[Hemodynamics and physical capacity in patients with left ventricular assist devices : An overview]. / Hämodynamik und körperliche Belastbarkeit bei Patienten mit Linksherzunterstützungssystem : Ein Überblick.

In the course of time implantation of left ventricular assist devices (LVAD) has become an alternative to heart transplantation due to the enormous technical developments and miniaturization of these systems. Following implantation most patients show a significant improvement in their clinical condition and exercise capacity as measured by the New York Heart Association (NYHA) classification; nevertheless, exercise tolerance remains clearly limited even after LVAD implantation. The complex physiological and hemodynamic changes in LVAD patients both at rest and during exercise are ultimately not completely understood. The aim of this article is to describe the current state of scientific knowledge with respect to the physical capacity of patients with terminal heart failure after LVAD implantation at rest and during exercise. The influence of increasing the pump speed and continuous physical exercise training on the physical capacity in the long-term course is reviewed. The significance of new diagnostic tools, such as the non-invasive inert gas rebreathing method for measurement of cardiac output and arteriovenous oxygen difference (AVDO2) in assessment of the performance of LVAD patients is discussed.

Bosentan effects on hemodynamics and clinical outcome in heart failure patients with pulmonary hypertension awaiting cardiac transplantation.

BACKGROUND: In heart failure (HF) patients, pulmonary hypertension (PH) is associated with a poor prognosis. We assessed whether low dose treatment with the dual endothelin-1 receptor antagonist bosentan is associated with improved hemodynamics and clinical outcome in these patients. METHODS: We performed a retrospective data analysis in 82 end-stage heart failure patients on the waiting list for cardiac transplantation since January 2006. All patients had pulmonary arterial pressure >35 mmHg, pulmonary vascular resistance >240 dyn × s × cm-5, and/or a transpulmonary gradient (TPG) >15 mmHg. Fifty-four patients received a median dose of 125 mg bid bosentan (BOS group), and 28 patients received standard medical treatment (CON group). Data were assessed until June 2009. RESULTS: Hemodynamic parameters improved significantly in the BOS group but remained unchanged in the CON group. The percentage of patients who fell below the thresholds of PAP, PVR, and TPG for cardiac transplantation increased significantly by 20.3%, 34.5%, and 20.8%, respectively (p = 0.007-0.013) in the BOS group, but did not change significantly in the CON group. One-year survival on the waiting list was approximately 20% higher in the BOS group than in the CON group (p = 0.020). Bosentan treatment remained an independent predictor of reduced mortality risk on the waiting list after propensity score adjustment (relative risk = 0.107; 95% CI: 0.013-0.869; p = 0.036). CONCLUSION: Treatment with the endothelin-1 antagonist bosentan is associated with improvements in hemodynamics and clinical outcome in end-stage heart failure patients with PH. If these results can be confirmed by randomized controlled trials, bosentan may represent a treatment option in these patients.

Cardiac retransplantation: a 15-year single-center clinical experience.

BACKGROUND: Cardiac retransplantation is a controversial therapy because of the shortage of donor hearts. We retrospectively reviewed the short-term and long-term outcomes after cardiac retransplantation. METHODS AND RESULTS: Twenty-eight cases (18 males, 7 females; mean age, 50.3 +/- 13.5 years) underwent cardiac retransplantation: 25 first retransplantations and 3 second retransplantations. The indications for retransplantation were primary graft failure (PGF) in 11 patients (39.3%), intractable acute cardiac rejection (IACR) in 4 patients (14.3%), and coronary allograft vasculopathy (CAV) in 13 patients (46.4%). The patients had been supported as follows: prolonged cardiopulmonary bypass (CPB; n = 3), intra-aortic balloon pumping (IABP; n = 1), intravenous inotropic support (n = 7), extracorporeal membranoxygenator (ECMO; n = 3), ventricular assist device (VAD; n = 4), and no inotropic support (n = 10). There were 8 deaths within 30 days after retransplantation (28.6%). The overall 1-, 5-, 10-, and 15-year survival rates were 46.4%, 40.6%, 32.5%, and 32.5%, respectively. Acute cardiac rejection was the most common cause of death (43.8%). Thirty-day and 1-year survival rates of IACR, PGF, and CAV were 50.0%/0%, 63.6%/45.5%, and 84.6%/68.4%, respectively. CONCLUSIONS: Long-term survival after retransplantation was acceptable for patients with CAV and PGF; however, we must select patients for retransplantation carefully if the indication is IACR, because of the poor outcome.

Heart transplantation at the Heart Center North Rhine-Westfalia.

At the Heart Center North Rhine-Westfalia, Germany, more than 1,500 adult cardiac transplantations and more than 100 pediatric cardiac transplantations have been performed since the transplant program was initiated in 1989. Each year, we take care of 800 cardiac transplant recipients and 1,700 patients with heart failure who are in a long-term program for cardiac transplantation or on the Eurotransplant waiting list for cardiac transplantation. We have experience with ventricular assist device implantation as bridge to transplant in more than 300 patients. In total, our clinical know-how with cardiac transplant recipients is based on 10,800 patient-years of observation. In 2006, we transplanted the first donor heart worldwide with the Organ Care System, a technology capable of maintaining human organs in a functioning state ex-vivo. Usually, our transplant recipients have more preoperative risk factors than cardiac transplant recipients at other German heart centers. Our postoperative patient care is individualized with respect to immunosuppression and the performance of myocardial biopsies and coronary angiography. Since 1989, we have performed 31 cardiac retransplantations.

Direct detection of red blood cell fragments: a new flow cytometric method to evaluate hemolysis in blood pumps.

Pump induced hemolysis is presently evaluated by measuring plasma free hemoglobin (fHb). However, this method has disadvantages because quantification of fHb depends on hematocrit (HCT) and hemoglobin (Hb) levels. The aim of this work was to devise a hemoglobin independent method, capable of quantifying cell trauma directly by measuring the number of red blood cell (RBC) fragments. Whole blood flow cytometry was used to quantify circulating RBC fragments derived from a roller pump (Sarns, Inc. Model 2 M 6,002) and a centrifugal pump (Gyro C1E3, Kyocera Corp.). The pumps were tested in a mock circuit for 2 hr (5 L/min flow against 100 mm Hg pressure head). Red blood cell fragments were quantified by a phycoerythrin (PE) labeled glycophorin A antibody specific for erythrocytes. Red blood cell fragments were smaller than the intact RBC population and overlapped in size with the platelet population (based on forward- and side-light scattering measurements). For the roller pump, the values for RBC fragments increased from 1,090 +/- 260/microl at 0 min to 14,880 +/- 5,900/microl after 120 min. In contrast, using the centrifugal pump, there was little increase in RBC fragments (from 730 +/- 270/microl at 0 min to 1,400 +/- 840/microl after 120 min). Flow cytometry can be used for the rapid, sensitive, hemoglobin independent evaluation of pump induced RBC trauma.

Low dose systemic heparinization combined with heparin-coated extracorporeal circulation. Effects related to platelets.

BACKGROUND: A heparin coated cardiopulmonary bypass system combined with full and low dose systemic heparinization in coronary bypass surgery was investigated in a prospective, randomised study. Roller pumps, coronary suction and an open cardiotomy reservoir were used. METHODS: One hundred and nineteen patients were divided into 3 groups: group A (n=39) had a standard uncoated extracorporeal circulation (ECC)-set and systemic heparin was given in an initial dose of 400 IE/kg body weight. During ECC activated clotting time (ACT) was kept at = or >480 sec. Group B (n=42) had the same ECC-set completely coated with low molecular weight heparin, i.v. heparin was administered in the same dose as in group A, ACT was again kept at = or >480 sec. Group C (n=38) had the same coated ECC set as group B, but i.v. heparin was reduced to 150 IE/kg and during ECC ACT was maintained of = or >240 sec. RESULTS: Platelet decrease was significantly less in both groups utilizing coated circuitry as compared to control group A. Activation of thrombocytes as marked by b-thromboglobulin (not PF4) was significantly decreased in patients treated with coated circuits combined with low dose systemic heparinization and postoperative bleeding was significantly reduced. CONCLUSIONS: We conclude that in heparin coated extracorporeal circulation combined with either full dose or reduced systemic heparinization compared to uncoated circuits platelet count reduction is significantly less. Platelet activation as marked by b-thromboglobulin and postoperative blood loss are decreased with coated equipment and low i.v. heparinization.

Outcome of heart transplantation in patients previously infected with hepatitis C virus.

The lack of knowledge about the course of hepatitis C virus infection (HCV) before heart transplantation (HTx) prompted us to describe our experience with 4 such patients who presented with positive HCV serology before surgery. Two experienced non-liver related deaths at 3.5 and 5 years after HTx, and none of the patients developed signs of hepatic insufficiency during the follow-up (mean 3.8 years). Tests for HCV antibodies were frequently negative, whereas viral RNA was detected in 81% of the measurements, showing that virus detection techniques seem to be more sensitive than serology techniques in detecting HCV infection in this group of patients. Although immunosuppression promotes active HCV replication, it does not seem to change the chronic features of HCV infection during the first years in patients with good liver function.

Hemodynamic exercise response in calves with an implantable biventricular centrifugal blood pump.

An implantable biventricular assist device (BVAD) has been developed at Baylor College of Medicine using 2 centrifugal blood pumps. The aim of this study was to investigate the exercise-reflex response during nonpulsatile biventricular assistance and to evaluate to which degree the autoregulation of the system would accommodate the changed hemodynamic situation during physical exercise. The Baylor Gyro PI 710 BVAD has been implanted into 2 calves (strain half-Dexter) in a biventricular bypass fashion with native heart remaining. Allowing a 10 day convalescence, 2 animals were subjected to incremental exercise tests. The speed of the treadmill was increased at zero slope from 0.7 mph to 1.5 mph with increments of 0.2 mph every 3 min. During the exercise the pump flows were maintained at a fixed rate (6.93 +/- 0.01 L/min for the left ventricular assist device and 5.36 +/- 1.44 L/min for the right ventricular assist device). Hemodynamic parameters and pump performance were recorded continuously. The cardiac output (CO) and heart rate (HR) increased significantly during the exercise. CO increased from 11.1 +/- 0.3 to 13.1 +/- 0.4 L/min, and HR increased from 99 +/- 7.1 to 114 +/- 2.8 bpm, respectively. Mean aortic pressure, central venous pressure, and left arterial pressure did not change significantly. Also, no change was observed for the left and right pump flows. This totally implantable BVAD showed excellent long-term performance without any mechanical problems. It is feasible to operate without impairment under physical activity. However, the natural heart dominated the hemodynamic response during exercise under BVAD support. The left and the right pump flows did not increase spontaneously with exercise. We therefore conclude that a servo CO control system is necessary to regulate pump flows even during moderate exercise.

Analysis of the arterial blood pressure waveform during left ventricular nonpulsatile assistance in animal models.

When the rotary blood pump is used as a left ventricular assist device (LVAD), the arterial blood pressure waveform changes with the LVAD condition. Based on evidence from an in vitro study, the change of the arterial blood pressure waveform during left ventricular assistance was evaluated using animal models. After the left pleural cavity was opened through the fifth intercostal space under general anesthesia, a rotary blood pump was implanted as an LVAD into 6 healthy calves. The direct left carotid arterial blood pressure waveform was measured and recorded by an oscilloscope. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). Similar to the in vitro study, the PI and PPI decreased exponentially with the increase of the LVAD assist ratio. By using this analysis methodology, a physiologically effective ventricular assistance might be achieved.

Impeller design for a miniaturized centrifugal blood pump.

The impeller design for a miniature centrifugal blood pump is an important consideration since the small diameter impeller requires higher rotational speed, which may cause more blood trauma compared to the larger diameter impeller. Three different impeller vanes (straight vanes with a height of 4 mm and 8 mm, and 8 mm curved vanes) of which the diameter was 35 mm were subjected to hydraulic performance and hemolysis tests in the same pump housing. Both straight vane impellers attained left ventricular assist condition (5 L/min against 100 mm Hg) at 2,900 rpm while the curved vane required 3,280 rpm. There was no significant hemolysis difference between the tall and short vanes. The curved impeller vanes did not exhibit sufficient hydraulic performance when compared to the straight vanes. The straight vane impellers, even with different heights, were incorporated into the same pump housings, and the vane heights did not drastically change the hydraulic performance or hemolysis.

Cardiac transplantation in patients with insulin-treated diabetes mellitus.

BACKGROUND AND METHODS: As documented earlier the incidence of cardiac mortality in diabetic patients due to coronary artery disease is high. Cardiac transplantation for congestive heart failure due to coronary artery disease, cardiomyopathy, and valvular diseases is obviously a therapeutic option in patients suffering from insulin-treated diabetes mellitus. To shed more light on this problem we performed a retrospective analysis of 40 patients with insulin-treated diabetes mellitus (three type-1; 37 type-2: insulin-treated for at least three months before cardiac transplantation) referred to our transplant unit for cardiac transplantation between March 1989 and December 1996. RESULTS: Orthotopic cardiac transplantation was performed in 40 patients (4 women, 36 men) aged 32-73 years (mean 56 years) with an insulin-treated diabetes mellitus preexisting for 3-348 months (mean 65.1 months). Donor age ranged from 15 to 72 years (mean 35.5 years) matched for body weight and blood group. Overall mortality in this group was 40.0% with an early mortality of 12.5%. CONCLUSIONS: Our results show that type-1/2 insulin-treated diabetes mellitus preoperative to heart transplantation is not a contraindication in patients suffering from end-stage heart failure. Adequate therapy of diabetes mellitus as well as individual immunosuppressive therapy are important in order to minimize additional organ damage caused by the drugs themselves or resulting infectious complications.

Analysis of the arterial blood pressure waveform using Fast Fourier Transform technique during left ventricular nonpulsatile assistance: in vitro study.

The arterial blood pressure waveform is variable during left ventricular assistance. The aim of this study is to examine the correlation between the left ventricular assist device (LVAD) condition and the arterial blood pressure waveform in a fixed cardiac output condition using a mock circuit. This mock circulation loop was composed of an aortic compliance chamber, a left atrial compliance chamber, a pneumatic pulsatile pump as a native heart, and a rotary blood pump representing the LVAD with left atrial drainage. The Fast Fourier Transform technique was utilized to analyze the arterial blood pressure waveform and calculate the pulsatility index (PI) and the pulse power index (PPI). The PI and PPI decreased with the increase of the LVAD rotational speed, exponentially. There was a significant negative correlation between the PI, PPI, and the LVAD rotational speed, flow rate, and assist ratio. The best correlation was observed between the PPI and the assist ratio (r = 0.986). From this viewpoint, an ideal LVAD condition may be estimated from the pulsatility change of the arterial blood pressure waveform.

Preclinical evaluation of a hollow fiber silicone membrane oxygenator for extracorporeal membrane oxygenator application.

A silicone membrane hollow fiber oxygenator applicable for use as an extracorporeal membrane oxygenator (ECMO) has been developed in our laboratory. This silicone hollow fiber displays astonishing mechanical stability, is barely compressible or stretchable, and assembles easily while maintaining good gas permeability. The priming volume is 140 cc with a surface area of 0.8 m2. This study evaluated the gas transfer performances and biocompatibility of the oxygenator under ECMO and CPB conditions. In vitro studies that were performed at a blood flow rate of 2 L/min, and revealed O2 and CO2 gas transfer rates of 82.35 +/- 0.56 ml/m2/L/min and 38.72 +/- 2.88 ml/m2/L/min, respectively. The commercially available Kolobow (Avecor 1500) oxygenator was used as the control, and had O2 and CO2 gas transfer rates of 53.8 +/- 0.5 ml/m2/L/min and 24.7 +/- 2.0 ml/m2/L/min. To evaluate blood trauma, Normalized Index of Hemolysis (NIH) was measured according to American Society of Testing and Materials (ASTM) standards. The NIH findings were 0.0112 g/100L at a blood flow of 1 L/min, and 0.0152 g/100L at 5 L/min. Three ex vivo experiments, using a blood flow rate of 1 L/min, were performed with venoarterial bypass, and O2 transfer rate and CO2 transfer rate of the oxygenators were well maintained. This indicates that this preclinical silicone membrane hollow fiber oxygenator has superior efficiency, less blood trauma, and is smaller when compared with the only clinically available Kolobow oxygenator.

Particles released from the Gyro C1E3 during simulated extracorporeal circulation.

Evaluation of released particles from the blood pump during extracorporeal circulation is an important aspect because the particles may cause microembolism. The Gyro C1E3 is a centrifugal blood pump that has an impeller suspended by double pivot bearings inside the housing; therefore, it is important to evaluate the released particles. The C1E3 was driven for 14 days to simulate clinical left ventricular assist device (LVAD) and percutaneous cardiopulmonary support (PCPS). Also, a roller pump was driven for 2 days as a comparison. Released particles were weighed and examined by SEM. After 14 days of pumping, the particles from the C1E3 were 238.6 microg in an LVAD condition. The particles with the roller pump were 270.2 microg after only 2 days. Average particle sizes with the roller pump and C1E3 were 3.7 and 0.6 microm, respectively. These results suggest that the Gyro C1E3 substantially reduces the risk of microembolism from released particles.

Development of the NEDO implantable ventricular assist device with Gyro centrifugal pump.

The Gyro centrifugal pump, PI (permanently implantable) series, is being developed as a totally implantable artificial heart. Our final goal is to establish a "functional TAH," a totally implantable biventricular assist system (BiVAS) with centrifugal pumps. A plastic prototype pump, Gyro PI 601, was evaluated through in vitro and in vivo studies as a single ventricular assist device (VAD). Based upon these results, the pump head material was converted to a titanium alloy, and the actuator was modified. These titanium Gyro pumps, PI 700 series, also were subjected to in vitro and in vivo studies. The Gyro PI 601 and PI 700 series have the same inner dimensions and characteristics, such as the eccentric inlet port, double pivot bearing system, secondary vane, and magnet coupling system; however, the material of the PI 700 is different from the PI 601. The Gyro PI series is driven by the Vienna DC brushless motor actuator. The inlet cannula of the right ventricular assist system (RVAS) specially made for this system consists of 2 parts: a hat-shaped silicone tip biolized with gelatin and an angled wire reinforced tube made of polyvinylchloride. The pump-actuator package was implanted into 8 calves in the preperitoneal space, bypassing from the left ventricle apex to the descending aorta for the left ventricular assist system (LVAS) and bypassing the right ventricle to the main pulmonary artery for the RVAS. According to the PI 601 feasibility protocol, 2 LVAS cases were terminated after 2 weeks, and 1 LVAS case and 1 RVAS were terminated after 1 month. The PI 700 series was implanted into 4 cases: 3 LVAS cases survived for a long term, 2 of them over 200 days (72-283 days), and 1 RVAS case survived for 1 month and was terminated according to the protocol for a short-term antithrombogenic screening and system feasibility study. Regarding power consumption, the plastic pump cases demonstrated from 6.2 to 12.1 W as LVAS and 7.3 W as RVAS, the titanium pump cases showed from 10.4 to 14.2 W as LVAS and 15.8 W as RVAS. All cases exhibited low hemolysis. The renal function and the liver function were maintained normally in all cases throughout these experimental periods. In the 2 RVAS cases, pulmonary function was normally maintained. No calves demonstrated thromboembolic signs or symptoms throughout the experiments except Case 1 with the plastic pump. However, in the plastic pump cases, bilateral renal infarction was suspected in 2 cases during necropsy whereas no abnormal findings were revealed in the titanium pump cases. There were also no blood clots inside the PI 700 series. As for the 601, the explanted pumps demonstrated slight thrombus formations at the top and bottom pivots except in 1 case. The Gyro PI series, especially the PI 700 series, demonstrated superior performance, biocompatibility, antithrombogenicity and low hemolysis. Also, the durability of the actuator was demonstrated. Based on these results, this titanium centrifugal pump is suitable as an implantable LVAS and RVAS. It is likely that the Gyro PI series is a feasible component of the BiVAS functional TAH.

Long term results of uncemented Judet hip endoprostheses.

We reviewed 94 patients in whom 113 Judet uncemented total hip endoprostheses had been inserted; 83 had a mean follow up of 10.8 years (range 6 to 13 years). The Merle dAubigne and Harris hip scores were used for clinical evaluation. In the long term follow up, severe or moderate pain was present in 38.6% of hips. Radiographs were studied and radiolucent lines, and other evidence of loosening, were recorded. Twenty hips (24.1%) showed radiological signs of loosening of the acetabular cup and a displacement of more than 5 mm in 37.3%. The loosening rate of femoral stems was 32.5%, but only 8.4% showed subsidence. The cumulative survival rate at 6 years was 84.1%, decreasing to 55.1% after the eleventh year. Complications and other aspects of the outcome are discussed. Our results were on the whole not satisfactory and we cannot recommend this type of uncemented endoprosthesis for routine total hip replacement.

[Osteosynthesis of femur shaft fractures with the unreamed AO-femur nail. Surgical technique and initial clinical results standard lock fixation]. / Osteosynthese von Femurschaftfrakturen mit dem unaufgebohrten AO-Femurnagel (UFN). Operative Technik und erste klinische Ergebnisse mit Standardverriegelung.

Nailing technique has changed in recent years in some important aspects which are not limited to the omitted reaming procedure. These changes concern patient positioning, reduction technique and determination of implant length and diameter. Approach and exposure techniques have been modified to new, less invasive procedures, in order to fulfill technical, functional and aesthetic requirements. Techniques and tricks have been developed for avoidance of fragment diastasis, axial and torsional malalignment and leg length differences. Finally, simple algorithms have been elaborated for the management of bilateral femoral shaft or ipsilateral tibial shaft fractures and the number and location of locking bolts. These algorithms, techniques and procedures were developed in a series of 108 femoral shafts, which were stabilized wit the AO unreamed femoral nail (UFN) in a prospective study between 1991 and 1994. Of these, 39 cases with a mean follow-up of 19.3 (range 8-40) months after trauma were reviewed. Fractures were classified according to Müller (1990): 6 type A, 21 type B and 12 type C. Closed soft tissue damage was classified according to our classification: C0/I, n = 14; CII, n = 15 (Tscherne 1982). Among 10 open fractures 4 were OI, 4OII, 1OIIIA and 1OIIIB (Gustilo 1976). The major complications were breakage of locking bolts (n = 2), one nail breakage after 9 weeks and one case of osteitis.

[Long-term results of Judet's cementless total endoprosthesis of the hip joint]. / Langzeitergebnisse der zementlosen Totalendoprothese des Hüftgelenkes nach Judet.

AIM: Control of the long term results of the Judet-TEP. METHODS: From 1980-1985 124 Pat. have been operated. The follow up was done in the same collective of 83 patients after 2-6 years and > 6 years. RESULTS: The intraoperative complications have been fractures of the femur (19.3%) and the trochanter major (3.6%) and luxation (1.9%). In the follow up time the clinical results declined. The patients complained increasing pain in the thigh (26.5%) and the groin (13.2%). Radiological loosening of the acetabulum occurred especially in the medio-caudal area (61.5%) and in the proximal femur (32.5%). Cranial movement of the cup (31.3%) and varus deviation in the femur (40.9%) predominated. 28 prostheses were revised. After 11 years the cumulative success rate was 55.1%. CONCLUSIONS: The long term results are disappointing.