Biomedical subjects

Timothy J Myers

Publications and source records attributed to Timothy J Myers.

31 records · Page 2Linked to original sources

PubMed2004

First clinical use of the redesigned HeartMate II left ventricular assist system in the United States: a case report.

Axial flow ventricular assist devices show great promise as a potential treatment for patients with end-stage heart failure. The HeartMate II system, redesigned on the basis of initial clinical experiences in Europe, is now in clinical trials in the United States. We report on the 1st use of the newly redesigned HeartMate II in the United States. The system has unique features, which include an accurate flow estimator and the ability to automatically detect and correct excessive left ventricular unloading. The new design also incorporates changes in the texturing of the blood-contacting surfaces to prevent thrombosis. The implantation technique and configuration are similar to those of the HeartMate XVE LVAS and require a median sternotomy for access. The 1st patient to receive the device in the United States has had an uncomplicated perioperative course and now awaits transplantation.

Adolescent↗

PubMed2003

Continuous flow pumps and total artificial hearts: management issues.

Feasibility studies are underway for new axial flow ventricular assist systems and with a total artificial heart (TAH). The axial flow pumps provide continuous flow from the left ventricle (LV) to the aorta; the TAH provides pulsatile flow to the pulmonary and systemic circulation. Understanding the differences between these systems is necessary for appropriate patient selection and management. We compared the Jarvik 2000 axial-flow pump and the AbioCor TAH. The Jarvik 2000 pump is placed in the LV with its outflow graft anastomosed to the aorta. This system is used for bridge-to-transplantation and destination therapy. The AbioCor TAH provides complete circulatory support. The AbioCor is used for destination therapy in patients expected to die in less than 30 days. Worldwide, 45 patients have received the Jarvik 2000 as a bridge to transplantation (n = 34) or destination therapy (n = 11) for an average duration of support of 132.8 days (5 to 853 days). In 30 bridge-to-transplantation cases, 14 patients (47%) have undergone heart transplantation, 5 (17%) continue to be supported with the Jarvik 2000 device, and 11 (37%) have died. Five of 7 patients supported by the AbioCor TAH survived beyond the perioperative period; 4 were ambulatory, 2 were discharged from the hospital, and 1 is at home 13 months after implantation. Anticoagulation therapy and infection management are necessary for both systems. Therapy with inotropic agents, vasoactive drugs, a pacemaker, and electrolyte normalization is necessary for Jarvik patients. AbioCor-supported patients do not require medications to support heart function. Vasoactive agents may be useful for controlling blood pressure.

Heart Failure↗

PubMed2003

Continuous axial-flow left ventricular assist device (Jarvik 2000) maintains kidney and liver perfusion for up to 6 months.

BACKGROUND: The Jarvik 2000 axial flow left ventricular assist device (LVAD), under development for the past decade, has the potential to support patients temporarily until cardiac transplantation or as a permanent circulatory support, without the size limitations of other implantable systems. METHODS: To assess its ability to perfuse the kidneys and liver, we monitored renal and hepatic function in 10 patients who received the Jarvik 2000 LVAD as a bridge to transplantation. Left ventricular assistance was maintained for up to 214 days (> 6 months), and renal and hepatic function were monitored at least weekly. RESULTS: Renal function before LVAD implantation in these patients was normal in 7 (creatinine, < 1.5) and moderately impaired in 3 (creatinine, 1.2 to 2.0). Hepatic function was normal in 7 patients before LVAD implantation (total bilirubin< 1.2; serum glutamic-oxaloacetic transaminase (SGOT), < 40; serum glutamic-pyruvic transaminase (SGPT), < 50) and normal at the time of transplantation in all 10 patients. Of the 3 patients with abnormal hepatic function before LVAD implantation, 1 patient had also had moderate renal dysfunction. CONCLUSIONS: Despite reduced pulsatility, the Jarvik 2000 LVAD improves or maintains excellent renal and hepatic function during periods of circulatory assistance in patients awaiting transplantation.

Adult↗

PubMed2003

Use of the Jarvik 2000 left ventricular assist system as a bridge to heart transplantation or as destination therapy for patients with chronic heart failure.

OBJECTIVE: To evaluate the Jarvik 2000 axial flow left ventricular assist system (LVAS) as a bridge to transplant and as destination therapy. SUMMARY BACKGROUND DATA: The Jarvik 2000 LVAS was implanted in 22 patients (16 men, 6 women; mean age 53 years) as a bridge to transplant (in the United States) and in 4 patients (all men; mean age 62.8 years) as destination therapy (in the United Kingdom). All patients in both of these initial feasibility studies were in NYHA class 4. METHODS: The pump was implanted through a thoracotomy or median sternotomy incision with the aid of partial cardiopulmonary bypass in bridge-to-transplant patients. A skull-mounted percutaneous power delivery was used for the patients who received the pump as destination therapy. RESULTS: Of the 22 bridge-to-transplant patients, 13 underwent transplant; 7 died during support; and 2 studies are ongoing. The surviving patients have an average follow-up of 15 months; one died at 2.6 months after transplant, and the remaining patients are all in NYHA class 1. Support averaged 67.1 days. Deaths were due to acute myocardial infarction in two patients and multiorgan failure in five patients. Hemodynamic function improved with LVAS support. The average cardiac index increased 70.6% by 48 hours after implant, pulmonary capillary wedge pressure decreased 44%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Similar results have been seen in the patients who received the device as destination therapy. In that series, one patient died of subdural hematoma 380 days after implant. The other two patients are in NYHA class 1, 642 and 889 days after implant. The average cardiac index increased 89.5%, and pulmonary capillary wedge decreased 52.2%. CONCLUSIONS: The Jarvik 2000 axial-flow LVAS can be used safely in selected patients to provide support until transplant or as destination therapy. In this series, the patients who most benefited from this device were those who required true left ventricular assistance rather than total capture of left ventricular output. Current experience indicates that continuous offloading of the ventricle is most effective when there is enough residual myocardial function to maintain pulsatility and aortic root ejection and to maintain, with nonpulsatile pump support, a normal cardiac index as well as reinstitution of the Frank-Starling response to the native ventricle.

Adult↗

PubMed2003

TACE/ADAM17 processing of EGFR ligands indicates a role as a physiological convertase.

EGF family growth factors, including transforming growth factor-alpha (TGFalpha), amphiregulin (AR), and heparin-binding EGF (HB-EGF), are invariably expressed as transmembrane precursors that are cleaved at one or more sites in the extracellular domain to release soluble growth factor. Considerable attention has focused on the identification of proteases responsible for these processing events. We previously implicated tumor necrosis factor-alpha converting enzyme (TACE/ADAM17) in the generation of soluble TGFalpha from its transmembrane precursor, proTGFalpha. Here, we review our findings that primary keratinocytes from Tace(deltaZn/deltaZn) mice, which express a nonfunctional TACE, released dramatically lower levels of soluble TGFalpha compared to their normal counterparts, even though TGFalpha mRNA and cell-associated protein levels were similar in the two cell populations. Restoration of TACE activity in Tace(deltaZn/deltaZn) cells increased shedding of TGFalpha species, including the mature, 6-kDa protein. Further, exogenous TACE enzyme accurately cleaved the N-terminal processing site of proTGFalpha in cell lysates, as well as both physiologic sites of a soluble proTGFalpha ectodomain. TACE also accurately cleaved peptide substrates corresponding to the processing sites of several additional EGF family members, and restoration of TACE activity enhanced the shedding of soluble AR and HB-EGF proteins from Tace(deltaZn/deltaZn) cells. Finally, reduction of functional TACE gene dosage greatly exacerbated the open-eye defect of Egfr(wa-2/wa-2) newborns, which is regulated by redundant actions of several EGF family ligands. The implications of these results for the biology of the EGF family and TACE are discussed.

ADAM Proteins↗

PubMed2003

Anesthetic management for implantation of the Jarvik 2000 left ventricular assist system.

UNLABELLED: The Jarvik 2000 Heart(TM) is a left ventricular assist device that produces continuous nonpulsatile axial flow by means of a single, rotating, vaned impeller. Anesthetic and perioperative considerations of the Jarvik 2000 Heart(TM) differ from those of conventional assist devices. The Jarvik 2000 is implanted within the left ventricle through a left thoracotomy, which is aided by left lung isolation. A brief period of cardiopulmonary bypass and induced ventricular fibrillation facilitate implantation. Transesophageal echocardiography is essential to assure proper intraventricular positioning of the device and aortic outflow, confirmed by observation of aortic valve opening in the presence of adequate left ventricular volume. Because continuous flow devices function best in the presence of lower systemic and pulmonary vascular resistance, milrinone was preferentially used as an inotropic drug. In the first group of 10 patients to receive the Jarvik 2000, the pump provided a cardiac output of up to 8 L/min, depending on preload, afterload, and pump speed. There were no early perioperative deaths. The average support duration was 81.2 days; the range was 13-214 days. Seven of the 10 patients survived to transplantation. Survivors underwent complete physical rehabilitation during pump support. IMPLICATIONS: The Jarvik 2000 is a left ventricular assist device that produces continuous nonpulsatile axial flow by means of a rotating, vaned impeller. Because the anesthetic considerations differ from those of conventional left ventricular assist devices, we report the perioperative management of the first 10 patients who participated in a bridge-to-transplantation feasibility study of the Jarvik 2000.

Aged↗

PubMed2002

Initial clinical experience with the Jarvik 2000 implantable axial-flow left ventricular assist system.

BACKGROUND: Implantable left ventricular assist systems (LVASs) are used for bridging to transplantation, bridging to myocardial improvement, and for permanent circulatory support. Conventional implantable systems have inherent limitations that increase morbidity during support. In contrast, small, efficient, axial-flow pumps, which have been under development for the past decade, have the potential to improve the length and quality of life in patients with severe heart failure. Methods and Results- To assess the safety and clinical utility of the Jarvik 2000, we implanted this device in 10 transplant candidates (mean age 51.3 years) in New York Heart Association (NYHA) class IV. Implantation was achieved through a left thoracotomy during partial cardiopulmonary bypass. The mean support period was 84 days. Within 48 hours postoperatively, the cardiac index increased 43%, pulmonary capillary wedge pressure decreased 52%, systemic vascular resistance decreased significantly, and inotropic support became unnecessary. Eight patients underwent physical rehabilitation and returned to NYHA class I. Their left ventricular dimensions, cardiothoracic ratios, and pressure-volume loop analyses showed good left ventricular unloading. Seven patients underwent transplantation and 3 died during support. No device thrombosis was observed at explantation. CONCLUSIONS: The Jarvik 2000 functions as a true assist device by partially unloading the left ventricle, thereby optimizing the patient's hemodynamics. Our preliminary results indicate that this LVAS may safely provide circulatory assistance for heart transplant candidates.

Adult↗

PubMed2002

Use of autologous auricular chondrocytes for lining artificial surfaces: a feasibility study.

BACKGROUND: Auricular elastic cartilage is a potential source of autologous cells for lining the luminal surfaces of cardiovascular prostheses. We tested this potential in vitro and in vivo using a left ventricular assist device (LVAD) and a calf model. METHODS: In vitro, auricular cartilage was harvested from the anesthetized ear of a calf, isolated, and cultured on tissue culture dishes. Primary chondrocytes were typed by immunocytochemistry, transferred into culture media, passaged twice, and seeded onto the blood-contacting luminal surfaces of four LVADs (HeartMate; Thoratec Corporation, Woburn, MA). Seeded cell linings were preconditioned under simulated flow conditions to promote cell adhesion to luminal surfaces. Seeding efficiency and cumulative cell loss under flow conditions were quantitated. In vivo, one of the four autologous chondrocyte-lined and preconditioned LVADs was implanted into the tissue-donor calf; run for 7 days; explanted; and evaluated grossly, by scanning electron microscopy, and by transmission electron microscopy. RESULTS: The efficiency of seeding chondrocytes onto the luminal surfaces of the four LVADs was 95.11% +/- 4.23% (n = 4). Cumulative cell loss during preconditioning under flow conditions in vitro did not exceed 12% (n = 4). After 7 days of in vivo implantation, the luminal surfaces of the implanted LVAD demonstrated an intact, strongly adherent cellular lining. CONCLUSIONS: Auricular elastic cartilage is a ready and easily accessible source of chondrocytes whose ability to produce collagen II and other important extracellular matrix constituents allows them to adhere strongly to the luminal surfaces of LVADs. The simple method of isolating and expanding auricular chondrocytes presented here could be used to provide strongly adherent autologous cell linings for LVADs and other cardiovascular devices. If and when chondrocytes can be genetically engineered to produce antithrombogenic factors and then used to line the luminal surfaces of LVADs or other cardiovascular prostheses, they may be able to improve the hemocompatibility of the blood-biomaterial interface in such devices. Our successful feasibility study in a calf model warrants further studies of this concept in vivo.

Animals↗

PubMed2002

Reverse remodeling of the failing human heart with mechanical unloading. Emerging concepts and unanswered questions.

Anecdotal and clinical evidence suggests that mechanical unloading may restore cardiac function by inducing changes in the biological properties of the failing heart. This challenges the notion that the progression of end-stage heart failure is an irreversible process ending in either death of the patient or transplantation. Although it is still not clear how mechanical unloading of the failing heart improves cardiac function, the process likely involves adaptive responses of cardiac myocytes on the cellular, extracellular, and subcellular levels.

Heart Failure↗

PubMedDate not supplied

Quality of life in bridge-to-transplant patients with chronic heart failure after implantation of an axial flow ventricular assist device.

Research suggests that ventricular assist devices improve quality of life for congestive heart failure patients awaiting heart transplantation. Axial flow ventricular assist devices like the Jarvik 2000 (Jarvik Heart, Inc., New York, NY) represent the newest type of ventricular assist device technology, but their effects on quality of life are not well understood. Therefore, the authors administered the Minnesota Living with Heart Failure Questionnaire to patients who had the Jarvik 2000 implanted as a bridge to heart transplantation. Patients completed the Minnesota Living with Heart Failure Questionnaire immediately before device implantation, 1 month after implantation, immediately before heart transplantation, and 1 month after transplantation. One month after implantation of the device, the nine patients who completed the study showed significant improvements in physical (p<0.008), emotional (p<0.02), and overall (p<0.008) quality of life. These improvements were maintained until the device was explanted. The authors conclude that implantation of the Jarvik 2000 ventricular assist device can substantially improve quality of life for patients awaiting heart transplantation.

Adult↗

PubMedDate not supplied

Vascular thrombosis during support with continuous flow ventricular assist devices: correlation with computerized flow simulations.

Continuous flow pumps are increasingly used to treat severe heart failure. These pumps alter flow physiology by lowering pulsatility in the arterial circulation. In patients with peripheral stenosis, continuous flow pumps may lead to thrombosis of peripheral vessels, possibly predisposing to vascular thrombosis in areas of non-flow-limiting stenosis. The authors performed a computerized flow modeling simulation to analyze the effects of altered hemodynamics in a stenotic area. Drawing on previous clinical experience, we modeled a stenotic area in the common carotid artery. Computerized flow modeling revealed blood stagnation zones with low shear stress and velocity adjacent to the stenotic area during nonpulsatile flow. Such stagnation was not present during pulsatile flow. These results indicate a mechanism by which altered physiologic flow may accelerate occlusion of arterial conduits in patients with preexisting stenosis. This finding may be important for patients with continuous flow devices who have peripheral vascular disease; therefore, further study is warranted.

Blood Flow Velocity↗

PubMedDate not supplied

Myocardial perfusion as assessed by positron emission tomography during long-term mechanical circulatory support.

Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n = 2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n = 4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100 - 110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased > 5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of > 5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium.

Adult↗

PubMedDate not supplied

Left ventricular unloading with an assist device results in receptor relocalization as well as increased beta-adrenergic receptor numbers: are these changes indications for outcome?

BACKGROUND: The use of left ventricular (LV) assist devices (LVADs) can improve performance and recovery of failing human hearts. AIM: Following our alpha-adrenergic receptor work, we hypothesized that mechanical unloading in patients with low output syndrome and LV failure would yield similar results with beta-adrenergic receptors ((beta)AR), that being increased numbers and intra-myocytic relocalization. METHODS: (beta)AR density and localization were investigated by fluorescence deconvolution microscopy and compared at LVAD insertion and removal in 13 heart failure patients, the patients therefore acting as their own control. (beta)AR densities and distribution were determined in snap frozen sections of human core biopsy left ventricular apical tissue. Samples were probed with tagged CGP 12177 for visualization of (beta)AR and challenged with cold agonists and antagonists. (beta)AR density was measured by two independent methods. Localization of receptors was examined in reconstructed, deconvoluted, stacked section images. RESULTS: There was an increase in (beta)AR density following ventricular unloading in most of the patients, and also significant normalization in the location of the receptors in the myocardium comparing pre- and post-LVAD tissue. CONCLUSIONS: These findings suggest that supporting an ailing heart via unloading initiates mechanisms and pathways responsible for myocardial recovery and repair. With appropriate pharmacological support, patients with LVAD might recover to the point where they no longer depend on eventual organ transplantation, and (beta)AR number, type, and distribution in pre-LVAD myocardial tissue, could predict outcome with regard to recovery, repair, and improvement in cardiac function.

Female↗