Heart transplant (Tx) surgery is a well-established life-saving procedure, but is associated with post- interventional risks such as acute cardiac rejection (ACR) which is one of the leading causes of death in the first year after transplant. Beyond the first year, cardiac allograft vasculopathy (CAV) is the single greatest risk factor for 5-year mortality. Monitoring the patient for post-transplant events is thus paramount. The standard monitoring strategy, however, relies on frequent (12-16 monitoring nodes during year 1 alone) invasive and costly procedures including endomyocardial biopsies (EMB) and catheter angiography. Since EMB and catheter angiography have limited sensitivity due to sampling errors (ACR) or the diffuse nature of the disease (CAV), a reliable non-invasive alternative for the early detection of ACR and CAV would be desirable to reduce the need for invasive procedures, improve sensitivity, and reduce cost. We have recently developed and applied cardiac MRI techniques for the non-invasive assessment of myocardial edema (T2-mapping), diffuse fibrosis (pre- and post-contrast T1-mapping), myocardial velocities (tissue phase mapping), and microvascular quantitative perfusion. We have shown that these techniques can identify distinct regional structural and functional alterations in the heart that correlate with the status of the allograft. Based on these findings, a detailed cost-effective analysis using Markov modeling and decision tree analysis has demonstrated that cardiac MR has tremendous potential to reduce monitoring costs by 40-50% during the first year after Tx alone. This proposal builds on these promising findings and our aim is to develop an new 15-minute structure-function cardiac MRI protocol for the improved detection regional abnormalities associated with ACR (edema, fibrosis, dysfunction) and CAV (perfusion, dysfunction). Integration of MRI with echocardiography and intravascular Ultrasound (IVUS) will provide unique multi-modality assessment of the allograft. The application in a longitudinal clinical study coupled with state-of-the-art cost-effectiveness analysis will allow redefining the most effective post-Tx mixed monitoring strategy.
The aim i s to to help clinicians identify the optimal mixed monitoring strategy, i.e. the optimal combination of multi-modality imaging (structure-function MRI, echo, IVUS) and invasive procedures (EMB, catheter angiography) which provide best outcome (quality adjusted life days) and lowest cost for the individual cardiac transplant patient.

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We propose to develop a multi-modality imaging protocol for the non-invasive characterization of tissue and function of the left and right heart in patients after heart transplantation. Our aim is to develop a new non- invasive 15 minute diagnostic test in order to provide a previously unattainable quantitative characterization of myocardial structure-function deficits in cardiac transplant patients. The application in a longitudinal clinial study coupled with cost-effectiveness analysis and decision tree modeling will allow to improve current monitoring strategies by combining cardiac MRI, echocardiography, intravascular ultrasound and invasive tests (biopsy, catheter angiography) to provide the best outcome (quality of life days, mortality) and lowest cost for the individual cardiac transplant patient.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Medical Imaging Study Section (MEDI)
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Shah, Monica R
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Northwestern University Chicago
Schools of Medicine
United States
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