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Background: The prognostic efficacy of a coronary computed tomography angiography (CCTA)-derived myocardial radiomics model in patients with chronic myocardial infarction (MI) is unclear., Methods: In this retrospective study, a cohort of 236 patients with chronic MI who underwent both CCTA and cardiac magnetic resonance (CMR) examinations within 30 days were enrolled and randomly divided into training and testing datasets at a ratio of 7:3. The clinical endpoints were major adverse cardiovascular events (MACE), defined as all-cause death, myocardial reinfarction and heart failure hospitalization. The entire three-dimensional left ventricular myocardium on CCTA images was segmented as the volume of interest for the extraction of radiomics features. Five models, namely the clinical model, CMR model, clinical+CMR model, CCTA-radiomics model, and clinical+CCTA-radiomics model, were constructed using multivariate Cox regression. The prognostic performances of these models were evaluated through receiver operating characteristic curve analysis and the index of concordance (C-index)., Results: Fifty-one (20.16%) patients experienced MACE during a median follow-up of 1439.5 days. The predictive performance of the CCTA-radiomics model surpassed that of the clinical model, CMR model, and clinical+CMR model in both the training (area under the curve (AUC) of 0.904 vs. 0.691, 0.764, 0.785; C-index of 0.88 vs. 0.71, 0.75, 0.76, all p values <0.001) and testing (AUC of 0.893 vs. 0.704, 0.851, 0.888; C-index of 0.86 vs. 0.73, 0.85, 0.85, all p values <0.05) datasets., Conclusions: The CCTA-based myocardial radiomics model is a valuable tool for predicting adverse outcomes in chronic MI, providing incremental value to conventional clinical and CMR parameters., Competing Interests: Declaration of competing interest All authors disclosed no relevant conflicts., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood., Methods: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated., Results: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004)., Conclusions: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI., Competing Interests: Declaration of competing interest M.K. received research grants from KOWA company, Ltd. and FUJIREBIO Inc. Y.A. received scholarship grants from Abbott Medical Japan and Terumo. T.F. received a research grant from General Electric. Y.S. received an honorarium from Astra-Zeneca, Nippon Boehringer-Ingelheim Co., Ltd., Daiichi-Sankyo Company, and Novartis., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: The potential benefit on long term outcomes of Percutaneous Coronary Intervention (PCI) on Unprotected Left Main (ULM) driven by IntraVascular UltraSound (IVUS) remains to be defined., Methods: IMPACTUS LM-PCI is an observational, multicenter study that enrolled consecutive patients with ULM disease undergoing coronary angioplasty in 13 European high-volume centers from January 2002 to December 2015. Major Adverse Cardiovascular Events (MACEs) a composite of cardiovascular (CV) death, target vessel revascularization (TVR) and myocardial infarction (MI) were the primary endpoints, while its single components along with all cause death the secondary ones., Results: 627 patients with ULM disease were enrolled, 213 patients (34%) underwent IVUS-guided PCI while 414 (66%) angioguided PCI. Patients in the two cohorts had similar prevalence of risk factors except for active smoking and clinical presentation. During a median follow-up of 7.5 years, 47 (22%) patients in the IVUS group and 211 (51%) in the angio-guided group underwent the primary endpoint (HR 0.42; 95% CI [0.31-0.58] p < 0.001). After multivariate adjustment, IVUS was significantly associated with a reduced incidence of the primary endpoint (adj HR 0.39; 95% CI [0.23-0.64], p < 0.001), mainly driven by a reduction of TVR (ad HR 0.30, 95% CI [0.15-0.62], p = 0.001) and of all-cause death (adj HR 0.47, 95% CI [0.28-0.82], p = 0.008). IVUS use, age, diabetes, side branch stenosis, DES and creatinine at admission were independent predictors of MACE., Conclusions: In patients undergoing ULM PCI, the use of IVUS was associated with a reduced risk at long-term follow-up of MACE, all-cause death and subsequent revascularization., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: In this study, we aimed to assess and compare the distribution of demographic and clinical characteristics and composite adverse clinical outcomes after primary percutaneous coronary intervention (PCI) among "very premature", "premature", and "non-premature" patients with "ST-segment elevation acute coronary syndrome (STE-ACS)" presented at a tertiary care center., Methods: We included consecutive patients diagnosed with STE-ACS undergoing primary PCI. The "very premature" was defined as ≤40 years for males and ≤ 45 years for females, "premature" as <55 years for males and < 65 years for females, and "non-premature" as ≥55 years for males and ≥ 65 years for females. Clinical characteristics, angiographic patterns, and hospital course were compared among the three groups., Results: In a sample of 4686 patients, 78.8%(3691) were male, and the average age was 55.6 ± 11 years. In total, 12%(561) were categorized as very premature, 38.3%(1797) as premature, and 49.7%(2328) as non-premature. The distribution of clinical characteristics in very premature, premature, and non-premature groups were as follows; hypertension in 44.6% vs. 53.5% vs. 54.9%; p < 0.001, diabetes in 30.3% vs. 36.8% vs. 35.5%; p = 0.018, smoking in 29.6% vs. 23.3% vs. 26.3%; p = 0.005, obesity in 19.4% vs. 18.4% vs. 15.3%; p = 0.008, single vessel diseases in 58.8% vs. 37.8% vs. 28.8%; p < 0.001, and composite adverse clinical outcomes in 14.1% vs. 16.7% vs. 21.8%; p < 0.001, respectively., Conclusion: In conclusion, we have a substantial burden of premature STE-ACS. Very premature STE-ACS was found to be associated with a better prognosis, but a substantial burden of composite adverse clinical outcomes was also observed., Competing Interests: Declaration of Competing Interest None to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Acute myocardial infarction (AMI) is the prototypical cause of cardiogenic shock (CS), yet CS due to heart failure (HF-CS) is increasingly common. Little is known regarding cardiac function in AMI-CS versus HF-CS. We compared transthoracic echocardiography (TTE) findings in AMI-CS versus HF-CS and identified predictors of mortality in AMI-CS patients., Methods: We performed a single-center, retrospective analysis of CS admissions between 2007 and 2018. We compared baseline demographic and TTE parameters in patients with AMI-CS and HF-CS as well as ST elevation myocardial infarction (STEMI)-CS versus non-ST elevation myocardial infarction (NSTEMI)-CS., Results: We included 893 unique patients, including 581 (65%) with AMI-CS. AMI-CS patients were older but had lower illness severity and non-cardiac comorbidity burden. AMI-CS patients had better left ventricular function (LVEF 35% versus 28%), lower biventricular filling pressures, and higher stroke volume versus those with HF-CS. Among TTE measurements, myocardial contraction fraction had the highest discrimination for mortality in AMI-CS (AUC: 0.64); AUC values for LVEF and SOFA score were 0.61 and 0.65, respectively. Differences in TTE findings between STEMI-CS versus NSTEMI-CS were modest. There were no significant differences in unadjusted or adjusted in-hospital mortality between AMI-CS and HF-CS (31% versus 35%) or STEMI-CS and NSTEMI-CS (31% versus 30%) groups (all p > 0.05)., Conclusions: Patients with HF-CS and AMI-CS differ in terms of clinical and TTE variables yet have similar prognoses. TTE is useful in determining prognosis of patients admitted with AMI-CS and may allow for early triage and directed therapy., Competing Interests: Declaration of Competing Interest Narayana Sarma V. Singam is a co-founder and owner of High Enroll, LLC. None of the authors report a direct conflict of interest for this work., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Myocardial infarction leads to complex changes in left ventricular (LV) hemodynamics. It remains unknown how four-dimensional acute changes in LV-cavity blood flow kinetic energy affects LV-remodeling., Methods and Results: In total, 69 revascularised ST-segment elevation myocardial infarction (STEMI) patients were enrolled. All patients underwent cardiovascular magnetic resonance (CMR) examination within 2 days of the index event and at 3-month. CMR examination included cine, late gadolinium enhancement, and whole-heart four-dimensional flow acquisitions. LV volume-function, infarct size (indexed to body surface area), microvascular obstruction, mitral inflow, and blood flow KEi (kinetic energy indexed to end-diastolic volume) characteristics were obtained. Adverse LV-remodeling was defined and categorized according to increase in LV end-diastolic volume of at least 10%, 15%, and 20%. Twenty-four patients (35%) developed at least 10%, 17 patients (25%) at least 15%, 11 patients (16%) at least 20% LV-remodeling. Demographics and clinical history were comparable between patients with/without LV-remodeling. In univariable regression-analysis, A-wave KEi was associated with at least 10%, 15%, and 20% LV-remodeling (p = 0.03, p = 0.02, p = 0.02, respectively), whereas infarct size only with at least 10% LV-remodeling (p = 0.02). In multivariable regression-analysis, A-wave KEi was identified as an independent marker for at least 10%, 15%, and 20% LV-remodeling (p = 0.09, p < 0.01, p < 0.01, respectively), yet infarct size only for at least 10% LV-remodeling (p = 0.03)., Conclusion: In patients with STEMI, LV hemodynamic assessment by LV blood flow kinetic energetics demonstrates a significant inverse association with adverse LV-remodeling. Late-diastolic LV blood flow kinetic energetics early after acute MI was independently associated with adverse LV-remodeling., Competing Interests: Declaration of Competing Interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Plaque rupture occurs when the structural stress inside plaques exceeds the capacity of the overlying fibrous cap. Plaque structural stress has been acknowledged as an index to evaluate the risk of plaque rupture. However, impacting factors associated with the level of plaque structural stress in ST-segment elevated myocardial infarction patients with ruptured plaques remain unknown., Methods: Based on optical coherence tomography, we analyzed the plaque characteristics and calculated the maximal plaque stress of the culprit lesions in 162 patients with plaque rupture by performing finite element analysis. All enrolled patients were divided into two groups according to the level of maximal plaque stress. Cardiovascular risk factors, laboratory findings and clinical outcomes were compared between the two groups., Results: Hemoglobin A1c (HbA1c) was significantly higher in the high stress group than in the low stress group (7.0% ± 1.8 vs. 6.3% ± 1.2, p = 0.003). The maximal plaque stress of patients with diabetes was significantly higher than that of patients without diabetes (538.7 kPa [346.2-810.6] vs. 425.9 kPa [306.2-571.4], p = 0.006). Moreover, the level of maximal plaque stress was significantly associated with HbA1c (Pearson's correlation coefficient: r = 0.289, P < 0.001). OCT findings showed that the fibrous cap thickness and maximal lipid arc were significantly associated with maximal plaque stress (r = -0.163, p = 0.038; r = 0.194, p = 0.013, respectively)., Conclusion: OCT-based finite-element analysis showed that HbA1c was independently associated with the level of maximal plaque stress in STEMI patients with plaque rupture, thus indicating the importance of glucose control in patients with coronary atherosclerotic disease., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Cerebrovascular accidents (CVAs) can complicate the follow-up of patients with acute myocardial infarction (AMI). Intracavitary blood stasis evaluation can be useful to stratify cardioembolic risk and optimize medical therapy. Cardiac magnetic resonance (CMR) imaging is increasingly used in AMI patients for prognostic purposes. Slow-flow artefact is common on T2-weighted images in presence of left ventricular (LV) blood stasis., Methods and Results: In this observational retrospective study, all patients with AMI undergoing CMR in our hospital were included. T2-weighted images were used to assess the presence of LV blood stasis. Among the 209 patients enrolled (males 72%, mean age 61 ± 12 years), LV blood stasis was detected in 48 (23%) and was significantly more prevalent in patients with extensive anterior or antero-apical AMI, lower LV ejection fraction, greater infarct size and microvascular obstruction. During follow-up (54 months, IQR 41-70), 8 CVAs and 6 cardiovascular deaths occurred. LV blood stasis emerged as a significant risk factor for both endpoints (logRank p < 0.001 and p = 0.008, respectively) and remained independent predictor of CVAs (HR 9.819, 95% CI 1.733-55.617, p = 0.010)., Conclusions: LV blood stasis identified with CMR predicts the occurrence of CVAs in patients with AMI. These results may be helpful to personalize antithrombotic therapy for prevention strategies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Remote ischemic postconditioning (RIPostC) has recently emerged as a potential novel therapeutic strategy to achieve protection against acute myocardial infarction (AMI) injury. We aimed to evaluate the longitudinal cardioprotective effects of RIPostC on AMI using 99m Tc-MIBI SPECT myocardial perfusion imaging (MPI) and gated 18 F-FDG PET (GPET) in pigs., Methods: MI was induced in 12 Chinese pigs. RIPostC was conducted by four 5 min cycles of blood pressure cuff inflation applied to the lower limb immediately after AMI. MPI and GPET were performed longitudinally at baseline, 3rd, 14th, 28th, and 56th days after AMI. Total perfusion defect (TPD), hibernating myocardium (HM), scar, left ventricular (LV) remodeling (End diastolic volume, EDV), and bone marrow (BM) metabolic activity were analyzed, and inflammation biomarkers were measured., Results: In outcome evaluation, there was a significant attenuation in TPD (Δ value, at 14th, 28th and 56th days), HM (Δ value, at 14th, 56th days) and Scar (Δ value, at 14th, 28th days) in the RIPostC group compared with the control group (P < 0.05). Additionally, RIPostC attenuated LV enlargement (ΔEDV, at 14th day) (P < 0.05) in comparison to controls. BM 18 F-FDG uptake activity in the RIPostC group was lower than the control group (P < 0.05) at the 3rd day after AMI. There was a non-statistically significant trend of decreased MMP-2 levels in the RIPostC group post-AMI (P > 0.05)., Conclusions: RIPostC presented the longitudinal cardioprotective effects by preserving myocardial viability, reducing infarct size, attenuating LV remodeling at early stage post-AMI, and may also have an anti-inflammatory effect at the acute phase., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Intravascular ultrasound (IVUS) can overcome the intrinsic limitations of coronary angiography for lesion assessment and stenting. IVUS improves outcomes of patients presenting with stable or complex coronary artery disease, but dedicated data on the impact of IVUS-guided percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) remains scarce., Methods: We systematically searched Embase, MEDLINE, Web of Science Core Collection, Cochrane Central Register of Controlled Trials and Google Scholar for studies that compared clinical outcomes for IVUS- versus angio-guided PCI in patients with AMI. The primary endpoint was all-cause mortality and the secondary endpoint major adverse cardiovascular events (MACE). Mantel-Haenszel random-effects model was used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI)., Results: Nine studies (8 observational, 1 RCT) with a total of 838.902 patients (796.953 angio-guided PCI, 41.949 IVUS-guided PCI) were included. In patients with AMI, IVUS-guided PCI was associated with a significantly lower risk of all-cause mortality (pooled RR: 0.70; 95% CI, 0.59-0.82; p < 0.01), MACE (pooled RR: 0.86; 95% CI, 0.74-0.99; p = 0.04) and target vessel revascularization (TVR) (pooled RR: 0.83; 95% CI, 0.73-0.95; p < 0.01). In the subset of patients presenting with ST-segment elevation, IVUS-guided PCI remained associated with a reduced risk for both all-cause mortality (pooled RR: 0.79; 95% CI, 0.66-0.95, p = 0.01) and MACE (pooled RR: 0.86; 95% CI, 0.74-0.99, p = 0.04)., Conclusions: This is the first systematic review and meta-analysis comparing IVUS- versus angio-guided PCI in patients with AMI, showing a beneficial effect of IVUS-guided PCI on all-cause mortality, MACE and TVR. Results of ongoing dedicated prospective studies are needed to confirm these findings., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Cardiac magnetic resonance (CMR) performed early after ST-segment elevation myocardial infarction (STEMI) can improve major adverse cardiac event (MACE) risk prediction. We aimed to create a simple clinical-CMR risk score for early MACE risk stratification in STEMI patients., Methods: We performed a multicenter prospective registry of reperfused STEMI patients (n = 1118) in whom early (1-week) CMR-derived left ventricular ejection fraction (LVEF), infarct size and microvascular obstruction (MVO) were quantified. MACE was defined as a combined clinical endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (NF-MI) or re-admission for acute decompensated heart failure (HF)., Results: During a median follow-up of 5.52 [2.63-7.44] years, 216 first MACE (58 CV deaths, 71 NF-MI and 87 HF) were registered. Mean age was 59.3 ± 12.3 years and most patients (82.8%) were male. Based on the four variables independently associated with MACE, we computed an 8-point risk score: time to reperfusion >4.15 h (1 point), GRACE risk score > 155 (3 points), CMR-LVEF <40% (3 points), and MVO >1.5 segments (1 point). This score permitted MACE risk stratification: MACE per 100 person-years was 1.96 in the low-risk category (0-2 points), 5.44 in the intermediate-risk category (3-5 points), and 19.7 in the high-risk category (6-8 points): p < 0.001 in multivariable Cox survival analysis., Conclusions: A novel risk score including clinical (time to reperfusion >4.15 h and GRACE risk score > 155) and CMR (LVEF <40% and MVO >1.5 segments) variables allows for simple and straightforward MACE risk stratification early after STEMI. External validation should confirm the applicability of the risk score., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Myocardial infarction with non-obstructed coronary arteries (MINOCA) is a distinct entity among patients presenting with troponin-positive acute chest pain. We have previously reported on the incremental diagnostic capability of cardiovascular magnetic resonance (CMR) in this cohort. There is paucity of evidence on the long-term (> 5 years) clinical outcomes of these patients as graded by their acute CMR diagnosis., Methods and Results: A total of 229 patients with a working diagnosis of MINOCA who underwent CMR assessment during the acute admission (2010-2017) were prospectively studied. The primary endpoint was major adverse cardiac events (MACE) defined as a composite of all-cause mortality and cardiovascular readmissions, identified from hospital and primary care records. CMR performed at a median of 6 days (IQR 2, 8) from presentation provided a diagnosis in 85% of the patients (38% myocarditis, 28% acute myocardial infarction and 19% Takotsubo cardiomyopathy). Over a median follow-up of 7.1 years (IQR 3.7, 8.2), 56 (24%) patients experienced a MACE. We found a strong association between CMR diagnosis and MACE (log rank 30.47, p < 0.001). In multivariate analysis, age (hazard ratio = 1.07; 95% confidence interval = 1.05, 1.10; p < 0.001) and CMR diagnosis of acute myocardial infarction (hazard ratio = 8.87; 95% confidence interval = 2.58, 30.4; p = 0.001) were independent predictors of MACE., Conclusions: In a large cohort of patients with a working diagnosis of MINOCA, one in four suffer a MACE during long-term clinical follow-up. CMR diagnosis of acute myocardial infarction and age were significant predictors of MACE even in the absence of significant coronary artery obstruction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Cardiac magnetic resonance (CMR) imaging provides valuable prognostic information in patients with ST-elevation myocardial infarction (STEMI). The peri-infarct zone (PIZ) is a potential marker for post-infarction risk stratification. The aim of this study was to assess the prognostic impact of PIZ in a large multicenter STEMI-trial., Methods: The study population consisted of 704 consecutive patients undergoing CMR within 10 days after STEMI to assess established parameters of myocardial injury and additionally the extent of PIZ. The primary clinical endpoint was major adverse cardiac events (MACE) consisting of death, re-infarction and new congestive heart failure within 1 year after infarction., Results: The median heterogeneous PIZ-volume in the overall population was 14 ml (interquartile range [IQR] 7 to 24 ml). Male sex, infarct size, and left ventricular ejection fraction were identified as independent predictors of larger PIZ alterations. Patients with MACE had a significantly larger PIZ volume compared to patients without adverse events (21 ml [IQR 12 to 35 ml] versus 14 ml [IQR 7 to 23 ml]; p = 0.001). In stepwise multivariable Cox regression analysis, PIZ > median (>14 ml) emerged as an independent predictor of MACE (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.34 to 6.00; p = 0.006) in addition to the Thrombolysis In Myocardial Infarction (TIMI) risk score (HR 1.53; 95% CI 1.19 to 1.53; p < 0.001). Addition of PIZ to a CMR risk model comprising LVEF, infarct size and microvascular obstruction resulted in net reclassification improvement of 0.46 (0.19-0.73, p < 0.001)., Conclusion: In this currently largest prospective, multicenter CMR study assessing PIZ, the extent of PIZ emerged as an independent predictor of MACE and a potential novel marker for optimized risk stratification in STEMI patients. ClinicalTrials.gov: NCT00712101., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Backgorund: Right atrial thrombi are rarely found straddling a patent foramen ovale (PFO). A thrombus straddling a PFO (TSPFO), also known as impending paradoxical embolism, is a medical emergency associated with up to 11.5% risk of death within 24 h of being diagnosed. We hypothesized that acute myocardial infarction (MI) and ischemic stroke (IS) diagnosed upon the admission of patients with TSPFO are associated with increased risk of death. We also investigated if specific acute therapies are associated with reduced in-hospital mortality., Methods: We performed a systematic search including case reports and series of adult patients with TSPFO published from 1950 to October 30, 2020. We gathered patient-level data and we applied a logistic regression model to evaluate on the risk of in-hospital death. We performed time-trends and several sensitivity analyses., Results: We included 386 cases with a TSPFO comprised in 359 publications. The median age was 61 years and 51.2% were females. Fifty (13.0%) patients died during hospital stay, 82 (21.2%) had an acute IS, and 18 (4.6%) had an acute MI diagnosed upon admission. Acute MI (OR 7.83, 95%CI 2.70-22.7; P < 0.0001), but not IS, was associated with increased risk of death. Right atrial thrombectomy was associated with a 65% decreased in-hospital mortality (OR 0.35, 95%CI 0.18-0.70, P = 0.003). Results remained unchanged on sensitivity analyses., Conclusion: In this systematic review of 386 cases of TSPFO, acute MI but not IS was associated with 8-fold increased risk of death, while surgical thrombectomy was associated with a significant 65% reduction of in-hospital mortality., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Novel therapies that can limit or reverse damage caused by myocardial infarction (MI) could ease the increasing burden of heart failure. In this regard Platelet Derived Growth Factor (PDGF) has been previously shown to contribute to cardiac repair after MI. Here, we use a rodent model of MI and recombinant adeno-associated virus 9 (rAAV9)-mediated gene transfer to overexpress Pdgf-a in the injured heart and assess its therapeutic potential., Methods and Results: Sprague Dawley rats underwent temporary occlusion of the left anterior descending coronary artery, followed immediately by systemic delivery of 1 × 10^11 vector genomes of either rAAV9 Pdgf-a or rAAV9 Empty vector (control). At day 28 post-MI echocardiography showed significantly improved left ventricular (LV) function (fractional shortening) after rAAV9 Pdgf-a (0.394 ± 0.019%) treatment vs control (0.304 ± 0.018%). Immunohistochemical analysis demonstrated significantly increased capillary and arteriolar density in the infarct border zone of rAAV9 Pdgf-a treated hearts together with a significant reduction in infarct scar size (rAAV9 Pdgf-a 6.09 ± 0.94% vs Empty 12.45 ± 0.92%). Western blot and qPCR analyses confirmed overexpression of PDGF-A and showed upregulation of smooth muscle alpha actin (Acta2), collagen type III alpha 1 (Col3a1) and lysyl oxidase (Lox) genes in rAAV9 Pdgf-a treated infarcts., Conclusion: Overexpression of Pdgf-a in the post-MI heart can modulate scar composition and improve LV function. Our study highlights the potential of rAAV gene transfer of Pdgf-a as a cardio-reparative therapy., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The ATI (Age-Thrombus burden-Index of Microvascular Resistance [IMR]) score was developed to predict suboptimal myocardial reperfusion in patients with ST-Elevation Myocardial Infarction (STEMI). When applied in the early phases of revascularization (e.g. before stent insertion), it predicts which patients are most likely to have a larger infarct size. In this study, we assessed the score's utility in determining which STEMI patients are at highest risk of clinical events during follow-up., Methods: The ATI-score was calculated prospectively in 254 STEMI patients using age (>50 years = 1 point), pre-stenting IMR (>40 U and < 100 U = 1 point; ≥100 U = 2 points) and angiographic thrombus score (4 = 1 point, 5 = 3 points); the cohort was stratified in high vs. low-intermediate ATI-score strata (≥4 vs. < 4, respectively)., Results: After 3 years of follow-up, patients with high ATI-score presented a higher rate of Major Adverse Cardiac Events (MACE) defined as the composite of all-cause mortality, resuscitated cardiac arrest and new heart failure diagnosis (Hazard Ratio [HR]: 3.07; 95% Confidence Interval [CI]: 1.19-7.93; p = 0.02). The ATI-score showed a moderate discriminative power (c-stat: 0.69), not significantly different from that of other risk scores used in the STEMI setting. A high ATI-score was an independent predictor of MACE (HR: 3.24; 95% CI: 1.22-8.58; p = 0.018)., Conclusions: The ATI-score can discriminate patients at higher risk of long-term adverse events. The score allows predication of subsequent events even before coronary stenting, and consequently it may allow the option of individualized therapy in the early stages of the clinical care-pathway., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: To assess the prognostic implications of cardiac magnetic resonance imaging (CMR) in patients with clinical suspicion of myocardial infarction with non-obstructed coronary arteries (MINOCA)., Methods: A total of 145 patients (58 ± 15 years, 97 men) were retrospectively enrolled in this single-center, longitudinal observational study. All patients underwent CMR including cine, edema-sensitive, and late gadolinium enhancement acquisitions, within a median of 3 days after cardiac catheterization. Follow-up was performed by medical records chart review and phone interviews; the median follow-up time was 4.2 years. The primary endpoint was defined as a combination of death, stroke, new onset of congestive heart failure, recurrent hospitalization, or the need for an invasive cardiac procedure., Results: In 143 (98.6%) cases, CMR revealed the following cardiac pathologies: myocarditis (n = 48, 33.1%), structural cardiomyopathies (n = 40, 27.6%), "true" myocardial infarction (n = 22, 15.1%), hypertensive heart disease (n = 19, 13.1%), and Tako-Tsubo cardiomyopathy (n = 14, 9.7%). Only two patients (1.4%) had a normal CMR examination. There were significant prognostic differences between different etiologies, e.g. myocarditis and Tako-Tsubo cardiomyopathy had a more favorable prognosis then structural cardiomyopathies. Age, end-diastolic volume index and time-to-CMR showed significant association with the primary endpoint in multi-variate Cox regression., Conclusions: CMR performed early after the onset of clinical symptoms allows discrimination between acute myocardial injury from "true" MINOCA in patients presenting with chest pain and elevated cardiac biomarkers, thereby helping to identify the underlying pathology in suspected MINOCA and allowing risk stratification based on the established diagnosis. Furthermore, CMR parameters allow for improved prediction of adverse events compared to clinical and laboratory parameters., Competing Interests: Declaration of Competing Interest TE has received a speaker fee and travel support from Siemens Healthineers, AVS receives institutional research support and travel support from Siemens Healthineers and is consultant for Bayer and Elucid Bioimaging. UJS has received institutional research support and/or honoraria for speaking and consulting from Astellas, Bayer, Bracco, Elucid BioImaging, General Electric, Guerbet, HeartFlow Inc., and Siemens Healthineers. None of these companies supported this studies and none of the authors reports a conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The effectiveness of treatment and prognosis of patients with type 1 myocardial infarction are highly correlated with time of diagnosis. This study aimed to develop a type 1 MI rapid screening scale (T1MIrs scale) suitable for emergency pre-diagnosis., Methods: A total of 1928 patients who underwent coronary angiography were enrolled. Multivariate regression analysis was used to identify the independent risk factors of type 1 MI. And the T1MIrs scale was developed and evaluated according to the multivariate regression result., Results: The incidence of type 1 MI was 23.3% in the population with suspected acute coronary syndrome. After 5 adjusting for relevant factors, MEWS score (OR = 1.809, 95%CI 1.623-2.016, P < .001), typical symptoms (OR = 9.826, 95%CI 7.379-13.084, P < .001), male (OR = 2.184, 95%CI 1.602-2.979, P < .001), age (OR = 1.021, 95%CI 1.009-1.033, P = .001), history of diabetes (OR = 2.174, 95%CI 1.594-2.963, P < .001) and current smoker (OR = 2.498, 95%CI 1.550-4.026, P < .001) were the independent risk factors for type 1 MI. The T1MIrs scale is established based on risk factors, with a range of 0-8 points. The incidence of type 1 MI is ascending with the scale (0.3% vs. 3.7% vs. 14.3% vs. 34.9% vs. 57% vs. 76.4% vs. 84.2% vs. 87.5% vs. 100%, P for trend <0.001)., Conclusions: Type 1 MI is common in patients with suspected acute coronary syndrome in emergency department. The T1MIrs scale could act as a rapid pre-examination triage of suspected population in emergency department, which is meaningful to screen out type 1 MI patients as soon as possible., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: It has been widely documented that circannual variation has an impact on the incidence and prognosis of cardiovascular diseases. It is unclear why cold ambient temperature increase the incidence of acute myocardial infarction (AMI). We investigated the relationship between the ambient temperature at the onset of AMI, the morphology of the culprit lesion in patients with AMI., Methods: We investigated 202 consecutive patients with AMI who underwent optical coherence tomography (OCT). The participants were divided into lower (n = 100) and higher (n = 102) temperature groups based on the ambient temperature. The culprit lesion morphology was compared between the two groups., Results: The median temperature at the onset of AMI was 16.6 °C. The prevalence of plaque ruptures was higher at lower temperatures (lower 66% vs. higher 45%, p = .003), whereas OCT-erosion was more frequent in the higher temperature group (lower 13% vs. higher 26%, p = .021). The lower temperature group showed more cholesterol crystals (lower 71% vs. higher 54%, p = .014)., Conclusion: The peak incidence of AMI in the winter is formed by increased plaque rupture, suggesting environmental temperature has an influence on the pathogenesis of AMI., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Treatment with newer direct-acting anti-platelet drugs (Ticagrelor and Prasugrel) prior to primary percutaneous coronary intervention (PCI) is associated with improved outcome in patients with ST-segment elevation myocardial infarction (STEMI) when compared with Clopidogrel. We compared infarct size following treatment with Ticagrelor/Prasugrel versus Clopidogrel in the DANish trial in Acute Myocardial Infarction (DANAMI-3) population of STEMI patients treated with primary PCI., Methods and Results: Patients were loaded with Clopidogrel, Ticagrelor or Prasugrel in the ambulance before primary PCI. Infarct size and myocardial salvage index were calculated using cardiac magnetic resonance (CMR) during index admission and at three-month follow-up. Six-hundred-and-ninety-three patients were included in this analysis. Clopidogrel was given to 351 patients and Ticagrelor/Prasugrel to 342 patients. The groups were generally comparable in terms of baseline and procedural characteristics. Median infarct size at three-month follow-up was 12.9% vs 10.0%, in patients treated with Clopidogrel and Ticagrelor/ Prasugrel respectively (p < 0.001), and myocardial salvage index was 66% vs 71% (p < 0.001). Results remained significant in a multiple regression model (p < 0.001)., Conclusions: Pre-hospital loading with Ticagrelor or Prasugrel compared to Clopidogrel, was associated with smaller infarct size and larger myocardial salvage index at three-month follow-up in patients with STEMI treated with primary PCI., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier B.V.)

Background: Accurate risk stratification in patients with known coronary artery disease (CAD) is critical for patient management. Prior myocardial infarction (MI) or revascularization without MI are often equated as known CAD. We compared the prognostic significance of prior MI and previous revascularization in patients undergoing single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI)., Methods: Consecutive patients undergoing SPECT MPI at Cedars-Sinai Medical Center between 1992 and 2012 were included. Medical history, including history of MI or revascularization, was collected prospectively. Association with all-cause mortality was assessed with multivariable Cox analysis, adjusted for patient demographics, medical history, medications, and SPECT MPI results., Results: In total, 50,121 patients were identified including 7428 (14.8%) with a history of previous MI and 3608 (7.2%) with a history of revascularization without prior MI. During a median follow-up of 8.0 years, 19,696 (39.3%) patients died including 4467 (60.1%) with a history of MI and 1880 (52.1%) with a history of revascularization. Prior MI (adjusted HR 1.12, p=0.001) and prior revascularization without MI (adjusted HR 1.15, p<0.001) were independently associated with increased all-cause mortality. Previous MI (adjusted HR 1.27, p<0.001) and previous revascularization without MI (adjusted HR 1.21, p<0.001) were significantly associated with increased all-cause mortality only in patients without ischemia., Conclusions: In this large cohort of patients undergoing SPECT MPI, previous MI and previous revascularization without MI were independent predictors of all-cause mortality, with no significant difference in associated risk. History of CAD may be particularly important for risk stratification in patients without ischemia., Competing Interests: Declaration of competing interest The work was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation. Drs. Berman and Slomka participate in software royalties for QPS software at Cedars-Sinai Medical Center., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Studies indicate no clear impact of intracoronary injection of bone-marrow unselected mononuclear cells (BM-MNC) after acute myocardial infarction (AMI) on left-ventricular function (LVEF). Strain parameters by cardiovascular magnetic resonance (CMR) have been proposed to be more sensitive to functional changes of the heart. The aim of the present study was to assess changes of global longitudinal (GLS) and circumferential strain (GCS) in a group of patients treated with BM-MNC after AMI., Methods: One-hundred and forty-nine patients with successfully reperfused AMI and LV dysfunction (LVEF<45%) were retrospectively included into this sub-study of the SWISS-AMI multicentre trial. Patients were divided into control (N = 54), early (5-7 days after AMI, N = 51) and late BM-MNC treatment groups (3-4 weeks, N = 44). The endpoint was the change of GLS and GCS as obtained from cine sequences 4 and 12 months after AMI using feature tracking algorithm., Results: In unadjusted analyses, the absolute change of GLS for the early treatment group from baseline to 4 months was 2.5 ± 4.3 (p < 0.01), to 12 months 2.7 ± 5.7% (p = 0.004). For late treatment, it was 1.5 ± 4.0% (p = 0.039, 4 months) and 2.5 ± 5.6% (p = 0.015, 12 months). For controls 0.7 ± 4.7% (p = 0.378), 0.8 ± 3.9% (p = 0.253) respectively. Adjusting for different baseline values, neither an overall treatment effect (both time-points) of BM-MNC nor a treatment time-related (only early or late) effect could be shown for all functional parameters., Conclusions: Among patients after AMI with successful reperfusion and LV dysfunction, intracoronary infusion of BM-MNC early or late after AMI did not improve global strain parameters at 4- or 12-months follow-up., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00355186., Competing Interests: Declaration of competing interest None declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Regional and global longitudinal strain (RLS-GLS) are considered reliable indexes of myocardial viability in chronic ischemic patients and prediction of left ventricular (LV) functional recovery after acute myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF). We tested in the present study whether RLS and GLS could also identify transmural extent of myocardial scar and predict LV functional recovery and remodeling in patients with reduced LVEF after acute MI., Methods: Echocardiography and late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) were performed in 71 patients with reduced LVEF (≤45%) after acute MI treated with acute percutaneous coronary intervention. At 8-month follow-up, echocardiography was repeated to determine global LV functional recovery and remodeling., Results: RLS was worse in transmural than in non-transmural infarcted segments (-6.6 ± 6.1% vs -10.3 ± 5.9%, p < 0.0001) and in non-transmural than in normal segments (-10.3 ± 5.9% vs -14.5 ± 6.4%, p < 0.0001). RLS > -12% had sensitivity of 78% and specificity of 69% to identify transmural infarcted segments (AUC = 0.79; 95% CI, 0.77-0.81, p < 0.0001). GLS > -11.3% had sensitivity of 53% and specificity of 100% to predict the absence of LV global functional improvement (AUC = 0.73, CI, 0.55-0.87, p = 0.01) at 8-month follow-up. GLS < -12.5% predicted the absence of adverse LV remodeling with sensitivity of 100% and specificity of 54% (AUC = 0.83; CI, 0.66-0.94, p < 0.0001). GLS > -11.5% was associated with a poor prognosis., Conclusions: In patients with reduced LVEF after acute MI, RLS and GLS allow: (1) identification of transmural extent of myocardial scar and (2) predict LV global functional recovery and remodeling at 8-month follow-up., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Serine proteinase inhibitor A3 (Serpina3), initially discovered as an acute phase plasma protease inhibitor, has been demonstrated in the pathology of complex human disorders, but it is yet to be discovered following acute myocardial infarction (AMI) in clinical practice. Therefore, we aimed to evaluate the relationship between Serpina3 concentrations at admission and the risk of major adverse cardiovascular events (MACE) in patients with AMI., Methods: A total of 120 AMI patients and 60 healthy participants were consecutively enrolled in our study. Clinical parameters variables were collected, and MACE was followed since hospitalization., Results: Plasma concentrations of Serpina3 were elevated after AMI [159.11 (121.81, 237.07) vs. 300.18 (187.90, 478.59) μg/mL, P < 0.001]. Multivariate linear regression analysis indicated that total cholesterol (standardized β = -0.204, P = 0.024) and ESR (standardized β = 0.513, P < 0.001) were independent factors for Serpina3. Based on the median value of Serpina3 in the AMI population, patients were divided into the high-Serpina3 group (≥300.18 μg/mL, n = 65) and the low-Serpina3 group (<300.18 μg/mL, n = 60). After a median follow-up of 9 months, Kaplan-Meier survival analysis revealed that the MACE-free survival rate was significantly lower in AMI patients with higher Serpina3 levels (P = 0.002). Multivariate Cox proportional hazards analyses demonstrated that Serpina3 was a positive predictor of MACE (hazard ratios 4.03, 95% CI 1.25-12.98, P = 0.019)., Conclusions: Increased circulating Serpina3 levels following AMI is significantly associated with MACE, which suggest that Serpina3 may be a potential predictive marker of clinical outcomes in AMI., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Manganese-enhanced MRI (MEMRI) detects viable cardiomyocytes based on the intracellular manganese uptake via L-type calcium-channels. This study aimed to quantify myocardial viability based on manganese uptake by viable myocardium in the infarct core (IC), peri-infarct region (PIR) and remote myocardium (RM) using T1 mapping before and after MEMRI and assess their association with cardiac function and arrhythmogenesis., Methods: Fifteen female swine had a 60-minute balloon ischemia-reperfusion injury in the LAD. MRI (Signa 3T, GE Healthcare) and electrophysiological study (EPS) were performed 4 weeks later. MEMRI and delayed gadolinium-enhanced MRI (DEMRI) were acquired on LV short axis. The DEMRI positive total infarct area was subdivided into the regions of MEMRI-negative non-viable IC and MEMRI-positive viable PIR. T1 mapping was performed to evaluate native T1, post-MEMRI T1, and delta R1 (R1 post -R1 pre , where R1 equals 1/T1) of each territory. Their correlation with LV function and EPS data was assessed., Results: PIR was characterized by intermediate native T1 (1530.5 ± 75.2 ms) compared to IC (1634.7 ± 88.4 ms, p = 0.001) and RM (1406.4 ± 37.9 ms, p < 0.0001). Lower post-MEMRI T1 of PIR (1136.3 ± 99.6 ms) than IC (1262.6 ± 126.8 ms, p = 0.005) and higher delta R1 (0.23 ± 0.08 s -1 ) of PIR than IC (0.18 ± 0.09 s -1 , p = 0.04) indicated higher myocardial manganese uptake of PIR compared to IC. Post-MEMRI T1 (r = -0.57, p = 0.02) and delta R1 (r = 0.51, p = 0.04) of PIR correlated significantly with LVEF., Conclusions: PIR is characterized by higher manganese uptake compared to the infarct core. In the subacute phase post-IR, PIR viability measured by post-MEMRI T1 correlates with cardiac function., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: CD4 + T cells are key players in regulating the inflammatory processes and physiological repair mechanisms engaged after acute myocardial infarction (AMI). Although signaling through the CD27-CD70 co-stimulatory pathway are known to be important in CD4 + T cell activation and proliferation in certain contexts, the role of the CD27-CD70 pathway in AMI remains unclear., Methods and Results: A total of 43 control subjects, 42 unstable angina patients, and 90 AMI patients were enrolled in the present study. The serum levels of soluble CD27 (sCD27) in patients were measured, revealing a significant increase in serum sCD27 levels in AMI patients within 24 h of the cardiac event, after which they decreased. Correlation analyses revealed that serum sCD27 was positively correlated with cardiac troponin I (c-TnI) (r = 0.267, P = 0.011). When anti-CD70 antibody was used to block the CD27-CD70 pathway in MI model mice, we found that this treatment increased left ventricular end-diastolic dimension (LVEDD) (P < 0.01) and left ventricular end-systolic dimension (LVESD) (P < 0.01), and decreased ejection fraction (P < 0.01). Flow cytometric analysis revealed that the percentage of regulatory T cells was lower in blocking antibody-treated mice (P < 0.01), while neutrophils levels were higher (P < 0.01). The number of CD31-positive endothelial cells (P = 0.026) and α-smooth muscle actin-positive arterioles (P < 0.01) were significantly down-regulated in anti-CD70 treated-AMI mice. The formation of the extracellular matrix (ECM) was also impaired., Conclusion: Serum sCD27 may be a potential biomarker for AMI. Blockade of the CD27-CD70 pathway worsens cardiac dysfunction, aggravates left ventricular remodeling, and impairs scar healing after AMI, resulting in heart failure., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Acute myocardial infarction (AMI) patients are at increased risk of death and recurrent ischemic events. We aimed to elaborate a risk score, based on the PEGASUS-TIMI 54 criteria, to predict mortality and non-fatal AMI in AMI patients., Methods: We retrospectively analyzed two prospectively collected AMI cohorts. We calculated a cut-off for the developed score and investigated its 1-year prognostic power in the derivation cohort (n = 1257). We externally validated our score in 913 AMI patients with a longer follow-up., Results: In the derivation cohort, the area under the curve of the score for the primary endpoint (1-year death and non-fatal AMI) was 0.70 (95% CI 0.65-0.76; P < 0.0001) and a cut-off of 6 was identified. The primary endpoint incidence in patients with a score above and below the cut-off was 12% and 3% (P < 0.001) in the derivation cohort and 16% and 6% in the validation cohort (P < 0.001). At multivariate analysis, the HR for the primary endpoint associated with a score ≥ 6 was 4.45 (P < 0.0001) in the derivation cohort and 2.86 (P < 0.0001) in the validation cohort. One-year major bleeding rate was low (<0.2% overall) and similar between risk groups. The prognostic performance of the score cut-off persisted beyond the first year after AMI in the validation cohort, maintaining a similar risk for death and non-fatal AMI (HR 3) at every following year., Conclusions: Our score, based on the PEGASUS-TIMI 54 criteria, may identify AMI patients at high risk of recurrent ischemic events, who might benefit from thorough preventive strategies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In patients with acute anterior myocardial infarction (MI), sometimes an "apical ballooning" contractile dysfunction pattern that exceeds factual myocardial injury is identified in the ventriculography and bedside echocardiography. The hemodynamic consequences/sequela of this "Tako-tsobu effect" has not been well delineated. Of note, this anatomic imaging finding often misleads frontline physicians who assume reciprocal causation of persistent cardiac pump failure and ventricular pressure overload., Methods and Results: Using real-time myocardial perfusion contrast echocardiography (MCE), we investigated myocardial (microvascular) perfusion in 60 patients after acute MI and coronary revascularization. Twenty-eight percent of the studied patients showed significantly mismatched myocardial perfusion and contractile defects. In these patients, an integrated imaging assessment with coronary angiography/ventriculography, deformation echocardiography, and MCE proved that the myocardial mechanic abnormalities significantly exceeded the defected perfusion areas. Compared with 72% of the patients without perfusion-contractility mismatch, apparently worse systolic functions (left ventricular ejection, wall motion score, and systolic longitudinal strain) in these patients did not change diastolic ventricular filling pressures (E/E' and E/A) or hemodynamic consequences/adverse events. Both systolic and diastolic functions in patients with perfusion-contractility mismatch appeared to be comparable with those in patients with Tako-tsubo syndrome., Conclusions: Real-time MCE identifies discrepant myocardial microvascular perfusion and mechanics in patients with acute MI. The "Tako-tsubo effect" in patients with perfusion-contractility mismatch does not cause diastolic filling pressure change or worse hemodynamic consequence/cardiac event., (Copyright © 2018. Published by Elsevier B.V.)

Aims: To describe the contemporary management by cardiologists of patients after an episode of myocardial infarction (MI)., Methods: The EYESHOT Post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients referring to cardiologists 1 to 3 years from the last MI event., Results: Over a 3-month period, 1633 consecutive patients [median 22 (IQR 15-28) months from MI] were enrolled: 1028 (63.0%) at the second and 605 (37.0%) at the third year from MI. During the 12 months prior to enrolment, the majority of patients received a transthoracic echocardiogram (60% and 54%), followed by coronary angiography (24% and 16%, in the second and third year from MI groups, respectively). At the time of enrolment, the majority of patients were prescribed on statins (93%) and beta-blockers (82%), without significant differences between the 2 groups. A dual antiplatelet therapy (DAPT) was used more frequently among patients presenting during the second compared to the third year from MI (40% vs 24%; p < 0.0001). At multivariable analysis, the time interval from last MI (2 vs 3 years: OR 2.27; 95% CI 1.79-2.88; p < 0.0001) and a previous percutaneous coronary intervention with multiple stents (OR 3.46; 95% CI 2.19-5.47; p < 0.0001) resulted as the major independent predictors of DAPT persistence at the time of enrolment., Conclusions: This contemporary registry provides unique insights into the current management of post-MI patients and represents an opportunity to further improve the long-term treatment of this high-risk population., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Identifying risk factors for specific modes of death in patients with heart failure (HF) or left ventricular (LV) dysfunction after acute myocardial infarction (MI) may help to avert events. We sought to evaluate LV ejection fraction (LVEF) as a prognosticator of specific death modes., Methods and Results: In an individual patient data meta-analysis of four merged trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT), Cox modelling was performed to study the association between baseline LVEF from 19,740 patients and types of death during follow-up. Over a median follow-up of 707 days 3419 deaths occurred. The distribution pattern for mode of death was similar across categories (LVEF < 25%, LVEF 25-35%, and LVEF > 35%). In multivariable models, the risk of all types of death increased with decreasing LVEF. If compared to LVEF > 35%, LVEF < 25% was associated with a 113% increased risk of sudden death (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.53-2.98), a 170% increased risk of HF death (HR 2.70, 95% CI 1.83-3.98), a 66% increased risk of other cardiovascular (CV) death (HR 1.66, 95% CI 1.14-2.42), and a 90% increased risk of non CV death (HR 1.90, 95% CI 1.15-3.14)., Conclusion: In patients with HF or LV dysfunction after acute MI, low LVEF is a ubiquitous risk marker associated with death regardless of type. The different modes of death are fairly equally represented throughout the categories of LVEF and sudden death remains a significant mode of death also in patients with LVEF > 35%., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Substance P (SP) may attenuate ischemia-reperfusion injury by reducing inflammation. We assessed cardioprotective effect of SP in a porcine model of acute myocardial infarction (AMI)., Methods: AMI was induced by occlusion of the left anterior descending artery on 28 swine, randomized to SP 5 nmol/kg (group 1, n = 14) and normal saline (group 2, n = 14) given intravenously 5 min before reperfusion. Blood samples were collected at baseline, 3 days and 4 weeks. Echocardiography and myocardial perfusion single photon emission computed tomography (SPECT) were performed at 1 week and 4 weeks. Histomorphometric infarct size assessment was done at 4 weeks., Results: Left ventricular (LV) ejection fraction (EF) (LVEF) after AMI induction was higher in group 1 than group 2 (37.9 ± 4.6% vs. 29.4 ± 3.2%, p = 0.001) but not different at 4 weeks. No significant difference was observed in perfusion defect extent and total perfusion defect on SPECT at 1 week and 4 weeks. Pathologic infarct size (% LV) was significantly smaller in group 1 than group 2 (2.4 ± 2.3% vs. 5.7 ± 2.5%, p = 0.020). The ratio of neutrophil to lymphocyte on day 3 and serum creatinine concentration at 4 weeks after AMI were lower in group 1., Conclusions: In a porcine model of AMI, SP improved LVEF early post-MI and reduced infarct size. SP may be beneficial in reducing inflammation and ischemia-reperfusion injury after AMI., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: High-sensitivity cardiac troponin T (hs-cTnT) blood concentrations were shown to exhibit a diurnal rhythm, characterized by gradually decreasing concentrations throughout daytime, rising concentrations during nighttime and peak concentrations in the morning. We aimed to investigate whether this also applies to (h)s-cTnI assays and whether it would affect diagnostic accuracy for acute myocardial infarction (AMI)., Methods: Blood concentrations of cTnI were measured at presentation and after 1 h using four different cTnI assays: three commonly used sensitive (s-cTnI Architect, Ultra and Accu) and one experimental high-sensitivity assay (hs-cTnI Accu) in a prospective multicenter diagnostic study of patients presenting to the emergency department with suspected AMI. These concentrations and their diagnostic accuracy for AMI (quantified by the area under the curve (AUC)) were compared between morning (11 p.m. to 2 p.m.) and evening (2 p.m. to 11 p.m.) presenters., Results: Among 2601 patients, AMI was the final diagnosis in 17.6% of patients. Concentrations of (h)s-cTnI as measured using all four assays were comparable in patients presenting in the morning versus patients presenting in the evening. Diagnostic accuracy for AMI of all four (h)s-cTnI assays were high and comparable between patients presenting in the morning versus presenting in the evening (AUC at presentation: 0.90 vs 0.93 for s-cTnI Architect; 0.91 vs 0.94 for s-cTnI Ultra; 0.89 vs 0.94 for s-cTnI Accu; 0.91 vs 0.94 for hs-cTnI Accu)., Conclusions: Cardiac TnI does not seem to express a diurnal rhythm. Diagnostic accuracy for AMI is very high and does not differ with time of presentation., Clinical Trial Registration: NCT00470587, http://clinicaltrials.gov/show/NCT00470587., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Milk thistle (Silybum marianum; SM) is an herb commonly used for hepatoprotection with antioxidant and antifibrotic properties. We investigated in pigs the cardiac effects of SM intake during the acute phase of myocardial infarction (MI) and remodeling period post-MI., Methods: Study-1 tested the effect of SM use on the acute phase of MI. Hence, animals were distributed to a control group or to receive SM prior infarction (1.5 h ischemia). Animals were sacrificed after 2.5 h of reperfusion. Study-2 tested the effect of SM use in the cardiac remodeling phase. Accordingly, animals received for 10 d diet ± SM prior MI and followed the same regime for 3 weeks and then sacrificed. Study-3 tested the effect of SM in a non-infarcted heart; therefore, animals received for 10 d diet ± SM and then sacrificed., Results: Animals taking SM before MI showed a reduction in cardiac damage (decreased oxidative damage, ROS production and xanthine oxidase levels; preserved mitochondrial function; and increased myocardial salvage; p < 0.05) versus controls. Animals that remained on chronic SM intake post-MI improved left ventricular remodeling. This was associated with the attenuation of the TGFß 1 /TßRs/SMAD2/3 signaling, lower myofibroblast transdifferentiation and collagen content in the border zone (p < 0.05 vs. all other groups). Cardiac contractility improved in animals taking SM (p < 0.05 vs. post-MI-control). No changes in cardiac function or fibrosis were detected in animals on SM but without MI., Conclusion: Intake of SM protects the heart against the deleterious effects of an MI and favors cardiac healing. These benefits may be attributed to the antioxidant and antifibrotic properties of SM., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: While preinfarction angina pectoris (pre-IA) is recognized as favorable effects on acute myocardial infarction (AMI), the detail has not been fully investigated. The aims of the current study were to clarify patient characteristics, lesion morphologies determined by optical coherence tomography (OCT), and cardiac outcomes related to pre-IA in patients with AMI., Methods: Clinical data and outcomes were compared between AMI patients with pre-IA (pre-IA group, n = 507) and without pre-IA (non-pre-IA group, n = 653). Angiography and OCT findings were analyzed in patients with pre-intervention OCT and compared between groups of pre-IA (n = 219) and non-pre-IA (n = 269)., Results: ST-segment elevation myocardial infarction (61% vs. 75%, p < 0.001) and cardiogenic shock (8% vs. 14%, p = 0.001) were less prevalent in pre-IA group. Peak creatine kinase-MB levels were lower in pre-IA group (median 83 IU/mL vs. 126 IU/mL, p < 0.001). In pre-intervention coronary angiography findings, initial TIMI flow grade 0/1 (43% vs. 56%, p = 0.019) and Rentrop collateral circulation 0/1 (69% vs. 79%, p = 0.018) were less frequently observed in pre-IA than in non-pre-IA patients. In post-thrombectomy OCT images, plaque rupture (39% vs. 56%, p = 0.003) and red thrombi (42% vs. 54%, p = 0.027) were also less frequently observed in pre-IA group. Kaplan-Meier estimate survival curves showed that cardiac death at 12-months was lower in pre-IA group than in non-pre-IA group (6.9% vs. 10.1%, p = 0.036)., Conclusions: Patients with pre-IA had less severe AMI on admission, smaller infarction size, and more favorable long-term survival, which may be caused by difference of lesion morphology between patients with and without pre-IA., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: In a pig model of acute myocardial infarction (AMI), we validated a functional computed tomography (CT) technique for concomitant assessment of myocardial edema and ischemia through extravscualar contrast distribution volume (ECDV) and myocardial perfusion (MP) measurements from a single dynamic imaging session using a single contrast bolus injection., Methods: In seven pigs, balloon catheter was used to occlude the distal left anterior descending artery for one hour followed by reperfusion. CT and cardiac magnetic resonance (CMR) imaging studies were acquired on 3 days and 12 ± 3 day post ischemic insult. In each CT study, 0.7 ml/kg of iodinated contrast was intravenously injected at 3-4 ml/s before dynamic contrast-enhanced (DCE) cardiac images were acquired with breath-hold using a 64-row CT scanner. DCE cardiac images were analyzed with a model-based deconvolution to generate ECDV and MP maps. ECDV as an imaging marker of edema was validated against CMR T2 weighted imaging in normal and infarcted myocardium delineated from ex-vivo histological staining., Results: ECDV in infarcted myocardium was significantly higher (p < 0.05) than that in normal myocardium on both days post AMI and was in agreement with the findings of CMR T2 weighted imaging. MP was significantly lower (p < 0.05) in the infarcted region compared to normal on both days post AMI., Conclusion: This imaging technique can rapidly and simultaneously assess myocardial edema and ischemia through ECDV and MP measurements, and may be useful for delineation of salvageable tissue within at-risk myocardium to guide reperfusion therapy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Cystathionine is a thio-ether and a metabolite formed from homocysteine during transsulfuration. Elevated plasma cystathionine levels are reported in patients with cardiovascular disease; however prospective relationships with acute myocardial infarction (AMI) are unknown. We investigated associations between plasma cystathionine and AMI among patients with suspected and/or verified coronary heart disease (CHD)., Methods: Subjects from two independent cohort studies, the Western Norway Coronary Angiography Cohort (WECAC) (3033 patients with stable angina pectoris; 263 events within 4.8 years of median follow-up) and the Norwegian Vitamin Trial (NORVIT) (3670 patients with AMI; 683 events within 3.2 years of median follow-up) were included., Results: In both cohorts, plasma cystathionine was associated with several traditional CHD risk factors (P < 0.001). Comparing the cystathionine quartile 4 to 1, age and gender adjusted hazard ratios (95% confidence intervals) for AMI were 2.08 (1.43-3.03) and 1.41 (1.12-1.76) in WECAC and NORVIT, respectively. Additional adjustment for traditional risk factors slightly attenuated the risk estimates, which were generally stronger in both cohorts among non-smokers, patients with higher age, and lower BMI or PLP status (P-interaction ≤ 0.04). Risk associations also tended to be stronger in patients not treated with B-vitamins. Additionally, in a subset of 80 WECAC patients, plasma cystathionine associated strongly negatively with glutathione, an important antioxidant and positively with lanthionine, a marker of H 2 S production (P < 0.001)., Conclusions: Plasma cystathionine is associated with increased risk of AMI among patients with either suspected or verified coronary heart disease, and is possibly related to altered redox homeostasis., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Mechanisms underlying increased mortality in patients with chronic total occlusion (CTO) of a non-infarct-related artery (non-IRA) are unknown. Cardiac magnetic resonance (CMR) is uniquely suited to provide important mechanistic and pathophysiological information on myocardial damage and reperfusion injury. Aim of this study was to investigate the association of a CTO in a non-IRA with myocardial damage assessed by CMR in patients with ST-elevation myocardial infarction (STEMI)., Methods: STEMI patients (n = 791) were stratified according to the presence of single-vessel disease (SVD), multivessel disease (MVD) without a CTO and MVD with a concomitant CTO in a non-IRA. CMR parameters of myocardial injury and clinical outcome after 12 months (major adverse cardiac events [MACE]: death, re-infarction, readmission for heart failure) were compared between groups., Results: A CTO in a non-IRA was present in 74 patients (9%), whereas 372 (47%) had MVD without a CTO and 345 (44%) had SVD. Patients with a CTO in a non-IRA had significantly larger infarcts, a lower myocardial salvage index and lower left ventricular ejection fraction as compared to patients with SVD or MVD without a CTO. MACE rates were significantly higher in patients with MVD and concomitant non-IRA CTO (9.7%) versus MVD patients without CTO (6.5%) and SVD patients (4.1%) (p = 0.015). MVD with non-IRA CTO was a significant independent predictor of clinical outcome [hazard ratio 2.06, 95% confidence interval 1.11-3.82, p = 0.021]., Conclusion: In patients with acute reperfused STEMI, the presence of a CTO in a non-IRA was associated with larger myocardial damage and increased MACE rates., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCAs) is an increasingly recognized entity. No previous study has evaluated predictors for new major adverse cardiacvascular events (MACEs) and death in patients with MINOCA., Methods: We conducted an observational study of MINOCA patients recorded between July 2003 and June 2013 and followed until December 2013 for outcome events. Out of 199,163 MI admissions, 9092 consecutive unique patients with MINOCA were identified. The mean age was 65.5 years and 62% were women. MACE was defined as all-cause mortality, rehospitalization for acute MI, ischemic stroke and heart failure. Hazard ratio and 95% confidence interval (HR; 95% CI) was calculated using Cox-regression., Results: A total of 2147 patients (24%) experienced a new MACE and 1254 patients (14%) died during the mean follow-up of 4.5 years. Independent predictors for MACE after adjustment, were older age (1.05; 1.04-1.06), diabetes (1.44; 1.21-1.70), hypertension (1.25; 1.09-1.43), current smoking (1.38; 1.15-1.66), previous myocardial infarction (1.38; 1.04-2.82), previous stroke (1.69; 1.35-2.11), peripheral vascular disease (1.55; 1.97-2.23), chronic obstructive pulmonary disease (1.63; 1.32-2.00), reduced left ventricular ejection fraction (2.00; 1.54-2.60), lower level of total cholesterol (0.88; 0.83-0.94) and higher level of creatinine (1.01; 1.00-1.03). Independent predictors for all cause death were age, current smoking, diabetes, cancer, chronic obstructive pulmonary disease, previous stroke, reduced left ventricular fraction, lower level of total cholesterol and higher levels of creatinine and CRP., Conclusions: The clinical factors predicting new MACE and death of MINOCA patients seem to be strikingly similar to factors previously shown to predict new cardiovascular events in patients with MI and obstructive coronary artery disease., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The role of systemic atherosclerosis in myocardial infarction (MI) patients is not fully understood. We investigated the incremental prognostic value of coronary and systemic atherosclerosis after acute MI by estimating extra-cardiac artery disease (ECAD) and extent of coronary atherosclerosis., Methods and Results: The study included 544 prospective MI patients undergoing coronary angiography. For all patients, the longitudinal coronary atherosclerotic extent, expressed as Sullivan extent score (SES) was calculated. In addition, the patients underwent non-invasive screening for ECAD in the carotid, aortic, renal and lower limb. SES was found to be associated with ECAD independent of baseline clinical parameters [adjusted odds ratio (OR) 1.04 95% confidence interval (CI) 1.02-1.06, P < 0.001]. Extensive systemic atherosclerosis, defined as the combination of extensive coronary disease (SES ≥ 17) and ECAD, was associated with higher risk for all-cause mortality compared to limited systemic atherosclerosis (SES < 17 and no ECAD) (hazard ratio [HR] 2.9 95% CI 1.9-4.5, P < 0.001, adjusted for Global Registry of Acute Coronary Events risk score parameters 1.8, 95% CI 1.1-3.0, P = 0.019). The risk for the composite endpoint of cardiovascular death or hospitalization was significantly higher in patients with extensive systemic atherosclerosis compared to patients with limited systemic atherosclerosis (HR 3.1, 95% CI 2.1-4.7, P < 0.001, adjusted HR 1.9, 95% CI 1.2-3.1, P < 0.004)., Conclusions: Visual estimation of the longitudinal coronary atherosclerotic extent at the time of MI predicts ECAD. Coexistence of extensive coronary disease and ECAD defines a group with particularly poor prognosis after MI., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: It is unclear why among patients with first acute myocardial infarction and an occluded culprit artery only some present ST segment elevation. In fact, there is no study that compares the angiographic area at risk and the collateral circulation in first NSTEMI vs STEMI patients., Methods and Results: 205 patients admitted for myocardial infarction with occluded culprit artery were included, 132 STEMI and 73 NSTEMI. Demographic data, the area at risk determined by the BARI score and collateral supply by the Rentrop score from the 2 groups were compared. NSTEMI patients showed lower peak Tn I than STEMI in the overall group but also in the 3 subsets with different culprit arteries (p < .001). They also presented a higher rate of left circumflex coronary artery (CFX) as culprit artery (52% vs 14%, p < .001), smaller BARI score area of the culprit artery (5.4 vs 7.6, p < .001), and higher frequency of well-developed collaterals (Rentrop score ≥ 2, 1.82 vs 0.41, p < .001). The latter was also higher in each of the 3 different culprit arteries (p = .002-<0.001) Among 38 NSTEMI patients with CFX occlusion, 20 with ≥1 mm ST depression in V2 to V4 (possible posterior infarction) showed a similar Rentrop score than the 18 with other ECG changes but lower Tn I peak (p = .012)., Conclusions: In first acute myocardial infarction with an occluded culprit artery NSTEMI patients - including those with possible posterior infarction - present smaller infarct size and higher collateral blood supply than STEMI patients in each of the 3 main culprit arteries., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Angiotensin receptor neprilysin inhibitor (ARNi) enhances beneficial natriuretic peptides by inhibiting their breakdown through neprilysin. Although the first-in-class ARNi sacubitril/valsartan (LCZ696) reduced mortality and morbidity in heart failure (HF) with reduced ejection fraction (EF) compared to angiotensin converting enzyme inhibitor (ACEi), mechanistic data on ARNi are scarce. ARNi may be superior to ACEi in attenuating adverse cardiac remodeling and dysfunction post-myocardial infarction (MI)., Methods: Rats randomized at 1 week post-MI were administered LCZ696 (60 mg/kg, N = 12), the ACEi perindopril (2 mg/kg, N = 11) or vehicle (corn oil, N = 13), orally for 4 weeks. Sham rats received vehicle (corn oil, N = 9). Echocardiography was assessed before and after treatment, prior to invasive hemodynamics using pressure-volume analysis. Hypertrophy and fibrosis was evaluated by histochemical staining, and analysis of myocardial gene and protein expression using real-time quantitative PCR and Western blot., Results: Compared to Sham, MI groups had large infarcts (>40%) and reduced left ventricular (LV) EF. LCZ696 improved LVEF and end systolic pressure-volume relationship compared to perindopril (P < 0.05). LCZ696 but not perindopril reduced lung weight and LV filling pressures post-MI. Reductions in cardiac hypertrophy and fibrosis were similar, however gene expression of hypertrophic markers, ANP and βMHC were reduced with LCZ696 versus perindopril. LCZ696 versus perindopril reduced myocardial TIMP2 gene expression with a trend (P = 0.067) to lowering collagen I., Conclusion: LCZ696 attenuated adverse cardiac remodeling and dysfunction and reduced pulmonary congestion and hypertrophic markers after MI compared to perindopril. This study supports clinical evaluation of ARNi versus ACEi in targeting post-MI cardiac dysfunction and remodeling., (Copyright © 2017 Elsevier B.V. All rights reserved.)