PMID- 36644821 OWN - NLM STAT- MEDLINE DCOM- 20230428 LR - 20230501 IS - 1879-0844 (Electronic) IS - 1388-9842 (Linking) VI - 25 IP - 4 DP - 2023 Apr TI - Effect of allogeneic adipose tissue-derived mesenchymal stromal cell treatment in chronic ischaemic heart failure with reduced ejection fraction - the SCIENCE trial. PG - 576-587 LID - 10.1002/ejhf.2772 [doi] AB - AIMS: The 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 RESULTS: The 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. CONCLUSION: The 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. CI - (c) 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. FAU - Qayyum, Abbas Ali AU - Qayyum AA AUID- ORCID: 0000-0002-1620-0002 AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - van Klarenbosch, Bas AU - van Klarenbosch B AD - Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Frljak, Sabina AU - Frljak S AD - Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Cerar, Andraz AU - Cerar A AD - Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Poglajen, Gregor AU - Poglajen G AD - Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Traxler-Weidenauer, Denise AU - Traxler-Weidenauer D AD - Department of Cardiology, Medical University of Vienna, Vienna, Austria. FAU - Nadrowski, Pawel AU - Nadrowski P AD - Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland. FAU - Paitazoglou, Christina AU - Paitazoglou C AD - Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany. FAU - Vrtovec, Bojan AU - Vrtovec B AD - Advanced Heart Failure and Transplantation Center, University Medical Centre Ljubljana, Ljubljana, Slovenia. FAU - Bergmann, Martin W AU - Bergmann MW AD - Department of Cardiology, Asklepios Klinik St. Georg, Hamburg, Germany. FAU - Chamuleau, Steven A J AU - Chamuleau SAJ AD - Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Wojakowski, Wojtek AU - Wojakowski W AD - Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland. FAU - Gyongyosi, Mariann AU - Gyongyosi M AD - Department of Cardiology, Medical University of Vienna, Vienna, Austria. FAU - Kraaijeveld, Adriaan AU - Kraaijeveld A AD - Department of Cardiology and Regenerative Medicine Center, University Medical Center Utrecht, Utrecht, The Netherlands. FAU - Hansen, Kristian Schultz AU - Hansen KS AD - Faculty of Social Sciences and the Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Vrangbaek, Karsten AU - Vrangbaek K AD - Faculty of Social Sciences and the Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark. FAU - Jorgensen, Erik AU - Jorgensen E AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Helqvist, Steffen AU - Helqvist S AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Joshi, Francis Richard AU - Joshi FR AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Johansen, Ellen Monsted AU - Johansen EM AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Follin, Bjarke AU - Follin B AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Juhl, Morten AU - Juhl M AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Hojgaard, Lisbeth Drozd AU - Hojgaard LD AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Mathiasen, Anders Bruun AU - Mathiasen AB AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Ekblond, Annette AU - Ekblond A AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Haack-Sorensen, Mandana AU - Haack-Sorensen M AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. FAU - Kastrup, Jens AU - Kastrup J AD - Department of Cardiology and Cardiology Stem Cell Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. CN - SCIENCE Investigators LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230131 PL - England TA - Eur J Heart Fail JT - European journal of heart failure JID - 100887595 SB - IM CIN - Eur J Heart Fail. 2023 Apr;25(4):588-590. PMID: 36823785 MH - Humans MH - Chronic Disease MH - *Heart Failure MH - *Hematopoietic Stem Cell Transplantation MH - *Mesenchymal Stem Cells MH - Quality of Life MH - Stroke Volume MH - Treatment Outcome MH - Ventricular Function, Left MH - Double-Blind Method OTO - NOTNLM OT - Adipose tissue derived-mesenchymal stromal cells OT - Allogeneic therapy OT - Clinical trial OT - Heart failure OT - Ischaemic cardiomyopathy OT - Stem cells EDAT- 2023/01/17 06:00 MHDA- 2023/04/28 06:41 CRDT- 2023/01/16 03:33 PHST- 2022/11/27 00:00 [revised] PHST- 2022/07/24 00:00 [received] PHST- 2023/01/08 00:00 [accepted] PHST- 2023/04/28 06:41 [medline] PHST- 2023/01/17 06:00 [pubmed] PHST- 2023/01/16 03:33 [entrez] AID - 10.1002/ejhf.2772 [doi] PST - ppublish SO - Eur J Heart Fail. 2023 Apr;25(4):576-587. doi: 10.1002/ejhf.2772. Epub 2023 Jan 31.