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. 2024 Nov 26.
doi: 10.1002/ejhf.3522. Online ahead of print.

Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF

Emerson C Perin  1 , Kenneth M Borow  2 , Timothy D Henry  3 , Margaret Jenkins  4 , Olga Rutman  2 , Jack Hayes  2 , Christopher W James  2 , Eric Rose  2 , Hicham Skali  5 , Silviu Itescu  6 , Barry Greenberg  7
Affiliations

Mesenchymal precursor cells reduce mortality and major morbidity in ischaemic heart failure with inflammation: DREAM-HF

Emerson C Perin et al. Eur J Heart Fail. .

Abstract

Aims: Progressive heart failure with reduced ejection fraction (HFrEF) is adversely affected by alterations in the myocardial balance between bone marrow-derived pro-inflammatory cardiac macrophages and embryo-derived reparative cardiac resident macrophages. Mesenchymal precursor cells (MPCs) may restore this balance and improve clinical outcomes when inflammation is present. The purpose was to (i) identify risk factors for cardiovascular death (CVD) in control patients with HFrEF in the DREAM-HF trial, and (ii) determine if MPCs improve major clinical outcomes (CVD, myocardial infarction [MI], stroke) in high-risk patients with ischaemic HFrEF and inflammation.

Methods and results: Cause-specific regression analyses were used to identify CVD risk factors in DREAM-HF control patients. Aalen-Johansen cumulative incidence curves were used to examine CVD, 2-point major adverse cardiovascular events (MACE) (MI or stroke), and 3-point MACE (CVD or MI or stroke) by treatment group in ischaemic vs non-ischaemic HFrEF and in patients with or without baseline inflammation. In control DREAM-HF patients, factors portending the greatest risk for CVD were inflammation (baseline plasma high-sensitivity C-reactive protein ≥2 mg/L; p = 0.003) and ischaemic HFrEF aetiology (p = 0.097), with increased CVD risk of 61% and 38%, respectively. Over 30-month mean follow-up, MPCs reduced 2-point and 3-point MACE by 88% (p = 0.005) and 52% (p = 0.018), respectively, in patients with ischaemic HFrEF and inflammation compared to controls.

Conclusion: Ischaemic aetiology and inflammation were identified as major risk factors for MACE in control DREAM-HF patients. A single intramyocardial MPC administration produced the most significant, sustained reduction in 2-point and 3-point MACE in patients with ischaemic HFrEF and inflammation.

Keywords: 2‐point MACE; 3‐point MACE; Cardiovascular death; Heart failure with reduced ejection fraction; High‐sensitivity C‐reactive protein; Mesenchymal precursor cells.

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References

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