Cardiac Allograft VasculopathyNCT02798731
Physiologic Assessment of Microvascular Function in Heart Transplant Patients
An observational study of Cardiac Allograft Vasculopathy, run by Samsung Medical Center at 1 site in South Korea.
Trial summary
The aim of the study is to evaluate the impact of early microvascular disease assessed by coronary physiologic indices such as fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR) on future occurrence of cardiac allograft vasculopathy (CAV) in heart transplant recipients. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Cardiac Allograft Vasculopathy
- How many people
- 200 participants
- Where
- 1 siteSouth Korea
- Study dates
- May 2016to Dec 2030
- How long will I take part?
- 6 Years
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Consecutive patients who received heart transplant undergoing coronary angiography for evaluation of coronary disease
Who may be able to join
- Subject over age of 18
- Patients received heart transplant
Who cannot join
- Patients with cardiogenic shock
- Patients with unstable vital sign that precludes coronary angiography
- Patients with major bleeding in last 3 months
- Patients with active bleeding
- Patients with coagulopathy
- Patients with severe valvular heart disease
- Patients who refused to provide informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
South Korea1 site, 1 recruiting
- Recruiting
Samsung Medical Center
Seoul
Joo Myung Lee, MD, MPH, 82-2-3410-1246, drone80@hanmail.net
About this study
Official title: Physiologic Assessment of Microvascular Function and Its Impact on Cardiac Allograft Vasculopathy in Heart Transplant Patients: Prospective Registry and Pilot Study
The aim of the study is to evaluate the impact of early microvascular disease assessed by coronary physiologic indices such as fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR) on future occurrence of cardiac allograft vasculopathy (CAV) in heart transplant recipients.
Read the detailed description
Cardiac allograft vasculopathy (CAV) or acute cellular rejection (ACR) are a leading cause of mortality and morbidity in heart transplant recipients. Most of the cases occur within 5 years after transplant and later incidence was known to be infrequent.
Mechanisms of CAV or ACR are thought to be multi-factorial involving both immunologic and non-immunologic factors that leads to injury of coronary endothelium and intimal hyperplasia. This unique mechanism results in long, diffuse and concentric stenosis of coronary arteries, different from those with conventional coronary atherosclerosis.
Due to lack of typical ischemic symptoms by denervated heart, diagnosis of CAV depends on routine screening tests rather than symptom based investigation. International Society for Heart and Lung Transplantation (ISHLT) guideline recommends annual or biannual coronary angiography screening until 5 years after transplant, but sensitivity of coronary angiography is limited because of diffuse involvement of all segments of coronary arteries. Alternatively, Intravascular ultrasound (IVUS) is a current standard for diagnosis and prognostication of CAV. It is well studied that progressive intimal thickening during the first year after transplant predicts future incidence of CAV and poor prognosis. However, the use of IVUS in the diagnosis of CAV is not generalized due to technical issues, high cost, procedure complications and ISHLT guideline states it is an option to exclude donor coronary artery disease, to detect rapidly progressive CAV, and provide prognostic information.
Recent development of single guidewire thermodilution technique enabled simple way to measure microvascular indices such as FFR, CFR, IMR. Our previous study shows, in patients with ischemic heart disease, presence of microvascular disease defined by low CFR and high IMR, predicts poor prognosis even without apparent epicardial disease. Considering its mechanism to involve diffuse coronary vasculature, CAV is believed to affect microvascular circulation in the early phase and spread to epicardial disease in its course. For this reason, by evaluating coronary physiology early after transplant, it may be possible to predict future progression of CAV.
There were previous studies which evaluated microvascular dysfunction in heart transplant patients. These studies indicated microvascular dysfunction at time of transplantation is related to progression of epicardial disease during first year after transplant, but lack of follow up prohibited from drawing any conclusion on occurrence of CAV later on. Another study by the same group evaluated microvascular dysfunction at 1 year after transplant and revealed it was associated with allograft vasculopathy at 5 years after transplant. However, this study did not evaluate impact of earlier assessments of microvascular dysfunction at time of transplantation on occurrence of CAV.
Therefore the current study will perform early physiologic assessments including fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance in patients who received heart transplant and evaluate the impact of initial microvascular dysfunction on future occurrence of CAV or ACR during 6 years of follow up. The investigators hope to develop strong predictors of CAV or ACR that can be evaluated early after heart transplant and to improve outcome by preemptive therapy before overt development of the disease.
This study will be a pilot study and target sample size will be 200 consecutive patients to receive heart transplant.
- Conditions
- Cardiac Allograft Vasculopathy
- Keywords
- Heart transplant, Microvascular dysfunction, Cardiac allograft vasculopathy, Fractional flow reserve, Coronary flow reserve, Index of microvascular resistance
What is being measured
The primary outcome is the main question the study is designed to answer.
Rates of cardiac death between patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 2-year follow-up after heart transplantation
Measured: 72 months
Acute cellular rejection between patients with or without overt microvascular disease
Measured: 72 months
Secondary outcomes (5)
Occurrence of anatomically significant cardiac allograft vasculopathy (% diameter stenosis > 50% on CCTA)
Measured: 72 months
Comparison of total aggregated plaque volume and presence of adverse plaque characteristics on CCTA between transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25).
Measured: 72 months
Comparison of all-cause mortality in transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 2-year follow-up after heart transplantation.
Measured: 24 months
Comparison of rates of cardiac death in transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 1-year follow-up after heart transplantation.
Measured: 72 months
Comparison of IVUS and physiologic indices in prediction of CAV progression.
Measured: 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2016 (estimated)
- Study startMay 2016
- Primary completionJun 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiac Allograft VasculopathyStudies of the same condition, open and under way.
- More trials run by Samsung Medical CenterThe 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)
- Target duration
- 6 Years
Sponsor and investigators
- Lead sponsor
- Samsung Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joo Myung Lee, Samsung Medical Center
- Investigators
- Joo Myung Lee, MD, MPH, Principal investigator, Samsung Medical CenterJin-Oh Choi, MD, PhD, Principal investigator, Samsung Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02798731
- Sponsor's protocol ID
- HTPL2016-05-024
- Status last verified
- Mar 2025
- First submitted
- 9 Jun 2016
- Last updated
- 14 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
Publications
Ha J, Lee SH, Choi KH, Shin D, Hong D, Kim D, Yang JH, Cho YH, Sung K, Park M, Kim JS, Park TK, Song YB, Hahn JY, Choi SH, Gwon HC, Oh JK, Choi JO, Lee JM. Microvascular Resistance Reserve and Prognosis After Heart Transplantation. JACC Cardiovasc Interv. 2025 Feb 24;18(4):439-452. doi: 10.1016/j.jcin.2024.11.011.
PubMed 40010915Lee JM, Choi KH, Choi JO, Shin D, Park Y, Kim J, Lee SH, Kim D, Yang JH, Cho YH, Sung K, Choi JY, Park M, Kim JS, Park TK, Song YB, Hahn JY, Choi SH, Gwon HC, Oh JK, Jeon ES. Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation. Circulation. 2021 Nov 2;144(18):1459-1472. doi: 10.1161/CIRCULATIONAHA.121.056158. Epub 2021 Sep 3.
PubMed 34474597Lee SH, Choi KH, Lee JM, Hwang D, Rhee TM, Park J, Kim HK, Cho YK, Yoon HJ, Park J, Song YB, Hahn JY, Doh JH, Nam CW, Shin ES, Hur SH, Koo BK. Physiologic Characteristics and Clinical Outcomes of Patients With Discordance Between FFR and iFR. JACC Cardiovasc Interv. 2019 Oct 28;12(20):2018-2031. doi: 10.1016/j.jcin.2019.06.044. Epub 2019 Sep 25.
PubMed 31563683
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiologic Assessment of Microvascular Function and Its Impact on Cardiac Allograft Vasculopathy in Heart Transplant Patients: Prospective Registry and Pilot Study
- ClinicalTrials.gov ID
- NCT02798731
- Acronym / sponsor ID
- HTPL2016-05-024
- Conditions
- Cardiac Allograft Vasculopathy
- Keywords
- Heart transplant, Microvascular dysfunction, Cardiac allograft vasculopathy, Fractional flow reserve, Coronary flow reserve, Index of microvascular resistance
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Samsung Medical CenterUniversity, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- Jun 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 14 Jun 2016 (estimated)
- 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.
The aim of the study is to evaluate the impact of early microvascular disease assessed by coronary physiologic indices such as fractional flow reserve (FFR), coronary flow reserve (CFR), index of microvascular resistance (IMR) on future occurrence of cardiac allograft vasculopathy (CAV) in heart transplant recipients.
Detailed description
Cardiac allograft vasculopathy (CAV) or acute cellular rejection (ACR) are a leading cause of mortality and morbidity in heart transplant recipients. Most of the cases occur within 5 years after transplant and later incidence was known to be infrequent.
Mechanisms of CAV or ACR are thought to be multi-factorial involving both immunologic and non-immunologic factors that leads to injury of coronary endothelium and intimal hyperplasia. This unique mechanism results in long, diffuse and concentric stenosis of coronary arteries, different from those with conventional coronary atherosclerosis.
Due to lack of typical ischemic symptoms by denervated heart, diagnosis of CAV depends on routine screening tests rather than symptom based investigation. International Society for Heart and Lung Transplantation (ISHLT) guideline recommends annual or biannual coronary angiography screening until 5 years after transplant, but sensitivity of coronary angiography is limited because of diffuse involvement of all segments of coronary arteries. Alternatively, Intravascular ultrasound (IVUS) is a current standard for diagnosis and prognostication of CAV. It is well studied that progressive intimal thickening during the first year after transplant predicts future incidence of CAV and poor prognosis. However, the use of IVUS in the diagnosis of CAV is not generalized due to technical issues, high cost, procedure complications and ISHLT guideline states it is an option to exclude donor coronary artery disease, to detect rapidly progressive CAV, and provide prognostic information.
Recent development of single guidewire thermodilution technique enabled simple way to measure microvascular indices such as FFR, CFR, IMR. Our previous study shows, in patients with ischemic heart disease, presence of microvascular disease defined by low CFR and high IMR, predicts poor prognosis even without apparent epicardial disease. Considering its mechanism to involve diffuse coronary vasculature, CAV is believed to affect microvascular circulation in the early phase and spread to epicardial disease in its course. For this reason, by evaluating coronary physiology early after transplant, it may be possible to predict future progression of CAV.
There were previous studies which evaluated microvascular dysfunction in heart transplant patients. These studies indicated microvascular dysfunction at time of transplantation is related to progression of epicardial disease during first year after transplant, but lack of follow up prohibited from drawing any conclusion on occurrence of CAV later on. Another study by the same group evaluated microvascular dysfunction at 1 year after transplant and revealed it was associated with allograft vasculopathy at 5 years after transplant. However, this study did not evaluate impact of earlier assessments of microvascular dysfunction at time of transplantation on occurrence of CAV.
Therefore the current study will perform early physiologic assessments including fractional flow reserve, coronary flow reserve, and index of microcirculatory resistance in patients who received heart transplant and evaluate the impact of initial microvascular dysfunction on future occurrence of CAV or ACR during 6 years of follow up. The investigators hope to develop strong predictors of CAV or ACR that can be evaluated early after heart transplant and to improve outcome by preemptive therapy before overt development of the disease.
This study will be a pilot study and target sample size will be 200 consecutive patients to receive heart transplant.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 6 Years
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Consecutive patients who received heart transplant undergoing coronary angiography for evaluation of coronary disease
Key inclusion criteria (2 listed)
- Subject over age of 18
- Patients received heart transplant
Key exclusion criteria (7 listed)
- Patients with cardiogenic shock
- Patients with unstable vital sign that precludes coronary angiography
- Patients with major bleeding in last 3 months
- Patients with active bleeding
- Patients with coagulopathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rates of cardiac death between patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 2-year follow-up after heart transplantation
Time frame: 72 months
Acute cellular rejection between patients with or without overt microvascular disease
Time frame: 72 months
5 secondary outcomes
Occurrence of anatomically significant cardiac allograft vasculopathy (% diameter stenosis > 50% on CCTA)
Time frame: 72 months
Comparison of total aggregated plaque volume and presence of adverse plaque characteristics on CCTA between transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25).
Time frame: 72 months
Comparison of all-cause mortality in transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 2-year follow-up after heart transplantation.
Time frame: 24 months
Comparison of rates of cardiac death in transplant patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 1-year follow-up after heart transplantation.
Time frame: 72 months
Comparison of IVUS and physiologic indices in prediction of CAV progression.
Time frame: 72 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 14 Mar 2025.
- Derived from this study: PubMed 40010915Ha J, Lee SH, Choi KH, Shin D, Hong D, Kim D, Yang JH, Cho YH, Sung K, Park M, Kim JS, Park TK, Song YB, Hahn JY, Choi SH, Gwon HC, Oh JK, Choi JO, Lee JM. Microvascular Resistance Reserve and Prognosis After Heart Transplantation. JACC Cardiovasc Interv. 2025 Feb 24;18(4):439-452. doi: 10.1016/j.jcin.2024.11.011.
- Derived from this study: PubMed 34474597Lee JM, Choi KH, Choi JO, Shin D, Park Y, Kim J, Lee SH, Kim D, Yang JH, Cho YH, Sung K, Choi JY, Park M, Kim JS, Park TK, Song YB, Hahn JY, Choi SH, Gwon HC, Oh JK, Jeon ES. Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation. Circulation. 2021 Nov 2;144(18):1459-1472. doi: 10.1161/CIRCULATIONAHA.121.056158. Epub 2021 Sep 3.
- Derived from this study: PubMed 31563683Lee SH, Choi KH, Lee JM, Hwang D, Rhee TM, Park J, Kim HK, Cho YK, Yoon HJ, Park J, Song YB, Hahn JY, Doh JH, Nam CW, Shin ES, Hur SH, Koo BK. Physiologic Characteristics and Clinical Outcomes of Patients With Discordance Between FFR and iFR. JACC Cardiovasc Interv. 2019 Oct 28;12(20):2018-2031. doi: 10.1016/j.jcin.2019.06.044. Epub 2019 Sep 25.
- Individual participant dataSharing planned: Yes. After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked
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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.
Joo Myung Lee, MD, MPH principal investigator
Samsung Medical Center
Jin-Oh Choi, MD, PhD principal investigator
Samsung Medical Center
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 Cardiac Allograft Vasculopathy, run by Samsung Medical Center at 1 site in South Korea.
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 7 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 14 Mar 2025. 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 South Korea. 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 Joo Myung Lee, MD, MPH (82-2-3410-1246, drone80@hanmail.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of cardiac death between patients with or without overt microvascular disease (CFR≤2 and IMR≥25) diagnosed with physiologic evaluation at 2-year follow-up after heart transplantation (time frame: 72 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02798731, which also lists 3 linked publications.
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 14 Mar 2025.