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

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/m(2), 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.

Intramyocardial injection of skeletal myoblasts: long-term follow-up with pressure-volume loops.

The human heart has a limited capacity for self-repair because, unlike most other cells, cardiomyocytes do not regenerate. Therefore, if a substantial number of myocytes is lost after a myocardial infarction, the performance of the heart may become severely limited, leading to a condition of heart failure. Recently, cell transplantation has emerged as a potential therapy for patients with end-stage heart failure. Of the various cell types being investigated for this purpose, skeletal myoblasts are an attractive option, because they are readily available from muscle biopsies and, if autologous cells are used, immunosuppression is not required and ethical issues are avoided. Several studies have shown that the cells can survive and differentiate after transplantation, and promising clinical results have been reported. However, effects of this therapy on left ventricular function remain largely unknown. In the present study, we investigated the long-term hemodynamic effects of intramyocardial injection of autologous skeletal myoblasts in patients with ischemic heart failure. Our findings indicate hemodynamic improvement after follow-up for up to 1 year, which is especially promising in view of the expected decline in left ventricular function in these patients.

Myocardial repair by percutaneous cell transplantation of autologous skeletal myoblast as a stand alone procedure in post myocardial infarction chronic heart failure patients.

AIMS: In this first multicentre study we assessed the safety and efficacy of percutaneous transendocardial skeletal myoblast injection as a stand alone procedure in congestive heart failure patients. METHODS AND RESULTS: 15 patients (14 male), age 63+/-7 (Mean+/-SD), NYHA class 2-4 were injected with 216+/-119 cells (81+/-19% Desmin+) using a NOGA or fluoroscopy guided injection catheter. The cells were injected in the scarred regions 6+/-4 years after myocardial infarction as a stand alone procedure. After treating the first 6 patients, the protocol was amended to require that remaining patients be fitted with an ICD prior to the cellular cardiomyoplasty procedure. Holter monitoring, ECG and ICD readings were obtained at multiple intervals. Stress echocardiography and LV angiography was performed at baseline, 3, 6 and 12 months post procedure.After 1 year follow-up 13 patients were still alive. Patient # 6 died suddenly 9 days post procedure. Patient #15 (ICD patient) survived an electrical storm 12 days post procedure, but died 2 days later due to cardiogenic shock. Two non-ICD patients received an ICD because of observed ventricular arrhythmias. It remains unknown whether these events are directly related to the cell injections.LV ejection fraction (%) changed from 34.4+/-10.3 to 36.6+/-10.4 (baseline versus 12 months FU, p=0.26). Wall motion score index improved both at rest (3.0+/-0.5 to 2.7+/-0.7, p=0.049) and under low-dose dobutamine stress (2.8+/-0.4 to 2.5+/-0.6, p=0.07, baseline versus 12 months FU). CONCLUSION: Percutaneous autologous skeletal myoblast injection is feasible, resulting in wall motion and functional class improvement, but is potentially associated with an increased risk for ventricular arrhythmias. Randomised studies are needed, however, to further assess overall safety, efficacy and the potential for initial increased risk for arrhythmia following cell injection in these high-risk patients.

Catheter-based intramyocardial injection of autologous skeletal myoblasts as a primary treatment of ischemic heart failure: clinical experience with six-month follow-up.

OBJECTIVES: We report on the procedural and six-month results of the first percutaneous and stand-alone study on myocardial repair with autologous skeletal myoblasts. BACKGROUND: Preclinical studies have shown that skeletal myoblast transplantation to injured myocardium can partially restore left ventricular (LV) function. METHODS: In a pilot safety and feasibility study of five patients with symptomatic heart failure (HF) after an anterior wall infarction, autologous skeletal myoblasts were obtained from the quadriceps muscle and cultured in vitro for cell expansion. After a culturing process, 296 +/- 199 million cells were harvested (positive desmin staining 55 +/- 30%). With a NOGA-guided catheter system (Biosense-Webster, Waterloo, Belgium), 196 +/- 105 million cells were transendocardially injected into the infarcted area. Electrocardiographic and LV function assessment was done by Holter monitoring, LV angiography, nuclear radiography, dobutamine stress echocardiography, and magnetic resonance imaging (MRI). RESULTS: All cell transplantation procedures were uneventful, and no serious adverse events occurred during follow-up. One patient received an implantable cardioverter-defibrillator after transplantation because of asymptomatic runs of nonsustained ventricular tachycardia. Compared with baseline, the LV ejection fraction increased from 36 +/- 11% to 41 +/- 9% (3 months, p = 0.009) and 45 +/- 8% (6 months, p = 0.23). Regional wall analysis by MRI showed significantly increased wall thickening at the target areas and less wall thickening in remote areas (wall thickening at target areas vs. 3 months follow-up: 0.9 +/- 2.3 mm vs. 1.8 +/- 2.4 mm, p = 0.008). CONCLUSIONS: This pilot study is the first to demonstrate the potential and feasibility of percutaneous skeletal myoblast delivery as a stand-alone procedure for myocardial repair in patients with post-infarction HF. More data are needed to confirm its safety.