Stress Cardiac MRI for Evaluation of Nonspecific Allograft Dysfunction

NCT ID: NCT02597543

Last Updated: 2017-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2016-06-30

Brief Summary

The investigators will use cardiac MRI to measure the myocardial perfusion reserve and amount of myocardial edema and fibrosis in heart-transplant patients with nonspecific allograft dysfunction in contrast to those with normal graft function. The investigators hypothesize that patients with nonspecific allograft dysfunction will demonstrate decreased myocardial perfusion reserve, related to microvascular allograft vasculopathy, compared to those with normal graft function.

Detailed Description

Adult heart-transplant patients, excluding those with a GFR less than 30 mL/min/1.73m2, contraindications to MRI and allergies to either regadenoson or gadolinium contrast, will be enrolled over 10 months. Patients will be recruited from UC San Diego and San Diego Veterans Affairs. The investigators will specifically enroll patients with nonspecific allograft dysfunction and patients with normal graft function.

Brief protocol:

Cardiac MRI is performed. Cine images in standard views are obtained. T2 mapping sequences are performed on short axis images. For stress imaging, intravenous regadenoson is given as a 0.4 mg bolus followed by a 5 mL saline flush. After 30 seconds, short-axis images are acquired for 30 consecutive heartbeats with administration of gadolinium. Rest imaging is performed 30 minutes after stress imaging. Lastly, late gadolinium enhancement images are obtained in standard views. Images are analyzed offline by a blinded independent reader. Patients will be followed for one month after enrollment for MACE.

Conditions

Heart Transplant; Acute Graft Rejection; Chronic Graft Rejection

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: SINGLE

Study Groups

Nonspecific allograft dysfunction

Patients with nonspecific allograft dysfunction will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

For use in stress myocardial perfusion imaging.

Gadolinium

Intervention Type: DRUG

For use in both perfusion imaging and late gadolinium enhancement.

Cardiac MRI

Intervention Type: PROCEDURE

Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.

Normal graft function

Patients with normal graft function will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart.

Group Type: EXPERIMENTAL

Regadenoson

Intervention Type: DRUG

For use in stress myocardial perfusion imaging.

Gadolinium

Intervention Type: DRUG

For use in both perfusion imaging and late gadolinium enhancement.

Cardiac MRI

Intervention Type: PROCEDURE

Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.

Interventions

Regadenoson

For use in stress myocardial perfusion imaging.

Intervention Type: DRUG

Gadolinium

For use in both perfusion imaging and late gadolinium enhancement.

Intervention Type: DRUG

Cardiac MRI

Cardiac MRI will be the imaging modality for perfusion imaging, late gadolinium enhancement and obtaining mean T1 segmental values of the heart.

Intervention Type: PROCEDURE

Other Intervention Names

Lexiscan; Magnevist

Eligibility Criteria

Inclusion Criteria

• Age greater than or equal to 18 years old.
• At least three months status post heart transplantation.
• Heart-transplant patients with normal graft function (left ventricular ejection fraction equal to or greater than 55%) and no prior history of clinically significant acute rejection episodes that required modification of the immunosuppressive regimen or cardiac allograft vasculopathy.
• Heart-transplant patients with nonspecific allograft dysfunction (left ventricular ejection fraction equal to or less than 50% AND decrease from post-transplant baseline ejection fraction by an absolute difference of 10% or greater, no formal diagnosis of allograft vasculopathy by coronary angiogram or coronary vascular ultrasonography, and no history of prior acute rejection episodes known to have decreased left ventricular ejection fraction to or less than 50%).

Exclusion Criteria

• Biopsy proven acute rejection episode in the past 3 months.
• Patients with symptoms or signs of acute myocardial ischemia or recent acute coronary syndrome in the past 3 months.
• Uncontrolled obstructive ventilatory disease including asthma and COPD.
• Second or third degree AV nodal block.
• Sinus node dysfunction.
• Contraindications to MRI including pacemakers or implantable cardioverter-defibrillators.
• Renal dysfunction with an estimated GFR less than 30 mL/min/1.73m2.
• Prior adverse reaction to either regadenoson or gadolinium contrast. Prior adverse reaction to adenosine will be assessed on a case-by-case basis.
• Any invasive procedure, including endomyocardial biopsy and left coronary angiogram, performed within one week.
• Systolic blood pressure greater than 180 or less than 85 mmHg.
• Diastolic blood pressure greater than 120 or less than 40 mmHg.
• Resting heart rate greater than 120 or less than 45 beats per minute.
• Severe claustrophobia.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Inc

INDUSTRY

Sponsor Role: collaborator

Paul Kim

OTHER

Sponsor Role: lead

Responsible Party

Paul Kim

Cardiology Fellow

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Paul J Kim, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

UC San Diego

La Jolla, California, United States

Countries

United States

References

Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dobbels F, Kirk R, Rahmel AO, Hertz MI. The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report--2011. J Heart Lung Transplant. 2011 Oct;30(10):1078-94. doi: 10.1016/j.healun.2011.08.003. No abstract available.

Reference Type: BACKGROUND

PMID: 21962016 (View on PubMed)

Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015. No abstract available.

Reference Type: BACKGROUND

PMID: 21555100 (View on PubMed)

Costanzo MR, Dipchand A, Starling R, Anderson A, Chan M, Desai S, Fedson S, Fisher P, Gonzales-Stawinski G, Martinelli L, McGiffin D, Smith J, Taylor D, Meiser B, Webber S, Baran D, Carboni M, Dengler T, Feldman D, Frigerio M, Kfoury A, Kim D, Kobashigawa J, Shullo M, Stehlik J, Teuteberg J, Uber P, Zuckermann A, Hunt S, Burch M, Bhat G, Canter C, Chinnock R, Crespo-Leiro M, Delgado R, Dobbels F, Grady K, Kao W, Lamour J, Parry G, Patel J, Pini D, Towbin J, Wolfel G, Delgado D, Eisen H, Goldberg L, Hosenpud J, Johnson M, Keogh A, Lewis C, O'Connell J, Rogers J, Ross H, Russell S, Vanhaecke J; International Society of Heart and Lung Transplantation Guidelines. The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients. J Heart Lung Transplant. 2010 Aug;29(8):914-56. doi: 10.1016/j.healun.2010.05.034. No abstract available.

Reference Type: BACKGROUND

PMID: 20643330 (View on PubMed)

Uretsky BF, Murali S, Reddy PS, Rabin B, Lee A, Griffith BP, Hardesty RL, Trento A, Bahnson HT. Development of coronary artery disease in cardiac transplant patients receiving immunosuppressive therapy with cyclosporine and prednisone. Circulation. 1987 Oct;76(4):827-34. doi: 10.1161/01.cir.76.4.827.

Reference Type: BACKGROUND

PMID: 3308166 (View on PubMed)

Fang JC, Kinlay S, Beltrame J, Hikiti H, Wainstein M, Behrendt D, Suh J, Frei B, Mudge GH, Selwyn AP, Ganz P. Effect of vitamins C and E on progression of transplant-associated arteriosclerosis: a randomised trial. Lancet. 2002 Mar 30;359(9312):1108-13. doi: 10.1016/S0140-6736(02)08154-0.

Reference Type: BACKGROUND

PMID: 11943259 (View on PubMed)

Pham MX, Teuteberg JJ, Kfoury AG, Starling RC, Deng MC, Cappola TP, Kao A, Anderson AS, Cotts WG, Ewald GA, Baran DA, Bogaev RC, Elashoff B, Baron H, Yee J, Valantine HA; IMAGE Study Group. Gene-expression profiling for rejection surveillance after cardiac transplantation. N Engl J Med. 2010 May 20;362(20):1890-900. doi: 10.1056/NEJMoa0912965. Epub 2010 Apr 22.

Reference Type: BACKGROUND

PMID: 20413602 (View on PubMed)

Bhalodolia R, Cortese C, Graham M, Hauptman PJ. Fulminant acute cellular rejection with negative findings on endomyocardial biopsy. J Heart Lung Transplant. 2006 Aug;25(8):989-92. doi: 10.1016/j.healun.2006.04.002. Epub 2006 Jun 30.

Reference Type: BACKGROUND

PMID: 16890123 (View on PubMed)

Miller CA, Sarma J, Naish JH, Yonan N, Williams SG, Shaw SM, Clark D, Pearce K, Stout M, Potluri R, Borg A, Coutts G, Chowdhary S, McCann GP, Parker GJ, Ray SG, Schmitt M. Multiparametric cardiovascular magnetic resonance assessment of cardiac allograft vasculopathy. J Am Coll Cardiol. 2014 Mar 4;63(8):799-808. doi: 10.1016/j.jacc.2013.07.119. Epub 2013 Dec 18.

Reference Type: BACKGROUND

PMID: 24355800 (View on PubMed)

Marie PY, Angioi M, Carteaux JP, Escanye JM, Mattei S, Tzvetanov K, Claudon O, Hassan N, Danchin N, Karcher G, Bertrand A, Walker PM, Villemot JP. Detection and prediction of acute heart transplant rejection with the myocardial T2 determination provided by a black-blood magnetic resonance imaging sequence. J Am Coll Cardiol. 2001 Mar 1;37(3):825-31. doi: 10.1016/s0735-1097(00)01196-7.

Reference Type: BACKGROUND

PMID: 11693758 (View on PubMed)

Butler CR, Thompson R, Haykowsky M, Toma M, Paterson I. Cardiovascular magnetic resonance in the diagnosis of acute heart transplant rejection: a review. J Cardiovasc Magn Reson. 2009 Mar 12;11(1):7. doi: 10.1186/1532-429X-11-7.

Reference Type: BACKGROUND

PMID: 19284612 (View on PubMed)

Kubrich M, Petrakopoulou P, Kofler S, Nickel T, Kaczmarek I, Meiser BM, Reichart B, von Scheidt W, Weis M. Impact of coronary endothelial dysfunction on adverse long-term outcome after heart transplantation. Transplantation. 2008 Jun 15;85(11):1580-7. doi: 10.1097/TP.0b013e318170b4cd.

Reference Type: BACKGROUND

PMID: 18551063 (View on PubMed)

Solberg OG, Ragnarsson A, Kvarsnes A, Endresen K, Kongsgard E, Aakhus S, Gullestad L, Stavem K, Aaberge L. Reference interval for the index of coronary microvascular resistance. EuroIntervention. 2014 Jan 22;9(9):1069-75. doi: 10.4244/EIJV9I9A181.

Reference Type: BACKGROUND

PMID: 24457279 (View on PubMed)

Other Identifiers

1186278

Identifier Type: -

Identifier Source: org_study_id