Mr Michał Tendera
The number of patients with end-stage cardiac disease including refractory angina pectoris and end-stage ischemic heart failure is increasing. This is mostly due to the increasingly successful treatment of acute myocardial infarction by primary PCI, in addition to aging in the general population. Myocardial infarction survivors have a damaged myocardium that in many cases does not have sufficient regenerative capability to prevent further deterioration of cardiac function, with potential progression to chronic overt heart failure. Also, residual myocardial ischemia may further compromise cardiac function, and may lead to debilitating refractory angina. Therefore, additional treatment options are needed for this growing patient population. The session addressed the potential use and limitations of cell therapy in patients with heart failure and refractory angina. Dr. Douwe Atsma from Leiden (NL) presented the results of a pilot trial in no-option patients with refractory angina and documented myocardial ischemia. In this study they demonstrated the safety and feasibility of intramyocardial injection of autologous bone marrow-derived mononuclear cells (BMC) into ischemic myocardium. The BMCs were injected transendocardially using an electro-mechanical mapping system (NOGA). High density electrophysiological mapping of the target areas before and 3 months after cell injection demonstrated no adverse effects of the cell injection procedure on the electrophysiological properties of the treated myocardium. The procedure was associated with a decrease in complaints and an increase in myocardial perfusion and LVEF. Based on these data, they performed a randomized, placebo-controlled, double-blind trial to assess the efficacy of intramyocardial injection of autologous BMC in patients with refractory angina and documented myocardial ischemia. Patients were randomized to cell injection (100 million BMCs, n = 25 patients) or placebo injection (vehicle, n = 25 patients). In the cell injection group they found an improvement in symptoms, quality of life, exercise capacity, LVEF and myocardial perfusion. This effect was preserved after 12 months. In the placebo group there was also an improvement in symptoms and quality of life, though significantly smaller than in the cell injection group. In the placebo group there was no improvement in LVEF and myocardial perfusion. These results indicate that autologous cell therapy in chronic angina pectoris patients may improve symptoms and cardiac function. Dr. Sian Harding from London (UK) addressed the mechanisms of benefit in the cell based cardiac repair. She emphasized that 1 gram of cardiac tissue contains about 4x107 cardiomyocytes, and a medium sized infarction induces a loss of 2x109 cells. Therefore currently used numbers of cells seem to be too low. In addition, cell homing is very limited. Implanted cells may develop into immature cardiomyocytes that persist in the recipient tissue, exert no mechanical function, but may influence the function of host myocytes and play a role in the paracrine effect leading to improved neovascularization. Dr. Gerd Hasenfuss from Goettingen (DE) discussed cell therapy for non-ischemic cardiomyopathy. He showed the results of recently published studies, in which the improvement in left ventricular ejection fraction after cell therapy in this setting was comparable to that in patients with recent myocardial infarction. He emphasized that we do not fully understand the mechanism of cell damage in non-ischemic cardiomyopathies, and therefore tailored treatment is difficult. Dr. Anthony Mathur from London (UK) addressed cell therapy for ischemic cardiomyopathy. He stated that meta-analysis of clinical trials of stem cell therapy for the treatment of myocardial dysfunction following acute myocardial infarction suggests biological effectiveness of this approach. Little data is available for the benefit of cell therapy in patients with ischemic cardiomyopathy. He presented the preliminary results of the REGENERATE-IHD randomized trial of cell therapy in chronic heart disease and discussed the current evidence for this treatment strategy. This session provided evidence that many pivotal questions still need to be answered before cell therapy reaches the stage of clinical applicability.
Cell therapy for chronic heart disease
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