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Background: Little is known about the occurrence and implications of persistent microvascular obstruction (MVO) after reperfused ST-segment elevation myocardial infarction (STEMI)., Objectives: The authors used cardiac magnetic resonance (CMR) to characterize the impact of persistent MVO on adverse left ventricular remodeling (ALVR)., Methods: A prospective registry of 471 STEMI patients underwent CMR 7 (IQR: 5-10) days and 198 (IQR: 167-231) days after infarction. MVO (≥1 segment) and ALVR (relative increase >15% at follow-up CMR) of left ventricular end-diastolic index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were determined., Results: One-week MVO occurred in 209 patients (44%) and persisted in 30 (6%). The extent of MVO (P = 0.026) and intramyocardial hemorrhage (P = 0.001) at 1 week were independently associated with the magnitude of MVO at follow-up CMR. Compared with patients without MVO (n = 262, 56%) or with MVO only at 1 week (n = 179, 38%), those with persistent MVO at follow-up (n = 30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, and 50%; P = 0.003) and ALVR-LVESVI (20%, 21%, and 53%; P < 0.001). After adjustment, persistent MVO at follow-up (≥1 segment) was independently associated with ΔLVEDVI (relative increase, %) (P < 0.001) and ΔLVESVI (P < 0.001). Compared with a 1:1 propensity score-matched population on CMR variables made up of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs 50%; P = 0.003) and ALVR-LVESVI (12% vs 53%; P = 0.001)., Conclusions: MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodeling. These findings fuel the need for further research on microvascular injury repair., Competing Interests: Funding Support and Author Disclosures This work was supported by Instituto de Salud Carlos III and Fondos Europeos de Desarrollo Regional FEDER (grant numbers PI20/00637, CIBERCV16/11/00486, CIBERCV16/11/00420, CIBERCV16/11/00479, and a postgraduate contract CM21/00175 to V.M.-G.), by Conselleria de Educación–Generalitat Valenciana (PROMETEO/2021/008) and by Sociedad Española de Cardiología (grant SEC/FEC-INV-CLI 21/024). Dr Gavara has received financial support from the Agencia Estatal de Investigación (grant FJC2020-043981-I/AEI/10.13039/501100011033). Dr Moratal has received financial support from the Conselleria d’Educació, Investigació, Cultura i Esport, Generalitat Valenciana (grants AEST/2019/037, AEST/2020/029). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Stress cardiac MRI permits comprehensive evaluation of patients with known or suspected chronic coronary syndromes (CCS). The impact of sex on the use of invasive cardiac angiography (ICA) after vasodilator stress cardiac MRI is unclear., Purpose: To evaluate the impact of sex on ICA use after vasodilator stress cardiac MRI., Study Type: Retrospective., Population: A total of 6229 consecutive patients (age [mean ± standard deviation] 65.2 ± 11.5 years, 38.1% women)., Field Strength/sequence: A 5-T; a steady-state free-precession cine sequence; stress first-pass perfusion imaging; late enhancement imaging., Assessment: Patients underwent vasodilator stress cardiac MRI for known or suspected CCS. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model)., Statistical Tests: Multivariate logistic regression was used to evaluate the potential differential association between ischemic burden and use of cardiac MRI-related ICA across sex., Results: A total of 1109 (17.8%) patients were referred to ICA, among which there were significantly more men (762, 19.7%) than women (347, 14.6%). Overall, after multivariate adjustment, female sex was not associated with lower use of ICA (odds ratio [OR] = 0.99; confidence interval [CI] 95%: 0.84-1.18, P = 0.934). However, significant sex differences were detected across ischemic burden. Whereas women with nonischemic vasodilator stress cardiac MRI (0 ischemic segments) were less commonly submitted to ICA (OR = 0.49; CI 95%: 0.35-0.69) in patients with ischemia (>1 ischemic segment), adjusted use of ICA was more frequent in women than men (OR = 1.27; CI 95%: 1.1-1.5)., Data Conclusions: In patients with known or suspected CCS submitted to undergo vasodilator stress cardiac MRI, cardiac MRI-related ICA may be overused in men without ischemia. Furthermore, ICA referral in patients with negative ischemia resulted in greater odds of revascularization in men., Evidence Level: 3 TECHNICAL EFFICACY: Stage 5., (© 2022 International Society for Magnetic Resonance in Medicine.)

This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies., Competing Interests: The authors declare no conflict of interest.

Background: Following myocardial infarction (MI), we aimed to characterize morphometric and genetic changes in extracellular matrix (ECM) components from ischemia onset until late phases after coronary reperfusion in necrotic and salvaged myocardium., Results: Swine were divided into one control (n = 5) and three MI groups: 90-min of ischemia without reperfusion, or followed by 1-week or 1-month reperfusion (n = 5 per group). In samples from the necrotic and salvaged areas, ECM components were morphometrically quantified and mRNA levels of factors involved in ECM remodeling were evaluated. After 90-min of ischemia, fibronectin, laminin, and elastic fibers content as well as upregulated mRNA expression of tissue inhibitors of metalloproteinases (TIMP)1, TIMP2, TIMP3 and connective tissue growth factor increased in the necrotic and salvaged myocardium. In both reperfused MI groups, collagen-I, collagen-III, elastic fibers, glycosaminoglycans, laminin, and fibronectin levels heightened in the necrotic but not the salvaged myocardium. Moreover, mRNA expression of TIMP1, TIMP2 and TIMP3, as well as metalloproteinase-2 and metalloproteinase-9 heightened in the necrotic but not in the salvaged myocardium., Conclusions: Matrix remodeling starts after ischemia onset in both necrotic and salvaged myocardium. Even if ECM composition from the salvaged myocardium was altered after severe ischemia, ECM makes a full recovery to normal composition after reperfusion. Therefore, rapid coronary reperfusion is essential not only to save cardiomyocytes but also to preserve matrix, thus avoiding impaired left ventricular remodeling.

Delayed enhancement cardiovascular magnetic resonance (MR) is the gold-standard for non-invasive assessment after myocardial infarction (MI). MR microscopy (MRM) provides a level of detail comparable to the macro objective of light microscopy. We used MRM and correlative histopathology to identify infarct and remote tissue in contrast agent-free multi-sequence MRM in swine MI hearts. One control group (n = 3 swine) and two experimental MI groups were formed: 90 min of ischemia followed by 1 week (acute MI = 6 swine) or 1 month (chronic MI = 5 swine) reperfusion. Representative samples of each heart were analysed by contrast agent-free multi-sequence (T1-weighting, T2-weighting, T2*-weighting, T2-mapping, and T2*-mapping). MRM was performed in a 14-Tesla vertical axis imager (Bruker-AVANCE 600 system). Images from MRM and the corresponding histopathological stained samples revealed differences in signal intensities between infarct and remote areas in both MI groups (p-value < 0.001). The multivariable models allowed us to precisely classify regions of interest (acute MI: specificity 92% and sensitivity 80%; chronic MI: specificity 100% and sensitivity 98%). Probabilistic maps based on MRM images clearly delineated the infarcted regions. As a proof of concept, these results illustrate the potential of MRM with correlative histopathology as a platform for exploring novel contrast agent-free MR biomarkers after MI.

Objectives: The aim of this study was to evaluate the prognostic value of strain as assessed by tissue tracking (TT) cardiac magnetic resonance (CMR) soon after ST-segment elevation myocardial infarction (STEMI)., Background: The prognostic value of myocardial strain as assessed post-STEMI by TT-CMR is unknown., Methods: The authors studied the prognostic value of TT-CMR in 323 patients who underwent CMR 1 week post-STEMI. Global (average of peak segmental values [%]) and segmental (number of altered segments) longitudinal (LS), circumferential, and radial strain were assessed using TT-CMR. Global and segmental strain cutoff values were derived from 32 control patients. CMR-derived left ventricular ejection fraction, microvascular obstruction, and infarct size were determined. Results were validated in an external cohort of 190 STEMI patients., Results: During a median follow-up of 1,085 days, 54 first major adverse cardiac events (MACE), which included 10 cardiac deaths, 25 readmissions for heart failure, and 19 readmissions for reinfarction were documented. MACE was associated with more severe abnormalities in all strain indexes (p < 0.001), although only global LS was an independent predictor (p < 0.001). The MACE rate was higher in patients with a global LS of ≥-11% (22% vs. 9%; p = 0.001). After adjustment for baseline and CMR variables, global LS (hazard ratio [HR]: 1.21; 95% confidence interval [CI]: 1.11 to 1.32; p < 0.001) was associated with MACE. In the external validation cohort, a global LS ≥-11% was seen in a higher proportion of patients with MACE (34% vs. 9%; p < 0.001). Global LS predicted MACE after adjustment for baseline and CMR variables (HR: 1.18; 95% CI: 1.04 to 1.33; p = 0.008). The addition of global LS to the multivariate models, including baseline and CMR variables, did not significantly improve the categorical net reclassification improvement index in either the study group (-0.015; p = 0.7) or in the external validation cohort (-0.019; p = 0.9)., Conclusions: TT-CMR provided prognostic information soon after STEMI. However, it did not substantially improve risk reclassification beyond traditional CMR indexes., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

In extensive nonreperfused myocardial infarction (MI), remote fibrosis has been documented. Early reperfusion by primary angioplasty represents the gold standard method to minimize the extension of the infarction. We aimed to ascertain whether fibrosis also affects remote regions in reperfused MI in swine and patients. Swine were subjected to a transient occlusion of the left anterior descending artery followed by 1-week or 1-month reperfusion. Collagen content in the remote area macroscopically, microscopically, by magnetic resonance microimaging, and at the molecular level was similar to controls. In patients with previous MI, samples from autopsies displayed a significant increase in collagen content only in the infarct region. In patients with previous MI submitted to cardiac magnetic resonance-T1 mapping, the extracellular volume fraction in remote segments was similar to that for controls. In all scenarios, the remote region did not show a significant increase of collagen content in comparison with controls.

We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction., (© 2015 Anatomical Society.)

Introduction and Objectives: Microvascular obstruction exerts deleterious effects after myocardial infarction. To elucidate the role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction, we performed a preliminary methodological study to accurately define this process in an in vivo model., Methods: Myocardial infarction was induced in swine by means of 90-min of occlusion of the mid left anterior descending coronary artery using angioplasty balloons. Intracoronary infusion of thioflavin-S was applied and compared with traditional intra-aortic or intraventricular instillation. The left anterior descending coronary artery perfused area and microvascular obstruction were quantified in groups with no reperfusion (thioflavin-S administered through the lumen of an inflated over-the-wire balloon) and with 1-min, 1-week, and 1-month reperfusion (thioflavin-S administered from the intracoronary catheter after balloon deflation)., Results: In comparison with intra-aortic and intraventricular administration, intracoronary infusion of thioflavin-S permitted a much clearer assessment of the left anterior descending coronary artery perfused area and of microvascular obstruction. Ischemia-reperfusion injury exerted a decisive role on the occurrence and dynamics of microvascular obstruction. The no-reperfusion group displayed completely preserved perfusion. With the same duration of coronary occlusion, microvascular obstruction was already detected in the 1-min reperfusion group (14%±7%), peaked in the 1-week reperfusion group (21%±7%), and significantly decreased in the 1-month reperfusion group (4%±3%; P<.001)., Conclusions: We present proof-of-concept evidence on the crucial role of ischemia-reperfusion injury on the occurrence and dynamics of microvascular obstruction. The described porcine model using intracoronary injection of thioflavin-S permits accurate characterization of microvascular obstruction after myocardial infarction., (Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)