Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)

Abstract

Objective: To assess the effect of intracoronary infusion of mesenchymal stem cells on the development of post-myocardial infarction heart failure.

Design: Phase 3 randomised clinical trial.

Setting: Three tertiary hospitals in Shiraz, Iran.

Participants: 420 patients with a first ST segment elevation acute myocardial infarction and left ventricular ejection fraction <40% were enrolled and randomised in a 1:2 ratio to receive intervention or standard care.

Intervention: Intracoronary infusion of allogenic Wharton's jelly derived mesenchymal stem cells within 3-7 days of acute myocardial infarction in addition to standard care.

Main outcome measures: The primary endpoint was incidence of heart failure. Secondary endpoints included readmission to hospital for heart failure, all cause mortality, cardiovascular mortality, and readmission to hospital for myocardial infarction. Changes in left ventricular ejection fraction within six months post-myocardial infarction were compared between groups.

Results: A total of 396 patients (136 in the intervention group and 260 in the control group) were included in the final analysis, with a median follow-up of 33.2 months. Intracoronary infusion of mesenchymal stem cells had a preventive effect for incidence of heart failure (2.77 v 6.48 per 100 person years; hazard ratio 0.43, 95% confidence interval 0.21 to 0.89; P=0.024), readmission to hospital for heart failure (0.92 v 4.20 per 100 person years; 0.22, 0.06 to 0.74; P=0.015), and a composite endpoint of cardiovascular mortality and readmission for myocardial infarction or heart failure (2.80 v 7.16 per 100 person years; 0.39, 0.19 to 0.82; P=0.012). The intervention did not have a statistically significant effect on readmission to hospital for myocardial infarction (1.23 v 3.06 per 100 person years; hazard ratio 0.40, 0.14 to 1.19; P=0.10), all cause mortality (1.81 v 1.66 per 100 person years; 1.10, 0.40 to 3.02; P=0.86), or cardiovascular mortality (0.91 v 1.33 per 100 person years; 0.68, 0.18 to 2.57; P=0.57). Left ventricular ejection fraction in the intervention group showed a significantly greater improvement from baseline at six months compared with the control group (β=5.88, 95% confidence interval 4.00 to 7.76; P<0.001).

Conclusions: Intracoronary infusion of Wharton's jelly derived mesenchymal stem cells significantly reduced the risk of incidence of heart failure, readmission to hospital for heart failure, and the composite endpoint of cardiovascular mortality and readmission to hospital for heart failure or myocardial infarction in patients after an acute myocardial infarction, suggesting that this technique may serve as a valuable adjunctive procedure after myocardial infarction to prevent the development of heart failure and reduce the risk of future adverse events.

Trial registration: ClinicalTrials.gov NCT05043610.

Fig 1

CONSORT diagram of patient flow in PREVENT-TAHA8 trial. IQR=interquartile range; LVEF=left ventricular ejection fraction; MI= myocardial infarction; WJ-MSC=Wharton’s jelly derived mesenchymal stem cells

Fig 2

Cumulative hazard estimates and log-rank test of PREVENT-TAHA8 trial’s endpoints: heart failure (HF) incidence (development) (primary endpoint), readmission to hospital for HF, all cause mortality, cardiovascular mortality, readmission to hospital for myocardial infarction (MI), and composite endpoint of cardiovascular mortality and readmission to hospital for HF or MI. An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/25452455/

Fig 3

Crude and optimized Cox regression analysis for endpoints in PREVENT-TAHA8 trial. Top: crude hazard ratios from Cox regression analysis for trial endpoints. Bottom: optimised Cox regression models analysing treatment allocation and covariates for incidence of heart failure (HF) and readmission to hospital for HF. An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/25427034/

Fig 4

Change in left ventricular ejection fraction (LVEF) at 6 month follow-up analysis. Top: box plot of baseline and 6 month LVEF. Bottom: Wilcoxon test results. Wilcoxon matched pairs signed rank test was used to assess differences between post-6 month LVEF and baseline LVEF within both intervention and control groups. To compare LVEF changes between treatment groups, Wilcoxon rank sum test was used