MRI to Predict Rejection and Failure in Transplant and Cardiomyopathy Patients

NCT03822442 | Completed

• 1 other identifier: 11408
• Study Type: observational
• Target: 113
• Locations: 1 country
• Sites: 1

Brief Summary

Overall Research Strategy of this protocol is to refine and validate noninvasive CMR imaging sequences with invasive hemodynamic and pathology results to create a comprehensive, noninvasive, radiation-reduced regimen for pediatric cardiomyopathy and cardiac transplant assessment. We were the first to perform MR-guided cardiac catheterization in US children, and have accumulated the largest US experience, having performed over 75 procedures to date. Our unique experience puts us in strong position to leverage this technology to improve care of children with cardiomyopathy and transplant. Using an integrated approach, we will simultaneously (1) validate imaging measures of cardiac edema and fibrosis by correlating T1 and T2 map images with endomyocardial biopsy (EMB) results in Aim 1; (2) overlay T1, T2 map images into our x-ray system to display "hotspots" of T1 and T2 abnormalities to guide EMB in Aim 2; and (3) obtain radiation-free hemodynamic data in a highly vulnerable pediatric population by using CMR to guide catheter manipulation in the ICMR suite in Aim 3. Age and diagnosis-matched historical controls will be identified from the last 10 years at Children's National as a control population for specific purposes of comparing (1) EMB yield without image overlay and (2) Radiation exposure during X-ray guided right heart catheterization. Identical information will be obtained and stored in the same 45CFR compliant database. Historical controls will be identified from the cardiac catheterization database by searching for age and diagnosis. A waiver of consent will be applicable here, as it would be inconvenient, insensitive and not feasible to consent families who have already undergone treatment.

Conditions

Heart Failure; Cardiac Imaging Techniques; Congenital Heart Defects

Keywords

Cardiomyopathy, cardiomegaly; cardiac transplant

Outcome Measures

Primary Outcomes (1)

• Correlate MRI imaging results to biopsy results Correlate MRI imaging with endomyocardial biopsy

  Correlate MRI imaging sequences that can detect inflammation and fibrosis to quantities of inflammation and fibrosis seen on biopsy specimens taken from the same region.

  At the end of each catheterization procedure through study completion,up to 5 years

Secondary Outcomes (2)

• Compare yield of biopsy specimen collection using x-ray vs x-ray fused MRI images

  At the end of each catheterization procedure through study completion,up to 5 years

• Radiation exposure

  At the end of each catheterization procedure through study completion,up to 5 years

Eligibility Criteria

• Age: 6 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals referred to Children's National Medical Center with heart transplant or cardiomyopathy (i.e. "pre-transplant") to undergo clinically-indicated cardiac catheterization will be considered candidates for inclusion.

You may qualify if:

• Children and adults of any age with heart transplant, suspected or confirmed cardiomyopathy
• Undergoing clinically-indicated ("medically necessary") cardiovascular catheterization

You may not qualify if:

• Cardiovascular instability including hemodynamic instability (such as requiring significant vasoactive infusion support) or mechanical hemodynamic support.
• Women who are pregnant
• Women who are nursing and who do not plan to discard breast milk for 24 hours
• Central nervous system aneurysm clips
• Implanted neural stimulator
• Implanted cardiac pacemaker or defibrillator which are not MR safe or MR conditional according to the manufacturer
• Cochlear implant
• Ocular foreign body (e.g. metal shavings)
• Implanted Insulin pump
• Metal shrapnel or bullet.
• Renal disease with estimated glomerular filtration rate \[eGFR\] \< 30 ml/min/1.73 m2 body surface area
• The eGFR will be used to estimate renal function if reported by the laboratory.
• The Schwartz equation 33 for estimation of GFR in children as recommended by the NKDEP is as follows:
• GFR (mL/min/1.73 m2) = (k × height) / serum creatinine concentration
• where k = constant defined as follows: k = 0.33 in premature infants k = 0.45 in term infants to 1 year of age k = 0.55 in children to 13 years of age k = 0.70 in adolescent males (not females because of the presumed increase in male muscle mass, the constant remains 0.55 for females) Height in cm Serum creatinine in mg/dL

Sponsors & Collaborators

• Children's National Research Institute: lead

Study Sites (1)

Children's National Health System

Washington D.C., District of Columbia, 20010, United States

Location

Related Publications (26)

• Hsu DT, Pearson GD. Heart failure in children: part I: history, etiology, and pathophysiology. Circ Heart Fail. 2009 Jan;2(1):63-70. doi: 10.1161/CIRCHEARTFAILURE.108.820217. No abstract available.

  PMID: 19808316 BACKGROUND

• Lee TM, Hsu DT, Kantor P, Towbin JA, Ware SM, Colan SD, Chung WK, Jefferies JL, Rossano JW, Castleberry CD, Addonizio LJ, Lal AK, Lamour JM, Miller EM, Thrush PT, Czachor JD, Razoky H, Hill A, Lipshultz SE. Pediatric Cardiomyopathies. Circ Res. 2017 Sep 15;121(7):855-873. doi: 10.1161/CIRCRESAHA.116.309386.

  PMID: 28912187 BACKGROUND

• Lipshultz SE, Cochran TR, Briston DA, Brown SR, Sambatakos PJ, Miller TL, Carrillo AA, Corcia L, Sanchez JE, Diamond MB, Freundlich M, Harake D, Gayle T, Harmon WG, Rusconi PG, Sandhu SK, Wilkinson JD. Pediatric cardiomyopathies: causes, epidemiology, clinical course, preventive strategies and therapies. Future Cardiol. 2013 Nov;9(6):817-48. doi: 10.2217/fca.13.66.

  PMID: 24180540 BACKGROUND

• McKenna WJ, Maron BJ, Thiene G. Classification, Epidemiology, and Global Burden of Cardiomyopathies. Circ Res. 2017 Sep 15;121(7):722-730. doi: 10.1161/CIRCRESAHA.117.309711.

  PMID: 28912179 BACKGROUND

• Badano LP, Miglioranza MH, Edvardsen T, Colafranceschi AS, Muraru D, Bacal F, Nieman K, Zoppellaro G, Marcondes Braga FG, Binder T, Habib G, Lancellotti P; Document reviewers. European Association of Cardiovascular Imaging/Cardiovascular Imaging Department of the Brazilian Society of Cardiology recommendations for the use of cardiac imaging to assess and follow patients after heart transplantation. Eur Heart J Cardiovasc Imaging. 2015 Sep;16(9):919-48. doi: 10.1093/ehjci/jev139. Epub 2015 Jul 2.

  PMID: 26139361 BACKGROUND

• Dayton JD, Kanter KR, Vincent RN, Mahle WT. Cost-effectiveness of pediatric heart transplantation. J Heart Lung Transplant. 2006 Apr;25(4):409-15. doi: 10.1016/j.healun.2005.11.443. Epub 2006 Feb 8.

  PMID: 16563970 BACKGROUND

• Wagner K, Oliver MC, Boyle GJ, Miller SA, Law YM, Pigula F, Webber SA. Endomyocardial biopsy in pediatric heart transplant recipients: a useful exercise? (Analysis of 1,169 biopsies). Pediatr Transplant. 2000 Aug;4(3):186-92. doi: 10.1034/j.1399-3046.2000.00100.x.

  PMID: 10933318 BACKGROUND

• Johnson JN, Hornik CP, Li JS, Benjamin DK Jr, Yoshizumi TT, Reiman RE, Frush DP, Hill KD. Cumulative radiation exposure and cancer risk estimation in children with heart disease. Circulation. 2014 Jul 8;130(2):161-7. doi: 10.1161/CIRCULATIONAHA.113.005425. Epub 2014 Jun 9.

  PMID: 24914037 BACKGROUND

• Andreassi MG, Ait-Ali L, Botto N, Manfredi S, Mottola G, Picano E. Cardiac catheterization and long-term chromosomal damage in children with congenital heart disease. Eur Heart J. 2006 Nov;27(22):2703-8. doi: 10.1093/eurheartj/ehl014. Epub 2006 May 22.

  PMID: 16717079 BACKGROUND

• Ait-Ali L, Andreassi MG, Foffa I, Spadoni I, Vano E, Picano E. Cumulative patient effective dose and acute radiation-induced chromosomal DNA damage in children with congenital heart disease. Heart. 2010 Feb;96(4):269-74. doi: 10.1136/hrt.2008.160309. Epub 2009 Aug 16.

  PMID: 19687017 BACKGROUND

• Beels L, Bacher K, De Wolf D, Werbrouck J, Thierens H. gamma-H2AX foci as a biomarker for patient X-ray exposure in pediatric cardiac catheterization: are we underestimating radiation risks? Circulation. 2009 Nov 10;120(19):1903-9. doi: 10.1161/CIRCULATIONAHA.109.880385. Epub 2009 Oct 26.

  PMID: 19858412 BACKGROUND

• Singh V, Mendirichaga R, Savani GT, Rodriguez A, Blumer V, Elmariah S, Inglessis-Azuaje I, Palacios I. Comparison of Utilization Trends, Indications, and Complications of Endomyocardial Biopsy in Native Versus Donor Hearts (from the Nationwide Inpatient Sample 2002 to 2014). Am J Cardiol. 2018 Feb 1;121(3):356-363. doi: 10.1016/j.amjcard.2017.10.021. Epub 2017 Oct 31.

  PMID: 29197471 BACKGROUND

• Subherwal S, Kobashigawa JA, Cogert G, Patel J, Espejo M, Oeser B. Incidence of acute cellular rejection and non-cellular rejection in cardiac transplantation. Transplant Proc. 2004 Dec;36(10):3171-2. doi: 10.1016/j.transproceed.2004.10.048.

  PMID: 15686721 BACKGROUND

• Parsai C, O'Hanlon R, Prasad SK, Mohiaddin RH. Diagnostic and prognostic value of cardiovascular magnetic resonance in non-ischaemic cardiomyopathies. J Cardiovasc Magn Reson. 2012 Aug 2;14(1):54. doi: 10.1186/1532-429X-14-54.

  PMID: 22857649 BACKGROUND

• Piehler KM, Wong TC, Puntil KS, Zareba KM, Lin K, Harris DM, Deible CR, Lacomis JM, Czeyda-Pommersheim F, Cook SC, Kellman P, Schelbert EB. Free-breathing, motion-corrected late gadolinium enhancement is robust and extends risk stratification to vulnerable patients. Circ Cardiovasc Imaging. 2013 May 1;6(3):423-32. doi: 10.1161/CIRCIMAGING.112.000022. Epub 2013 Apr 18.

  PMID: 23599309 BACKGROUND

• Olivieri L, Cross R, O'Brien KJ, Xue H, Kellman P, Hansen MS. Free-breathing motion-corrected late-gadolinium-enhancement imaging improves image quality in children. Pediatr Radiol. 2016 Jun;46(7):983-90. doi: 10.1007/s00247-016-3553-7. Epub 2016 Feb 17.

  PMID: 26886912 BACKGROUND

• Kellman P, Arai AE. Cardiac imaging techniques for physicians: late enhancement. J Magn Reson Imaging. 2012 Sep;36(3):529-42. doi: 10.1002/jmri.23605.

  PMID: 22903654 BACKGROUND

• Moon JC, Messroghli DR, Kellman P, Piechnik SK, Robson MD, Ugander M, Gatehouse PD, Arai AE, Friedrich MG, Neubauer S, Schulz-Menger J, Schelbert EB; Society for Cardiovascular Magnetic Resonance Imaging; Cardiovascular Magnetic Resonance Working Group of the European Society of Cardiology. Myocardial T1 mapping and extracellular volume quantification: a Society for Cardiovascular Magnetic Resonance (SCMR) and CMR Working Group of the European Society of Cardiology consensus statement. J Cardiovasc Magn Reson. 2013 Oct 14;15(1):92. doi: 10.1186/1532-429X-15-92.

  PMID: 24124732 BACKGROUND

• Messroghli DR, Moon JC, Ferreira VM, Grosse-Wortmann L, He T, Kellman P, Mascherbauer J, Nezafat R, Salerno M, Schelbert EB, Taylor AJ, Thompson R, Ugander M, van Heeswijk RB, Friedrich MG. Clinical recommendations for cardiovascular magnetic resonance mapping of T1, T2, T2* and extracellular volume: A consensus statement by the Society for Cardiovascular Magnetic Resonance (SCMR) endorsed by the European Association for Cardiovascular Imaging (EACVI). J Cardiovasc Magn Reson. 2017 Oct 9;19(1):75. doi: 10.1186/s12968-017-0389-8.

  PMID: 28992817 BACKGROUND

• Mavrogeni S, Bratis K, Georgakopoulos D, Karanasios E, Kolovou G, Pavlides G, Papadopoulos G. Evaluation of myocarditis in a pediatric population using cardiovascular magnetic resonance and endomyocardial biopsy. Int J Cardiol. 2012 Oct 18;160(3):192-5. doi: 10.1016/j.ijcard.2011.04.019. Epub 2011 May 10.

  PMID: 21561672 BACKGROUND

• Kellman P, Wilson JR, Xue H, Ugander M, Arai AE. Extracellular volume fraction mapping in the myocardium, part 1: evaluation of an automated method. J Cardiovasc Magn Reson. 2012 Sep 10;14(1):63. doi: 10.1186/1532-429X-14-63.

  PMID: 22963517 BACKGROUND

• Ugander M, Bagi PS, Oki AJ, Chen B, Hsu LY, Aletras AH, Shah S, Greiser A, Kellman P, Arai AE. Myocardial edema as detected by pre-contrast T1 and T2 CMR delineates area at risk associated with acute myocardial infarction. JACC Cardiovasc Imaging. 2012 Jun;5(6):596-603. doi: 10.1016/j.jcmg.2012.01.016.

  PMID: 22698528 BACKGROUND

• Abu Hazeem AA, Dori Y, Whitehead KK, Harris MA, Fogel MA, Gillespie MJ, Rome JJ, Glatz AC. X-ray magnetic resonance fusion modality may reduce radiation exposure and contrast dose in diagnostic cardiac catheterization of congenital heart disease. Catheter Cardiovasc Interv. 2014 Nov 1;84(5):795-800. doi: 10.1002/ccd.25473. Epub 2014 Mar 20.

  PMID: 24619541 BACKGROUND

• McGuirt D, Mazal J, Rogers T, Faranesh AZ, Schenke W, Stine A, Grant L, Lederman RJ. X-ray Fused With Magnetic Resonance Imaging to Guide Endomyocardial Biopsy of a Right Ventricular Mass. Radiol Technol. 2016 Jul;87(6):622-6.

  PMID: 27390230 BACKGROUND

• Saikus CE, Lederman RJ. Interventional cardiovascular magnetic resonance imaging: a new opportunity for image-guided interventions. JACC Cardiovasc Imaging. 2009 Nov;2(11):1321-31. doi: 10.1016/j.jcmg.2009.09.002.

  PMID: 19909937 BACKGROUND

• Ratnayaka K, Faranesh AZ, Hansen MS, Stine AM, Halabi M, Barbash IM, Schenke WH, Wright VJ, Grant LP, Kellman P, Kocaturk O, Lederman RJ. Real-time MRI-guided right heart catheterization in adults using passive catheters. Eur Heart J. 2013 Feb;34(5):380-9. doi: 10.1093/eurheartj/ehs189. Epub 2012 Aug 1.

  PMID: 22855740 BACKGROUND

MeSH Terms

Conditions

Heart Failure; Heart Defects, Congenital; Cardiomyopathies; Cardiomegaly

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hypertrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Laura Olivieri, MD

  Children's National Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics/Cardiologist

Study Record Dates

• First Submitted: January 28, 2019
• First Posted: January 30, 2019
• Study Start: December 10, 2019
• Primary Completion: November 30, 2025
• Study Completion: December 31, 2025
• Last Updated: March 31, 2026

Record last verified: 2026-03

Locations

US (1)