Modifications in surgical implantation of the Penn State electric total artificial heart.

BACKGROUND: Two modifications of the surgical implantation protocol for the Penn State Total Artificial Heart (ETAH) were evaluated: Phrenic nerve ischemia was prevented by minimizing dissection and traction; and hemostasis was augmented and ETAH cuff anastomoses reinforced by using fibrin glue. METHODS: Thirteen Holstein calves underwent orthotopic surgical implantation of the Penn State ETAH between February 1998 and August 2000. Mean hemodynamic and laboratory chemistry variables from the first postoperative week were compared between calves receiving the original (n = 7) and modified (n = 6) protocol. RESULTS: Calves assigned to the modified protocol displayed an improvement in the Po2/FiO2 ratio compared to original (419.4 +/- 17.5 vs 336.3 +/- 35.4, respectively; p = 0.05). All additional parameters were equivalent between groups. The percent survival of animals receiving the modified protocol at 2, 4, and 12 weeks was higher than that of animals that underwent the original protocol. Original-protocol calf deaths consisting of hemothorax (n = 3), and respiratory failure (n = 1) were prevented in the modified protocol. CONCLUSIONS: Our results suggest that manipulations in surgical protocol may promote increased survival in calves implanted with the Penn State ETAH.

The LionHeart LVD-2000: a completely implanted left ventricular assist device for chronic circulatory support.

Management of patients with end-stage cardiac disease remains a vexing problem. Limitations in medical management and a fixed supply of donor organs for cardiac transplant have a continued impact on this growing population of patients. Mechanical circulatory support has proved very successful as a means of bridging patients to cardiac transplant when all medical options have been exhausted. The development of a chronic system of circulatory support has been underway at the Pennsylvania State University for nearly 30 years. These efforts have been recently merged with the industrial partnership with Arrow International toward the development of the LionHeart LVD-2000 (Arrow International, Reading, PA) completely implanted left ventricular support system. We present an overview of the system, details of implantation, a review of preclinical studies, and a synopsis of the first European implants. Early results have demonstrated the system to be safe, effective, and reliable. Transcutaneous energy transmission and the compliance chamber have been validated.

Testing of a 50 cc stroke volume completely implantable artificial heart: expanding chronic mechanical circulatory support to women, adolescents, and small stature men.

The development of a completely implanted total artificial heart at our institution has progressed to successful in vivo and in vitro testing of a device that is nearing clinical testing. This system consists of a 70 cc stroke volume pump originally designed to be used in men of average stature. Implantation of this system remains limited by patient size; hence, many women and adolescent patients will likely be precluded from support because of their smaller stature. A system similar in design, but with a 50 cc stroke volume pump has been developed. The first in vivo study of this device has been undertaken. A calf was supported for 33 days. The animal was extubated and ambulatory within the first 6 hours of implantation, and remained healthy until the thirty-third postoperative day when it suffered an embolic neurologic event. The pump and operating system worked flawlessly throughout the period of support. Further in vivo and in vitro testing will be undertaken. Development of a scaled down total artificial heart system expands this type of circulatory support to those critically ill patients previously deemed poor candidates because of their smaller body habitus.

Detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations: consensus image acquisition and interpretation using two different cineradiographic imaging technologies.

BACKGROUND: Conventional cineradiology has been used clinically to detect partially broken outlet struts (single leg separations, SLSs) in normally functioning Björk-Shiley convexo-concave (C/C) heart valves. The value of radiographic screening has, however, been debated in the medical literature. This study uses the same radiographic technique in sheep implanted with known-status C/C valves in combination with a newly developed geometric image magnification radiography system. This study was designed to test whether sensitivity and specificity of radiographic screening of C/C valves in detecting SLSs could be improved through the combination of readers and imaging modalities. METHODS: Twenty-one sheep with mitral C/C valves were studied on both systems. Five were used for extensive scanning training. When operators were expert on both systems, 16 blinded study valves (4 intact and 12 with outlet strut SLSs) were scanned twice on both systems, first on a modified conventional and then a prototype geometric image magnification (Feinfocus(TM)) cineradiographic system by two expert physicians working together. RESULTS: Among the 32 scanned valves, the two combined expert physicians were required to evaluate 40 intact legs and 24 with an SLS. For all SLS valves, the conventional and Feinfocus systems separately detected 50 (12/24) and 54% (13/24), respectively. When the two systems were combined, the final consensus score was correct in 67% (16/24) of all SLS valves. CONCLUSIONS: Combined modality, paired expert physicians detected 67% of all SLSs. The Feinfocus system might be best reserved for those patients in whom the Siemens screening study demonstrates in minimally suspicious (grade 2) or suspicious (grade 3) appearance of a C/C valve outlet strut leg.

Steady state hemodynamic and energetic characterization of the Penn State/3M Health Care Total Artificial Heart.

Total Artificial Heart (TAH) development at Penn State University and 3M Health Care has progressed from design improvements and manufacturing documentation to in vitro and in vivo testing to characterize the system's hemodynamic response and energetic performance. The TAH system is completely implantable and intended for use as an alternative to transplantation. It includes a dual pusher plate pump and rollerscrew actuator, welded electronics and battery assembly, transcutaneous energy transmission system, telemetry, and a compliance chamber. In vitro testing was conducted on a Penn State mock circulatory loop with glycerol/water solution at body temperature. Tests were performed to characterize the preload and afterload response, left atrial pressure control, and power consumption. A sensitive preload response was demonstrated with left atrial pressure safely maintained at less than 15 mm Hg for flow rates up to 7.5 L/min. Variations in aortic pressure and pulmonary vascular resistance were found to have minimal effects on the preload sensitivity and left atrial pressure control. In vivo testing of the completely implanted system in its final configuration was carried out in two acute studies using implanted temperature sensors mounted on the electronics, motor, and energy transmission coil in contact with adjacent tissue. The mean temperature at the device-tissue interface was less than 4 degrees C above core temperature.

Ventriculoarterial coupling with intra-aortic balloon pump in acute ischemic heart failure.

PURPOSE: We analyzed the mechanism of effects of intra-aortic balloon pumping using the pressure-volume relationship and ventriculoarterial coupling in the normal and failing hearts. MATERIALS: In 12 anesthetized Holstein calves (weight, 94 +/- 8 kg), the ventricular end-systolic and arterial elastances, pressure-volume area, and external work were analyzed during steady-state contractions with traditional hemodynamic parameters with intra-aortic balloon pumping-off and -on (1:1 synchronous ratio). An acute ischemic heart failure was induced by injecting 10 microm microspheres (4.2 +/- 1.8 x 10(7). 100g left ventricular weight-1) into the left main coronary artery; all measurements were repeated. RESULTS: Intra-aortic balloon pumping did not change hemodynamic parameters in the control. However, during heart failure, intra-aortic balloon pumping decreased the arterial elastance from 3.6 +/- 1.3 mm Hg to 2.9 +/- 1.2 mm Hg. mL-1 while not affecting the ventricular end-systolic elastance, this resulted in an improvement of the ventriculoarterial coupling ratio from 3.1 +/- 0.8 to 2.3 +/- 0.8. Intra-aortic balloon pumping decreased not only end-systolic pressure (from 69 +/- 16 mm Hg to 64 +/- 19 mm Hg) but end-diastolic volume and pressure (from 139 +/- 38 mL to 137 +/- 37 mL and from 13. 9 mm Hg to 12.8 mm Hg, respectively) with the leftward shift of the pressure-volume loop. Pressure-volume area decreased (from 914 +/- 284 mm Hg to 849 +/- 278 mm Hg. mL) although stroke volume increased (from 21 +/- 6 mL to 24 +/- 6 mL). CONCLUSION: Reduction of the arterial elastance with intra-aortic balloon pumping improved the ventriculoarterial coupling ratio and increased stroke volume. Leftward shift of the pressure-volume loop resulted in the reduction of pressure-volume area, which suggests the conservation of the myocardial oxygen consumption.

Postoperative pulmonary complications in calves after implantation of an electric total artificial heart.

In long-term studies testing the Penn State Total Artificial Heart involving 30 calves, seven calves died of pulmonary complications within 2 weeks after receiving the implant (Group 1 [G1]) and seven calves survived from 2 weeks to 3 months without infection (Group 2 [G2]). Comparative studies were performed using multiple variables: cardiopulmonary bypass (CPB) time, cardiac index, central venous pressure, leukocyte count, hematocrit, total protein, albumin, serum glutamic oxaloacetic transaminase (GOT), creatinine, water balance, and transfused blood volume. In G1, CPB time was longer than in G2 (182 +/- 19 vs 156 +/- 17 minutes, respectively, p = 0.018). Postoperative minimum total protein and albumin in G1 were lower than those in G2 (56.5% +/- 6.0% and 59.0% +/- 5.5% of preoperative values vs 68.4% +/- 8.5% and 67.8% +/- 6.1%, respectively, p = 0.011 and 0.015). Water balance in G2 was more positive than in G1 (11.7 +/- 6.8 vs 1.4 +/- 8.3 L, respectively, p = 0.020). Other variables showed no significant differences. Microscopic findings of the lung in G1 were congestion, hemorrhage, aggregation of neutrophils, and proteinaceous material within the interstitial tissues and alveoli.

In vivo accuracy of two radiographic systems in the detection of Björk-Shiley convexo-concave heart valve outlet strut single leg separations.

OBJECTIVE: Modified cineradiographic systems have been used clinically to detect partially broken outlet struts in normally functioning Björk-Shiley convexo-concave heart valves. Almost all such valves were explanted, presuming that full failure would likely follow. Inasmuch as the clinical setting only rarely permits examination of normally rated valves, the accuracy of radiographic detection cannot be clinically defined. This study uses the clinical radiographic technique in sheep implanted with known-status convexo-concave valves, comparing its accuracy and that of a newly developed, geometric image magnification radiography system. METHODS: Twenty-one sheep with mitral convexo-concave valves were studied on both systems. Five were used for extensive training. When operators were expert with both systems, images of four intact valves and 12 valves with outlet strut single leg separations, along with a seventeenth single leg separation valve used for calibration, were integrated into 112 image sets organized into a balanced incomplete block design for evaluation by eight trained, blinded reviewers. RESULTS: Cineradiography sensitivity was 24% versus 31% for direct image magnification. The odds ratio for detection of single leg separation by direct image magnification versus cineradiography was 2.0 (95% confidence interval, 0.76 to 5.9; p = 0.13). Cineradiography specificity was 93% versus 90% for direct image magnification. Sensitivity and specificity varied markedly by reviewer, with sensitivity ranging from 8% to 55% and specificity from 51% to 100% for the combined technologies. CONCLUSIONS: The data support the need for more intensive training for convexo-concave valve imaging and further investigation of unconventional radiographic technologies. Clinical cineradiography of convexo-concave valves may detect as little as 25% of valves having a single leg separation, underestimating the prevalence of single leg separations and thereby implying more rapid progression to full fracture than is actually the case.

Recent improvements in a completely implanted total artificial heart.

The total artificial heart under development by the Pennsylvania State University and 3M Health Care has undergone a number of design improvements to improve reliability, manufacturability, implantability, and performance. These improvements are nearing completion in preparation for formal durability testing. The redesigned implanted electronics canister, consisting of a welded titanium shell with hermetic connectors, contains the control, telemetry, and energy transmission electronics, as well as a 9 cell, 800 mAhr Ni-Cd battery pack. Functional changes include a reduction in the battery recharge time from 14 hours to 4 hours, and a new inductive telemetry system. The energy transmission system operating frequency has been increased from 160 kHz to 200 kHz. Electromagnetic interference filters and a more efficient control mode have also been implemented. The energy converter has been modified to incorporate a new motor with integral Hall effect position sensors, and new cable, and compliance chamber conduit fittings. High flex life cable is now used for the motor and coil cables. Two prototype durability mock circulatory loops have been built and are being tested. Substantial progress has been made in the completion of manufacturing documentation, and in the implementation of a quality system.

Bridging to transplant. Equal extended survival for patients undergoing LVAD support when compared with long-term medical management.

Implantation of ventricular assist devices (VADs) to support patients awaiting cardiac transplant has become an effective means of assuring that these critically ill patients survive to transplant. The authors undertook a retrospective analysis of 115 consecutive patients listed for cardiac transplant from January 1992 through June 1995. A VAD was implanted in 19 of these patients. Survival was calculated by intent to treat from the time of transplant listing through heart transplant, if it occurred. The analysis demonstrates that the patients who underwent implantation of a VAD as bridge to transplant had survival times similar to those of patients with medical management. These survival statistics demonstrate the utility of VADs as an effective means to bridge critically ill patients until a suitable donor organ becomes available. In addition, as previous studies have suggested for acute results, earlier implementation and better patient selection may lead to improved long-term survival.

In vivo observation of cavitation on prosthetic heart valves.

In this study, a method to determine the existence of prosthetic heart valve cavitation in vivo is presented. Pennsylvania State University Left Ventricular Assist Devices (LVADs) were implanted in two separate calves for this study. Björk-Shiley Monostrut (Irvine, CA) 27 mm and 25 mm valves with Delrin occluders were used in the mitral and aortic positions, respectively. A high fidelity, piezoelectric pressure transducer was mounted approximately 1.25 cm proximal to the mitral valve and measured the high frequency pressure fluctuations caused by cavitation bubble formation and collapse after valve closure. The root mean square (RMS) value of the mitral pressure signal during a 5 ms interval after valve closure was used as a measure of cavitation intensity. The pressure signals observed in vivo were similar to ones observed in vitro with the same type of pressure transducer and were associated with the visually observed cavitation. The percentage of beats with cavitation increased from 20.3% to 67.7% when pump filling was decreased by increasing beat rate. A blood test conducted during post-operative days 1-3 showed a significant increase in plasma hemoglobin during the low filling condition. However, blood tests conducted later (post-operative days 7-44) did not show a significant change in plasma hemoglobin during low filling conditions.

Results of mechanical ventricular assistance for the treatment of post cardiotomy cardiogenic shock.

The voluntary submission of data on patients who receive mechanical circulatory assistance for post cardiotomy cardiogenic shock and acute myocardial infarction has resulted in an established data base for the ongoing evaluation of these devices. Since its inception in 1985, there have been 1,279 cases reported of implanted ventricular assist devices for post cardiotomy cardiogenic shock. The average duration of support for these devices is approximately 4 days. Those patients who underwent implantation of a centrifugal pump had significantly shorter periods of support when compared with the pneumatically supported group. Patients had similar periods of support when comparing clinical outcome. Approximately 70% of the reported cases underwent centrifugal assistance. The majority of reported cases were supported with isolated left ventricular assistance. There was no significant difference in overall outcome statistics when comparing type or mode of support. Approximately 45% of reported patients were weaned from circulatory assistance, and 25% of all patients survived to discharge. These numbers remain consistent with previously reported statistics. The results with acute myocardial infarction remain limited. Of the 96 reported patients, 26% were weaned from support and only 11.5% survived to discharge. This report continues to support the use and research for advancement of these devices toward the treatment of post cardiotomy cardiogenic shock.

Total artificial heart: from bridge to transplantation to permanent use.

BACKGROUND: Pneumatic artificial hearts have played an important role in supporting the circulation in patients before cardiac transplantation. Pneumatic hearts have also been used for permanent cardiac replacement, but most agree they have serious limitations. METHODS: Several groups are now developing electric artificial hearts in which electrical energy crosses the skin using a wireless technique. The electrical energy powers a small direct-current motor, which actuates the blood pump. RESULTS: Important progress in these devices has resulted in animal survival with electric hearts of more than 1 year. CONCLUSIONS: Extensive bench testing and animal testing will be performed before the initial clinical use of these devices will be initiated. One of the early scientific achievements of the 21st century will be the initial use of the electric artificial heart in humans.

Pierce-Donachy pediatric VAD: progress in development.

BACKGROUND: Despite the successful use of ventricular assist devices in adults over the past 15 years, relatively little has been done to develop similar devices for pediatric patients. Consequently, no such device is currently available. A review of clinical data suggests that the majority of patients in need of a pediatric ventricular assist device, either for postcardiotomy cardiogenic shock or as a bridge to cardiac transplantation, are neonates weighing 3 to 5 kg. Attempts to "scale down" an adult blood pump to make an appropriate device for these patients have been difficult due to the lack of sufficiently small, commercially available valves and the tendency for thrombus to develop in these small pumps. METHODS: We report on progress in the development of the Pierce-Donachy pediatric ventricular assist device, which incorporates 10-mm-diameter bileaflet valve prototypes. Particle image velocimetry is used to quantify the velocity field inside the pump. RESULTS AND CONCLUSIONS: Particle image velocimetry velocity maps demonstrate the complexity of the flow patterns in these pumps and suggest that improved flow patterns may result from the use of valves with improved hemodynamic performance. Animal tests to determine whether improved flow patterns and better "washing" of the pump's blood-contacting surfaces will reduce thrombus formation are underway.

Left ventricular mechanoenergetics during asynchronous left atrial-to-aortic bypass. Effects of pumping rate on cardiac workload and myocardial oxygen consumption.

The purpose of this study was to analyze left ventricular energetics during asynchronous, pulsatile left atrial to aortic bypass in the failing heart with the use of the pressure-volume relationship. In 12 anesthetized Holstein calves (body weight 94 +/- 7 kg), 10 microns microspheres (3.3 x 10(7) +/- 1.1 x 10(7)/100 gm left ventricular weight) were injected into the left main coronary artery to induce heart failure. Baseline left ventricular end-systolic elastance significantly decreased from 7.9 +/- 0.7 to 5.5 +/- 0.4 mm Hg/ml 100 gm left ventricular weight. Left ventricular pressure was measured with a micromanometer, and ultrasonic dimension transducers measured left ventricular orthogonal diameters. Ellipsoidal geometry was used to calculate simultaneous left ventricular volume. End-systolic elastance, pressure-volume area, external work, potential energy, and myocardial oxygen consumption were analyzed during steady-state contractions. After pre-pulsatile left atrial to aortic bypass measurements were taken, the measurements were repeated during asynchronous pulsatile left atrial to aortic bypass at the maximal pumping rate (69 +/- 13 beats/min) termed 100%, and then 80%, 60%, and 40% of the maximal pumping rate in the full to empty mode. With increases in pumping rate, pressure-volume area and external work proportionally decreased, whereas potential energy remained unchanged except for 100% of maximal pumping rate. Pressure-volume area correlated linearly with myocardial oxygen consumption during asynchronous pulsatile left atrial to aortic bypass (r = 0.971). As a result, pumping rate correlated linearly with conservation of myocardial oxygen consumption (r = 0.998). In conclusion, decreased pressure-volume area accounts for the reduction in myocardial oxygen consumption during asynchronous pulsatile left atrial to aortic bypass. Conservation of myocardial oxygen consumption is mainly attributed to the reduction of external work.

Mechanical ventricular assistance: an economical and effective means of treating end-stage heart disease.

BACKGROUND: Heightened awareness of medical costs has escalated criticism toward expensive medical therapy. METHODS: The use of ventricular assistance devices (VADs) at Pennsylvania State University as a bridge to transplantation was reviewed. Records of 43 patients listed as status 1 from July 1991 to July 1994 were compared. RESULTS: This analysis demonstrated that for all patients treated with the intent to transplant, those who were bridged with a VAD exhibited a trend toward an improved transplantation rate (92% versus 68%) and a significantly greater rate of discharge from the hospital (92% versus 55.4%; p = 0.023) than the medically managed patients. Although overall charges and costs were higher in VAD-supported patients, this was related to significantly longer pretransplantation hospitalization. When normalized to daily costs and charges, this discrepancy in expenses was eliminated. CONCLUSIONS: The superior rate of discharge at equitable daily costs and charges for the VAD patients draws continued enthusiasm toward use of these devices as a bridge to transplantation. Furthermore, development of outpatient care for VAD-supported patients and continued advances in the use of these devices may further reduce the cost of managing these critically ill patients.

Long-term left ventricular assist device use before transplantation.

Between September 1992 and April 1995, 19 patients at the authors' institution received pneumatic, pulsatile left ventricular assist devices (LVADs) for bridging to cardiac transplantation. The mean (+/- SD) age of the patients was 51 +/- 14 years (range, 19-64 years). Nine (47%) patients had end-stage idiopathic cardiomyopathy, five (26%) had ischemic cardiomyopathy, and five (26%) other recipients were in cardiogenic shock caused by acute myocardial infarction (AMI). Fifteen (79%) patients were supported with an intraaortic balloon pump or centrifugal LVAD at the time of LVAD insertion (duration, 5.5 +/- 4.1 days). Aprotinin was given to limit bleeding; heparin, followed by warfarin sodium, was used for anticoagulation. A vigorous exercise and nutrition protocol was followed. Cardiac index averaged 2.94 +/- 0.87 L/min/m2 immediately after the implantation procedure. No patient required placement of a right VAD. Average duration of LVAD support was 45 +/- 39 days (range, 3-153 days). Major complications included bleeding requiring reoperation (three patients); cerebrovascular accident (three patients); and severe dysrhythmias requiring direct current cardioversion (four patients). Fourteen (74%) patients underwent transplantation, with one patient still being mechanically supported. All of the patients receiving transplants were discharged from the hospital. Of the individuals who died while supported with the LVAD, 75% were patients with AMI. Timely application of LVADs as part of the interdisciplinary management of end-stage heart disease has generated excellent results for transplant candidates. Right ventricular dysfunction has not necessitated right VAD placement in the authors' experience. Patients with AMI have a higher risk of death while being supported with the device than do more chronically ill recipients.

Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart in conjunction with heart transplantation: sixth official report--1994.

BACKGROUND: The Combined Registry has existed since 1985 with a design toward the voluntary submission of data from centers undertaking mechanical circulatory assistance. METHODS: The compiled results of the Combined Registry for the Clinical Use of Mechanical Ventricular Assist Pumps and the Total Artificial Heart was reviewed and subjected to strict statistical evaluation. RESULTS: More than 2000 implanted devices have been reported through January 1994, and 584 of these have been placed with the intention of bridge to heart transplantation. Nearly 70% of these patients have subsequently undergone heart transplantation, and 69% of those patients have survived to discharge from the hospital. Outcome statistics continue to favor isolated left ventricular support, although only discharge rates are significantly improved over right (p = 0.01) or biventricular assistance (p < 0.001) and the total artificial heart (p < 0.001). Within the group of left ventricular devices no individual mode of support proved advantageous over the others for transplantation or discharge rates. The 30-day mortality for all devices is approximately 36%, which remains much higher than that for orthotopic heart transplants. Isolated left ventricular support, however, had a 30-day mortality of only 9% with similar improvement in 12- and 24-month survival. CONCLUSIONS: These data show the continued success with these devices for bridging critically ill patients to transplantation. Additionally, it supports the ongoing development of devices implanted for long-term use, which might replace orthotopic transplantation for those patients currently deemed marginal candidates.