Ferumoxytol-Enhanced Cardiac MRI for Ischemic Heart Disease

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Project Summary Ischemic heart disease (IHD) and chronic kidney disease (CKD) are frequent bedfellows, but IHD as the leading cause of death in this population is under-diagnosed. Although patients with CKD and post-renal transplant have the highest risk for IHD, reliable estimation of ischemic burden remains a challenge. Accurate quantification of ischemic burden is crucial for clinical management because invasive interventions may worsen kidney function. In patients with CKD, cardiovascular event rates increase significantly with increasing stage of CKD. Contrast-enhanced cardiac magnetic resonance imaging (MRI) is attractive due to the absence of ionizing radiation and its inherent ability to provide high spatial resolution images. But perfusion cardiac MRI for defining ischemia relies on the first-pass bolus of gadolinium, which has intrinsic technical shortcomings. Late gadolinium enhancement for viability is also dependent on gadolinium contrast kinetics. Both are less suitable for patients with CKD. In patients with renal failure, gadolinium-associated nephrogenic systemic fibrosis may be fatal and more recently, autopsy results in patients with normal kidney function support gadolinium accumulation in certain organs and tissues. Our goal is to test and validate a non-nephrotoxic, steady-state cardiac MRI strategy that overcomes many drawbacks of gadolinium-enhanced cardiac MRI to detect inducible ischemia and viability. We build upon our collective experience with ferumoxytol-enhanced MRI and ischemic heart disease. Because ferumoxytol is well-tolerated in patients with renal impairment and has broad clinical approval for intravenous treatment of iron deficiency anemia, if proven successful, our steady state stress cardiac MRI approach may also be valuable for other applications.