at the apex, adjacent to the cannula. One unresolved question is whether the standard practice of inserting the LVAD inflow cannula several mm into the LV could be revised to reduce thrombus formation. To address this, a "tipless" inflow cannula was designed for the EVAHEART LVAS, and assessed in a mock circulatory loop of the LVAD-supported heart. Customized transparent silicone models of a dilated LV were connected to the EVAHEART LVAS at the apex with a clear polycarbonate inflow cannula for flow visualization using particle image velocimetry (PIV). The "tipless" cannula was inserted flush with the endocardial border and did not protrude into the LV. This condition was compared to the standard cannula position with a 1-cm insertion into the LV. The Pre-LVAD condition corresponded to a severe heart failure patient (ejection fraction of 24%) with a dilated LV (180 mL). LVAD support was provided at speeds of 1.8 and 2.3 krpm. At the lower LVAD speed, 63% of the flow passed through the LVAD, with the remainder ejecting through the aortic valve. When LVAD speed was increased, nearly all flow (98%) left the LV through the LVAD. Both LVAD speed conditions produced a vortex ring similar to the Pre-LVAD condition in diastole. However, the protruding inflow cannula interrupted the growth and restricted the movement of the vortex, and produced areas of low velocity and pulsatility adjacent to the cannula. The tipless cannula exhibited an uninterrupted pattern of the mitral jet toward the LV apex, which allowed the diastolic vortex to grow and aid in the washout of this region. In addition, the tipless cannula increased aortic valve flow, which reduces stasis in the left ventricular outflow tract. The EVAHEART LVAS tipless inflow cannula design improved regional velocity, pulsatility, and vortex formation compared to the standard protruding design, which all reduce the risk of thrombus formation. The clinical significance of the differences observed in the flow field will be dependent on other factors such as the cannula material and surface characteristics, as well as the patients' coagulation status.

Preclinical Evaluation of the EVAHEART 2 Centrifugal Left Ventricular Assist Device in Bovines.

The EVAHEART 1 left ventricular assist device was miniaturized to the EVAHEART 2, with a new inflow cannula designed to mitigate the risks of malposition. To evaluate the safety of the new double-cuff tipless inflow cannula, in vivo studies were performed in healthy bovines. Eight consecutive studies were done: five short-term studies of hematological adaptation and three long-term studies of tissue adaptation. Each inflow cannula was purposefully implanted in the worst-case setting with marked malposition. Two studies terminated early: one because of an animal-specific ancillary component and one because of an accidental radial fracture. Six studies reached the study endpoint without major adverse events. One animal could not achieve proper anticoagulation because of warfarin resistance. Pump speed and power were maintained within stable, normal ranges. There were no major organ dysfunction or suction events. Necropsy results showed two cases of pannus formation around the inflow ostium because of warfarin resistance and hyperinflammation at the inflow cuff suture line. There was one case of trivial pannus; four cases were pannus-free, with no evidence of ventricular wall suction. No wedge thrombus formation occurred. The EVAHEART 2 tipless inflow cannula may reduce adverse events attributable to the inflow cannula, such as stroke.

Virtual Fitting and Hemodynamic Simulation of the EVAHEART 2 Left Ventricular Assist Device and Double-Cuff Tipless Inflow Cannula.

Inflow malposition during surgery, postoperative pump migration, inflow obstruction, and right ventricular compression are major contributors to low flow and adverse events in patients with ventricular assist devices (VADs). These position abnormalities can lead to adverse events including ischemic stroke. To address these problems, we conducted a virtual anatomical fitting study and hemodynamic simulation on iterative cannula designs, resulting in the EVAHEART 2 with the novel double-cuff tipless (DCT) inflow cannula and smaller pump design. Anatomical fitting was based on computed tomography scans of six patients with heart failure, and a fluid-structure-integration (FSI) model of the left ventricle with a lumped parameter model of the entire cardiovascular system during VAD support was created. Using this model, the hemodynamics of three inflow cannula insertion lengths for two patient-specific ventricles were calculated for both full and partial VAD support. The DCT cannula with the smaller pump housing proved resistant to obstruction even when the pump housing was adjusted. The complete system also had a smaller pump pocket size than the other designs and avoided position abnormalities that commonly lead to adverse events. Compared with conventional cadaver studies, virtual fitting and numerical simulations are more beneficial and economical for iteratively designing medical devices.

The Effect of Inflow Cannula Length on the Intraventricular Flow Field: An In Vitro Flow Visualization Study Using the Evaheart Left Ventricular Assist Device.

Left ventricular assist device (LVAD) inflow cannula malposition is a significant risk for pump thrombosis. Thrombus development is influenced by altered flow dynamics, such as stasis or high shear that promote coagulation. The goal of this study was to measure the intraventricular flow field surrounding the apical inflow cannula of the Evaheart centrifugal LVAD, and assess flow stasis, vortex structures, and pulsatility for a range of cannula insertion depths and support conditions. Experimental studies were performed using a mock loop with a customized silicone left ventricle (LV) and the Evaheart LVAD. A transparent inflow cannula was positioned at 1, 2, or 3 cm insertion depth into the LV and the velocity field in the LV midplane was measured for 2 levels of LVAD support: 1800 and 2300 rpm. The LV velocity field exhibits a diastolic vortex ring whose size, path, and strength are affected by the flow conditions and cannula position. During diastole, the large clockwise midplane vortex grows, but its circulation and kinetic energy are reduced with cannula insertion depth. The counterclockwise vortex is smaller and exhibits more complex behavior, reflecting a flow split at 3 cm. Overall, the 1 cm cannula insertion depth produces the flow pattern that exhibits the least apical flow stasis and greatest pulsatility and should correlate to a lower risk of thrombus formation.

Optimization of axial-pump pressure sensitivity for a continuous-flow total artificial heart.

BACKGROUND: In this study, we describe the potential advantages of a continuous-flow total artificial heart (CFTAH) comprising two small, non-pulsatile pumps with optimized responsiveness to the pressure gradient. METHODS: We modified a MicroMed DeBakey axial-flow pump by increasing its inducer-impeller inlet angle, thereby increasing its pressure responsivity. We obtained the in vitro pressure gradient response and compared it with those of the clinically used, unmodified MicroMed DeBakey pump, Jarvik 2000 FlowMaker and HeartMate II. RESULTS: The modified pump showed an increased response to changes in the pressure gradient at pump flow rates of between 2 and 4 liters/min. The maximum pressure responsivity of the modified pump was 2.5 liters/min/mm Hg; the corresponding maximum responsivities of the Jarvik 2000, HeartMate II and MicroMed DeBakey ventricular assist devices (VADs) were 0.12, 0.09 and 0.38 liters/min/mm Hg, respectively. CONCLUSIONS: Because of the inherent properties of non-pulsatile pumps, the CFTAH may potentially respond to changes in inflow and outflow pressures while maintaining physiologic flow rates sufficient for normal daily activity. In addition, the hemodynamic interplay between the two optimized pumps should allow a physiologic response to normal flow imbalances between the pulmonary and systemic circulations. Improved responsiveness to inflow pressure may further simplify and improve the CFTAH and affect its potential clinical use as a meaningful therapy for terminal heart failure.

Continuous flow total artificial heart: modeling and feedback control in a mock circulatory system.

We developed a mock circulatory loop and used mathematical modeling to test the in vitro performance of a physiologic flow control system for a total artificial heart (TAH). The TAH was constructed from two continuous flow pumps. The objective of the control system was to maintain loop flow constant in response to changes in outflow resistance of either pump. Baseline outflow resistances of the right (pulmonary vascular resistance) and the left (systemic vascular resistance) pumps were set at 2 and 18 Wood units, respectively. The corresponding circuit flow was 4 L/min. The control system consisted of two digital integral controllers, each regulating the voltage, hence, the rotational speed of one of the pumps. The in vitro performance of the flow control system was validated by increasing systemic and pulmonary vascular resistances in the mock loop by 4 and 8 Wood units (simulating systemic and pulmonary hypertension conditions), respectively. For these simulated hypertensive states, the flow controllers regulated circuit flow back to 4 L/min within seconds by automatically adjusting the rotational speed of either or both pumps. We conclude that this multivariable feedback mechanism may constitute an adequate supplement to the inherent pressure sensitivity of rotary blood pumps for the automatic flow control and left-right flow balance of a dual continuous flow pump TAH system.

Ambulatory oxygenator right ventricular assist device for total right heart and respiratory support.

BACKGROUND: Our goal is ambulatory total respiratory and right heart assistance allowing a bridge to lung transplant. To that end, we have coupled a compact paracorporeal gas exchange device with a right ventricular assist device (RVAD) to create an "OxyRVAD." METHODS: Through a limited left thoracotomy, the main pulmonary artery (PA) and right atrium (RA) were exposed in 5 anesthetized sheep. After a systemic heparin bolus, a 12-mm outer diameter crimped graft glued to tubing was anastomosed (end to side) to the main PA and a VAD atrial cannula was placed through the RA appendage. The chest was drained and closed, then the PA graft flowed at 1 to 2 L/min as a shunt to the RA overnight. The next day, the animal was reanticoagulated, and the shunt cannulae clamped and divided. The OxyRVAD unit, consisting of commercially available components including an axial flow pump and low-resistance cardiopulmonary bypass gas exchange device, was interposed. Pumping from RA to PA was maintained at 3 L/min. RESULTS: Five consecutive sheep survived the implant, and stood and ate normally after initiation of the OxyRVAD. Three survived the full 2-week study, and a fourth was sacrificed on day 13 owing to a storm-related power failure. For these 4 sheep, pump flow was stable at 3 L/min. Carbon dioxide removal was constant and total during the experiment at 200 +/- 19 mL/min. Oxygen transfer was 144 +/- 44 mL/min. One sheep had progressive thrombocytopenia and was sacrificed on day 5 after implant. CONCLUSIONS: Our ambulatory OxyRVAD can provide total assistance for the right heart and lungs in normal awake sheep for 14 days.

Advanced suction detection for an axial flow pump.

An automatic detection system for ventricular collapse was developed and tested in a first clinical trial as part of a physiological speed control concept for axial flow pumps. From this clinical experience, and based on the acquired data during this trial, an optimization of the developed system was performed. An already-existing database of 784 individual cases was extended. For harmonization of this database an additional 412 snap files were extracted from continuous data recordings and classified manually using a standardized procedure. The already-developed and clinically tested algorithms were supplemented by one additional indicator derived from a preexisting criterion. One threshold value was replaced by application of a numerically optimized nonlinear characteristic curve dependent on heart rate. Finally, in a multidimensional optimization process of the entire suction detection system, 7 individual indicators were adjusted by using 17 independent threshold values. The optimization criteria were applied using a three-level hierarchical system. Within the final database consisting of 1196 snap shots the overall amount of maldetections could be reduced to 23 cases including 5 false positive events (0.42%) and 18 false negative decisions (1.5%). By application of the clinical experience from the first clinical trial of a physiologic control system it became possible to optimize the sensitivity and specificity of the suction detection system to unprecedented accuracy.

First clinical experience with an automatic control system for rotary blood pumps during ergometry and right-heart catheterization.

BACKGROUND: At present, most clinically implanted rotary blood pumps are operated at constant speed and adjusted by the physician. It is generally assumed that an adaptation of pump speed to the patient's physiologic requirements would be beneficial. The data provided in this paper, based on hemodynamic and spirometric data during exercise in which a pre-load-sensitive control was used, lend quantitative support to this assumption. METHODS: An automatic speed control was developed and implemented with Matlab on a dSpace controller board. The system uses pump speed, pump power, and pump flow as its only input signals. It was connected to the clinical hardware of the DeBakey VAD System. The control is pre-load-sensitive and uses an expert system to detect excessive unloading and eventual suction. This system was used to quantify the cardiovascular reaction of patients to both automatically controlled and constant pump speed. A sub-group of 5 patients underwent bicycle ergometry with Swan-Ganz catheterization and spiroergometry. RESULTS: The automatic, closed-loop speed control showed robust and stable performance. It provided an increase in pump flow (+0.94 +/- 0.5 liters/min, p < 0.05) compared with constant-speed mode in response to physical activity. Pulmonary arterial (PAP) and capillary wedge pressure (PCWP) clearly decreased (-7.4 +/- 4.1 mm Hg for PAP and -8.3 +/- 4.2 mm Hg for PCWP, p < 0.05), and venous oxygen saturation moderately increased (+5.2%). CONCLUSION: An automatic speed-control system for rotary blood pumps was developed and demonstrated by spiroergometry to be appropriately responsive to physiologic demand.

Development of a reliable automatic speed control system for rotary blood pumps.

BACKGROUND: Axial blood pumps have been very successfully introduced into the arena of prolonged clinical support. However, they do not offer inherent load-responsive mechanisms for adjusting pumping performance to venous return and changes in physiologic requirements of the patient. To provide for these adjustments we developed an algorithm for demand-responsive pump control based on a reliable suction detection system. METHODS: A PC-based system that analyzes pump performance based on available flow, heart rate and short-term performance history was developed. The physician defines levels of "desired flow" at rest and during exercise, depending on heart rate. In case this desired flow cannot be maintained due to limited venous return, the maximal available flow level is determined from an analysis of the actual pump data (flow, speed and power consumption). An expert system continuously checks the flow signal for any indication of suction. Periodic speed variations then adapt pump performance to the patient's condition. RESULTS: First, stability and functionality were proven under various settings in vitro. The algorithms were then tested in 15 patients in intensive care, in the standard ward, and during bicycle exercise. The system reacted properly to demand changes, at exercise level, in response to coughing and at various Valsalva maneuvers. Suction could also be successfully prevented during severe arrhythmia and in patients with critical cardiac geometry. Exercise tests showed decreases in pulmonary arterial pressure (-22 +/- 9.9%) and pulmonary capillary wedge pressure (-42 +/- 18.54%), and an increase in pump flow (19 +/- 9.5%) and workload (8 +/- 6.1%), all when compared with constant-speed pumping. CONCLUSIONS: A closed-loop control system equipped with an expert system for reliable suction detection was developed that improves response to change in venous return for rotary pump recipients. The system was robust, stable and safe under a wide range of everyday living conditions.

Suction detection for the MicroMed DeBakey Left Ventricular Assist Device.

The MicroMed DeBakey Ventricular Assist Device (MicroMed Technology, Inc., Houston, TX) is a continuous axial flow pump designed for long-term circulatory support. The system received CE approval in 2001 as a bridge to transplantation and in 2004 as an alternative to transplantation. Low volume in the left ventricle or immoderate pump speed may cause ventricular collapse due to excessive suction. Suction causes decreased flow and may result in patient discomfort. Therefore, detection of this critical condition and immediate adaptive control of the device is desired. The purpose of this study is to evaluate and validate system parameters suitable for the reliable detection of suction. In vitro studies have been performed with a mock loop allowing pulsatile and nonpulsatile flow. Evidence of suction is clearly shown by the flow waveform reported by the implanted flow probe of the system. For redundancy to the implanted flow probe, it would be desirable to use the electronic motor signals of the pump for suction detection. The continuously accessible signals are motor current consumption and rotor/impeller speed. The influence of suction on these parameters has been investigated over a wide range of hydrodynamic conditions, and the significance of the respective signals individually or in combination has been explored. The reference signal for this analysis was the flow waveform of the ultrasonic probe. To achieve high reliability under both pulsatile and nonpulsatile conditions, it was determined that motor speed and current should be used concurrently for suction detection. Using the amplified differentiated current and speed signals, a suction-detection algorithm has been optimized, taking into account two different working points, defined by the value of the current input. The safety of this algorithm has been proven in vitro under pulsatile and nonpulsatile conditions over the full spectrum of possible speed and differential pressure variations. The algorithm described herein may be best utilized to provide redundancy to the existing flow based algorithm.

Development of a suction detection system for axial blood pumps.

Axial flow blood pumps for cardiac assistance have proven their clinical viability and benefit in recent years. However, the clinical systems to date have no direct mechanism to decrease pump speed when adequate supply is not available. This may lead to ventricular collapse or increase the probability of hemolysis and thrombotic risks. Based on various experiences with left ventricular assist device (LVAD) patients in various states of recovery, at implant, in the intensive care unit, in the standard ward, and during physical exercise, 11 different algorithms were developed for the automatic detection of ventricular suction. These detection algorithms analyze the flow pattern for the presence of distinct suction indicators. For selection and optimization of the algorithms, 1000 records from approximately 100 patients were collected. Each record contains 5 s of pump flow, current, and arterial pressure. Three experts classified these records in terms of suction probability and other abnormalities. The optimization was developed in Matlab, capable of solving a fifth-dimensional optimization problem with 256 different algorithm combinations. The optimization resulted in a set of 6 algorithms, each with specific thresholds. The system detects 100% of the known suction events with 0.28% of false-positive interpretations. If tuned to avoid any false-positive detection, 90.7% of the certain events would be detected. A strategy for the development of a robust suction detection system for axial blood pumps was found. This system will be integrated into an automatic pump speed control system to provide adequate perfusion for the LVAD recipient, without excessive unloading of the ventricle.

Development of a Pivot Bearing Supported Sealless Centrifugal Pump for Ventricular Assist.

Since 1991, in our laboratory, a pivot bearing-supported, sealless, centrifugal pump has been developed as an implantable ventricular assist device (VAD). For this application, the configuration of the total pump system should be relatively small. The C1E3 pump developed for this purpose was anatomically compatible with the small-sized patient population. To evaluate an-tithrombogenicity, ex vivo 2-week screening studies were conducted instead of studies involving an intracorpore-ally implanted VADs using calves. Five paracorporeal LVAD studies were performed using calves for longer than 2 weeks. The activated clotting time (ACT) was maintained at approximately 250 s using heparin. All of the devices demonstrated trouble-free performances over 2 weeks. Among these 5 studies, 3 implantations were subjected to 1-month system validation studies. There were no device-induced thrombus formations inside the pump housing, and plasma-free hemoglobin levels in calves were within the normal range throughout the experiment (35, 34, and 31 days). There were no incidents of system malfunction. Subsequently, the mass production model was fabricated and yielded a normalized index of hemolysis of 0.0014, which was comparable to that of clinically available pumps. The wear life of the impeller bearings was estimated at longer than 8 years. In the next series of in vivo studies, an implantable model of the C1E3 pump will be fabricated for longer term implantation. The pump-actuator will be implanted inside the body; thus the design calls for substituting plastic for metallic parts.