Is the New Infant Jarvik 2015 Suitable for Patients<8 kg? In Vitro Study Using a Hybrid Simulator.

Our aim was to study the feasibility of implanting the Infant Jarvik 2015 in patients weighing less than 8 kg. The Infant Jarvik 2015 left ventricular assist device (LVAD) was tested in a hybrid simulator of the cardiovascular system reproducing specific patients' hemodynamics for different patient weights (2-7 kg). For each weight, the sensitivity of the pump to different circulatory parameters (peripheral resistance, left ventricular elastance, right ventricular elastance, heart rate, and heart filling characteristics) has been tested repeating for each experiment a pump ramp (10 000-18 000 rpm). The increase in the pump speed causes a decrease (increase) in the left (right) atrial pressure, an increase (decrease) in the arterial systemic (pulmonary) pressure, an increase in the right ventricular pressure, a decrease (increase) in the left (right) ventricular volume, a decrease in the left ventricular cardiac output, an increase in the LVAD output and an increase in the right ventricular cardiac output (total cardiac output). Suction was observed for lower weight patients and for higher pump speed in the case of vasodilation, left ventricular recovery, bradycardia, right ventricular failure, and left ventricular hypertrophy. Backflow was observed in the case of left ventricular recovery at lower pump speed. In the hybrid simulator, the Infant Jarvik 2015 could be suitable for the implantation in patients lower than 8 kg because of the stability of the device respect to the cardio/circulatory changes (low frequency of suction and backflow) and because of the capability of the device to maintain adequate patient hemodynamics.

The miniaturized pediatric continuous-flow device: Preclinical assessment in the chronic sheep model.

BACKGROUND: The Infant Jarvik 2015 is an implantable axial-flow ventricular assist device (VAD) that has undergone the major evolutionary design modifications to improve hemocompatibility. This study was conducted in anticipation of data submission to the US Food and Drug Administration to obtain Investigational Device Exemption approval. METHODS: The VAD was implanted via a left thoracotomy in Barbado sheep (n = 10, 26 (19-34] kg). Anticoagulation was maintained with coumadin, with a target international normalized ratio of greater than the individual sheep's baseline values. The VAD was managed at the highest possible speed as clinically tolerable. Complete necropsy was performed at the end of the study. RESULTS: There were 2 early mortalities: tension pneumothorax (n = 1) and shower emboli of the fragmented myocardium (n = 1). The remaining 8 sheep (2 with 30-day and 6 with 60-day protocols) completed the anticipated study duration in excellent condition, with the 6 completing 60-day sheep showing appropriate weight gain during support. There were no signs of clinically significant hemolysis, with the final plasma-free hemoglobin of 2 (1-17) mg/dL. Necropsy showed old renal infarction in 7 sheep. Although thromboembolism can be the potential etiology, given the mild anticoagulation regimen, other sources of emboli were identified in 2 sheep (graft coating material and fragmented myocardium). Flow study demonstrated favorable increase in flow (up to 3.0 L/min) in proportion to change in pump speed. CONCLUSIONS: This study has demonstrated that the Infant Jarvik 2015 VAD is capable of maintaining its functionality for an extended period of time with minimal hemolysis.

Closing in on the PumpKIN Trial of the Jarvik 2015 Ventricular Assist Device.

The Infant Jarvik ventricular assist device (VAD; Jarvik Heart, Inc., New York, NY) has been developed to support the circulation of infants and children with advanced heart failure. The first version of the device was determined to have elevated hemolysis under certain conditions. The objective of this work was to determine appropriate modifications to the Infant Jarvik VAD that would result in acceptably low hemolysis levels. In vitro hemolysis testing revealed that hemolysis was related to the shape of the pump blade tips and a critical speed over which hemolysis would occur. Various design modifications were tested and a final design was selected that met the hemolysis performance goal. The new version was named the Jarvik 2015 VAD. Chronic in vivo tests, virtual fit studies, and a series of other performance tests were carried out to assess the device's performance characteristics. In vivo test results revealed acceptable hemolysis levels in a series of animals and virtual fit studies showed that the device would fit into children 8 kg and above, but could fit in smaller children as well. Additional FDA-required testing has been completed and all of the data are being submitted to the FDA so that a clinical trial of the Jarvik 2015 VAD can begin. Development of a Jarvik VAD for use in young children has been challenging for various reasons. However, with the hemolysis issue addressed in the Jarvik 2015 VAD, the device is well-poised for the start of the PumpKIN clinical trial in the near future.

Diamond coated artificial cardiovascular devices.

Ultrananocrystalline diamond (UNCD), an extremely smooth, low cost diamond coating was successfully developed herein for antithrombogenic application which requires high biocompatibility, low wear, low friction, and chemical inertness. The substrate materials utilized in the Jarvik 2000 ventricular assist device (VAD), silicon carbide and titanium alloy, provide an excellent substrate match for UNCD integration. The paper addresses the development of medical-quality UNCD films to significantly improve the knowledge base regarding the defect mechanisms of UNCD films, to reduce or eliminate known wear-inducing imperfections in the film, and to thoroughly characterize and test the films as well as assembled UNCD-coated VADs. After the defect reduction and seeding experiments to improve film adhesion and coating quality, the best candidate deposition method has been down-selected for coating and assembly of VAD parts from Jarvik Heart. The coated and assembled devices have been tested with mechanical and blood-simulating fluid hydrodynamic testing at Jarvik Heart for full verification of the new coating technology. UNCD interface takes advantage of combining unmatched durability and antithrombogenicity.

Jarvik 2000 pump technology and miniaturization.

Blood-pump miniaturization has made amazing progress, reducing the pump diameter to one-tenth of the size of previous positive displacement pumps. In particular, axial-flow-pump technology allows tiny pumps running at high speeds to deliver from 2 to 10 L/min. A review of the background inventions of the Jarvik 2000 technology is presented, together with the reason that making pumps smaller than demanded by the particular application for which they are designed is counterproductive. Pump miniaturization is nearing its practical limit. The optimization of performance and patient outcomes should remain our primary design goal.

Pre-clinical evaluation of the infant Jarvik 2000 heart in a neonate piglet model.

BACKGROUND: The infant Jarvik 2000 heart is a very small, hermetically sealed, intracorporeal, axial-flow ventricular assist device (VAD) designed for circulatory support in neonates and infants. The anatomic fit, short-term biocompatibility and hemodynamic performance of the device were evaluated in a neonate piglet model. METHODS: The infant Jarvik 2000 heart with two different blade profiles (low- or high-flow blade design) was tested in 6 piglets (8.8 ± 0.9 kg). Using a median sternotomy, the pump was placed in the left ventricle through the apex without cardiopulmonary bypass. An outflow graft was anastomosed to the ascending aorta. Hemodynamics and biocompatibility were studied for 6 hours. RESULTS: All 6 pumps were implanted without complication. Optimal anatomic positioning was found with the pump body inserted 2.4 cm into the left ventricle. Hemodynamics demonstrated stability throughout the 6-hour duration. The pump flow increased from 0.27 to 0.95 liter/min at increasing speeds from 18 to 31 krpm for the low-flow blade design, whereas the pump flow increased from 0.54 liter/min to 1.12 liters/min at increasing speeds from 16 krpm to 31 krpm for the high-flow blade design. At higher speeds, >80% of flow could be supplied by the device. Blood chemistry and final pathology demonstrated no acute organ injury or thrombosis for either blade design. CONCLUSIONS: The infant Jarvik 2000 heart is anatomically and biologically compatible with an short-term neonate piglet model. This in vivo study demonstrates the future feasibility of this device for clinical use.

Transplant or VAD?

Major advances in vascular assist device (VAD) technology and the clinical acceptance of destination therapy for patients with contraindications to transplant raise the questions of what patient benefit is necessary to recommend VAD implant for long-term support in patients who are transplant candidates. What are the appropriate indications for use and timing considerations for long-term VAD therapy in patients who qualify for transplant but are unlikely to obtain a donor? The authors suggest that VAD implantation for the indication of "maintenance therapy" where patients must remain on the VAD for two years before becoming transplant eligible, would constitute an appropriate clinical avenue to study these issues.

Study of flow-induced hemolysis using novel Couette-type blood-shearing devices.

To assist the development and application of blood-contacting medical devices, two novel flow-through Couette-type blood-shearing devices have been developed to study the quantitative relationship between blood damage indexes and flow-dependent parameters. One device is an axial flow-through Couette-type device supported by a pair of pin bearings adapted from the adult Jarvik 2000 blood pump. The other is a centrifugal flow-through Couette-type device supported with magnetic bearings adapted from the CentriMag blood pump. In both devices, a rotor spindle was used to replace the original impeller blades so that a small gap was created between the housing and the rotating spindle surface. Computational fluid dynamics simulations have shown that a uniform, high shear stress region can be generated inside the small gap while the shear stresses elsewhere are relatively low. The possibility of secondary blood damage caused by mechanical seals was eliminated due to the use of a magnetic rotor system. Blood flow through the gap was driven by an externally pressurized reservoir. By adjusting the rotational speed and blood flow rate, shear-induced hemolysis was quantified at a matrix of exposure time (0.039 to 1.48 s) and shear stress (50 to 320 Pa). All of the experiments were conducted at room temperature using heparinized ovine blood with a hematocrit value of 30%. The measured hemolysis levels were much lower than those published in the literature, and the overestimation of those earlier studies may be attributable to device-related secondary blood-damaging effects. A new set of coefficients for the power law model was derived from the regression of the experimental data.

In vivo experience of the child-size pediatric Jarvik 2000 heart: update.

Data from early in vivo experiments demonstrated that the child-size Jarvik heart was capable of providing partial to nearly complete circulatory support with acceptable adverse effects on blood. However, bearing thrombosis was responsible for device malfunction in most cases. To overcome this problem, original pin bearings were replaced with novel conical bearings. This study evaluated chronic in vivo performance of the modified child-size Jarvik heart in the pediatric setting. Six juvenile sheep were implanted with the modified child-size Jarvik heart. Cardiac and pump output were measured daily. Serial blood samples were drawn to evaluate hematology, biocompatibility, and end-organ function. End-organ damage and device thrombosis were examined at necropsy. No device malfunction occurred during animal experiments up to 70 days. Mean cardiac output of the animals was 3.4 L/min. The child-size Jarvik heart was able to deliver a blood flow ranging from 1.4 to 2.5 L/min at speed from 10,000 rpm to 14,000 rpm. Mean plasma-free hemoglobin was 9.8 +/- 5.6 mg/dl, indicating no hemolysis. Acute elevation occurred in some organ function tests after the implant surgery but returned to normal range thereafter. These indices and necropsy showed no end-organ damage. No device thrombosis was observed. The current in vivo experience shows that the modified child Jarvik 2000 heart retained its hemodynamic function and excellent biocompatibility, and the conical bearings permitted it to remain free of thrombus.

Early in vivo experience with the pediatric Jarvik 2000 heart.

The need for smaller, more efficient ventricular assist devices that can be used in a more chronic setting have led to exploration of mechanical circulatory support in the pediatric population. The pediatric Jarvik 2000 heart (child size), under development, was implanted in six juvenile sheep and studied for both acute fit and chronic performance evaluation. Daily hemodynamic measurements of cardiac output and pump output at varying pump speeds were taken. In addition, plasma free hemoglobin, lactic acid dehydrogenase, and platelet activation from blood samples were determined at baseline, after implantation, and twice a week thereafter. The measured flow through the outflow graft at increasing speeds from 10,000 rpm to 14,000 rpm with an increment of 1,000 rpm were 1.47 +/- 0.43, 1.89 +/- 0.52, 2.36 +/- 0.61, 2.80 +/- 0.73, and 3.11 +/- 0.86 (L/min). The baseline plasma free hemoglobin was 11.95 +/- 4.76 (mg/dL), with subsequent mean values being <30 mg/dL at postimplantation and weekly postimplantation measurements. Both lactic acid dehydrogenase and platelet activation showed an acute increase within the first week after implantation with subsequent return to baseline by 2 weeks after surgery. Our initial animal in vivo experience with the pediatric Jarvik 2000 heart shows that a small axial flow pump can provide partial to nearly complete circulatory support with minimal adverse effects on blood components.

Mechanical reliability of the Jarvik 2000 Heart.

BACKGROUND: Device failure is a limitation of permanent mechanical circulatory support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial flow pump with ceramic bearings designed to provide more than 10 years' durability. METHODS: The Jarvik 2000 Heart was implanted in 102 patients between April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were implanted as a bridge-to-transplantation, and 19 with postauricular power supply as lifetime therapy. Eighteen pumps were recovered intact after clinical use and run continuously on the bench to further assess durability. RESULTS: No implantable component failure occurred either in patients or during bench testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and 51 years in vitro. The mean support time for bridge-to-transplant recipients was 159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients were supported moer than 2 years, with the longest ongoing approaching 5 years. External cables caused three system failures, with a 95% freedom from system failure at 4 years. Device malfunctions, related to external cables (9) and lack of a backup battery (1), caused no adverse consequences. Before introduction of noncorrosive, gold-plated stainless steel connectors, corrosion was observed on three connectors to the retroauricular power supply. CONCLUSIONS: The Jarvik 2000 Heart has had no implantable component failure. Meaningful durability data and failure mode can only be established by real-time testing in patients. The reliability and dependability of this device, in addition to the exchangeability of external components, give promise for long-term circulatory support in critically ill heart failure patients.

The National Heart, Lung, and Blood Institute Pediatric Circulatory Support Program.

Options for the circulatory support of pediatric patients under the age of 5 years are currently limited to short-term extracorporeal devices, the use of which is often complicated by infection, bleeding, and thromboembolism. Recognizing this void, the National Heart, Lung, and Blood Institute solicited proposals for the development of novel circulatory support systems for infants and children from 2 to 25 kg with congenital or acquired cardiovascular disease. Five contracts were awarded to develop a family of devices that includes (1) an implantable mixed-flow ventricular assist device designed specifically for patients up to 2 years of age, (2) another mixed-flow ventricular assist device that can be implanted intravascularly or extravascularly depending on patient size, (3) compact integrated pediatric cardiopulmonary assist systems, (4) apically implanted axial-flow ventricular assist devices, and (5) pulsatile-flow ventricular assist devices. The common objective for these devices is to reliably provide circulatory support for infants and children while minimizing risks related to infection, bleeding, and thromboembolism. The devices are expected to be ready for clinical studies at the conclusion of the awards in 2009.

The effect of intermittent low speed mode upon aortic valve opening in calves supported with a Jarvik 2000 axial flow device.

We assessed the effects of an axial flow left ventricular assist device (LVAD) upon aortic valve opening, pump outflow, and biologic and hematologic parameters when operated in intermittent low speed (ILS) mode. An ILS controller equipped Jarvik 2000 LVAD was implanted in six calves. Pump speed was maintained at 10,000 rpm, and pump outflow was measured throughout the study period (71 +/- 6 days [mean +/- SD]). Hematologic and biochemical parameters were analyzed daily for the first 10 days, weekly for the first month, and biweekly thereafter to monitor for kidney or liver dysfunction, hemolysis, bleeding, or infection. Before study termination, esmolol hydrochloride was infused to induce low cardiac output and totally impair aortic valve opening. Radiopaque cineaortography was performed over 30 second intervals (10 seconds before, 10 seconds during, and 10 seconds immediately after ILS controller activation) to assess the effect of ILS mode upon aortic valve opening. After study termination, major end organs and the major vascular tree were removed and examined macroscopically and histologically for thrombus formation and infarction; the aortic valve was examined for thickening and fusion. All pumps were explanted and examined for thrombus formation. All six calves recovered without surgical or mechanical complications. Hematologic and biochemical parameters did not change significantly between baseline and study termination. The aortic valve successfully opened when ILS mode was activated, even under low cardiac output conditions. No thrombus was detected in the major end organs and vascular tree, except for some small renal infarcts in three calves that did not affect renal function. These results indicate that operating an axial flow LVAD in ILS mode allows aortic valve opening and aortic root washout.

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.

The Jarvik 2000 Heart. Clinical validation of the intraventricular position.

OBJECTIVE: Heart failure is now a public health epidemic. Donor hearts are severely restricted in availability. Permanent mechanical circulatory support or bridge to myocardial recovery are emerging alternatives. After extensive laboratory experience we sought to evaluate the intraventricular Jarvik 2000 Heart in patients with endstage heart failure. METHODS: The Jarvik 2000 Heart is a novel thumb-sized left ventricular assist device (LVAD) which is fitted within the apex of the native left ventricle. A vascular graft off loads this to the descending thoracic aorta. The pump rotor spins at between 8000 and 12,000 rpm providing 5-6 litres blood flow per minute. We have used the device with skull-mounted power delivery for seven permanent implants and trans-abdominal drive line for ten bridge-to-transplant patients. RESULTS: All patients survived the operation. Three died from non-device related complications. Survivors had early resolution of heart failure with return to NYHA I/II. All had pulsatile circulation. The device was user-friendly and imperceptible to the patient. Both the pump and native left ventricle contributed to the cardiac output during exercise. Seven patients have been transplanted successfully. All explanted devices were free from thrombus formation. Two permanent implant patients left hospital as early as 3 weeks postoperatively. CONCLUSIONS: The Jarvik 2000 is an effective user-friendly LVAD which allows early discharge from hospital. The intraventricular position has distinct advantages especially through absence of an inflow cannula. Synergy develops between the LVAD and native left ventricle. Early experience suggests that this may be a realistic LVAD to treat heart failure routinely in the outpatient setting.

Circulatory support for long-term treatment of heart failure: experience with an intraventricular continuous flow pump.

BACKGROUND: A lifetime mechanical solution for advanced heart failure must be reliable, with a low risk of life-threatening complications. After extensive laboratory testing, we began clinical trials with an axial flow pump for long-term treatment of New York Heart Association class IV, transplant-ineligible patients. METHODS AND RESULTS: The Jarvik 2000 is a continuous flow device that is implanted in the apex of the left ventricle with offloading to the descending thoracic aorta. Skull-based percutaneous power delivery was derived from cochlear implant technology. We used this system in 4 patients with end-stage dilated cardiomyopathy. Exercise capacity, quality of life, device parameters, and native heart function were monitored serially. One patient died from right heart failure at 3 months. The other patients were discharged from hospital between 3 and 8 weeks postoperatively and are currently New York Heart Association I or II. Follow-up lasted between 9 and 20 months. There has been no device failure or hemolysis. Native heart function and quality of life were markedly improved. CONCLUSIONS: The Jarvik 2000 is a true assist (rather than replacement) device that functions synergistically with the native left ventricle and provides excellent quality of life. Adverse events are infrequent. This blood pump may provide a mechanical solution for end-stage heart failure in the community.

Initial clinical experience with the Jarvik 2000 implantable axial-flow left ventricular assist system.

BACKGROUND: Implantable left ventricular assist systems (LVASs) are used for bridging to transplantation, bridging to myocardial improvement, and for permanent circulatory support. Conventional implantable systems have inherent limitations that increase morbidity during support. In contrast, small, efficient, axial-flow pumps, which have been under development for the past decade, have the potential to improve the length and quality of life in patients with severe heart failure. Methods and Results- To assess the safety and clinical utility of the Jarvik 2000, we implanted this device in 10 transplant candidates (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation was achieved through a left thoracotomy during partial cardiopulmonary bypass. The mean support period was 84 days. Within 48 hours postoperatively, the cardiac index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Eight patients underwent physical rehabilitation and returned to NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and pressure-volume loop analyses showed good left ventricular unloading. Seven patients underwent transplantation and 3 died during support. No device thrombosis was observed at explantation. CONCLUSIONS: The Jarvik 2000 functions as a true assist device by partially unloading the left ventricle, thereby optimizing the patient's hemodynamics. Our preliminary results indicate that this LVAS may safely provide circulatory assistance for heart transplant candidates.

Implant technique for the Jarvik 2000 Heart.

The Jarvik 2000 Heart is a silent compact axial flow impeller pump which is now undergoing clinical trials for both bridge to transplantation and permanent mechanical circulatory support. The pump is implanted into the apex of the failing left ventricle by left thoracotomy. A vascular graft offloads to the descending thoracic aorta so that only the left pleural cavity is opened. Power supply is through an abdominal drive line or postauricular titanium pedestal according to the treatment strategy.

Postauricular percutaneous power delivery for permanent mechanical circulatory support.

OBJECTIVE: Percutaneous driveline infection continues to detract from both quality and length of life in patients with a left ventricular assist device. We have pursued an alternative route by using a skull-mounted percutaneous pedestal similar to cochlear implant technology. We have now used this method in patients implanted with the Jarvik 2000 heart (Jarvik Heart, Inc, New York, NY) as destination therapy for end-stage (New York Heart Association class IV) heart failure. METHODS: Four men with cardiomyopathy aged 61 to 72 years received the Jarvik 2000 heart with postauricular power delivery for permanent mechanical circulatory support. The power cable was brought through the second posterior intercostal space and routed through the neck to a percutaneous titanium implant screwed to the skull. This joins with the cable to the external controller and battery. RESULTS: In 3 patients the pedestal healed well and remained free from infection up to 1 year. The system was user friendly, and the whole external apparatus is exchangeable. The second patient had a subdural hematoma. This caused us to improve the preparation and modify the implant procedure. CONCLUSION: For widespread use, permanent implantable circulatory support requires a reliable, user-friendly device with freedom from powerline infection. Our early experience with the Jarvik 2000 heart suggests that rigid fixation and the vascularity of scalp skin promote healing and reduce the risk of driveline infection.