BAG3-DCM Natural History Study

This is an observational study with both retrospective and prospective data collection. The study is designed to describe the natural history of BAG3-DCM including the signs and symptoms, key clinical events, and impact of the disease on quality of life as managed with the current standard of care. A hybrid (retrospective and prospective data collection) approach is being used to generate robust and longitudinal data.

Primary outcomes

• Cardiac structure and function [48 months]: Evaluate cardiovascular health as assessed by cardiac biomarkers and the occurrence of clinical outcomes related to the cardiovascular system.

Secondary outcomes

• NYHA Classification [48 months]: Evaluation over duration of follow up
• Change in arrhythmias or risk factor for ventricular arrhythmias [48 months]: Evaluate changes in health status as assessed by occurrence of clinical outcomes
• Heart rhythm and rate monitoring measures [48 months]: Evaluation of change over duration of follow up
• Cardiac biomarkers and blood proteomics [48 months]: Evaluation of change over duration of follow up
• Evaluate patient reported outcomes and quality of life measures [48 months]: Evaluate patient reported outcomes and quality of life measures using validated questionnaire.
• Evaluate changes in health status [48 months]: Evaluate changes in health status as assessed by occurrence of clinical outcomes
• Event free survival [48 months]: Evaluation over duration of follow up
• Anti-AAV9 titer [48 months]: Change in antibody assay findings over time
• Tissue expression of BAG3 protein and DCM features [48 months]: Change in protein expression and histopathologic features

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

Subjects are eligible for inclusion into the study only if all the following criteria apply:

General:

1. Adult patients 18 years or older at the time of providing informed consent (i.e., signing the ICF).
2. Capable and willing to provide signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and protocol.
3. Diagnosis of DCM as defined by mild to moderate systolic dysfunction performed within 12 months of enrollment and confirmed by the principal investigator that the DCM is predominantly non-ischemic.
4. Documentation of a pathogenic or likely pathogenic variant in BAG3 by a CLIA-certified or equivalent genetic testing laboratory.
5. NYHA class I-III

Key Exclusion Criteria:

All Cohorts:

1\. Concurrent enrollment in any other clinical investigation involving use of an investigational agent for any condition at time of enrollment to this study that could confound interpretation of this study results 2. Previous treatment with gene therapy 2. Gene testing indicates that the patient's arrhythmia or cardiomyopathy may be related to a genetic etiology other than BAG3 variant.

4\. NYHA class IV HF. 5. Presence or requirement for MCS or predicted need for MCS or heart transplantation within 6 months prior to enrollment.

6\. Prior heart transplantation. 7. Known infection with human immunodeficiency virus (HIV). 8. Unwillingness to comply with study procedures, including follow-up as specified by this protocol, or unwillingness to fully cooperate with the investigator.