Low Incidence of Myocardial Recovery After Left Ventricular Assist Device Implantation in Patients With Chronic Heart Failure
From the Divisions of Circulatory Physiology (D.M.M., A.B., M.E.C.) and Cardiology (D.M.M., A.B., H.L., M.D., S.S.) and the Division of Cardiothoracic Surgery (K.C., M.F., E.R., M.O.), Columbia Presbyterian Medical Center, New York, NY.
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Abstract |
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Background—Mechanical, histological, and biochemical improvement has been described in patients after left ventricular assist device (LVAD) support. Explantation of the LVADs without heart transplantation has been described in selected patients who received this therapy as a bridge to transplantation.
Methods and Results—A retrospective review of patients receiving
a mechanical bridge to transplantation at Columbia Presbyterian
Hospital after July 21, 1991, was performed to determine the
incidence of patients in whom the device was successfully explanted.
From August 1, 1996, to February 1, 1998, we prospectively attempted to
identify potential explant candidates by the use of exercise testing.
During this time, we recruited 39 consecutive patients after insertion
of the Thermo Cardiosystems vented electric device to participate in
the following study. Approximately 3 months after device implantation,
a maximal exercise test with hemodynamic monitoring and
respiratory gas analysis was performed with the LVAD in the
automated mode. The electric device was interfaced with a pneumatic
console such that the rate could be decreased to 20 cycles/min.
Hemodynamic measurements were recorded as the
device rate was decreased. A repeat exercise test was then performed if
the patient remained hemodynamically stable. A
retrospective chart review of 111 LVAD recipients at our institution
identified only 5 successful explant patients. Eighteen of the 39
patients were studied. Fifteen patients exercised with maximal device
support. At peak exercise, 
O2 averaged
14.5±3.6 mL · kg-1 · min-1;
LVAD flow, 8.0±1.3 L/min; Fick cardiac output, 11.4±3.3 L/min; and
pulmonary capillary wedge pressure, 13±4 mm Hg. Seven
patients remained normotensive and could exercise at a fixed rate of 20
cycles/min. In these patients, peak
O2 declined from 17.3±3.9 to 13.0±6.1
mL · kg-1 · min-1. In one of
these patients, the device was explanted.
Conclusions—Significant myocardial recovery after LVAD therapy in patients with end-stage congestive heart failure occurs in a small percentage of patients. Most of these patients have dilated cardiomyopathy. Exercise testing may be a useful modality to identify those patients in whom the device can be explanted.
Key Words: heart-assist device • heart failure
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Introduction |
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Improvement of indices of cardiac function has been observed in patients on mechanical left ventricular assist devices (LVADs) awaiting cardiac transplantation.1 2 3 4 LVADs provide profound LV volume and pressure unloading while simultaneously restoring total systemic blood flow in end-stage congestive heart failure (CHF) patients. Mechanical, histological, and metabolic improvement after LVAD support has been demonstrated in some patients. Levin et al5 demonstrated reverse remodeling with a decreased LV mass and leftward shifts of the end-diastolic pressure-volume relationship in LVAD-supported patients. A reduction of cellular edema,6 more efficient myocardial mitochondria function,7 improved myocyte contraction,8 decreased apoptosis,9 and reversal of neurohormonal stimulation10 have also been described. Recently, Muller et al4 reported the explantation of LVADs, ie, the removal of mechanical support in lieu of transplantation in 5 of 17 patients with dilated cardiomyopathy. A retrospective review of our experience with 111 Thermo Cardiosystems (TCI) devices implanted as a bridge to cardiac transplantation was performed to identify explant patients. Only 5 patients were identified.
From August 1, 1996, to February 1, 1998, we attempted to prospectively identify patients with sufficient myocardial recovery after LVAD insertion by the use of exercise testing with respiratory gas analysis, echocardiographic, and hemodynamic measurements. Measurements were recorded in the fully supported state and as patients were withdrawn from device support. We reasoned that hemodynamic parameters measured at rest and during stress with the ventricle reloaded could potentially quantify myocardial recovery and guide therapy, ie, whether to proceed to transplantation or to explant the device.
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Methods |
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Patient Population
After 1991, 111 patients underwent placement of an LVAD as a bridge to transplantation at Columbia Presbyterian Medical Center. All patients had New York Heart Association class IV CHF, a cardiac index <2 L · min-1 · m-2, pulmonary capillary wedge pressure >25 mm Hg, systolic blood pressure <80 mm Hg, and LV ejection fraction (LVEF) <20%. All patients were supported with multiple inotropic agents and/or intra-aortic balloon counterpulsation. The average age of these patients was 50±13 years; 89 were men and 22 were women. The cause of CHF was coronary artery disease in 60 patients and dilated cardiomyopathy in 51 patients. Duration of implant averaged 100±97 days.
Retrospective Analysis
A retrospective chart review was performed to identify all
explant patients. Clinical outcome and assessment of LV function were
retrieved.
Prospective Analysis
From August 1, 1996, to February 1, 1998, 39 patients had a TCI
vented electric device implanted. Eighteen patients were studied.
Patients were excluded for the following reasons:
perioperative mortality (n=9), awaiting study (n=2),
refusal (n=4), extensive cerebrovascular accident (n=1),
active infection (n=1), and transplanted before study scheduled
(n=4).
The average age of the 13 men and 5 women studied was 47±13 years, 15 of the 18 patients were ambulatory, and preimplant LVEF averaged 19±5%. Twelve patients had dilated cardiomyopathy and 6 patients coronary artery disease. New York Heart Association CHF class was class I in 2 patients, class II in 9, class III in 5, and class IV in 2. Studies were performed an average of 86 days after implantation (range, 34 to 216 days). Medical therapy included digoxin in 4 patients, diuretics in 11, and ACE inhibitors in 5. One patient was on ß-blockers.
Recovery Protocol
Under local anesthesia, a Swan-Ganz catheter
(Abbott) was inserted. In nonambulatory patients, resting
hemodynamic, echocardiographic, and
LVAD sensor measurements were recorded with the patient in the auto
mode of the device (ie, full hemodynamic support) and
then with the device at the lowest fixed rate, ie, 50 cycles/min. The
patients were then heparinized. The electrical device was interfaced
with the pneumatic stroke volume limiter so that the device rate could
be reduced to 20 cycles/min. Downtitration of the LVAD rate by 10
cycles/min was performed with hemodynamic and
echocardiographic measurements every 10 minutes until
the patient developed symptoms or a rate of 20 cycles/min was achieved.
Because the stroke volume of the device is 
80 mL, a fixed rate of 20
cycles/min generates 1.6 L/min flow.
In ambulatory patients, after insertion of a Swan-Ganz catheter, hemodynamic, echocardiographic, metabolic, LVAD sensor, and exercise measurements were made during exercise in the automated mode of the device, during downtitration of the device, and during exercise at a fixed rate of 20 cycles/min. Patients performed exercise in the fasting state and on their usual medical regimen. The subject was seated on a Monark ergometer and connected to a Medical Graphics 2001 Metabolic Cart with a disposable Pneumotach. The transducer was positioned at the level of the fourth intercostal space in the midaxillary line. Resting pulmonary artery, pulmonary wedge, and right atrial pressures and respiratory gases were measured, and blood samples were obtained. Arterial blood pressure was assessed by cuff sphygmomanometer. Baseline echocardiogram was recorded from the parasternal position. After a 3-minute rest period, the patient began bicycle exercise at 0 W. Work was increased by 25-W increments every 3 minutes until exhaustion. Respiratory gas and heart rate measurements were made continuously. Blood sampling, arterial blood pressure, and LVAD sensor measurements were performed during the last minute of each exercise stage. Echocardiograms were recorded in the first minute of recovery.
The arteriovenous oxygen difference was calculated as (arterial-venous O2 saturation)x(1.34 mL O2/g hemoglobin)x(hemoglo-bin concentration). Cardiac output was calculated by use of the Fick equation.
Echocardiographic Measurements
Two-dimensional Doppler echocardiography
was performed with a Hewlett-Packard Sonos 500 imaging system and
recorded with simultaneous ECG. The data were saved on
1/2-in VHS tape for subsequent analysis. Parasternal
long- and short-axis views with color Doppler were recorded.
End-diastolic and end-systolic diameters of the
left ventricle were measured from the parasternal short-axis views.
Average values of 3 successive beats were used for statistical
analysis. Fractional shortening was calculated as the
difference between end-diastolic and end-systolic
diameters divided by the end-diastolic diameter. LV mass
was calculated from the formula of Devereux.11
Aortic valve opening in the parasternal long-axis view was quantified
as a percentage at rest and at peak exercise of the number of beats
with an opened aortic valve over the 10 consecutive cardiac beats
examined. Color Doppler recordings for determination of
device inflow valve insufficiency were also recorded.
Statistical Analysis
Statistical analysis was performed with paired and
nonpaired t tests as appropriate.
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Results |
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Clinical Outcome of Explant Patients
Only 5 patients at our institution have had the devices successfully explanted (Table 1
, Figure 1). Patient 1 was a 18-year-old man with
a cardiomyopathy who was supported with the device
for 186 days. Explantation rather than transplantation was performed.
His LVEF decreased rapidly from 72% to 20%, and he died of CHF 3
months after explantation. Patient 2 was a 47-year-old man with
coronary artery disease who underwent coronary artery
bypass graft surgery, which was complicated by heart failure and
ventricular tachycardia. He underwent LVAD
placement and was supported for 101 days before explantation due to
device infection. He remained in class II CHF until he died suddenly.
There was minimal change in his LVEF over these 2 years. Patient 3 is a
30-year-old man with a cardiomyopathy complicated
by atrial tachyarrhythmias. Explantation rather than
transplantation was performed. The duration of LVAD support was 66
days. At 22 months after explantation, he was readmitted with severe
CHF requiring inotropic support. His LVEF had slowly deteriorated from
45% to 28% over 18 months. He had a cardiac arrest and required
reimplantation of the LVAD 684 days after explantation. The patient
sustained anoxic brain damage after arrest. Sixty days after the second
device implantation, the LVAD failed. Unsupported LVEF had again risen
to 50%.
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Patient 4 is a 47-year-old man with cardiomyopathy who was supported for 58 days before explantation for device infection. He remains in class I CHF 15 months after explantation. His LVEF has remained stable. Patient 5's device was explanted 380 days after device insertion because of infection. Despite treatment with diuretics, digoxin, ACE inhibition, and carvedilol, she experienced a rapid decline in LV function and required reimplantation of the device at 170 days.
Exercise Studies in the Automated Mode
Rest and peak exercise parameters are shown in Table 2. Peak
O2 averaged 14.6 mL ·
kg-1 · min-1 in
the automated mode of the device. At rest, Fick estimates of resting
cardiac output and LVAD sensor measurements were not significantly
different. Only 3 patients had intermittent aortic valve opening. At
peak exercise, Fick cardiac outputs were significantly greater than
LVAD sensor measurements, with aortic valve opening occurring in at
least 7 patients.
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Rest and peak exercise echocardiograms demonstrated that LV cavity size was normal in all but 2 patients. Both of these patients had Doppler signals suggesting inflow valve insufficiency, with LV end-diastolic diameter at rest of 5.9 and 7 cm, respectively. LV mass measurements averaged 186±97 g, reduced from the preimplant estimates of LV mass, which was 332±81 g (P<0.001). Both of these estimates were significantly below the actual explanted heart weights of 400±55 g.
Hemodynamic and Echocardiographic
Measurements With Downtitration of the Device
Hemodynamic measurements recorded during LVAD
downtitration are shown in Table 3. Most
patients could not tolerate downtitration of the device. With
downtitration, heart rate increased, mean arterial blood
pressure fell from 91 to 70 mm Hg, pulmonary artery
capillary wedge pressure rose, and cardiac output fell significantly.
LV diastolic dimension increased. Aortic valve opening was
now present in almost all patients. Figure 2 shows parasternal short-axis views at
rest of end systole and end diastole with maximal and
minimal LVAD support for 1 patient.
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Dizziness and/or diaphoresis occurred in 11 of 18 subjects. Only 7 patients remained hemodynamically stable at a fixed rate of 20 cycles/min.
Exercise at a Fixed Rate of 20 Cycles/min
The clinical characteristics of the 7 patients able to exercise at
a fixed rate of 20 cycles/min are shown in Table 4. Six of the 7 patients had
cardiomyopathy. The mean duration of implant was 4
months. The exercise response in the automated and fixed modes for
these 7 patients is shown in Table 5.
Because of technical problems, we were unable to measure Fick cardiac
outputs in patient 1. In patient 2, echocardiographic
images were suboptimal.
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In these 7 patients, peak O2
decreased from 17.3 to 13 mL · kg-1
· min-1. For patient 2, exercise in the
automated mode showed comparable peak LVAD sensor and Fick cardiac
output. During exercise in the fixed rate, Fick cardiac output was
severely reduced. This suggested that the device could not be explanted
in this patient. In contrast, patients 3 and 4 had higher Fick cardiac
outputs than were recorded by the LVAD sensor during exercise in
the automated mode. In the fixed mode, peak Fick cardiac outputs were
maintained, peak O2
approximated 20 mL · kg-1 ·
min-1, and aortic valve opening was present.
However, patient 3 showed LV dilatation with decreased fractional
shortening, whereas patient 4 had a normal-size left ventricle with a
normal fractional shortening. This suggested that patient 4 had
complete recovery.
Outcome
At the time of transplantation, with the device off, patients 1,
2, and 6 had poor LV function and proceeded to transplantation. In
patients 3 and 7, LV function could not be evaluated because of
surgical problems. Patient 4 underwent successful explantation. Patient
5 had LV function in the range of 35%. Because right nuclear ejection
fraction measured by first-pass radionuclide examination was 14% and
peak O2 was only 9.9 mL
· kg-1 · min-1
with the device at a fixed rate, he proceeded to transplantation.
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Discussion |
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Several studies suggest that the profound ventricular pressure and volume unloading provided by LVAD support leads to reverse remodeling on genetic, biochemical, histological, and functional levels.1 2 3 4 5 6 7 8 9 10 12 Normalization of the LV pressure-volume relationship with regression of LV hypertrophy has been reported.5 A decrease in fibrosis4 and reduction in myocardial matrix metalloproteinase expression may play a role in reverse remodeling.12 Decrease in stretch, profound volume/pressure unloading, increased myocardial perfusion, normalization of neurohormones, and reduction in cytokine release are all potential mechanisms for the reversal of the remodeling process.
In our present study, retrospective analysis identified few patients in whom the devices could be successfully explanted. Similarly, prospective analysis using hemodynamic, echocardiographic, and exercise measurements at rest and during ventricular loading revealed few patients with adequate myocardial recovery to permit explantation. Despite the small number of patients either retrospectively or prospectively identified as explant candidates, the results of this study are strikingly important. All of these patients had presumably irreversible end-stage heart failure, yet these patients demonstrated that their LV function could be dramatically modified and almost returned to normal for short periods.
A recent report from Germany by Muller et al4 identified 5 of 17 patients with dilated cardiomyopathy supported by an LVAD for >160 days in whom the devices were successfully explanted and who maintained normal cardiac function. Our report is similar to that of Muller et al, because the majority of our explant candidates also had dilated cardiomyopathy, and in our prospective analysis, most patients able to support themselves with the ventricle reloaded had dilated cardiomyopathies. In contrast to the German study, in which 29% of the dilated cardiomyopathy patients were explant candidates, the frequency of this phenomenon in our patient population was much lower, including only 5% of all our patients and 8% of the patients with dilated cardiomyopathies. All our patients were on multiple inotropic agents before device insertion; thus, the ability of patients to exercise at a low fixed rate demonstrates intermediate degrees of myocardial recovery. The frequency of partial recovery increases to 50% (6 of 12) in patients with dilated cardiomyopathy and 17% (1 of 6) in patients with coronary artery disease.
In the German report, all LVAD patients received treatment with digoxin, diuretics, ACE inhibitors, ß-blockers, coenzyme Q10, and other nutritional supplements. Our study differs from that of Muller et al4 in that our LVAD patients did not receive the benefit of maximal medical therapy. In our study, <20% of patients received ACE inhibitors or ß-blockers. Initiation of aggressive heart failure therapy might have improved our explantation rates.
Our study also differed from that of Muller et
al4 in that LVAD support duration was shorter and
a rapid rather than prolonged weaning was used to assess recovery. In
our study, duration of device support was determined by the waiting
time for transplantation, which averaged 100 days. Our rapid weaning
may not have allowed the neurohormonal system and/or an atrophied
muscle sufficient time to readjust to the reduction in cardiac output
or to the increased workload. This is unlikely because, although
hypertrophy regresses in device-supported patients,
significant hypertrophy persists, as evidenced by the
increased weights of the explanted hearts in our sample.
Another important difference between the present report and that of Muller et al4 is that normalization of LV function in our explant patients has not been sustained despite aggressive medical therapy. Three of our 5 patients have experienced redilation of the LV, with a decrease in LVEF and recurrence of symptoms after device removal.
A possible explanation for device removal is spontaneous recovery, which has been described in up to 37% of recent-onset cardiomyopathy.13 In a study of 49 patients with new-onset CHF referred for transplant evaluation, 27% showed improvement, with LVEF increasing from 22% to 49%.14 In the NIH trial using immunosuppressive therapy in patients with biopsy-proven myocarditis, LVEF improved significantly.15 Shorter duration of disease and higher LVEF at presentation are predictive of recovery. It is unlikely that our observations are due to spontaneous recovery. None of our explant patients had new-onset CHF or acute myocarditis. Moreover, 3 of 5 patients have developed recurrence of severe heart failure after device explantation. In 1 patient, reinsertion after LVAD again resulted in normalization of EF, thus demonstrating the reproducibility of the phenomenon.
The small percentage of explant candidates may be due to device malfunction, ie, regurgitation or obstruction at the inflow valve, negating the extreme ventricular volume or pressure unloading. Inflow valve regurgitation interferes with reverse remodeling.16 Again, this explanation is unlikely, because the abnormal Doppler flow pattern at the inflow valve characteristic of this malfunction was observed in only 2 patients.
Exercise Performance of LVAD Patients
Measurements recorded during exercise in the automated mode of
the device are comparable to previous reports of exercise
performance in LVAD patients. Average reported peak
O2 during upright exercise of
patients with the Novacor or TCI devices ranges from 14 to 17 mL
· kg-1 ·
min-1.17 18 19 20 Recently, we
compared the exercise hemodynamic response of LVAD
patients with that of patients with severe heart failure awaiting
cardiac transplantation.21 The reduction in
pulmonary pressures and peak exercise performance is
similar to that in this prior report.21
Clinical Parameters to Assess Recovery
Our findings suggest that the ability to exercise at a low fixed
rate to a O2 >20 mL ·
kg-1 · min-1
and/or a peak cardiac output >10 L/min provides sufficient
cardiovascular reserve to tolerate explantation.
Echocardiographic parameters such as
consistent aortic valve opening, normal shortening fraction,
and absence of marked ventricular dilation may also help to
distinguish explant candidates. Additional studies are needed to create
an accurate profile to identify patients with sufficient recovery.
Study Limitations
This study is limited by the small sample size with a low
enrollment rate due to complications related to the device and/or
unpredictable timing of cardiac transplantation. Patients were
frequently reluctant to proceed with a test that would decrease device
support.
A major limitation of this study is that it is descriptive. No attempt was made to identify the mechanism for recovery. Investigators at our institution are currently studying the molecular effects of LVAD support.
Inability to completely turn off the device limited our ability to assess recovery of LVAD function. Although we elected to use exercise as a stress to evaluate LV recovery with the device set at a low fixed rate, other interventions, such as volume loading or pharmacological challenges, might also have provided clinically relevant information.
Clinical Implications
The observations described in this report are important in that
they illustrate that patients at the end stages of heart failure still
possess myocardium that can be restored to normal or
near-normal function. Restoration of function and structure in what had
been believed to be an irreversible state demonstrates the plasticity
of the myocardium. The low incidence of myocardial recovery
described may be improved with medical and/or surgical adjuvant
therapies. Patients with intermediate degrees of recovery could be
identified and targeted for more aggressive CHF therapy and restudied.
In addition, alternative surgical approaches, such as explantation plus
mitral valve repair and/or ventricular reduction surgery,
could be considered.
In the future, heart failure could conceivably be reversed rather than just managed. Implantation of an LVAD is not a practical solution for large numbers of patients because of the high cost and invasiveness of this procedure. Nonetheless, the clinical application of these devices may be able to provide insight into the mechanisms that signal reverse remodeling and thus open the way to cure.
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Acknowledgments |
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This study was supported by a grant from the Division of Research Resources, General Clinical Research Centers Program, NIH 5-M01-RR-00645.
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Footnotes |
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Reprint requests to Donna M. Mancini, MD, Division of Circulatory Physiology, Department of Medicine, Columbia Presbyterian Medical Center, 622 W 168th St, New York, NY 10032.
Received May 27, 1998; revision received July 29, 1998; accepted August 13, 1998.
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References |
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17. Murali S, Uretsky B, Estrada-Quintero T, Tokarczyk T, Cannon Y, Betchart A, Kormos K, Griffith B. Metabolic and ventilatory responses to exercise in heart failure patients on a left ventricular assist system support. Circulation. 1991;84(suppl II):II-354. Abstract.
18. Jaski BE, Branch KR, Adamson R, Peterson KL, Gordon JB, Hoagland PM, Smith SC Jr, Daily PO, Dembitsky WP. Exercise hemodynamics during long-term implantation of a left ventricular assist device in patients awaiting heart transplantation. J Am Coll Cardiol. 1993;22:1574–1580.[Abstract]
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21.
Mancini D, Goldsmith R, Levin H, Beniaminovitz A,
Rose E, Catanese K, Flannery M, Oz M. Comparison of exercise
hemo- dynamic measurements in patients with severe
heart failure and left ventricular assist devices.
Circulation. 1998;98:1178–1183.Some patients who have
received left ventricular assist device (LVAD) support as a
bridge to transplant have developed myocardial recovery, which allowed
explantation of the device. To determine the incidence of explantation
in mechanically bridged patients, we performed a retrospective review
of 111 LVAD patients. Prospective identification of explant candidates
was attempted by exercise testing with hemodynamic,
echocardiographic, and ventilatory measurements with
maximal and minimal LVAD support. The device was explanted in only 5
patients. Seven of the 39 patients could exercise with the device at a
low fixed rate. The device was explanted in 1 of these patients.
Significant myocardial recovery after LVAD therapy occurs in only a
small percentage of patients.
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S. Klotz, A.H. J. Danser, R. F. Foronjy, M. C. Oz, J. Wang, D. Mancini, J. D'Armiento, and D. Burkhoff The Impact of Angiotensin-Converting Enzyme Inhibitor Therapy on the Extracellular Collagen Matrix During Left Ventricular Assist Device Support in Patients With End-Stage Heart Failure J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1166 - 1174. [Abstract] [Full Text] [PDF]
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H. Bugger, S. Leippert, D. Blum, P. Kahle, B. Barleon, D. Marme, and T. Doenst Subtractive hybridization for differential gene expression in mechanically unloaded rat heart Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2714 - H2722. [Abstract] [Full Text] [PDF]
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 E. J. Birks, P. D. Tansley, J. Hardy, R. S. George, C. T. Bowles, M. Burke, N. R. Banner, A. Khaghani, and M. H. Yacoub Left Ventricular Assist Device and Drug Therapy for the Reversal of Heart Failure N. Engl. J. Med., November 2, 2006; 355(18): 1873 - 1884. [Abstract] [Full Text] [PDF]
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 S. Klotz, J. Stypmann, H. Welp, C. Schmid, G. Drees, A. Rukosujew, and H. H. Scheld Does Continuous Flow Left Ventricular Assist Device Technology Have a Positive Impact on Outcome Pretransplant and Posttransplant? Ann. Thorac. Surg., November 1, 2006; 82(5): 1774 - 1778. [Abstract] [Full Text] [PDF]
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M. E. Cullen, A. H.Y. Yuen, L. E. Felkin, R. T. Smolenski, J. L. Hall, S. Grindle, L. W. Miller, E. J. Birks, M. H. Yacoub, and P. J.R. Barton Myocardial Expression of the Arginine:Glycine Amidinotransferase Gene Is Elevated in Heart Failure and Normalized After Recovery: Potential Implications for Local Creatine Synthesis Circulation, July 4, 2006; 114(1_suppl): I-16 - I-20. [Abstract] [Full Text] [PDF]
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J. Wohlschlaeger, K. J. Schmitz, C. Schmid, K. W. Schmid, P. Keul, A. Takeda, S. Weis, B. Levkau, and H. A. Baba Reverse remodeling following insertion of left ventricular assist devices (LVAD): A review of the morphological and molecular changes Cardiovasc Res, December 1, 2005; 68(3): 376 - 386. [Abstract] [Full Text] [PDF]
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G. Matsumiya, O. Monta, N. Fukushima, Y. Sawa, T. Funatsu, K. Toda, and H. Matsuda Who would be a candidate for bridge to recovery during prolonged mechanical left ventricular support in idiopathic dilated cardiomyopathy? J. Thorac. Cardiovasc. Surg., September 1, 2005; 130(3): 699 - 704. [Abstract] [Full Text] [PDF]
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M. A. Simon, R. L. Kormos, S. Murali, P. Nair, M. Heffernan, J. Gorcsan, S. Winowich, and D. M. McNamara Myocardial Recovery Using Ventricular Assist Devices: Prevalence, Clinical Characteristics, and Outcomes Circulation, August 30, 2005; 112(9_suppl): I-32 - I-36. [Abstract] [Full Text] [PDF]
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P. J. R. Barton, L. E. Felkin, E. J. Birks, M. E. Cullen, N. R. Banner, S. Grindle, J. L. Hall, L. W. Miller, and M. H. Yacoub Myocardial Insulin-Like Growth Factor-I Gene Expression During Recovery From Heart Failure After Combined Left Ventricular Assist Device and Clenbuterol Therapy Circulation, August 30, 2005; 112(9_suppl): I-46 - I-50. [Abstract] [Full Text] [PDF]
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H. Tsuneyoshi, W. Oriyanhan, H. Kanemitsu, R. Shiina, T. Nishina, S. Matsuoka, T. Ikeda, and M. Komeda Does the {beta}2-Agonist Clenbuterol Help to Maintain Myocardial Potential to Recover During Mechanical Unloading? Circulation, August 30, 2005; 112(9_suppl): I-51 - I-56. [Abstract] [Full Text] [PDF]
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E. J. Birks, J. L. Hall, P. J.R. Barton, S. Grindle, N. Latif, J. P. Hardy, J. E. Rider, N. R. Banner, A. Khaghani, L. W. Miller, et al. Gene Profiling Changes in Cytoskeletal Proteins During Clinical Recovery After Left Ventricular-Assist Device Support Circulation, August 30, 2005; 112(9_suppl): I-57 - I-64. [Abstract] [Full Text] [PDF]
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D. Mancini and D. Burkhoff Mechanical Device-Based Methods of Managing and Treating Heart Failure Circulation, July 19, 2005; 112(3): 438 - 448. [Abstract] [Full Text] [PDF]
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S. Klotz, R. F. Foronjy, M. L. Dickstein, A. Gu, I. M. Garrelds, A.H. Jan Danser, M. C. Oz, J. D'Armiento, and D. Burkhoff Mechanical Unloading During Left Ventricular Assist Device Support Increases Left Ventricular Collagen Cross-Linking and Myocardial Stiffness Circulation, July 19, 2005; 112(3): 364 - 374. [Abstract] [Full Text] [PDF]
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T. Mizuno, R. D. Weisel, and R.-K. Li Reloading the heart: A new animal model of left ventricular assist device removal J. Thorac. Cardiovasc. Surg., July 1, 2005; 130(1): 99 - 106. [Abstract] [Full Text] [PDF]
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R. D. Patten, D. DeNofrio, M. El-Zaru, R. Kakkar, J. Saunders, F. Celestin, K. Warner, H. Rastegar, K. R. Khabbaz, J. E. Udelson, et al. Ventricular Assist Device Therapy Normalizes Inducible Nitric Oxide Synthase Expression and Reduces Cardiomyocyte Apoptosis in the Failing Human Heart J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1419 - 1424. [Abstract] [Full Text] [PDF]
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R. C. Starling Inducible Nitric Oxide Synthase in Severe Human Heart Failure: Impact of Mechanical Unloading J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1425 - 1427. [Full Text] [PDF]
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S. Klotz, A. Barbone, S. Reiken, J. W. Holmes, Y. Naka, M. C. Oz, A. R. Marks, and D. Burkhoff Left ventricular assist device support normalizes left and right ventricular beta-adrenergic pathway properties J. Am. Coll. Cardiol., March 1, 2005; 45(5): 668 - 676. [Abstract] [Full Text] [PDF]
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P. H. Colson, F. Ryckwaert, M. Saussine, M. Ferriere, and B. Albat Monitoring weaning from BIVAD thoratec with peak oxygen consumption Ann. Thorac. Surg., May 1, 2004; 77(5): 1808 - 1810. [Abstract] [Full Text] [PDF]
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S. Klotz, M. C. Deng, J. Stypmann, J. Roetker, M. J. Wilhelm, D. Hammel, H. H. Scheld, and C. Schmid Left ventricular pressure and volume unloading during pulsatile versus nonpulsatile left ventricular assist device support Ann. Thorac. Surg., January 1, 2004; 77(1): 143 - 149. [Abstract] [Full Text] [PDF]
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L. W. Stevenson and E. A. Rose Left Ventricular Assist Devices: Bridges to Transplantation, Recovery, and Destination for Whom? Circulation, December 23, 2003; 108(25): 3059 - 3063. [Full Text] [PDF]
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J. K. F. Hon and M. H. Yacoub Bridge to recovery with the use of left ventricular assist device and clenbuterol Ann. Thorac. Surg., June 1, 2003; 75(90060): S36 - 41. [Abstract] [Full Text] [PDF]
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B. C. Blaxall, B. M. Tschannen-Moran, C. A. Milano, and W. J. Koch Differential gene expression and genomic patient stratification following left ventricular assist device support J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1096 - 1106. [Abstract] [Full Text] [PDF]
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D. C. Lee, W. Ting, and M. C. Oz Myocardial Revascularization after Acute Myocardial Infarction Card. Surg. Adult, January 1, 2003; 2(2003): 639 - 658. [Full Text]
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E. L. Kukuy, M. C. Oz, and Y. Naka Long-Term Mechanical Circulatory Support Card. Surg. Adult, January 1, 2003; 2(2003): 1491 - 1506. [Full Text]
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H. T. Tevaearai, G. B. Walton, A. D. Eckhart, J. R. Keys, and W. J. Koch Heterotopic transplantation as a model to study functional recovery of unloaded failing hearts J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1149 - 1156. [Abstract] [Full Text]
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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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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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Y. Y. Li, Y. Feng, C. F. McTiernan, W. Pei, C. S. Moravec, P. Wang, W. Rosenblum, R. L. Kormos, and A. M. Feldman Downregulation of Matrix Metalloproteinases and Reduction in Collagen Damage in the Failing Human Heart After Support With Left Ventricular Assist Devices Circulation, September 4, 2001; 104(10): 1147 - 1152. [Abstract] [Full Text] [PDF]
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Y. Ochiai, L. A.R. Golding, A. L. Massiello, A. L. Medvedev, R. L. Gerhart, J.-F. Chen, M. Takagaki, and K. Fukamachi In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump in calves Ann. Thorac. Surg., September 1, 2001; 72(3): 747 - 752. [Abstract] [Full Text] [PDF]
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A. Barbone, J. W. Holmes, P. M. Heerdt, A. H.S. The', Y. Naka, N. Joshi, M. Daines, A. R. Marks, M. C. Oz, and D. Burkhoff Comparison of Right and Left Ventricular Responses to Left Ventricular Assist Device Support in Patients With Severe Heart Failure: A Primary Role of Mechanical Unloading Underlying Reverse Remodeling Circulation, August 7, 2001; 104(6): 670 - 675. [Abstract] [Full Text] [PDF]
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J. D. Madigan, A. Barbone, A. F. Choudhri, D. L. S. Morales, B. Cai, M. C. Oz, and D. Burkhoff Time course of reverse remodeling of the left ventricle during support with a left ventricular assist device J. Thorac. Cardiovasc. Surg., May 1, 2001; 121(5): 902 - 908. [Abstract] [Full Text] [PDF]
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M.H. Yacoub A novel strategy to maximize the efficacy of left ventricular assist devices as a bridge to recovery Eur. Heart J., April 1, 2001; 22(7): 534 - 540. [PDF]
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M. A. Acker Mechanical circulatory support for patients with acute-fulminant myocarditis Ann. Thorac. Surg., March 1, 2001; 71 (2007): S73 - S76. [Abstract] [Full Text] [PDF]
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R. Hetzer, J. H. Muller, Y.-g. Weng, R. Meyer, and M. Dandel Bridging-to-recovery Ann. Thorac. Surg., March 1, 2001; 71 (2007): S109 - S113. [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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E. Vermes, R. Houel, M. Simon, P. Le Besnerais, and D. Loisance Doppler tissue imaging to predict myocardial recovery during mechanical circulatory support Ann. Thorac. Surg., December 1, 2000; 70(6): 2149 - 2151. [Abstract] [Full Text] [PDF]
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P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [Abstract] [Full Text] [PDF]
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S. Mital, K. E. Loke, L. J. Addonizio, M. C. Oz, and T. H. Hintze Left ventricular assist device implantation augments nitric oxide dependent control of mitochondrial respiration in failing human hearts J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1897 - 1902. [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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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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S. J. Park, D. Q. Nguyen, A. J. Bank, S. Ormaza, and R. M. Bolman III Left ventricular assist device bridge therapy for acute myocardial infarction Ann. Thorac. Surg., April 1, 2000; 69(4): 1146 - 1151. [Abstract] [Full Text] [PDF]
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M. C. Deng, T. D.T. Tjan, B. Asfour, and H. H. Scheld Left ventricular assist devices -- reasons to be enthusiastic Eur J Heart Fail, August 31, 1999; 1(3): 289 - 291. [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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