Physiologic Assessment of Microvascular Function in Heart Transplant Patients

Cardiac Allograft Vasculopathy Clinical Trial

Official title:

Physiologic Assessment of Microvascular Function and Its Impact on Cardiac Allograft Vasculopathy in Heart Transplant Patients: Prospective Registry and Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02798731
• Other study ID #: HTPL2016-05-024
• Status: Recruiting
• Start date: May 2016
• Est. completion date: December 2025

Study information

• Verified date: September 2022
• Source: Samsung Medical Center
• Contact: Joo Myung Lee, MD, MPH
• Phone: 82-2-3410-1246
• Email: drone80[@]hanmail.net
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiac Allograft Vasculopathy
• Vascular Diseases

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		72 months
Primary	Acute cellular rejection between patients with or without overt microvascular disease		72 months
Secondary	Occurrence of anatomically significant cardiac allograft vasculopathy (% diameter stenosis > 50% on CCTA)		72 months
Secondary	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).		72 months
Secondary	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.		24 months
Secondary	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.		72 months
Secondary	Comparison of IVUS and physiologic indices in prediction of CAV progression.		72 months