In patients with chronic postinfarction heart failure, bone marrow-derived mononuclear cell (BMC) therapy has demonstrated mixed results to date. One possible reason for this is that cell retention by the heart is more difficult in the stable setting in comparison to therapies given following acute myocardial infarction, however a recent discovery found that extracorporeal application of focused low-energy shock waves can upregulate chemokine expression and improve homing and attachment of cell therapies. The purpose of this study was to determine whether this new technique could improve left ventricular ejection fraction (LVEF) in patients with chronic heart failure.
CELLWAVE was a radomised, double-blind, placebo-controlled trial. Patients were given single-blind low-dose (n=42), high-dose (n=40), or placebo (n=21) shock wave pretreatment targeted to the left ventricular anterior wall. The following day, patients receiving shock wave pretreatment were randomised to then receive a double-blind intracoronary infusion of BMCs or placebo, while patients receiving placebo shock wave therapy received intracoronary infusion of BMCs. The primary endpoint was a change in LVEF from baseline to four months, and secondary endpoints included regional left ventricular function assessed by MRI, and clinical events.
In patients who received shock wave treatment followed by BMCs, the primary endpoint was significantly improved (absolute change in LVEF, 3.2%), compared with the shock wave and placebo infusion group (1.0%; P=.02). Regional wall thickening also improved significantly in the former group but not the latter. Furthermore, the shock wave and BMC group had fewer major adverse clinical events compared to both treatment groups (P=.02).
This study of patients with chronic heart failure found that shock wave therapy augmented treatment with intracoronary bone-marrow cells, leading to a small but significant improvement in left ventricular function. Further work will investigate whether this translates into improved clinical outcomes.
- Assmus B, Walter DH, Seeger FH et al. Effect of Shock Wave-Facilitated Intracoronary Cell Therapy on LVEF in Patients with Chronic Heart Failure. The CELLWAVE Randomized Clinical Trial. JAMA 2013;309:1622-1631.