title: The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.
abstract: OBJECTIVE
  To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients.
  
  
  BACKGROUND
  Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions.
  
  
  METHODS
  The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]). Patients with an EF ≥20% but ≤45%, multivessel coronary artery disease (CAD) not amenable to revascularization, inducible ischemia, and symptoms of either angina (CCS II-IV) or heart failure (NYHA Class II-III) on maximal medical therapy were enrolled. All patients underwent fat harvest procedure (≤450 mL adipose), on-site cell processing (Celution® System, Cytori Therapeutics), electromechanical mapping, and IM delivery of ADRCs or placebo.
  
  
  RESULTS
  Enrollment was terminated prematurely due to non-ADRC-related adverse events and subsequent prolonged enrollment time. Thirty-one patients (17-ADRCs, 14-placebo) mean age 65 ± 8 years, baseline LVEF(%) 31.1 ± 8.7 (ADRC), 31.8 ± 7.7 (placebo) were enrolled. Change in V02max favored ADRCs (+45.4 ± 222 vs. -9.5 ± 137 mL/min) but there was no difference in left ventricular function or volumes. At 12-months, heart failure hospitalizations occurred in 2/17 (11.7%) [ADRC] and 3/14 (21.4%) [placebo]. Differences in NYHA and CCS classes favored ADRCs at 12-months with significant improvement in MLHFQ (-21.6 + 13.9 vs. -5.5 + 23.8, P = 0.038).
  
  
  CONCLUSIONS
  A small volume fat harvest, automated local processing, and IM delivery of autologous ADRCs is feasible with suggestion of benefit in "no option" CAD patients. Although the sample size is limited, the findings support feasibility and scalability for treatment of ischemic cardiomyopathy with ADRCs. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Henry
authors.affiliation: University of Florida, Gainesville, Florida.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Pepine
authors.affiliation: Pepin Heart Institute, Tampa, Florida.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Lambert
authors.affiliation: Minneapolis Heart Institute, Minneapolis, Minnesota.
authors.forename: Jay H
authors.initials: JH
authors.lastname: Traverse
authors.affiliation: Scripps Green Hospital, San Diego, California.
authors.forename: Richard
authors.initials: R
authors.lastname: Schatz
authors.affiliation: University Hospital Case Western, Cleveland, Ohio.
authors.forename: Marco
authors.initials: M
authors.lastname: Costa
authors.affiliation: Duke Clinical Research Institute and Duke Medicine, Durham, North Carolina.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Povsic
authors.affiliation: University of Florida, Gainesville, Florida.
authors.forename: R
authors.initials: R
authors.lastname: David Anderson
authors.affiliation: Texas Heart Institute, Houston, Texas.
authors.forename: James T
authors.initials: JT
authors.lastname: Willerson
authors.affiliation: Cytori Therapeutics, San Diego, California.
authors.forename: Steven
authors.initials: S
authors.lastname: Kesten
authors.affiliation: Texas Heart Institute, Houston, Texas.
authors.forename: Emerson C
authors.initials: EC
authors.lastname: Perin
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000368:Aged; D002908:Chronic Disease; D018450:Disease Progression; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005240:Feasibility Studies; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D010359:Patient Readmission; D011446:Prospective Studies; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013318:Stroke Volume; D013997:Time Factors; D014182:Transplantation, Autologous; D016896:Treatment Outcome; D014481:United States; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D016277:Ventricular Function, Left
keywords: cardiomyopathy; heart failure; stem cell/regenerative therapy