Analysis of the arterial blood pressure waveform during left ventricular nonpulsatile assistance in animal models

When the rotary blood pump is used as a left ventricular assist device (LVAD), the arterial blood pressure waveform changes with the LVAD condition. Based on evidence from an in vitro study, the change of the arterial blood pressure waveform during left ventricular assistance was evaluated using animal models. After the left pleural cavity was opened through the fifth intercostal space under general anesthesia, a rotary blood pump was implanted as an LVAD into 6 healthy calves. The direct left carotid arterial blood pressure waveform was measured and recorded by an oscilloscope. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). Similar to the in vitro study, the PI and PPI decreased exponentially with the increase of the LVAD assist ratio. By using this analysis methodology, a physiologically effective ventricular assistance might be achieved.     

Estimation of the Native Cardiac Output from a Rotary Blood Pump Flow: In Vitro Study

Abstract The rotary blood pump will be an implantable left ventricular assist device (LVAD) in the near future. However, the best control method and the interrelationship between the rotary blood pump and native heart functions are unclear. An estimation was made of the native heart cardiac output from the change of an LVAD's outflow waveform. The mock circulation loop was composed of an aortic compliance chamber, left arterial chamber, total artificial heart as a native heart, and a rotary blood pump that was placed as an LVAD with left ventricular drainage. The fast Fourier transform (FFT) technique was utilized to analyze the LVAD's outflow waveform and calculate the pulse power index (PPI) to examine a relation between the PPI and total artificial heart (TAH) output. The PPI increased with the increase of the TAH output; there was a positive correlation, and there was an inverse correlation between the PPI and the assist ratio. From this viewpoint, an estimation of the pulsatility change of the LVAD's outflow wave may indicate the native cardiac output.     

In Vitro Hydrodynamic Analysis of Pin and Cone Bearing Designs of the Jarvik 2000 Adult Ventricular Assist Device

The Jarvik 2000 adult ventricular assist device (VAD) is a second‐generation blood pump with mechanical contact bearings. The original configuration of the pump employed a pin bearing and a more recent configuration uses a cone bearing. We compare the hydrodynamic performance of the two designs under steady‐state and pulsatile flow conditions in vitro. Furthermore, we employ the Intermittent Low Speed (ILS) Flowmaker Controller to demonstrate the effect on pulsatility index (PI) performance of both device configurations. We use an open‐loop flow system in both steady‐state and pulsatile arrangements, complete with pressure transducers and flow probes. Working fluid was a 3.6 cP blood‐analog, glycerin‐water solution. Steady‐state flow tests were carried out to determine pressure‐flow (H‐Q) performance curves. Pulsatile tests under normotensive, hypertensive, and hypotensive conditions were executed with controller speed 3 (10 710 ± 250 rpm) at 100 beats per minute. Steady‐state tests show greater capacity for pressure and flow with the cone bearing, compared with pin bearing, with best efficiency point (BEP) 68% greater for cone bearing. Pulsatile tests show the cone bearing design to yield a 20% increase in Q_avg, a 17% decrease in pulsatility index (PI_Q), and a qualitative increase in pressure responsivity. The ILS mode (for both bearing designs) decreases Q_avg by 68% and likewise increases PI_Q by 360% and pulsatility ratio (R_pul) by 200%. The ILS controller regularly reduces the flow, increasing pulsatility index during device operation. The Jarvik 2000 continuous‐flow VAD can sustain pulsatile flow under pulsating pressure conditions. The new cone bearing design yields increased flow rates over the earlier pin bearing design.     

Physiological control of a rotary blood pump with selectable therapeutic options: control of pulsatility gradient

A control strategy for rotary blood pumps meeting different user-selectable control objectives is proposed: maximum support with the highest feasible flow rate versus medium support with maximum ventricular washout and controlled opening of the aortic valve (AoV). A pulsatility index (PI) is calculated from the pressure difference, which is deduced from the axial thrust measured by the magnetic bearing of the pump. The gradient of PI with respect to pump speed (GPI) is estimated via online system identification. The outer loop of a cascaded controller regulates GPI to a reference value satisfying the selected control objective. The inner loop controls the PI to a reference value set by the outer loop. Adverse pumping states such as suction and regurgitation can be detected on the basis of the GPI estimates and corrected by the controller. A lumped-parameter computer model of the assisted circulation was used to simulate variations of ventricular contractility, pulmonary venous pressure, and aortic pressure. The performance of the outer control loop was demonstrated by transitions between the two control modes. Fast reaction of the inner loop was tested by stepwise reduction of venous return. For maximum support, a low PI was maintained without inducing ventricular collapse. For maximum washout, the pump worked at a high PI in the transition region between the opening and the permanently closed AoV. The cascaded control of GPI and PI is able to meet different control objectives and is worth testing in vitro and in vivo.     

HeartMate left ventricular assist devices: a multigeneration of implanted blood pumps

The HeartMate family of implanted left ventricular assist devices (LVADs) developed by Thermo Cardiosystems, Inc. (TCI) span a time frame that goes back to the beginning of clinical use of mechanical circulatory support and will stretch well into the foreseeable future. Associated blood pump technology employed in the HeartMates range from an original pusher plate concept to the most advanced rotary pump devices. Starting initially with a pneumatic actuated pusher plate pump, clinical use of the HeartMate I began in 1986. In 1990, electric motor-actuated versions of the HeartMate I began to be used clinically. Presently, the HeartMate I has been implanted in some 2,300 patients worldwide, and this LVAD is a standard by which all others are currently measured. Following the HeartMate I is TCI's next-generation, the HeartMate II, a rotary-pump-based LVAD that uses an axial flow blood pump having blood immersed mechanical bearings. Clinical trials of the HeartMate II were initiated in 2000. The HeartMate III, representing TCI's next-generation LVAD, is structured around a centrifugal blood pump that uses a magnetically levitated rotating assembly. Compared to the HeartMate II, the HeartMate III has the potential for higher overall efficiency. The pump's operating life is not dependent on bearing wear. Given the significantly advanced LVAD technology represented by HeartMates II and III, coupled with the experience of HeartMate I, TCI is well-poised to keep its LVAD products as industry standards in the future.     

Assessment of right pump outflow banding and speed changes on pulmonary hemodynamics during biventricular support with two rotary left ventricular assist devices

The absence of an effective, easily implantable right ventricular assist device (RVAD) significantly diminishes long‐term treatment options for patients with biventricular heart failure. The implantation of a second rotary left ventricular assist device (LVAD) for right heart support is therefore being considered; however, this approach exhibits technical challenges when adapting current devices to produce the lower pressures required of the pulmonary circulation. Hemodynamic adaptation may be achieved by either reducing the rotational speed of the right pump impeller or reducing the diameter of the right outflow cannula by the placement of a restricting band; however, the optimal value and influence of changes to each parameter are not well understood. Hemodynamics were therefore investigated using different banding diameters of the right outflow cannula (3–6.5 mm) and pump speeds (500–4500 rpm), using two identical rotary blood pumps coupled to a pulsatile mock circulation loop. Reducing the speed of the right pump from 4900 rpm (for left ventricle support) to 3500 rpm, or banding the Ø10 mm (area 78.5 mm²) right outflow graft to Ø5.4 mm (22.9 mm²) produced suitable hemodynamics. Pulmonary pressures were most sensitive to banding diameters, especially when RVAD flow exceeded LVAD flow. This occurred between Ø5.3 and Ø6.5 mm (22.05–38.5 mm²) and speeds between 3200 and 4400 rpm, with the flow imbalance potentially leading to pulmonary congestion. Total flow was not affected by banding diameters and speeds below this range, and only increased slightly at higher values. Both right outflow banding or right pump speed reduction were found to be effective techniques to allow a rotary LVAD to be used directly for right heart support. However, the observed sensitivity to diameter and speed indicate that challenges may be presented when setting appropriate values for each patient, and control over these parameters is desirable.     

The Heartmate III: design and in vivo studies of a maglev centrifugal left ventricular assist device

A compact implantable centrifugal left ventricular assist device (LVAD) (HeartMate III) featuring a magnetically levitated impeller is under development. The goal of our ongoing work is to demonstrate feasibility, low hemolysis, and low thrombogenicity of the titanium pump in chronic bovine in vivo studies. The LVAD is based on so-called bearingless motor technology and combines pump rotor, drive, and magnetic bearing functions in a single unit. The impeller is rotated (theta z) and levitated with both active (X, Y) and passive (Z, theta x, theta y) suspension. Six prototype systems have been built featuring an implantable titanium pump (69 mm diameter, 30 mm height) with textured blood contacting surfaces and extracorporeal electronics. The pumps were implanted in 9 calves (< or = 100 kg at implant) that were anticoagulated with Coumadin (2.5 < or = INR < or = 4.0) throughout the studies. Six studies were electively terminated (at 27-61 days), 1 study was terminated after the development of severe pneumonia and lung atelectasis (at 27 days) another study was terminated after cardiac arrest (at 2 days) while a final study is ongoing (at approximately 100 days). Mean pump flows ranged from 2 to 7 L/min, except for brief periods of exercise at 6 to 9 L/min. Plasma free hemoglobin ranged from 4 to 10 mg/dl. All measured biochemical indicators of end organ function remained within normal range. The pumps have met performance requirements in all 9 implants with acceptable hemolysis and no mechanical failures.     

European experience of DuraHeart™ magnetically levitated centrifugal left ventricular assist system

Objective: The DuraHeart (Terumo Heart, Inc., Ann Arbor, Michigan, USA) is the world's first approved magnetically levitated centrifugal left ventricular assist system designed for long-term circulatory support. We report the clinical outcomes of 68 patients implanted with the DuraHeart as a bridge to cardiac transplantation in Europe. Methods: Sixty-eight patients with advanced heart failure (six females), who were eligible for cardiac transplantation were implanted with the DuraHeart between January 2004 and July 2008. Median age was 58 (range: 29–74) years with 31% over 65 years. Thirty-three of these patients received the device as a part of the European multi-center clinical trial. Survival analyses were conducted for 68 patients and other safety and performance data were analyzed based on 33 trial patients. Results: Mean support duration was 242 ± 243 days (range: 19–1148, median: 161) with a cumulative duration of 45 years. Thirty-five patients (51%) remain ongoing, 18 transplanted, 1 explanted, and 14 died during support with a median time to death of 62 days. The Kaplan–Meier survival rate during support was 81% at 6 months and 77% at 1 year. Of the 13 patients (21%) supported for >1 year, 4 supported for >2 years, 1 supported >3 years, 2 transplanted, 2 died, and 9 ongoing with a mean duration of 744 ± 216 days (range: 537–1148, median: 651). Major adverse events included driveline/pocket infection, stroke, bleeding, and right heart failure. There was no incidence of pump mechanical failure, pump thrombosis, or hemolysis. Conclusions: The DuraHeart was able to provide safe and reliable long-term circulatory support with an improved survival and an acceptable adverse event rate in advanced heart failure patients who were eligible for transplantation.     

Balloon-pump-induced pulsatility improves coronary and carotid flows in an experimental model of BioMedicus left ventricular assistance

The aim of this study is to evaluate the benefit of the simultaneous use of a BioMedicus left ventricular assistance device (Medtronic, Minneapolis, MN, U.S.A.) and an intra-aortic balloon pump on regional blood flows, pressure, and pulsatility. Twelve pigs are studied. A BioMedicus pump was placed between the left atrium and the ascending aorta and an intra-aortic balloon pump was inserted through the left femoral artery. Blood flow and pressure were measured in the carotid, femoral, and coronary arteries and in the thoracic aorta below the intra-aortic balloon in the basal experimental condition with a full-flow BioMedicus pump and with a full-flow BioMedicus pump + intra-aortic balloon. The BioMedicus pump eliminates pulsatility in all sites and significantly decreases coronary and carotid blood flow. The adjunction of an intra-aortic balloon restores pulsatility to values comparable to those recorded in basal conditions. Coronary and carotid flows even increase to values higher than in the basal conditions. The simultaneous use of an intra-aortic balloon combined with the BioMedicus pump provides a pulsatile flow and increases coronary and carotid blood flows in pigs. An intra-aortic balloon can easily be combined with a BioMedicus pump whenever possible and may improve myocardial recovery in patients with postcardiotomy ventricular failure.     

Performance characterization of a rotary centrifugal left ventricular assist device with magnetic suspension

Abstract:  The MiTiHeart (MiTiHeart Corporation, Gaithersburg, MD, USA) left ventricular assist device (LVAD), a third-generation blood pump, is being developed for destination therapy for adult heart failure patients of small to medium frame that are not being served by present pulsatile devices. The pump design is based on a novel, patented, hybrid passive/active magnetic bearing system with backup hydrodynamic thrust bearing and exhibits low power loss, low vibration, and low hemolysis. Performance of the titanium alloy prototype was evaluated in a series of in vitro tests with blood analogue to map out the performance envelop of the pump. The LVAD prototype was implanted in a calf animal model, and the in vivo pump performance was evaluated. The animal's native heart imparted a strong pulsatility to the flow rate. These tests confirmed the efficacy of the MiTiHeart LVAD design and confirmed that the pulsatility does not adversely affect the pump performance.     

The Heartmate II: design and development of a fully sealed axial flow left ventricular assist system

Our group is developing the control and power transmission components required to implement a permanent and fully sealed left ventricular assist system (LVAS). Starting with the percutaneously powered HeartMate II blood pump, our development efforts are focused in the following areas: a complete redesign of the transcutaneous energy transmission system (TETS) to include a rectification network and autonomous voltage regulation within the secondary coil, a hermetically sealed electronics package containing a miniaturized implementation of the existing redundant drive and control electronics with several power-input options, an implanted rechargeable lithium ion battery pack capable of providing up to 1 h of untethered operation, implantable electrical connectors that allow components to be connected after placement in the body or to be replaced if needed, and a radio telemetry subsystem to transmit diagnostic information and to permit remote adjustment of selected parameters.     

Left ventricular mechanical support with the Impella Recover left direct microaxial blood pump: a single-center experience

The Impella Recover left direct (LD) is a new intravascular microaxial blood pump, intended as a short-term mechanical support especially in case of acutely reduced left ventricular function. From September 2002 to October 2004, Impella was used to support 12 patients: six patients were supported as bridge-to-heart transplant (HTx); three patients were treated for fulminant acute myocarditis, and three patients for postcardiotomy low-output syndrome. Mean support time was 8.8 +/- 2.3 days. Overall mortality was 50%. Four patients were successfully HTxed; two patients supported as bridge-to-HTx died on left ventricular assist device. Two patients with myocarditis died of septic shock; two patients in the group of postcardiotomy died of multiorgan failure. The latter two patients were slowly weaned from the device, and at 3-months follow-up showed good improvement of the left ventricular function. Our initial experience with Impella Recover LD as mechanical support for patients in cardiogenic shock of various etiology is promising, yielding a good survival in a population of particularly compromised patients.     

Incorporation of electronics within a compact,fully implanted left ventricular assist device

The promise of expanded indications for left ventricular assist devices in the future for very long-term applications (10+ years) prompts sealed (i.e. fully implanted) systems and less-obtrusive and more reliable implanted components than their external counterparts in percutaneous configurations. Furthermore, sealed systems increase the fraction of total power losses dissipated intracorporeally, a disadvantage that must be carefully managed. We set out to incorporate the motor drive and levitation control electronics within the HeartMate III blood pump without substantially increasing the pump's size. Electronics based on a rigid-flex satellite printed circuit board (PCB) arrangement that could be folded into a very compact, dense package were designed, fabricated, and tested. The pump's lower housing was redesigned to accommodate these PCBs without increasing any dimension of the pump except the height, and that by only 5 mm. The interconnect cable was reduced from 22 wires to 10 (two fully redundant sets of 5). An ongoing test of the assembled pump in vitro has demonstrated no problems in 5 months. In addition, a 20-day in vivo test showed only 1 degrees C temperature rises, equivalent to pumps without incorporated electronics at similar operating conditions.     

Evaluation of the optimal driving mode during left ventricular assist with pulsatile catheter pump in calves

The pulsatile catheter (PUCA) pump, a left ventricular assist device, was tested during acute experiments in calves using asynchronous and ECG-synchronous assist modes. The aim of the study is to compare ECG-synchronous and asynchronous assist and to find the optimal driving mode for the PUCA pump with respect to left ventricular myocardial oxygen consumption (LV MVO2), pump flow, and coronary flow. LV MVO2 decreased significantly during the asynchronous (from 7.77 to 6.46 ml/min/100 g) as well as during the ECG-synchronous mode (from 8.88 to 7.84 ml/min/100 g). The pump flow was highest during the ECG-synchronous assist (2.94 L/min), followed by the asynchronous assist (2.79 L/min). The peak coronary flow depended strongly on pump ejection timing and showed the best flow patterns during the ECG-synchronous assist. We concluded that for PUCA pump support both asynchronous and ECG-synchronous assists significantly reduce LV MVO2 and that the pump flow generated is enough to maintain the systemic circulation. However, we find the ECG-synchronous mode preferable because this mode optimizes coronary flow patterns at the same time.     

Evaluation of cardiac function during left ventricular assist by a centrifugal blood pump

In this study, the effects on varying cardiac function during a left ventricular (LV) bypass from the apex to the descending aorta using a centrifugal blood pump were evaluated by analyzing the left ventricular pressure and the motor current of the centrifugal pump in a mock circulatory loop. Failing heart models (preload 15 mm Hg, afterload 40 mm Hg) and normal heart models (preload 5 mm Hg, afterload 100 mm Hg) were simulated by adjusting the contractility of the latex rubber left ventricle. In Study 1, the bypass flow rate, left ventricular pressure, aortic pressure, and motor current levels were measured in each model as the centrifugal pump rpm were increased from 1,000 to 1,500 to 2,000. In Study 2, the pump rpm were fixed at 1,300, 1,500, and 1,700, and at each rpm, the left ventricular peak pressure was increased from 40 to 140 mm Hg by steps of 20 mm Hg. The same measurements as in Study 1 were performed. In Study 1, the bypass flow rate and mean aortic pressure both increased with the increase in pump rpm while the mean left ventricular pressure decreased. In Study 2, a fairly good correlation between the left ventricular pressure and the motor current of the centrifugal pump was obtained. These results suggest that cardiac function as indicated by left ventricular pressure may be estimated from a motor current analysis of the centrifugal blood pump during left heart bypass.     

Evaluation of left ventricular relaxation in rotary blood pump recipients using the pump flow waveform: a simulation study

In heart failure, diastolic dysfunction is responsible for about 50% of the cases, with higher prevalence in women and elderly persons and contributing similarly to mortality as systolic dysfunction. Whereas the cardiac systolic diagnostics in ventricular assist device patients from pump parameters have been investigated by several groups, the diastolic behavior has been barely discussed. This study focuses on the determination of ventricular relaxation during early diastole in rotary blood pump (RBP) recipients. In conventional cardiology, relaxation is usually evaluated by the minimum rate and the time constant of left ventricular pressure decrease, dP/dt(min) and τ(P) . Two new analogous indices derived from the pump flow waveform were investigated in this study: the minimum rate and the time constant of pump flow decrease, dQ/dt(min) and τ(Q) . The correspondence between the indices was investigated in a numerical simulation of the assisted circulation for different ventricular relaxation states (τ(P) ranging from 24 to 68 ms) and two RBP models characterized by linear and nonlinear pressure-flow characteristics. dQ/dt(min) and τ(Q) always correlated with the dP/dt(min) and τ(P) , respectively (r>0.97). These relationships were influenced by the nonlinear pump characteristics during partial support and by the pump speed during full support. To minimize these influences, simulation results suggest the evaluation of dQ/dt(min) and τ(Q) at a pump speed that corresponds to the borderline between partial and full support. In conclusion, at least in simulation, relaxation can be derived from pump data. This noninvasively accessible information could contribute to a continuous estimation of the remaining cardiac function and its eventual recovery.     

Fully autonomous preload-sensitive control of implantable rotary blood pumps

A pulsatility-based control algorithm with a self-adapting pulsatility reference value is proposed for an implantable rotary blood pump and is to be tested in computer simulations. The only input signal is the pressure difference across the pump, which is deduced from measurements of the pump's magnetic bearing. A pulsatility index (PI) is calculated as the mean absolute deviation from the mean pressure difference. As a second characteristic, the gradient of the PI with respect to the pump speed is derived. This pulsatility gradient (GPI) is used as the controlled variable to adjust the operating point of the pump when physiological variables such as the systemic arterial pressure, left ventricular contractility, or heart rate change. Depending on the selected mode of operation, the controller is either a linear controller or an extremum-seeking controller. A supervisory mechanism monitors the state of the system and projects the system into the region of convergence when necessary. The controller of the GPI continuously adjusts the reference value for PI. An underlying robust linear controller regulates the PI to the reference value in order to take into account changes in pulmonary venous return. As a means of reacting to sudden changes in the venous return, a suction detection mechanism was included. The control system is robustly stable within a wide range of physiological variables. All the clinician needs to do is to select between the two operating modes. No other adjustments are required. The algorithm showed promising results which encourage further testing in vitro and in vivo.     

Chronic evaluation of the Cleveland Clinic CorAide left ventricular assist system in calves

The Cleveland Clinic CorAide left ventricular assist system is based on a third-generation, implantable, centrifugal pump in which a rotating assembly is suspended fully. To evaluate chronic in vivo system performance and biocompatibility, the CorAide blood pump was implanted in 18 calves for either 1 month or 3 months. Hemodynamics were stable in all calves with a mean pump flow of 5.9 +/- 1.2 L/min and a mean systemic arterial pressure of 98 +/- 5 mm Hg. There were no incidences of bleeding, organ dysfunction, or mechanical failure in any of the 18 calves. Hemolysis occurred in only 1 calf due to outflow graft stenosis. Thrombus inside the pump, seen in 4 of the first 6 cases, was totally eliminated by a final redesign in the remaining cases, including the last 6 implants conducted without anticoagulation therapy. The CorAide blood pump demonstrated good biocompatibility and reliable, effective system performance.     

Response of rotary blood pumps to changes in preload and afterload at a fixed speed setting are unphysiological when compared with the natural heart

Responses of four rotary blood pumps (Incor, Heartmate II, Heartware, and Duraheart) at a single speed setting to changes in preload and afterload were assessed using the human left ventricle as a benchmark for comparison. Data for the rotary pumps were derived from pressure flow relations reported in the literature while the natural heart was characterized by the Frank-Starling curve adjusted to fit outputs at different afterloads reported in the literature. Preload sensitivity (mean ± SD) for all pumps at all afterloads tested was 0.105 ± 0.092 L/min/mm Hg, while afterload sensitivity was 0.09 ± 0.034 L/min/mm Hg-values that were not significantly different (t-test, P = 0.56). By contrast, preload sensitivity of the natural heart was over twice as high (0.213 ± 0.03 L/min/mm Hg) and afterload sensitivity about one-third (0.03 ± 0.01 L/min/mm Hg) the values recorded for rotary pumps (t-test, P < 0.001). Maximum preload sensitivity and minimum afterload sensitivity allow the right and left ventricles to synchronize outputs without neural or humoral intervention. This theoretical study reinforces the need to provide preload sensitive control mechanisms of sufficient power to enable the pump and left ventricle in combination to adapt to changes in right ventricular output automatically.