Assessment of Cardiac Allograft Vasculopathy by Optical Coherence Tomography

Summary

Cardiac allograft vasculopathy (CAV) is characterized by marked intimal proliferation and concentric vascular thickening and fibrosis. CAV remains the leading cause of late morbidity and mortality in heart transplant recipients. Optical coherence tomography (OCT) is a new generation catheter-based modality that acquires images at a spatial resolution of 10-20 μm which is 10-fold greater than that of intravascular ultrasound (IVUS). OCT is currently the most sensitive imaging technique for early CAV detection. Recent studies proved that circulating human leukocyte antigen (HLA) directed donor-specific antibodies correlate with increased mortality and CAV. Contradiction of scientific results has been reported regarding increased resting heart rate and development of CAV. Larger prospective studies using more sensitive CAV detecting methods are required to enhance our understanding. Novel immunosuppressants, mechanistic target of rapamycin (mTOR) inhibitors, may attenuate CAV progression and may improve long-term allograft survival owing to favorable coronary remodeling.

Aim of the study: Use OCT imaging for identification of patients with early rapid progression of CAV (rapid progressors) and to identify the critical risk factors responsible for CAV progression. The impact of conventional and heart transplant (HTx) specific risk factors, such as donor-specific antibodies or rapid heart rate will be studied in a prospective, national-level cohort study. The implication of OCT results will lead to adjustment of immunosuppressive therapy in one year after heart transplant to prevent further progression of the disease in CAV rapid progressors.

Working hypotheses:

1. Patients with rapid progression of cardiac allograft vasculopathy can be identified by increased titers of donor specific anti-human leukocyte antigen (anti-HLA) and/or antibodies against major histocompatibility complex (MHC) class I-related chain A (MICA) antibodies.
2. Specific high-risk characteristics of anti-HLA antibodies can be identified that are associated with particularly high rate of CAV progression (vascular complement activation in biopsies, certain HLA haplotypes).
3. Tachycardia in heart transplant recipients represents a risk factor for development of cardiac allograft vasculopathy.
4. Influence of anti-HLA antibodies and increased heart rate is independent of already established risk factors of CAV.

Conditions

• Disorder Related to Cardiac Transplantation

Interventions

DEVICE

Optical coherence tomography

Optical coherence tomography performed during regular coronary angiography

Sponsors & Collaborators

• St. Anne

  collaborator UNKNOWN

• Institute for Clinical and Experimental Medicine

  lead OTHER_GOV

Principal Investigators

• Michal Pazdernik, M.D. · Institute for Clinical and Experimental Medicine

Study Design

Allocation

NA

Purpose

DIAGNOSTIC

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-09-01

Primary Completion

2019-03-01

Completion

2019-06-01

Countries

• Czechia

Study Locations