Final results of a phase IIa, randomised, open-label trial to evaluate the percutaneous intramyocardial transplantation of autologous skeletal myoblasts in congestive heart failure patients: the SEISMIC trial

Abstract

Aims: The SEISMIC study was an open-label, prospective, randomised study to assess the safety and feasibility of percutaneous myoblast implantation in heart failure patients with implanted cardioverter-defibrillators (ICD). Methods and results: Patients were randomised 2:1 to autologous skeletal myoblast therapy vs. optimal medical treatment. The primary safety end-point was defined as the incidence of procedural and device related serious adverse events, whereas the efficacy endpoints were defined as the change in global LVEF by MUGA scan, change in NYHA classification of heart failure and in the distance achieved during a sixminute walk test (6MW) at 6-month follow-up. Forty subjects were randomised to the treatment arm (n=26), or to the control arm (n=14). There were 12 sustained arrhythmic events and one death after episodes of ventricular tachycardia (VT) in the treatment group and 14 events in the control group (P=ns). At 6-month follow-up, 6MW distance improved by 60.3±54.1 meters in the treated group as compared to no improvement in the control group (0.4±185.7 meters; P=ns). In the control group, 28.6% experienced worsening of heart failure status (4/14), while 14.3% experienced an improvement in NYHA classification (2/14). In the myoblast-treatment arm, one patient experienced a deterioration in NYHA classification (8.0%), whereas five patients improved one or two classes (20.0%; P=0.06). However, therapy did not improve global LVEF measured by MUGA at 6-month follow-up. Conclusions: These data indicate that implantation of myoblasts in patients with HF is feasible, appears to be safe and may provide symptomatic relief, though no significant effect was detected on global LVEF.

Meta-Analysis of Cell Therapy Trials for Patients With Heart Failure

“…20 One trial administered cardiac stem cells, obtained from a right atrial appendage biopsy followed by magnetic separation and culture of c-kit-positive cells. 49 The remaining 4 trials isolated SM from muscle biopsies followed by culture of the cells ex vivo and identification of a SM population 37,42,44,51 containing ≥50% of CD56-positive cells. 37,42,51 Finally, 1 trial administered adipose-derived regenerative cells obtained by liposuction and followed by enzymatic digestion of the adipose tissue, cell separation, and cell elution using commercially available devices.…”

“…49 The remaining 4 trials isolated SM from muscle biopsies followed by culture of the cells ex vivo and identification of a SM population 37,42,44,51 containing ≥50% of CD56-positive cells. 37,42,51 Finally, 1 trial administered adipose-derived regenerative cells obtained by liposuction and followed by enzymatic digestion of the adipose tissue, cell separation, and cell elution using commercially available devices. 21 The cell dose ranged from 5×10 Fifteen trials compared cells with a placebo, 9,11,21,22,28,29,[31][32][33][34][35]42,44 generally consisting of a cell-free solution, either the participants own serum or a saline solution containing heparin.…”

“…The authors of 18 trials were contacted for clarification of data, including apparent discrepancies and insufficient detail in the reporting of methods or results 19,[22][23][24][25][26][27][28][29] or for mean and standard deviation values of outcomes where not explicitly reported 11,19,25,[30][31][32][33][34][35][36] or where reported graphically. 9,10,[37][38][39] Responses were obtained from authors of 7 trials (see Acknowledgments section). Where possible, for results presented graphically and where actual data values were not forthcoming from study authors (4 studies), mean and standard deviation values were estimated independently by 2 reviewers and the average values were used.…”

Safety and Efficacy of Autologous Skeletal Myoblast Sheets (TCD-51073) for the Treatment of Severe Chronic Heart Failure Due to Ischemic Heart Disease

“…3 Among these treatments, using autologous skeletal myoblasts has been investigated in clinical trials, mainly in Western countries, in which cell transplantation was performed using myocardial injection during a surgical procedure through a thoracotomy, such as coronary artery bypass grafting (CABG) or LVAS implantation, 4 or using myocardial injection of cells through a cardiac catheter. 5 However, results from a European phase II clinical study (MAGIC trial) demonstrated that transplantation ver the past 20 years or so, the treatment of chronic heart failure (HF) has been progressed by use of drug therapies such as β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), and aldosterone antagonists, or device therapy such as cardiac resynchronization therapy. Hence, clinical outcomes of patients with chronic HF are now significantly better, but patients with severe chronic HF who do not respond well to standard drug therapies still have poor outcomes.…”

Cardiac Repair Using Stem Cells Conditioned Media Based Therapy in a Rodent Model of Myocardial Infarction and Heart Failure

“…human and animal models, to varying degrees of success [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] . In animal models, these cellbased therapies have demonstrated effectiveness in reducing infarct size and ventricular dilatation, and improving myocardial function [24][25][26] .…”