Effective ventricular unloading by left ventricular assist device varies with stage of heart failure: cardiac simulator study

Although the use of left ventricular assist devices (LVADs) as a bridge-to-recovery (BTR) has shown promise, clinical success has been limited due to the lack of understanding the timing of implantation, acute/chronic device setting, and explantation. This study investigated the effective ventricular unloading at different heart conditions by using a mock circulatory system (MCS) to provide a tool for pump parameter adjustments. We tested the hypothesis that effective unloading by LVAD at a given speed varies with the stage of heart failure. By using a MCS, systematic depression of cardiac performance was obtained. Five different stages of heart failure from control were achieved by adjusting the pneumatic systolic/diastolic pressure, filling pressure, and systemic resistance. The Heart Mate II? (Thoratec Corp., Pleasanton, CA) was used for volumetric and pressure unloading at different heart conditions over a given LVAD speed. The effective unloading at a given LVAD speed was greater in more depressed heart condition. The rate of unloading over LVAD speed was also greater in more depressed heart condition. In conclusion, to get continuous and optimal cardiac recovery, timely increase in LVAD speed over a period of support is needed while avoiding the akinesis of aortic valve.     

Theoretical estimation of cannulation methods for left ventricular assist device support as a bridge to recovery

Left ventricular assist device (LVAD) support under cannulation connected from the left atrium to the aorta (LA-AA) is used as a bridge to recovery in heart failure patients because it is non-invasive to ventricular muscle. However, it has serious problems, such as valve stenosis and blood thrombosis due to the low ejection fraction of the ventricle. We theoretically estimated the effect of the in-series cannulation, connected from ascending aorta to descending aorta (AA-DA), on ventricular unloading as an alternative to the LA-AA method. We developed a theoretical model of a LVAD-implanted cardiovascular system that included coronary circulation. Using this model, we compared hemodynamic responses according to various cannulation methods such as LA-AA, AA-DA, and a cannulation connected from the left ventricle to ascending aorta (LV-AA), under continuous and pulsatile LVAD supports. The AA-DA method provided 14% and 18% less left ventricular peak pressure than the LA-AA method under continuous and pulsatile LVAD conditions, respectively. The LA-AA method demonstrated higher coronary flow than AA-DA method. Therefore, the LA-AA method is more advantageous in increasing ventricular unloading whereas the AA-DA method is a better choice to increase coronary perfusion.     

A novel counterpulsation mode of rotary left ventricular assist devices can enhance myocardial perfusion

The effect of rotary left ventricular assist devices (LVADs) on myocardial perfusion has yet to be clearly elucidated, and several studies have shown decreased coronary flow under rotary LVAD support. We have developed a novel pump controller that can change its rotational speed (RS) in synchronization with the native cardiac cycle. The aim of our study was to evaluate the effect of counterpulse mode, which increases the RS in diastole, during coronary perfusion. Experiments were performed on ten adult goats. The EVAHEART LVAD was installed by the left ventricular uptake and the descending aortic return. Ascending aortic flow, pump flow, and coronary flow of the left main trunk were monitored. Coronary flow was compared under four conditions: circuit-clamp, continuous mode (constant pump speed), counterpulse mode (increased pump speed in diastole), and copulse mode (increased pump speed in systole). There were no significant baseline changes between these groups. In counterpulse mode, coronary flow increased significantly compared with that in continuous mode. The waveform analysis clearly revealed that counterpulse mode mainly resulted in increased diastolic coronary flow. In conclusion, counterpulse mode of rotary LVADs can enhance myocardial perfusion. This novel drive mode can provide great benefits to the patients with end-stage heart failure, especially those with ischemic etiology.     

Recovery directed left ventricular assist device: a new concept

To promote cardiac recovery, we developed a recovery directed left ventricular assist device (RDLVAD) that consists of a valved apical conduit, an afterload controlling chamber (ACC), and a pump. We evaluated its efficacy by comparison with an ordinary LVAD. In each of six pigs with ischemia-induced heart failure, flow and pressure measurements were made while maintaining the total blood flow and arterial pressure equal in the two groups. RDLVAD was able to direct all the blood ejected from the LV into the ACC (0-15 mm Hg) but not into the aorta (73 mm Hg). In the ordinary LVAD, however, some ejection occurred into the aorta despite vigorous suction of the LV. Thus, RDLVAD increased DPTI/SPTI 2.3 times (p < 0.005) and decreased left ventricular end-diastolic pressure by 40% and maximum dP/dt by 20% (p < 0.05). Even the apical valve, at approximately half the diameter of the aortic valve, was able to allow all the blood ejected from the LV to enter the ACC. In one control group pig that achieved almost no ejection into the aorta, left ventricular relaxation and dilatation was extremely limited. RDLVAD may promote cardiac recovery by ensuring less LV work, a greater blood supply/demand ratio in the coronary circulation, and full ventricular relaxation.     

Continuous flow left ventricular pump support and its effect on regional left ventricular wall stress: finite element analysis study

Left ventricular assist device (LVAD) support unloads left ventricular (LV) pressure and volume and decreases wall stress. This study investigated the effect of systematic LVAD unloading on the 3-dimensional myocardial wall stress by employing finite element models containing layered fiber structure, active contractility, and passive stiffness. The HeartMate II^® (Thoratec, Inc., Pleasanton, CA) was used for LV unloading. The model geometries and hemodynamic conditions for baseline (BL) and LVAD support (LV_support) were acquired from the Penn State mock circulatory cardiac simulator. Myocardial wall stress of BL was compared with that of LV_support at 8,000, 9,000, 10,000 RPM, providing mean pump flow (Q _mean) of 2.6, 3.2, and 3.7 l/min, respectively. LVAD support was more effective at unloading during diastole as compared to systole. Approximately 40, 50, and 60 % of end-diastolic wall stress reduction were achieved at Q _mean of 2.6, 3.2, and 3.7 l/min, respectively, as compared to only a 10 % reduction of end-systolic wall stress at Q _mean of 3.7 l/min. In addition, there was a stress concentration during systole at the apex due to the cannulation and reduced boundary motion. This modeling study can be used to further understand optimal unloading, pump control, patient management, and cannula design.     

Evaluation of recovery directed left ventricular assist device using isolated perfused rabbit hearts

We have developed a recovery directed left ventricular assist device (RDLVAD) that can promote cardiac recovery by achieving very low ventricular work and ensuring full ventricular relaxation and filling. It consists of a valved apical conduit, an afterload controlling chamber, and a centrifugal pump. To test the previously described effects of RDLVAD on the left ventricle, we made an RDLVAD suitable for isolated perfused rabbit hearts. The control LVAD was of a continuous flow type (CLVAD). Thirty-two rabbits were used. The working left heart model proved inappropriate for evaluation of LVAD. In the isolated heart-lung preparation (n = 4), the CLVAD showed a substantial backward flow and a severe negative pressure during diastole. This negative pressure may have resulted in severe restriction of ventricular relaxation and filling. In contrast, in the RDLVAD with the afterload controlling chamber pressure kept as low as possible, the pump flow was stable and increased by 86% (NS), and the peak left ventricular pressure, max dP/dt, and systolic pressure time index decreased by 22.3% (p = 0.022), 29.4% (p = 0.017), and 42% (p = 0.022), respectively. In conclusion, these results indicate that the RDLVAD does not restrict ventricular relaxation or filling and greatly reduces ventricular workload. The RDLVAD, therefore, can promote cardiac recovery.     

Heterotopic transplantation of the failing rat heart as a model of left ventricular mechanical unloading toward recovery

The left ventricular assist device (LVAD) is usually used in patients with end-stage heart failure as a bridge to transplantation. Recently, some studies have reported functional recovery with the use of an LVAD, although the mechanisms responsible for recovery are not fully understood. We investigated the functional recovery of the infarcted, failing rat heart in response to mechanical unloading after heterotopic transplantation. Heart failure was induced in Lewis rats by ligating the left anterior descending artery. After 4 weeks, the infarcted hearts were harvested and heterotopically transplanted. The transplanted infarcted heart was removed after 2 weeks of unloading and examined for hypertrophy and fibrosis, as well as for mRNA levels encoding for brain natriuretic peptide, sarco(endo)plasmic reticulum Ca(2+)-ATPase2a (SERCA2a), and beta1- and beta2-adrenergic receptors. Normal and infarcted rats without transplantation served as control animals. The infarcted heart was hypertrophied as evidenced by an increase in heart weight and myocyte diameter. After unloading the infarcted heart for 2 weeks, there was a decrease in heart weight and myocyte diameter. However, the percentage of myocardial fibrosis increased after unloading. The mRNA expression of brain natriuretic peptide and the beta2-adrenergic receptor significantly improved after mechanical unloading. The levels of SERCA2a mRNA tended to increase after unloading. In conclusion, unloading the failing, infarcted heart can help normalize left ventricular hypertrophy and cardiac gene expression. This unloading model appears to partially mimic the conditions of hemodynamic support with an LVAD in heart failure patients and potentially offers insights into the mechanisms of functional recovery.     

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.     

Quantitative changes in mast cell populations after left ventricular assist device implantation

Mast cells have been implicated as important in tissue remodeling and fibrosis. We investigated the effect of mechanical ventricular unloading upon myocardial fibrosis and cardiac mast cell density in patients undergoing left ventricular assist device (LVAD) implantation. Paired myocardial tissue samples were obtained from 30 patients with end-stage cardiomyopathy at the time of LVAD implantation and at the time of removal and were compared with samples taken from donor hearts. Tissue sections were stained and quantitated for mast cells and myocardial fibrosis. Mast cell density (tryptase positive cells) in cardiomyopathy was higher than that in donor hearts (33.5 +/- 3.6 SEM cells/10 fields vs.15.2 +/- 2.0 SEM cells/10 fields respectively, p = 0.04) and was lower than LVAD supported hearts (33.5 +/- 3.6 SEM cells/10 fields vs. 49.8 +/- 5.7 SEM cells/10 fields respectively, p = 0.01). Mast cells are primarily localized in areas of increased interstitial fibrosis adjacent to myocardial cells and not vessels. There was statistically significant correlation between mast cells and interstitial collagen (p = 0.03) in patients before LVAD implantation that did not persist after mechanical support (p = 0.18). These results suggest that mechanical support with left ventricular assist devices induces an increase in mast cell number in the myocardium and an associated decrease in myocardial fibrosis. We believe these data demonstrate a dual role for cardiac mast cells in the increase in fibrosis in heart failure and the decrease after LVAD and its associated cardiac improvement.     

Acute in vivo evaluation of an implantable continuous flow biventricular assist system

An implantable biventricular assist device offers a considerable opportunity to save the lives of patients with combined irreversible right and left ventricular failure. The purpose of this study was to evaluate the hemodynamic and physiologic performance of the combined implantation of the CorAide left ventricular assist device (LVAD) and the DexAide right ventricular assist device (RVAD). Acute hemodynamic responses were evaluated after simulating seven different physiological conditions in two calves. Evaluation was performed by fixing the speed of one individual pump and increasing the speed of the other. Under all conditions, increased LVAD or RVAD speed resulted in increased pump flow. The predominant pathophysiologic effect of independently varying DexAide and CorAide pump speeds was that the left atrial pressure was very sensitive to increasing RVAD speed above 2,400 rpm, whereas the right atrial pressure demonstrated much less sensitivity to increasing LVAD speed. An increase in aortic pressure and RVAD flow was observed while increasing LVAD speed, especially under low contractility, ventricular fibrillation, high pulmonary artery pressure, and low circulatory blood volume conditions. In conclusion, a proper RVAD-LVAD balance should be maintained by avoiding RVAD overdrive. Additional studies will further investigate the performance of these pumps in chronic animal models.     

Mechanical support of the left ventricle in ischemia induced left ventricular failure: an experimental study.

OBJECTIVE: this study compares the hemodynamic effects of intra-aortic balloon pumping (IABP), left ventricular assist device (LVAD), and extracorporeal membrane oxygenation (ECMO) in left ventricular failure in pigs. METHODS: In 29 pigs weighing 12 +/- 0.7 kg left ventricular failure was induced by ligating the left anterior descending coronary artery. Eight animals served as controls. Eight pigs were treated by IABP, seven by LVAD, and six by ECMO. The study period lasted four hours. Hemodynamic and oxygen transport/uptake parameters were measured continuously or intermittently. RESULTS: Six animals of the ECMO and LVAD groups survived the 4 hour period, but only 3 and 4 animals of the IABP and control groups survived (p less than 0.05). Cardiac index decreased about 48% and 22% in the control and IABP groups (p less than 0.05), whereas there was only a slight decrease in the ECMO (9%) and LVAD (14%) groups. Oxygen delivery fell significantly in the control and IABP groups (p less than 0.05), compared with only a slight change in the LVAD and ECMO groups. CONCLUSION: ECMO is the most effective system for temporary circulatory support in severe ventricular failure. LVAD maintains cardiac output when pulmonary blood flow is provided. IABP is less efficient in supporting the failing heart, especially in the presence of severe ventricular arrhythmias.     

Sonomicrometric studies on the effects of long-term pumping of cardiac assist device on the bulk and regional mechanics of the normal left ventricle in goat.

Pneumatically driven, diaphragm type left ventricular assist devices (LVADs) were implanted into 2 goats with normal hearts for approximately 1 month to study the effects of long-term pumping of LVAD on the cardiac mechanics. One sham-operated goat was used to obtain control data. Diameters and myocardial segment lengths of the left ventricle were measured with an ultrasonic displacement meter to calculate the bulk mechanical work (BMW) and regional myocardial mechanical work (RMW), respectively. The LVAD was pumped in the 2:1 drive mode (one counterpulsated pumping in every two cardiac cycles), and was temporarily driven in the 1:1 mode (one pumping in every cardiac cycle) or stopped to obtain the data under these conditions. During the second half of the post-operative period while the animal condition was stable, the BMW in the 2:1 and 1:1 modes were approximately 59% and 72% of that observed under the temporary pump-off condition (0.22 W/(100 g)), respectively. The RMW in the 2:1 and 1:1 modes were 69% and 74% of that obtained during pump-off (6.2 mW/cm3), respectively. The myocyte diameter in the subendocardial layer was reduced by unloading effect of 1-month pumping, whereas those in middle and subepicardial layer showed little change.     

Computational analysis of the effect of the type of LVAD flow on coronary perfusion and ventricular afterload

We developed a computational model to investigate the hemodynamic effects of a pulsatile left ventricular assist device (LVAD) on the cardiovascular system. The model consisted of 16 compartments for the cardiovascular system, including coronary circulation and LVAD, and autonomic nervous system control. A failed heart was modeled by decreasing the end-systolic elastance of the ventricle and blocking the mechanism controlling heart contractility. We assessed the physiological effect of the LVAD on the cardiovascular system for three types of LVAD flow: co-pulsation, counter-pulsation, and continuous flow modes. The results indicated that the pulsatile LVAD with counter-pulsation mode gave the most physiological coronary blood perfusion. In addition, the counter-pulsation mode resulted in a lower peak pressure of the left ventricle than the other modes, aiding cardiac recovery by reducing the ventricular afterload. In conclusion, these results indicate that, from the perspective of cardiovascular physiology, a pulsatile LVAD with counter-pulsation operation is a plausible alternative to the existing LVAD with continuous flow mode. An erratum to this article can be found at     

Effect of left ventricular assistance on sympathetic tone

To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was detected in acute animal experiments. Our TH-7B pneumatically driven, sac-type ventricular assist device was used in 7 adult mongrel dogs. RSNA was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator circuit. The area of the integrated nerve discharge per unit time was calculated in the computer system and expressed as RSNA per unit time. During LVAD pumping, RSNA decreased with increase in blood pressure, with an increase in pulmonary artery flow, and with a decrease in left atrial pressure. These data suggest that LVAD has an effect on the sympathetic nervous system which is mediated by the aortic and cardiopulmonary baroreflex system.     

Simple implantation of a temporary right ventricular device for right ventricular failure after left ventricular device implantation via a left lateral thoracotomy

Right ventricular (RV) support in the case of RV failure after left ventricular assist device (LVAD) implantation is a well-established surgical therapeutic option. However, there is a serious limitation of RV support after the insertion of a LVAD through lateral thoracotomy in patients who have undergone previous multiple cardiac operations. We describe a modified surgical approach for implantation of right ventricular assist devices (RVADs) via left lateral thoracotomy, with venous cannulation via a femoral vein and transpericardial outflow cannulation of the main pulmonary artery by Seldinger technique under echocardiographic monitoring. This technique was successfully used in a case with subsequent weaning from the RVAD after 10 days of support.     

Left heart pressures can be the key to know the limitation of left ventricular assist device support against progression of aortic insufficiency

Aortic insufficiency (AI) is a worrisome complication under left ventricular assist device (LVAD) support. AI progression causes LVAD-left ventricular (LV) recirculation and can require surgical intervention to the aortic valve. However, the limitations of LVAD support are not well known. Using an animal model of LVAD with AI, the effect of AI progression on hemodynamics and myocardial oxygen metabolism were investigated. Five goats (Saanen 48?±?2 kg) underwent centrifugal type LVAD, EVAHEART, implantation. The AI model was established by placing a vena cava filter in the aortic valve. Cardiac dysfunction was induced by continuous beta-blockade (esmolol) infusion. Hemodynamic values and myocardial oxygen extraction ratio (O₂ER) were evaluated while changing the degree of AI which was expressed as the flow rate of LVAD-LV recirculation (recirculation rate). Diastolic aortic pressure was decreased with AI progression and correlated negatively with the recirculation rate (p?=?0.00055). Systolic left ventricular pressure (LVP) and mean left atrial pressure (LAP) were increased with AI progression and correlated positively with the recirculation rate (p?=?0.010, 0.023, respectively). LVP and LAP showed marked exponential increases when the recirculation rate surpassed 40%. O₂ER was also increased with AI progression and had a significant positive correlation with the recirculation rate (p?=?0.000043). O₂ER was increased linearly, with no exponential increase. AI progression made it difficult to reduce the cardiac pressure load, worsening myocardial oxygen metabolism. The exponential increase of left heart pressures could be the key to know the limitation of LVAD support against AI progression.     

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.     

Prolonged but successful weaning from left ventricular assist device after cardiac decompensation due to late-recognized coarctation of the aorta in a toddler

A 2-year-old boy was presented with late-recognized coarctation of the aorta and pulmonary hypertension due to left ventricular failure. The coarctation was corrected at the day of admission with a good postoperative result. However, weaning from the respirator failed despite multiple drug support due to left ventricular failure. Consequently, a left ventricular assist device (LVAD) was implanted 22 days later. The further course was complicated by systemic hypertension and ongoing pulmonary hypertension requiring extensive antihypertensive therapy. The first attempt to wean from LVAD failed and the left ventricle was left completely unloaded for additional 4 weeks. The second weaning attempt, using a very smooth weaning protocol, led to a recovered left ventricle and facilitated the removal of the assist device after a total of 120 days. The patient was discharged with normal cardiac function, but he still requires antihypertensive therapy. We believe that the slow reduction of the LVAD support was the key measure that leads to the successful weaning of the patient, thereby avoiding heart transplantation.     

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.     

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.