Clin Res Cardiol 101, Suppl 1, April 2012

P994 - Cardiac Extracorporal Shock Wave Application to Enhance the Efficiency of Intracoronary Cell Therapy in Chronic Heart Failure - Results of the randomized double-blind Placebo-controlled CELLWAVE trial
B. Aßmus1, D. Walter2, F. Seeger1, D. Leistner1, A. Lutz3, W. Khaled3, S. Dimmeler4, A. M. Zeiher1
1Zentrum Innere Medizin III, Schwerpunkt Kardiologie, Universitätsklinikum Frankfurt am Main, Frankfurt am Main; 2Cardiologicum Hamburg, Hamburg; 3Dornier Med Tech Systems GmbH, Wessling; 4Zentrum für Molekulare Medizin, Goethe Universität, Institut für Kardiovaskuläre Regeneration, Frankfurt am Main;
Introduction: Initial clinical studies have demonstrated that intracoronary administration of autologous bone marrow-derived mononuclear cells (BMC) may improve left ventricular contractile function (LVEF) in patients with chronic post-infarction heart failure (CHF), although to a rather limited extent. The lack of a more pronounced effect has been attributed to impaired recruitment and homing of the applied cells to the remodelled heart in these patients. Extracorporal shockwave (SW) treatment was experimentally shown to increase the expression of homing factors like SDF-1 in the target tissue, resulting in enhanced homing and neovascularization following application of BMC. Therefore, we performed the randomized, double-blind, Placebo-controlled CELLWAVE trial, designed to demonstrate improved recovery of LVEF by combining targeted SW application with subsequent BMC application in patients with CHF.
Methods: Patients were randomized to receive echo-guided low-dose (0.014mJ/mm²; n=39), high-dose (0.051mJ/mm², n=43) or Placebo (n=21) SW (Biotripter, Dornier) targeted to the LV anterior wall 24 hours prior to BMC administration. Then, patients with SW pretreatment were further randomized (1:1; double-blind) to either intracoronary administration of autologous BMC or cell-free medium (Placebo), whereas patients with Placebo-SW pretreatment received intracoronary BMC application (figure A). Main exclusion criteria were the presence of LV thrombus and poor ultrasound access to the heart.
Results: A total of 103 patients with stable advanced CHF (baseline LVEF 32.8±12%; NYHA class 2.3±0.6), at least 3 months old previous anterior myocardial infarction (time from last AMI 5.7±6.1 years) and an open infarct-related artery were randomized. SW treatment was well tolerated and safe with no induction of arrhythmias or release of troponin T. The primary efficacy endpoint, which was absolute change in global LVEF, measured by quantitative LV angiography, at 4 months, was significantly improved in patients receiving SW treatment and BMC infusion (abs. Δ LVEF +3.2±3.2%; n=37) compared to patients with SW treatment only (abs. Δ LVEF +1.0±4.0%; n=32; figure B). This effect was even more pronounced in patients with baseline LVEF < 40% (SW & BMC treatment abs. Δ LVEF +3.4±3.1%; n=27; versus SW treatment only abs. Δ LVEF +0.4±4.1%; n=24).
Likewise, NYHA class improved significantly from 2.3±0.6 to 2.0±0.7 (p=0.03) in the SW and BMC group, compared to no change in the SW only treated patients (NYHA from 2.1±0.6 to 2.2±0.8, p=0.16; figure C). In addition, NT-proBNP levels were significantly reduced at 4 months only in patients treated with SW and BMC (from 1384±1538 to 1095 ± 1241, p=0.04), whereas the only SW-treated patients did not show a significant reduction (1367±1546 to 1174±1207, p=0.18).
Conclusion: 12-month follow-up will be completed for all patients in March 2012. The results of serial NT-proBNP testing as well as clinical events of this first recruitment-enhancing phase II cell therapy trial in patients with CHF will be reported ( NCT00326989).



Clin Res Cardiol 101, Suppl 1, April 2012
Zitierung mit Vortrags- oder Posternummer s.o.
DOI 10.1007/s00392-012-1100-6