CardioSeq: Impact of WGS in Individuals With CVD

Study Overview
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Brief Summary
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This is a prospective, single-center, open-label study to investigate the diagnostic efficacy of the TruGenome CVD test and its impact on clinical management compared to usual care in individuals with cardiovascular disease. Diagnostic yield and changes of management (CoM) will be assessed both within the WGS group and compared to a contemporaneous, matched (2:1) usual care (UC) group sourced from EHR records.

Detailed Description
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The TruGenome Cardiovascular Disease (CVD) test which consists of an in-silico 200 gene cardiovascular disease panel, a further 4 genes with cardiovascular disease risk alleles, 10 pharmacogenomic genes, 35 non-cardiovascular ACMG secondary finding genes and a polygenic risk score (PRS) for coronary artery disease (CAD) will be utilized in this study.

Official Title
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CardioSeq: A Prospective, Single-Center, Open-label Study to Evaluate the Impact of Whole Genome Sequencing (WGS) in Individuals With Cardiovascular Disease

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Diagnostic Test: TruGenome Cardiovascular Disease test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals ≥18 years of age Stable ambulatory patients with a cardiology visit within the past year or scheduled within the next 90 days. At least one of the following clinical diagnoses: A. Any aortopathy, B. Dyslipidemia, C. Coronary or peripheral arterial disease, D. Heart Failure or cardiomyopathy, E. Any arrythmia Must be able to read, understand, and sign an informed consent Exclusion Criteria: Individuals with a previously confirmed molecular diagnosis of a known genetic disease with an associated cardiovascular phenotype inclusive of monogenic cardiovascular diseases, chromosomal aneuploidies, and microdeletion disorders. Bone marrow transplant recipients Individuals with severe cognitive dysfunction or diminished capacity who are unable to provide informed consent Patients undergoing active chemotherapy treatment for cancer Patients with end-stage renal disease Patients with poor medical prognosis with a life expectancy <1 year Principal Investigator decides for any reason the study is not in the best interest of the patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single Arm<br>To investigate the diagnostic efficacy of WGS and its impact on clinical management compared to usual care in individuals with cardiovascular disease. Diagnostic yield and changes of management (CoM) will be assessed both within the WGS group and compared to a contemporaneous, matched (2:1) usual care (UC) group sourced from EHR records. | Diagnostic Test: TruGenome Cardiovascular Disease test<br>* The TruGenome Cardiovascular Disease (CVD) test which consists of an in-silico 200 gene cardiovascular disease panel, a further 4 genes with cardiovascular disease risk alleles, 10 pharmacogenomic genes, 35 non-cardiovascular ACMG secondary finding genes and a polygenic risk score (PRS) for coronary artery disease (CAD) will be utilized in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who receive a new monogenic cardiovascular disease finding | Quantify the proportion of patients who receive a new monogenic cardiovascular disease finding from the TruGenome CVD test | 42 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients who receive any monogenic cardiovascular disease, cardiovascular risk allele, or cardiovascular pharmacogenomic findings. | Quantify the proportion of patients who receive monogenic cardiovascular disease, cardiovascular risk allele and/or cardiovascular pharmacogenomic findings. | 42 Months | 
| Number of patients who receive monogenic cardiovascular disease, cardiovascular risk allele, or cardiovascular pharmacogenomic findings leading to a CoM within 3 months (90 days) and 6 months (180 days) after Return of Results (RoR). | Quantify the proportion of patients who receive monogenic cardiovascular disease, cardiovascular risk allele, or cardiovascular pharmacogenomic findings leading to a CoM within 3 months (90 days) and 6 months (180 days) after Return of Results (RoR). | Within 3 months (90 days) and 6 months (180 days) after Return of Results |