Skip Navigation

European Journal of Heart Failure 2006 8(6):641-648; doi:10.1016/j.ejheart.2005.12.004
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Biagini, E.
Right arrow Articles by Serruys, P. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Biagini, E.
Right arrow Articles by Serruys, P. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2005 European Society of Cardiology

Stress and tissue Doppler echocardiographic evidence of effectiveness of myoblast transplantation in patients with ischaemic heart failure

Elena Biagini, Marco Valgimigli, Pieter C. Smits, Don Poldermans, Arend F.L. Schinkel, Vittoria Rizzello, Emile E.M. Onderwater-, Manolis Bountioukos and Patrick W. Serruys*

Department of Cardiology, Thoraxcenter, Erasmus MC Bd406, Dr. Molewaterplein 40, 3015-GD Rotterdam, The Netherlands

* Corresponding author. E-mail address: p.w.j.c.serruys{at}erasmusmc.nl (P.W. Serruys).


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Clinical implications and...
 References
 
Background: There is experimental evidence that transplanting skeletal myoblasts (SM) into the post-infarction myocardial scar improves regional and global left ventricular (LV) function.

Aims: To evaluate short- and long-term regional and global LV functional effects of percutaneously transplanted SM in patients with ischaemic heart failure.

Methods and results: Ten patients (mean age 60 ± 10 years, 8 males) with dilated ischaemic cardiomyopathy underwent percutaneous injection of autologous myoblasts. Regional and global LV function was evaluated by 2-dimensional echocardiography and tissue Doppler imaging (TDI) at rest and during low-dose dobutamine infusion to assess contractile reserve. After a baseline examination, sequential follow-ups were performed at 1, 3, and 6 months and 1 year. NYHA functional class decreased from 2.7 ± 0.5 to 1.9 ± 0.5 (p < 0.01) at one year. LV function and volumes at rest remained unchanged while contractile reserve significantly improved during follow-up. At low-dose dobutamine infusion, the peak systolic velocity in the regions of myoblasts injection significantly increased at TDI examination (from 7.7 ± 2.1 to 8.6 ± 1.8 cm/s, p = 0.02); LV ejection fraction improved (from 40 ± 9% to 46 ± 8%, p < 0.0001) and end-systolic volumes decreased (from 56 ± 28 to 50 ± 25 ml/m2, p = 0.001) at 1 year.

Conclusion: In patients with ischaemic heart failure, percutaneous injection of autologous myoblasts may improve regional and global LV systolic function during dobutamine infusion, at 1-year follow-up.

Key Words: Myocardial infarction • Cell transplantation • LV function • Stress echocardiography • Tissue Doppler imaging

Received May 5, 2005; Revised August 18, 2005; Accepted December 8, 2005


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 5. Clinical implications and...
 References
 
The clinical syndrome of heart failure has become the most prevalent cause of mortality, morbidity and hospitalisation in industrialized countries over recent years [1,2]. The incidence of HF is expected to increase in the future due to improved survival rates following acute myocardial infarction, which is the principal aetiology of heart failure in >70% of patients [3]. The mechanisms leading to heart failure following acute myocardial infarction are only partially understood [4,5], according to current understanding, a progressive decrease in the number of viable myocytes after an acute myocardial infarction could at least partially explain the transition. Therefore, myocardial infarction and subsequent heart failure can be viewed as a disease of cellular deficiency [6].

Myocardial cell replacement therapy by transplantation of skeletal myoblasts (SM) or bone marrow stem cells into the region of infarcted myocardium has been proposed as an alternative treatment in patients with ischaemic cardiomyopathy and severe, drug-refractory heart failure [7-9]. Indeed, recent studies have suggested that the transdifferentiation of c-kit-positive bone marrow cells into cardiomyocytes is controversial and the number of cells undergoing this process may be too low to affect cardiac function [10]. SM are the only cell types that have been proven to form areas of cellular engraftment with histological evidence of viability (development into myotubes and expression of human myosin heavy chain) [11,12] when injected into the heart. Moreover, SM are relatively more resistant to myocardial ischaemia compared to cardiomyocytes. Studies in animal models have shown improvement in regional and global LV function late after myoblast transplantation, and initial observations on humans have confirmed this finding [13-18].

Although cardiac magnetic resonance imaging (MRI) has emerged during the last decade as the gold standard to assess regional and global LV function, its availability may be limited for the evaluation of large numbers of patients. Moreover, the need to implant a cardioverter-defibrillator may further limit the use of MRI in this patient population. Two-dimensional echocardiography with dobutamine infusion is an established technique to quantify regional and global myocardial systolic dysfunction [19]. Moreover, the ability to assess even minor changes in regional LV function has been recently redefined by the introduction of tissue Doppler imaging (TDI) in the clinical setting [20,21]. Therefore we sought to evaluate the short- and long-term impact of percutaneously transplanted SM in patients with ischaemic heart failure as assessed by two-dimensional echocardiography and TDI during dobutamine infusion.


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 5. Clinical implications and...
 References
 
2.1. Patient population
Patients with a previous myocardial infarction involving the anterior, lateral or inferior walls, depressed LV function (LV ejection fraction [EF] between 20% and 45%), and NYHA class ≥II despite optimized medical therapy were included in the study. Myocardial infarction had to be >4 weeks old at the time of implantation. The presence and location of a myocardial scar were defined by: akinesia or dyskinesia at rest during echocardiography or LV angiography and no contractile reserve during dobutamine stress echocardiography (DSE). Exclusion criteria for myoblast injections were: target region wall thickness <5 mm by echocardiography, presence of ischaemia during dobutamine stress echocardiography, and positive serologic test results for human immunodeficiency virus, hepatitis B or C, or syphilis. Patients with <5 mm infarct wall thickness were excluded because it has previously been shown that this is associated with scar tissue and probably with extensive fibrosis that virtually excludes recovery of contractile function [22].

Five patients were part of a previously reported [9] single centre pilot study to assess safety and feasibility. The remaining five patients were enrolled in a multicentre European study (005-006). A TDI substudy was performed only in patients enrolled at the Thoraxcenter, in Rotterdam.

2.2. Muscle biopsy
Biopsy of the quadriceps muscle was done under local anaesthesia. All biopsy procedures were uneventful and done on an outpatient basis. Biopsies were placed in a bottle containing a proprietary solution designed to preserve the biopsy during controlled shipment. The bottle was put in an insulated thermobox with frozen and refrigerated gel packs to maintain temperatures between 2 and 8 °C during transit. The transport conditions were monitored by the use of a programmable temperature monitor (Sensitech, Beverly, Massachusetts). The container was sent to clinical Good Manufacture Practice (BioWhittaker, Cambrex Corp., Walkersville, Maryland) for myoblast cell isolation and expansion.

2.3. Cell transplantation
The cell-culturing process was performed as previously described [9]. The cell transplantation procedure was done in the cardiac catheterization laboratory. Access was obtained through the femoral artery, and 100 IU/kg heparin was given. The target activated clotting time was between 250 and 300 s and was regularly checked every half hour. After a coronary and biplane LV angiogram (left anterior oblique 60° and right anterior oblique 30°) was obtained, an outline of the LV chamber in end diastole was drawn on transparent tabloids that were taped to the fluoroscopy monitors to assist navigation and documentation of injection locations. Then a 3D electromechanical NOGA map [23] of the LV was obtained using a 7F NOGASTAR catheter (F-curve) connected to the NOGA console (Biosense-Webster, Waterloo, Belgium).

After mapping the LV, the mapping catheter was exchanged for an injection catheter (Myostar, Biosense-Webster, Waterloo, Belgium). Injections of 0.1 cc each (approximately 15 million cells per injection) were made, using the acquired NOGA map for navigating the tip of the injection catheter along the endomyocardium to the target locations. After the injection procedure, a control biplane LV angiogram was obtained. Afterwards, patients underwent ECG monitoring for 18 h, and cardiac enzymes were checked twice at 6- to 8-h intervals.

2.4. Two-dimensional echocardiography
Two-dimensional echocardiography was performed at baseline and 1, 3, and 6 months and 1 year of follow-up using a commercially available imaging system equipped with a 1.8 MHz transducer and second harmonic imaging to optimize the endocardial border (Hewlett Packard Sonos 5500, Andover, Massachusetts, USA). Short-axis parasternal view and apical 4-, 3-, and 2-chamber views were recorded in a quad-screen format.

2.5. Dobutamine stress protocol
Before cell transplantation was performed, patients underwent a complete dobutamine stress test, targeting the achievement of 85% of maximal age- and sex-predicted heart rate. Dobutamine-atropine stress testing was performed according to a standard protocol as previously reported [24]. After obtaining a baseline echocardiogram, dobutamine was administered intravenously at a starting dose of 5-10 µg/kg/min for 5 min (low dose). Incremental dobutamine doses of 10 µg/kg/min were given at 3-min intervals up to a maximum dose of 40 µg/kg/min. If the test end-point was not reached at a dobutamine dose of 40 µg/kg/min, atropine (up to 2 mg) was given intravenously. Blood pressure, heart rate, and electrocardiography were constantly monitored. Subsequent tests at 1, 3, and 6 months and 1 year were performed at low-dose dobutamine infusion and were stopped after data acquisition at 10 µg/kg/min dobutamine infusion.

Two-dimensional echocardiographic images were acquired at rest, during dobutamine stress, and recovery. The echocardiograms were recorded in a quad-screen format. Two experienced observers, blinded to the clinical data, scored the echocardiograms using a standard 16-segment model. In case of disagreement, a consensus decision was achieved by a third observer. Regional wall motion and systolic wall thickening were scored on a 5-point scale (1 = normal, 2 = mild hypokinesia, 3 = severe hypokinesia, 4 = akinesia, 5 = dyskinesia). Ischaemia was defined as new or worsened wall motion abnormalities during stress, indicated by an increase of wall motion score ≥1 grade in ≥1 segment. For each patient, a wall motion score index (WMSI) was calculated by dividing the sum of scores of visualized segments by the total number of segments. LV volumes were measured from both resting and low-dose dobutamine stress echocardiography (before and sequentially after myoblast injection). All measurements were performed off line in random order by 2 experienced readers blinded to patient data and the time of the studies. LV volumes were measured by the biplane modified Simpson's rule [25]. LV volumes were normalized to the body surface area to obtain the end-diastolic volume index and the end-systolic volume index [26]. The intra-observer variability was 4±1 ml/m2 for the end-diastolic volume index and 3±1 ml/m2 for the end-systolic volume index. The inter-observer variability was 5±1 ml/m2 for the end-diastolic volume index and 4±1 ml/m2 for the end-systolic volume index.

2.6. Tissue Doppler imaging
Pulsed-wave TDI was performed with the same system used for the assessment of wall motion abnormalities, with a pulse repetition frequency of 45 to 60 KHz and a sample volume of 4 mm3. To minimize the variability induced by respiration [23], the measurement of myocardial velocity was sampled using a six-segment model in 3 apical views (4-chamber, 2-chamber, and long-axis) close to the mitral annulus and during a minimum of 5 consecutive beats. The depth of the sample volume of every region was kept constant during dobutamine stress echocardiography to make sure that the LV myocardium was sampled close to the mitral annulus. The electrocardiogram and phonocardiogram were simultaneously recorded with the pulsed-wave TDI velocity profile. Images were both recorded on tape and digitally stored on an Enconcert workstation (Philips, Eindhoven, The Netherlands). The velocity values (centimetres per second) were obtained on calibrated still frames by manually measuring the distance between the zero baselines and the peak Doppler profile of the ejection phase, in reference to the electrocardiogram and calculated as the mean value of 3 measurements. Cardiac cycles with extrasystolic, postextrasystolic beats, or rhythm disturbance were excluded. Recordings and measurements were performed at baseline and during low-dose (10 µg/kg/min) dobutamine infusion rate. A second observer, blinded to the results of the first observer, measured tissue Doppler velocities of the same patients. The inter-observer and intra-observer agreement for systolic velocities were 96% and 97%, respectively.

2.7. Statistical analysis
Continuous data were expressed as mean value±SD. The Student's t test was used to analyze continuous data. Proportions for dichotomous data were compared by Chi-square analysis. Repeated measurements were analyzed using repeated measurements analysis of variance (ANOVA) to evaluate differences over time. Measurements were represented at defined time-points. To provide a robust comparison between the post-transplantation end-points, all measurements that were presented are the average of 3 repeated measurements. Mean values with standard error and standard deviations were used at each control. For all tests, a two-tailed p value <0.05 was considered statistically significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 5. Clinical implications and...
 References
 
3.1. Patient characteristics
Baseline clinical characteristics and cell-culturing results of the 10 patients (mean age 60±10 years, 80% men) are listed in Table 1. Mean time interval between the occurrence of previous myocardial infarction and the study procedure was 7 years (range 2 to 18 years). No procedural complications occurred. A minor elevation of creatine kinase MB (<2 times upper level) and troponin T (<0.16 µg/l) was noted after the procedure in 3 patients.


View this table:
[in this window]
[in a new window]

  		Table 1 Baseline characteristics (n=10)

 
NYHA functional class decreased from 2.7±0.5 to 1.9±0.5 (p<0.01), at one year. During a mean follow-up of 29±8 months, 1 patient was readmitted to the hospital due to heart failure symptoms. Two patients out of the 6 with an ICD had appropriate shocks due to major arrhythmias. No patients experienced myocardial infarction.

3.2. Resting contractile function and contractile reserve
The mean LV EF at baseline was 36±8% at rest and 41±9% during low-dose dobutamine infusion. In 160 segments evaluated at baseline echocardiography, 23 (14%) were defined as having a normal contractile function, while 137 (86%) were defined as dysfunctional, of these 29 (18%) were mildly hypokinetic, 51 (32%) severely hypokinetic, and 57 (36%) akinetic. Of the 137 dysfunctional segments, 105 (77%) showed contractile reserve during dobutamine infusion (increase in WMSI by one grade or more during low-dose dobutamine infusion). No segments showed myocardial ischaemia at peak of stress. The baseline WMSI at rest and during low-dose dobutamine infusion was 6.4±1.9 and 7.8±2.5 cm/s, respectively. The haemodynamic response at rest and during dobutamine test at baseline is shown in Table 2.


View this table:
[in this window]
[in a new window]

  		Table 2 Dobutamine stress echocardiographic data

 
3.3. WMSI and TDI changes during the follow-up
There were no significant changes in WMSI at rest and low-dose dobutamine infusion at 1-year follow-up (from 6.4±1.9 to 6.4±0.9 cm/s for resting WMSI, p=0.4, from 7.8±2.5 to 8.0±1.9 cm/s for stress WMSI, p=0.67), (Table 3). Similarly, no significant improvement in global peak systolic velocity determined by TDI at both rest echocardiogram (from 6.5±1.9 to 6.5±1.2 cm/s, p=0.19) and during low-dose dobutamine infusion (from 7.9±2.4 to 8.2±2.1 cm/s, p=0.13) was found at 1-year follow-up. Selecting systolic velocity in the regions of myoblast injections, no significant changes were found at 1-year follow-up in the rest measurements, whereas a significant improvement was observed during low-dose dobutamine infusion (from 7.7±2.1 to 8.6±1.8 cm/s, p=0.02) (Table 3 and Figs. 1 and 2).


View this table:
[in this window]
[in a new window]

  		Table 3 Wall Motion Score Index (WMSI) and global peak systolic velocity measured by tissue Doppler imaging (TDI) over the one-year follow-up

 


Figure 1
View larger version (11K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Changes in peak systolic velocity measured by TDI in the region of the myoblast injection during 1-year follow-up. (Figure 1 mean, Figure 1 mean±standard error, Figure 1 mean±standard deviation).

 


Figure 2
View larger version (45K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Peak systolic velocity in the region of myoblast injection measured by TDI at baseline (upper part) and at 1 year of follow-up (lower part) at rest (panel A and B) and during low-dose dobutamine stress echocardiography (panel C and D). A significant increase in velocity is shown during low-dose dobutamine infusion between baseline and 1-year follow-up.

 
3.4. Ejection fraction and left ventricular volumes
No significant improvement in resting LV EF was observed at 1-year follow-up (Table 4 and Fig. 3). Similarly, resting end-diastolic and end-systolic volume index did not significantly change during the follow-up. Conversely, during low-dose dobutamine infusion, a significant improvement in EF was observed (from 40±9% to 46±8%, p<0.0001). LV end-diastolic volume index did not significantly change, whereas end-systolic volume index significantly decreased (from 56±28% to 50±25%, p=0.0001).


View this table:
[in this window]
[in a new window]

  		Table 4 Left ventricular ejection fraction (LV EF), end-diastolic and end-systolic volume index over the one-year follow-up

 


Figure 3
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Changes in LV EF at rest (panel A) and during low-dose dobutamine infusion (panel B) during 1-year follow-up.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
5. Clinical implications and...
 References
 
Transplantation of SM into the region of infarcted myocardium has recently emerged as a promising alternative treatment for severe ischaemic LV dysfunction. Our substudy investigation showed an improvement of target wall systolic velocity and of global LV function during low-dose dobutamine infusion, indicating an improvement of contractile reserve. It is interesting to note that the observed improvement in LV performance was sustained over time, persisting for up to 1 year, underscoring the potential of this novel percutaneous approach in the treatment of end-stage ischaemic LV dysfunction. The widely available and relatively inexpensive two-dimensional stress echocardiography and TDI appeared to be promising tools for monitoring the effect of SM injections in this patient population.

4.1. Comparison to previous studies
Experimental studies have suggested an improvement in regional and global LV performance after cell transplantation. Ghostine et al. [18] studied global and regional LV functional changes by echocardiography and TDI, in a sheep model (n=16) of infarction 4 and 12 months after in-scar injections of autologous SM (n=8) or culture medium (n=8). LV end-diastolic volume increased to a greater extent over time in the control group compared to the myoblast group at 4 months, whereas LV EF significantly decreased in the control animals but remained unchanged in the myoblast animals. TDI showed a decrease in the systolic myocardial velocity gradient in the control group but an increase in the myoblast group, but the difference between the two groups was only marginally significant.

Menasché et al. [8] studied 10 patients with severe ischaemic cardiomyopathy who underwent autologous skeletal myoblast transplantation during bypass surgery. In 8 of the 9 operative survivors, LV EF significantly increased after treatment, due to a decrease in end-systolic LV volume, whereas the end-diastolic volume remained unchanged postoperatively. Moreover, 14 out of 22 implanted in-scar segments demonstrated new-onset echocardiographic systolic shortening. However, the improvement in regional and global systolic function may reflect the efficacy of myocardial revascularisation and cannot be solely ascribed to the injection of myoblasts.

In a recent pilot study [9], our group reported an initial experience in 5 patients who underwent catheter-based cell transplantation with autologous skeletal myoblasts. A significant improvement in LV EF was observed at three months by angiography but not by nuclear or magnetic resonance imaging assessment. At six months, a trend toward increased LV EF was observed by both angiography and nuclear scan. Similarly, the TDI results showed a trend towards increased contraction velocity at six months follow-up.

4.2. Possible explanation for the findings
The mechanism whereby an improvement in regional and global function occurs during low-dose dobutamine infusion indicating an improvement of contractile reserve remains uncertain. In animal models an increase in contractility assessed by two-dimensional echocardiography as well as TDI or colour kinesis has been shown to be related, at least in part, to the success of the procedure [13,18]. The assumption that the islets of implanted cells could be mechanically recruited by the contraction of the surrounding recipient myocardium, even in the absence of gap junctions, may explain an improvement in contractile reserve and systolic function under catecholamine stimulation.

Although the improvement in global LV function during low-dose dobutamine infusion at follow-up could be related to a compensatory phenomenon in the myocardium adjacent to the scar tissue, the improvement in systolic velocity at the sites of myoblast injection assessed by TDI can be only explained by an increased systolic contractility of these regions. Moreover, no patients developed an increase in LV volumes and subsequent LV remodelling during the follow-up. Initial data suggested that in patients with ischaemic cardiomyopathy the reversal of ongoing LV remodelling after revascularisation has to be considered an important end-point [27], and myocardial viability (assessed by the presence of contractile reserve) represents the most important parameter to determine the direction of LV volume changes [28].

4.3. Limitations
The study population is limited. Further studies, including larger numbers of patients, are ongoing in the attempt to confirm and possibly extend our current findings. Echocardiographic measurements were not analyzed by independent core lab. This study was not a "controlled" trial including a comparison group to control for the effect of cell type, vehicle, and time; thus the effects of saline injection in a control group of patients were not examined. It is possible that the injection procedure alone could stimulate a number of cascades that may lead to angiogenesis and thereby provide some beneficial effects. Thus, a direct link between the autologous myoblasts injection and the observed improvement can not be made conclusively.


   5. Clinical implications and conclusions
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Clinical implications and...
References
 
In patients with ischaemic heart failure, percutaneous injection of autologous myoblasts may improve regional and global LV systolic function during dobutamine infusion, at 1-year follow-up.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 5. Clinical implications and...
 References
 

  1. Cleland J.G., Khand A., Clark A. The heart failure epidemic: exactly how big is it? Eur Heart J (2001) 22:623–626.[Free Full Text]
  2. Gheorghiade M., Bonow R.O. Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation (1998) 97:282–289.[Free Full Text]
  3. Challapalli S., Bonow R.O., Gheorghiade M. Medical management of heart failure secondary to coronary artery disease. Coron Artery Dis (1998) 9:659–674.[Web of Science][Medline]
  4. Valgimigli M., Merli E., Malagutti P., et al. Hydroxyl radical generation, levels of tumor necrosis factor-alpha, and progression to heart failure after acute myocardial infarction. J Am Coll Cardiol (2004) 43:2000–2008.[Abstract/Free Full Text]
  5. Cohn J.N., Ferrari R., Sharpe N. Cardiac remodeling—concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an international forum on cardiac remodeling. J Am Coll Cardiol (2000) 35:569–582.[Abstract/Free Full Text]
  6. Kostin S., Pool L., Elsasser A., et al. Myocytes die by multiple mechanisms in failing human hearts. Circ Res (2003) 92:715–724.[Abstract/Free Full Text]
  7. Menasche P., Hagege A.A., Scorsin M., et al. Myoblast transplantation for heart failure. Lancet (2001) 357:279–280.[CrossRef][Web of Science][Medline]
  8. Menasche P., Hagege A.A., Vilquin J.T.B., et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol (2003) 41:1078–1083.[Abstract/Free Full Text]
  9. Smits P.C., van Geuns R.J., Poldermans D., et al. Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up. J Am Coll Cardiol (2003) 42:2063–2069.[Abstract/Free Full Text]
  10. Murry C.E., Soonpaa M., Reinecke H., et al. Haematopoietic stem cells do not transdifferentiate into cardiac myocytes in myocardial infarcts. Nature (2004) 428:664–668.[CrossRef][Medline]
  11. Pagani F.D., DerSimonian H., Zawadzka A., et al. Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans. Histological analysis of cell survival and differentiation. J Am Coll Cardiol (2003) 41:879–888.[Abstract/Free Full Text]
  12. Hagege A.A., Carrion C., Menasche P., et al. Viability and differentiation of autologous skeletal myoblast grafts in ischaemic cardiomyopathy. Lancet (2003) 361:491–492.[CrossRef][Web of Science][Medline]
  13. Rajnoch C., Chachques J.C., Berrebi A., Bruneval P., Benoit M.O., Carpentier A. Cellular therapy reverses myocardial dysfunction. J Thorac Cardiovasc Surg (2001) 121:871–878.[Abstract/Free Full Text]
  14. Pouzet B., Ghostine S., Vilquin J.T., et al. Is skeletal myoblast transplantation clinically relevant in the era of angiotensin-converting enzyme inhibitors? Circulation (2001) 104(Suppl_1):I223–I228.[Web of Science][Medline]
  15. Pouzet B., Vilquin J.T., Hagege A.A., et al. Intramyocardial transplantation of autologous myoblasts: can tissue processing be optimized? Circulation (2000) 102(Suppl 3):III210–III215.[Medline]
  16. Atkins B.Z., Hueman M.T., Meuchel J.M., Cottman M.J., Hutcheson K.A., Taylor D.A. Myogenic cell transplantation improves in vivo regional performance in infarcted rabbit myocardium. J Heart Lung Transplant (1999) 18:1173–1180.[CrossRef][Web of Science][Medline]
  17. Scorsin M., Hagege A., Vilquin J.T., et al. Comparison of the effects of fetal cardiomyocyte and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg (2000) 119:1169–1175.[Abstract/Free Full Text]
  18. Ghostine S., Carrion C., Souza L.C., et al. Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation (2002) 106(Suppl 1):I131–I136.[Web of Science][Medline]
  19. Williams M.J., Odabashian J., Lauer M.S., Thomas J.D., Marwick T.H. Prognostic value of dobutamine echocardiography in patients with left ventricular dysfunction. J Am Coll Cardiol (1996) 27:132–139.[Abstract]
  20. Gorcsan J. 3rd, Strum D.P., Mandarino W.A., Gulati V.K., Pinsky M.R. Quantitative assessment of alterations in regional left ventricular contractility with color-coded tissue Doppler echocardiography. Comparison with sonomicrometry and pressure-volume relations. Circulation (1997) 95:2423–2433.[Abstract/Free Full Text]
  21. Wilkenshoff U.M., Sovany A., Wigstrom L., et al. Regional mean systolic myocardial velocity estimation by real-time color Doppler myocardial imaging: a new technique for quantifying regional systolic function. J Am Soc Echocardiogr (1998) 11:683–692.[CrossRef][Web of Science][Medline]
  22. Cwajg J.M., Cwajg E., Nagueh S.F., et al. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol (2000) 35:1152–1161.[Abstract/Free Full Text]
  23. Ben-Haim S.A., Osadchy D., Schuster I., Gepstein L., Hayam G., Josephson M.E. Nonfluoroscopic, in vivo navigation and mapping technology. Nat Med (1996) 2:1393–1395.[CrossRef][Web of Science][Medline]
  24. Poldermans D., Fioretti P.M., Boersma E., et al. Long-term prognostic value of dobutamine-atropine stress echocardiography in 1737 patients with known or suspected coronary artery disease: a single-center experience. Circulation (1999) 99:757–762.[Abstract/Free Full Text]
  25. Schiller N.B., Shah P.M., Crawford M., et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American society of echocardiography committee on standards, subcommittee on quantitation of two-dimensional echocardiograms. J Am Soc Echocardiogr (1989) 2:358–367.[Medline]
  26. Du Bois D., Du Bois E.F. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition (1989) 5:303–313.[Web of Science][Medline]
  27. Mule J.D., Bax J.J., Zingone B., et al. The beneficial effect of revascularization on jeopardized myocardium: reverse remodeling and improved long-term prognosis. Eur J Cardiothorac Surg (2002) 22:426–430.[Abstract/Free Full Text]
  28. Rizzello V., Poldermans D., Boersma E., et al. Opposite patterns of left ventricular remodeling after coronary revascularization in patients with ischemic cardiomyopathy: role of myocardial viability. Circulation (2004) 110:2383–2388.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 CirculationHome page
P. Menasche, O. Alfieri, S. Janssens, W. McKenna, H. Reichenspurner, L. Trinquart, J.-T. Vilquin, J.-P. Marolleau, B. Seymour, J. Larghero, et al.
The Myoblast Autologous Grafting in Ischemic Cardiomyopathy (MAGIC) Trial: First Randomized Placebo-Controlled Study of Myoblast Transplantation
Circulation, March 4, 2008; 117(9): 1189 - 1200.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart J SupplHome page
T. Siminiak, E. Meliga, O. Jerzykowska, and P. W. Serruys
Percutaneous transplantation of skeletal myoblast in the treatment of post-infarction injury
Eur. Heart J. Suppl., December 1, 2006; 8(suppl_H): H57 - H64.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (9)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Biagini, E.
Right arrow Articles by Serruys, P. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Biagini, E.
Right arrow Articles by Serruys, P. W.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?