Cardiac gene and
cell therapy have both entered clinical trials aimed at ameliorating
ventricular dysfunction in patients with chronic
congestive heart failure. The transduction of myocardial cells with viral constructs encoding a specific cardiomyocyte Ca(2+) pump in the sarcoplasmic reticulum (SR), SRCa(2+)-
ATPase has been shown to correct deficient Ca(2+) handling in cardiomyocytes and improvements in contractility in preclinical studies, thus leading to the first clinical trial of gene therapy for
heart failure. In
cell therapy, it is not clear whether beneficial effects are cell-type specific and how improvements in contractility are brought about. Despite these uncertainties, a number of clinical trials are under way, supported by safety and efficacy data from trials of
cell therapy in the setting of
myocardial infarction. Safety concerns for gene therapy center on inflammatory and immune responses triggered by viral constructs, and for
cell therapy with myoblast cells, the major concern is increased incidence of ventricular
arrhythmia after
cell transplantation. Principles and mechanisms of action of gene and
cell therapy for
heart failure are discussed, together with the potential influence of
reactive oxygen species on the efficacy of these treatments and the status of myocardial-delivery techniques for viral constructs and cells.