Hypertrophic Cardiomyopathy Registry, Biobank and Imaging Data Repository

Brief Title

Hypertrophic Cardiomyopathy Registry, Biobank and Imaging Data Repository

Official Title

Hearts in Rhythm Organization Hypertrophic Cardiomyopathy Registry, Biobank and Imaging Data Repository (HiRO-HCM)

Brief Summary

      The Hearts in Rhythm Organization (HiRO) is a national network of Canadian
      researchers/clinicians, working towards a better understanding of the rare genetic causes of
      sudden cardiac death (SCD). The HiRO Hypertrophic Cardiomyopathy registry, biobank and
      imaging data repository (HiRO-HCM) is a multicenter study that will prospectively enroll
      patients with HCM as well as those carrying sarcomeric gene variants predisposing to HCM.

      The objectives of HiRO-HCM are:

        1. to better understand the natural history of the disease and identify clinical markers
           and biomarkers for adverse outcomes;

        2. to derive and validate risk prediction models for disease expression, complications and
           response to therapy;

        3. to better define the genetic architecture of sarcomeric and non-sarcomeric HCM.

Detailed Description


      Eligible patients will be included from HiRO sites or collaborating centres. Patients will be
      contacted by the local investigator or a research coordinator. Willing individuals will be
      interviewed by the research coordinator and given information about HiRO-HCM. The consent
      form will be reviewed and discussed with the coordinator. The investigators will also be
      available for any questions that the coordinator is unable to answer. Potential participants
      will have sufficient time to consider participating in HiRO-HCM. Written informed consent
      will be obtained from eligible patients or legal guardians. Participants will be able to
      withdraw their participation at any time.


      Clinical data will be collected from willing/consented registry participants. All demographic
      and medical information pertaining to the cardiac history and comorbidities of eligible
      patients will be collected at baseline, including clinical information, diagnostic test
      results, genetic testing results, family history and ethnicity, as well as current and
      previous treatments. Healthcare information will be coded in compliance with Canada's
      Tri-Council Policy Statement criteria: direct identifiers will be removed and replaced with a
      unique study code that does not use personal information such as the participant's health
      number, social insurance number or name. The coded data will be transferred into the clinical
      research database using a web-based electronic case report form (eCRF), using REDcap. The
      clinical research database will be managed by the Montreal Health Innovations Coordinating
      Center (MHICC; mhicc.org). Study participants will be identified by subject number only
      (research HiRO-HCM ID). The research ID uniquely identifying each subject eCRF within the
      database will be attributed in REDcap but the master list of registry participants with their
      study identifiers will be kept separately from the clinical research database. This master
      list will be stored in an encrypted file within the research office of each site
      investigators under their supervision. Only the site investigators and their local research
      staff will have access to this list.


      Consented participants will undergo biosampling at enrollment for the primary purpose of DNA
      isolation and genetic studies. The preferred biosampling method is blood sampling using a
      standard venipuncture. Blood sampling allows for high quality DNA extraction as well as
      collection of plasma for future circulating biomarkers studies. As an alternative to blood
      sampling, collection of saliva using DNA genotek kits, or equivalent, is allowed in the
      following contexts:

        -  Patient enrollment is performed remotely. This is particularly relevant in the context
           of the ongoing SARS-CoV-2 pandemic, where physical distancing is preferred.

        -  Patient is a child <14 years old without planned clinically indicated blood sampling.

      Participants for which saliva collection is chosen should be made aware of the possibility to
      request a blood sample in the future.

      The HiRO-HCM biobank will be directed by the Beaulieu-Saucier Pharmacogenomics Center (PGx;
      http://www.pharmacogenomics.ca), operating under Good Laboratory/Clinical Practices (GLP/GCP)

      DNA isolation and long-term storage will be done at PGx, while long-term storage of plasma
      samples will be done at the MHI research center, in dedicated freezers located in a room with
      restricted access. Samples of subjects that withdraw their participation will be destroyed.


      For all consented participants, de-identified transthoracic echocardiography (TTE) and
      cardiac magnetic resonance (CMR) imaging data will be transferred to the Montreal Heart
      Institute imaging core-lab for central interpretation and long term storage. At minimum, the
      following imaging studies are requested:

        1. First available TTE

        2. First available CMR, preferably with gadolinium injection

        3. Last available TTE

        4. Last available CMR, preferably with gadolinium injection

      For patients that underwent alcohol septal ablation, surgical myectomy and/or cardiac
      transplantation, the last available TTE and CMR studies prior to all these interventions
      should also be transferred.

      Digital Imaging and Communications in Medicine (DICOM) imaging data will be de-identified
      prior to transfer. De-identification will be performed at each site, by removing the
      patient's name and replacing the clinical identification number with the research HiRO-HCM
      ID. DICOM data will be stored using the Canadian Imaging network infrastructure


      Participants with a clinical diagnosis of HCM are expected to undergo yearly clinic visits,
      as per standard care. Participants without yearly clinic visits will be contacted by phone.
      Follow-up visits will assess for living status, functional class, as well as for arrhythmic,
      heart failure and thromboembolic events. Follow-up data will be entered by the local
      investigator and/or research coordinator into an eCRF managed by the MHICC. De-identified
      documentation of clinical events including ECG, intracardiac tracing, clinical notes, imaging
      reports, and procedural reports will be uploaded to the database for centralized ad-hoc event

      De-identified DICOM images of TTE and CMR studies performed clinically during follow-up will
      be uploaded to the MHI imaging core-lab similarly as for baseline imaging studies.

      For participants that will undergo septal myectomy for drug-refractory obstructive HCM, or
      cardiac transplantation, surgical tissue samples will be collected using the Qiagen PAXgene
      tissue preservation system or equivalent, allowing for future somatic DNA, RNA and proteomic
      analyses. The samples will be stored at the MHI research center.

Study Type

Observational [Patient Registry]

Primary Outcome

Create a Canadian Research Database, a biobank and an imaging data repository for those affected by hypertrophic cardiomyopathy (HCM) or carrying a sarcomeric gene variant associated with HCM


Hypertrophic Cardiomyopathy


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Estimated Enrollment


Start Date

February 23, 2021

Completion Date

August 23, 2027

Primary Completion Date

February 23, 2026

Eligibility Criteria

        Inclusion Criteria:

        Patients with (1) AND/OR (2)

          1. Clinical diagnosis of HCM, defined as

               1. maximal LVWT ≥15mm, or

               2. maximal LVWT ≥13mm, in presence of a diagnosis of first degree relative with HCM,

               3. septal wall thickness with z-score >2 in a child


          2. Carrier of a pathogenic or likely pathogenic genetic variant in a sarcomeric gene
             (ACTC1, FHOD3, MYBPC3, MYH7, MYL2, MYL3, TNNI3, TNNT2, TPM1). Variant classification
             should be performed by a certified diagnostic laboratory according to the American
             College of Medical Genetics and Genomics (ACMG) guidelines.

        Exclusion Criteria:

          1. Clinical or molecular diagnosis of Noonan syndrome or other Rasopathies

          2. Clinical or molecular diagnosis of metabolic disease associated with cardiomyopathy,
             such as Pompe (GAA), Fabry (GLA), Danon (LAMP2), AMP-kinase (PRKAG2), and carnitine

          3. Clinical diagnosis of a neuromuscular disease associated with cardiomyopathy, such as
             Friedrich's ataxia

          4. Clinical diagnosis of cardiac amyloidosis with or without the presence of genetic
             variants in TTR

          5. Clinical or molecular diagnosis of mitochondrial cardiomyopathy

          6. Diagnosis of HCM >65 years old AND absence of pathogenic or likely pathogenic variant
             in a sarcomeric gene (as defined in inclusion criterion 1B above)

          7. History of myocardial infarction

          8. History of moderate or severe aortic stenosis

          9. History of congenital heart defects requiring percutaneous or surgical correction

         10. History of severe hypertension defined as a systolic blood pressure >180 mmHg and/or
             diastolic blood pressure >110 mmHg AND absence of pathogenic or likely pathogenic
             variant in a sarcomeric gene (as defined in inclusion criterion 1B above)

         11. Refusal to provide informed consent or to provide a biospecimen for DNA analysis

         12. No possibility to upload transthoracic echocardiogram or cardiac magnetic resonance
             imaging for core lab interpretation




N/A - N/A

Accepts Healthy Volunteers



Rafik Tadros, Dr., , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Montreal Heart Institute


 Canadian Institutes of Health Research (CIHR)

Study Sponsor

Rafik Tadros, Dr., Principal Investigator, Montreal Heart Institute

Verification Date

May 2022