NCT02077764

Brief Summary

Objective:

  • To assess the relationship between coronary allograft vasculopathy (CAV) and graft function, and to evaluate non-invasive methods for CAV diagnosis.
  • To assess left ventricular (LV) and right ventricular (RV) function in the acute phase and serially during the first year after transplantation.
  • To evaluate the impact of acute and repetitive rejection on the longitudinal myocardial function Hypothesis
  • Timing of development and degree of CAV can be measured non-invasively combining myocardial longitudinal deformation (by advanced echocardiography) and coronary flow velocity reserve (CFVR) (by echocardiography and PET). This combination of methods can detect CAV before it is angiographically visual and gives supplementary information of the impact on myocardial graft function.
  • Longitudinal deformation, 3D echocardiography, cardiac magnetic resonance imaging (CMRI) and PET can be used for RV and LV myocardial function assessment and represent more valid markers of the function than standard echocardiography in heart transplant (HTX) patients.
  • Myocardial longitudinal deformation is a better marker of acute rejections than conventional ejection fraction (EF).
  • CAG
  • CFVR measurement by advanced echocardiography and PET. Graft function will be evaluated by:
  • Advanced echocardiography at rest end during bicycle exercise.
  • CMRI including assessment of LV and RV EF, strain and mass.
  • During rest and bicycle exercise echocardiography simultaneously right heart catheterization are performed for hemodynamic measurement Study 2 A prospective cohort study with 20-25 newly transplanted patients over a period of 12 months. LV and RV function will be measured by:
  • Advanced echocardiography
  • CFVR measurement (echocardiography and PET)
  • CMRI for LV and RV EF, strain and mass
  • Right heart catheterization Study 3 Prospective examination of correlation between graft function, CAV and rejection. Information of former episodes of acute rejection is collected retrospective. Study objectives are all living HTX patients (approx. 200) in the period of 2011-2013. Advanced echocardiography (including longitudinal deformation), biopsies (rejection evaluation) and CAG (CAV evaluation).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
65

participants targeted

Target at P25-P50 for all trials

Timeline
Completed

Started Sep 2013

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2013

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

February 28, 2014

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 4, 2014

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

April 14, 2016

Status Verified

April 1, 2016

Enrollment Period

2.3 years

First QC Date

February 28, 2014

Last Update Submit

April 13, 2016

Conditions

Heart Transplant Recipients

Keywords

heart transplantation,rejectioncardiac vasculopathyoptical coherence tomographyspeckle trackingPositron Emission Tomography .exercise capacity

Outcome Measures

Primary Outcomes (4)

  • Coronary flow velocity reserve

    Assessed by tissue Doppler echocardiography and H215O-PET

    September 2013 to January 2016

  • pulmonary capillary wedge pressure

    At rest and during exercise

    September 2013 to January 2016

  • global longitudinal strain

    At rest and during exercise

    September 2013 to January 2016

  • cardiac allograft vasculopathy

    Assessed by coronary angiography and optical coherence tomography

    September 2013 to January 2016

Secondary Outcomes (6)

  • RV-EF

    September 2013 to January 2016

  • Quality of life

    September 2013 to January 2016

  • CRP, TNT, Nt-ProBNP and fibrosis markers

    September 2013 to January 2016

  • tissue Doppler

    September 2013 to January 2016

  • Cardiac output

    September 2013 to January 2016

  • +1 more secondary outcomes

Other Outcomes (2)

  • Correlation between Rubidium and H2O PET

    May 2014 to January 2016

  • 3D echocardiography as a tool to diagnose vasculopathy

    September 2013 to January 2016

Study Arms (2)

Controls, healthy individuals

controls

Procedure: Echocardiography

Heart transplanted patients

Patients

Procedure: OCT and coronary angiographyProcedure: Right heart cat.Radiation: PETProcedure: EchocardiographyProcedure: exercise testOther: blood samples

Interventions

OCT and coronary angiographyPROCEDURE
Heart transplanted patients
Right heart cat.PROCEDURE
Heart transplanted patients
PETRADIATION
Heart transplanted patients
EchocardiographyPROCEDURE
Controls, healthy individualsHeart transplanted patients
exercise testPROCEDURE
Heart transplanted patients
blood samplesOTHER
Heart transplanted patients

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Design: A cross sectional study consisting of 50 stabile HTX patients. These will be selected with 25 patients with no or light CAV and 25 patients with moderate or severe CAV. 25 matched controls.

You may qualify if:

  • Age 18-100
  • Informed and signed consent

You may not qualify if:

  • \- Coronary stenosis within the first 3 mounts after HTX (donor transmitted coronary atherosclerosis).
  • Severe asthma or COLD with FEV1 \< 50%
  • ° or 3° AV block
  • Pregnancy
  • S-creatinine \>200 µmol/l
  • Allergy towards the contrast agent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Aarhus University Hospital, Skejby

Aarhus, Aarhus N, 8200, Denmark

Location

Related Publications (13)

  • Clemmensen TS, Munk K, Tram EM, Ilkjaer LB, Severinsen IK, Eiskjaer H. Twenty years' experience at the Heart Transplant Center, Aarhus University Hospital, Skejby, Denmark. Scand Cardiovasc J. 2013 Dec;47(6):322-8. doi: 10.3109/14017431.2013.845688. Epub 2013 Oct 16.

    PMID: 24131212BACKGROUND

  • Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Hertz MI; International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report--2012. J Heart Lung Transplant. 2012 Oct;31(10):1052-64. doi: 10.1016/j.healun.2012.08.002. No abstract available.

    PMID: 22975095BACKGROUND

  • Sipahi I, Starling RC. Cardiac allograft vasculopathy: an update. Heart Fail Clin. 2007 Jan;3(1):87-95. doi: 10.1016/j.hfc.2007.02.007.

    PMID: 17545012BACKGROUND

  • Tona F, Osto E, Tarantini G, Gambino A, Cavallin F, Feltrin G, Montisci R, Caforio AL, Gerosa G, Iliceto S. Coronary flow reserve by transthoracic echocardiography predicts epicardial intimal thickening in cardiac allograft vasculopathy. Am J Transplant. 2010 Jul;10(7):1668-76. doi: 10.1111/j.1600-6143.2010.03160.x.

    PMID: 20642688BACKGROUND

  • Khandhar SJ, Yamamoto H, Teuteberg JJ, Shullo MA, Bezerra HG, Costa MA, Selzer F, Lee JS, Marroquin OC, McNamara DM, Mulukutla SR, Toma C. Optical coherence tomography for characterization of cardiac allograft vasculopathy after heart transplantation (OCTCAV study). J Heart Lung Transplant. 2013 Jun;32(6):596-602. doi: 10.1016/j.healun.2013.02.005. Epub 2013 Mar 15.

    PMID: 23499356BACKGROUND

  • Syeda B, Hofer P, Pichler P, Vertesich M, Bergler-Klein J, Roedler S, Mahr S, Goliasch G, Zuckermann A, Binder T. Two-dimensional speckle-tracking strain echocardiography in long-term heart transplant patients: a study comparing deformation parameters and ejection fraction derived from echocardiography and multislice computed tomography. Eur J Echocardiogr. 2011 Jul;12(7):490-6. doi: 10.1093/ejechocard/jer064. Epub 2011 Jun 2.

    PMID: 21636605BACKGROUND

  • Logstrup BB, Hofsten DE, Christophersen TB, Moller JE, Botker HE, Pellikka PA, Egstrup K. Correlation between left ventricular global and regional longitudinal systolic strain and impaired microcirculation in patients with acute myocardial infarction. Echocardiography. 2012 Nov;29(10):1181-90. doi: 10.1111/j.1540-8175.2012.01784.x. Epub 2012 Aug 3.

    PMID: 22862151BACKGROUND

  • Wu YW, Chen YH, Wang SS, Jui HY, Yen RF, Tzen KY, Chen MF, Lee CM. PET assessment of myocardial perfusion reserve inversely correlates with intravascular ultrasound findings in angiographically normal cardiac transplant recipients. J Nucl Med. 2010 Jun;51(6):906-12. doi: 10.2967/jnumed.109.073833. Epub 2010 May 19.

    PMID: 20484427BACKGROUND

  • Fyfe DA, Mahle WT, Kanter KR, Wu G, Vincent RN, Ketchum DL. Reduction of tricuspid annular doppler tissue velocities in pediatric heart transplant patients. J Heart Lung Transplant. 2003 May;22(5):553-9. doi: 10.1016/s1053-2498(02)00653-8.

    PMID: 12742418BACKGROUND

  • Goland S, Siegel RJ, Burton K, De Robertis MA, Rafique A, Schwarz E, Zivari K, Mirocha J, Trento A, Czer LS. Changes in left and right ventricular function of donor hearts during the first year after heart transplantation. Heart. 2011 Oct;97(20):1681-6. doi: 10.1136/hrt.2010.220871. Epub 2011 May 17.

    PMID: 21586422BACKGROUND

  • D'Andrea A, Riegler L, Nunziata L, Scarafile R, Gravino R, Salerno G, Amarelli C, Maiello C, Limongelli G, Di Salvo G, Caso P, Bossone E, Calabro R, Pacileo G, Russo MG. Right heart morphology and function in heart transplantation recipients. J Cardiovasc Med (Hagerstown). 2013 Sep;14(9):648-58. doi: 10.2459/JCM.0b013e32835ec634.

    PMID: 23442808BACKGROUND

  • Clemmensen TS, Holm NR, Eiskjaer H, Logstrup BB, Christiansen EH, Dijkstra J, Barkholt TO, Terkelsen CJ, Maeng M, Poulsen SH. Layered Fibrotic Plaques Are the Predominant Component in Cardiac Allograft Vasculopathy: Systematic Findings and Risk Stratification by OCT. JACC Cardiovasc Imaging. 2017 Jul;10(7):773-784. doi: 10.1016/j.jcmg.2016.10.021. Epub 2017 Mar 15.

    PMID: 28330670DERIVED

  • Clemmensen TS, Eiskjaer H, Logstrup BB, Mellemkjaer S, Andersen MJ, Tolbod LP, Harms HJ, Poulsen SH. Clinical features, exercise hemodynamics, and determinants of left ventricular elevated filling pressure in heart-transplanted patients. Transpl Int. 2016 Feb;29(2):196-206. doi: 10.1111/tri.12690. Epub 2015 Oct 5.

    PMID: 26369751DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

At each visit blood samples are taken. These will include: 1 x 10 ml EDTA-blood 1 x 10 ml Lithiumheparin-blood 1 x 10ml Koagel -blood

MeSH Terms

Conditions

Rejection, Psychology

Interventions

Exercise TestBlood Specimen Collection

Condition Hierarchy (Ancestors)

Social BehaviorBehavior

Intervention Hierarchy (Ancestors)

Heart Function TestsDiagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisRespiratory Function TestsDiagnostic Techniques, Respiratory SystemErgometryInvestigative TechniquesSpecimen HandlingClinical Laboratory TechniquesPuncturesSurgical Procedures, Operative

Study Officials

  • Steen H Poulsen, M.D. DMSc

    Aarhus University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Target Duration
5 Years
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D., PhD student

Study Record Dates

First Submitted

February 28, 2014

First Posted

March 4, 2014

Study Start

September 1, 2013

Primary Completion

January 1, 2016

Study Completion

January 1, 2016

Last Updated

April 14, 2016

Record last verified: 2016-04

Locations

DK(1)