TY - JOUR

T1 - Effect of allogeneic adipose tissue derived mesenchymal stromal cell treatment in chronic ischemic heart failure with reduced ejection fraction – The SCIENCE Trial

AU - Qayyum, Abbas Ali

AU - Van Klarenbosch, Bas

AU - Frljak, Sabina

AU - Cerar, Andraz

AU - Poglajen, Gregor

AU - Traxler‐weidenauer, Denise

AU - Nadrowski, Pawel

AU - Paitazoglou, Christina

AU - Vrtovec, Bojan

AU - Bergmann, Martin W.

AU - Chamuleau, Steven A.j.

AU - Wojakowski, Wojtek

AU - Gyöngyösi, Mariann

AU - Kraaijeveld, Adriaan

AU - Hansen, Kristian Schultz

AU - Vrangbæk, Karsten

AU - Jørgensen, Erik

AU - Helqvist, Steffen

AU - Joshi, Francis Richard

AU - Johansen, Ellen Mønsted

AU - Follin, Bjarke

AU - Juhl, Morten

AU - Højgaard, Lisbeth Drozd

AU - Mathiasen, Anders Bruun

AU - Ekblond, Annette

AU - Haack‐sørensen, Mandana

AU - Kastrup, Jens

PY - 2023

Y1 - 2023

N2 - AimsThe aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF).Methods and resultsThe study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II–III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (−2.0 ± 6.0 ml, p = 0.736) and LVEF (−1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups.ConclusionThe SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.

AB - AimsThe aim of the SCIENCE trial was to investigate whether a single treatment with direct intramyocardial injections of adipose tissue-derived mesenchymal stromal cells (CSCC_ASCs) was safe and improved cardiac function in patients with chronic ischaemic heart failure with reduced ejection fraction (HFrEF).Methods and resultsThe study was a European multicentre, double-blind, placebo-controlled phase II trial using allogeneic CSCC_ASCs from healthy donors or placebo (2:1 randomization). Main inclusion criteria were New York Heart Association (NYHA) class II–III, left ventricular ejection fraction (LVEF) <45%, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels >300 pg/ml. CSCC_ASCs or placebo (isotonic saline) were injected directly into viable myocardium. The primary endpoint was change in left ventricular end-systolic volume (LVESV) at 6-month follow-up measured by echocardiography. A total of 133 symptomatic HFrEF patients were included. The treatment was safe without any drug-related severe adverse events or difference in cardiac-related adverse events during a 3-year follow-up period. There were no significant differences between groups during follow-up in LVESV (0.3 ± 5.0 ml, p = 0.945), nor in secondary endpoints of left ventricular end-diastolic volume (−2.0 ± 6.0 ml, p = 0.736) and LVEF (−1.6 ± 1.0%, p = 0.119). The NYHA class improved slightly within the first year in both groups without any difference between groups. There were no changes in 6-min walk test, NT-proBNP, C-reactive protein or quality of life the first year in any groups.ConclusionThe SCIENCE trial demonstrated safety of intramyocardial allogeneic CSCC_ASC therapy in patients with chronic HFrEF. However, it was not possible to improve the pre-defined endpoints and induce restoration of cardiac function or clinical symptoms.

U2 - 10.1002/ejhf.2772

DO - 10.1002/ejhf.2772

M3 - Journal article

C2 - 36644821

VL - 25

SP - 576

EP - 587

JO - European Journal of Heart Failure

JF - European Journal of Heart Failure

SN - 1567-4215

IS - 4

ER -