First Mononuclear Cells Injected in the United States Conducted by the CCTRN - FOCUS-CCTRN

Mar 24, 2012
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)–sponsored Cardiovascular Cell Therapy Research Network (CCTRN).
Date Presented:
01/01/2012
Date Published:
01/01/2012
Date Updated:
03/24/2012
Original Posted Date:
03/24/2012
References

Description:

The goal of the trial was to evaluate transendocardial injection of bone marrow–derived mononuclear cells compared with placebo among patients with chronic ischemic cardiomyopathy.

Hypothesis:

Bone marrow mononuclear cells will improve left ventricular (LV) function and perfusion.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Patients at least 18 years of age with chronic ischemic cardiomyopathy (LVEF ≤45%)
  • Heart failure symptoms: New York Heart Association (NYHA) class II-III and/or angina symptoms: Canadian Cardiovascular Society (CCS) class II-IV
  • Perfusion defect on SPECT with no revascularization options while on optimal medical therapy

    Number of screened applicants: 153
    Number of enrollees: 92
    Duration of follow-up: 6 months
    Mean patient age: 64 years
    Percentage female: 13%
    Ejection fraction: 32%
    NYHA class: 52%–II, 38%–III
    CCS class: 44%–II, 30%–III

Exclusions:

  • Atrial fibrillation/flutter or significant uncontrolled arrhythmias
  • Implantable cardioverter-defibrillator shock within last 30 days
  • Unstable angina
  • High-risk acute coronary syndrome or myocardial infarction in the last month
  • LV thrombus
  • Vascular anatomy that precludes catheterization
  • Severe valvular disease or mechanical valve that would preclude catheter transit into the ventricle
  • Thrombocytopenia (<100,000/mm3)
  • Leukopenia (<2000/mm3)
  • Revascularization within last 30 days
  • Stroke or transient ischemic attack within last 60 days
  • Bleeding diathesis
  • Nonbasal cell carcinoma within last 5 years
  • Human immunodeficiency virus, or hepatitis B/C
  • Previous transplant requiring immunosuppressive medication
  • LV wall thickness <8 mm
  • Inability to walk on a treadmill
  • Enrollment in another study within last 30 days
  • Liver or renal disease
  • Pregnancy

Primary Endpoints:

  • Change in LV end-systolic volume
  • Change in maximal oxygen consumption
  • Change in reversibility on SPECT

Drug/Procedures Used:

Patients with symptoms due to chronic ischemic heart failure were randomized to transendocardial injection of bone marrow–derived mononuclear cells (n = 61) versus transendocardial injection of placebo (n = 31).

Bone marrow was aspirated from the iliac crest. LV injection sites were guided by electromechanical mapping of the endocardial surface.

Concomitant Medications:

Medications at the time of randomization:

  • 61% angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker
  • 15% aldosterone inhibitor
  • 93% beta-blocker
  • 16% warfarin
  • 67% diuretics
  • 64% nitrates
  • 72% statins
  • 34% ranolazine

Principal Findings:

Overall, 92 patients were randomized. The mean age was 64 years, 13% were women, mean body mass index was 30 kg/m2, 34% had diabetes, 93% had a prior myocardial infarction, mean blood pressure was 121/71 mm Hg, and mean ejection fraction (EF) was 32%.

Difference in the change in LV end-systolic volume index between bone marrow cells and placebo: -0.9 ml/m2, p = 0.73.

Difference in the maximum consumption between bone marrow cells and placebo: 1.0, p = 0.17, and difference in reversible defect by single-photon emission computed tomography (SPECT) between bone marrow cells and placebo: -1.2, p = 0.84.

Interpretation:

Among patients with chronic ischemic cardiomyopathy, the endocardial injection of bone marrow–derived mononuclear cells was not beneficial. This therapy did not improve LV end-systolic volume index, maximal oxygen consumption, or reversibility on SPECT. These results are consistent with a similar patient population studied in the FOCUS-HF trial. Smaller studies designed to study safety overestimated efficacy from injection of bone marrow–derived mononuclear cells.

References:

Perin EC, Willerson JT, Pepine CJ, et al., on behalf of the Cardiovascular Cell Therapy Research Network (CCTRN). Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: The FOCUS-CCTRN Trial. JAMA 2012;Mar 24:[Epub ahead of print].

Presented by Dr. Emerson Perin at ACC.12 & ACC-i2 with TCT, Chicago, IL, March 24, 2012.

Keywords: Myocardial Infarction, Myocardial Ischemia, Bone Marrow Cells, Body Mass Index, Oxygen Consumption, Ventricular Function, Left, Tomography, Emission-Computed, Single-Photon, Cardiomyopathies, Heart Failure, Blood Pressure, Diabetes Mellitus


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