Cleveland Clinic Continuous-Flow Total Artificial Heart: Progress Report and Technology Update.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) is being developed at our institution and has demonstrated system reliability and optimal performance. Based on the results from recent chronic in vivo experiments, CFTAH has been revised, especially to improve biocompatibility. The purpose of this article is to report our progress in developing CFTAH. To improve biocompatibility, the right impeller, the pump housing, and the motor were reviewed for design revision. Updated design features were based on computational fluid dynamics analysis and observations from in vitro and in vivo studies. A new version of CFTAH was created, manufactured, and tested. All hemodynamic and pump-related parameters were observed and found to be within the intended ranges, and the new CFTAH yielded acceptable biocompatibility. Cleveland Clinic's continuous-flow total artificial heart has demonstrated reliable performance, and has shown satisfactory progress in its development.

Preservation of pulsatility with universal ventricular assist device: In vitro assessment for biventricular support.

BACKGROUND: The objective of this study was to assess the pulsatility preservation capability of the universal ventricular assist device (UVAD) when used as a biventricular assist device (BVAD). This evaluation was conducted through an in vitro experiment, utilizing a pulsatile biventricular circulatory mock loop. METHODS: Two UVAD pumps were tested in a dual setup (BVAD) in the circulatory model with the simulated conditions of left heart failure (HF), right HF, and moderate/severe biventricular HF (BHF). The total flow, aortic pulse pressure, the pulse augmentation factor (PAF), the energy-equivalent pressure (EEP), and the surplus hemodynamic energy (SHE) were observed at various pump speeds to evaluate the pulsatility. RESULTS: The aortic pulse pressure increased from the baseline (without pump) in all simulated hemodynamic conditions. The PAF ranged from 17%-35% in healthy, left HF, right HF, and mild BHF conditions, with the highest PAF of 90% being observed in the severe BHF condition. The EEP correlated with LVAD flow in all groups (R2 = 0.87-0.97) and increased from the baseline in all cases. The SHE peaked at approximately 5-6 L/min of LVAD support and was likely to decrease at higher LVAD pump flow. The largest decrease in SHE from the baseline, 53%, was observed in the mild BHF conditions with the highest LVAD and RVAD support. CONCLUSIONS: The UVAD successfully demonstrated the ability to preserve pulsatility in vitro, and to optimize the cardiac output, as an isolated circulatory support device option (RVAD or LVAD) and when used for BVAD support.

Human fitting of pediatric and infant continuous-flow total artificial heart: visual and virtual assessment.

Background: This study aimed to determine the fit of two small-sized (pediatric and infant) continuous-flow total artificial heart pumps (CFTAHs) in congenital heart surgery patients. Methods: This study was approved by Cleveland Clinic Institutional Review Board. Pediatric cardiac surgery patients (n = 40) were evaluated for anatomical and virtual device fitting (3D-printed models of pediatric [P-CFTAH] and infant [I-CFTAH] models). The virtual sub-study consisted of analysis of preoperative thoracic radiographs and computed tomography (n = 3; 4.2, 5.3, and 10.2 kg) imaging data. Results: P-CFTAH pump fit in 21 out of 40 patients (fit group, 52.5%) but did not fit in 19 patients (non-fit group, 47.5%). I-CFTAH pump fit all of the 33 patients evaluated. There were critical differences due to dimensional variation (p < 0.0001) for the P-CFTAH, such as body weight (BW), height (Ht), and body surface area (BSA). The cutoff values were: BW: 5.71 kg, Ht: 59.0 cm, BSA: 0.31 m2. These cutoff values were additionally confirmed to be optimal by CT imaging. Conclusions: This study demonstrated the range of proper fit for the P-CFTAH and I-CFTAH in congenital heart disease patients. These data suggest the feasibility of both devices for fit in the small-patient population.

Artificial Deep Neural Network for Sensorless Pump Flow and Hemodynamics Estimation During Continuous-Flow Mechanical Circulatory Support.

The objective of this study was to compare the estimates of pump flow and systemic vascular resistance (SVR) derived from a mathematical regression model to those from an artificial deep neural network (ADNN). Hemodynamic and pump-related data were generated using both the Cleveland Clinic continuous-flow total artificial heart (CFTAH) and pediatric CFTAH on a mock circulatory loop. An ADNN was trained with generated data, and a mathematical regression model was also generated using the same data. Finally, the absolute error for the actual measured data and each set of estimated data were compared. A strong correlation was observed between the measured flow and the estimated flow using either method (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error was smaller in the ADNN estimation (mathematical, 0.3 L/min; ADNN 0.12 L/min; p < 0.01). Furthermore, strong correlation was observed between measured and estimated SVR (mathematical, R = 0.97, p < 0.01; ADNN, R = 0.99, p < 0.01). The absolute error for ADNN estimation was also smaller than that of the mathematical estimation (mathematical, 463 dynes·sec·cm -5 ; ADNN, 123 dynes·sec·cm -5 , p < 0.01). Therefore, in this study, ADNN estimation was more accurate than mathematical regression estimation. http://links.lww.com/ASAIO/A991.

Biventricular circulatory support using single-device and dual-device configurations: Initial pump characterization in simulated heart failure model.

Objective: Severe biventricular heart failure (BHF) can be remedied using a biventricular assist device (BVAD). Two devices are currently in development: a universal ventricular assist device (UVAD), which will be able to assist either the left, right, or both ventricles, and a continuous-flow total artificial heart (CFTAH), which replaces the entire heart. In this study, the in vitro hemodynamic performances of two UVADs are compared to a CFTAH acting as a BVAD. Methods: For this experiment, a biventricular mock circulatory loop utilizes two pneumatic pumps (Abiomed AB5000™, Danvers, MA, USA), in conjunction with a dual-output driver, to create heart failure (HF) conditions (left, LHF; right, RHF; biventricular, BHF). Systolic BHF for four different situations were replicated. In each situation, CFTAH and UVAD devices were installed and operated at two distinct speeds, and cannulations for ventricular and atrial connections were evaluated. Results: Both CFTAH and UVAD setups achieved our recommended hemodynamic criteria. The dual-UVAD arrangement yielded a better atrial balance to alleviate LHF and RHF. For moderate and severe BHF scenarios, CFTAH and dual UVADs both created excellent atrial pressure balance. Conversely, when CFTAH was atrial cannulated for LHF and RHF, the needed atrial pressure balance was not met. Conclusion: Comprehensive in vitro testing of two different BVAD setups exhibited self-regulation and exceptional pump performance for both (single- and dual-device) BHF support scenarios. For treating moderate and severe BHF, UVAD and CFTAH both functioned well with respect to atrial pressure regulation and cardiac output. Though, the dual-UVAD setup yielded a better atrial pressure balance in all BHF testing scenarios.

Left atrial assist device for heart failure with preserved ejection fraction: initial results with torque control mode in diastolic heart failure model.

A novel pump, the left atrial assist device (LAAD), is a device specifically for the treatment of heart failure with preserved ejection fraction (HFpEF). The LAAD is a mixed-flow pump that is implanted in the mitral position and delivers blood from the left atrium to the left ventricle. During the development process, we aimed to explore whether device activation in torque control (TC) mode would improve the function of the LAAD. The TC mode causes adjustment of the pump speed automatically during each cardiac cycle in order to maintain a specified torque. In this study, we tested four different TC settings (TC modes 0.9, 1.0, 1.25, and 1.5) using an in vitro mock circulatory loop. Mild, moderate, and severe diastolic heart failure (DHF) conditions, as well as normal heart condition, were simulated with the four TC modes. Also, we evaluated the LAAD in vivo with three calves. The LAAD was implanted at the mitral position with four TC settings (TC modes 0.9, 1.0, 1.1, 1.2). With LAAD support, the in vitro cardiac output and aortic pressure recovered to normal heart levels at TC 1.25 and 1.5 even under severe DHF conditions with little pump regurgitation. The TC mode tested in vivo with three calves, and it also showed favorable result without elevating the left ventricular end-diastolic pressure. These initial in vitro and in vivo results suggest that the TC mode could be potentially effective, and the LAAD could be a treatment option for HFpEF patients.

Characterization of left atrial assist device implantation: Early results of ex vivo anatomical assessment.

BACKGROUND: The left atrial assist device (LAAD) is a novel pump that was developed specifically for the treatment of heart failure with preserved ejection fraction. The device is surgically implanted in the mitral position. This study aimed to characterize the various device-fitting configurations in the mitral annular position. METHODS: Rapidly prototyped LAAD models (n = 5) were fabricated with five different driveline configurations: (A) annulus level/intra-cuff running; (B) supra-cuff/below coronary sinus (CS); (C) infra-cuff; (D) supra-annulus/supra-CS; (E) left ventricular free wall level. The 3D-printed models were implanted in extracted fresh porcine hearts (80-100 kg, adult, healthy porcine) and the proximity of anatomical structures between the driveline and CS and coronary artery (CA) were measured. RESULTS: All five device configurations were evaluated for fitting. For the purpose of preventing blood clot formation around the driveline, the mitral annulus (MA) as a driveline pass-way (configuration A) has been considered advantageous with the current device, in that the driveline exposure to blood has been avoided. The CS does not exist at exactly the same level as the MA, and there is less risk of injuring it than using the left atrial free wall. However, there is an inevitable risk of damaging the CA, so careful visual inspection before inserting the driveline is needed. CONCLUSIONS: Several options of driveline exteriorization were demonstrated, and the safety of each configuration was evaluated. Using the MA as a pathway for the driveline exit is considered to be a reasonable and safe method.

Mechanical circulatory support devices and treatment strategies for right heart failure.

The importance of right heart failure (RHF) treatment is magnified over the years due to the increased risk of mortality. Additionally, the multifactorial origin and pathophysiological mechanisms of RHF render this clinical condition and the choices for appropriate therapeutic target strategies remain to be complex. The recent change in the United Network for Organ Sharing (UNOS) allocation criteria of heart transplant may have impacted for the number of left ventricular assist devices (LVADs), but LVADs still have been widely used to treat advanced heart failure, and 4.1 to 7.4% of LVAD patients require a right ventricular assist device (RVAD). In addition, patients admitted with primary left ventricular failure often need right ventricular support. Thus, there is unmet need for temporary or long-term support RVAD implantation exists. In RHF treatment with mechanical circulatory support (MCS) devices, the timing of the intervention and prediction of duration of the support play a major role in successful treatment and outcomes. In this review, we attempt to describe the prevalence and pathophysiological mechanisms of RHF origin, and provide an overview of existing treatment options, strategy and device choices for MCS treatment for RHF.

Novel approaches for left atrial pressure relief: Device-based monitoring and management in heart failure.

The importance of the left atrium (LA) has been emphasized in recent years as the features of heart failure (HF), especially with regard to variability in patient and pathology phenotypes, continue to be uncovered. Of note, among the population with HF with preserved ejection fraction (HFpEF), pressure or size of the LA have become a target for advanced monitoring and a therapeutic approach. In the case of diastolic dysfunction or pulmonary hypertension, which are often observed in patients with HFpEF, a conventional approach with clinical symptoms and physical signs of decompensation turned out to have a poor correlation with LA pressure. Therefore, to optimize HF treatment for these populations, several devices that are applied directly to the LA have been developed. First, two LA pressure (LAP) sensors (Heart POD and V-LAP Device) were developed and may enable patient self-management remotely with LAP-guided and physician-directed style. Second, there are device-based approaches that aim to decompress the LA directly. These include: (1) interatrial shunt devices; (2) left ventricular assist devices with LA cannulation; and (3) the left atrial assist device. While these novel device-based therapies are not yet commercially available, there is expected to be a rise in the proposition and adoption of a wider range of choices for monitoring or treating LA using device-based options, based on LA dimensional reduction and optimization of the clinically significant pressure relief. Further development and evaluation are necessary to establish a more favorable management strategy for HF.

Evaluation of centrifugal blood pump performances for biventricular support in the virtual simulation model.

BACKGROUND: Despite the advances in the left ventricular assist device (LVAD), there are still situations that require a biventricular assist device (BVAD) system. The purpose of this study was to explore and compare the system performance interactions with the HeartMate3 (HM3) and HeartWare (HVAD) in a BVAD configuration using the virtual mock loop (VML) simulation tool. METHODS: The VML simulation tool is an in silico implementation of a lumped parameter model of the cardiovascular system with mechanical circulatory support. Patients with ejection fractions of 60%, 20%, and 15% were simulated in VML, and the HVAD and HM3 in a BVAD with ventricular cannulation were applied to simulated conditions. Pump speeds that restored baseline normal hemodynamics were determined. To determine the optimal speeds for BVAD, the left and right arterial pressures (LAP, RAP) were plotted. RESULTS: In the HVAD, LAP and RAP are balanced at 11 mm Hg with LVAD 3500 rpm, right ventricular assist device (RVAD) 2200 rpm; at 13 mm Hg with LVAD 3000 rpm, RVAD 1700 rpm; and at 14 mm Hg with LVAD 2500 rpm, RVAD 1300 rpm. For the HM3, at 8 mm Hg with LVAD 7000 rpm, RVAD 5000 rpm; at 9 mm Hg with LVAD 6000 rpm, RVAD 4300 rpm; and at 9.5 mm Hg with LVAD 5000 rpm, RVAD 3500 rpm. CONCLUSION: The RVAD/LVAD speed ratios required for atrial balance were approximately 0.6 for the HVAD and 0.7 for the HM3. However, the HVAD required RVAD speeds below its range of operation.

Pulsatility hemodynamics during speed modulation of continuous-flow total artificial heart in a chronic in vivo model.

BACKGROUND: The evaluation of pulsatile flow created by the new Cleveland Clinic continuous-flow total artificial heart (CFTAH100), which has a re-designed right impeller and motor, had not been tested in vivo. The purpose of this study was to evaluate the feasibility of pulsatility with the CFTAH100 during the application of pump speed modulation protocols in a chronic animal model. METHODS: A 30-day chronic animal experiment was conducted with a calf. Five pulsatile studies were performed on the alert animal. The mean pump speed was set at 2800 rpm, and modulated sinusoidally within a range of 0 to ± 35% of mean speed, in increments of 5% at 80 beats per minute (bpm). The pressures and pump flow were collected and a pulsatility index (PI) was calculated. RESULTS: The calf was supported with the CFTAH100 without any major complications. The maximum and minimum pump flows changed significantly from baseline in all conditions, while the mean pump flow did not change. All flow pulsatility (FP) readings in all conditions significantly increased from baseline, and the percent modulation (%S) and FP had a strong positive correlation (r = 0.99, p < 0.01). The PI also increased significantly in all conditions (maximum at %S of 35%, 2.2 ± 0.05, p < 0.01), and a positive correlation between %S and PI (r = 0.99, p < 0.01) was observed. CONCLUSION: The CFTAH100 showed the feasibility of creating pulsatile circulation with sinusoidal pump speed modulation.

Left Atrial Circulatory Assistance in Simulated Diastolic Heart Failure Model: First in Vitro and in Vivo.

BACKGROUND: We are developing a left atrial assist device (LAAD) that is implanted at the mitral position to treat diastolic heart failure (DHF) represented by heart failure with preserved ejection fraction. METHODS: The LAAD was tested at 3 pump speeds on a pulsatile mock loop with a pneumatic pump that simulated DHF conditions by adjusting the diastolic drive. The LAAD was implanted in 6 calves, and the hemodynamics were assessed. In 3 cases, DHF conditions were induced by using a balloon inserted into the left ventricle, and in 2 cases, mitral valve replacement was also performed after the second aortic cross-clamp. RESULTS: DHF conditions were successfully induced in the in vitro study. With LAAD support, cardiac output, aortic pressure and left atrial pressure recovered to normal values, whereas pulsatility was maintained for both in vivo and in vitro studies. Echocardiography showed no left ventricular outflow tract obstruction, and the LAAD was successfully replaced by a mechanical prosthetic valve. CONCLUSIONS: These initial in vitro and in vivo results support our hypothesis that use of the LAAD increases cardiac output and aortic pressure and decreases left atrial pressure, while maintaining arterial pulsatility.

Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass-An experimental pilot.

BACKGROUND: Non-pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. METHODS: Ocular surface microcirculation in small tissue volumes (~0.1 mm3 ) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. RESULTS: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. CONCLUSION: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets.

Large animal models of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by diastolic dysfunction and multiple comorbidities. The number of patients is continuously increasing, with no improvement in its unfavorable prognosis, and there is a strong need for novel treatments. New devices and drugs are difficult to assess at the translational preclinical step due to the lack of high-fidelity large animal models of HFpEF. In this review, we describe the summary of historical and evolving techniques for developing large animal models. The representative methods are pressure overload models, including (1) aortic banding, (2) aortic stent, (3) renal hypertension, and (4) mineralocorticoid-induced hypertension. Diet-induced metabolic syndromes are also used. A new technique with an inflatable balloon inside the left ventricle can be used during acute/chronic in vivo surgeries to simulate HFpEF-like hemodynamics for pump-based therapies. Canines and porcine are most widely used, but other non-rodent animals (sheep, non-human primates, felines, or calves) have been used. Feline models present the most well-simulated HFpEF pathology, but small size is a concern, and the information is still very limited. The rapid and reliable establishment of large animal models for HFpEF, and novel methodology based on the past experimental attempts with large animals, are needed.

Computational Fluid Dynamics Model of Continuous-Flow Total Artificial Heart: Right Pump Impeller Design Changes to Improve Biocompatibility.

Cleveland Clinic is developing a continuous-flow total artificial heart (CFTAH). This novel design operates without valves and is suspended both axially and radially through the balancing of the magnetic and hydrodynamic forces. A series of long-term animal studies with no anticoagulation demonstrated good biocompatibility, without any thromboemboli or infarctions in the organs. However, we observed varying degrees of thrombus attached to the right impeller blades following device explant. No thrombus was found attached to the left impeller blades. The goals for this study were: (1) to use computational fluid dynamics (CFD) to gain insight into the differences in the flow fields surrounding both impellers, and (2) to leverage that knowledge in identifying an improved next-generation right impeller design that could reduce the potential for thrombus formation. Transient CFD simulations of the CFTAH at a blood flow rate and impeller rotational speed mimicking in vivo conditions revealed significant blade tip-induced flow separation and clustered regions of low wall shear stress near the right impeller that were not present for the left impeller. Numerous right impeller design variations were modeled, including changes to the impeller cone angle, number of blades, blade pattern, blade shape, and inlet housing design. The preferred, next-generation right impeller design incorporated a steeper cone angle, a primary/splitter blade design similar to the left impeller, and an increased blade curvature to better align the incoming flow with the impeller blade tips. The next-generation impeller design reduced both the extent of low shear regions near the right impeller surface and flow separation from the blade leading edges, while maintaining the desired hydraulic performance of the original CFTAH design.

Total Artificial Heart Computational Fluid Dynamics: Modeling of Stator Bore Design Effects on Journal-Bearing Performance.

Cleveland Clinic's continuous-flow total artificial heart (CFTAH) is a double-ended centrifugal blood pump that has a single rotating assembly with an embedded magnet, which is axially and radially suspended by a balance of magnetic and hydrodynamic forces. The key to the radial suspension is a radial offset between the stator bearing bore and the magnet's steel laminations. This offset applies a radial magnetic force, which is balanced by a hydrodynamic force as the rotating assembly moves to a "force-balanced" radial position. The journal-bearing blood passage is a narrow flow path between the left and right impellers. The intent of this study was to determine the impact of the stator-bearing bore radius on the journal-bearing hydraulic performance while satisfying the geometric design constraints imposed by the pump and motor configuration. Electromagnetic forces on the journal bearing were calculated using the ANSYS EMAG program, Version 18 (ANSYS, Canonsburg, PA). ANSYS CFX Version 19.2 was then used to model the journal-bearing flow paths of the most recent design of the CFTAH. A transient, moving mesh approach was used to locate the steady state, force-balanced position of the rotating assembly. The blood was modeled as a non-Newtonian fluid. The computational fluid dynamics simulations showed that by increasing stator bore radius, rotor power, stator wall average shear stress, and blood residence time in journal-bearing decrease, while blood net flow rate through the bearing increases. The results were used to select a new bearing design that provides an improved performance compared with the baseline design. The performance of the new CFTAH-bearing design will be confirmed through upcoming in vitro and in vivo testing.