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Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6-15 % of MI patients. Cardiac magnetic resonance (CMR) imaging identifies MINOCA etiologies, but access may be limited., Methods: We assessed associations between the index electrocardiogram (ECG) and CMR in MINOCA. Women with MI and < 50 % angiographic stenosis in all vessels were prospectively enrolled at 16 sites. CMR (median 6d from MI) was analyzed for late gadolinium enhancement (LGE), myocardial edema, and wall motion. We assessed ECGs for T-wave inversions (TWI), Q-waves (QW), ST-elevations (STE), ST-depressions (STD), and fragmented QRS complexes (fQRS). We calculated the DETERMINE score (# leads TWI + # fQRS +2*[# QW], excluding aVR, V1)., Results: Among 112 women with interpretable ECG, 81.3 % (91/112) had abnormal ECG; 50 % (56/112) had ≥1 TWI. CMR was abnormal in 74.1 % (83/112), with LGE in 49.1 % (55/112) and myocardial edema in 61.6 % (69/112). DETERMINE score ≥ 3 was associated with abnormal CMR (adjusted odds ratio [aOR] aOR 6.06 [1.89, 24.6], p = 0.002) and LGE (aOR 3.10 [1.26, 8.00], p = 0.013), but not edema (aOR 1.86 [0.80, 4.43], p = 0.152). TWI was also associated with abnormal CMR and LGE after adjustment (aOR 3.13 [1.08, 10.1], p = 0.036, aOR 3.23 [1.27, 8.63], p = 0.013, respectively), but not edema (aOR 1.26 [0.54, 2.96], p = 0.589). Specificity for abnormal CMR was 0.83 for DETERMINE score ≥ 3 and 0.75 for TWI. No other ECG findings were associated with CMR abnormality., Conclusion: DETERMINE score ≥ 3 and the presence of any TWI were associated with abnormal CMR and with LGE in MINOCA. Our findings demonstrate that the index ECG can provide insight on CMR findings but without sensitivity or specificity required to forgo the CMR. We reaffirm the central role of CMR in elucidating MINOCA pathophysiology., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Adverse left ventricular remodeling (ALVR) and subsequent heart failure after myocardial infarction (MI) remain a major cause of patient morbidity and mortality worldwide. Overt inflammation has been identified as the common pathway underlying myocardial fibrosis and development of ALVR post-MI. With its ability to simultaneously provide information about cardiac structure, function, perfusion, and tissue characteristics, cardiac magnetic resonance (CMR) is well poised to inform prognosis and guide early surveillance and therapeutics in high-risk cohorts. Further, established and evolving CMR-derived biomarkers may serve as clinical endpoints in prospective trials evaluating the efficacy of novel anti-inflammatory and antifibrotic therapies. This review provides an overview of post-MI ALVR and illustrates how CMR may help clinical adoption of novel therapies via mechanistic or prognostic imaging markers., Competing Interests: Funding Support and Author Disclosures Dr Gissler was supported by the IMM-PACT-Programme for Clinician Scientists, Department of Medicine II, Medical Center–University of Freiburg and Faculty of Medicine, University of Freiburg, funded by the Deutsche Forschungsgemeinschaft—413517907. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Early invasive revascularization guided by moderate to severe ischemia did not improve outcomes over medical therapy alone, underlying the need to identify high-risk patients for a more effective invasive referral. CMR could determine the myocardial extent and matching locations of ischemia and infarction., Objectives: This study sought to investigate if CMR peri-infarct ischemia is associated with adverse events incremental to known risk markers., Methods: Consecutive patients were included in an expanded cohort of the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study. Peri-infarct ischemia was defined by the presence of any ischemic segment neighboring an infarcted segment by late gadolinium enhancement imaging. Primary outcome events included acute myocardial infarction and cardiovascular death, whereas secondary events included any primary events, hospitalization for unstable angina, heart failure hospitalization, and late coronary artery bypass surgery., Results: Among 3,915 patients (age: 61.0 ± 12.9 years; 54.7% male), ischemia, infarct, and peri-infarct ischemia were present in 752 (19.2%), 1,123 (28.8%), and 382 (9.8%) patients, respectively. At 5.3 years (Q1-Q3: 3.9-7.2 years) of median follow-up, primary and secondary events occurred in 406 (10.4%) and 745 (19.0%) patients, respectively. Peri-infarct ischemia was the strongest multivariable predictor for primary and secondary events (HR adjusted : 1.72 [95% CI: 1.23-2.41] and 1.71 [95% CI: 1.32-2.20], respectively; both P < 0.001), adjusted for clinical risk factors, left ventricular function, ischemia extent, and infarct size. The presence of peri-infarct ischemia portended to a >6-fold increased annualized primary event rate compared to those with no infarct and ischemia (6.5% vs 0.9%)., Conclusions: Peri-infarct ischemia is a novel and robust prognostic marker of adverse cardiovascular events., Competing Interests: Funding Support and Author Disclosures SPINS was funded in part by the Society for Cardiovascular Magnetic Resonance. The Society for Cardiovascular Magnetic Resonance was supported by a joint research grant from Bayer AG and Siemens Medical Systems. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Omega-3 polyunsaturated fatty acids (O3-FA) have been shown to reduce inflammation and adverse cardiac remodeling after acute myocardial infarction (AMI). However, the impact of O3-FA on long-term clinical outcomes remains uncertain., Aims: To investigate the impact of O3-FA on adverse cardiac events in long-term follow up post AMI in a pilot-study., Methods: Consecutive patients with AMI were randomized 1:1 to receive 6 months of O3-FA (4 g/daily) or placebo in the prospective, multicenter OMEGA-REMODEL trial. Primary endpoint was a composite of major adverse cardiovascular events (MACE) encompassing all-cause death, heart failure hospitalizations, recurrent acute coronary syndrome, and late coronary artery bypass graft (CABG)., Results: A total of 358 patients (62.8% male; 48.1 ± 16.1 years) were followed for a median of 6.6 (IQR: 5.0-9.1) years. Among those receiving O3-FA (n = 180), MACE occurred in 65 (36.1%) compared to 62 (34.8%) of 178 assigned to placebo. By intention-to-treat analysis, O3-FA treatment assignment did not reduce MACE (HR = 1.014; 95%CI = 0.716-1.436; p = 0.938), or its individual components. However, patients with a positive response to O3-FA treatment (n = 43), defined as an increase in the red blood cell omega-3 index (O3I) ≥5% after 6 months of treatment, had lower annualized MACE rates compared to those without (2.9% (95%CI = 1.2-5.1) vs 7.1% (95%CI = 5.7-8.9); p = 0.001). This treatment benefit persisted after adjustment for baseline characteristics (HR adjusted  = 0.460; 95%CI = 0.218-0.970; p = 0.041)., Conclusion: In long-term follow-up of the OMEGA-REMODEL randomized trial, O3-FA did not reduce MACE after AMI by intention to treat principle, however, patients who achieved a ≥ 5% increase of O3I subsequent to treatment had favorable outcomes., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management., Methods and Results: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P <0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% ( P <0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men ( P =0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P =0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P =0.49), with no significant sex-by-treatment-group interactions., Conclusions: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial., Registration: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

Background: Myocardial infarction with nonobstructive coronary arteries (MINOCA) occurs in 6% to 15% of myocardial infarctions (MIs) and disproportionately affects women. Scientific statements recommend multimodality imaging in MINOCA to define the underlying cause. We performed coronary optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) imaging to assess mechanisms of MINOCA., Methods: In this prospective, multicenter, international, observational study, we enrolled women with a clinical diagnosis of myocardial infarction. If invasive coronary angiography revealed <50% stenosis in all major arteries, multivessel OCT was performed, followed by CMR (cine imaging, late gadolinium enhancement, and T2-weighted imaging and T1 mapping). Angiography, OCT, and CMR were evaluated at blinded, independent core laboratories. Culprit lesions identified by OCT were classified as definite or possible. The CMR core laboratory identified ischemia-related and nonischemic myocardial injury. Imaging results were combined to determine the mechanism of MINOCA, when possible., Results: Among 301 women enrolled at 16 sites, 170 were diagnosed with MINOCA, of whom 145 had adequate OCT image quality for analysis; 116 of these underwent CMR. A definite or possible culprit lesion was identified by OCT in 46.2% (67/145) of participants, most commonly plaque rupture, intraplaque cavity, or layered plaque. CMR was abnormal in 74.1% (86/116) of participants. An ischemic pattern of CMR abnormalities (infarction or myocardial edema in a coronary territory) was present in 53.4% (62/116) of participants undergoing CMR. A nonischemic pattern of CMR abnormalities (myocarditis, takotsubo syndrome, or nonischemic cardiomyopathy) was present in 20.7% (24/116). A cause of MINOCA was identified in 84.5% (98/116) of the women with multimodality imaging, higher than with OCT alone ( P <0.001) or CMR alone ( P =0.001). An ischemic cause was identified in 63.8% of women with MINOCA (74/116), a nonischemic cause was identified in 20.7% (24/116) of the women, and no mechanism was identified in 15.5% (18/116)., Conclusions: Multimodality imaging with coronary OCT and CMR identified potential mechanisms in 84.5% of women with a diagnosis of MINOCA, 75.5% of which were ischemic and 24.5% of which were nonischemic, alternate diagnoses to myocardial infarction. Identification of the cause of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02905357.

Background: Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia., Objectives: This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia., Methods: In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE)., Results: UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE., Conclusions: In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891)., (Copyright © 2020 American College of Cardiology Foundation. All rights reserved.)

Insulin resistance early after acute myocardial infarction is associated with increased heart failure and mortality. OMEGA-REMODEL was a prospective double-blind 1:1 randomized control trial of patients with AMI. We reported that 6-month treatment with omega-3 fatty acid (O-3FA) 4 g/day attenuated cardiac remodeling accompanied by reduction in inflammation. We hypothesized that insulin resistance modifies the therapeutic effect of O-3FA on post-MI cardiac remodeling. The OMEGA-REMODEL study group was dichotomized according to cohort- and gender-specific median cutoff value of leptin-to-adiponectin ratio (LAR) at baseline (LAR-Hi vs LAR-Lo). Mixed model regression analyses were used to evaluate effect modification of O-3FA on reduction of left ventricular end-systolic volume index (LVESVI) by LAR status. Baseline LAR was evaluated on 325 patients (59 ± 11 years, 81% male). A total of 168 patients were categorized in LAR-Lo, and 157 in LAR-Hi. O-3FA treatment resulted in significant LVESVI reduction in patients with LAR-Lo but not with LAR-Hi (p = 0.0002 vs 0.66, respectively). Mixed model regression analysis showed significant modification of LAR on O-3FA's treatment effect in attenuating LVESVI (p = 0.021). In conclusion, this post-hoc efficacy analysis suggests that LAR status significantly modified O-3FA's treatment effect in attenuating cardiac remodeling. During the convalescent phase of acute infarct healing, patients with lower insulin resistance estimated by LAR appear to derive more therapeutic response from O-3FA toward improvement of LVESVI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The double-blind OMEGA-REMODEL placebo-controlled randomized trial of high-dose omega-3 fatty acids (O-3FA) post-acute myocardial infarction (AMI) reported improved cardiac remodeling and attenuation of non-infarct myocardial fibrosis. Fatty acid desaturase 2 (FADS2) gene cluster encodes key enzymes in the conversion of essential omega-3 and omega-6 fatty acids into active arachidonic (ArA) and eicosapentaenoic acids (EPA), which influence cardiovascular outcomes., Methods and Results: We tested the hypothesis that the genotypic status of FADS2 (rs1535) modifies therapeutic response of O-3FA in post-AMI cardiac remodeling in 312 patients. Consistent with known genetic polymorphism of FADS2, patients in our cohort with the guanine-guanine (GG) genotype had the lowest FADS2 activity assessed by arachidonic acid/linoleic acid (ArA/LA) ratio, compared with patients with the adenine-adenine (AA) and adenine-guanine (AG) genotypes (GG:1.62±0.35 vs. AA: 2.01±0.36, p<0.0001; vs. AG: 1.76±0.35, p = 0.03). When randomized to 6-months of O-3FA treatment, GG patients demonstrated significant lowering of LV end-systolic volume index (LVESVi), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and galectin-3 levels compared to placebo (-4.4 vs. 1.2 ml/m2, -733 vs. -181 pg/mL, and -2.0 vs. 0.5 ng/mL; p = 0.006, 0.006, and 0.03, respectively). In contrast, patients with either AA or AG genotype did not demonstrate significant lowering of LVESVi, NT-proBNP, or galectin-3 levels from O-3FA treatment, compared to placebo. The odds ratios for improving LVESVi by 10% with O-3FA treatment was 7.2, 1.6, and 1.2 in patients with GG, AG, and AA genotypes, respectively., Conclusion: Genetic profiling using FADS2 genotype can predict the therapeutic benefits of O-3FA treatment against adverse cardiac remodeling during the convalescent phase of AMI., Clinical Trial Registration Information: clinicaltrials.gov Identifier: NCT00729430., Competing Interests: The commercial affiliation of author WH with OmegaQuant does not alter our adherence to PLOS ONE policies on sharing data and materials.

Despite substantial declines in mortality following myocardial infarction (MI), subsequent left ventricular remodeling (LVRm) remains a significant long-term complication. Extracellular small non-coding RNAs (exRNAs) have been associated with cardiac inflammation and fibrosis and we hypothesized that they are associated with post-MI LVRm phenotypes. RNA sequencing of exRNAs was performed on plasma samples from patients with "beneficial" (decrease LVESVI ≥ 20%, n = 11) and "adverse" (increase LVESVI ≥ 15%, n = 11) LVRm. Selected differentially expressed exRNAs were validated by RT-qPCR (n = 331) and analyzed for their association with LVRm determined by cardiac MRI. Principal components of exRNAs were associated with LVRm phenotypes post-MI; specifically, LV mass, LV ejection fraction, LV end systolic volume index, and fibrosis. We then investigated the temporal regulation and cellular origin of exRNAs in murine and cell models and found that: 1) plasma and tissue miRNA expression was temporally regulated; 2) the majority of the miRNAs were increased acutely in tissue and at sub-acute or chronic time-points in plasma; 3) miRNA expression was cell-specific; and 4) cardiomyocytes release a subset of the identified miRNAs packaged in exosomes into culture media in response to hypoxia/reoxygenation. In conclusion, we find that plasma exRNAs are temporally regulated and are associated with measures of post-MI LVRm., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown., Methods: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size., Results: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P=0.017), and noninfarct myocardial fibrosis (-5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy., Conclusions: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430., (© 2016 American Heart Association, Inc.)

Background: Strategies for prevention of sudden cardiac death focus on severe left ventricular (LV) dysfunction, although most sudden cardiac death postmyocardial infarction occurs in patients with mild/moderate LV dysfunction. We tested the hypothesis that infarct heterogeneity by cardiac magnetic resonance is associated with mortality beyond LV ejection fraction (LVEF) in patients with coronary artery disease and LV dysfunction. In addition, we examined the association between infarct heterogeneity and mortality in those with LVEF >35%., Methods and Results: We studied 301 patients with coronary artery disease and LV dysfunction referred for cardiac magnetic resonance. We quantified total infarct mass, infarct core mass, and peri-infarct zone (PIZ) normalized for total infarct mass (%PIZ) using signal-intensity criteria of >2 SDs, >3 SDs, and 2- to -3 SDs above remote myocardium, respectively. Mean LVEF was 41 ± 14%. After 3.9 years median follow-up, 66 (22%) patients died (13 sudden cardiac death; 33 with LVEF >35%). In patients with LVEF >35%, below-median %PIZ carried an annual death rate of 2.8% versus 12% in patients with above-median %PIZ (P<0.001). In a multivariable model, %PIZ maintained strong association with mortality adjusted to patient age, LVEF, right ventricular ejection fraction, prolonged QT interval, and total infarct size and resulted in improve risk reclassification 0.492 (95% confidence interval, 0.183-0.817)., Conclusions: Cardiac magnetic resonance infarct heterogeneity has a strong association with mortality independent of LVEF in patients with coronary artery disease and LV dysfunction, particularly in patients with mild or moderate LV dysfunction. Further studies incorporating cardiac magnetic resonance in clinical decision making for defibrillator therapy are warranted., (© 2014 American Heart Association, Inc.)

Background: Regenerative medicine, including cell therapy, is a promising strategy for recovery of the damaged myocardium. C-kit-positive cardiac stem cells (CSCs) have been shown to improve myocardial function after ischemic injury in animal models and in early clinical experience. We used a chronic large animal model of myocardial infarction with substantial reductions in left-ventricular (LV) ejection fraction and adverse remodeling to examine the effect of late autologous CSC intramyocardial injection on long-term cardiac structure and function., Methods and Results: Thoracotomy and ligation of the proximal left anterior descending artery, additional diagonal branches, and atrial biopsy for CSC culture were performed in canines. Baseline cardiac MRI was performed at 6 weeks postinfarct followed by repeat thoracotomy for randomization to intramyocardial injection of CSCs (n=13) or vehicle alone (n=6). At 30 weeks postmyocardial infarction, repeat MRI was performed. Data were analyzed using nonparametric tests (Wilcoxon signed-rank and rank-sum tests). In control animals, LV end-systolic volume and end-diastolic volume increased from 6 to 30 weeks (median and interquartile range, 51.3 mL [43.3-57.4] to 76.1 mL [72.0-82.4]; P=0.03 and 78.5 mL [69.7-86.1] to 99.2 mL [97.1-100.4]; P=0.03). Left-ventricular ejection fraction declined further (35.2% [27.9-38.7] to 26.4% [22.0-31.0]; P=0.12). In the cell-treated animals, this late adverse LV remodeling was attenuated (LV end-systolic volume, 42.6 mL [38.5-50.5] to 56.1 mL [50.3-63.0]; P=0.01 versus control). There was a nonsignificant attenuation in the increase in LV end-diastolic volume (64.8 mL [60.7-71.3] to 83.5 mL [74.7-90.8]; P=0.14 versus control) and LV ejection fraction change over time differed (30.5% [28.4-33.4] to 32.9% [28.6-36.9]; P=0.04 versus control)., Conclusions: Intramyocardial injection of autologous CSCs in a late phase model of chronic infarction resulted in less increase in LV end-systolic volume and preservation of LV ejection fraction.

Patients with type 1 diabetes (T1D) suffer excessive morbidity and mortality after myocardial infarction (MI) that is not fully explained by the metabolic effects of diabetes. Acute MI is known to trigger a profound innate inflammatory response with influx of mononuclear cells and production of proinflammatory cytokines that are crucial for cardiac repair. We hypothesized that these same pathways might exert "adjuvant effects" and induce pathological responses in autoimmune-prone T1D hosts. Here, we show that experimental MI in nonobese diabetic mice, but not in control C57BL/6 mice, results in a severe post-infarction autoimmune (PIA) syndrome characterized by destructive lymphocytic infiltrates in the myocardium, infarct expansion, sustained cardiac autoantibody production, and T helper type 1 effector cell responses against cardiac (α-)myosin. PIA was prevented by inducing tolerance to α-myosin, demonstrating that immune responses to cardiac myosin are essential for this disease process. Extending these findings to humans, we developed a panel of immunoassays for cardiac autoantibody detection and found autoantibody positivity in 83% post-MI T1D patients. We further identified shared cardiac myosin autoantibody signatures between post-MI T1D patients and nondiabetic patients with myocarditis, which were absent in post-MI type 2 diabetic patients, and confirmed the presence of myocarditis in T1D by cardiac magnetic resonance imaging techniques. These data provide experimental and clinical evidence for a distinct post-MI autoimmune syndrome in T1D. Our findings suggest that PIA may contribute to worsened post-MI outcomes in T1D and highlight a role for antigen-specific immunointervention to selectively block this pathway.

Objectives: The major aim of this study is to test the hypothesis that stress cardiac magnetic resonance (CMR) imaging can provide robust prognostic value in women presenting with suspected ischemia, to the same extent as in men., Background: Compelling evidence indicates that women with coronary artery disease (CAD) experience worse outcomes than men owing to a lack of early diagnosis and management. Numerous clinical studies have shown that stress CMR detects evidence of myocardial ischemia and infarction at high accuracy. Compared to nuclear scintigraphy, CMR is free of ionizing radiation, has high spatial resolution for imaging small hearts, and overcomes breast attenuation artifacts, which are substantial advantages when imaging women for CAD., Methods: We performed stress CMR in 405 patients (168 women, mean age 58 ± 14 years) referred for ischemia assessment. CMR techniques included cine cardiac function, perfusion imaging during vasodilating stress, and late gadolinium enhancement imaging. All patients were followed for major adverse cardiac events (MACE)., Results: At a median follow-up of 30 months, MACE occurred in 36 patients (9%) including 21 cardiac deaths and 15 acute myocardial infarctions. In women, CMR evidence of ischemia (ISCHEMIA) demonstrated strong association with MACE (unadjusted hazard ratio: 49.9, p < 0.0001). While women with ISCHEMIA(+) had an annual MACE rate of 15%, women with ISCHEMIA(-) had very low annual MACE rate (0.3%), which was not statistically different from the low annual MACE rate in men with ISCHEMIA(-) (1.1%). CMR myocardial ischemia score was the strongest multivariable predictor of MACE in this cohort, for both women and men, indicating robust cardiac prognostication regardless of sex., Conclusions: In addition to avoiding exposure to ionizing radiation, stress CMR myocardial perfusion imaging is an effective and robust risk-stratifying tool for patients of either sex presenting with possible ischemia., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies suggested that bone marrow (BM) cell implantation in patients with severe chronic coronary artery disease (CAD) resulted in modest improvement in symptoms and cardiac function. This study sought to investigate the functional changes that occur within the chronic human ischaemic myocardium after direct endomyocardial BM cells implantation by cardiovascular magnetic resonance (CMR)., Methods and Results: We compared the interval changes of left ventricular ejection fraction (LVEF), myocardial perfusion reserve and the extent of myocardial scar by using late gadolinium enhancement CMR in 12 patients with severe CAD. CMR was performed at baseline and at 6 months after catheter-based direct endomyocardial autologous BM cell (n = 12) injection to viable ischaemic myocardium as guided by electromechanical mapping. In patients randomized to receive BM cell injection, there was significant decrease in percentage area of peri-infarct regions (-23.6%, P = 0.04) and increase in global LVEF (+9.0%, P = 0.02), the percentage of regional wall thickening (+13.1%, P= 0.04) and MPR (+0.25%, P = 0.03) over the target area at 6-months compared with baseline., Conclusions: Direct endomyocardial implantation of autologous BM cells significantly improved global LVEF, regional wall thickening and myocardial perfusion reserve, and reduced percentage area of peri-infarct regions in patients with severe CAD.

Background: Recent studies have demonstrated the significant prognostic value of stress cardiac magnetic resonance (CMR) myocardial perfusion imaging. Apart from characterizing reversible perfusion defect (RevPD) from flow-limiting coronary stenosis, CMR late gadolinium enhancement (LGE) imaging is currently the most sensitive method for detecting subendocardial infarction (MI). We therefore tested the hypothesis that characterization of these 2 processes from coronary artery disease by CMR can provide complementary prognostic values., Methods and Results: We performed CMR myocardial perfusion imaging followed by LGE imaging on 254 patients referred with symptoms of myocardial ischemia. At a median follow-up of 17 months, 49 cardiac events occurred, including 12 cardiac deaths, 16 acute MIs, and 21 cardiac hospitalizations. RevPD and LGE both maintained a >3-fold association with cardiac death or acute MI (death/MI) when adjusted for each other and for the effects of patient age and gender (adjusted hazard ratio, 3.31; P=0.02; and hazard ratio, 3.43; P=0.01, respectively). In patients without a history of MI who had negative RevPD, LGE presence was associated with a >11-fold hazards increase in death/MI. Patients with neither RevPD nor LGE had a 98.1% negative annual event rate for death/MI. For association with major adverse cardiac events, RevPD was the strongest multivariable variable in the best overall model (hazard ratio, 10.92; P<0.0001)., Conclusions: CMR imaging provides robust risk stratification for patients who present with symptoms of ischemia. Characterization of RevPD and LGE by CMR provides strong and complementary prognostic implication for cardiac death or acute MI.

Assessment of viability is pivotal to the prognosis of patients with chronic coronary artery disease (CAD) and left ventricular dysfunction. Patients with viable myocardium have a better prognosis with revascularization; however, patients with nonviable myocardium have worse outcomes with higher perioperative morbidity and mortality subsequent to revascularization. Cardiac magnetic resonance (CMR) imaging not only is the current reference standard technique in measuring cardiac chamber size and function and myocardial mass and volume but also provides spatially registered 2- or 3-dimensional data sets in myocardial perfusion and myocardial contrast enhancement in the same imaging session. Late gadolinium enhancement by CMR is the best current technique in discriminating myocardial scar versus viable myocardium. An extensive body of preclinical evidence has validated the detection and characterization of the morphology of infarcted tissue. In clinical studies, infarct characteristics by CMR has demonstrated a strong clinical utility in the prediction of left ventricular functional recovery and patient prognosis. In this paper, we aim to review the current CMR techniques in characterizing the spectrum of myocardial changes because of CAD, in the prediction of myocardial viability, and the current evidence of CMR's role in patient prognosis. In addition, we will also review the current literature comparing the clinical utility of CMR with other established imaging modalities in the assessment of CAD.

Objectives: We sought to determine whether right ventricular (RV) function late after myocardial infarction (MI) impacts long-term prognosis., Background: Right ventricular failure predicts early mortality in patients with acute MI. The prognostic impact of RV function late after MI is not well defined. Accordingly, we determined whether RV dysfunction late after MI influences survival beyond traditional risk predictors, including patient age, left ventricular ejection fraction (LVEF), and infarct size., Methods: We studied 147 consecutive patients >30 days after MI (mean age of infarct 6.7 +/- 8.2 years) who were referred for contrast-enhanced cardiovascular magnetic resonance imaging. We assessed hazard ratios for death by RV ejection fraction (RVEF). The association of RVEF with mortality adjusted to traditional risk predictors was examined by using multivariable Cox proportional hazards regression models., Results: A total of 26 deaths occurred during a median follow-up of 17 months (range 6 to 53 months). By univariable analysis, RVEF <40% was strongly associated with mortality (unadjusted hazard ratio 4.02; p = 0.0007). By multivariable analysis that adjusted for patient age, left ventricular (LV) infarct size, and LVEF, RVEF <40% remained a significant independent predictor of mortality (adjusted hazard ratio 2.86; p = 0.03)., Conclusions: Right ventricular ejection fraction quantified late after MI is an important predictor of prognosis adjusted for patient age, LV infarct size, and LVEF. Accordingly, evaluation of RVEF using cardiovascular magnetic resonance imaging can improve risk-stratification and potentially refine patient management after MI.

Background: Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI). Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality., Methods and Results: We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (>3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDE(periphery)). After a median follow-up of 2.4 years, 29 (20%) patients died. Patients with an above-median %MDE(periphery) were at higher risk for death compared with those with a below-median %MDE(periphery) (28% versus 13%, log-rank P<0.01). Multivariable analysis showed that left ventricular systolic volume index and %MDE(periphery) were the strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for %MDE(periphery), 1.45 per 10% increase; P=0.002) and cardiovascular mortality (adjusted HR, 1.51 per 10% increase; P=0.009). Similarly, after adjusting for age and left ventricular ejection fraction, %MDE(periphery) maintained strong and independent associations with all-cause mortality (adjusted HR, 1.42; P=0.005) and cardiovascular mortality (adjusted HR, 1.49; P=0.01)., Conclusions: In patients with a prior MI, the extent of the peri-infarct zone characterized by CMR provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. Infarct characteristics by CMR may prove to be a unique and valuable noninvasive predictor of post-MI mortality.

Purpose: While both first-pass perfusion and late gadolinium enhancement by cardiovascular magnetic resonance (CMR) can assess coronary microvascular status in acute myocardial infarction (AMI), there are only limited data on their respective diagnostic utility. We aim to evaluate: the utility of first-pass perfusion and late gadolinium enhancement imaging in the detection and quantification of microvascular dysfunction after reperfused acute myocardial infarction, using TIMI frame count (TIMI FC) as the reference standard of microvascular assessment; and their relationship with infarct size and ventricular function., Methods: First-pass perfusion and late gadolinium enhancement imaging were performed in 25 consecutive AMI patients (84% men, age 58 +/- 10) within 72 h of successful reperfusion. We assessed the myocardial extent of microvascular dysfunction using the size of the perfusion defect on first-pass perfusion (PD%) and the hypoenhanced core region within late gadolinium enhancement (MDEcore%). PD%, MDEcore%, and TIMI FC were analyzed independently of each other and with blinding to clinical data. We adjusted PD% and MDEcore% to the myocardial mass subtended by the infarct-related artery according to the 16-segment model., Results: Median infarct size involved 13.9% (interquartile range: 8.5 to 22.2%) of the left ventricle and median left ventricular ejection fraction was 52% (interquartile range: 43 to 61%). PD% demonstrated evidence of microvascular dysfunction more frequently (84% vs. 36% of patients, p < 0.002) and involved a larger myocardial extent (23.5 +/- 17.5% vs. 3.5 +/- 7.7%, p < 0.001) compared to MDEcore%. PD% had strong correlations with TIMI FC (Spearman rho = 0.62, p < 0.001) and infarct size (rho = 0.64, p < 0.001), and a moderate correlation with LVEF (rho = -0.39, p = 0.055). MDEcore% also correlated with TIMI FC (rho = 0.54, p = 0.005) and infarct size (rho = 0.52, p < 0.01) but not with LVEF (p = NS)., Conclusions: PD% appeared to provide a stronger noninvasive assessment of the microvascular function than MDEcore% and correlated well with prognostic markers such as left ventricular ejection fraction and infarct size. Future studies should consider quantitative analyses of both first-pass perfusion and late gadolinium enhancement imaging in the evaluation of novel therapies targeted to the microvasculature of the infarct-related artery.

Aims We aimed to use optical coherence tomography (OCT) to identify differences in atherosclerotic culprit lesion morphology in women with myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) compared with MI with obstructive coronary artery disease (MI-CAD). Methods and results Women with an OCT-determined atherosclerotic aetiology of non-ST segment elevation (NSTE)-MINOCA (angiographic diameter stenosis <50%) who were enrolled in the multicentre Women's Heart Attack Research Program (HARP) study were compared with a consecutive series of women with NSTE-MI-CAD who underwent OCT prior to coronary intervention at a single institution. Atherosclerotic pathologies identified by OCT included plaque rupture, plaque erosion, intraplaque haemorrhage (IPH, a region of low signal intensity with minimum attenuation adjacent to a lipidic plaque without fibrous cap disruption), layered plaque (superficial layer with clear demarcation from the underlying plaque indicating early thrombus healing), or eruptive calcified nodule. We analysed 58 women with NSTE-MINOCA and 52 women with NSTE-MI-CAD. Optical coherence tomography features of underlying vulnerable plaque (thin-cap fibroatheroma) were less common in MINOCA (3 vs. 35%) than in MI-CAD. Intraplaque haemorrhage (47 vs. 2%) and layered plaque (31 vs. 12%) were more common in MINOCA than MI-CAD, whereas plaque rupture (14 vs. 67%), plaque erosion (8 vs. 14%), and calcified nodule (0 vs. 6%) were less common in MINOCA. The angle of ruptured cavity was smaller and thrombus burden was lower in MINOCA. Conclusion The prevalence of atherothrombotic culprit lesion subtype varied substantially between MINOCA and MI-CAD. A majority of culprit lesions in MINOCA had the appearance of IPH or layered plaque. Clinical Trial Registration Information Clinical Trial Name: Heart Attack Research Program-Imaging Study (HARP); ClinicalTrial.gov Identifier. NCT02905357; URL: https://clinicaltrials.gov/ct2/show/NCT02905357 [ABSTRACT FROM AUTHOR]

Background--Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction, reduced exercise capacity, nondiagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. Methods and Results--A consecutive cohort of 173 patients with diabetes mellitus (mean age, 61.7±11.9 years; 37% women) with suspected myocardial ischemia underwent stress perfusion cardiac magnetic resonance imaging. Patients were evaluated for adverse cardiac events after cardiac magnetic resonance imaging with mean follow-up time of 2.9±2.5 years. Mean hemoglobin A1c for the population was 7.9±1.8%. Primary end point was a composite of cardiac death and nonfatal myocardial infarction. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared with 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a low annual cardiac event rate (0.5% per year). The presence of inducible ischemia was the strongest unadjusted predictor (hazard ratio, 4.86; P<0.01) for cardiac death and nonfatal myocardial infarction. This association remained robust in adjusted stepwise multivariable Cox regression analysis (hazard ratio, 4.28; P=0.02). In addition, categorical net reclassification index using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with net reclassification index of 0.38 (95% confidence interval, 0.20-0.56; P<0.0001). Conclusions--Stress perfusion cardiac magnetic resonance imaging provided independent prognostic utility and effectively reclassified risk in patients with diabetes mellitus referred for ischemic assessment. Further evaluation is required to determine whether a noninvasive imaging strategy with cardiac magnetic resonance imaging can favorably affect downstream outcomes and improve cost-effectiveness of care in diabetics. [ABSTRACT FROM AUTHOR]

The recent FAME 2 study highlights the importance of myocardial ischemia assessment, particularly in the post-COURAGE trial era of managing patients with stable coronary artery disease. Qualitative assessment of myocardial ischemia by stress cardiovascular magnetic resonance imaging (CMR) has gained widespread clinical acceptance and utility. Despite the high diagnostic and prognostic performance of qualitative stress CMR, the ability to quantitatively assess myocardial perfusion reserve and absolute myocardial blood flow remains an important and ambitious goal for non-invasive imagers. Quantitative perfusion by stress CMR remains a research technique that has yielded progressively more encouraging results in more recent years. The ability to safely, rapidly, and precisely procure quantitative myocardial perfusion data would provide clinicians with a powerful tool that may substantially alter clinical practice and improve downstream patient outcomes and the cost effectiveness of healthcare delivery. This may also provide a surrogate endpoint for clinical trials, reducing study population sizes and costs through increased power. This review will cover emerging quantitative CMR techniques for myocardial perfusion assessment by CMR, including novel methods, such as 3-dimensional quantitative myocardial perfusion, and some of the challenges that remain before more widespread clinical adoption of these techniques may take place. [ABSTRACT FROM AUTHOR]

Proper assessment of the physiologic impact of coronary artery stenosis on the LV myocardium can affect patient prognosis and treatment decisions. Cardiac magnetic resonance imaging (CMR) assesses myocardial perfusion by imaging the myocardium during a first-pass transit of an intravenous gadolinium bolus, with spatial and temporal resolution substantially higher than nuclear myocardial perfusion imaging. Coupled with late gadolinium enhancement (LGE) imaging for infarction during the same imaging session, CMR with vasodilating stress perfusion imaging can qualitatively and quantitatively assess the myocardial extent of hypoperfusion from coronary stenosis independent of infarcted myocardium. This approach has been validated experimentally, and multiple clinical trials have established its diagnostic robustness when compared to stress single-photon emission computed tomography. In specialized centers, dobutamine stress CMR has been shown to have incremental diagnostic value above stress echocardiography due to its high imaging quality and ability to image the heart with no restriction of imaging window. This paper reviews the technical aspects, diagnostic utility, prognostic values, challenges to clinical adaptation, and future developments of stress CMR imaging. [ABSTRACT FROM AUTHOR]

Abstract: Assessment of myocardial ischemia in symptomatic patients remains a common and challenging clinical situation faced by physicians. Risk stratification by presence of ischemia provides important utility for both prognostic assessment and management. Unfortunately, current noninvasive modalities possess numerous limitations and have limited prognostic capacity. More recently, ischemia assessment by cardiovascular magnetic resonance (CMR) has been shown to be a safe, available, and potentially cost-effective alternative with both high diagnostic and prognostic accuracy. Cardiovascular magnetic resonance has numerous advantages over other noninvasive methods, including high temporal and spatial resolution, relatively few contraindications, and absence of ionizing radiation. Furthermore, studies assessing the clinical utility and cost effectiveness of CMR in the short-term setting for patients without evidence of an acute myocardial infarction have also demonstrated favorable results. This review will cover techniques of ischemia assessment with CMR by both stress-induced wall motion abnormalities as well as myocardial perfusion imaging. The diagnostic and prognostic performance studies will also be reviewed, and the use of CMR for ischemia assessment will be compared with other commonly used noninvasive modalities. [Copyright &y& Elsevier]

Detecting acute coronary syndrome in the emergency department using cardiac magnetic resonance imaging (MRI)was studied in 161 consecutive patients in a prospective observational study. Patients with ST-elevation myocardial infarction were excluded. A rest (non-stress) MRI was performed within 12 hours of presentation. The sensitivity and specificity for detecting acute coronary syndrome was 84%and 85%, respectively by MRI. The MRI was more sensitive than strict electrocardiogram criteria for ischemia (p < 0.001) and peak troponin-I (p < 0.001). The MRI was more specific than an abnormal electrocardiogram (p < 0.001). Multivariate logistic regression analysis showed MRI was the strongest predictor of acute coronary syndrome and added diagnostic value over clinical parameters (p < 0.001). A nonstress cardiac MRI was feasible and exhibited diagnostic operating characteristics suitable for triage of patients with chest pain in the emergency department. MRI accurately detected a high fraction of patients with acute coronary syndrome, including patients with enzyme-negative unstable angina. [ABSTRACT FROM AUTHOR]

The article discusses the relationship between inducible ischemia severity, coronary artery disease (CAD) extent, and exercise capacity in patients with chronic coronary disease. The study, called ISCHEMIA, analyzed data from 858 participants who underwent exercise treadmill testing. The results showed that neither ischemia severity nor CAD extent were significant predictors of aerobic exercise capacity beyond demographic and clinical characteristics. These findings are surprising given the expected relationship between exercise limitation and CAD, but recent studies have also questioned this relationship. The study has some limitations, such as the skewed cohort and the lack of follow-up exercise testing. Overall, the article provides valuable insights into the association between ischemia severity, CAD extent, and exercise capacity in patients with chronic coronary disease. [Extracted from the article]

An abstract of the article "Diabetes remains an independent risk factor for adverse remodeling following acute myocardial infarction even with quantification of total infarct size and change in myocardial extracellular volume fraction by CMR," by Bobby Heydari and colleagues is presented.

An abstract of the article "Left atrial volume during the early convalescent phase of acute MI is strongly related to expansion of myocardial extracellular matrix during infarct healing and ventricular remodeling," by Hoshang Farhad and colleagues is presented.

An abstract of the paper "Characterization of Peri-Infarct Zone by CMR Is a Robust Predictor of Major Adverse Events and Is Strongly Associated With Systemic Inflammatory Response Post-Myocardial Infarction," by Andrei Sposito and colleagues is presented.

An abstract of the paper "Prediction of Modifications in Size and Peri-Infarct Zone by T2-Imaging After an Acute Myocardial Infarction During Longitudinal Follow-Up by Cardiac MRI," by Damien Mandry and colleagues is presented.

Objectives: This study sought to identify the frequency, pattern, and prognostic significance of left ventricular (LV) late gadolinium enhancement (LGE) in patients with atrial fibrillation (AF).Background: There are limited data on the presence, pattern, and prognostic significance of LV myocardial fibrosis in patients with AF. LGE during cardiac magnetic resonance imaging is a marker for myocardial fibrosis.Methods: A group of 664 consecutive patients without known prior myocardial infarction who were referred for radiofrequency ablation of AF were studied. Cardiac magnetic resonance imaging was requested to assess pulmonary venous anatomy.Results: Overall, 73% were men, with a mean age of 56 years and a mean LV ejection fraction of 56 ± 10%. LV LGE was found in 88 patients (13%). The endpoint was all-cause mortality, and in this cohort, 68 deaths were observed over a median follow-up period of 42 months. On univariate analysis, age (hazard ratio [HR]: 1.05; 95% confidence interval [CI]: 1.03 to 1.08; chi-square likelihood ratio [LRχ(2)]: 15.2; p = 0.0001), diabetes (HR: 2.39; 95% CI: 1.41 to 4.09; LRχ(2): 10.3; p = 0.001), a history of heart failure (HR: 1.78; 95% CI: 1.09 to 2.91; LRχ(2): 5.37; p = 0.02), left atrial dimension (HR: 1.04; 95% CI: 1.01 to 1.08; LRχ(2): 6.47; p = 0.01), presence of LGE (HR: 5.08; 95% CI: 3.08 to 8.36; LRχ(2): 28.8; p < 0.0001), and LGE extent (HR: 1.15; 95% CI: 1.10 to 1.21; LRχ(2): 35.6; p < 0.0001) provided the strongest associations with mortality. The mortality rate was 8.1% per patient-year in patients with LGE compared with 2.3% patients without LGE. In the best overall multivariate model for mortality, age and the extent of LGE were independent predictors of mortality. Indeed, each 1% increase in the extent of LGE was associated with a 15% increased risk for death.Conclusions: In patients with AF, LV LGE is a frequent finding and is a powerful predictor of mortality. [ABSTRACT FROM AUTHOR]