Cardiopoietic stem cell therapy in ischaemic heart failure: long‐term clinical outcomes

ESC Heart Failure

for the CHART Program¹  Ricardo Sanz‐Ruiz²  Marco Metra³  Jozef Bartunek⁴  Andre Terzic⁴  Guy R. Heyndrickx⁴  Warren Sherman⁵  Wojciech Wojakowski⁶  Michal Tendera⁶  Atta Behfar⁷  Bernard J. Gersh⁷  Thomas J. Povsic⁸  Stefanie Senger⁹  Beth A. Davison⁹  Gad Cotter⁹  Gerasimos S. Filippatos^1,10  Roger Hajjar^1,11  John R. Teerlink^1,12  Scott A. Waldman^1,13  Timothy D. Henry^1,14  William Wijns^1,15 

[1] ;Cardiology Department Hospital General Universitario Gregorio Marañón and CIBERCV (Instituto de Salud Carlos III) Madrid Spain;Cardiology, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health University and Spedali Civili Brescia Italy;Cardiovascular Center OLV Hospital Moorselbaan 164 Aalst B‐9300 Belgium;Consultant South Egremont MA USA;Department of Cardiology and Structural Heart Disease Medical University of Silesia Katowice Poland;Department of Cardiovascular Medicine Mayo Clinic, Center for Regenerative Medicine 200 First Street SW Rochester MN 55905 USA;Duke Clinical Research Institute and Duke University Medical Center Durham NC USA;Momentum Research, Inc. Durham NC USA;National and Kapodistrian University of Athens, School of Medicine Attikon University Hospital Athens Greece;Phospholamban Foundation Amsterdam Netherlands;School of Medicine University of California San Francisco San Francisco CA USA;Sidney Kimmel Medical College Thomas Jefferson University Philadelphia PA USA;The Carl Edyth Lindner Center for Research and Education at The Christ Hospital Cincinnati OH USA;The Lambe Institute for Translational Medicine and Curam National University of Ireland Galway and Saolta University Healthcare Group Galway Ireland;

关键词: Cardiopoiesis;    Clinical trial;    Heart failure;    Longitudinal;    Regenerative medicine;    Stem cell;   

DOI  :  10.1002/ehf2.13031

来源: DOAJ

【 摘 要 】

Abstract Aims This study aims to explore long‐term clinical outcomes of cardiopoiesis‐guided stem cell therapy for ischaemic heart failure assessed in the Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART‐1) trial. Methods and results CHART‐1 is a multinational, randomized, and double‐blind trial conducted in 39 centres in heart failure patients (n = 315) on standard‐of‐care therapy. The ‘active’ group received cardiopoietic stem cells delivered intramyocardially using a retention‐enhanced catheter. The ‘control’ group underwent patient‐level sham procedure. Patients were followed up to 104 weeks. In the entire study population, results of the primary hierarchical composite outcome were maintained neutral at Week 52 [Mann–Whitney estimator 0.52, 95% confidence interval (CI) 0.45–0.59, P = 0.51]. Landmark analyses suggested late clinical benefit in patients with significant left ventricular enlargement receiving adequate dosing. Specifically, beyond 100 days of follow‐up, patients with left ventricular end‐diastolic volume of 200–370 mL treated with ≤19 injections of cardiopoietic stem cells showed reduced risk of death or cardiovascular hospitalization (hazard ratio 0.38, 95% CI 0.16–0.91, P = 0.031) and cardiovascular death or heart failure hospitalization (hazard ratio 0.28, 95% CI 0.09–0.94, P = 0.040). Cardiopoietic stem cell therapy was well tolerated long term with no difference in safety readouts compared with sham at 2 years. Conclusions Longitudinal follow‐up documents that cardiopoietic stem cell therapy is overall safe, and post hoc analyses suggest benefit in an ischaemic heart failure subpopulation defined by advanced left ventricular enlargement on tolerable stem cell dosing. The long‐term clinical follow‐up thus offers guidance for future targeted trials.

【 授权许可】

Unknown