Aortic RegurgitationNCT06780241
Novel Characterization of Sex Specific Biologic Signatures in Valvular Heart Disease
An observational study of Aortic Regurgitation and Mitral Regurgitation, run by The Cleveland Clinic at 1 site in United States.
Trial summary
This project aims to validate sex-specific biologic signatures associated with aortic valve disease developed in a large multicenter CMR registry, using unsupervised phenomapping. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Aortic Regurgitation, Mitral Regurgitation, Aortic Stenosis
- What is being tested?
- CMR and Quality of Life Questionnaire
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2024to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with at least moderate Aortic Stenosis or Aortic Regurgitation who are scheduled for a surgical repair or replacement of their aortic valve.
Who may be able to join
- Age 18-90 years of age
- Suspected moderate or severe (2-3+ or more) aortic regurgitation, or moderate or more aortic stenosis on the basis of prior known clinical history, echocardiogram or cardiac MRI.
Who cannot join
- Acute traumatic cardiac injury
- Aortic dissection or aortic root rupture
- Congenital heart diseases such as patent ductus arteriosus, coarctation of aorta, ASD and VSD
- Presence of A-V fistula or intracardiac shunts
- Any contraindications to cardiac MRI including:
- Patients with any MR-incompatible implant, including cardiac pacemakers or defibrillators, or older types of cerebral aneurysm clips.
- Patients who weigh more than 440 lbs. or have a very wide waist circumference.
- Patients with claustrophobia may have difficulty tolerating the exam.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Degorah Kwon, MD, 216-444-8526
Lydia DeAngelo, 401-225-1929, deangel2@ccf.org
About this study
This project aims to validate sex-specific biologic signatures associated with aortic valve disease developed in a large multicenter CMR registry, using unsupervised phenomapping.
The aim to use standard and advanced CMR techniques (MRF, DTI, chemical exchange transfer, and radiomics analysis) is to determine advanced CMR predictors of reverse remodeling following aortic valve surgery and develop sex-specific thresholds for risk. Infrastructure developed by this study will enable development of an innovative, scalable, sex-specific precision medicine cardiovascular imaging pipeline to determine overall risk and treatment response.
Read the detailed description
Chronic valvular heart disease leads to significant left ventricular (LV) remodeling. Current national guidelines for surgical/procedural referral for valvular heart disease do not consider sex differences in presence of symptoms, LV remodeling and dysfunction. However, our prior research in patients with chronic aortic regurgitation, validated by our recent multicenter study, demonstrated that despite higher left ventricular function, and less ventricular dilation, females experienced more heart failure symptoms, fewer referrals for surgical intervention, and higher prevalence of adverse outcomes compared to males. Similarly, published HVTI data have demonstrated increased adverse outcomes in women referred for surgical mitral valve intervention.
Cardiac magnetic resonance (CMR) provides an exciting opportunity to characterize sex differences in LV remodeling.In combination with conventional CMR measures, novel CMR techniques such as Magnetic Resonance Fingerprinting (MRF), Diffusion Tensor imaging (DTI) and radiomics analysis provide tissue level specificity with potential to enhance phenomapping.
Limitations in understanding sex-specific remodeling patterns stem from heterogeneity of presentation, which confound traditional analytic methods. Phenomapping, a method of machine learning, clusters imaging features and patients into distinct phenotypic groups. Unsupervised phenomapping enables unbiased grouping of patients by both clinical characteristics as well as complex imaging features. In recent studies, this unbiased phenomapping approach demonstrates superior risk stratification of cardiac disease compared to traditional approaches that can be used to guide individualized treatment
The aim to use advanced CMR techniques (MRF, DTI, chemical exchange transfer, and radiomics analysis) is to determine advanced CMR predictors of reverse remodeling following procedural valve intervention and develop sex-specific thresholds for risk. Results from this study would enable the development of sex-specific precision medicine pathway, augmented by advanced imaging features, to better predict overall risk and treatment response, and thus enable novel patient selection criteria.
Study hypothesis: Radiomics, MRF, chemical exchange transfer, and DTI will elucidate distinct sex-specific biologic signatures, in addition to standard CMR imaging features, and are associated with adverse outcomes, and reverse remodeling following surgical/procedural valve intervention.
- Conditions
- Aortic Regurgitation, Mitral Regurgitation, Aortic Stenosis
- Being tested
- CMR, Quality of Life Questionnaire
- Medical subject headings
- Aortic Valve Insufficiency, Mitral Valve Insufficiency, Aortic Valve Stenosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CMRDiagnostic test
CMR (with contrast at baseline and non-contrast at follow-up)
Quality of Life QuestionnaireOther
Rapid Assessment of Physical Activity questionnaire and the Kansas City Cardiomyopathy Questionnaire
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Cardiac MRI (CMR) with Magnetic Resonance Fingerprinting (MRF), fSENC (a new CMR technology which may detect subclinical signs of myocardial damage by measuring myocardial strain), Diffusion Tensor imaging (DTI), and chemical exchange transfer imaging with contrast at baseline and without contrast at follow up.
Rapid Assessment of Physical Activity questionnaire Kansas City Cardiomyopathy Questionnaire Receives: Diagnostic Test: CMR; Other: Quality of Life Questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in LV Dilation and/or change in LVEF
Significant change in LV remodeling will be defined as a change in EF by 10 units (reverse remodeling is defined at least 10 unit decrease) or change in LV end-diastolic/systolic volume by 10% (Reverse remodeling is defined as at least decrease in LV end-diastolic/systolic volume by 10%
Measured: 6-12 months
Secondary outcomes (4)
Change in Aortic Regurgiation
Change in Aortic Regurgitant Fraction will be modeled as a continuous variable, as well as a threshold change of 5 points or more, as measured by cardiac MRI
Measured: 6-12 months
Change in BNP
NT-proBNP will be modeled as a continuous variable as well as a threshold change of 30% or decrease to level < 1000
Measured: 6-12 months
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
KCCQ will be modeled as a continuous variable, as well as a threshold change of 5 points or more.
KCCQ scoring transforms Likert-scale answers into 0-100 scores (higher is better) for domains like Physical Limitation, Symptom Frequency, Quality of Life, and Social Limitations, with a summary score reflecting overall health, where 0-24 is very poor, 25-49 poor/fair, 50-74 fair/good, and 75-100 good/excellent health.
Measured: 6-12 months
6 minute walk test
6 minute walk test will be modeled as a continuous variable as well as a threshold change of 30meters or more
Measured: 6-12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2025
- Study start10 Dec 2024
- Primary completion31 Dec 2030 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aortic RegurgitationStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Deborah Kwon, MD, The Cleveland Clinic
- Investigators
- Deborah Kwon, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06780241
- Sponsor's protocol ID
- 24-861
- Status last verified
- Dec 2025
- First submitted
- 13 Jan 2025
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Characterization of Sex Specific Biologic Signatures in Valvular Heart Disease
- ClinicalTrials.gov ID
- NCT06780241
- Acronym / sponsor ID
- 24-861
- Conditions
- Aortic Regurgitation, Mitral Regurgitation, Aortic Stenosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- 10 Dec 2024 (actual)
- Primary completion
- 31 Dec 2030 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 17 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This project aims to validate sex-specific biologic signatures associated with aortic valve disease developed in a large multicenter CMR registry, using unsupervised phenomapping.
The aim to use standard and advanced CMR techniques (MRF, DTI, chemical exchange transfer, and radiomics analysis) is to determine advanced CMR predictors of reverse remodeling following aortic valve surgery and develop sex-specific thresholds for risk. Infrastructure developed by this study will enable development of an innovative, scalable, sex-specific precision medicine cardiovascular imaging pipeline to determine overall risk and treatment response.
Detailed description
Chronic valvular heart disease leads to significant left ventricular (LV) remodeling. Current national guidelines for surgical/procedural referral for valvular heart disease do not consider sex differences in presence of symptoms, LV remodeling and dysfunction. However, our prior research in patients with chronic aortic regurgitation, validated by our recent multicenter study, demonstrated that despite higher left ventricular function, and less ventricular dilation, females experienced more heart failure symptoms, fewer referrals for surgical intervention, and higher prevalence of adverse outcomes compared to males. Similarly, published HVTI data have demonstrated increased adverse outcomes in women referred for surgical mitral valve intervention.
Cardiac magnetic resonance (CMR) provides an exciting opportunity to characterize sex differences in LV remodeling.In combination with conventional CMR measures, novel CMR techniques such as Magnetic Resonance Fingerprinting (MRF), Diffusion Tensor imaging (DTI) and radiomics analysis provide tissue level specificity with potential to enhance phenomapping.
Limitations in understanding sex-specific remodeling patterns stem from heterogeneity of presentation, which confound traditional analytic methods. Phenomapping, a method of machine learning, clusters imaging features and patients into distinct phenotypic groups. Unsupervised phenomapping enables unbiased grouping of patients by both clinical characteristics as well as complex imaging features. In recent studies, this unbiased phenomapping approach demonstrates superior risk stratification of cardiac disease compared to traditional approaches that can be used to guide individualized treatment
The aim to use advanced CMR techniques (MRF, DTI, chemical exchange transfer, and radiomics analysis) is to determine advanced CMR predictors of reverse remodeling following procedural valve intervention and develop sex-specific thresholds for risk. Results from this study would enable the development of sex-specific precision medicine pathway, augmented by advanced imaging features, to better predict overall risk and treatment response, and thus enable novel patient selection criteria.
Study hypothesis: Radiomics, MRF, chemical exchange transfer, and DTI will elucidate distinct sex-specific biologic signatures, in addition to standard CMR imaging features, and are associated with adverse outcomes, and reverse remodeling following surgical/procedural valve intervention.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | – | Diagnostic Test: CMR, Other: Quality of Life QuestionnaireCardiac MRI (CMR) with Magnetic Resonance Fingerprinting (MRF), fSENC (a new CMR technology which may detect subclinical signs of myocardial damage by measuring myocardial strain), Diffusion Tensor imaging (DTI), and chemical exchange transfer imaging with contrast at baseline and without contrast at follow up. Rapid Assessment of Physical Activity questionnaire Kansas City Cardiomyopathy Questionnaire |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with at least moderate Aortic Stenosis or Aortic Regurgitation who are scheduled for a surgical repair or replacement of their aortic valve.
Key inclusion criteria (2 listed)
- Age 18-90 years of age
- Suspected moderate or severe (2-3+ or more) aortic regurgitation, or moderate or more aortic stenosis on the basis of prior known clinical history, echocardiogram or cardiac MRI.
Key exclusion criteria (8 listed)
- Acute traumatic cardiac injury
- Aortic dissection or aortic root rupture
- Congenital heart diseases such as patent ductus arteriosus, coarctation of aorta, ASD and VSD
- Presence of A-V fistula or intracardiac shunts
- Any contraindications to cardiac MRI including:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CMRCMR (with contrast at baseline and non-contrast at follow-up) | Diagnostic test | Intervention |
| Quality of Life QuestionnaireRapid Assessment of Physical Activity questionnaire and the Kansas City Cardiomyopathy Questionnaire | Other | Intervention |
Primary outcome
Change in LV Dilation and/or change in LVEF
Time frame: 6-12 months
Significant change in LV remodeling will be defined as a change in EF by 10 units (reverse remodeling is defined at least 10 unit decrease) or change in LV end-diastolic/systolic volume by 10% (Reverse remodeling is defined as at least decrease in LV end-diastolic/systolic volume by 10%
4 secondary outcomes
Change in Aortic Regurgiation
Time frame: 6-12 months
Change in BNP
Time frame: 6-12 months
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score
Time frame: 6-12 months
6 minute walk test
Time frame: 6-12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deborah Kwon, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Regurgitation and Mitral Regurgitation, run by The Cleveland Clinic at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Deborah Kwon, MD (216-444-8526, kwond@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in LV Dilation and/or change in LVEF (time frame: 6-12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026; AzTrials last refreshed its copy on 8 Nov 2026.