Efficacy assessment of repeat intramyocardial injection of autologous bone marrow cells in previously responding no-option patients with residual refractory angina pectoris and documented ischemia - Repeat cell therapy for refractory angina

INTERVENTION: Product Name: Bone marrow‐derived mononuclear cells Product Code: P10 Pharmaceutical Form: Suspension for injection CONDITION: In coronary artery disease atherosclerosis leads to a decrease in lumen diameter of the large epicardial arteries, causing a deficit in blood flow known as ischemia. This ischemia can cause chest pain, referred to as angina pectoris. Refractory angina pectoris is a disabling condition with an adverse prognosis with a high mortality rate. This severe disorder has a significant morbidity and impact on quality of life. Many patients have very limiting complaints, despite optimal medical therapy. PRIMARY OUTCOME: Main Objective: We intend to assess the efficacy of repeat injection of bone marrow cells in patient with residual or recurrent refractory angina pectoris. Specifically, we want to answer the question whether injection of autologous mononuclear bone marrow cells into the myocardium of no‐option patients with refractory angina and documented ischemia leads to an improvement in quality of life, myocardial perfusion, excercise capacity and myocardial function. Primary end point(s): Efficacy:; ‐ Gated‐SPECT: stress and rest perfusion score; ‐ FDG‐SPECT: assessing viability and hibernation; ‐ MRI: left ventricular global ejection fraction; ‐ Echocardiography:left ventricular wall motion ; ‐ Exercise tolerance testing with VO2 max determination; ‐ Quality of Life will be assessed using the Seattle Angina Questionnaire, translated into Dutch.; ; Safety:; ‐ holter recording: to assess the occurrence of arrhytmia's; ‐ blood sampels: to assess possible inflammation and myocardial damage Secondary Objective: Repeat injection of autologous mononuclear bone marrow cells into the myocardium of no‐option patients with residual or recurrent refractory angina pectoris and documented ischemia is safe with respect to arrhythmia's and periprocedural myocardial damage. INCLUSION CRITERIA: ‐ Having received intramyocardial bone marrow cell injection in study P02.051 (Injection of Autologous Bone Marrow Cells into Damaged Myocardium of No‐option Patients with Refractory Angina Pectoris and Ischemia, a two‐phased study of safety, feasibility and efficacy) or P05.025 (Efficacy assessment of intramyocardial injection of autologous bone marrow cells in no‐option patients with refractory angina pectoris and documented ischemia, a randomized, double blind, placebo controlled study) ‐ Disabling refractory angina pectoris despite optimal medical therapy ‐ Residual reversible ischemia on GATED‐SPECT imaging ‐ No candidate for (repeat) revascularization. ‐ Male or female, > 18 years old ‐ Patients must be stable and not be in a setting of life‐threatening heart failure (LVEF>35%) ‐ Able to perform an exercise tolerance test prior to therapy ‐ Able and willing to undergo all the tests used in this protocol including the traveling involv