Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.     

Late tamponade with mechanical circulatory support

BACKGROUND: Circulatory support with mechanical devices often leads to bleeding and tamponade. METHODS: We report a series of three patients that required mechanical circulatory support for postcardiotomy ventricular dysfunction. RESULTS: Late tamponade occurred in each patient with different clinical presentations. Early postoperative bleeding occurred in 2 patients. There was no active bleeding in any of the 3 patients. Transesophageal echocardiography was not helpful in making the diagnosis. CONCLUSION: Late tamponade, which may be the result of hematoma with earlier bleeding, can present as dyspnea, hypoxia, or forms of hemodynamic collapse. Exploratory media sternotomy is required to definitively make the diagnosis and to evacuate the hematoma.     

Platelet morphology in patients with mechanical circulatory support

OBJECTIVE: Mechanical circulatory support is a therapy for patients with end stage cardiac insufficiency. The thromboembolic events are feared complications during support, due to the surface thrombogenicity of the implanted device. Activated blood platelets play a major role in this context. Consequently the platelet morphology of patients was investigated. METHODS: Platelets of eight patients were observed by means of scanning electron microscopy during the period of support with the Novacor left ventricular assist system N100. Blood was collected preoperatively and daily during the first week as well as weekly during the first 3 months. Samples were fixed with cacodylic-acid buffered glutaraldehyde. Platelet alterations were classified as non-activated, activated and aggregated, based on the so-called 'shape change' morphology. In addition, blood coagulation parameters were evaluated (e.g. activated partial thromboplastin time, prothrombin time, antithrombin III). RESULTS: Preoperatively, 15.0 +/- 4.6% (overall mean values) of activated platelets were found. Within the first postoperative week, the mean level of activated platelets increased to 32.8 +/- 8.0% (P < 0.05). Comparing short- (< 30 days; n = 4) vs. long-period (> 30 days; n = 4) support, a significant difference of activated platelets was evaluated (24.3 +/- 3.3% vs. 34.8 +/- 3.4%, P = 0.004). A correlation was found between the values of activated clotting time and activated platelets. Specific platelet deformations and damages appeared during support, which could not be found preoperatively. CONCLUSIONS: The platelet morphology showed alterations in all patients probably most strongly induced by the surface activation of the implanted device. These observations should be taken into consideration in management of postoperative anticoagulation therapy.     

Jarvik 2000 heart: potential for bridge to myocyte recovery

BACKGROUND: Mechanical bridge to left ventricular recovery is an emerging strategy for the treatment of heart failure. We sought to validate the use of a new intracardiac axial flow impeller pump for this purpose. METHODS and RESULTS: The Jarvik 2000 Heart was implanted into 30 sheep to ascertain mechanical reliability, biocompatibility, and hemodynamic function. We attempted but failed to anticoagulate with warfarin. Elective explants with survival were performed in 3 animals to simulate bridge to recovery. Extensive autopsy studies were performed in all other animals. At speeds between 8000 and 12 000 rpm the device pumped up to 8 L/min, captured all mitral flow, and augmented cardiac output with elevation of mean arterial pressure. The pump was silent and hemolysis negligible. Nonpulsatile flow did not adversely affect neurological or renal function. Device removal proved straightforward and safe. A fractured inflow bearing occurred in 1 early model. There were no other pump failures, but power interruption occurred when the sheep chewed the cables or head-butted the percutaneous pedestal. At autopsy, there was no thromboembolism or primary thrombus formation in any device. Pump occlusion occurred in 2 sheep with bacterial endocarditis. One electively explanted pump, previously switched off for 5 months, had no thrombus in the device or vascular graft. CONCLUSIONS: The Jarvik 2000 Heart is a major advance in blood-pump technology and increases the scope of mechanical circulatory support. Reliability and ease of removal favor its use for bridge to myocyte recovery, as well as for bridge to transplantation or long-term support.     

Prolonged total circulatory support using direct mechanical ventricular actuation

Direct mechanical ventricular actuation (DMVA) is a unique, non blood contacting method for biventricular cardiac assist. Although DMVA has successfully provided cardiac assist for more than 7 days in humans, with long-term survival, its potential for long-term circulatory support has not been adequately investigated. DMVA has not been studied in the large ruminants commonly used to evaluate support devices. To develop a large animal experimental model of prolonged total circulatory support using DMVA, Suffolk sheep (n = 10) underwent sterile instrumentation for hemodynamic and chemistry monitoring. After baseline values were obtained, a left lateral thoracotomy and pericardotomy were performed. Upon electrical ventricular fibrillation (VF), DMVA was begun and the thoracotomy closed. Total circulatory support was continued until mean arterial pressure (MAP) persisted below 50% of the baseline value for more than 1 hr, with a goal of 7 days' support. Mean duration (plus or minus the standard deviation [SD]) of circulatory support was 65.9 +/- 56.8 hr (range, 10-168 hr). Pressors were not used during DMVA support. The subject supported for the maximal time (7 days) was defibrillated into sinus rhythm. No CK-MB fraction was greater than 1%, suggesting that DMVA, even with prolonged application during VF, does not result in myocardial injury. Blood urea nitrogen and creatinine levels indicate renal function was preserved. The model described represents the longest period any animal has been supported in VF using DMVA. This new model will be useful in determining what limitations, if any, exist to the prolonged use of DMVA for circulatory support.     

Determinants of clinical results of mechanical circulatory support for ventricular failure after cardiotomy

To clarify determinants of clinical results of circulatory support for ventricular failure after cardiotomy, we examined 53 patients (33 men and 20 women) who underwent circulatory support for post operative heart failure from 1984 to October 1995. Their ages ranged from 22 to 74 years (mean, 51 years). In 53 patients, 32 had valvular, 19 had ischemic, and 2 had congenital heart disease. After operation, 21 patients underwent venoarterial bypass, 20 underwent biventricular bypass, and 8 underwent left ventricular bypass. The remaining 4 patients received a pulsatile left ventricular assist device. Weaning and discharge rates of the patients by type of support were 52.4% and 28.6% with venoarterial bypass, 75.0% and 55.0% with biventricular bypass, 87.5% and 37.5% with left ventricular bypass, and 75.0% and 50.0% with left ventricular assist device, respectively. The results of this series (67.9% weaning rate and 41.5% discharge rate) were acceptable. Peri-operative variables before and during circulatory support were analyzed multivariately by logistic regression analysis. Selected independent determinants (odds ratio) of significant difference (p < .05) were type of support (7.547) for non weaning and pre support cardiogenic shock (17.246), and type of support (8.780) and support duration (1.487) for mortality. These results suggest that early application before profound shock and appropriate selection of type of support might be key factors in successful circulatory support for ventricular failure occurring after cardiotomy.     

AB-180 circulatory support system: summary of development and phase I clinical trial

The AB-180 Circulatory Support System (AB-180 CSS; Cardiac Assist Technologies, Pittsburgh, PA) is a left ventricular assist system for investigational use in patients with postcardiotomy cardiogenic shock who are refractory to standard treatment with an intra-aortic balloon pump, pharmacologic treatment, or both. The intent of the AB-180 CSS is to provide temporary (up to 14 days) mechanical circulatory support until the heart recovers adequate mechanical function. The system consists of a small implantable centrifugal pump and a controller. A unique infusion system produces a hydrodynamic bearing between rotational and stationary components of the AB-180 CSS pump. This infusion system also provides a source of heparin for localized anticoagulation. Extensive bench and animal work has illustrated anticoagulation requirements, established operating guidelines, and demonstrated safety and efficacy. An investigational device exemption has been granted for a Phase I, five patient feasibility study at Allegheny General Hospital in Pittsburgh, Pennsylvania. To date, the pump has been implanted in one patient. The results from this first case are presented here.     

The Concerted Action ''Heart'' European registry on clinical application of mechanical circulatory support systems: bridge to transplant. The Registry Scientific Committee

Endemic helminthic infection is a major public-health problem and affects a large proportion of the world's population. In Australia, helminthic infection is endemic in Aboriginal communities living in tropical northern regions of the continent. Such infection is associated with nonspecific (polyclonal) stimulation of IgE synthesis and highly elevated total serum IgE levels. There is evidence that worm-infection variance (i.e., human capacity of resistance) and total serum IgE levels may be related to the presence of a major codominant gene. The beta chain of the high-affinity IgE receptor, Fc epsilon R1-beta, has been previously identified as a candidate for the close genetic linkage of the 11q13 region to IgE responses in several populations. We show a biallelic RsaI polymorphism in Fc epsilon R1-beta to be associated with total serum IgE levels (P = .0001) in a tropical population of endemically parasitized Australian Aborigines (n = 234 subjects). The polymorphism explained 12.4% of the total residual variation in serum total IgE and showed a significant (P = .0000) additive relationship with total serum IgE levels, across the three genotypes. These associations were independent of familial correlations, age, gender, racial admixture, or smoking status. Alleles of a microsatellite repeat in intron 5 of the same gene showed similar associations. The results suggest that variation in Fc epsilon R1-beta may regulate IgE-mediated immune responses in this population.     

Medos/HIA-assist system: first experiences with mechanical circulatory assist in infants and children

The Medos/HIA-System is a new pneumatically driven system for mechanical circulatory assist. The system is characterized by excellent efficiency at high heart rates and is available with three ventricles of 10, 25 and 60ml stroke volume. It can be used as left-, right- or biventricular assist device. Our preliminary experiences with this novel system for support of infants and children are reported.     

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.     

Physiologic profiles in circulatory support and management of the critically ill

An automated system has been developed for measuring hemodynamic, oxygen transport and tissue utilization functions. Rapid measurement and data analysis of physiologic profiles by paramedical personnel allow prompt evaluation of altered cardiovascular function. Evaluation of physiologic function allows therapeutic interventions to be instituted on a timely basis, appropriately directed toward improvement of the measured cardiovascular abnormalities. Physiologic profile studies were performed on 1016 occasions in 580 patients during a three-year period and form the basis of this report. Although utilized on hospitalized patients, there are implications for use in evaluating and treating all critically ill patients.     

The influence of trazodone on the circulatory system in patients with endogenous depression. I. Basic circulatory parameters

In patients with endogenous depression in remission, decline of systolic blood pressure and a statistically significant shortening of pulse time were found.     

Coupling of skeletal muscle to a prosthesis for circulatory support

A durable bond between the end of skeletal muscles and prosthetic structures could, with appropriate linkage, allow circulatory support power by synchronous and/or sequential contraction of several in situ conditioned muscles. Potential advantages relative to a myoplasty wrap involve 1) less traumatic dissection, 2) efficient linear force development, 3) selectable contraction rate, 4) greater stroke work, 5) independent control of muscle pre-load and end diastolic pressure, and 6) independent control of duration of muscle tension and ejection time. However, no existing means of tissue-prosthetic bonding appears adequate. Practicality would demand that full tension bearing capacity by the bond take no longer than muscle conditioning. A prosthesis was developed to achieve those goals. As scaled for this study, it is made of 7,200-7,800 unspun, unplaited, 22 to 26 microns diameter polyester fibers swaged into four taper needles for weaving through distal muscle. The other end is formed into a polyurethane sheathed kernmantel cord for distal fixation. Devices were implanted in six 3 to 4 kg rabbits (unilateral posterior tibial tendon replacement, random side selection with contralateral dissection/closure controls), and their tensile strength was tested at 30 days. All healed well; leg movements were normal after 1 week. Limbs were frozen at -70 degrees C between death and testing. Control failure occurred at 243 +/- 94 N and experimental at 163 +/- 44 N (p = 0.065, t-test); highest estimated requirement was 17.2 N. Interface strength was adequate by 30 days. Continued investigations, addressing other questions, are warranted.