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Ann Thorac Surg 1996;62:675-681
© 1996 The Society of Thoracic Surgeons
Division of Cardiopulmonary Transplantation, Texas Heart Institute at St. Luke's Episcopal Hospital and Divisions of Cardiology and Pathology, University of Texas Medical School, Houston, Texas
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Abstract |
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Methods. We reviewed data from 31 patients (30 men, 1 woman) supported more than 30 days (mean, 137 days; range, 31 to 505 days) with the HeartMate left ventricular assist system. The patients' mean age was 46 years (range, 22 to 64 years); 17 had idiopathic and 14 had ischemic cardiomyopathy. Data (anatomic, physiologic, hemodynamic, histologic, and biochemical) were collected at the time of HeartMate implantation, during support with the device temporarily off, and at the time of device explantation.
Results. Routine chest roentgenogram showed improvement in cardiothoracic ratio (0.62 ± 0.04 to 0.55 ± 0.03; p < 0.0001). Echocardiography performed with the pump off showed a significant decrease in left ventricular end-diastolic dimension (6.81 ± 0.87 cm to 5.39 ± 1.08 cm; p < 0.0005) and a significant improvement in ejection fraction (0.11 ± 0.05 to 0.22 ± 0.17; p < 0.02). Cardiac index increased (1.96 ± 0.52 L • min-1 • m-2 to 2.93 ± 0.73 L • min-1 • m-2; p < 0.0001), mean aortic pressure increased (71.40 ± 10.63 mm Hg to 76.33 ± 16.84 mm Hg; p = 0.48), pulmonary capillary wedge pressure decreased (24.18 ± 6.27 mm Hg to 14.48 ± 3.01 mm Hg; p < 0.0001), and pulmonary vascular resistance decreased (3.34 ± 2.00 Wood units to 2.51 ± 0.88 Wood units; p < 0.05). Comparisons of tissue samples taken at the time of implantation and at the time of transplantation showed a marked reduction in myocytolysis. Calcium uptake, calcium-binding rates, and lipid levels normalized in patients studied. Plasma norepinephrine levels decreased to near normal levels.
Conclusion. Prospective studies are now indicated to determine whether device removal without transplantation may be beneficial in selected patients.
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Introduction |
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B efore the advent of current medical and surgical therapies, bed rest was the standard treatment for patients with chronic heart failure. In the 1945 edition of Clinical Heart Disease, Samuel Levine [1] stated that "The first principle in the treatment of such a patient is rest." More than 20 years later, McDonald and colleagues [2], using this principle to treat patients with congestive heart failure, reported that "with maximal reduction in the work load of the dilated heart by prolonged bed rest one can often achieve some degree of recovery." Today, prolonged bed rest in the hospital is not medically or economically feasible. Furthermore, bed rest, either in the hospital or at home, renders the patient immobile, adversely affecting musculoskeletal function and quality of life. The implantable left ventricular assist device, however, provides significantly greater unloading of the heart, thereby allowing the heart to rest while the patient remains active.
Under the supervision of Norman [3], the Texas Heart Institute in Houston began clinical trials in the mid-1970s of an implantable left ventricular assist device as temporary support for patients with postcardiotomy cardiogenic shock. One of these patients became the first to receive an implanted left ventricular assist device as a bridge to transplantation [4]. Although few of the patients in this study survived, those patients supported more than 24 hours showed improvement in ventricular function [5].
Development of the left ventricular assist device continued, and in 1985 the HeartMate (Thermo Cardiosystems, Inc, Woburn, MA) left ventricular assist system (LVAS) was approved by the Food and Drug Administration for initial clinical trials as a bridge to transplantation. In 1986, this LVAS was first used for this application. Originally, however, the HeartMate was developed as a long-term implantable device (RFP NHLBI-HL-80–3). As waiting times for donor hearts increased, durations of implantation for patients supported by the LVAS also increased. Although these patients suffered from advanced chronic heart failure, we began to notice clinical and histologic improvements in the native ventricles of the patients who were supported for prolonged periods. In many, indices of left ventricular function approached normal values by the time of transplantation.
Thus, to determine whether prolonged unloading with a HeartMate LVAS would improve left ventricular function in patients with congestive heart failure, we retrospectively compared selected anatomic, physiologic, hemodynamic, histologic, and biochemical parameters of the native left ventricle before implantation, at varying times during use, and at the time of explantation of the device. Because this study was retrospective, data were not available on all patients, particularly for the calcium flux, lipid, and neurohormonal studies. Although many of our findings are preliminary, we hope that our observations will stimulate further investigation in this field.
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Material and Methods |
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Histologic Studies
Tissue samples from the core of the left ventricular apex removed at time of implant were compared with samples from the explanted heart at time of transplant. Tissue was fixed in 10% buffered formaldehyde and routinely processed into Paraplast. Cross-sections of the left ventricular wall, including subendocardial, midventricular, and subepicardial zones, were stained with hematoxylin-eosin and Masson's trichrome. The extent of myocytolysis was assessed in 10 patients with dilated cardiomyopathy. Myocytolysis was assessed using a grading scale from 0 (no myocytolysis) to 5 (severe myocytolysis). The scores of the midventricular and subepicardial zones from each sample were combined. Because subendocardial areas and areas close to grossly apparent scars are associated with severe myocytolysis in surviving cardiac myocytes, such areas were purposely omitted from the study.
Calcium Determination Studies
Calcium uptake and calcium-binding studies of isolated sarcoplasmic reticulum vesicles were performed on five pre-LVAS and five post-LVAS samples. Tissue samples from the core of the left ventricular apex were removed and immediately dropped into 10 volumes of ice-cold isolation buffer (25 mmol/L imidazole, 200 µmol/L phenylmethylsulfonylfluoride, 10 mmol/L dithiothreitol, pH 7.0), finely minced with scissors, then homogenized with a polytron for three 14-second pulses at full speed. The homogenate was cooled in ice for 2 minutes between each homogenization. The homogenate was then poured through one layer of cheesecloth and centrifuged at 5,000 rpm in a cooled, bench-top centrifuge. The resulting supernatant was again passed through one layer of cheesecloth, then centrifuged at 10,000 g in a Sorvall 50 Ti rotor for 30 minutes. The pellets were discarded, and the supernatant was centrifuged at 100,000 g for 1 hour. The final pellet was resuspended in membrane buffer (25 mmol/L imidazole, 100 mmol/L KCl, 10 mmol/L DTT, pH 7.0), using a glass/Teflon homogenizer. The protein was estimated with a Bio-Rad protein assay solution, using bovine serum albumin as standard.
The sarcoplasmic reticulum protein was diluted to 1 mg/mL with membrane buffer. To determine calcium uptake, the sarcoplasmic reticulum was incubated with solutions containing 5 mmol/L of sodium oxalate (a calcium chelator that diffuses into the sarcoplasmic reticulum). Samples were incubated at 37°C for 2 minutes in the reaction mixture (40 mmol/L Tris-maleate, pH 6.8, 100 mmol/L KCl, 10 mmol/L MgCl2, 10 mmol/L NaN2, containing 100 µmol/L 45CaCl2 [5,000 cpm/nmol]). The reaction was initiated by adding 1 mmol/L adenosine triphosphate. The sodium oxalate within the sarcoplasmic reticulum serves to chelate or trap any calcium taken up by the sarcoplasmic reticulum. The calcium concentration was then measured over time. Samples were removed from the reaction mixture after 1, 5, 10, and 20 minutes, then filtered through a 0.45-µmol/L millipore filter. The filters were washed with 5 mL of cold assay medium, placed in vials containing Ecolume scintillant, then counted for calcium content in a LKB Rackbeta. Calcium-binding assays were also performed on freshly isolated microsomes over a 20-minute period using the same buffered solution and sampling intervals. All values were corrected for basal calcium levels, determined in the presence of 10 mmol/L ethylene glycol-bis (ß-aminoethyl ether).
Lipid Analyses
A small portion (approximately 50 to 100 mg) of fresh core sample was placed in 2 mL of 2:1 cold chloroform/methanol and homogenized with a polytron for 10 seconds at high speed. The mixture was decanted into a glass, screw-capped tube containing a small stir bar. The tube was then evacuated with nitrogen, capped, and placed on a stir plate for 30 to 60 minutes. The extract was poured through a plug of glass wool in a microfunnel. The upper aqueous layer was removed and discarded, and the organic layer was blown to dryness under a stream of nitrogen. The residue was resuspended in 100 µL of 2:1 CHCl3-MeOH, and 10 µL was spotted on 20 by 20-cm silica gel Type 60 plates (EM Science, Gibbstown, NJ; 0.25 mm thick) for phospholipid headgroup determinations. The silica gel TLC plates were developed in two directions in a solvent system (CHCl3/MeOH/HAc/water [70:30:4:1]), then dried and exposed to iodine vapor. The spots were marked, then scraped into Pyrex tubes. The samples were digested for 2 hours in a heating block at 100°C with five drops of concentrated sulfuric acid. Five drops of 70% hydrogen peroxide were added, and the tubes heated as before. Next, 2% ammonium molybdate was added, and the phosphate content determined spectrophotometrically [8]. The remaining sample was mixed with 1 mL of boron trifluoride (Supelco, Inc, Bellefonte, PA), boiled for 3 minutes, cooled, mixed with 1 mL of methanolic base (Supelco), and boiled for another 3 minutes. After cooling, 5 mL of petroleum ether was added, and the mixture was shaken vigorously for 2 minutes and allowed to separate at room temperature. The upper, organic layer was removed, evaporated to dryness under nitrogen, and reconstituted in 50 µL of carbon disulfide. Samples were examined for phospholipid (pre-LVAS, n = 9; post-LVAS, n = 6) and fatty acid chain (pre-LVAS, n = 8; post-LVAS, n = 5) content by gas–liquid chromatography on a 6-m Carbowax column, housed in an Antek 3000 GLC. Temperature was maintained at 240°C and sample volume was 2 µL.
Plasma Norepinephrine Studies
Plasma norepinephrine levels were measured in five patients just before LVAS implantation, and then weekly for 5 weeks. Blood samples were collected through venous cannulation after 30 minutes of bed rest, and were cold centrifuged within 1 hour at 1,500 rpm for 15 minutes. The serum was then stored in a -70°C freezer until processing. Analysis was performed with a radioenzymatic microassay developed by Hussain and Benedict [9].
Statistical Methods
All data were analyzed using t tests and 
2 tests where appropriate. A p value of 0.05 was considered statistically significant.
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Results |
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). Echocardiography also showed significant improvement. Left ventricular end-diastolic dimension decreased (6.81 ± 0.87 cm to 5.39 ± 1.08 cm; p < 0.0005) and ejection fraction increased (0.11 ± 0.05 to 0.22 ± 0.17; p < 0.02). Hemodynamic parameters on and off the LVAS showed effective ventricular unloading. Cardiac index increased (1.96 ± 0.52 L • min-1 • m-2 to 2.93 ± 0.73 L • min-1 • m-2; p < 0.0001), mean aortic pressure increased (71.40 ± 10.63 mm Hg to 76.33 ± 16.84 mm Hg; p = 0.48), pulmonary capillary wedge pressure decreased (24.18 ± 6.27 mm Hg to 14.48 ± 3.01 mm Hg; p < 0.0001), and pulmonary vascular resistance decreased (3.34 ± 2.00 Wood units to 2.51 ± 0.88 Wood units; p < 0.05). Myocytolysis was reduced from a mean score of 2.9 (median, 2.5) in apical core specimens to a score of 1.0 (median, 1.0) in explanted hearts (Fig 2).
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). The rates of calcium uptake at each time point were higher in the post-LVAS samples than in the pre-LVAS samples. Also, calcium-binding values (in the absence of sodium oxalate) were two to three times higher in the post-LVAS samples than in the pre-LVAS preparations (Table 2). Fatty acid determinations revealed greater than normal levels of palmitic, palmitoleic, and oleic acids in the pre-LVAS tissue, whereas levels in the post-LVAS tissue returned to near normal (Table 3). Lisophospholipid levels also decreased (Table 4). Finally, plasma norepinephrine levels decreased to near normal levels in patients supported with the LVAS (from 2,948 pg/mL at baseline to 673 pg/mL [normal value, 150 to 350 pg/mL]) after 5 weeks of unloading (Fig 3).
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Previous studies at our institution [12, 13] demonstrated that cardiac atrophy does not occur in patients undergoing support with a mechanical assist device; rather, unloading of the heart resulted in marked improvement of myocyte architecture [14]. In our current study, clinical data from patients supported for more than 30 days confirmed that prolonged mechanical unloading of the failing heart promotes ventricular recovery: cardiothoracic ratio, end-diastolic dimension, ejection fraction, pulmonary capillary wedge pressure, and pulmonary vascular resistance each improved. We also observed recovery in certain histologic markers of heart failure. After prolonged unloading by the LVAS, we found a consistent decrease in the level of myocytolysis, a condition that is commonly observed in tissue specimens from patients in advanced heart failure. The most marked decreases were observed in patients having idiopathic cardiomyopathy with marked cardiomegaly. In addition, we noticed that patients who were supported for longer periods tended to show a greater degree of recovery. For example, the patient who underwent the longest period of unloading (505 days) demonstrated distinct histologic improvement. This histologic improvement corresponded with a significant improvement in ventricular function.
Calcium "leakage" and decreased rate of calcium binding by the sarcoplasmic reticulum of cardiac cells are biochemical characteristics of heart failure. These defects may precede clinical manifestations of heart failure, suggesting a relationship between the calcium-handling ability of the sarcoplasmic reticulum and the decreased contractility of the failing heart [15]. When the calcium-handling ability of the cell is reduced, intracellular and extracellular concentrations of calcium increase, reflecting a loss in integrity of the membrane of the sarcoplasmic reticulum. Phospholipase (a calcium-dependent enzyme) is activated and phospholipids are cleaved into lysophospholipids and fatty acids. This results in further damage to cells and organelle membrane bilayers [16]. This loss of membrane integrity further increases calcium concentrations, leading to more calcium leakage and even higher calcium levels and phospholipase activity.
Examination of oxalate-supported uptake in the sarcoplasmic reticulum showed marked signs of calcium leakage in samples taken at time of implantation (Table 1
), and calcium-binding rates in the pre-LVAS sarcoplasmic reticulum were markedly reduced (Table 2). Phospholipid levels and fatty acid levels increased (Tables 3, 4). After prolonged support with the LVAS, however, calcium uptake studies showed little evidence of calcium leakage; calcium-binding ability became more efficient and phospholipid and fatty acid levels normalized. These findings reflect a reversal of the deranged function of the sarcoplasmic reticulum (pre-LVAS), which is typical of patients with severe, advanced heart failure. Although preliminary, these data may suggest that unloading the heart with a mechanical assist device may allow some degree of recovery of the calcium-handling ability and membrane integrity in the organelles of cardiac cells. A larger study is necessary to confirm these findings.
The level of plasma norepinephrine is considered a reliable indicator of severity of heart failure [17]. Studies have shown a decrease in norepinephrine levels in patients whose hearts are unloaded pharmacologically [18]. In our study, patients who had undergone prolonged unloading with the HeartMate experienced a decrease in plasma norepinephrine to near normal levels (Fig 3). Again, our findings are preliminary, but these data suggest that plasma norepinephrine levels may also be a reliable indicator for cardiac recovery and could be useful in choosing candidates for removal of the LVAS.
Although certain conditions are known to increase risk of cardiomyopathy (chronic alcohol use, pregnancy, systemic hypertension, some infections, and cigarette smoking), the etiology of most cardiomyopathies is unclear [19]. Some investigators have associated these disorders with viral infections, genetic abnormalities, or autoimmune disorders [20]. However, although the pathophysiologic characteristics of the cardiomyopathic heart are well known (myocardial hypertrophy, myocyte hypertrophy with attenuation of nuclei, attenuation of fibers, loss of myocytes, and interstitial fibrosis [21]), no immunologic, morphologic, microbiological, or histochemical markers for cardiomyopathy have yet been identified that can definitively explain its etiology.
For decades, patients with heart failure were treated with bed rest. Burch [22] proposed that bed rest could reverse many of the effects of congestive heart failure, resulting in decreased heart rate, arterial blood pressure, cardiac output, heart size, and myocardial contraction. Bed rest would unload the ventricle and promote recovery of ventricular structure and function. Today, resting the heart remains the cornerstone of medical therapy for patients with congestive heart failure. Pharmacologic agents such as angiotensin-converting enzyme inhibitors [23] and ß-blockers [24] have been found to produce some ventricular unloading. Prolonged bed rest, however, is no longer a feasible treatment for patients with chronic heart failure. The mechanical assist device can unload the heart much more effectively without undermining the patient's quality of life.
The HeartMate was initially designed for long-term support of patients with congestive heart failure. The study we report here was part of a larger clinical trial. In that trial [7], the pretransplantation mortality rate of patients supported by the LVAS was 55% less than that of the control group who did not receive the LVAS. Patients in the control group died (64%) or underwent transplant (36%) an average of 12 days after enrollment in the study.
Since our initial experience with the HeartMate LVAS, we have observed consistent improvements in native ventricular function at the time of transplantation. Other studies have also reported significant improvements in ventricular function after support with an assist device, including reversal of ventricular dilatation [25], improvements in ventricular structure [26], marked decreases in neurohormone levels [27], and a decrease in end-systolic elastance [28]. Such observations, along with the data presented in this study, seem to indicate that some patients supported with assist devices may not require cardiac transplantation. Instead, their ventricular function may recover enough that the device could be removed and the patients treated medically. If the device could be safely removed without being replaced, the potential complications of long-term support (infection, thromboembolism, device failure) could be avoided. In addition, this therapy could help the thousands of patients each year who are unable to receive a transplant because of the donor shortage. Since we first presented our data in 1994 [29], investigators in Germany and Japan have removed the LVAS from selected patients who showed ventricular recovery after 4 to 6 months of support (personal communications, R. Hetzer, MD, and T. Nakatani, MD).
What remains to be seen is how long this recovery will be sustained without support of an assist device. The LVAS offers an opportunity to study the effects of prolonged unloading of the left ventricle. This study has shown that easily assessed clinical parameters improve in patients supported chronically by the LVAS. In addition, our preliminary data show that biochemical (calcium and lipid) and systemic (neurohormonal) markers of heart failure at the cellular and subcellular levels also improve. Further studies are warranted to substantiate the findings of this investigation and to assess the long-term benefits of removing the assist device after prolonged unloading.
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentAcknowledgmentsReferences |
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Address reprint requests to Dr Frazier, Texas Heart Institute, PO Box 20345, Houston, TX 77225-0345.
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H. T. Tevaearai, A. D. Eckhart, G. B. Walton, J. R. Keys, K. Wilson, and W. J. Koch Myocardial Gene Transfer and Overexpression of {beta}2-Adrenergic Receptors Potentiates the Functional Recovery of Unloaded Failing Hearts Circulation, July 2, 2002; 106(1): 124 - 129. [Abstract] [Full Text] [PDF]
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D. A. Cooley Initial Clinical Experience With the Jarvik 2000 Implantable Axial-Flow Left Ventricular Assist System Circulation, June 18, 2002; 105(24): 2808 - 2809. [Full Text] [PDF]
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S. Miyagawa, Y. Sawa, S. Taketani, N. Kawaguchi, T. Nakamura, N. Matsuura, and H. Matsuda Myocardial Regeneration Therapy for Heart Failure: Hepatocyte Growth Factor Enhances the Effect of Cellular Cardiomyoplasty Circulation, May 28, 2002; 105(21): 2556 - 2561. [Abstract] [Full Text] [PDF]
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N. de Jonge, D. F. van Wichen, M. E. I. Schipper, J. R. Lahpor, F. H. J. Gmelig-Meyling, E. O. Robles de Medina, and R. A. de Weger Left ventricular assist device in end-stage heart failure: persistence of structural myocyte damage after unloading: An immunohistochemical analysis of the contractile myofilaments J. Am. Coll. Cardiol., March 20, 2002; 39(6): 963 - 969. [Abstract] [Full Text] [PDF]
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K. Shirota, Y. Huang, O. Kawaguchi, T. Yuasa, P. W. Brady, Y. Ueda, and S. N. Hunyor Functional recovery of the native heart after cardiomyoplasty in sheep with heart failure: passive and dynamic effects of volume loading Ann. Thorac. Surg., March 1, 2002; 73(3): 849 - 854. [Abstract] [Full Text] [PDF]
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F. Grabellus, B. Levkau, A. Sokoll, H. Welp, C. Schmid, M. C Deng, A. Takeda, G. Breithardt, and H. A Baba Reversible activation of nuclear factor-{kappa}B in human end-stage heart failure after left ventricular mechanical support Cardiovasc Res, January 1, 2002; 53(1): 124 - 130. [Abstract] [Full Text] [PDF]
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R. Sodian, M. Loebe, C. Schmitt, E. V. Potapov, H. Siniawski, J. Muller, H. Hausmann, H. R. Zurbruegg, Y. Weng, and R. Hetzer Decreased plasma concentration of brain natriuretic peptide as a potential indicator of cardiac recovery in patients supported by mechanical circulatory assist systems J. Am. Coll. Cardiol., December 1, 2001; 38(7): 1942 - 1949. [Abstract] [Full Text] [PDF]
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O. H. Frazier, E. A. Rose, M. C. Oz, W. Dembitsky, P. McCarthy, B. Radovancevic, V. L. Poirier, and K. A. Dasse Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation J. Thorac. Cardiovasc. Surg., December 1, 2001; 122(6): 1186 - 1195. [Abstract] [Full Text] [PDF]
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J. D. Harding, V. Piacentino III, J. P. Gaughan, S. R. Houser, and K. B. Margulies Electrophysiological Alterations After Mechanical Circulatory Support in Patients With Advanced Cardiac Failure Circulation, September 11, 2001; 104(11): 1241 - 1247. [Abstract] [Full Text] [PDF]
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D. L. Mann and H. Taegtmeyer Dynamic Regulation of the Extracellular Matrix After Mechanical Unloading of the Failing Human Heart: Recovering the Missing Link in Left Ventricular Remodeling Circulation, September 4, 2001; 104(10): 1089 - 1091. [Full Text] [PDF]
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D. C. Welsh, K. Dipla, P. H. McNulty, A. Mu, K. M. Ojamaa, I. Klein, S. R. Houser, and K. B. Margulies Preserved contractile function despite atrophic remodeling in unloaded rat hearts Am J Physiol Heart Circ Physiol, September 1, 2001; 281(3): H1131 - H1136. [Abstract] [Full Text] [PDF]
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M. L. Ogletree-Hughes, L. B. Stull, W. E. Sweet, N. G. Smedira, P. M. McCarthy, and C. S. Moravec Mechanical Unloading Restores {beta}-Adrenergic Responsiveness and Reverses Receptor Downregulation in the Failing Human Heart Circulation, August 21, 2001; 104(8): 881 - 886. [Abstract] [Full Text] [PDF]
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G. S. Kumpati, P. M. McCarthy, and K. J. Hoercher Left ventricular assist device bridge to recovery: a review of the current status Ann. Thorac. Surg., March 1, 2001; 71 (2007): S103 - S108. [Abstract] [Full Text] [PDF]
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O.H. Frazier, T. J. Myers, R. K. Jarvik, S. Westaby, D. W. Pigott, I. D. Gregoric, T. Khan, D. W. Tamez, J. L. Conger, and M. P. Macris Research and development of an implantable, axial-flow left ventricular assist device: the Jarvik 2000 Heart Ann. Thorac. Surg., March 1, 2001; 71 (2007): S125 - S132. [Abstract] [Full Text] [PDF]
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M. S. Slaughter, M. A. Silver, D. J. Farrar, A. J. Tatooles, and P. S. Pappas A new method of monitoring recovery and weaning the thoratec left ventricular assist device Ann. Thorac. Surg., January 1, 2001; 71(1): 215 - 218. [Abstract] [Full Text] [PDF]
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R. Hetzer, J. H. Muller, Y.-G. Weng, M. Loebe, and G. Wallukat Midterm follow-up of patients who underwent removal of a left ventricular assist device after cardiac recovery from end-stage dilated cardiomyopathy J. Thorac. Cardiovasc. Surg., November 1, 2000; 120(5): 843 - 855. [Abstract] [Full Text] [PDF]
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 E. A. Bocchi, A. Esteves-Filho, G. Bellotti, F. Bacal, L. F. Moreira, N. Stolf, and J. F. Ramires Left ventricular regional wall motion, ejection fraction, and geometry after partial left ventriculectomy. Influence of associated mitral valve repair Eur. J. Cardiothorac. Surg., October 1, 2000; 18(4): 458 - 465. [Abstract] [Full Text] [PDF]
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D. N. Helman, S. W. Maybaum, D. L.S. Morales, M. R. Williams, A. Beniaminovitz, N. M. Edwards, D. M. Mancini, and M. C. Oz Recurrent remodeling after ventricular assistance: is long-term myocardial recovery attainable? Ann. Thorac. Surg., October 1, 2000; 70(4): 1255 - 1258. [Abstract] [Full Text] [PDF]
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 A K Mahmood, J M Courtney, S Westaby, M Akdis, and H Reul Critical review of current left ventricular assist devices Perfusion, September 1, 2000; 15(5): 399 - 420. [PDF]
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S. Westaby New implantable blood pumps for medium and long-term circulatory support Perfusion, July 1, 2000; 15(4): 319 - 325. [PDF]
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D R Wheeldon, P G. Jansen, and P M Portner The Novacor electrical implantable left ventricular assist system Perfusion, July 1, 2000; 15(4): 355 - 361. [PDF]
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O.H. Frazier, S. Gradinac, A. M. Segura, P. Przybylowski, Z. Popovic, J. Vasiljevic, A. Hernandez, H. A. McAllister Jr, M. Bojic, and B. Radovancevic Partial left ventriculectomy: which patients can be expected to benefit? Ann. Thorac. Surg., June 1, 2000; 69(6): 1836 - 1841. [Abstract] [Full Text] [PDF]
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H. Suma, T. Isomura, T. Horii, T. Sato, N. Kikuchi, K. Iwahashi, and J. Hosokawa NONTRANSPLANT CARDIAC SURGERY FOR END-STAGE CARDIOMYOPATHY J. Thorac. Cardiovasc. Surg., June 1, 2000; 119(6): 1233 - 1245. [Abstract] [Full Text] [PDF]
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 S. Westaby HEART FAILURE: Non-transplant surgery for heart failure Heart, May 1, 2000; 83(5): 603 - 603. [Full Text]
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Y. Takeishi, T. Jalili, B. D. Hoit, D. L. Kirkpatrick, L. E. Wagoner, W. T. Abraham, and R. A. Walsh Alterations in Ca2+ cycling proteins and G{alpha}q signaling after left ventricular assist device support in failing human hearts Cardiovasc Res, March 1, 2000; 45(4): 883 - 888. [Abstract] [Full Text] [PDF]
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A. S. Shah, R. E. Lilly, A. P. Kypson, O. Tai, J. A. Hata, A. Pippen, S. C. Silvestry, R. J. Lefkowitz, D. D. Glower, and W. J. Koch Intracoronary Adenovirus-Mediated Delivery and Overexpression of the {beta}2-Adrenergic Receptor in the Heart : Prospects for Molecular Ventricular Assistance Circulation, February 1, 2000; 101(4): 408 - 414. [Abstract] [Full Text] [PDF]
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R. Houel, E. Vermes, D. B. Tixier, P. Le Besnerais, N. Benhaiem-Sigaux, and D. Y. Loisance Myocardial recovery after mechanical support for acute myocarditis: is sustained recovery predictable? Ann. Thorac. Surg., December 1, 1999; 68(6): 2177 - 2180. [Abstract] [Full Text] [PDF]
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B. Bartling, H. Milting, H. Schumann, D. Darmer, L. Arusoglu, M. M. Koerner, A. El-Banayosy, R. Koerfer, J. Holtz, and H.-R. Zerkowski Myocardial Gene Expression of Regulators of Myocyte Apoptosis and Myocyte Calcium Homeostasis During Hemodynamic Unloading by Ventricular Assist Devices in Patients With End-Stage Heart Failure Circulation, November 9, 1999; 100 (2009): II-216 - II-223. [Abstract] [Full Text] [PDF]
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G. Torre-Amione, S. J. Stetson, K. A. Youker, J.-B. Durand, B. Radovancevic, R. M. Delgado, O. H. Frazier, M. L. Entman, and G. P. Noon Decreased Expression of Tumor Necrosis Factor-{alpha} in Failing Human Myocardium After Mechanical Circulatory Support : A Potential Mechanism for Cardiac Recovery Circulation, September 14, 1999; 100(11): 1189 - 1193. [Abstract] [Full Text] [PDF]
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 S Westaby, O Franklin, and M Burch New developments in the treatment of cardiac failure Arch. Dis. Child., September 1, 1999; 81(3): 276 - 277. [Full Text]
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O.H. Frazier and T. J. Myers Left ventricular assist system as a bridge to myocardial recovery Ann. Thorac. Surg., August 1, 1999; 68(2): 734 - 741. [Abstract] [Full Text] [PDF]
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R. Hetzer, J. Muller, Y. Weng, G. Wallukat, S. Spiegelsberger, and M. Loebe Cardiac recovery in dilated cardiomyopathy by unloading with a left ventricular assist device Ann. Thorac. Surg., August 1, 1999; 68(2): 742 - 749. [Abstract] [Full Text] [PDF]
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Y. Nose, K.-i. Nakata, M. Yoshikawa, G. V. Letsou, A. Fujisawa, E. Wolner, and H. Schima Development of a totally implantable biventricular bypass centrifugal blood pump system Ann. Thorac. Surg., August 1, 1999; 68(2): 775 - 779. [Abstract] [Full Text] [PDF]
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O.H Frazier Left ventricular assist device as a bridge to partial left ventriculectomy Eur. J. Cardiothorac. Surg., January 1, 1999; 15(suppl_1): 20 - 25. [Abstract] [Full Text] [PDF]
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D. L. Mann and J. T. Willerson Left Ventricular Assist Devices and the Failing Heart : A Bridge to Recovery, a Permanent Assist Device, or a Bridge Too Far? Circulation, December 1, 1998; 98(22): 2367 - 2369. [Full Text] [PDF]
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D. M. Mancini, A. Beniaminovitz, H. Levin, K. Catanese, M. Flannery, M. DiTullio, S. Savin, M. E. Cordisco, E. Rose, and M. Oz Low Incidence of Myocardial Recovery After Left Ventricular Assist Device Implantation in Patients With Chronic Heart Failure Circulation, December 1, 1998; 98(22): 2383 - 2389. [Abstract] [Full Text] [PDF]
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S. Westaby, T. Katsumata, R. Houel, R. Evans, D. Pigott, O. H. Frazier, and R. Jarvik Jarvik 2000 Heart : Potential for Bridge to Myocyte Recovery Circulation, October 13, 1998; 98(15): 1568 - 1574. [Abstract] [Full Text] [PDF]
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W. E. Pae Jr, J. M. Anderson, E. H. Blackstone, H. S. Boroevetz, A. Ciarkowski, J. G. Copeland III, M. R. Costanzo-Nordin, K. Daase, M. A. Dew, M. J. Domanski, et al. Bethesda conference: conference for the design of clinical trials to study circulatory support devices for chronic heart failure Ann. Thorac. Surg., October 1, 1998; 66(4): 1452 - 1465. [Full Text] [PDF]
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A. Zafeiridis, V. Jeevanandam, S. R. Houser, and K. B. Margulies Regression of Cellular Hypertrophy After Left Ventricular Assist Device Support Circulation, August 18, 1998; 98(7): 656 - 662. [Abstract] [Full Text] [PDF]
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S. A. Hunt and O.H. Frazier Mechanical Circulatory Support and Cardiac Transplantation Circulation, May 26, 1998; 97(20): 2079 - 2090. [Full Text] [PDF]
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L. F. P. Moreira, N. A. G. Stolf, E. A. Bocchi, F. Bacal, M. C. P. Giorgi, J. R. Parga, and A. D. Jatene Partial left ventriculectomy with mitral valve preservation in the treatment of patients with dilated cardiomyopathy J. Thorac. Cardiovasc. Surg., April 1, 1998; 115(4): 800 - 807. [Abstract] [Full Text] [PDF]
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R. Jarvik, S. Westaby, T. Katsumata, D. Pigott, and R. D. Evans LVAD Power Delivery: A Percutaneous Approach to Avoid Infection Ann. Thorac. Surg., February 1, 1998; 65(2): 470 - 473. [Abstract] [Full Text] [PDF]
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S. Westaby, X. Y. Jin, T. Katsumata, D. P. Taggart, A. J. S. Coats, and O. H. Frazier Mechanical Support in Dilated Cardiomyopathy: Signs of Early Left Ventricular Recovery Ann. Thorac. Surg., November 1, 1997; 64(5): 1303 - 1308. [Abstract] [Full Text]
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T. Katsumata and S. Westaby Left Ventricular Reduction Operation in Ischemic Cardiomyopathy: A Note of Caution Ann. Thorac. Surg., October 1, 1997; 64(4): 1154 - 1156. [Abstract] [Full Text]
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S. Westaby, T. Katsumata, R. Evans, D. Pigott, D. P. Taggart, and R. K. Jarvik THE JARVIK 2000 OXFORD SYSTEM: INCREASING THE SCOPE OF MECHANICAL CIRCULATORY SUPPORT J. Thorac. Cardiovasc. Surg., September 1, 1997; 114(3): 467 - 474. [Abstract] [Full Text]
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J. Muller, G. Wallukat, Y.-G. Weng, M. Dandel, S. Spiegelsberger, S. Semrau, K. Brandes, V. Theodoridis, M. Loebe, R. Meyer, et al. Weaning From Mechanical Cardiac Support in Patients With Idiopathic Dilated Cardiomyopathy Circulation, July 15, 1997; 96(2): 542 - 549. [Abstract] [Full Text]
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