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Randomized Controlled Trial
. 2023 Mar 7;81(9):849-863.
doi: 10.1016/j.jacc.2022.11.061.

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure

Emerson C Perin  1 , Kenneth M Borow  2 , Timothy D Henry  3 , Farrell O Mendelsohn  4 , Leslie W Miller  5 , Elizabeth Swiggum  6 , Eric D Adler  7 , David H Chang  8 , R David Fish  9 , Alain Bouchard  4 , Margaret Jenkins  10 , Alex Yaroshinsky  11 , Jack Hayes  12 , Olga Rutman  12 , Christopher W James  12 , Eric Rose  13 , Silviu Itescu  13 , Barry Greenberg  14
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Free article
Randomized Controlled Trial

Randomized Trial of Targeted Transendocardial Mesenchymal Precursor Cell Therapy in Patients With Heart Failure

Emerson C Perin et al. J Am Coll Cardiol. .
Free article

Abstract

Background: Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF).

Objectives: This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF.

Methods: This randomized, double-blind, multicenter study evaluated a single transendocardial administration procedure of MPCs or sham-control in 565 intention-to-treat patients with HFrEF on guideline-directed therapies. The primary endpoint was time-to-recurrent events caused by decompensated HFrEF or successfully resuscitated symptomatic ventricular arrhythmias. Hierarchical secondary endpoints included components of the primary endpoint, time-to-first terminal cardiac events, and all-cause death. Separate and composite major adverse cardiovascular events analyses were performed for myocardial infarction or stroke or cardiovascular death. Baseline and 12-month echocardiography was performed. Baseline plasma high-sensitivity C-reactive protein levels were evaluated for disease severity.

Results: The primary endpoint was similar between treatment groups (HR: 1.17; 95% CI: 0.81-1.69; P = 0.41) as were terminal cardiac events and secondary endpoints. Compared with control subjects, MPCs increased left ventricular ejection fraction from baseline to 12 months, especially in patients with inflammation. MPCs decreased the risk of myocardial infarction or stroke by 58% (HR: 0.42; 95% CI: 0.23-0.76) and the risk of 3-point major adverse cardiovascular events by 28% (HR: 0.72; 95% CI: 0.51-1.03) in the analysis population (n = 537), and by 75% (HR: 0.25; 95% CI: 0.09-0.66) and 38% (HR: 0.62; 95% CI: 0.39-1.00), respectively, in patients with inflammation (baseline high-sensitivity C-reactive protein ≥2 mg/L).

Conclusions: The primary and secondary endpoints of the trial were negative. Positive signals in prespecified, and post hoc exploratory analyses suggest MPCs may improve outcomes, especially in patients with inflammation.

Keywords: cell therapy; heart failure with reduced ejection fraction; major adverse cardiovascular events; mesenchymal precursor cells.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by Mesoblast, Inc. Drs Borow, Yaroshinsky, and Ms Jenkins are consultants for Mesoblast. Drs Hayes, Rutman, and James are employees of Mesoblast. Dr Rose is the Chief Medical Officer of Mesoblast, Ltd. Dr Itescu is the Chief Executive Officer of Mesoblast, Ltd, and is a major shareholder. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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