Assessment of timing right ventricular assist device withdrawal using left ventricular assist device filling characteristics

Right ventricular assist devices (RVAD) are often needed on a short term basis in patients who develop RV failure after left ventricular assist device (LVAD) implantation. The purpose of this study was to use LVAD filling characteristics to help determine the timing for weaning a patient from RVAD support. Eleven patients (age 50 years +/- 15) supported with an LVAD (Novacor) and an RVAD (Biomedicus or ABIOMED) were studied. Eight patients (RV recovery group) were studied before RVAD removal and all were successfully weaned from RVAD support. Five patients (RV failure group) were studied at the time of RVAD placement to determine baseline characteristics of RV failure. Simultaneous measures of LVAD volume and routine hemodynamics were recorded during periods of high and low RVAD flow. The LVAD filling was assessed as the first derivative of LVAD volume and the mean filling rate for each cardiac cycle was calculated and averaged over 10 sec periods at both RVAD flows. The mean pump rate corrected filling rates did not change in the RV recovery group (89 +/- 13 vs. 87 +/- 8 ml/beat) and significantly decreased in the RV failure group (84 +/- 19 vs. 62 +/- 22 ml/ beat) (p < 0.001) with decreasing RVAD flow. These data suggest that LVAD filling rates may be used to assess RV systolic function and the proper timing of RVAD removal in selected patients.     

Clinical experience for ventricular assist device

We began applying of our VAD system clinically in 1982 and have subsequently obtained good results. The first case treated with the VAD returned to normal life. In a total of 70 cases of clinical applications this system there has been instance of apparatus dysfunction. Confirming the reliability and safety promised by the results of biological experiments. Here, we report the results of clinical application of the system in a total of 61 cases between August, 1985 and March, 1989. The following conclusions were reached: 1) Satisfactory weaning and survival rates were obtained i.e. 18 cases out of 61 cases (30%) survived over one month and 13 cases (21%) are currently surviving, even in elderly patients of 60 years of age or older. 2) The weaning rate and survival rates were good after approximately 1 week of support. Detailed evaluation of the recovery of the heart and functions of other major organs has led to the conclusion that the results can be improved further when the weaning period is carefully determined. 3) With regard to surgical factors, good findings were obtained when the artificial heart-lung bypass time was less than 6 hours. The VAD can be used in the early stages without vainly attempting weaning from the artificial heart-lung bypass. 4) There were no mechanical problems with the hardware of the blood pump drive assembly, etc., or noteworthy side effects.     

Long-distance transportation of patients with a paracorporeal left ventricular assist device

Patients in cardiogenic shock refractory to basic medical therapy may require specialised assistance in a multispeciality environment distant to the institution where they are first admitted. In such situations, transportation of these critical patients may be difficult and involve many risks. Here we describe the case histories of two patients who underwent implantation of a paracorporeal left ventricular assist device and were transferred to specialised institutions for extended treatment. The distance of transportation was 400 km and the patients were transported by ambulance and helicopter. Some aspects of logistics and complexity of long-distance transportation are also commented on.     

Replacement of an intracorporeal left ventricular assist device

An intracorporeal left ventricular assist device was placed as a bridge to cardiac transplantation in a 51-year-old man after an acute myocardial infarction. After 126 days of support, the left ventricular assist device malfunctioned. The pump, which had a tear in its pneumatic drive line, was successfully replaced.     

Circulatory support with pneumatic paracorporeal ventricular assist device in infants and children

BACKGROUND: Mechanical circulatory support in intractable heart failure in children has been limited to centrifugal pumps and extracorporeal membrane oxygenation: Since 1990 small adult-size pulsatile air-driven ventricular assist devices "Berlin Heart" (VAD) and, since 1992 miniaturized pediatric VAD (12, 15, 25, 30 mL pumps), have been used in our institution. Since 1994 the blood-contacting surfaces of the device system have been heparin-coated. In this report the experiences with VAD support in 28 children are presented. METHODS: In 28 children-ages between 6 days and 16 years-the Berlin Heart VAD has been applied for periods of between 12 hours and 98 days (mean, 16.9 days) aiming at keeping the patient alive and allowing for recovery from shock sequelae until later transplantation or myocardial recovery. There were three groups. Group I: with primary intention of "bridge-to-transplantation" in various forms of cardiomyopathy (n = 13) or chronic stages of congenital heart disease (n = 5). Group II: "Rescue" in intractable heart failure early after corrective surgery for congenital heart disease (n = 4) or in early graft failure after a heart transplantation (n = 1). Group III: "Acute myocarditis" (n = 5) aiming at either myocardial recovery or transplantation. Twelve were brought to the operating room under cardiac massage and 25 had been on the respirator for more than 24 hours. RESULTS: Twelve patients died on the system from sequelae of profound shock-multiorgan failure, sepsis, loss of peripheral circulatory resistance-or from hemorrhagic complications (n = 4) or brain death (n = 1). Thirteen patients (groups I and III) were transplanted after support periods of between 3 and 98 days with 7 long-term survivors living now up to 7.5 years (mean, 4.4 years). Three patients (groups II and III) were weaned from the system with two long-term survivors (both in group III). There were no patients in group II who survived and the "rescue" indication has been discarded for VAD since 1992. Such patients are since treated by extracorporeal membrane oxygenation (ECMO) in our institution. Out of the 8 patients placed on VAD during 1996 and 1997, 7 were successfully supported until transplantation or weaning. Thirteen patients were extubated and mobilized on the system. Whereas with the earlier systems thrombi in the blood pumps were seen in 15 instances and 2 patients suffered from thromboembolic complications, no thrombotic events occurred with the heparin-coated systems. CONCLUSIONS: After accumulating clinical experience and several technical improvements since 1990 the use of the pediatric Berlin Heart VAD has matured into a reliable and safe system to keep patients with otherwise intractable heart failure alive until complete myocardial recovery is reached or transplantation becomes feasible. Whereas heart failure early after cardiac operation is now primarily treated by ECMO, acute myocarditis appears to be a promising precondition for complete cardiac recovery during VAD support.     

Emergency versus elective/urgent left ventricular assist device implantation

BACKGROUND: The risk and outcome in patients undergoing left ventricular assist device (LVAD) implantation on an emergency basis is still unclear. METHODS: Since April 1993, 40 patients received a Novacor and 8 patients a Heartmate LVAD in our institution. Patients with emergency LVAD placement were compared with the remainder in a retrospective manner. Parameters studied included underlying heart disease, preimplantation dysfunction of kidney, liver, lung, and cerebrum, interval of mechanical support, outcome, and complications. RESULTS: Patients with emergency LVAD placement predominantly were seen with postcardiotomy heart failure (47%) or acute myocarditis (20%) (group A) whereas elective and urgent candidates for LVAD implantation mainly had dilative cardiomyopathy (67%) or ischemic heart disease (30%) (group B). The incidence of secondary organ failure was significantly higher for all organs in group A patients (p < .01). Mean support interval in patients who underwent emergency LVAD implantation was lower (74+/-79 days vs 115+/-80 days), and fewer patients could be forwarded to heart transplantation in this group (22% vs 78%, p < .01). Moreover, bleeding complications were increased in group A (66% vs 30%, p < .01), but not thromboembolism and infection. CONCLUSION: In conclusion, the overall success rate after emergency LVAD implantation was lower, with bleeding being the most frequent complication. To achieve acceptable outcomes in disastrous situations, LVADs should be placed as early as possible.     

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). Conclusion: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.     

Low incidence of myocardial recovery after left ventricular assist device implantation in patients with chronic heart failure

BACKGROUND: Mechanical, histological, and biochemical improvement has been described in patients after left ventricular assist device (LVAD) support. Explantation of the LVADs without heart transplantation has been described in selected patients who received this therapy as a bridge to transplantation. METHODS AND RESULTS: A retrospective review of patients receiving a mechanical bridge to transplantation at Columbia Presbyterian Hospital after July 21, 1991, was performed to determine the incidence of patients in whom the device was successfully explanted. From August 1, 1996, to February 1, 1998, we prospectively attempted to identify potential explant candidates by the use of exercise testing. During this time, we recruited 39 consecutive patients after insertion of the Thermo Cardiosystems vented electric device to participate in the following study. Approximately 3 months after device implantation, a maximal exercise test with hemodynamic monitoring and respiratory gas analysis was performed with the LVAD in the automated mode. The electric device was interfaced with a pneumatic console such that the rate could be decreased to 20 cycles/min. Hemodynamic measurements were recorded as the device rate was decreased. A repeat exercise test was then performed if the patient remained hemodynamically stable. A retrospective chart review of 111 LVAD recipients at our institution identified only 5 successful explant patients. Eighteen of the 39 patients were studied. Fifteen patients exercised with maximal device support. At peak exercise, VO2 averaged 14.5+/-3.6 mL. kg-1. min-1; LVAD flow, 8.0+/-1.3 L/min; Fick cardiac output, 11.4+/-3.3 L/min; and pulmonary capillary wedge pressure, 13+/-4 mm Hg. Seven patients remained normotensive and could exercise at a fixed rate of 20 cycles/min. In these patients, peak VO2 declined from 17.3+/-3.9 to 13.0+/-6.1 mL. kg-1. min-1. In one of these patients, the device was explanted. CONCLUSIONS: Significant myocardial recovery after LVAD therapy in patients with end-stage congestive heart failure occurs in a small percentage of patients. Most of these patients have dilated cardiomyopathy. Exercise testing may be a useful modality to identify those patients in whom the device can be explanted.     

Monocyte tissue factor-like activity in post myocardial infarction patients

It is widely recognized that thrombosis is the major event in the evolution of stable vascular disease to unstable ischaemic syndromes including myocardial infarction and stroke. The purpose of this case-control study was to establish clinical and laboratory data on the possible relationship between specific components of the haemostatic system and coronary heart disease. The procoagulant activity (PCA) of peripheral monocytes and polymorphonuclear neutrophils was assessed in 21 males who had suffered a myocardial infarction (MI) and in age-matched controls. In addition, total factor VII activity, fibrinogen, tissue factor pathway inhibitor (TFPI). D-dimers, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), tumour necrosis factor-alpha (TNF-alpha) and full blood counts were measured. Post MI patients had significantly higher monocyte PCA, higher plasma concentrations of TFPI, fibrinogen, t-PA, T/P100 and also higher total white blood cell and neutrophil counts compared to age-matched controls. This elevated procoagulant state in post MI patients could further exacerbate the disease process and increase the risk of subsequent acute ischaemic events.     

Hemodynamic and physiologic changes during support with an implantable left ventricular assist device

To evaluate hemodynamic effectiveness and physiologic changes on the HeartMate 1000 IP left ventricular assist device (Thermo Cardiosystems, Inc., Woburn, Mass.), we studied 25 patients undergoing bridge to heart transplantation (35 to 63 years old, mean 50 years). All were receiving inotropic agents before left ventricular assist device implantation, 21 (84%) were supported with a balloon pump, and 7 (28%) were supported by extracorporeal membrane oxygenation. Six patients died, primarily of right ventricular dysfunction and multiple organ failure. Nineteen (76%) were rehabilitated, received a donor heart, and were discharged (100% survival after transplantation). Pretransplantation duration of support averaged 76 days (22 to 153 days). No thromboembolic events occurred in more than 1500 patient-days of support with only antiplatelet medications. Significant hemodynamic improvement was measured (before implantation to before explantation) in cardiac index (1.7 +/- 0.3 to 3.1 +/- 0.8 L/min per square meter; p < 0.001), left atrial pressure (23.7 +/- 7 to 9 +/- 7.5 mm Hg; p < 0.001), pulmonary artery pressure, pulmonary vascular resistance, and right ventricular volumes and ejection fraction. Both creatinine and blood urea nitrogen levels were significantly higher before implantation in patients who died while receiving support. Renal and liver function returned to normal before transplantation. We conclude that support with the HeartMate device improved hemodynamic and subsystem function before transplantation. Long-term support with the HeartMate device has a low risk of thromboemboli and makes a clinical trial of a portable HeartMate device a realistic alternative to medical therapy.     

Long-term in vivo left ventricular assist device study with a titanium centrifugal pump

A totally implantable centrifugal artificial heart has been developed. The plastic prototype, Gyro PI 601, passed 2 day hemodynamic tests as a functional total artificial heart, 2 week screening tests for antithrombogenicity, and 1 month system feasibility. Based on these results, a metallic prototype, Gyro PI 702, was subjected to in vivo left ventricular assist device (LVAD) studies. The pump system employed the Gyro PI 702, which has the same inner dimensions and the same characteristics as the Gyro PI 601, including an eccentric inlet port, a double pivot bearing system, and a magnet coupling system. The PI 702 is driven with the Vienna DC brushless motor actuator. For the in vivo LVAD study, the pump actuator package was implanted in the preperitoneal space in two calves, from the left ventricular apex to the descending aorta. Case 1 achieved greater than 9 month survival without any complications, at an average flow rate of 6.6 L/min with 10.2 W input power. Case 2 was killed early due to the excessive growth of the calf, which caused functional obstruction of the inlet port. There was no blood clot inside the pump. During these periods, neither case exhibited any physiologic abnormalities. The PI 702 pump gives excellent results as a long-term implantable LVAD.     

Influence of longer term left ventricular assist device support on valvular regurgitation

The authors previously published data that describe acute alterations in ventricular dimensions and in the severity of mitral and tricuspid regurgitation (MR/TR) after initiation of left ventricular assist device (LVAD) pumping. In the current study, measurements of ventricular size and regurgitant jet area acquired after LVAD implantation are presented. Eight patients had LVAD implanted pending cardiac transplantation (duration of assist 70-279 days; mean, 162 +/- 29 days). Echocardiograms were obtained at the time of LVAD implant and later during LVAD support (mean time for late echo, 95 +/- 32 days post-implant). Comparisons of pre-implant with late post-implant data showed: increased TR jet area (4.8 +/- 1.0 cm2 vs. 8.0 +/- 1.7 cm2 P < 0.05); increased right ventricular (RV) end-systolic dimension (31 +/- 4 vs 40 +/- 5 mm, P < 0.05); and increased RV end-diastolic dimension (35 +/- 4 vs. 45 +/- 5 mm, P < 0.065). Decreased MR jet area and decreased LV dimensions (P < 0.05) also were noted on comparison of pre-implant and late post-implant data. There were no significant differences between any immediate post-implant and late post-implant echocardiographic measurements. No patient had clinical evidence of RV failure. LV mechanical assist causes an acute increase in TR, presumably by volume loading the RV. TR and RV enlargement persisted but did not discernibly worsen on subsequent post-implant echocardiograms. LV dimensions and MR remained less than the pre-implant values on later post-implant determinations.     

Platelet glycoprotein IIb/IIIa inhibitor attenuates complement activation during in vitro ventricular assist circulation

Complement activity and platelet glycoprotein (GP) IIb/IIIa dysfunction have been demonstrated during in vitro ventricular assist device circulation. Platelets contain C1 serine protease inhibitor (C1 INH) in secretory granules, which normally regulates complement. Complement activity may result from a loss of platelet regulation on complement during ventricular assist device circulation as platelets lose viability. The purpose of this study was to assess the ability of a platelet GP IIb/IIIa receptor inhibitor to attenuate ventricular assist device associated complement activation during in vitro ventricular assisted circulation. Eight in vitro nonpulsatile centrifugal ventricular assist device circuits were simulated for 4 days using 450 ml fresh human whole blood. Cardiac index, temperature, pH, PO2, PCO2, Ca, glucose, and activated clotting time were maintained at physiologic levels. Levels of C1 INH and C3a were measured with and without a reversible glycoprotein IIb/IIIa inhibitor (MK-383). Concentrations of C1 INH increase on exposure to ventricular assist device, and decrease to a plateau within 12 hr. The decrease in circulating unbound C1 INH was attenuated with pre treatment with MK-383. Concentrations of C3a increase 34 fold within 4 hr of exposure to a ventricular assist device with and 22 fold without pre treatment with MK-383. These findings suggest that protection of the platelet GP IIb/IIIa complex delays complement activation during in vitro ventricular assist device circulation.     

Extracorporeal life support as a post left ventricular assist device implant supplement

Extracorporeal life support (ECLS) is indicated following left ventricular assist device (LVAD) implant for right heart failure or pulmonary dysfunction. From December 1991 to December 1996, 100 patients were supported with the implantable HeartMate LVAD. Of these, 12 patients were supported with ECLS post LVAD implant. Pre-operatively, 10 patients (83%) were on an intra-aortic balloon pump, 9 patients (75%) were intubated, and 8 patients (67%) required ECLS bridge to LVAD implant. Six patients (50%) were men, and patient age ranged from 28 to 63 years (mean 46 +/- 10 years). Duration of ECLS averaged 3 +/- 2 days (range, 1-9 days). Eight patients (67%) required a right ventricular assist device (RVAD) with an ECLS circuit, three patients (25%) required peripheral veno-venous ECLS, and one patient peripheral veno-arterial ECLS. Forty-five percent supported with ECLS post LVAD survived to transplant compared with the 81% supported with LVAD only. Early in this experience, three patients had RVAD support only and all three patients died. RVAD support (with or without ECLS) was 11% overall and declined from 14% in the first 50 patients to 8% in the second 50. ECLS post LVAD is relatively uncommon and its use is associated with reduced survival, but helps salvage these critically ill patients.     

A novel implantable electromechanical ventricular assist device. First acute animal testing

A method for the simultaneous determination of eight kinds of conjunct bile acids in human bile was developed by HPLC. They were separated on a YWG-C18 (3 microns) column at 30 degrees C, with methanol/water (65/35, V/V, pH3.0) as mobile phase, and detection wavelength at UV 210 nm. The linear ranges were 50-1,000 microns.ml-1, the recoveries were 91.2%-108.6%. The biles of 30 cases with cholelithiasis cholecystolithiasis and 20 cases without gallstone were detected by HPLC. The results showed that the constitution of bile acids was different between patients with cholelithiasis cholecystolithiasis and patients without gallstone.