Mayo AVC Registry and Biobank

NCT03049254 | Recruiting

• 1 other identifier: 17-004169
• Study Type: observational
• Target: 1,000
• Locations: 2 countries
• Sites: 2

Brief Summary

Arrhythmogenic ventricular cardiomyopathy (AVC) is a genetic condition which affects the heart and can lead to heart failure and rhythm problems, of which, sudden cardiac arrest or death is the most tragic and dangerous. Diagnosis and screening of blood-relatives is very difficult as the disease process can be subtle, but sufficient enough, so that the first event is sudden death. The Mayo Clinic AVC Registry is a collaboration between Mayo Clinic, Rochester, USA and Papworth Hospital, Cambridge University Hospitals, Cambridge, UK. The investigators aim to enroll patients with a history of AVC or sudden cardiac death which may be due to AVC, from the US and UK. Family members who are blood-relatives will also be invited, including those who do not have the condition. Data collected include symptoms, ECG, echocardiographic, MRI, Holter, loop recorder, biopsies, exercise stress testing, blood, buccal and saliva samples. Objectives of the study:

1. 1.Discover new genes or altered genes (variants) which cause AVC
2. 2.Identify biomarkers which predict (2a) disease onset, (2b) disease progression, (2c) and the likelihood of arrhythmia (ventricular, supra-ventricular and atrial fibrillation)
3. 3.Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally using clinical, electrocardiographic and imaging data.
4. 4.Characterize desmosomal changes in buccal mucosal cells with genotype and validate with gold-standard endomyocardial biopsies

Conditions

Sudden Cardiac Arrest; Arrhythmogenic Right Ventricular Dysplasia; Arrhythmogenic Ventricular Cardiomyopathy; Familial Dilated Cardiomyopathy; Cardiovascular Abnormalities; Sarcoidosis; Cardiac Arrhythmia; Cardiac Sarcoidosis; Myocarditis; Inflammatory Cardiomyopathy; Ventricular Tachycardia; Right Ventricular Outflow Tract Ventricular Tachycardia; Arrhythmogenic Right Ventricular Cardiomyopathy; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Sudden Cardiac Death

Outcome Measures

Primary Outcomes (2)

• Genotyping

  Using family 'trios' discover novel pathogenic variants and characterize them

  3 years

• Correlate genotype with phenotype

  Correlate genotype with phenotype in confirmed cases of AVC followed longitudinally as per 2010 Task Force Criteria

  3-6 years

Secondary Outcomes (5)

• Natural history and secular trends of AVC

  3-6 years

• Natural history and secular trends of AVC

  3-6 years

• Natural history and secular trends of AVC

  3-6 years

• Cellular and Tissue phenotyping

  3 years

• Risk factors for sudden death or appropriate ICD discharge

  5-10 years

Study Arms (2)

Proband

Proband - the person who is the first to present with a diagnosis of AVC

Family members (consultands)

First-degree relatives of probands with AVC (who may be living or deceased) In some circumstances where multiple family members are or may be affected, they may be eligible.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients seen at any Mayo Clinic facility or Papworth Hospital.Cambridge University Hospitals, who have AVC will be evaluated via their medical records (retrospective chart review) according to 2010 Task Force Criteria. Family members who are being screened for AVC are also eligible, as are patients with overlapping conditions (phenocopies such as myocarditis, sarcoidosis, inflammatory cardiomyopathies, outflow tract tachycardias and Brugada pattern, and familial dilated cardiomyopathy). Patients seen at other institutions who wish to enroll are encourgaed to apply and may be eligible. For the optional novel genetic variant discovery and biobank phases, patients will be invited to participate and undergo written consent.

You may qualify if:

• Patients with a diagnosis of a non-MI SCA who survived
• Patients with a non-MI SCD
• Patient with a SCA associated with seizures, epilepsy, syncope, drowning and near-drowning, where a cardiomyopathy is suspected
• Family member of a patient diagnosed with primary cardiomyopathy (including HCM, idiopathic DCM, AVC)

You may not qualify if:

• Patients with a clear, unambiguous known cause of SCA or SCD such as myocardial infarction or heart failure secondary to ischemic heart disease
• Significant coronary artery disease (Epicardial coronary artery stenosis \>50%) which can explain degree of LV dysfunction
• Those unwilling to provide written consent or assent

Sponsors & Collaborators

• Mayo Clinic: lead
• Cambridge University Hospitals NHS Foundation Trust: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Royal Papworth Hospital NHS Foundation Trust

Papworth Everard, Cambridge, CB23 3RE, United Kingdom

RECRUITING

Related Links

• Mayo Clinic Clinical Trials

Biospecimen

Retention: SAMPLES WITH DNA

For participants who volunteer and consent to the biobank arm, a baseline blood sample, saliva sample and buccal scrapings will be collected and stored for analyses in the future. The investigators will initially test for exisiting and novel pathogenic variants using next generation whole exome sequencing, which is not approved for clinical diagnosis. However, technologies are rapidly evolving, and samples may be used for whole genome and epigenome analyses. Blood will also be stored for measuring known blood-biomarkers of disease progression (such as high-sensitivity cardiac troponins, natriuretic peptides, high-sensitivity CRP and cytokines). Blood will also be stored for high throughput 'omics (transcriptomics, metabolomics and proteomics) to develop new biomarkers for diagnosis and disease progression.

MeSH Terms

Conditions

Arrhythmogenic Right Ventricular Dysplasia; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Death, Sudden, Cardiac; familial dilated cardiomyopathy; Cardiovascular Abnormalities; Sarcoidosis; Arrhythmias, Cardiac; Myocarditis; Tachycardia, Ventricular

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Arrest; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Hypersensitivity, Delayed; Hypersensitivity; Immune System Diseases; Tachycardia; Cardiac Conduction System Disease

Study Officials

• Virend Somers, PhD, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nicholas Wozniak

CONTACT

+1 507 2558794; wozniak.nicholas@mayo.edu

Anwar A Chahal, Ph.D.

CONTACT

chahal.anwar@mayo.edu

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 30, 2017
• First Posted: February 10, 2017
• Study Start: February 9, 2018
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1); US (1)