Assessment of Cardiac Allograft Vasculopathy by Optical Coherence Tomography

NCT02503566 | Unknown

• 1 other identifier: KKIKEM
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 2

Brief 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. 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. 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. 3.Tachycardia in heart transplant recipients represents a risk factor for development of cardiac allograft vasculopathy.
4. 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

Keywords

CAV; OCT; heart rate; antibodies

Outcome Measures

Primary Outcomes (1)

• Rapid progression of cardiac allograft vasculopathy

  OCT imaging will be used for identification of patients with early rapid progression of cardiac allograft vasculopathy. Normalized intimal volume, normalized lumen volume, mean intima thickness and mean intima-to-media ratio (I/M) will be used to identify fast progression of CAV.

  1 year

Secondary Outcomes (2)

• Donor specific anti-HLA and/or MICA antibodies

  1 year

• Heart rate

  1 year

Study Arms (1)

All patients

EXPERIMENTAL

Optical coherence tomography will be performed in all patients

Device: Optical coherence tomography

Interventions

Optical coherence tomography DEVICE

Optical coherence tomography performed during regular coronary angiography

All patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All new cardiac transplant recipients ≥18 years

You may not qualify if:

• Severe renal dysfunction (GFR less than 30 ml/min)
• Active infection
• Active cellular/humoral rejection
• Unwilling or unable to sign informed consent

Sponsors & Collaborators

• Institute for Clinical and Experimental Medicine: lead
• St. Anne: collaborator

Study Sites (2)

Helena Bedanova

Brno, 65691, Czechia

Location

Michal Pazdernik

Prague, 14021, Czechia

Location

Related Publications (8)

• Costanzo MR, Naftel DC, Pritzker MR, Heilman JK 3rd, Boehmer JP, Brozena SC, Dec GW, Ventura HO, Kirklin JK, Bourge RC, Miller LW. Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database. J Heart Lung Transplant. 1998 Aug;17(8):744-53.

  PMID: 9730422 BACKGROUND

• Stehlik J, Edwards LB, Kucheryavaya AY, Aurora P, Christie JD, Kirk R, Dobbels F, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: twenty-seventh official adult heart transplant report--2010. J Heart Lung Transplant. 2010 Oct;29(10):1089-103. doi: 10.1016/j.healun.2010.08.007. No abstract available.

  PMID: 20870164 BACKGROUND

• Wehner J, Morrell CN, Reynolds T, Rodriguez ER, Baldwin WM 3rd. Antibody and complement in transplant vasculopathy. Circ Res. 2007 Feb 2;100(2):191-203. doi: 10.1161/01.RES.0000255032.33661.88.

  PMID: 17272820 BACKGROUND

• Kaczmarek I, Deutsch MA, Kauke T, Beiras-Fernandez A, Schmoeckel M, Vicol C, Sodian R, Reichart B, Spannagl M, Ueberfuhr P. Donor-specific HLA alloantibodies: long-term impact on cardiac allograft vasculopathy and mortality after heart transplant. Exp Clin Transplant. 2008 Sep;6(3):229-35.

  PMID: 18954302 BACKGROUND

• Palatini P, Julius S. Elevated heart rate: a major risk factor for cardiovascular disease. Clin Exp Hypertens. 2004 Oct-Nov;26(7-8):637-44. doi: 10.1081/ceh-200031959.

  PMID: 15702618 BACKGROUND

• Olmetti F, Pinna GD, Maestri R, D'Armini A, Pellegrini C, Vigano M, Lilleri D, Gerna G, Febo O, La Rovere MT. Heart rate and cardiac allograft vasculopathy in heart transplant recipients. J Heart Lung Transplant. 2011 Dec;30(12):1368-73. doi: 10.1016/j.healun.2011.07.009. Epub 2011 Aug 15.

  PMID: 21840733 BACKGROUND

• Keogh A, Richardson M, Ruygrok P, Spratt P, Galbraith A, O'Driscoll G, Macdonald P, Esmore D, Muller D, Faddy S. Sirolimus in de novo heart transplant recipients reduces acute rejection and prevents coronary artery disease at 2 years: a randomized clinical trial. Circulation. 2004 Oct 26;110(17):2694-700. doi: 10.1161/01.CIR.0000136812.90177.94. Epub 2004 Jul 19.

  PMID: 15262845 BACKGROUND

• Garrido IP, Garcia-Lara J, Pinar E, Pastor-Perez F, Sanchez-Mas J, Valdes-Chavarri M, Pascual-Figal DA. Optical coherence tomography and highly sensitivity troponin T for evaluating cardiac allograft vasculopathy. Am J Cardiol. 2012 Sep 1;110(5):655-61. doi: 10.1016/j.amjcard.2012.04.047. Epub 2012 May 26.

  PMID: 22640973 BACKGROUND

MeSH Terms

Interventions

Tomography, Optical Coherence

Intervention Hierarchy (Ancestors)

Tomography, Optical; Optical Imaging; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Investigative Techniques

Study Officials

• Michal Pazdernik, M.D.

  Institute for Clinical and Experimental Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Study Record Dates

• First Submitted: July 15, 2015
• First Posted: July 21, 2015
• Study Start: September 1, 2014
• Primary Completion: March 1, 2019
• Study Completion: June 1, 2019
• Last Updated: October 23, 2018

Record last verified: 2018-10

Locations

CZ (2)