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.
OBJECTIVE
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).


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 six-minute 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.
Thoraxcenter, Erasmus University Medical Center, Rotterdam, The Netherlands. h.duckers@erasmusmc.nl
Henricus J
HJ
Duckers
Jaco
J
Houtgraaf
Christoph
C
Hehrlein
Joachim
J
Schofer
Johannes
J
Waltenberger
Anthony
A
Gershlick
Jozef
J
Bartunek
Christoph
C
Nienaber
Carlos
C
Macaya
Nicholas
N
Peters
Peter
P
Smits
Thomasz
T
Siminiak
Walter
W
van Mieghem
Victor
V
Legrand
Patrick W
PW
Serruys
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000627:therapeutic use; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy; D002478:Cells, Cultured; D018450:Disease Progression; D015716:Electrocardiography, Ambulatory; D017079:Exercise Tolerance; D005260:Female; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009206:Myocardium; D013318:Stroke Volume; D014182:Transplantation, Autologous / Q000009:adverse effects / Q000379:methods; D016277:Ventricular Function, Left
D000889:Anti-Arrhythmia Agents; D000638:Amiodarone