Clinical Investigation
Heart Failure
Adipose-derived regenerative cells in patients with ischemic cardiomyopathy: The PRECISE Trial

https://doi.org/10.1016/j.ahj.2014.03.022Get rights and content

Aims

Adipose-derived regenerative cells (ADRCs) can be isolated from liposuction aspirates and prepared as fresh cells for immediate administration in cell therapy. We performed the first randomized, placebo-controlled, double-blind trial to examine the safety and feasibility of the transendocardial injections of ADRCs in no-option patients with ischemic cardiomyopathy.

Methods and results

Procedural, postoperative, and follow-up safety end points were monitored up to 36 months. After baseline measurements, efficacy was assessed by echocardiography and single-photon emission computed tomography (6, 12, and 18 months), metabolic equivalents and maximal oxygen consumption (MVO2) (6 and 18 months), and cardiac magnetic resonance imaging (6 months). We enrolled 21 ADRC-treated and 6 control patients. Liposuction was well tolerated, ADRCs were successfully prepared, and transendocardial injections were feasible in all patients. No malignant arrhythmias were seen. Adverse events were similar between groups. Metabolic equivalents and MVO2 values were preserved over time in ADRC-treated patients but declined significantly in the control group. The difference in the change in MVO2 from baseline to 6 and 18 months was significantly better in ADRC-treated patients compared with controls. The ADRC-treated patients showed significant improvements in total left ventricular mass by magnetic resonance imaging and wall motion score index. Single-photon emission computed tomography results suggested a reduction in inducible ischemia in ADRC-treated patients up to 18 months.

Conclusion

Isolation and transendocardial injection of autologous ADRCs in no-option patients were safe and feasible. Our results suggest that ADRCs may preserve ventricular function, myocardial perfusion, and exercise capacity in these patients.

Section snippets

Study design

This was a prospective, randomized, placebo-controlled, double-blind, safety and feasibility study designed to enroll up to 36 patients at 4 clinical sites (online Appendix Supplementary material). The study was approved by the institutional review boards at all participating sites and was conducted according to the Declaration of Helsinki and ICH E6 Good Clinical Practice Guidelines (ClinicalTrials.gov identifier: NCT00426868). Written informed consent was obtained from all patients before

Study population

Between January 2007 and May 2009, 27 patients (average age, 63.6 ± 7.5 years; 21 men [78%]) were enrolled at the 4 study sites: 21 ADRC-treated patients and 6 control patients. Most baseline characteristics were similar between the groups, but patients in the treatment group were older and had higher diastolic blood pressure (Table I).

Cell preparation and injections

Adipose tissue was successfully harvested from all patients (mean volume, 361 ± 122 mL). The ADRCs were prepared successfully from each patient; the average ADRC

Discussion

In this multicenter, randomized, placebo-controlled, double-blind study, we have shown for the first time that the harvest and transendocardial injection of ADRCs are safe and feasible in no-option patients with ischemic cardiomyopathy. Moreover, cell therapy with ADRCs in these patients may preserve functional capacity over time and could exert a modest beneficial effect on myocardial perfusion, scar size, and left ventricular contractility.

Adipose tissue comprises a mixed cell source

Conclusion

Our findings indicate that obtaining autologous ADRCs via liposuction and delivering them by transendocardial injection are safe and feasible in patients with ischemic cardiomyopathy. Moreover, our trial provides a sound basis for testing the efficacy of ADRC therapy in a larger group of patients with chronic myocardial ischemia.

Disclosures

Dr Perin receives consulting fees from Cytori Therapeutics, Inc.

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