The TIME Trial - Effect of Timing of Stem Cell Delivery Following ST-Elevation Myocardial Infarction on the Recovery of Global and Regional Left Ventricular Function: Final 2-Year Analysis
Rationale: The TIME trial was the first cell therapy trial sufficiently powered to determine if timing of cell delivery following ST-elevation myocardial infarction (STEMI) affects recovery of left ventricular (LV) function.
Objective: To report the 2-year clinical and cardiac magnetic resonance imaging (cMRI) results and their modification by microvascular obstruction (MVO).
Methods and Results: TIME was a randomized, double-blind, placebo-controlled trial comparing 150 million bone marrow mononuclear cells (BMC) vs. placebo in 120 patients with anterior STEMIs resulting in LV dysfunction. Primary endpoints included changes in global (LV ejection fraction (LVEF)) and regional (infarct and border zone) function. Secondary endpoints included changes in LV volumes, infarct size and major adverse cardiac events. Here, we analyzed the continued trajectory of these measures out to 2 years and the influence of MVO present at baseline on these long-term outcomes. At 2 years (n=85), LVEF was similar in the BMC (48.7%) and placebo groups (51.6%) with no difference in regional LV function. Infarct size and LV mass decreased > 30% in each group at 6-months and declined gradually to 2-years. LV volumes increased approximately 10% at 6-months and remained stable to 2-years. MVO was present in 48 patients at baseline and was associated with significantly larger infarct size (56.5 g vs. 36.2 g), greater adverse LV remodeling, and marked reduction in LVEF recovery (0.2 vs. 6.2).
Conclusions: In one of the longest serial cMRI imaging analyses of patients with large anterior STEMIs, BMC administration did not improve recovery of LV function over 2-years. MVO was associated with reduced recovery of LV function, greater adverse LV remodeling and more device implantations. The use of cardiac MRI leads to greater drop-out of patients over time due to device implantation in patients with more severe LV dysfunction resulting in overestimation of clinical stability of the cohort.
- Received June 6, 2017.
- Revision received November 29, 2017.
- Accepted December 1, 2017.