Effect of shock wave-facilitated intracoronary cell therapy on LVEF in patients with chronic heart failure: the CELLWAVE randomized clinical trial.

IMPORTANCE: The modest effects of clinical studies using intracoronary administration of autologous bone marrow-derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs. OBJECTIVE: To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure. DESIGN, SETTING, AND PARTICIPANTS: The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011. INTERVENTIONS: Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular 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. MAIN OUTCOMES AND MEASURES: Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events. RESULTS: The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, -0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, -1.2% to 2.1%]) (P = .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 = .02). CONCLUSIONS AND RELEVANCE: Among patients with postinfarction chronic heart failure, shock wave-facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00326989.

Ultrasonic strain imaging and reconstructive elastography for biological tissue.

Mechanical properties of biological tissue represent important diagnostic information and are of histological and pathological relevance. In order to obtain non-invasively mechanical properties of tissue, we developed a real-time strain imaging system for clinical applications. The output data of this system also allow an inverse elastography approach leading to the spatial distribution of the relative elastic modulus of tissue. The internal displacement field of biological tissue is determined using the above mentioned strain imaging system by applying quasi-static compression to the considered tissue. Axial displacements are calculated by comparing echo signal sets obtained prior to and immediately following less than 0.1% compression, using the fast root seeking technique. Strain images representing mechanical tissue properties in a non-quantitative manner are displayed in real-time mode. For additional quantitative imaging, the stiffness distribution is calculated from the displacement field assuming the investigated material to be elastic, isotropic, and nearly incompressible. Different inverse problem approaches for calculating the shear modulus distribution using the internal displacement field have been implemented and compared. The results of an ongoing clinical study with more than 200 patients show, that our real-time strain imaging system is able to differentiate malignant and benign tissue areas in the prostate with a high degree of accuracy (sensitivity=76% and specificity=89%). The reconstruction approaches applied to the strain image data deliver quantitative tissue information and seem promising for an additional differential diagnosis of lesions in biological tissue. Our real-time system has the potential of improving diagnosis of prostate and breast cancer.