Randomized Trial Of Targeted Transendocardial Delivery Of Mesenchymal Precursor Cells In High-risk Chronic Heart Failure Patients With Reduced Ejection Fraction

Presented at the American Heart Association’s Scientific Sessions 2021 by: Emerson Perin, MD, PhD - Houston, TX, USA.

Introduction and methods

Aim of the study

Allogeneic mesenchymal precursor cells (MPCs) may exert immunomodulatory and angiogenic effects. This study investigated whether a single transendocardial administration of MPCs from healthy adult donors in addition to guideline-directed medical therapy for HF provides benefit in patients with NYHA class II/III chronic HFrEF.

Study design

This randomized, double-blind, sham-controlled, multicenter study randomized a total of 565 patients to receive either a 150 million dose of MPCs (n=261) or a sham procedure (n=276) in the cath lab. Cells were directly injected into targeted areas of the heart muscle. Mean follow-up was 30 months.

Outcomes

The primary endpoint was recurrent decompensated HF events. Pre-specified irreversible morbidity and mortality endpoints included non-fatal MI, non-fatal stroke, and cardiac death.

Main results

• MPC treatment did not reduce the primary outcome of recurrent decompensated HF events, compared to the sham-procedure.
• MPC treatment did reduce non-fatal MI or non-fatal stroke by 65% (MPV 12/261[4.6%] vs. control 36/276 [13.0%], HR 0.346, 95% CI 0.180-0.664, P=0.001).
• MPC treatment did not reduce cardiac death in the total population nor in patients with NYHA class III, but CV death was reduced in the MPC group in patients with NYHA class II (MPV 8/100[8.0%] vs. control 21/106 [19.8%], HR 0.433, 95% CI 0.191-0.979, P=0.044).
• Time-to-first-event of cardiac death or non-fatal MI or non-fatal stroke was reduced in MPC-treated patients with baseline hsCRP≥2 mg/L (MPV 29/153 [19.0%] vs. control 48/148 [32.4%], HR 0.551, 95% CI 0.346-0.876, P=0.012).

Conclusion

The DREAM HF trial showed that MPC treatment had no effect on decompensated congestive HF events. However, non-fatal MI or non-fatal stroke and cardiac death were reduced in specific subgroups.

Discussion

The discussant Bikyem Bozkurt, MD, PhD (Houston, TX, USA) said that DREAM HF provided further insights into potential subgroups of patients that may benefit from stem cell therapies. The study showed no benefit in the primary endpoint. However, exploratory study results showed improvements with MPC therapy in certain subgroups of patients. The question that remains is whether the subgroup analysis is a reflection of a powered analysis at a subgroup level. Are the differences due to small number of events in a small number of patients or is this a unique therapy for patients with baseline inflammation or NYHA class II status? Bozkurt said that this needs to be determined in future studies.

-Our reporting is based on the information provided at the American Heart Association’s Scientific Sessions 2021-