Effect of Shock Wave–Facilitated Intracoronary Cell Therapy on LVEF in Patients With Chronic Heart Failure: The CELLWAVE Randomized Clinical Trial
What is the effect of targeted cardiac shock wave pretreatment with subsequent application of bone marrow–derived mononuclear cells (BMCs) on recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure (CHF)?
The CELLWAVE double-blind, randomized, placebo-controlled trial was conducted among patients with CHF treated at Goethe University Frankfurt, Germany, between 2006 and 2011. This was a single-blind study of low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the LV anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs. The primary endpoint was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion versus shock wave + BMCs; secondary endpoints included regional LV function assessed by magnetic resonance imaging and clinical events.
The primary endpoint was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2%; 95% confidence interval [CI], 2.0%-4.4%), compared with the shock wave + placebo infusion group (1.0%; 95% CI, −0.3% to 2.2%; p = 0.02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6%; 95% CI, 2.0%-5.2%), but not in the shock wave + placebo infusion group (0.5%; 95% CI, −1.2% to 2.1%; p = 0.01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58; 95% CI, 0.40-0.85; p = 0.02).
The authors concluded that among patients with postinfarction CHF, shock wave–facilitated intracoronary administration of BMCs versus shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months.
The present trial investigated the effects of combining target-tissue preconditioning by extracorporeal shock wave application with intracoronary infusion of autologous BMCs on LV function in patients with chronic postinfarction HF. It appears that shock wave–facilitated infusion of BMCs beneficially affects global and regional LV contractile function in these chronically ill patients. Determining whether the increase in contractile function will translate into improved clinical outcomes will require confirmation in large, prospective, double-blind trials with clinical endpoints.
Keywords: Carbamates, Chronic Disease, Stem Cells, Germany, Single-Blind Method, Magnetic Resonance Imaging, Cell- and Tissue-Based Therapy, Heart Diseases, Bone Marrow, Benzimidazoles, Heart Failure, Stroke Volume, Ventricular Function, High-Energy Shock Waves, Confidence Intervals
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