Physicians' Academy for Cardiovascular Education
Cardiopoietic stem cell therapy induced left ventricular remodelling

Cardiopoietic stem cell therapy induced left ventricular remodelling

News - May 1, 2017

Paris, France | Cardiopoietic stem cell therapy improved left ventricular remodeling: longitudinal results from the CHART-1 study

Presented at ESC Heart Failure 2017 by John R TEERLINK (San Francisco, CA, USA)


The CHART-1 (Congestive Heart Failure Cardiopoietic Regenerative Therapy) trial randomised patients with chronic HF secondary to ischaemic heart disease with LVEF <35% on optimal medical therapy to intramyocardial injection of lineage-directed cardiopoietic stem cells or a sham procedure. 120 patients received cardiopoietic cell injections, and 151 a sham procedure.

Lineage-directed cardiopoietic stem cells are generated through harvesting of bone marrow, followed by isolation and expansion of mesenchymal stem cells. These cells are stimulated to derive cardiopoietic stem cells. Autologous cardiopoietic stem cells were delivered endomyocardially using a catheter-based procedure.

The CHART-1 primary results showed that the primary hierarchical composite endpoint at 39 weeks was not significantly improved in those who received stem cell injections. Patients with low (200-370 mL) LVEDV at baseline seemed to do a little better.

Echocardiography (standard transthoracic 2-dimensional echocardiography using harmonic mode imaging) was performed at baseline and weeks 26, 39 and 52 post-procedure. This presentation focussed on the 52 week results.

Main results

Different patterns of intramyocardial injections were tested: up to 20 injections of 0.5 mL, each spaced ~1 cm apart over the left ventricle where it was at least 8 mm thick. 29 patients received ≤16 injections, 35 received 17/18/19, and 56 patients received at least 20 injections. The sham procedure did not have intramyocardial injections, but consisted of intramyocardial manipulations.


These data show that in this population of patients with advanced HF, intramyocardial administration of cardiopoietic stem cells induced significant reverse left ventricular remodelling after 52 weeks. Effects on remodelling appear most pronounced in patients who received a moderate number of injections.

It should be noted that this is a post-hoc analysis of the CHART-1 study. Naturally, patients who died did not have echo follow-up, but the number of deaths was similar in both treatment groups. Another limitation is that the analysis of treatment effects by number of injections lacks a robust control, as the placebogroup did not receive injections.

During the discussion, Javed BUTLER (Atlanta, GA, USA) wished to look at the bigger picture of these findings. We have been trying to develop stem cell therapy for decades now, and still it is not clear if it works. We need a definitive proof that it works, both for financial and clinical reasons. That raises the question whether we are going to apply normal efficacy and safety standards? If yes, that means we will need bigger trials. If not, we need to change our standards.

Butler applauded the presentation for the balanced picture it gives, and he thinks this trial gives direction on how to move forward. Possibly by setting up bigger trials. More insight is needed on what are the best stem cells, what is the best method to administer the cells, and what is the optimal number of injections. Moreover, we need to know what placebo injections do, as they may exert some effect, irrespective of the stem cells.


Our coverage of ESC HF 2017 is based on the information provided during the congress.

The first results of the CHART-1 study have been published in Eur Heart J

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