Flow visualization of a pediatric ventricular assist device during stroke volume reductions related to weaning

The aim of this study is to define the fluid mechanics of a pulsatile pneumatically driven pediatric ventricular assist device (PVAD), for the reduced flow rates encountered during device weaning and myocardial recovery, and relate the results to the potential for thromboembolic events. We place an acrylic model of the PVAD in a mock circulatory loop filled with a viscoelastic blood analog and operate at four stroke volumes (SVs), each with two different filling conditions, to mimic how the flow rate of the device may be reduced. Particle image velocimetry is used to acquire flow field data. We find that a SV reduction method provides better rotational flow and higher wall shear rates than a beat rate reduction method; that a quick filling condition with a compressed diastolic time is better than a slow filling condition; and, that a reduction in SV to 40% led to greatly reduced fluid movement and wall shear rates that could increase the thrombogenicity of the device. SV reduction is a viable option for flow reduction during weaning, however, it does lead to significant changes to the device flow field and future studies are needed to develop operational protocols for the PVAD during bridge-to-recovery.     

Simulation of systolic and diastolic left ventricular dysfunction in a mock circulation: the effect of arterial compliance

Arterial compliance (AC) is expected to play a major role on cardiac efficacy by acute or long-term mechanisms. The aim of this study was to investigate the purely mechanical effect of AC on left ventricular (LV) performance, for different conditions of LV dysfunction (systolic versus diastolic). A hydraulic, Windkessel model of systemic circulation was used. LV function and aortic flow were simulated using a left ventricular assist device (LVAD). Two cases of LV dysfunction were simulated: Case A, systolic and Case B, diastolic dysfunction. In Case A, AC increased from 1.14 to 2.85 ml mm Hg(-1) leading to an increase in LVAD stroke volume up to 6%, while no significant effect was observed in Case B. LVAD systolic work was decreased by 4% in systolic and by 11% in diastolic LVAD dysfunction. The purely mechanical effect of AC changes on LVAD function was different between systolic and diastolic dysfunction. It might be expected that even an acute reduction in arterial stiffness could enhance LV performance by different means in systolic compared to diastolic dysfunction.     

Simulation of systolic and diastolic left ventricular dysfunction in a mock circulation: the effect of arterial compliance

Arterial compliance (AC) is expected to play a major role on cardiac efficacy by acute or long-term mechanisms. The aim of this study was to investigate the purely mechanical effect of AC on left ventricular (LV) performance, for different conditions of LV dysfunction (systolic versus diastolic). A hydraulic, Windkessel model of systemic circulation was used. LV function and aortic flow were simulated using a left ventricular assist device (LVAD). Two cases of LV dysfunction were simulated: Case A, systolic and Case B, diastolic dysfunction. In Case A, AC increased from 1.14 to 2.85 ml mm Hg &#109 1 leading to an increase in LVAD stroke volume up to 6%, while no significant effect was observed in Case B. LVAD systolic work was decreased by 4% in systolic and by 11% in diastolic LVAD dysfunction. The purely mechanical effect of AC changes on LVAD function was different between systolic and diastolic dysfunction. It might be expected that even an acute reduction in arterial stiffness could enhance LV performance by different means in systolic compared to diastolic dysfunction.     

The 12 cc Penn State pulsatile pediatric ventricular assist device: flow field observations at a reduced beat rate with application to weaning

Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because the number of available organs is insufficient, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. During myocardial recovery, the system must be weaned from the patient to prepare for explant; for pulsatile devices, this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes in flow need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time, and wall shear rates above 500 s, can help prevent thrombus deposition. Particle image velocimetry was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric VAD (PVAD) at a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed an earlier loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.     

Effects of mechanical valve orifice direction on the flow pattern in a ventricular assist device

We have been developing a pneumatic ventricular assist device (PVAD) system consisting of a diaphragm-type blood pump. The objective of the present study was to evaluate the flow pattern inside the PVAD, which may greatly affect thrombus formation, with respect to the inflow valve-mount orientation. To analyze the change of flow behavior caused by the orifice direction (OD) of the valve, the flow pattern in this pump was visualized. Particle image velocimetry was used as a measurement technique to visualize the flow dynamics. A monoleaflet mechanical valve was mounted in the inlet and outlet ports of the PVAD, which was connected to a mock circulatory loop tester. The OD of the inlet valve was set at six different angles (OD = 0°, 45°, 90°, 135°, 180°, and 270°, where the OD opening toward the diaphragm was defined as 0°) and the pump rate was fixed at 80 bpm to create a 5.0 l/min flow rate. The main circular flow in the blood pump was affected by the OD of the inlet valve. The observed regional flow velocity was relatively low in the area between the inlet and outlet port roots, and was lowest at an OD of 90°. In contrast, the regional flow velocity in this area was highest at an OD of 135°. The OD is an important factor in optimizing the flow condition in our PVAD in terms of preventing flow stagnation, and the best flow behavior was realized at an OD of 135°.     

Improvement in early oxygen uptake kinetics with left ventricular assist device support

Sustained myocardial recovery and reversal of heart failure has been reported with the use of left ventricular assist devices (LVADs). However, clinical predictors of sustained recovery have not been clearly defined, and little information exists regarding exercise improvement in LVAD patients. Therefore, we sought to determine whether peripheral oxygen delivery and utilization were improved with LVAD support. Eleven patients with available pre- and post-LVAD cardiopulmonary exercise (CPX) data were studied retrospectively. Five patients received a HeartMate XVE for destination therapy (DT) and six patients received a Thoratec PVAD pneumatic LVAD for bridge-to-recovery (BTR). Oxygen uptake kinetics was assessed by fitting a single exponential function to the VO2 response. There was a significant improvement in several key parameters of cardiac performance including peak VO2, VO2 at anaerobic threshold (AT), oxygen kinetics as measured by mean response time (MRT), and oxygen deficit during LVAD support. Oxygen deficiency improved from 0.29 +/- 0.16 ml/kg to 0.16 +/- 0.06 ml/kg (p = 0.023), as did MRT 68 +/- 47.7 seconds to 35.8 +/- 13.3 seconds (p = 0.046) with LVAD support. Improved oxygen kinetics suggests improved peripheral utilization of oxygen, and may offer an additional clinical parameter to predict the likelihood of sustained recovery.     

CFD analysis of a Mag-Lev ventricular assist device for infants and children: fourth generation design

Thousands of pediatric patients suffering from heart failure would benefit from longer-term mechanical circulatory support. There are, however, few support systems available in the United States as viable mechanical assist alternatives for these patients. Therefore, we have designed and developed an axial flow pediatric ventricular assist device (PVAD) with an impeller that is fully suspended by magnetic bearings. This blood pump is designed to generate 0.5-4 L/min for pressure rises of 50-95 mm Hg over 6,000-9,000 rpm. We have performed four major design iterations. Building upon the third design phase, we made improvements to create the PVAD4 model. Numerical simulations of the PVAD4 under steady flow simulations were performed to compare the predictions of the latest PVAD4 model to the earlier PVAD3 design. The PVAD4 design resulted in lower fluid stress levels and an increase in pressure generation. A blood damage analysis was also completed. As compared with the earlier PVAD3 design, the damage analysis of the PVAD4 indicated a reduction in the mean and maximum damage index for the new design. All of these numerical findings are encouraging and demonstrate progress toward achieving a superior pump design.     

Effect of pump flow mode of novel left ventricular assist device upon end organ perfusion in dogs with doxorubicin induced heart failure

End organ effects of nonpulsatile (NP) and pulsatile (P) left ventricular assist device (LVAD) flow were compared in a canine model of doxorubicin-induced heart failure. After heart failure induction, a prototype bimodal LVAD was implanted. Hemodynamics, cardiac dimensions, and myocardial metabolism were monitored with the LVAD off (baseline) and on (in NP and P modes at 70% or 100% power). End organ perfusion was assessed by colored microsphere analysis. Seven dogs were used: two died before pump implantation and were excluded from analysis, and the remaining five survived to study termination. At 70% NP, ascending aortic flow and myocardial oxygen consumption (MVO2) decreased significantly. At 100% NP, LV dimensions decreased, aortic systolic, pulse, and LV pressures decreased but not significantly, and ascending aorta flow reversed. At 100% NP, coronary blood flow, MVO2, and LV free wall subepicardial and subendocardial blood flows decreased significantly. However, as NP support increased, the subepicardial/subendocardial blood flow ratio remained near baseline. At 100% NP, right ventricular perfusion decreased but not significantly, cerebral perfusion decreased significantly, and renal perfusion stayed constant. P mode results were similar, except that ascending aorta flow decreased significantly at 100% P instead of reversing as at 100% NP. These results suggest that end organ perfusion is not differentially affected by LVAD flow mode during chronic heart failure.     

Left ventricular outflow tract obstruction associated with chronic ventricular assist device support

Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63-1, 339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.     

Myocardial size and fibrosis changes during left ventricular assist device support

Previous studies have demonstrated that left ventricular assist device (LVAD) implantation significantly decreases myocyte size and reduces fibrosis of the left ventricle (LV). The objectives of the present study were to evaluate LV functional recovery after LVAD implantation and to assess its predictive factors, including histological findings of LV. Six patients with idiopathic cardiomyopathy underwent LVAD support with an EVAHEART implantable centrifugal pump (Sun Medical Technology Research, Nagano, Japan) for an average support duration of 2.91 years. Histologic samples were obtained from their LV apexes at the time of implantation. At 1 month and at 24 months after implantation, brain natriuretic peptide (BNP) and echocardiographic parameters were evaluated. Brain natriuretic peptide values, LV end-diastolic dimension, LV end-systolic dimension, functional shortening, and right ventricular systolic pressure (RVSP) were improved after LVAD implantation. Patients with developing fibrosis had longer durations of heart-failure history and higher pulmonary artery pressures. Patients with hypertrophic myocytes had smaller FS preoperatively. There was a correlation between the amount of fibrosis and the rate of BNP value change after LVAD implantation. In patients with less fibrosis and smaller myocytes preoperatively, improvement in LV function was observed during LVAD support.     

Development of a miniature motor-driven pulsatile LVAD driven by a fuzzy controller

We have been developing a small, lightweight motor-driven pulsatile left ventricular assist device (LVAD) with a ball screw. The motor-driven LVAD consists of a brushless DC motor and a ball screw. The attractive magnetic force between Nd–Fe–B magnets (with a diameter of 5 mm and a thickness of 1.5 mm) mounted in holes in a silicone rubber sheet (thickness 2 mm) and an iron plate adhered onto the a diaphragm of the blood pump can provide optimum active blood filling during the pump filling phase. The LVAD has a stroke volume of 55 ml and an overall volume of 285 ml; it weighs 360 g. The controller mainly consists of a fuzzy logic position and velocity controller to apply doctors' and engineers' knowledge to control the LVAD. Each unit of the controller consists of a functionally independent program module for easy improvement of the controller's performance. The LVAD was evaluated in in vitro experiments using a mock circulation. A maximum pump outflow of 5.1 l/min was obtained at a drive rate of 95 bpm against an afterload of 95 mmHg, and active filling using the attractive magnetic force provided a pump output of 3.6 l/min at a drive rate of 75 bpm under a preload of 0 mmHg. The operating efficiency of the LVAD was measured at between 8% and 10.5%. While the LVAD can provide adequate pump outflow for cardiac assistance, further upgrading of the software and improvement of the blood pump are required to improve pump performance and efficiency.     

Prosthetic valve selection for a pulsatile LVAD

During the final development of a unique Magnetically Actuated Left Ventricle Assist Device (MALVAD), three of the most widely used clinical prosthetic valves were evaluated to determine their suitability for the stringent requirements for LVAD use, in both the inflow and outflow positions. The three valves (St. Jude Medical-SJM; Medtronic Hall-MH; Bjork-Shiley Convex-Concave-BSCC), with lumen size of 25 mm, were tested in the same appropriate mock loop to the following set of hydraulic parameters: 1) after-load systemic pressure = constant 100 mmHg; 2) preload pressure ranged from 3 mm to 18 mmHg; 3) beat rate ranged from 60 bpm to 80 bpm. Pump actuator power was held constant, correspondent with specific bpm rate, for all valves tested. Results from a series of 10 bench tests per valve showed that the SJM was significantly better, on a statistical basis, than both the MH and BSCC valves, at fill pressures of 5 mmHg. At 10-mm fill pressure, however, the statistical flow rates for both the SJM and the MH valves were significantly superior to the BSCC valve, so that the BSCC valve was classified as a marginal candidate for LVAD use. The SJM and MH valves had bench test flow-rate values whose numerical difference was too small to serve conclusively as an arbitrary basis for valve choice. Because of this, the two valves were further evaluated in terms of two widely recognized, mandatory LVAD valve design criteria: (1) comparative mechanical ruggedness, and (2) relative ease and simplicity of LVAD design inclusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulsatile pediatric ventricular assist devices

A pulsatile pediatric ventricular assist device (PVAD) is being developed at The Pennsylvania State University to provide mechanical circulatory support in infants and children. The PVAD is based on the design of the adult-sized Pierce-Donachy VAD (Thoratec VAD). The infant-sized PVAD has a dynamic stroke volume of approximately 13 ml. A larger 25-ml size for children is also planned. The stroke volumes, beat rates, and pulsatility are comparable to normal physiologic values. The expected maximum duration of use is 6 months. The PVAD is intended to be placed paracorporeally, although the pump may be implanted for bridge-to-transplant applications. The pneumatically actuated PVAD uses a full-to-empty control mode, which allows maximum flexibility in its application for left, right, or biventricular assistance. The device may be used with atrial or ventricular inlet cannulation, with blood return to the aorta or pulmonary artery. In vitro testing is underway to measure hydrodynamic performance, hemolysis, and flow velocities using particle image velocimetry. In vivo implantation studies will be performed in juvenile goats or sheep after the completion of baseline studies to assess hematology and surgical fit.     

Influence of LVAD function on mechanical unloading and electromechanical delay: a simulation study

This study hypothesized that a left ventricular assist device (LVAD) shortens the electromechanical delay (EMD) by mechanical unloading. The goal of this study is to examine, by computational modeling, the influence of LVAD on EMD for four heart failure (HF) cases ranging from mild HF to severe HF. We constructed an integrated model of an LVAD-implanted cardiovascular system, then we altered the Ca²⁺ transient magnitude, with scaling factors 1, 0.9, 0.8, and 0.7 representing HF1, HF2, HF3, and HF4, respectively, in order of increasing HF severity. The four HF conditions are classified into two groups. Group one is the four HF conditions without LVAD, and group two is the conditions treated with continuous LVAD pump. The single-cell mechanical responses showed that EMD was prolonged with the higher load. The findings indicated that in group one, the HF-induced Ca2 + transient remodeling prolonged the mechanical activation time (MAT) and decreased the contractile tension, which reduced the left ventricle (LV) pressure, and increased the end-diastolic strain. In group two, LVAD shortened MAT of the ventricles. Furthermore, LVAD reduced the contractile tension, and end-diastolic strain, but increased the aortic pressure. The computational study demonstrated that LVAD shortens EMD by mechanical unloading of the ventricle.     

Clinical evaluation of right ventricular function in patients with left ventricular assist device (LVAD).

Right ventricular function (RVF) during LVAD support can be a threat for patient survival. Despite extensive research, RVF and its interference with left heart function is unclear. This study examines RVF in a retrospective analysis of 14 patients. Hemodynamic data were collected, including heart rate (HR), central venous pressure (CVP), mean pulmonary artery pressure (mPAP), total cardiac output (CO), calculated stroke volume index (SVI) and right ventricular stroke work index (RVSWI). In all patients, CO increased gradually throughout the study period; CVP showed no significant decrease; mPAP and PCWP decreased significantly over the time period; SVI improved and RVSWI increased from the starting level prior to implantation of the LVAD. We conclude that the CO improved with a lowering of the right ventricular afterload combined with a decrease in total circulating volume. The improvement of RVF with LV assist makes this device an option as a bridge to transplant.     

Analysis and prediction of left ventricular performance under load changes during cardiac catheterization

The applicability of a computer model, which relates the transmural mechanical distribution in the left ventricle (LV) to its global function at different loading conditions, was evaluated in patients with normal to near normal LV function undergoing cardiac catheterization. Left ventriculography and measurements of aortic and LV pressures were performed at baseline conditions and repeated following rapid volume expansion with intravenous infusion of 250 to 300 ml of physiologic saline and also after sublingual isosorbide-dinitrate (ISDN) administration. Twenty patients (18 men and 2 women, average age=53 years) underwent coronary angiography and left ventriculography. Sixteen patients had coronary artery disease with one- to three-vessel involvement and 4 had normal coronary arteries. The measured input data into the model included the end-diastolic LV volume and wall thickness, aortic pressure, heart rate, and the peripheral resistance. The model parameters of myocardial contractility and arterial system capacitance for the control baseline conditions were estimated so that an accurate match was obtained between the predicted and the measured end-systolic (ES) volume and pressure. Using these parameters, model predictions for the two load perturbations were compared to the measurements. An excellent correlation was found between the predicted and measured LV ES volumes and peak-systolic pressures (PSP) (R²>0.994). In four patients, who developed ischemic symptoms during saline injection, the prediction of end-systole volumes were lower than the measured values, suggesting an actual reduction in contractility during acute ischemia. There-fore, the model is sensitive to, contractility changes. The model predicts global LV performance, under different loading conditions, including stroke work, peak developed wall stress, velocity of fiber shortening, and myocardial oxygen consumption.     

Numerical simulation of the influence of a left ventricular assist device on the cardiovascular system

The PUCA (pulsatile catheter) pump is a left ventricular assist device (LVAD) capable of unloading the left ventricle (LV) and improving coronary flow by providing a counterpulsation effect. It consists of an extracorporeal located membrane pump, coupled to a transarterial catheter that enters the body via a superficial artery and ends in the LV. Blood is aspirated from the LV and pumped in the ascending aorta through the same catheter guided by a valve system. Timing and frequency of the PUCA pump influence its efficacy. To study the influence of several pump parameters a numerical model of the device and the circulatory system has been developed. Results of animal experiments were used to validate the model. Optimization studies resulted in a pump configuration with a stroke volume of 50 cc and pump:heart frequency mode of 1:2 that starts ejection at the beginning of diastole.     

Initial report of bridge to recovery in a patient with DuraHeart LVAD

Continuous-flow left ventricular assist devices (LVADs) provide acceptable clinical results, but the long waiting period for heart transplantation leads to diverse complications. LVAD support can cause reverse left ventricular (LV) remodeling that results in the improvement of LV function and allows LVAD removal. We present a case of successful removal of a DuraHeart LVAD because of sufficient recovery of LV function. Before LVAD removal, we conducted an “LVAD weaning test” by decreasing pump speed and performing an additional normal saline infusion test. We consider that the LVAD weaning test can be used in place of the “pulsatile LVAD off test.”     

Relationship between ischaemic time and ischaemia/reperfusion injury in isolated Langendorff-perfused mouse hearts

Myocardial functional recovery and creatine kinase (CK) release following various periods of ischaemia were investigated in isolated mouse hearts. The hearts were perfused in the Langendorff mode with pyruvate-containing Krebs-Hensleit (KH) buffer under a constant perfusion pressure of 80 mmHg, and were subjected to either continuous perfusion or to 5, 15, 20, 25, 30, 45 or 60 min of global ischaemia followed by 45 min of reperfusion. In hearts subjected to ischaemic periods of 5, 15 or 20 min, there was a transient reduction in the left ventricular (LV) dP/dt max during the early phase of reperfusion, while the recovery at the end of reperfusion reached a level similar to that in hearts subjected to continuous perfusion. In hearts subjected to longer ischaemic periods, i.e. 25, 30, 45 or 60 min, the decrease in the cardiac performance was more pronounced and persistent, with significantly lower recovery in LV dP/dt max and higher LV end diastolic pressure (LVEDP) at the end of reperfusion than in the non-ischaemic hearts. There were no significant differences in the recoveries in coronary flow or in heart rate (HR) between groups. Similarly to the functional recovery, the release of CK showed a clear ischaemic length-related increase. In conclusion, the Langendorff-perfused isolated mouse heart could be a valuable model for studies of myocardial ischaemia/reperfusion injury. Future studies using gene-targeted mice would add valuable knowledge to the understanding of myocardial ischaemia/reperfusion injury.     

Preoperative beta-blocker treatment is a key for deciding left ventricular assist device implantation strategy as a bridge to recovery

To date, there have been few reports demonstrating preoperative predictors for left ventricular reverse remodeling (LVRR) after LV assist device (LVAD) implantation, especially among patients with dilated cardiomyopathy (DCM). We retrospectively analyzed 60 patients with stage D heart failure due to DCM who had received LVAD treatment [pulsatile flow (PF) type, 26; continuous flow type, 34]. Data were evaluated at 6 months or just before explantation of the LVAD. We defined “LV reverse remodeling” (LVRR) by the achievement of an LV ejection fraction (LVEF) of ≥35 % after 6 months of LVAD support or explantation of LVAD within 6 months. LVRR occurred in 16 of our patients (26.7 %). Uni/multivariate logistic regression analyses for LVRR demonstrated that of the preoperative variables evaluated, PF LVAD usage and insufficient preoperative β-blocker treatment were independent predictors for LVRR. Patients who accomplished LVRR had a better clinical course, including lower levels of aortic valve insufficiency and lower levels of plasma B-type natriuretic peptide. Of the six patients (10.0 %) in whom LVADs were eventually explanted, all had an LVEF of ≥35 % before explantation or at 6 months. Based on these results, we conclude that DCM patients with insufficient preoperative β-blocker treatment have a chance to achieve LVRR under LVAD support as a bridge to recovery.