Persistent (or late) microvascular obstruction (PMO) is an acute feature of myocardial infarctions (MI) where microvascular blood flow to the MI territory is lost despite reperfusion; it typically resolves in < 2 weeks, post-MI. PMOs are present in ~50% of acute MIs. In the past two decades, advances in cardiac MRI (CMR) have established that PMO is an independent predictor of adverse post-infarction ventricular remodeling. Notably, a multi-national consortium recently reported that the presence of PMO carries a 4-fold greater risk for major adverse cardiovascular events (hospitalization /death) in the chronic period than acute MI size. A frequent accompanying feature of PMO is reperfusion hemorrhage – extravasation of blood into the interstitium. These recent observations led us to report, which others later confirmed, that PMOs with hemorrhage lead to chronic iron deposition (CID) and persistent inflammation at 8 weeks post MI; and that this iron deposit is an independent marker of adverse remodeling in the chronic phase of MI in animals and patients. In the present study, we hypothesized that PMO, with or without reperfusion hemorrhage, can resolve into iron deposition within chronic MI (CMI) territories, and is associated with prolonged inflammation and adverse LV remodeling.Canines (n=33) were studied according to the protocols approved by the institutional Animal Care and Use Committee. Seventeen dogs were subjected to ischemia-reperfusion injury by occluding the left anterior descending (LAD) artery for 3 hours followed by reperfusion (Reperfused Group, IR). The remaining 16 dogs were subjected to permanent ligation of the LAD (Non-Reperfused Group, NR). All canines underwent MRI at 5 days (acute) and 56 days (chronic) post-MI in a 3T clinical MRI system (MAGNETOM Verio, Erlangen, Siemens Healthcare). ECG-triggered breath-held 2D cine-SSFP images (20-25 cardiac phases, TR/TE=3.5/1.75 ms, flip angle=70°, BW=930 Hz/pixel), T2*-weighted images (multiple gradient-echo, TR=12ms, 6 TEs = 2.0ms–9.5ms with ΔTE=1.5ms, flip angle=10° and BW=930Hz/pixel), and Late Gadolinium Enhancement images (IR-FLASH acquired 10-15 minutes following intravenous gadolinium infusion (Magnevist, Bayer Healthcare Pharmaceuticals Inc., Wayne, NJ), optimal TI to null remote myocardium, TR/TE=3.0/1.5 ms, flip angle=25°, BW=586 Hz/pixel) were acquired along the short-axis direction covering the entire LV. Commonly used imaging parameters for all the scans were: resolution = 1.4 x 1.4 x 6 mm3,. All quantitative image analyses were performed using the cvi42 (Circle Cardiovascular Imaging Inc.). LV structural remodeling was quantified using end-diastolic sphericity index (EDSI) measurements from cine-SSFP images. Animals were euthanized following the day 56 CMR scan and their hearts were excised for further histological assessment of chronic iron-driven inflammatory process.In the reperfused group, 9 canines had PMO and hemorrhage with subsequent chronic iron deposition (PMO+/T2*+), while 4 canines had no PMO, hemorrhage, or chronic iron deposition (PMO/T2*-) [Fig A]. The remaining 4 canines had PMO without hemorrhage (PMO+/T2*), but all subsequently had chronic iron deposition. In the non-reperfused group, 15 canines had PMO, and acute and subsequent chronic iron deposition (NRPMO+/T2*+); 1 canine had no PMO and acute or chronic iron deposition (NRPMO/T2*, Fig A). In both groups, PMO volume was significantly associated with both acute and chronic iron volumes (p<0.001, for all cases). In both groups, infarct and iron volumes measured in both acute and chronic phases were significant predictors of change in EDSI between acute and chronic phases (p<0.01 all cases). Histological sections of infarcts (56 days post-MI) were positive for presence of collagen (Elastin-modified Masson’s Trichrome stain) and revealed co-localization of chronic iron depositions (Prussian Blue stain, CID) with MAC387 (marker of newly recruited macrophages) and CD163 (marker indicating iron-specific macrophage activation) [Fig B], as well as the proinflammatory markers (IL-1β, TNF-α and MMP-9).PMO per se can lead to chronic iron-driven inflammatory response regardless of the presence or absence of hemorrhage in the acute MI setting, and is an independent predictor of adverse LV remodeling throughout the chronic post-MI phase.