UMIN-ICDS Clinical Trial

Public title

Cardiomyopathy HeterOgeneity and Risk stratification through Deep phenotyping (CHORD study)

Acronym

Cardiomyopathy HeterOgeneity and Risk stratification through Deep phenotyping (CHORD study)

Scientific Title

Cardiomyopathy HeterOgeneity and Risk stratification through Deep phenotyping (CHORD study)

Scientific Title:Acronym

CHORD study

Region

Japan

Condition

non-dilated left ventricular cardiomyopathy

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

YES

Narrative objectives1

The aim of this study is to comprehensively characterize the natural history and disease heterogeneity of NDLVC through deep phenotyping integrating clinical, imaging, genetic, and multi-omics data, and to scientifically validate its relevance and underlying structure as a novel phenotypic category proposed by the 2023 ESC Guidelines.
Specifically, this study aims to:
1. Characterize the natural history and clinical outcomes of NDLVC by integrating a 5-year prospective follow-up with a large-scale retrospective cohort;
2. Identify and reclassify distinct phenotypes and endotypes within NDLVC; and
3. Characterize dynamic disease processes based on longitudinal changes in multi-omics and imaging data.

Basic objectives2

Others

Basic objectives -Others

To integrate clinical, imaging, genetic, and multi-omics data obtained through deep phenotyping of NDLVC to establish risk stratification and prognostic models for clinical outcomes, including life-threatening arrhythmias, and to develop personalized management strategies according to individual disease profiles.

Trial characteristics_1

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

All-cause death
Cardiovascular death: sudden death; death due to heart failure/cardiogenic shock, acute myocardial infarction, or stroke; death related to cardiovascular procedures or bleeding (e.g., non-stroke intracranial hemorrhage, aortic rupture/dissection, cardiac tamponade); and other cardiovascular causes (e.g., pulmonary embolism, peripheral artery disease).
Non-cardiovascular death: pulmonary/respiratory failure, renal failure, gastrointestinal, hepatobiliary or pancreatic disease, infection including sepsis, inflammatory disease including SIRS/autoimmune/allergic disease, non-cardiovascular bleeding or procedures, trauma, suicide, drug intoxication, non-cardiovascular neurological disease, malignancy, or other causes.
Death of undetermined cause: death unclassifiable because of insufficient information; cardiovascular or non-cardiovascular classification is preferred.
Heart transplantation or ventricular assist device implantation
Worsening heart failure events: hospitalization, unscheduled visits requiring treatment such as intravenous diuretics, or treatment intensification (GDMT or diuretic dose escalation) for worsening heart failure
New-onset atrial fibrillation
Appropriate implantable cardioverter-defibrillator (ICD) therapy
Stroke (ischemic, hemorrhagic, or transient ischemic attack)
Other events requiring hospitalization
Changes in left ventricular ejection fraction (LVEF), dimensions, volumes, and mass
Changes in New York Heart Association (NYHA) functional class
Changes in oxygen consumption and VE/VCO2 slope on cardiopulmonary exercise testing
Changes in limb/trunk muscle strength, balance, and frailty measures
Changes in Kansas City Cardiomyopathy Questionnaire (KCCQ) scores
Patient experience measures (CG-CAHPS)
Changes in medications and doses (initiation, escalation, reduction, or discontinuation)
Omics data from blood, urine, exhaled volatile organic compounds (VOCs), stool, and myocardial tissue

Key secondary outcomes

Secondary Outcomes
Length of hospital stay
Invasive procedures performed, including:
Pacemaker implantation, implantable cardioverter-defibrillator (ICD) implantation, and cardiac resynchronization therapy (CRT)
Catheter ablation for atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia, and other arrhythmias
Other invasive procedures
Data obtained from wearable activity trackers and smartwatches
Inpatient and outpatient healthcare costs based on Diagnosis Procedure Combination (DPC) data

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Male and Female

Key inclusion criteria

1. Presence of late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR), irrespective of LVEF
2. Presence of left ventricular systolic dysfunction on transthoracic echocardiography
3. Left ventricular end-diastolic diameter within the upper limit of normal: <58 mm in men and <52 mm in women (no adjustment for body size required)

Key exclusion criteria

1. Patients diagnosed with primary cardiomyopathy (dilated, hypertrophic, restrictive, or arrhythmogenic right ventricular cardiomyopathy)
2. Patients diagnosed with secondary cardiomyopathy (e.g., cardiac amyloidosis, cardiac sarcoidosis, mitochondrial disease, Fabry disease, peripartum cardiomyopathy, post-myocarditis cardiomyopathy, drug-induced cardiomyopathy, or alcoholic cardiomyopathy)
3. Patients with significant coronary artery stenosis (50% or greater in the left main coronary artery or 75% or greater in any other major coronary artery), a history of myocardial infarction, or prior percutaneous coronary intervention or coronary artery bypass grafting
4. Patients with severe valvular heart disease
5. Patients with congenital heart disease
6. Patients with pulmonary hypertension other than Group 2 pulmonary hypertension
7. Patients with severe hepatic dysfunction or liver cirrhosis
8. Patients with severe renal dysfunction or those receiving dialysis
9. Patients with active cancer or a history of anthracycline therapy (use of other anticancer agents is permitted)
10. Patients with a life expectancy of less than 1 year
11. Patients deemed unsuitable for participation in the study by the principal investigator or co-investigators.

Target sample size

5000

Name of lead principal investigator

1st name	Masaki
Middle name
Last name	Ieda

Organization

Keio University School of Medicine

Division name

Department of Cardiology

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

03-5843-6702

Email

mieda@keio.jp

Name of contact person

1st name	Yasuyuki
Middle name
Last name	Shiraishi

Organization

Keio University School of Medicine

Division name

Department of Cardiology

Zip code

160-8582

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

TEL

03-5843-6702

Homepage URL

Email

white_cascade_libra@yahoo.co.jp

Institute

Keio University School of Medicine

Institute

Department

Personal name

Yasuyuki Shiraishi

Organization

Bridgestone Corporation

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Ethics Committee of Keio University School of Medicine

Address

35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

Tel

03-3353-1211

Email

med-rinri-jimu@adst.keio.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

慶應義塾大学病院、杏林大学医学部付属病院、防衛医科大学校病院、埼玉医科大学国際医療センター、国立病院機構 埼玉病院、さいたま市立病院、国立病院機構 東京医療センター、東京都済生会中央病院、国家公務員共済組合連合会立川病院、日野市立病院、川崎市立川崎病院、横浜市立市民病院、神奈川県警友会けいゆう病院、済生会宇都宮病院、
国際医療福祉大学市川総合病院

Date of disclosure of the study information

2026

Year

10

Month

15

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2025

Year

12

Month

16

Day

Date of IRB

2026

Year

02

Month

27

Day

Anticipated trial start date

2026

Year

10

Month

01

Day

Last follow-up date

2033

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Investigators and clinical research coordinators at each site will register patients using a centralized web-based system and enter data at baseline and at 6 months and 1, 2, 3, 4, and 5 years. Selected data will be cross-checked against DPC data obtained at each site. DPC data will be processed using a de-identification program developed by TRIGRAPH Co., Ltd. and shared via a secure data-sharing application (e.g., Box) for centralized data linkage and management.
1. Baseline data
a. Patient characteristics
b. Vital signs, HF stage (B-D), and NYHA class
c. Clinical Frailty Scale
d. Blood and urine tests
e. 12-lead and ambulatory ECG
f. Echocardiography
g. Cardiac MRI/CT, chest X-ray, and cardiopulmonary exercise testing
h. Right heart catheterization
i. Medications, including diuretics, RAS inhibitors, beta-blockers, MRAs, SGLT2 inhibitors, ivabradine, sGC stimulators, digitalis, calcium-channel blockers, antithrombotic/antiarrhythmic agents, antidiabetic drugs, lipid/uric acid-lowering agents, and potassium binders
j. Invasive treatments (catheter-based, device, and surgical therapies)
k. Physical activity and autonomic activity assessed using wearable devices
l. Muscle strength, balance, and frailty measures
m. Health-related QoL
n. Patient Experience (PX)
o. Omics analyses (blood, urine, exhaled VOCs, stool, and myocardium)
2. Follow-up data
a. Cardiovascular adverse events
b. Invasive procedures
c. Blood tests
d. Echocardiography
e. Cardiopulmonary exercise testing
f. Medications
g. Physical and autonomic activity
h. Muscle strength, balance, and frailty
i. Health-related QoL
j. Patient Experience (PX)
k. Omics analyses
l. Healthcare cost information based on DPC data

Registered date

2026

Year

09

Month

17

Day

Last modified on

2026

Year

10

Month

15

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000071987