Is the measurement of left ventricular ejection fraction the proper end point for cell therapy trials? An analysis of the effect of bone marrow mononuclear stem cell administration on left ventricular ejection fraction after ST-segment elevation myocardial infarction when evaluated by cardiac magnetic resonance imaging.

BACKGROUND: The measurement of left ventricular (LV) ejection fraction (LVEF) is a strong predictor of cardiovascular adverse events and mortality in patients with LV dysfunction and has become the most common primary end point in cardiovascular cell therapy trials after ST-segment elevation myocardial infarction (STEMI). Multiple small trials have been performed using bone marrow mononuclear stem cells (BMCs) in this setting with several meta-analyses demonstrating that BMC administration results in a small improvement in LVEF and may attenuate adverse LV remodeling. However, individual trial results have not been uniform, and the measurement of LVEF in these trials has relied on a variety of imaging techniques including LV angiograpnhy, single-photon emission computed tomography, echocardiography, or cardiac magnetic resonance imaging (cMRI).

METHODS: Because cMRI provides the most accurate measurement of LVEF, LV volumes, and infarct size in patients after STEMI, we reviewed all randomized cardiovascular stem cell trials (N = 10) that administered intracoronary BMCs versus placebo/control to 686 patients after primary percutaneous coronary intervention treatment of STEMI that used cMRI as their principal imaging measurement of LVEF at baseline and 3 to 6 months later.

RESULTS: Administration of BMCs was associated with a nonsignificant 0.9% ± 0.8% absolute increase in LVEF compared with placebo or control (95% CI -0.7 to 2.4) with a small but nonsignificant decrease LV end-diastolic and LV end-systolic volumes (LV end-diastolic volume -1.1 ± 1.5 mL/m(2), LV end-systolic volume -1.6 ± 1.4 mL/m(2)). Although infarct size uniformly decreased over time, the reduction was not improved by BMC administration (-0.3 ± 1.7 g).

CONCLUSIONS: The benefit of BMC administration after STEMI on LVEF, LV volumes, and infarct size is small when assessed by cMRI.