Long-term outcomes of autologous skeletal myoblast cell-sheet transplantation for end-stage ischemic cardiomyopathy

Abstract

We evaluated the cardiac function recovery following skeletal myoblast cell-sheet transplantation and the long-term outcomes after applying this treatment in 23 patients with ischemic cardiomyopathy. We defined patients as "responders" when their left ventricular ejection fraction remained unchanged or improved at 6 months after treatment. At 6 months, 16 (69.6%) patients were defined as responders, and the average increase in left ventricular ejection fraction was 4.9%. The responders achieved greater improvement degrees in left ventricular and hemodynamic function parameters, and they presented improved exercise capacity. During the follow-up period (56 ± 28 months), there were four deaths and the overall 5-year survival rate was 95%. Although the responders showed higher freedom from mortality and/or heart failure admission (5-year, 81% versus 0%; p = 0.0002), both groups presented an excellent 5-year survival rate (5-year, 93% versus 100%; p = 0.297) that was higher than that predicted using the Seattle Heart Failure Model. The stepwise logistic regression analysis showed that the preoperative estimated glomerular filtration rate and the left ventricular end-systolic volume index were independently associated with the recovery progress. Approximately 70% of patients with "no-option" ischemic cardiomyopathy responded well to the cell-sheet transplantation. Preoperative renal and left ventricular function might predict the patients' response to this treatment.

Keywords: heart failure; ischemic cardiomyopathy; regenerative therapy; responder; sheet transplantation; stem cell.

Graphical abstract

Figure 1

Freedom from all-cause mortality and composite adverse events in all cases and in each group (A) Freedom from all-cause mortality in all cases. (B) Composite adverse events in all cases. (C) Freedom from all-cause mortality in responders and non-responders. (D) Composite adverse events in responders and non-responders.

Figure 2

Serial echocardiographic assessments in the entire cohorts and according to responders and non-responders (A–E) Serial echocardiographic assessments in the entire cohorts. (F–J) Serial echocardiographic assessments according to responders and non-responders. (A and F) LVEDVI, (B and G) LVESVI, (C and H) LVEF, (D and I) LVEDD, and (E and J) LVESD. Data are presented as means ± standard error. LVEDVI, left ventricular end-diastolic volume index; LVESVI, left ventricular end-systolic volume index; LVEF, left ventricular ejection fraction; LVEDD, left ventricular end-diastolic dimension; LVESD, left ventricular end-systolic dimension. (A–E) ^∗p < 0.05.

Figure 3

Serial assessments of hemodynamic parameters in the entire cohorts and according to responders and non-responders (A–E) Serial assessments of hemodynamic parameters in the entire cohorts. (F–J) Serial assessments of hemodynamic parameters according to responders and non-responders. (A and F) Heart rate, (B and G) PCWP, (C and H) mean PAP, (D and I) PVR, and (E and J) LVSWI. Data are presented as means ± standard error. PCWP, pulmonary artery wedge pressure; PAP, pulmonary artery pressure; PVR, pulmonary vascular resistance; LVSWI, left ventricular stroke work index. (A–E) ^∗p < 0.05.

Figure 4

Serial assessments of functional parameters in the entire cohorts according to responders and non-responders (A–C) Serial assessments of functional parameters in the entire cohorts. (D–F) Serial assessments of functional parameters according to responders and non-responders. (A and D) NYHA FC, (B and E) BNP level, and (C and F) 6-min walk distance. Data are presented as means ± standard error. NYHA FC, New York Heart Association functional class; BNP, brain natriuretic peptide; 6MWD, 6-min walk distance. (B and C) ^∗p < 0.05.

Figure 5

Predicted and observed survival rates (A–C) Survival rates are shown in all cases (A), in responders (B), and in non-responders (C). Data are presented as means ± standard error.