Myocardial hemodynamics, physiology, and perfusion with an axial flow left ventricular assist device in the calf

The Jarvik 2000 axial flow left ventricular assist device (LVAD) is used clinically as a bridge to transplantation or as destination therapy in end-stage heart disease. The effect of the pump's continuous flow output on myocardial and end-organ blood flow has not been studied experimentally. To address this, the Jarvik 2000 pump was implanted in eight calves and then operated at speeds ranging from 8,000 to 12,000 rpm. Micromanometry, echocardiography, and blood oxygenation measurements were used to assess changes in hemodynamics, cardiac dimensions, and myocardial metabolism, respectively, at different speeds as compared with baseline (pump off, 0 rpm) in this experimental model. Microsphere studies were performed to assess the effects on heart, kidney, and brain perfusion at different speeds. The Jarvik 2000 pump unloaded the left ventricle and reduced end-diastolic pressures and left ventricular dimensions, particularly at higher pump speeds. The ratio of myocardial oxygen consumption to coronary blood flow and the ratio of subendocardial to subepicardial blood flow remained constant. Optimal adjustment of pump speed and volume status allowed opening of the aortic valve and contribution of the native left ventricle to cardiac output, even at the maximum pump speed. Neither brain nor kidney microcirculation was adversely affected at any pump speed. We conclude that the Jarvik 2000 pump adequately unloads the left ventricle without compromising myocardial metabolism or end-organ perfusion.     

B-type natriuretic peptide levels and continuous-flow left ventricular assist devices

We postulated that postoperative B-type natriuretic peptide (BNP) levels would be reflective of the degree of hemodynamic support rendered by various pump speeds settings (RPM) of continuous-flow left ventricular assist devices (LVADs). Twenty LVAD patients were evaluated prospectively (Jarvik 2000: n = 9, HeartMate II: n = 11). The mean age was 57.7 ± 14.9 years, and 14 were male. B-type natriuretic peptide levels were drawn while the patients were supported on LVADs at variable RPM settings. The RPM settings were correlated with the changes in BNP levels. Eleven patients underwent LVAD implantation for a lifelong support while the rest were as a bridge therapy to transplantation. Four patients required LVAD change out for various causes of pump failure. Postoperative BNP levels decreased dramatically with the initiation of LVAD support. The levels correlated inversely with the degree of hemodynamic support rendered at various RPM settings of the HeartMate II (p < 0.001). Overall, BNP levels decreased significantly in 2 days after RPM increase. We observed a significant inverse correlation between the postoperative BNP levels and the degree of LVAD support. The effective LVAD support seems to result in a marked reduction in BNP levels, and monitoring serial BNP levels may be helpful in managing patients supported on continuous LVAD.     

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.     

In vitro testing of a novel blood pump designed for temporary extracorporeal support

Extracorporeal blood pumps are used as temporary ventricular assist devices or for extracorporeal membrane oxygenation. The ideal pump would be intrinsically self-regulating, carry no risk of cavitation or excessive inlet suction, be afterload insensitive, and valveless thus reducing thrombogenicity. Currently used technology, including roller, centrifugal, and pneumatic pulsatile pumps, does not meet these requirements. We studied a nonocclusive peristaltic pump (M-Pump) in two mock circulatory loops and compared the performance to a frequently used centrifugal pump and a modified prototype of the M-Pump (the BioVAD). The simple resistance loop consisted of the investigated pump, a fixed height reservoir at 150 mm Hg, and a variable inflow reservoir. The pulsatile circulation used a mock patient simulator with adjustable resistance elements connected to a pneumatic pulsatile pump. The M-Pump intrinsically regulated flow with changing preload, was afterload insensitive, and did not cavitate, unlike the centrifugal pump. The BioVAD also demonstrated these features and could augment output with the use of vacuum assistance. A nonocclusive peristaltic pump may be superior for short-term extracorporeal circulatory assist by mitigating risks of excessive inlet suction, afterload sensitivity, and thrombosis.     

Biventricular support with the Jarvik 2000 ventricular assist device in a calf model of pulmonary hypertension

The Jarvik 2000 ventricular assist device (VAD) is clinically efficacious for treating end-stage left ventricular failure. Because simultaneous right ventricular support is also occasionally necessary, we developed a biventricular Jarvik 2000 technique and tested it in a calf model. One VAD was implanted in the left ventricle with outflow-graft anastomosis to the descending aorta. The other VAD was implanted in the right ventricle with outflow-graft anastomosis to the pulmonary artery. Throughout the 30 day study, hemodynamic values were continuously monitored. On day 30, both pumps were evaluated at different speeds, under various hemodynamic conditions. By gradually occluding the pulmonary artery proximally or distally, we simulated varying degrees of high pulmonary vascular resistance, right ventricular hypertension, global heart failure, or ventricular fibrillation. The two VADs maintained biventricular support even during pulmonary artery occlusion and ventricular fibrillation, yielding a cardiac output of 3-11 L/min, left ventricular end-diastolic pressure of 11-24 mm Hg, and central venous pressure of 9-25 mm Hg. End-organ function was unimpaired, and no major adverse events occurred. The dual VADs offered safe, effective biventricular assistance in the calf. Additional studies are needed to assess the effects of lowered pulse pressure upon the pulmonary circulation and to develop a single pump speed controller.     

Axial flow blood pumps

Each year, thousands of cardiac patients await healthy donor hearts for transplantation. Due to the current shortage of donor hearts (approximately 2300 per year), these patients often require supplemental circulatory support until a transplant becomes available. This supplemental support is often provided by a mechanical heart pump or left ventricular assist device (LVAD). This article explores one type of LVAD, specifically the design and development of axial flow ventricular assist devices (VAD). We discuss the design details, and experimental or clinical experience with the following axial flow support systems: Hemopump, MicroMed DeBakey VAD, Jarvik 2000, HeartMate II, Streamliner, Impella, Berlin INCOR I, Valvo pump, and IVAP. All of these devices demonstrate promise in providing bridge-to-transplant and ultimately destination therapy for adult cardiac failure patients.     

In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.     

In vitro hemodynamic evaluation of ventricular suction conditions of the EVAHEART ventricular assist pump

Purpose: Mismatches between pump output and venous return in a continuous-flow ventricular assist device may elicit episodes of ventricular suction. This research describes a series of in vitro experiments to characterize the operating conditions under which the EVAHEART centrifugal blood pump (Sun Medical Technology Research Corp., Nagano, Japan) can be operated with minimal concern regarding left ventricular (LV) suction. Methods: The pump was interposed into a pneumatically driven pulsatile mock circulatory system (MCS) in the ventricular apex to aorta configuration. Under varying conditions of preload, afterload, and systolic pressure, the speed of the pump was increased step-wise until suction was observed. Identification of suction was based on pump inlet pressure. Results: In the case of reduced LV systolic pressure, reduced preload (=10 mmHg), and afterload (=60 mmHg), suction was observed for speeds =2,200 rpm. However, suction did not occur at any speed (up to a maximum speed of 2,400 rpm) when preload was kept within 10-14 mmHg and afterload =80 mmHg. Although in vitro experiments cannot replace in vivo models, the results indicated that ventricular suction can be avoided if sufficient preload and afterload are maintained. Conclusion: Conditions of hypovolemia and/or hypotension may increase the risk of suction at the highest speeds, irrespective of the native ventricular systolic pressure. However, in vitro guidelines are not directly transferrable to the clinical situation; therefore, patient-specific evaluation is recommended, which can be aided by ultrasonography at various points in the course of support.     

A review of clinical ventricular assist devices

Given the limited availability of donor hearts, ventricular assist device (VAD) therapy is fast becoming an accepted alternative treatment strategy to treat end-stage heart failure. The field of mechanical ventricular assistance is littered with novel and unique ideas either based on volume displacement or rotary pump technology, which aim to sufficiently restore cardiac output. However, only a select few have made the transition to the clinical arena.Clinical implants were initially dominated by the FDA approved volume displacement Thoratec HeartMate I, IVAD, and PVAD, whilst Berlin Heart's EXCOR, and Abiomed's BVS5000 and AB5000 offered suitable alternatives. However, limitations associated with an inherently large size and reduced lifetime of these devices stimulated the development and subsequent implantation of rotary blood pump (RBP) technology. Almost all of the reviewed RBPs are clinically available in Europe, whilst many are still undergoing clinical trial in the USA. Thoratec's HeartMate II is currently the only rotary device approved by the FDA, and has supported the highest number of patients to date. This pump is joined by MicroMed Cardiovascular's Heart Assist 5 Adult VAD, Jarvik Heart's Jarvik 2000 FlowMaker and Berlin Heart's InCOR as the axial flow devices under investigation in the USA. More recently developed radial flow devices such as WorldHeart's Levacor, Terumo's DuraHeart, and HeartWare's HVAD are increasing in their clinical trial patient numbers. Finally CircuLite's Synergy and Abiomed's Impella are two mixed flow type devices designed to offer partial cardiac support to less sick patients.This review provides a brief overview of the volume displacement and rotary devices which are either clinically available, or undergoing the advanced stages of human clinical trials.     

HeartMate II implantation technique that spares the sternum and ascending aorta

Left ventricular assist devices (LVADs) have become the standard therapy for patients with end-stage heart failure, and the use of LVADs for long-term support has grown exponentially over the past decade. As the number of LVAD implantations has increased, surgeons have faced more challenging cases, such as those in which the patient has previously undergone a sternotomy. The HeartMate II is one of the most widely implanted LVADs. The standard procedure for HeartMate II implantation is median sternotomy and sewing the outflow graft to the ascending aorta. However, in patients with sternal comorbidities, it can be advantageous to use a less invasive approach that avoids this procedure. We describe the case of a 64-year-old man with a history of end-stage ischemic cardiomyopathy who had previously undergone a median sternotomy and a coronary artery bypass grafting operation and had patent grafts. He required a HeartMate II LVAD (destination therapy), which was implanted via a left subcostal incision; the pump was placed subdiaphragmatically, and the outflow graft was sewed to the descending aorta to avoid a complicated redo cardiac operation via median sternotomy and to minimize the risk of injuring the patent bypass grafts. The patient survived for more than 500 days postoperatively. This approach is feasible and could be a safer method for implanting a HeartMate II device in patients with serious comorbidities that preclude the use of the traditional implantation techniques.     

Hydrodynamic characterisation of ventricular assist devices

A new mock circulatory system (MCS) was designed to evaluate and characterise the hydraulic performance of ventricular assist devices (VADs). The MCS consists of a preload section and a multipurpose afterload section, with an adjustable compliance chamber (C) and peripheral resistor (Rp) as principal components. The MCS was connected to a pulse duplicator system for validation, simulating a wide range of afterload conditions. Both pressure and flow were measured, and the values of the different components calculated. The data perfectly fits a 4-element electrical analogon (EA). The MCS was further used to assess the hydrodynamic characteristics of the Medos VAD as an example of a displacement pump. Data was measured for various MCS settings and at different pump rates, yielding device specific pump function graphs for water and pig blood. Our data demonstrate (i) flow sensitivity to preload and afterload and (ii) the effect of test fluid on hemodynamic performance.     

An implantable Fabry-Pérot pressure sensor fabricated on left ventricular assist device for heart failure

Continuous flow left ventricular assist devices (LVADs) are commonly used as bridge-to-transplantation or destination therapy for heart failure patients. However, non-optimal pumping speeds can reduce the efficacy of circulatory support or cause dangerous ventricular arrhythmias. Optimal flow control for continuous flow LVADs has not been defined and calls for an implantable pressure sensor integrated with the LVAD for real-time feedback control of pump speed based on ventricular pressure. A MEMS pressure sensor prototype is designed, fabricated and seamlessly integrated with LVAD to enable real-time control, optimize its performance and reduce its risks. The pressure sensing mechanism is based on Fabry-Pérot interferometer principle. A biocompatible parylene diaphragm with a silicon mirror at the center is fabricated directly on the inlet shell of the LVAD to sense pressure changes. The sensitivity, range and response time of the pressure sensor are measured and validated to meet the requirements of LVAD pressure sensing.     

一种植入式磁悬浮离心血泵的体外流体力学实验研究

通过体外模拟循环实验台对一种植入式磁悬浮离心血泵进行体外流体力学实验。以新鲜羊血为循环介质,通过体外循环台测定在后负荷为100 mmHg,血泵在不同转速下的输出量;通过控制血泵的转速,测定在固定泵速下不同后负荷下的输出量。血泵测试工作电压为24 V,电流波动于0.3～0.75 A。血泵功率为7.2～18 W。在后负荷为100 mmHg下,泵速在2 900～3 900 rpm,输出流量为3～7.1 L/min。泵速为2500～3 500 rpm,血泵在后负荷69～163 mmHg下输出流量为1.02～5.87 L/min。在固定的转速下血泵的压力-流量呈负相关关系。体外实验血泵工作性能稳定,可以满足成人心室辅助的需求。血泵功率偏高仍需要进一步改进。     

Development of aortic insufficiency in patients supported with continuous flow left ventricular assist devices

Development of aortic insufficiency (AI) in patients supported with continuous flow left ventricular assist devices (LVAD) can adversely affect pump performance. In this study, we examined the incidence of new AI after LVAD implant at our institution. Pre- and postoperative echocardiograms of 66 patients who received HeartMate II or Heartware LVAD at our institution since June 2008 were reviewed for presence of new AI. Median LVAD support duration was 221 days. New AI developed in 6 patients (9.5%) after a median time of 374.5 days of support. There were no cases of severe or symptomatic AI. There was no significant difference between the AI incidence between HeartMate II and Heartware recipients. For patients who remained on LVAD support at 6 and 12 months, freedom from AI was 100% and 68.4%, respectively. Age, destination therapy status, and duration of support were predictors of new AI after LVAD implant. In conclusion, AI develops frequently during long-term support with continuous flow LVADs, particularly in those supported for longer than 6 months. As we move to the era of long-term LVAD support and destination therapy, further studies with longer follow-ups are required to determine the progression and clinical significance of AI in these patients.     

Pressures generated within the chambers of the MagScrew TAH: an in vitro study

Incompetent inflow valves have been reported with clinical pulsatile left ventricular assist devices that use bioprosthetic valves. Suspected as the cause of premature valve failure within these devices, absolute pressures and instantaneous pressure changes were evaluated in the MagScrew total artificial heart (TAH). The MagScrew TAH is a passively filling pulsatile pump which uses a reciprocating magnetic actuating mechanism under various control modes to propel blood into circulation. Both right and left ejection speeds were modulated and optimized at the onset of hydraulic eject. These various speed profiles were evaluated in vitro at 220 beats per minute (bpm), 100% pump fill, mean aortic pressure of 100 mm Hg and mean pulmonary artery pressure of 20 mm Hg. The pressure inside the left and right pump chambers was measured with Millar Mikro-Tip catheter and captured using Power Lab at a rate of 40 kHz. The pump chamber peak pressure, operating with unmodified eject speeds, measured on average 183 mm Hg for the left and 133 mm Hg for the right. Eject speed profiling for both pumps reduced the peak pressure by 10% and 28% for the left and right pump, respectively. Future studies will assess software controlled optimization of the eject speed profiles under any operating condition and how effective it is in vivo.     

轴流泵式全人工心脏的体外测试及对负荷反应特性

目的 在体外模拟循环台测试轴流泵式全人工心脏的基本负荷反应特性，为探索生理性控制方案提供基础。方法 轴流泵式全人工心脏样机采用2个轴流泵共同设置在刚性外壳中，直径65 mm，长度70 mm。于模拟循环台上串联连接组成全人工心脏的2个轴流泵，在外周动脉和肺动脉阻力不变的条件下观测前、后负荷变化对心脏输出量的影响。结果 在前负荷固定不变的条件下，增加后负荷时心脏输出流量逐步下降，增大泵转速可对抗后负荷对输出量的抑制，泵转速设定为右心泵8 500 r/min、左心泵11 000 r/min时，心脏输出压力为13.3 kPa（100 mmHg）和输出量6 L/min。当后负荷增大到26.7 kPa（200 mmHg）时心输出量下降为0 L/min。在后负荷固定不变的条件下，前负荷的增加不导致心脏输出量明显改变。设定左心泵转速为11 000 r/min、右心泵转速8 500 r/min时前负荷由0.27 kPa（2 mmHg）增加到1.87 kPa（14 mmHg），流量基本维持在7 L/min。结论 轴流泵式全人工心脏对后负荷增加表现出明显的流量抑制趋势，此趋势可通过调节泵转速改善。轴流泵式全人工心脏对前负荷反应不明显，有别于自然心脏，其机制及调节意义尚待进一步研究。     

Atrial, ventricular, or both cannulation sites to optimize left ventricular assistance?

The efficiency of left ventricular assist devices (LVADs) depends on the capacity of the inflow cannula to drain blood into the pump. Left atrial (LA) and left ventricular (LV) sites were compared in an animal model mimicking different hemodynamic conditions. Three calves (56.3+/-5.0 kg) were equipped with a Thoratec LVAD. A regular cardiopulmonary bypass (CPB) circuit was used as a right ventricular assist device (RVAD) (jugular vein/pulmonary artery), and preload conditions were adjusted by storage (or perfusion) of blood into (or from) the venous reservoir. LA and LV drainage, tested separately or simultaneously, was measured by its effect on the LVAD's performance. The LVAD was used alone on a beating heart or together with the RVAD (biVAD) on a beating and on a fibrillating heart. Increasing the central venous pressure (CVP) highlighted the differences between the LA and LV cannulation sites when the LVAD was tested either alone or together with the RVAD (biVAD) on a beating heart. Drainage through the LA or the LV was similar when CVP was set at 8 mm Hg, and increasing CVP to 14 mm Hg allowed for better drainage through the LV cannula. In contrast, after induction of fibrillation to mimic extreme heart failure, the drainage was better through the LA cannula. Using both LA and LV cannulae simultaneously did not improve the LVAD output in any of the conditions tested. LV cannulation provides better blood drainage when used on a normal beating heart and, therefore, allows for increased LVAD performance. However, in severe heart failure, blood drainage through the LV cannula decreases and the LA cannulation site is superior.     

Development of a small implantable right ventricular assist device

The purpose of this program is to design, develop, and clinically evaluate a new, implantable right ventricular assist device (RVAD) that can be used as a component of an implantable biventricular assist device for patients with severe biventricular heart failure. The initial phase of this program resulted in a prototype RVAD, named DexAide, a modified version of the CorAide left ventricular assist device. In vitro testing was performed in a stand-alone circuit and in a true RVAD mode to evaluate pump performance. Pump flow and power were measured under various afterload and pump speed conditions. The pump performance requirements of 2 to 6 l/min and a pressure rise of 20 to 60 mm Hg were successfully met with pump speeds between 1,800 and 3,200 rpm. The nominal design point of 4 l/min and 40 mm Hg pressure rise was achieved at 2,450 +/- 70 rpm with a power consumption of 3.0 +/- 0.2 W. The initial in vitro testing met the design criteria for the new DexAide RVAD. Initial in vivo testing is under way, which will be followed by preclinical readiness testing and a pilot clinical trial in this 5-year program.     

Hemodynamic and energetic assessment of calves implanted with a left ventricular assist device (LVAD)

Hemodynamic and ventricular energetic parameters were measured in calves implanted with the air driven Utah Ventricular Assist Device (UVAD). Uptake site was varied to determine the effect of control mode and vacuum augmentation of filing. Uptake was drawn solely from the left atrium or combined with a left ventricular apical vent. LVAD outflow returned to the descending, thoracic aorta. Control modes examined included asynchronous pumping as well as 1:1 and 1:2 synchronous diastolic counterpulsation. The 85cc LVAD, vacuum formed from PELLETHANE, was implanted acutely in four animals and chronically in six (7, 49 and 116 days paracorporeally, 1, 28 and 32 days intrathoracically). Instantaneous blood pressures, intramyocardial pressure, aortic outflow, oxygen consumption, LVAD output and drive parameters were recorded. LVAD output was independent of control mode when the natural heart rate was greater than or equal to 80 beats per minute. Intrathoracically positioned LVADs pumped a mean flow of approximately equal to 5 liters/min without vacuum augmentation of filling. Paracorporeally positioned LVADs pumped approximately equal to 3 liters/min mean flow without vacuum augmentation and up to approximately equal to 6 liters/min with 38 mm Hg of vacuum augmentation of filling. Instantaneous ascending aortic pressure and flow showed distinct beat-to-beat variation depending on LVAD control mode. Lower average ventricular afterload was observed when pumping the LVAD asynchronously or 1:2 synchronously. In one acute preparation, left ventricular myocardial oxygen consumption was reduced from the unassisted average control level by 37% for the asynchronous and 1:1 synchronous control modes with left atrial uptake.(ABSTRACT TRUNCATED AT 250 WORDS)