Continuous-flow Total Artificial Heart Research Articles

Simulated Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart Using the Virtual Mock Loop.

Our new Virtual Mock Loop (VML) is a mathematical model designed to simulate the human cardiovascular system and gauge performance of mechanical circulatory support devices. We aimed to mimic the hemodynamic performance of Cleveland Clinic's self-regulating continuous-flow total artificial heart (CFTAH) via VML and evaluate VML's accuracy versus bench data from our standard mock circulatory loop. The VML reproduced 23 hemodynamic conditions. Systemic/pulmonary vascular resistances and pump rotational speed were set for VML from bench test data. We compared outputs (pump flow, left/right pump pressure rise, normalized pump performance, and atrial pressure difference) of the two methods. Data from pump flow and left pump pressure rise were similar, but right pump pressure rise slightly differed. Left pump normalized pump performance curves were similar. Right pump VML results were within the same performance range indicated by bench tests. The plots of atrial pressure differences of VML versus bench-test data were similar, but slightly differed in the midrange of systemic/pulmonary gradients. Virtual Mock Loop successfully reproduced results from our mock circulatory loop of CFTAH test conditions. The CFTAH's self-regulation feature of right pump performance was also calculated effectively. We foresee using versions of the VML for training, simulating physiologic cardiac conditions, and patient monitoring.

Continuous-flow total artificial heart: hemodynamic and pump-related changes associated with posture in a chronic calf model.

This study aimed to evaluate the effects of posture (sitting [lying down]/standing) on hemodynamic and pump-related parameters in calves implanted with our institution's continuous-flow total artificial heart (CFTAH). These parameters were analyzed with posture information in four calves that had achieved the intended 14-, 30-, or 90-day durations of implantation. In each animal, postoperative hourly data gathered throughout the study were used to compare average values with the animal sitting vs. standing. Pump flow became significantly higher in the standing than sitting position at the same pump speed (standing 7.9 ± 0.8, sitting 7.4 ± 1.0 L/min, p = 0.028). Systemic vascular resistance (SVR) and aortic pressure (AoP) were significantly lower in the standing than sitting position (SVR standing 779 ± 145, sitting 929 ± 206dynes/cm5, p = 0.027; AoP standing 93 ± 7, sitting 103 ± 7mm Hg, p < 0.001). No substantial change occurred in pulmonary vascular resistance (PVR) or pulmonary arterial pressure (PAP) with posture (PVR standing 161 ± 39, sitting 164 ± 48dynes/cm5, p = 0.639; PAP standing 32 ± 3, sitting 33 ± 4mm Hg, p = 0.340). Posture affected some hemodynamic and pump-related parameters in calves with CFTAH, with implications for patients with implanted pumps.

Development of Continuous-Flow Total Artificial Heart for Use in Infants

Purpose Heart transplantation in infants and children is an accepted therapy for congenital heart disease, but donor organ availability remains unstable. Mechanical circulatory support is another standard option, but there is a lack of implantable devices due to size and functional range. The purpose of this study was to evaluate in vivo performance of the initial prototype of an infant continuous-flow total artificial heart (I-CFTAH) with one motor and one rotating assembly supported by a hydrodynamic bearing. Methods The I-CFTAH was designed to cover a range of 3 kg infant to 9 kg child (flange diameter - 26.9 mm; length - 44 mm), with nominal design point was matched to a 6 kg child, requiring 1.0 L/min of flow. I-CFTAH was tested using in silico virtual simulation mock loop (VML; MATLAB; MathWorks®) and simulated the hemodynamics as they surge through the system implanted with blood pump (run at 0.5 L/min for 3 kg infant). Lumped-parameter model including systemic/pulmonary circulation, values for impedance, beat rate, and blood volume was used. Results The in silico experiments showed intended performance of scaled down pump (left and right pump flows - 0.5 L/min at 4380 RPM). The difference between the left and right atrial pressures was maintained within ± 5-15 mm Hg. Simulation of I-CFTAH was successfully performed and allowed creating arterial pulsation with this device. Conclusion The present simulation-based approach showed feasibility of I-CFTAH design. The I-CFTAH met the proposed requirements for self-regulation, performance and pulse modulation. Further in vitro validation and in vivo implantation will be necessary to explore this technology in more detail.

Advantages of Integrating Pressure-Regulating Devices Into Mechanical Circulatory Support Pumps.

Control of mechanical circulatory support pump output typically requires that pressure-regulating functions be accomplished by active control of the speed or geometry of the device, with feedback from pressure or flow sensors. This article presents a different design approach, with a pressure-regulating device as the core design feature, allowing the essential control function of regulating pressure to be directly programmed into the hydromechanical design. We show the step-by-step transformation of a pressure-regulating device into a continuous-flow total artificial heart that passively balances left and right circulations without the need for pressure and flow sensors. In addition, we discuss a ventricular assist device that prevents backflow in the event of power interruption and also dynamically interacts with residual ventricle function to preserve pulsatility.

Lumbar muscle atrophy caused by harness replacement in a chronic calf model of total artificial heart implantation.

The postoperative care of animals implanted with mechanical circulatory support devices is complex. The standard of care requires continuous monitoring of hemodynamic parameters post implant, wound care, and maintenance of the animal's well-being, but also includes controlling the animal's biomechanics under conditions of continuous restraint and harnessing. In such studies, a harness provides secure fixation of the exteriorized device driveline and pressure lines and aids animal handling (lifting, position adjustment, and assistance with standing up). Harnessing is a key element in large-animal surgery. It affects the animal's conditions, safety, and post-procedure troubleshooting and thus may drastically worsen postoperative outcomes if improperly handled. Here we report a case associated with an unplanned harness replacement in a chronic animal model implanted with the Cleveland Clinic continuous-flow total artificial heart. Inadvertent changes to the harness resulted in posture change caused by muscular atrophy of the calf's spine that had been under long-term harness support.

Anatomical study of the Cleveland Clinic continuous-flow total artificial heart in adult and pediatric configurations.

The purpose of this study was to assess the smallest possible body sizes of patients in whom the Cleveland Clinic continuous-flow total artificial heart for adult (CFTAH) and pediatric configurations (P-CFTAH) can fit. One of the most critical dimensions is the vertebra-to-sternum distance at the junction of the right atrium to the inferior vena cava (V-S distance). Our previous CFTAH anatomical fitting study suggested that the CFTAH would fit patients of V-S distance ≥ 7.5cm and the P-CFTAH of V-S distance ≥ 5.25cm (70% of 7.5cm). To confirm this, we assessed the relationship between body surface area (BSA) and V-S distance in 15 adult patients (BSA 1.86-2.62m2) and 31 pediatric patients (BSA 0.17-1.80m2) whose computed tomography scans were available. We found a highly significant correlation between BSA and V-S distance (p < 1.0 × 10-25). It appears that the CFTAH will fit in most patients with BSA ≥ 1.0m2 (corresponding height of ≥ 130cm and age of 9years) and the P-CFTAH in patients with BSA ≥ 0.3m2 (corresponding height of ≥ 55cm and age of 1month). Further anatomical fitting studies are needed to evaluate the two pump models inside human chests to determine the smallest patient size/critical dimensions and device port configurations.

Early in vivo experience with the pediatric continuous-flow total artificial heart.

Heart transplantation in infants and children is an accepted therapy for end-stage heart failure, but donor organ availability is low and always uncertain. Mechanical circulatory support is another standard option, but there is a lack of intracorporeal devices due to size and functional range. The purpose of this study was to evaluate the in vivo performance of our initial prototype of a pediatric continuous-flow total artificial heart (P-CFTAH), comprising a dual pump with one motor and one rotating assembly, supported by a hydrodynamic bearing. In acute studies, the P-CFTAH was implanted in 4 lambs (average weight: 28.7 ± 2.3 kg) via a median sternotomy under cardiopulmonary bypass. Pulmonary and systemic pump performance parameters were recorded. The experiments showed good anatomical fit and easy implantation, with an average aortic cross-clamp time of 98 ± 18 minutes. Baseline hemodynamics were stable in all 4 animals (pump speed: 3.4 ± 0.2 krpm; pump flow: 2.1 ± 0.9 liters/min; power: 3.0 ± 0.8 W; arterial pressure: 68 ± 10 mm Hg; left and right atrial pressures: 6 ± 1 mm Hg, for both). Any differences between left and right atrial pressures were maintained within the intended limit of ±5 mm Hg over a wide range of ratios of systemic-to-pulmonary vascular resistance (0.7 to 12), with and without pump-speed modulation. Pump-speed modulation was successfully performed to create arterial pulsation. This initial P-CFTAH prototype met the proposed requirements for self-regulation, performance, and pulse modulation.

Initial in vitro testing of a paediatric continuous-flow total artificial heart.

Mechanical circulatory support has become standard therapy for adult patients with end-stage heart failure; however, in paediatric patients with congenital heart disease, the options for chronic mechanical circulatory support are limited to paracorporeal devices or off-label use of devices intended for implantation in adults. Congenital heart disease and cardiomyopathy often involve both the left and right ventricles; in such cases, heart transplantation, a biventricular assist device or a total artificial heart is needed to adequately sustain both pulmonary and systemic circulations. We aimed to evaluate the in vitro performance of the initial prototype of our paediatric continuous-flow total artificial heart. The paediatric continuous-flow total artificial heart pump was downsized from the adult continuous-flow total artificial heart configuration by a scale factor of 0.70 (1/3 of total volume) to enable implantation in infants. System performance of this prototype was evaluated using the continuous-flow total artificial heart mock loop set to mimic paediatric circulation. We generated maps of pump performance and atrial pressure differences over a wide range of systemic vascular resistance/pulmonary vascular resistance and pump speeds. Performance data indicated left pump flow range of 0.4-4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure difference was maintained within ±5 mmHg with systemic vascular resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without pump speed modulation, verifying expected passive self-regulation of atrial pressure balance. The paediatric continuous-flow total artificial heart prototype met design requirements for self-regulation and performance; in vivo pump performance studies are ongoing.

Hybrid Continuous-Flow Total Artificial Heart.

Clinical studies using total artificial hearts (TAHs) have demonstrated that pediatric and adult patients derive quality-of-life benefits from this form of therapy. Two clinically-approved TAHs and other pumps under development, however, have design challenges and limitations, including thromboembolic events, neurologic impairment, infection risk due to large size and percutaneous drivelines, and lack of ambulation, to name a few. To address these limitations, we are developing a hybrid-design, continuous-flow, implantable or extracorporeal, magnetically-levitated TAH for pediatric and adult patients with heart failure. This TAH has only two moving parts: an axial impeller for the pulmonary circulation and a centrifugal impeller for the systemic circulation. This device will utilize the latest generation of magnetic bearing technology. Initial geometries were established using pump design equations, and computational modeling provided insight into pump performance. The designs were the basis for prototype manufacturing and hydraulic testing. The study results demonstrate that the TAH is capable of delivering target blood flow rates of 1-6.5 L/min with pressure rises of 1-92 mm Hg for the pulmonary circulation and 24-150 mm Hg for the systemic circulation at 1500-10000 rpm. This initial design of the TAH was successful and serves as the foundation to continue its development as a novel, more compact, nonthrombogenic, and effective therapeutic alternative for infants, children, adolescents, and adults with heart failure.

(418) - Initial In Vitro Testing of a Pediatric Continuous-Flow Total Artificial Heart

(418) - Initial In Vitro Testing of a Pediatric Continuous-Flow Total Artificial Heart

Moderate hypothermia technique for chronic implantation of a total artificial heart in calves.

The benefit of whole-body hypothermia in preventing ischemic injury during cardiac surgical operations is well documented. However, application of hypothermia during in vivo total artificial heart implantation has not become widespread because of limited understanding of the proper techniques and restrictions implied by constitutional and physiological characteristics specific to each animal model. Similarly, the literature on hypothermic set-up in total artificial heart implantation has also been limited. Herein we present our experience using hypothermia in bovine models implanted with the Cleveland Clinic continuous-flow total artificial heart.

Thrombotic Depositions on Right Impeller of Double-Ended Centrifugal Total Artificial Heart In Vivo.

The development of total artificial heart devices is a complex undertaking that includes chronic biocompatibility assessment of the device. It is considered particularly important to assess whether device design and features can be compatible long term in a biological environment. As part of the development program for the Cleveland Clinic continuous-flow total artificial heart (CFTAH), we evaluated the device for signs of thrombosis and biological material deposition in four animals that had achieved the intended 14-, 30-, or 90-day durations in each respective experiment. Explanted CFTAHs were analyzed for possible clot buildup at "susceptible" areas inside the pump, particularly the right pump impeller. Depositions of various consistency and shapes were observed. We here report our findings, along with macroscopic and microscopic analysis post explant, and provide computational fluid dynamics data with its potential implications for thrombus formation.

Deairing Techniques for Double‐Ended Centrifugal Total Artificial Heart Implantation

The unique device architecture of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) requires dedicated and specific air-removal techniques during device implantation in vivo. These procedures comprise special surgical techniques and intraoperative manipulations, as well as engineering design changes and optimizations to the device itself. The current study evaluated the optimal air-removal techniques during the Cleveland Clinic double-endedcentrifugal CFTAH in vivo implants (n = 17). Techniques and pump design iterations consisted of developing a priming method for the device and the use of built-in deairing ports in the early cases (n = 5). In the remaining cases (n = 12), deairing ports were not used. Dedicated air-removal ports were not considered an essential design requirement, and such ports may represent an additional risk for pump thrombosis. Careful passive deairing was found to be an effective measure with a centrifugal pump of this design. In this report, the techniques and design changes that were made during this CFTAH development program to enable effective residual air removal and prevention of air embolism during in vivo device implantation are explained.

Mechanism of Self-Regulation and In Vivo Performance of the Cleveland Clinic Continuous-Flow Total Artificial Heart.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) provides systemic and pulmonary circulations using one assembly (one motor, two impellers). The right pump hydraulic output to the pulmonary circulation is self-regulated by the rotating assembly's passive axial movement in response to atrial differential pressure to balance itself to the left pump output. This combination of features integrates a biocompatible, pressure-balancing regulator with a double-ended pump. The CFTAH requires no flow or pressure sensors. The only control parameter is pump speed, modulated at programmable rates (60-120 beats/min) and amplitudes (0 to ±25%) to provide flow pulses. In bench studies, passive self-regulation (range: -5 mm Hg ≤ [left atrial pressure - right atrial pressure] ≤ 10 mm Hg) was demonstrated over a systemic/vascular resistance ratio range of 2.0-20 and a flow range of 3-9 L/min. Performance of the most recent pump configuration was demonstrated in chronic studies, including three consecutive long-term experiments (30, 90, and 90 days). These experiments were performed at a constant postoperative mean speed with a ±15% speed modulation, demonstrating a totally self-regulating mode of operation, from 3 days after implant to explant, despite a weight gain of up to 40%. The mechanism of self-regulation functioned properly, continuously throughout the chronic in vivo experiments, demonstrating the performance goals.

(328) - Generating Pulsatility by Pump Speed Modulation with Continuous-Flow Total Artificial Heart in Awake Calves

(328) - Generating Pulsatility by Pump Speed Modulation with Continuous-Flow Total Artificial Heart in Awake Calves

Median Sternotomy or Right Thoracotomy Techniques for Total Artificial Heart Implantation in Calves.

The choice of optimal operative access technique for mechanical circulatory support device implantation ensures successful postoperative outcomes. In this study, we retrospectively evaluated the median sternotomy and lateral thoracotomy incisions for placement of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) in a bovine model. The CFTAH was implanted in 17 calves (Jersey calves; weight range, 77.0-93.9 kg) through a median sternotomy (n = 9) or right thoracotomy (n = 8) for elective chronic implantation periods of 14, 30, or 90 days. Similar preoperative preparation, surgical techniques, and postoperative care were employed. Implantation of the CFTAH was successfully performed in all cases. Both methods provided excellent surgical field visualization. After device connection, however, the median sternotomy approach provided better visualization of the anastomoses and surgical lines for hemostasis confirmation and repair due to easier device displacement, which is severely limited following right thoracotomy. All four animals sacrificed after completion of the planned durations (up to 90 days) were operated through full median sternotomy. Our data demonstrate that both approaches provide excellent initial field visualization. Full median sternotomy provides larger viewing angles at the anastomotic suture line after device connection to inflow and outflow ports.

Sensorless Suction Recognition in the Self-Regulating Cleveland Clinic Continuous-Flow Total Artificial Heart.

The Cleveland Clinic continuous-flow total artificial heart passively regulates itself in regard to the relative performance of systemic and pulmonary pumps. The system incorporates real-time monitoring to detect any indication of incipient left or right suction as input for automatic controller response. To recognize suction, the external controller compares the waveforms of modulating speed input and power feedback. Deviations in periodic waveforms indicate sudden changes to flow impedance, which are characteristic of suction events as the pump speed is modulating. Incipient suction is indicated within 3 seconds of being detected in the power wave form, allowing timely controller response before mean flow is affected. This article describes the results obtained from subjecting the system to severe hemodynamic manipulation during an acute study in a calf.

Double-wire sternal closure technique in bovine animal models for total artificial heart implant.

In vivo preclinical testing of mechanical circulatory devices requires large animal models that provide reliable physiological and hemodynamic conditions by which to test the device and investigate design and development strategies. Large bovine species are commonly used for mechanical circulatory support device research. The animals used for chronic in vivo support require high-quality care and excellent surgical techniques as well as advanced methods of postoperative care. These techniques are constantly being updated and new methods are emerging.We report results of our double steel-wire closure technique in large bovine models used for Cleveland Clinic's continuous-flow total artificial heart development program. This is the first report of double-wire sternal fixation used in large bovine models.

Human Fitting Studies of Cleveland Clinic Continuous-Flow Total Artificial Heart.

Implantation of mechanical circulatory support devices is challenging, especially in patients with a small chest cavity. We evaluated how well the Cleveland Clinic continuous-flow total artificial heart (CFTAH) fit the anatomy of patients about to receive a heart transplant. A mock pump model of the CFTAH was rapid-prototyped using biocompatible materials. The model was brought to the operative table, and the direction, length, and angulation of the inflow/outflow ports and outflow conduits were evaluated after the recipient's ventricles had been resected. Thoracic cavity measurements were based on preoperative computed tomographic data. The CFTAH fit well in all five patients (height, 170 ± 9 cm; weight, 75 ± 24 kg). Body surface area was 1.9 ± 0.3 m (range, 1.6-2.1 m). The required inflow and outflow port orientation of both the left and right housings appeared consistent with the current version of the CFTAH implanted in calves. The left outflow conduit remained straight, but the right outflow direction necessitated a 73 ± 22 degree angulation to prevent potential kinking when crossing over the connected left outflow. These data support the fact that our design achieves the proper anatomical relationship of the CFTAH to a patient's native vessels.

Anatomy of the bovine ascending aorta and brachiocephalic artery found unfavorable for total artificial heart implant.

The biocompatibility assessment of the Cleveland Clinic continuous-flow total artificial heart is an important part of the device developmental program. Surgical and postoperative management are key factors in achieving optimal outcomes. However, the presence of vascular anatomical abnormalities in experimental animal models is often unpredictable and may worsen the expected outcomes. We report a technical impediment encountered during total artificial heart implantation complicated by unfavorable bovine anatomy of the ascending aorta and brachiocephalic arterial trunk.