Efficacy and Safety Study of Genetically Targeted Enzyme Replacement Therapy for Advanced Heart Failure

Inclusion Criteria: * Chronic ischemic or non-ischemic cardiomyopathy. Subjects with ischemic cardiomyopathy must have at least one major coronary vessel with Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. * Left ventricular ejection fraction (LVEF) ≤35% * Diagnosis of New York Heart Association (NYHA) Class III/IV heart failure for a minimum of 3 months prior to screening * Maximal oxygen consumption (VO2 max) ≤20 mL/kg/min within 90 days prior to enrollment * An implantable cardioverter defibrillator (ICD) implanted a minimum of 30 days prior to enrollment * Treatment with appropriate heart failure therapy as tolerated * All women of childbearing potential must have a negative urine pregnancy test prior to administration of investigational product and agree to use adequate contraception. Men capable of fathering a child must agree to use barrier contraception or limit activity to post-menopausal, surgically sterilized, or a contraception-practicing partner, for 3 months after administration of investigational product. * Ability to sign Informed Consent Form (ICF) and Release of Medical Information Form Exclusion Criteria: * Any intravenous therapy with positive inotropes, vasodilators, or diuretics within 30 days prior to enrollment * Restrictive cardiomyopathy, obstructive cardiomyopathy, pericardial disease, amyloidosis, infiltrative cardiomyopathy, uncorrected thyroid disease, or dyskinetic LV aneurysm * Cardiac surgery, percutaneous coronary intervention, or valvuloplasty within 30 days prior to enrollment * Clinically significant myocardial infarction (e.g., ST elevation MI \[STEMI\] or large non-STEMI) within 6 months prior to enrollment * Prior heart transplantation, left ventricular reduction surgery (LVRS), cardiomyoplasty, passive restraint device (e.g., CorCap™ Cardiac Support Device), surgically implanted LVAD or cardiac shunt * Likely to receive cardiac resynchronization therapy, cardiomyoplasty, LVRS, heart transplant, conventional revascularization procedure, or valvular repair within 6 months following enrollment * Patients with prior coronary artery bypass graft(s) (CABG) will reviewed on a case-by-case basis * No evidence of functional or viable myocardium * Exercise capacity primarily limited by obesity, peripheral vascular disease, intrinsic pulmonary disease or orthopedic problems and not by underlying heart failure * Known hypersensitivity to octafluoropropane (component of the intravenous echocardiography contrast agent, DEFINITY®) or other contrast dyes used for angiography; history of, or likely need for, high dose steroid pretreatment prior to contrast angiography * A left ventricle that is difficult to image or high quality echocardiography is not obtainable at screening * Significant left main or ostial right coronary lumenal stenosis in the opinion of the investigator * Expected survival \<1 year in the investigator's medical opinion * Suspected or active viral, bacterial, fungal, or parasitic infection within 48 hours prior to enrollment * Liver function tests (alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], alkaline phosphatase) \>2x Upper Limit of Normal (ULN) within 30 days prior to enrollment or known intrinsic liver disease (e.g., cirrhosis, chronic hepatitis B or hepatitis C virus infection) * Current or likely need for hemodialysis within 12 months following enrollment * Bleeding diathesis or thrombocytopenia defined as platelet count \<50,000 platelets/μL * Anemia defined as hemoglobin \<10 g/dL * Known AIDS or HIV-positive status, or a previous diagnosis of immunodeficiency with an absolute neutrophil count \<1000 cells/mm3 * Previous participation in a study of gene transfer * Presence of neutralizing anti-AAV1 antibodies at titer ≥1:2 within 3 months of screening * Receiving investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the investigational drug administration prior to enrollment * Pregnancy or lactation * Recent history of psychiatric disease (including drug or alcohol abuse) that is likely to impair subject's ability to comply with protocol-mandated procedures, in the opinion of the investigator * Other concurrent medical condition(s) that, while not explicitly excluded by the protocol, could jeopardize the safety of the patient or objectives of the study