Allograft Dysfunction in Heart Transplant

Phase 4

Recruiting

• Conditions: Heart Transplant Failure and Rejection
• Interventions: Drug: Regadenoson

• Registration Number: NCT03102125
• Lead Sponsor: Paul Kim

Brief Summary

The investigators will evaluate for early evidence of cardiac allograft dysfunction by cardiac MRI and single cell sequencing to determine underlying molecular and macroscopic causes.

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 60 months. Patients will be recruited from UCSD. The investigators will specifically enroll all eligible heart-transplant patients.

Brief protocol:

Cardiac MRI is performed. Cine images in standard views are obtained. T1 and T2 mapping sequences are performed on short axis images pre- and post-gadolinium contrast. 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 at least 1 year after enrollment for MACE.

Peripheral blood and endomyocardial biopsies will also be collected, timing as per usual clinical care as well as for-cause, for single cell RNAseq analyses.

Study Timeline

• Study First Submitted: 2017-03-29
• Study First Submitted QC: 2017-03-29
• Study First Posted: 2017-04-05
• Study Start: 2019-10-01
• Status Verified: 2024-01
• Last Update Submitted: 2024-05-06
• Last Update Posted: 2024-05-08
• Primary Completion: 2024-12-01
• Study Completion: 2024-12-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 376

Inclusion Criteria

• Age greater than or equal to 18 years old.
• At least three months status post heart transplantation.

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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.
• History of generalized tonic-clonic seizures.
• Second or third degree AV nodal block.
• Sinus node dysfunction.
• Contraindications to MRI including cardiovascular implantable electronic devices.
• 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 or dipyridamole will be assessed on a case-by-case basis.
• 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nonspecific allograft dysfunction	Regadenoson	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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
Normal graft function	Regadenoson	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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
ACR/AMR	Regadenoson	Patients with allograft dysfunction from prior episodes of acute cellular or antibody mediated rejection will undergo stress cardiac MRI with regadenoson in addition to performing late gadolinium enhancement and obtaining mean segmental T1 values of the heart. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.
Cardiac allograft vasculopathy	Regadenoson	Patients with allograft dysfunction from known cardiac 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. Peripheral blood and endomycardial biopsies will also be obtained for single cell RNAseq analyses.

Primary Outcome Measures

Name	Time	Method
Myocardial Perfusion Reserve	60 months

Secondary Outcome Measures

Name	Time	Method
native T1 and T2 myocardial values	60 months
extracellular volumes	60 months
myocardial strain rate	60 months
Rest and stress myocardial blood flow	60 months
LGE %	60 months
LVEF	60 months
LV end-diastolic volume index	60 months
LV mass index	60 months

Trial Locations

Locations (1)

UC San Diego; 🇺🇸 La Jolla, California, United States