Processed Fat Cells Show Potential to Treat Refractory Ischemia in ATHENA

May 5, 2016—Patients treated with processed autologous adipose-derived regenerative cells (ADRCs) injected into the heart muscle demonstrated symptomatic improvement and a trend toward lower rates of heart failure hospitalizations and angina, despite no improvement in left ventricle ejection fraction (LVEF) or ventricular volumes. 

These findings from the ATHENA trial were presented as a late-breaking clinical trial at the Society for Cardiovascular Angiography and Interventions (SCAI) 2016 scientific sessions in Orlando, Florida. The study was simultaneously published online by Timothy D. Henry, MD, et al in Catheterization and Cardiovascular Interventions.

According to SCAI, preclinical data indicates that ADRCs promote blood vessel growth, modulate inflammation, and reduce cell death. ADRCs—which are a combination of cell types, such as adult stem cells, vascular endothelial cells, and vascular smooth muscle cells—can be used in a variety of tissue types, including bone, cartilage, fat, skeletal muscle, smooth muscle, and cardiac muscle.

Dr. Henry, the study’s Lead Investigator, commented in the SCAI press release, “ADRCs consist of multiple cell types with multiple potential benefits. Based on the results seen with ADRCs in the PRECISE trial, we designed ATHENA to look at these cells as a possible treatment option for people with refractory chronic myocardial ischemia.” Dr. Henry is Director of the Division of Cardiology at the Cedars-Sinai Heart Institute in Los Angeles, California.

As summarized by SCAI, the phase 2 program was composed of two prospective, randomized double-blind, placebo-controlled, parallel group trials (ATHENA and ATHENA II). 

The patients (average age, 65 years) in each group (17 ADRCs, 14 placebo) were on the maximally tolerated medical management with an ejection fraction (EF) score of 20% to 45%. The baseline average EF score for both groups was 31.6%. A score of ≤ 35% can be an early indicator of heart failure. The patients were Canadian Cardiovascular Society angina class 2 to 4 and/or New York Heart Association class 2 to 3, and had ongoing ischemia and multivessel cardiovascular disease, but were not candidates for revascularization.

Using standard liposuction, a small volume of the patient’s fat tissue (< 450 mL) was extracted. The cells were then separated from the tissue and concentrated (Celution System, Cytori Therapeutics, Inc.) on-site. After cell processing, the ADRCs were injected directly into the patient’s heart muscle.

The investigators reported that at the 1-year mark, the ADRC-treated patients with at least one class improvement in heart failure class (57%) and angina class (67%) tended to be higher, relative to the placebo group (15% and 27%, respectively). Further, the cell-treated patients noted an improvement in the Minnesota Living with Heart Failure questionnaire (-21.6 vs -5.5; P = .038) and showed a trend toward relatively fewer heart failure hospitalizations (centrally adjudicated, 2/17 vs 2/24; 11.7% vs 21.4%). There were no between-group differences in LVEF or ventricular volume.

In the SCAI announcement, Dr. Henry noted that although ATHENA observed a small patient population, the results are promising and consistent with what was seen with PRECISE and should provide the foundation for a large phase 3 trial.

The study, designed to enroll 90 patients, was terminated prematurely due to three neurological events that prolonged trial enrollment, but were not cell related, advised SCAI.