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.     

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.     

In vivo evaluation of the miniaturized Gyro centrifugal pump as an implantable ventricular assist device

A method has been developed for the rapid molecular mass determination and structural elucidation of mixtures of oligosaccharides derived from plant cell walls. The oligosaccharides were fractionated using gel permeation chromatography and 'analytical' high-performance anion-exchange chromatography (HPAEC), neutralized, dried and the mixtures of eluent salt and oligosaccharides were per-O-acetylated directly. The derivatized oligosaccharides were isolated by dissolution in dichloromethane and the salts were removed by aqueous partitioning. The per-O-acetylated oligosaccharides were analysed using electrospray (ES) and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MS). Exploiting the fact that acid-catalysed per-O-acetylation of oligosaccharides can be achieved even under the extremely salty conditions that are found in post-column neutralized HPAEC fractions, and combining this derivatization step with off-line ESMS, allow rapid screening for molecular mass and thus yield information on the composition of the various oligosaccharides in these complex mixtures. Subsequent per-O-methylation of the per-O-acetylated, salt-free fractions and collision-induced dissociation tandem mass spectrometric analysis was used for additional sequence and branching determination of the oligosaccharides.     

Left ventricular diastolic filling alterations in subjects with mitral valve prolapse: a Doppler echocardiographic study

To assess left ventricular diastolic filling in mitral valve prolapse (MVP), we studied 22 patients with idiopathic MVP and 22 healthy controls matched for sex, age, body surface area and heart rate. A two-dimensional, M-mode and Doppler echocardiographic examination was performed to exclude any cardiac abnormalities. The two groups had similar diastolic and systolic left ventricular volumes, left ventricle mass and ejection fraction. Doppler measurements of mitral inflow were: E and A areas (the components of the total flow velocity-time integral in the early passive period of ventricular filling, E; and the late active period of atrial emptying, A), the peak E and A velocities (cm.s-1), acceleration and deceleration half-times (ms) of early diastolic rapid inflow, acceleration time of early diastolic flow (AT), total diastolic filling time (DFT) (ms), and the deceleration of early diastolic flow (cm.s-2). From these measurements were calculate: peak A/E ratio (A/E), E area/A area, the early filling fraction, the atrial filling fraction, AT/DFT ratio. All the Doppler measurements reported are the average of three cardiac cycles selected at end expiration. The mean peak A velocity, A/E velocity ratio, deceleration half time and atrial filling fraction were each significantly higher for subjects presenting a MVP (60 +/- 12 cm.s-1 vs 49 +/- 14, P < 0.008; 98 +/- 13% vs 64 +/- 12%, P < 0.0001; 120 +/- 36 ms vs 92 +/- 11, P < 0.002; 0.45 +/- 0.14 vs 0.36 +/- 0.08, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Left ventricular perimysial collagen fibers uncoil rather than stretch during diastolic filling

Workers in the pulp and paper industry are exposed to different substances, such as hydrogen sulfide and other reduced sulfur compounds, chlorine, chlorine dioxide, sulfur dioxide, terpenes, and paper dust. The exposure level depends on the process, i.e., sulfite, sulfate, groundwood, bleachery, or paper production. Hitherto, exposures have been poorly described and more studies are certainly needed. Workers with repeated exposure peaks to chlorine, e.g., bleachery workers, seem to have an impaired lung function and an increased prevalence of respiratory symptoms. Exposure to high levels of paper dust, (> 5 mg/m3) causes impaired lung function. Therefore, exposure to respiratory irritants is an important, and probably overlooked, occupational risk among certain groups of pulp and paper workers. Some studies indicate that sulfate workers with high exposure to reduced sulfur compounds have an increased mortality due to ischemic heart disease. However, before any definite conclusions can be drawn, the impact of important confounders, such as shift-work and smoking habits have to be further evaluated.     

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.     

Left ventricular systolic torsion and early diastolic filling by echocardiography in normal humans

This study describes a novel 2-dimensional echocardiographic technique to measure left ventricular (LV) systolic twist in humans and relates this measure to early ventricular filling. LV twist is the counterclockwise rotation of the left ventricle during systole when viewed from the apex. The effect of ventricular twist has been postulated to store potential energy, which ultimately aids in diastolic recoil, leading to ventricular suction. The generated negative early diastolic pressures may augment early ventricular filling. We measured ventricular twist in 40 patients with normal transthoracic echocardiograms. End-systolic twist was determined by measuring rotation of the anterolateral papillary muscle about the center of the ventricle. LV filling was assessed by analysis of transmitral Doppler flow velocities. The mean value obtained was 9 +/- 7 degrees of rotation. Twist measurements were highly reproducible with an intraobserver correlation coefficient of r = 0.881, p <0.001. The magnitude of ventricular twist was strongly correlated positively with acceleration of the mitral E-wave (r = 0.75; p <0.0001) and negatively with the mitral E-wave acceleration time (r = -0.83; p <0.0001).     

Right ventricular diastolic filling: evaluation with velocity-encoded cine MRI

BACKGROUND AND PURPOSE: It has been reported that some angiotensin converting enzyme inhibitors can prevent stroke-prone spontaneously hypertensive rats from stroke at much higher doses than clinical doses used for hypertension therapy. This study was performed to investigate the prophylactic effectiveness of imidapril against stroke in comparison with enalapril. METHODS: Salt-loaded stroke-prone spontaneously hypertensive rats were orally given imidapril (0.5, 1, 2, and 5 mg/kg per day), enalapril (2 and 5 mg/kg per day), or hydralazine (5 mg/kg per day). Stroke signs were scored, and blood pressure, protein concentration, and N-acetyl-beta-D-glucosaminidase activity in urine were measured. After 2 weeks of medication, angiotensin converting enzyme activities in the aorta were measured 24 hours after dosing. RESULTS: In the control group, severe hypertension developed, and all rats died within 12 weeks because of stroke. Imidapril and enalapril dose-dependently decreased the stroke-related mortality, and both agents at 5 mg/kg per day showed excellent prophylaxis, although they did not inhibit hypertensive development. Imidapril at 0.5 mg/kg per day significantly prevented stroke to almost the same extent as enalapril at 2 mg/kg per day or hydralazine at 5 mg/kg per day. Imidapril dose-dependently suppressed the elevation of the two urinary indexes, which was followed by stroke. Imidapril inhibited enzyme activity in the aorta more strongly than did enalapril at the same dose. CONCLUSIONS: Imidapril prevented the incidence of stroke in stroke-prone spontaneously hypertensive rats at a dose of 0.5 mg/kg per day or more by amelioration of kidney dysfunction. Reduction of blood pressure is not necessary, although enzyme inhibition in the vasculature may partly relate to the effect.     

Durability testing of components for the Jarvik 2000 completely implantable axial flow left ventricular assist device

A cable-lead tester and real time bearing tester have been developed with provisions to test future implantable electronics, transcutaneous energy transfer system (TETS), and related interconnect cabling designs. The cable/lead tester, used in 1997 to test a previously considered implantable bellows-connector-cabling system, can test up to 10 samples at a time. X-Y-Z-theta motions are applied to the proximal end of the test specimen with its distal end fixed. The real time bearing tester is of a mock loop configuration with the bearings under test housed in a fully functional, Good Manufacturing Practices assembled axial pump. A simulated left ventricular pulsatile preload is applied to the inflow of the axial pump, while its outflow is subjected to an 80 mmHg aortic afterload by pumping into a fixed height tube with no outflow restriction. The heated blood bath saline used in this system is UV sterilized and mechanically filtered by use of a commercial salt water conditioning system attached external to the main preload fluid reservoir. The cable-lead tester and real time bearing tester design include provisions to house a complete Jarvik 2000 left ventricular assist device (Transicoil Medical, Norristown, PA) for in vitro system testing.     

Transient normalization of systolic and diastolic function after support with a left ventricular assist device in a patient with dilated cardiomyopathy

A 19-year-old man who had fulminant heart failure caused by an idiopathic dilated cardiomyopathy was supported with a left ventricular assist device for 183 days as a bridge to heart transplantation. At the time of intended transplantation it was noted that the patient's heart had returned to normal size, had a normal ejection fraction, and was able to maintain normal pressures and flows. In view of the apparent recovery of cardiac properties, the left ventricular assist device was explanted and the transplantation was not performed. However, the heart dilated, ejection fraction worsened, and the patient died of heart failure exacerbated acutely by a systemic viral illness. Although such recovery of systolic function is uncommon, as use of the left ventricular assist devices becomes more widespread other physicians might encounter similar findings and, in this regard, they might find our experience useful as they contemplate their treatment options.     

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.     

Left ventricular diastolic stiffness in dogs with congestive cardiomyopathy and volume overload

Mean functional diastolic stiffness, an estimate of the left ventricular resistance to filling during diastole, was measured in 10 normal dogs, 7 dogs with diseases causing volume overload (patent ductus arteriosus and primary mitral valve insufficiency), and 4 dogs with idiopathic congestive cardiomyopathy. It was measured as the increase in pressure during diastole (deltaP), divided by the corresponding increase in volume (deltaV). The pressure was measured at cardiac catheterization, and the volume was derived by a cineangiocardiographic method. There was no increase in diastolic stiffness of the hearts with volume overload compared with the normal hearts, but those with cardiomyopathy had a large increase, although the end-diastolic volumes in cardiomyopathy were generally less than in volume overload.     

Left ventricular diastolic function in young men with high normal blood pressure

OBJECTIVE: Abnormalities in left ventricular (LV) diastolic filling have been reported in hypertensive patients. This study was designed to compare LV diastolic filling between individuals with high normal blood pressure (HNBP) and optimal blood pressure (OBP). SUBJECTS AND DESIGN: From a survey of 219 young male individuals (age 21 +/- 0.1 years), two groups were selected according to their BP (group A: systolic BP [SBP] 120 mmHg and diastolic BP [DBP] 80 mmHg, n = 23 and group B: SBP 130 to 139 mmHg and/or DBP 85 to 89 mmHg, n = 21). Subjects habits, anthropometric characteristics, LV structure and systolic and diastolic function were compared. RESULTS: No differences were detected between the two groups in habits, systolic function or early diastole. LV mass index (LVMI) was higher in group B (103.6 +/- 4.58 g/m2 versus 90.49 +/- 3.27 g/m2 in group A, P < 0.05), though the values were not high enough to indicate LV hypertrophy. The pattern of LV late filling was different between the two groups. The peak late diastolic flow velocity (A) was 0.45 +/- 0.02 m/s in group B and 0.52 +/- 0.03 m/s in group A (P < 0.05). The early peak velocity (E):A ratio was 1.82 +/- 0.08 in group A and 1.59 +/- 0.08 in group B (P < 0.05). The early filling fraction also demonstrated a significant shift to more prominent late diastolic filling in group B (0.68 +/- 0.01% versus 0.73 +/- 0.01% in group A, P < 0.05). This pattern in LV filling did not correlate to inheritance, age, sex, heart rate, habits or body mass index. CONCLUSIONS: This shift in filling pattern to a late flow in young men with HNBP seemed to be an early indicator of an increased dependence of LV filling on atrial contraction and may reflect an impairment in LV relaxation.     

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.