Potential benefit of autologous cell therapy in patients with ischaemic HFrEF?

Autologous mononuclear cells that were processed and delivered intramyocardially to patients with ischaemic heart failure with reduced ejection fraction (HFrEF) and select favourable cell characteristics was safe but did not meet the primary efficacy endpoint in the CardiAMP-HF trial. However, the investigators observed a positive signal of this therapy among a subgroup of patients with elevated NTproBNP levels, leading to the design of the follow-up trial CardiAMP-HF II.

“Previous studies among patients with ischaemic HFrEF evaluating autologous intramyocardially delivered mononuclear cells found that responders had higher numbers of certain cell populations, particularly CD34,” explained Prof. Amish Raval (University of Wisconsin – Madison, WI, USA) [1]. The current study recruited patients with chronic ischaemic HFrEF with left ventricular ejection fractions between 20% and 40% who had NYHA class II or III disease and were on the maximally tolerated dose of guideline-directed medical therapy. Participants who passed a cell-potency criteria assay, which comprised 62% of the screening population, were randomised 3:2 to 8–10 intramyocardial injections of collected and processed bone marrow mononuclear cells (n=74) or to a sham procedure (n=41). The primary endpoint was a hierarchical composite ranking of:

• Tier 1: all-cause death, cardiac transplant, left ventricular assist device.
• Tier 2: non-fatal HF hospitalisation, myocardial infarction, or stroke.
• Tier 3: change in 6-minute walk test.

At 12 months of follow-up, wins were 27% and 17% higher in the active treatment arm than in the control arm for tiers 1 and 2, respectively (see Figure). For tier 3, the win rate was 56% higher in the control arm than in the active arm, resulting in overall win numbers of 1,524 for the active arm and 1,505 for the control arm (win ratio 1.01; Finkelstein-Schoenfeld [F-S] P=0.95).

Figure: Primary efficacy outcome in CardiAMP-HF [1]



6MWT, 6-minute walk test; F-S, Finkelstein-Schoenfeld; LVAD, left ventricular assist device; MACE, major adverse cardiovascular events.

However, autologous cell therapy may have had a signal for possible benefit for participants with elevated NTproBNP or BNP at baseline. In this subgroup (n=57), the win ratio was 1.61 (F-S P=0.074). Prof. Raval mentioned that there was no procedure-related death, stroke, systemic embolism, or need for open cardiac surgery or major endovascular surgical repair at 30 days of follow-up. The 3 reported cases of pericardial effusion were all successfully drained.

The CardiAMP-HF trial did not demonstrate an efficacy benefit of intramyocardially delivered autologous mononuclear cells in patients with ischaemic HFrEF and selected cell characteristics. “Since the procedure was safe and a potential benefit for the subgroup of patients with elevated NTproBNP was seen, the CardiAMP-HF II trial is launched, testing the procedure in a larger group of patients with elevated NTproBNP,” Prof. Raval concluded.

1. Raval AN, et al. A double-blind, randomized controlled trial of an autologous cell therapy in patients with HFrEF: principal results from the CardiAMP-HF trial. Featured Science II, ACC 2025 Scientific Session, 29–31 March, Chicago, USA.

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Posted on 22 May 202522 May 2025