Timing in Myocardial Infarction Evaluation - TIME

Contribution To Literature:

The TIME trial failed to show that autologous BMC delivery improved global or regional LVEF at 6 and 12 months in patients who recently underwent PCI for anterior MI.

Description:

The goal of the trial was to evaluate the effect of timing of intracoronary autologous bone marrow mononuclear cell (BMC) delivery among patients who recently underwent primary percutaneous coronary intervention (PCI) for anterior myocardial infarction (MI).

Hypothesis:

Study Design

  • Randomized
  • Parallel

Patient Populations:

  • Number of screened applicants: 3,347
  • Number of enrollees: 132
  • Duration of follow-up: 6, 12, and 24 months
  • Mean patient age: 56 years
  • Percentage female: 12%
  • Ejection fraction: 36%

Exclusions:

  • Prior coronary artery bypass grafting or STEMI

Primary Endpoints:

  • Change in global and regional LV function by magnetic resonance imaging between baseline and 6 months

Secondary Endpoints:

  • Major adverse cardiovascular events

Drug/Procedures Used:

By factorial design, patients who underwent primary PCI for anterior MI and had LV systolic dysfunction (LV ejection fraction [EF] ≤45%) were randomized to delivery of study drug at day 3 (n = 69) versus day 7 (n = 63). Patients were randomized again to delivery of BMC versus placebo.

Concomitant Medications:

At the time of randomization, the use of aspirin was 98%, ADP receptor antagonist 98%, angiotensin-converting enzyme inhibitor 81%, beta-blocker 98%, and statin 91%.

Principal Findings:

Overall, 132 patients were randomized. The mean age was 56 years, 12% were women, mean body mass index was 31 kg/m2, mean LVEF was 36%, 23% had diabetes, mean blood pressure was 115/70 mm Hg, median ischemic time was 3.4 hours, median time from bone marrow aspiration to infusion was 8.4 hours, and 86% received a stent to the left anterior descending artery. No patient had a complication during bone marrow aspiration.

The within-group change in global LVEF from baseline to 6 months was 3.2% in the BMC group versus 3.3% in the placebo group (p = 0.96). There was also no improvement in LVEF when the infarct zone (p = 0.41) and border zone were considered (p = 0.78). There was no change in global LVEF when BMCs were delivered on day 3: -0.9% versus day 7: 1.1% (p = 0.70).

Clinical outcomes at 6 months for BMC versus placebo:
- Deaths: 1 vs. 0
- Reinfarction: 1 vs. 2
- Repeat revascularization: 7 vs. 4
- Hospitalization for heart failure: 4 vs. 1
- ICD placement: 3 vs. 3

Clinical outcomes at 12 months for BMC versus placebo:
- Deaths: 1 vs. 0
- Reinfarction: 2 vs. 3
- Repeat revascularization: 9 vs. 6
- Hospitalization for heart failure: 4 vs. 1
- ICD placement: 4 vs. 5

At 1 year, the mean LVEF was 49.5% in the BMC group versus 49.6% in the placebo group (p = 0.30 between groups).

Interpretation:

Among patients with anterior ST-segment elevation MI (STEMI) treated with primary PCI and LV systolic dysfunction, the use of autologous BMC delivery failed to improve global or regional LVEF at 6 and 12 months. There was also no signal for enhanced benefit when BMCs were delivered on day 3 or day 7. Major adverse events were rare with BMC delivery. Microvascular obstruction was associated with a significant reduction in the recovery of LV function and increased need for ICD implantation. Rapid primary perfusion and frequent use of guideline medications may have attenuated the opportunity to demonstrate a benefit with BMC delivery.

References:

Presented by Dr. Jay Traverse at the American Heart Association Annual Scientific Sessions (AHA 2016), New Orleans, LA, November 14, 2016.

Traverse JH, Henry TD, Pepine CJ, Willerson JT, Ellis SG. One-Year Follow-up of Intracoronary Stem Cell Delivery on Left Ventricular Function Following ST-Elevation Myocardial Infarction. JAMA 2014;311:301-302.

Presented by Dr. Jay Traverse at the American Heart Association Scientific Sessions, Dallas, TX, November 18, 2013.

Traverse JH, Henry TD, Pepine CJ, et al. Effect of the Use and Timing of Bone Marrow Mononuclear Cell Delivery on Left Ventricular Function After Acute Myocardial Infarction: The TIME Randomized Trial. JAMA 2012;308:2380-9.

Presented by Dr. Jay Traverse at the American Heart Association Scientific Sessions, Los Angeles, CA, November 6, 2012.

Clinical Topics: Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Acute Heart Failure

Keywords: AHA Annual Scientific Sessions, Myocardial Infarction, Follow-Up Studies, Bone Marrow, Body Mass Index, Heart Failure, Blood Pressure, Coronary Vessels, Ventricular Dysfunction, Left, Diabetes Mellitus, Stents, Percutaneous Coronary Intervention


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