Acquirement of Clinical and Genomic Data to Diagnose in Rare Inherited Cardiomyopathy

NCT06948344 | Recruiting

• 1 other identifier: 4-2023-0855
• Study Type: observational
• Target: 560
• Locations: 1 country
• Sites: 1

Brief Summary

"Background Information Cardiomyopathy is one of the leading causes of heart failure. In cases where cardiomyopathy does not respond to guideline-directed medical therapy for heart failure, the disease may progress to a stage where heart transplantation is the only viable treatment option. According to the 2022 Korean Organ Transplant Registry (KOTRY) report, cardiomyopathy accounted for approximately 65% of heart transplant indications in Korea, making it one of the most challenging unresolved issues in modern cardiology. Furthermore, cardiomyopathy is associated with a high risk of sudden cardiac death due to ventricular fibrillation or ventricular tachycardi and implantable cardioverter-defibrillators are often recommended as a preventive measure. Given that sudden cardiac death frequently occurs in young and middle-aged individuals, it is a major public health concern in developed countries such as North America and Western/Northern Europe, prompting ongoing societal and medical efforts to reduce its burden. The risk of sudden cardiac death imposes a persistent psychological burden on family members of patients with cardiomyopathy. Because sudden death can also occur in children and adolescents, current clinical guidelines recommend early cardiac evaluation and genetic counseling for family members of affected individuals. This study seeks to overcome the current limitations in the genetic diagnosis of cardiomyopathy, including the low diagnostic yield of currently available gene panels. To date, most genetic data on cardiomyopathy have been derived from Western populations. There is a significant lack of population-specific genomic data for East Asians, particularly Koreans, making it difficult to interpret the results of genetic testing in Korean patients. By developing bioinformatics algorithms that comprehensively analyze whole genome sequencing (WGS) data, including single nucleotide variants (SNVs), insertions/deletions (indels), and structural variations, this study aims to generate a reference dataset tailored to the Korean population. This will directly improve the genetic diagnosis of cardiomyopathy in Korean patients. Additionally, by identifying novel pathogenic variants through WGS, this study may elucidate new disease mechanisms underlying cardiomyopathy. These findings could provide a theoretical basis for developing novel diagnostic biomarkers, therapeutic targets, and even gene-based therapies. The present study is part of a multi-phase national research project supported by the Korea Disease Control and Prevention Agency and the Korea National Institute of Health, conducted as a registry cohort titled the ""Korean Cardiomyopathy Cohort (KCC)"". Objectives This study aims to establish a diagnostic research framework to elucidate the genetic architecture of rare inherited cardiomyopathies through comprehensive analysis of whole genome sequencing data, with the goal of identifying novel diagnostic approaches

Conditions

Cardiomyopathy; Whole Genome Sequencing

Outcome Measures

Primary Outcomes (1)

• Establishing genomic profiles of rare inherited cardiomyopathies

  This study aims to establish a diagnostic research framework to elucidate the genetic architecture of rare inherited cardiomyopathies through comprehensive analysis of whole genome sequencing data

  At the time of enrollment

Secondary Outcomes (2)

• Occurrence of adjudicated cardiovascular event

  From enrollment until the first occurrence of adjudicated clinical events, assessed up to 5 years

• Occurrence of adjudicated cardiovascular event

  up to 5 years

Study Arms (1)

WGS cohort

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with cardiomyopathy in whom a genetic etiology is strongly suspected and no pathogenic variants have been identified, or those with at least one first-degree relative diagnosed with the same cardiomyopathy subtype

You may qualify if:

• patients aged 19 years or older who have provided written consent for participation, have the capability to consent voluntarily and have been diagnosed with cardiomyopathy, as defined by one of the following criteria: -Ones with suspected genetic cardiomyopathy of unknown etiology, meeting at least one of the following conditions: i) Patients with idiopathic cardiomyopathy, for whom no clear secondary causes (e.g., history of hypertension, alcohol abuse, or chemotherapy) can be identified, and in whom a genetic etiology is strongly suspected.
• ii) Patients who have previously undergone genetic testing using an NGS panel, but no pathogenic variants were identified, and further evaluation with whole genome sequencing (WGS) is warranted.
• iii) Patients diagnosed with cardiomyopathy before the age of 50, without known contributing factors such as hypertension or excessive alcohol consumption, raising a strong suspicion of a genetic cause.
• Patients with a family history of genetic cardiomyopathy, defined as having at least one first-degree relative (parent, sibling, or child) diagnosed with the same type of cardiomyopathy, confirming a familial genetic pattern.

You may not qualify if:

• Patients with confirmed ischemic cardiomyopathy (when stenosis of 75% or more of major coronary arteries is confirmed on coronary artery imaging or ischemic cardiomyopathy findings such as transmural LGE on cardiac MRI)
• Heart failure with other etiologies (e.g., valvular heart disease, endocrine disease)

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Division of Cardiology, Severance Cardiovascular hospital Department of Internal Medicine, Yonsei University College of Medicine

Seoul, South Korea

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood (5-10 mL) will be collected in an EDTA tube, and genomic DNA (≥20 μg) will be extracted using the Theragen Bio platform

MeSH Terms

Conditions

Cardiomyopathies

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Byung-Su Yoo, MD, PhD

  Wonju Severance Christian Hospital

  PRINCIPAL INVESTIGATOR

• Jin-Oh Choi, MD, PhD

  Samsung Medical Center

  PRINCIPAL INVESTIGATOR

• Hyun-jai Cho, MD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

• Jae Young Cho, MD

  Chonnam National University Hospital

  PRINCIPAL INVESTIGATOR

• Soo Yong Lee, MD, PhD

  Pusan National University Yangsan Hospital

  PRINCIPAL INVESTIGATOR

• Ju-Hee Lee, MD

  Chungbuk National University

  PRINCIPAL INVESTIGATOR

• Junho Hyun, MD, MSc

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

• Minjae Yoon, MD

  Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

• Eui-Young Choi, MD, PhD

  Gangnam Severance Hospital

  PRINCIPAL INVESTIGATOR

• Jung Hyun Choi, MD

  Pusan National University Hospital

  PRINCIPAL INVESTIGATOR

• In-Cheol Kim, MD, PhD

  Keimyung University Dongsan Medical Center

  PRINCIPAL INVESTIGATOR

• Wook-Jin Chung, MD, PhD

  Gil Medical Center

  PRINCIPAL INVESTIGATOR

• Moon Seoung Soh, MD

  Ajou University School of Medicine

  PRINCIPAL INVESTIGATOR

• Jin-Ok Jeong, MD, PhD

  Chungnam National University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jaewon Oh, M.D. Ph.D.

CONTACT

ericjcoh@yuhs.ac

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2025
• First Posted: April 29, 2025
• Study Start: October 10, 2023
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): August 22, 2028
• Last Updated: May 13, 2025

Record last verified: 2025-05

Locations

KR (1)