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

• Published in: Journal of the American College of Cardiology Vol. 81; no. 9; pp. 849 - 863
• Main Authors: Perin, Emerson C., Borow, Kenneth M., Henry, Timothy D., Mendelsohn, Farrell O., Miller, Leslie W., Swiggum, Elizabeth, Adler, Eric D., Chang, David H., Fish, R. David, Bouchard, Alain, Jenkins, Margaret, Yaroshinsky, Alex, Hayes, Jack, Rutman, Olga, James, Christopher W., Rose, Eric, Itescu, Silviu, Greenberg, Barry
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 07.03.2023
• Subjects: C-Reactive Protein; Cardiovascular; cell therapy; Cell- and Tissue-Based Therapy; Heart Failure; heart failure with reduced ejection fraction; Humans; Inflammation; major adverse cardiovascular events; mesenchymal precursor cells; Myocardial Infarction; Stroke; Stroke Volume; Ventricular Function, Left; NYHA; MPC; mesenchymal precursor cells; GDMT; ITT; LVEF; LVESV; HFrEF; MACE; cell therapy; TCE; hsCRP; LVEDV; major adverse cardiovascular events; MI; heart failure with reduced ejection fraction; myocardial infarction; high-sensitivity C-reactive protein; intention-to-treat; Left ventricular end diastolic volume; left ventricular ejection fraction; terminal cardiac event; New York Heart Association; left ventricular end-systolic volume; major adverse cardiovascular event(s); guideline-directed medical therapy; mesenchymal precursor cell
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2022.11.061

Mesenchymal precursor cells (MPCs) are allogeneic, immunoselected cells with anti-inflammatory properties that could improve outcomes in heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of MPCs in patients with high-risk HFrEF. 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. 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). 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. [Display omitted]