Physiologic Assessment of Microvascular Function in Heart Transplant Patients

March 12, 2025 updated by: Joo Myung Lee, Samsung Medical Center

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.

Study Overview

Status

Recruiting

Conditions

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 Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Consecutive patients who received heart transplant undergoing coronary angiography for evaluation of coronary disease

Description

Inclusion Criteria:

  • Subject over age of 18
  • Patients received heart transplant

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
72 months
Acute cellular rejection between patients with or without overt microvascular disease
Time Frame: 72 months
72 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Occurrence of anatomically significant cardiac allograft vasculopathy (% diameter stenosis > 50% on CCTA)
Time Frame: 72 months
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
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
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
72 months
Comparison of IVUS and physiologic indices in prediction of CAV progression.
Time Frame: 72 months
72 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Samsung Medical Center

Investigators

  • Principal Investigator: Joo Myung Lee, MD, MPH, Samsung Medical Center
  • Principal Investigator: Jin-Oh Choi, MD, PhD, Samsung Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2016

Primary Completion (Estimated)

June 1, 2030

Study Completion (Estimated)

December 1, 2030

Study Registration Dates

First Submitted

June 9, 2016

First Submitted That Met QC Criteria

June 9, 2016

First Posted (Estimated)

June 14, 2016

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 12, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HTPL2016-05-024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

After publication of first manuscript and trial results, the de-identified data will be shared by permission of principle investigator, when asked

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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