Exercise Studies in Patients With Rotary Blood Pumps: Cause,Effects, and Implications for Starling‐Like Control of Changes in Pump Flow

This multicenter study examines in detail the spontaneous increase in pump flow at fixed speed that occurs in exercise. Eight patients implanted with the VentrAssist rotary blood pump were subjected to maximal and submaximal cycle ergometry studies, the latter being completed with patients supine and monitored with right heart catheter and echocardiography. Maximal exercise studies conducted in each patient at three different pump speeds on separate days established initially the magnitude and consistency of increases in pump flow that correlated well with changes in heart rate. However, there was considerable variation, coefficients of variation for mean heart rate and pump flow being 47.9 and 49.3%, respectively. Secondly, these studies indicated that increasing pump flows caused significant improvements in maximal exercise capacity. An increase of 2.1 L/min (35%) in maximum blood flow caused 12 W (16%) further increase in achievable work, 1.26 (9.3%) mL/kg/min in maximal oxygen uptake, and 2.3 (23%) mL/kg/min in anaerobic threshold. Mean increases in lactate were 0.85 mm (24%), but mean B‐type natiuretic peptide fell by 126 mm , (?78%). From submaximal supine exercise studies, multiple linear regression of pump flow on factors thought to underlie the spontaneous increase in pump flow indicated that it was associated with increases in heart rate (P = 0.039), pressure gradient across the left ventricle (P = 0.032), and right atrial pressure (P = 0.003). These changes have implications for the recently reported Starling‐like controller for pump flow based on pump pulsatility values, which emulates the Starling curve relating pump output to left ventricular preload. Unmodified, the controller would not permit the full benefits of this effect to be afforded to patients implanted with rotary blood pumps. A modification to the pump control algorithm is proposed to eliminate this problem     

In Vitro Evaluation of an Immediate Response Starling‐Like Controller for Dual Rotary Blood Pumps

Rotary ventricular assist devices (VADs) are used to provide mechanical circulatory support. However, their lack of preload sensitivity in constant speed control mode (CSC) may result in ventricular suction or venous congestion. This is particularly true of biventricular support, where the native flow‐balancing Starling response of both ventricles is diminished. It is possible to model the Starling response of the ventricles using cardiac output and venous return curves. With this model, we can create a Starling‐like physiological controller (SLC) for VADs which can automatically balance cardiac output in the presence of perturbations to the circulation. The comparison between CSC and SLC of dual HeartWare HVADs using a mock circulation loop to simulate biventricular heart failure has been reported. Four changes in cardiovascular state were simulated to test the controller, including a 700 reduction in circulating fluid volume, a total loss of left and right ventricular contractility, reduction in systemic vascular resistance ( ) from 1300 to 600 , and an elevation in pulmonary vascular resistance ( ) from 100 to 300 . SLC maintained the left and right ventricular volumes between 69–214 and 29–182 respectively, for all tests, preventing ventricular suction (ventricular volume = 0 ) and venous congestion (atrial pressures > 20 ). Cardiac output was maintained at sufficient levels by the SLC, with systemic and pulmonary flow rates maintained above 3.14 for all tests. With the CSC, left ventricular suction occurred during reductions in SVR, elevations in PVR, and reduction in circulating fluid simulations. These results demonstrate a need for a physiological control system and provide adequate in vitro validation of the immediate response of a SLC for biventricular support.     

In Vitro Evaluation of Aortic Insufficiency With a Rotary Left Ventricular Assist Device

Aortic insufficiency (AI) is usually repaired prior to rotary blood pump (RBP) implantation but can develop during support due, in part, to the sustained RBP‐induced high pressure gradient across the aortic valve. Repair of the aortic valve before or during RBP support predisposes these critically ill patients to even higher risks. This study used an in vitro mock circulation loop to identify the severity of AI and/or left heart failure (LHF) that might benefit from valve repair while investigating RBP operating strategies to reduce the hemodynamic influence of AI. Reproduction of AI with RBP‐supported LHF reduced device efficiency, particularly in the more severe cases of AI and LHF. The requirement for repair or closure of the aortic valve was demonstrated in all conditions other than those with only mild AI. When a sinusoidal RBP speed pulse was induced, small changes in systemic flow rate and regurgitant volume were observed with all degrees of AI. Variation of the pulse phase delay only resulted in minor changes to systemic flow rate, with a maximum difference of 0.17 L/min. Although the clinical implications of these small changes may be insignificant, changes in systemic flow rate and transvalvular pressure were shown when the sinusoidal RBP speed pulse was applied with no AI. In these cases, transvalvular pressure was reduced by up to 8% through sinusoidal copulsation of the RBP, which may prevent or delay the onset of AI. This in vitro study suggests that surgical intervention is required with moderate or worse AI and that RBP operating strategies should be further explored to delay the onset and reduce the harmful effects of AI.     

In Vivo Evaluation of Active and Passive Physiological Control Systems for Rotary Left and Right Ventricular Assist Devices

Preventing ventricular suction and venous congestion through balancing flow rates and circulatory volumes with dual rotary ventricular assist devices (VADs) configured for biventricular support is clinically challenging due to their low preload and high afterload sensitivities relative to the natural heart. This study presents the in vivo evaluation of several physiological control systems, which aim to prevent ventricular suction and venous congestion. The control systems included a sensor‐based, master/slave (MS) controller that altered left and right VAD speed based on pressure and flow; a sensor‐less compliant inflow cannula (IC), which altered inlet resistance and, therefore, pump flow based on preload; a sensor‐less compliant outflow cannula (OC) on the right VAD, which altered outlet resistance and thus pump flow based on afterload; and a combined controller, which incorporated the MS controller, compliant IC, and compliant OC. Each control system was evaluated in vivo under step increases in systemic (SVR ～1400–2400 dyne/s/cm⁵) and pulmonary (PVR ～200–1000 dyne/s/cm⁵) vascular resistances in four sheep supported by dual rotary VADs in a biventricular assist configuration. Constant speed support was also evaluated for comparison and resulted in suction events during all resistance increases and pulmonary congestion during SVR increases. The MS controller reduced suction events and prevented congestion through an initial sharp reduction in pump flow followed by a gradual return to baseline (5.0 L/min). The compliant IC prevented suction events; however, reduced pump flows and pulmonary congestion were noted during the SVR increase. The compliant OC maintained pump flow close to baseline (5.0 L/min) and prevented suction and congestion during PVR increases. The combined controller responded similarly to the MS controller to prevent suction and congestion events in all cases while providing a backup system in the event of single controller failure.     

Evaluation of Inflow Cannulation Site for Implantation of Right‐Sided Rotary Ventricular Assist Device

Right heart dysfunction is one of the most serious complications following implantation of a left ventricular assist device, often leading to the requirement for short‐ or long‐term right ventricular assist device (RVAD) support. The inflow cannulation site induces major hemodynamic changes and so there is a need to optimize the site used depending on the patient's condition. Therefore, this study evaluated and compared the hemodynamic influence of right atrial cannulation (RAC) and right ventricular cannulation (RVC) inflow sites. An in vitro variable heart failure mock circulation loop was used to compare RAC and RVC in mild and severe biventricular heart failure (BHF) conditions. In the severe BHF condition, higher ventricular ejection fraction (RAC: 13.6%, RVC: 32.7%) and thus improved heart chamber and RVAD washout were observed with RVC, which suggested this strategy might be preferable for long‐term support (i.e., bridge‐to‐transplant or destination therapy) to reduce the risk of thrombus formation. In the mild BHF condition, higher pulmonary valve flow (RAC: 3.33 L/min, RVC: 1.97 L/min) and lower right ventricular stroke work (RAC: 0.10 W, RVC: 0.13 W) and volumes were recorded with RAC. These results indicate an improved potential for myocardial recovery, thus RAC should be chosen in this condition. This in vitro study suggests that RVAD inflow cannulation site should be chosen on a patient‐specific basis with a view to the support strategy to promote myocardial recovery or reduce the risk of long‐term complications.     

Development of the Marseilles Pulsatile Rotary Blood Pump for Permanent Implantable Left Ventricular Assistance

Abstract: We have developed a low–speed, double–lobed hypocycloidal pump that furnishes a pulsatile flow without valves. The pump is coupled to a specially designed electric motor. The motor/pump unit is totally implantable and has been extensively tested in vitro and in vivo in animals. Because this pump is volumetric, it is necessary to control speed precisely to avoid overpumping. Our control system, which is based on analysis of the motor current wave form, can detect and prevent negative pressures before they occur. The physical properties and hemocompatibility of several construction materials have been studied to determine their suitability for clinical use. These materials include a graphite substrate, titanium nitrate surface coating, boric carbon, and amorphous diamond. The pumps currently being tested are made of titanium, but clinical versions will be made of composite materials selected from this preliminary study. In vivo testing of this pump confirmed its good hemodynamic performance, low hemolysis rate, and biocompatibility (i. e., low heat, noise, and vibration levels). Animal experiments were terminated after 15 days because of mechanical failure related to the accumulation of blood components on moving parts. A new pump in which the mechanism is completely sealed from the blood flow has been designed and will soon be tested. If this sealed design is effective, the pump should be ready for use as a permanent implantable ventricular assistance device.     

Physiological Control of Dual Rotary Pumps as a Biventricular Assist Device Using a Master/Slave Approach

Dual rotary left ventricular assist devices (LVADs) can provide biventricular mechanical support during heart failure. Coordination of left and right pump speeds is critical not only to avoid ventricular suction and to match cardiac output with demand, but also to ensure balanced systemic and pulmonary circulatory volumes. Physiological control systems for dual LVADs must meet these objectives across a variety of clinical scenarios by automatically adjusting left and right pump speeds to avoid catastrophic physiological consequences. In this study we evaluate a novel master/slave physiological control system for dual LVADs. The master controller is a Starling‐like controller, which sets flow rate as a function of end‐diastolic ventricular pressure (EDP). The slave controller then maintains a linear relationship between right and left EDPs. Both left/right and right/left master/slave combinations were evaluated by subjecting them to four clinical scenarios (rest, postural change, Valsalva maneuver, and exercise) simulated in a mock circulation loop. The controller's performance was compared to constant‐rotational‐speed control and two other dual LVAD control systems: dual constant inlet pressure and dual Frank–Starling control. The results showed that the master/slave physiological control system produced fewer suction events than constant‐speed control (6 vs. 62 over a 7‐min period). Left/right master/slave control had lower risk of pulmonary congestion than the other control systems, as indicated by lower maximum EDPs (15.1 vs. 25.2–28.4 mm Hg). During exercise, master/slave control increased total flow from 5.2 to 10.1 L/min, primarily due to an increase of left and right pump speed. Use of the left pump as the master resulted in fewer suction events and lower EDPs than when the right pump was master. Based on these results, master/slave control using the left pump as the master automatically adjusts pump speed to avoid suction and increases pump flow during exercise without causing pulmonary venous congestion.     

In Vivo Biocompatibility Evaluation of a New Resilient,Hard‐Carbon,Thin‐Film Coating for Ventricular Assist Devices

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard‐carbon, thin‐film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous‐flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF‐coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst‐case biocompatibility challenge. Postexplant evaluation of the blood‐contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.     

Theoretical Foundations of a Starling-Like Controller for Rotary Blood Pumps

A clinically intuitive physiologic controller is desired to improve the interaction between implantable rotary blood pumps and the cardiovascular system. This controller should restore the Starling mechanism of the heart, thus preventing overpumping and underpumping scenarios plaguing their implementation. A linear Starling‐like controller for pump flow which emulated the response of the natural left ventricle (LV) to changes in preload was then derived using pump flow pulsatility as the feedback variable. The controller could also adapt the control line gradient to accommodate longer‐term changes in cardiovascular parameters, most importantly LV contractility which caused flow pulsatility to move outside predefined limits. To justify the choice of flow pulsatility, four different pulsatility measures (pump flow, speed, current, and pump head pressure) were investigated as possible surrogates for LV stroke work. Simulations using a validated numerical model were used to examine the relationships between LV stroke work and these measures. All were approximately linear (r² (mean ± SD) = 0.989 ± 0.013, n = 30) between the limits of ventricular suction and opening of the aortic valve. After aortic valve opening, the four measures differed greatly in sensitivity to further increases in LV stroke work. Pump flow pulsatility showed more correspondence with changes in LV stroke work before and after opening of the aortic valve and was least affected by changes in the LV and right ventricular (RV) contractility, blood volume, peripheral vascular resistance, and heart rate. The system (flow pulsatility) response to primary changes in pump flow was then demonstrated to be appropriate for stable control of the circulation. As medical practitioners have an instinctive understanding of the Starling curve, which is central to the synchronization of LV and RV outputs, the intuitiveness of the proposed Starling‐like controller will promote acceptance and enable rational integration into patterns of hemodynamic management.     

Increasing the Transmitted Flow Pulse in a Rotary Left Ventricular Assist Device

Long‐term rotary left ventricular assist devices (LVADs) are increasingly employed to bridge patients with end‐stage heart failure to transplant or as a destination therapy. Significant recent device development has increased patient support times, shifting further development focus toward physiologically sensitive control of the pump operation. Sensorless control of these devices would benefit from increased observability of the ventricular volume/preload to the pump, in order to regulate flow based on preload, imitating the native Frank‐Starling flow control. Monitoring the transmitted flow pulse through the pump has been used as a surrogate for preload, although means of maximizing its transmission are not clear. However, it is known that a flat hydraulic performance curve of the rotary pump induces high changes in flow for a given change in pressure head. The aim of this study was to determine geometric pump parameters responsible for increasing this flow pulse transmission and to demonstrate this increase in vitro. The sensitivity of the performance gradient to blade angles, blade heights, blade clearance, and channel areas were studied. Resulting pressure head, flow, and hydraulic efficiency were analyzed with respect to textbook designed procedures. Then pumps with comparably “flat” and “steep” performance curves were used to simulate LVAD support in vitro over a range of pump flow rates to observe the transmitted flow pulsatility. It was found that an outlet blade angle of 90°, inlet blade angle between 25 and 45°, and large throat area generated a “flatter” performance curve. The transmitted flow pulsatility through a pump with a flat performance curve was 68% higher than that of a steep performance curve at a flow rate of 5 L/min. Substantial gains in the observability of LVAD preload/resident blood volume in the ventricle exist through the careful selection of specific pump geometries.     

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.     

Characterization of a Magnetic Bearing System and Fluid Properties for a Continuous Flow Ventricular Assist Device

This article presents the performance test results of the CFVAD3 continuous flow blood pump in an artificial human circulation system. The CFVAD3 utilizes magnetic bearings that support a thin pancake impeller, the shape of which allows for a very compact pump whose total axial length is less than 5 cm with a radial length of about 10 cm. This gives a total volume of about 275 cc. The impeller itself has 4 vanes with a designed operating point of 6 L/min at 100 mm Hg of differential pressure and 2,000 rpm. The advantages of magnetic bearings, such as large clearance spaces and no mechanical wear, are elaborated upon. Furthermore, bearing model parameters such as load capacity and current gains are described. These parameters in conjunction with the operating conditions during testing are then used to estimate the fluid forces, stiffness, and damping properties while pumping. Knowledge of these parameters is desirable because of their effects on pump behavior. In addition, a better plant model will allow more robust control algorithms to be devised that can boost pump performance and reliability.     

B‐Type Natriuretic Peptide Levels Predict Ventricular Arrhythmia Post Left Ventricular Assist Device Implantation

B‐type natriuretic peptide (BNP) levels have been shown to predict ventricular arrhythmia (VA) and sudden death in patients with heart failure. We sought to determine whether BNP levels before left ventricular assist device (LVAD) implantation can predict VA post LVAD implantation in advanced heart failure patients. We conducted a retrospective study consisting of patients who underwent LVAD implantation in our institution during the period of May 2009–March 2013. The study was limited to patients receiving a HeartMate II or HeartWare LVAD. Acute myocardial infarction patients were excluded. We compared between the patients who developed VA within 15 days post LVAD implantation to the patients without VA. A total of 85 patients underwent LVAD implantation during the study period. Eleven patients were excluded (five acute MI, four without BNP measurements, and two discharged earlier than 13 days post LVAD implantation). The incidence of VA was 31%, with 91% ventricular tachycardia (VT) and 9% ventricular fibrillation. BNP remained the single most powerful predictor of VA even after adjustment for other borderline significant factors in a multivariate logistic regression model (P < 0.05). BNP levels are a strong predictor of VA post LVAD implantation, surpassing previously described risk factors such as age and VT in the past.     

Remote Monitoring of Left Ventricular Assist Device Parameters After HeartAssist‐5 Implantation

Although several left ventricular assist devices (LVADs) have been used widely, remote monitoring of LVAD parameters has been available only recently. We present our remote monitoring experience with an axial‐flow LVAD (HeartAssist‐5, MicroMed Cardiovascular, Inc., Houston, TX, USA). Five consecutive patients who were implanted a HeartAssist‐5 LVAD because of end‐stage heart failure due to ischemic (n = 4) or idiopathic (n = 1) cardiomyopathy, and discharged from hospital between December 2011 and January 2013 were analyzed. The data (pump speed, pump flow, power consumption) obtained from clinical visits and remote monitoring were studied. During a median follow‐up of 253 (range: 80–394) days, fine tuning of LVADs was performed at clinical visits. All patients are doing well and are in New York Heart Association Class‐I/II. A total of 39 alarms were received from three patients. One patient was hospitalized for suspected thrombosis and was subjected to physical examinations as well as laboratory and echocardiographic evaluations; however, no evidence of thrombus washout or pump thrombus was found. The patient was treated conservatively. Remaining alarms were due to insufficient water intake and were resolved by increased water consumption at night and summer times, and fine tuning of pump speed. No alarms were received from the remaining two patients. We believe that remote monitoring is a useful technology for early detection and treatment of serious problems occurring out of hospital thereby improving patient care. Future developments may ease troubleshooting, provide more data from the patient and the pump, and eventually increase physician and patient satisfaction. Despite all potential clinical benefits, remote monitoring should be taken as a supplement to rather than a substitute for routine clinical visits for patient follow‐up.     

Simulation of Ventricular,Cavo‐Pulmonary,and Biventricular Ventricular Assist Devices in Failing Fontan

Considering the lack of donors, ventricular assist devices (VADs) could be an alternative to heart transplantation for failing Fontan patients, in spite of the lack of experience and the complex anatomy and physiopathology of these patients. Considering the high number of variables that play an important role such as type of Fontan failure, type of VAD connection, and setting (right VAD [RVAD], left VAD [LVAD], or biventricular VAD [BIVAD]), a numerical model could be useful to support clinical decisions. The aim of this article is to develop and test a lumped parameter model of the cardiovascular system simulating and comparing the VAD effects on failing Fontan. Hemodynamic and echocardiographic data of 10 Fontan patients were used to simulate the baseline patients’ condition using a dedicated lumped parameter model. Starting from the simulated baseline and for each patient, a systolic dysfunction, a diastolic dysfunction, and an increment of the pulmonary vascular resistance were simulated. Then, for each patient and for each pathology, the RVAD, LVAD, and BIVAD implantations were simulated. The model can reproduce patients’ baseline well. In the case of systolic dysfunction, the LVAD unloads the single ventricle and increases the cardiac output (CO) (35%) and the arterial systemic pressure (Pas) (25%). With RVAD, a decrement of inferior vena cava pressure (Pvci) (39%) was observed with 34% increment of CO, but an increment of the single ventricle external work (SVEW). With the BIVAD, an increment of Pas (29%) and CO (37%) was observed. In the case of diastolic dysfunction, the LVAD increases CO (42%) and the RVAD decreases the Pvci, while both increase the SVEW. In the case of pulmonary vascular resistance increment, the highest CO (50%) and Pas (28%) increment is obtained with an RVAD with the highest decrement of Pvci (53%) and an increment of the SVEW but with the lowest VAD power consumption. The use of numerical models could be helpful in this innovative field to evaluate the effect of VAD implantation on Fontan patients to support patient and VAD type selection personalizing the assistance.     

First Clinical Application of the DuraHeart Centrifugal Ventricular Assist Device for a Japanese Patient

The DuraHeart ventricular assist device (VAD) is a third-generation implantable centrifugal pump with a magnetically levitated impeller. Since February 2007, the device has been clinically applied with excellent results as a bridge to heart transplantation in Europe. As of this writing, however, the device has yet to be approved by the Ministry of Health, Labour and Welfare for clinical use in Japan. We herein report the first clinical application of this device for a Japanese patient. A 31-year-old man with dilated cardiomyopathy was transferred to the Heart and Diabetes Center NRW (HDZ-NRW) in Bad Oeynhausen, Germany, where he was to await heart transplantation. The transfer was safely completed under management with low-dose dopamine. His condition gradually deteriorated at HDZ-NRW, and the DuraHeart left ventricular assist device was implanted for the left ventricle at 7 weeks after admission. Shortly thereafter, however, on POD 7, a Thoratec VAD had to be inserted on the right side due to refractory right heart failure. The right ventricular assist device could be explanted after a 3-month assist, and the patient is now waiting for heart transplantation at home in Germany.