Abstract 14838: Cardiac Extracorporal Shock Wave- Facilitated Cell Therapy in Patients with Chronic Heart Failure (Cellwave Trial) - Mechanistic Insights by Magnetic Resonance Imaging

Abstract

Background: Intracoronary application of autologous mononuclear bone marrow derived cells (BMC) is associated with modest effects on left ventricular ejection(LVEF) in patients with chronic heart failure (CHF). Pretreatment of the LV target region by 2-D-echo guided extracorporal shock wave (SW) application 24 h prior to BMC administration was recently shown to significantly improve LVEF in CHF at 4 months follow-up (CellWave trial).

Methods: In the CellWave trial, a total of 103 patients with CHF were randomized to receive low-dose (n=39) or high-dose (n=43) SW (Biotripter, Dornier) targeted to the anterior LV wall. 24h post SW application, patients were further randomized to either intracoronary placebo or BMC administration. Improvement in LVEF by angiography (primary endpoint) was significantly greater (p= 0.01) in the SW + BMC group compared to SW + placebo group. In order to get insights into the underlying mechanisms, serial contrast-enhanced MRI was performed in 38 patients.

Results: The extent of myocardial scar tissue (LE) was similar in both groups at baseline. At 4 months follow-up, the extent of LE significantly decreased from 31.8 +/- 13% to 28.7 +/- 12% of the LV (p= 0.006) in the SW + BMC group (N=17), compared to a light increase in the SW + placebo group (25.9 +/- 10 to 31.1 +/- 13, n = 13, p> 0.01). In parallel, systolic wall thickening in LE segments increased significantly by absolute 3.4 +/- 3.2% (p< 0.02) in the SW + BMC group, but not in the SW + placebo group (0.4 +/- 3 (p= 0.03 vs SW + BMC)). Importantly, in the SW + BMC group, there was a significant correlation (p<0.01) between the reduction in LE and the increase in systolic wall thickening. Finally, both absolute and relative increases in systolic wall thickening at 4 months were inversely related to the transmural extent of LE at baseline in individual MRI segments.

Conclusions: Pretreatment of the LV target region with 2-D-echo guided cardiac SW application followed by intracoronary BMC administration is associated with a significant improvement in regional systolic wall thickening in the infarcted areas and with a profound reduction of LV LE.