Prediction of left ventricular thrombus after myocardial infarction: a cardiac magnetic resonance-based prospective registry.

BACKGROUND: Left ventricular thrombus (LVTh) is a severe complication after ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: We aim to predict LVTh occurrence by cardiac magnetic resonance (CMR) using clinical, echocardiographic, and electrocardiographic (ECG) variables readily available at admission. METHODS: We included 590 reperfused STEMI patients who underwent early (1-week) and/or late (6-month) CMR in our institution. Baseline clinical, echocardiographic (left ventricular ejection fraction -LVEF-) and ECG data (summatory of ST-segment elevation -sum-STE- and Q-wave and residual ST-elevation >1 mm -Q-STE-) during admission were registered. Multivariate binary logistic regression models and receiver operating characteristic curves were computed for LVTh prediction. RESULTS: LVTh was detected by CMR in 43 (7.3 %) patients and was predicted by previous chronic coronary syndrome (CCS, HR 4.74 [1.82-12.35], p = 0.001), anterior STEMI (HR 10.93 [2.47-48.31], p = 0.002), LVEF (HR 0.96 [0.93-0.99] per %, p = 0.008), maximum sum-STE (HR 1.04 [1.01-1.07] per mm, p = 0.04), and Q-STE (HR 1.31 [1.08-1.6] per lead, p = 0.008). High-risk patients with both major (anterior STEMI and Q-STE in ≥1 leads) and 1-3 minor (CCS, maximum sum-STE >10 mm, LVEF <50%) factors showed the highest LVTh risk (19.6 % within 6 months). The model showed excellent discrimination ability (area under the curve=0.85 [0.81-0.9], p < 0.001). Simplified 4-variable (excluding sum-STE) and 3-variable (also excluding CCS) risk scores showed similar discrimination ability and were externally validated. CONCLUSIONS: LVTh within 6 months post-STEMI can be predicted using pre-discharge clinical (anterior infarction and CCS), echocardiographic (LVEF), and ECG (sum-STE and Q-STE) data. Our results can help select patients who should undergo CMR after STEMI for LVTh detection.

Prognostic role of persistent angina after percutaneous revascularization in chronic coronary syndrome with altered angiography and stress CMR.

INTRODUCTION AND OBJECTIVES: In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization. METHODS: We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class ≥ 2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission. RESULTS: All patients had angina class ≥ 2 (mean: 2.8 ± 0.7), abnormal stress CMR (mean ischemic burden: 5.8 ± 2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.5-9.2; P = .005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P < .001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P = .001). CONCLUSIONS: In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure.

Novel Fibrillar and Non-Fibrillar Collagens Involved in Fibrotic Scar Formation after Myocardial Infarction.

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

Efecto del suero aislado de pacientes con infarto agudo de miocardio con elevación del segmento ST en las células endoteliales / Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells

Introducción y objetivos La reperfusión coronaria produce un daño en la microcirculación y, en concreto, las células endoteliales. Este estudio evalúa el efecto del suero aislado tras la revascularización de pacientes con un infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en la viabilidad celular, el grado de permeabilidad endotelial in vitro y la asociación de estos parámetros con una mayor extensión de los índices de resonancia magnética cardiaca (RMC) relacionados con el daño por reperfusión (edema, hemorragia y obstrucción microvascular). Métodos Se incubaron células endoteliales de arteria coronaria humana con suero aislado 24 h tras la revascularización de 43 pacientes con IAMCEST evaluados mediante RMC y 14 sujetos de control. Se testó el efecto del suero de pacientes con IAMCEST en la pérdida de viabilidad celular por activación de la apoptosis y la necrosis, así como en la permeabilidad y la estructura de la monocapa endotelial. Resultados El suero de pacientes con IAMCEST aumentó la apoptosis (p <0,01) y la necrosis (p <0,05) de células endoteliales de arteria coronaria humana y causó un incremento de la permeabilidad de la monocapa endotelial in vitro (p <0,01) debido a mayores espacios intercelulares (p <0,05 frente a los controles). Una mayor necrosis inducida por suero se asoció con más permeabilidad endotelial in vitro (p <0,05) y con una mayor extensión de los principales índices de daño tras reperfusión y mayor tamaño de infarto. Conclusiones El suero tras la reperfusión de pacientes con IAMCEST induce la apoptosis y la necrosis in vitro de las células endoteliales y la permeabilidad endotelial. Cuanto más potente sea el efecto inductor de necrosis, más deletéreas son las consecuencias en cuanto al daño estructural resultante. (AU)

Introduction and objectives Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). Methods Human coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. Results Serum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. Conclusions Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure. (AU)

Impact of Epicardial Adipose Tissue on Infarct Size and Left Ventricular Systolic Function in Patients with Anterior ST-Segment Elevation Myocardial Infarction.

We aimed to assess the correlation of cardiovascular magnetic resonance (CMR)-derived epicardial adipose tissue (EAT) with infarct size (IS) and residual systolic function in ST-segment elevation myocardial infarction (STEMI). We enrolled patients discharged for a first anterior reperfused STEMI submitted to undergo CMR. EAT, left ventricular (LV) ejection fraction (LVEF), and IS were quantified at the 1-week (n = 221) and at 6-month CMR (n = 167). At 1-week CMR, mean EAT was 31 ± 13 mL/m2. Patients with high EAT volume (n = 72) showed larger 1-week IS. After adjustment, EAT extent was independently related to 1-week IS. In patients with large IS at 1 week (>30% of LV mass, n = 88), those with high EAT showed more preserved 6-month LVEF. This association persisted after adjustment and in a 1:1 propensity score-matched patient subset. Overall, EAT decreased at 6 months. In patients with large IS, a greater reduction of EAT was associated with more preserved 6-month LVEF. In STEMI, a higher presence of EAT was associated with a larger IS. Nevertheless, in patients with large infarctions, high EAT and greater subsequent EAT reduction were linked to more preserved LVEF in the chronic phase. This dual and paradoxical effect of EAT fuels the need for further research in this field.

Effect of serum from patients with ST-segment elevation myocardial infarction on endothelial cells.

INTRODUCTION AND OBJECTIVES: Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). METHODS: Human coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. RESULTS: Serum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. CONCLUSIONS: Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.

Novel Targets Regulating the Role of Endothelial Cells and Angiogenesis after Infarction: A RNA Sequencing Analysis.

Endothelial cells (ECs) are a key target for cardioprotection due to their role in preserving cardiac microvasculature and homeostasis after myocardial infarction (MI). Our goal is to identify the genes involved in post-MI EC proliferation, EC apoptosis, and angiogenesis regulation via RNA-sequencing transcriptomic datasets. Using eight studies from the Gene Expression Omnibus, RNA-sequencing data from 92 mice submitted to different times of coronary ischemia or sham were chosen. Functional enrichment analysis was performed based on gene ontology biological processes (BPs). Apoptosis-related BPs are activated up to day 3 after ischemia onset, whereas endothelial proliferation occurs from day 3 onwards, including an overrepresentation of up to 37 genes. Endothelial apoptosis post-MI is triggered via both the extrinsic and intrinsic signaling pathways, as reflected by the overrepresentation of 13 and 2 specific genes, respectively. BPs implicated in new vessel formation are upregulated soon after ischemia onset, whilst the mechanisms aiming at angiogenesis repression can be detected at day 3. Overall, 51 pro-angiogenic and 29 anti-angiogenic factors displayed altered transcriptomic expression post-MI. This is the first study using RNA sequencing datasets to evaluate the genes participating in post-MI endothelium physiology and angiogenesis regulation. These novel data could lay the groundwork to advance understanding of the implication of ECs after MI.

Changes in the extracellular matrix at microvascular obstruction area after reperfused myocardial infarction: A morphometric study.

BACKGROUND: Extracellular matrix (ECM) suffers substantial alterations after myocardial infarction (MI), including the invasion of leukocyte subtypes. Despite a complete reopening at epicardial level, hypoperfusion within the infarcted myocardium, known as microvascular obstruction (MVO), occurs and exerts a negative impact on ventricular remodeling. In this study, ECM composition at MVO regions was described using a morphometric analysis. METHODS: MI was induced in female swine (n = 10) by transitory 90-minute coronary occlusion followed by seven days of reperfusion. Prior to euthanasia, intracoronary thioflavin-S was infused. Within the infarcted myocardium, regions displaying MVO (thioflavin-S-) or no MVO (thioflavin-S+) were isolated and stained to morphometrically compare ECM composition. RESULTS: As reflected by cell invasion through ECM, areas with MVO displayed an enlarged presence of neutrophils and lymphocytes, whilst no differences in the amount of macrophages and myofibroblasts were detected compared to infarcted myocardium without MVO. Indeed, those regions with macroscopic MVO showed lower capillary density than areas without MVO. Lastly, a significant reduction in the extension of total collagen, type I, but not type III, collagen, laminin, and fibronectin together with an augmentation of polysaccharides were noted in areas showing MVO compared to those without microvascular injury. CONCLUSIONS: ECM composition in infarcted regions with MVO isolated from female swine displays a higher presence of inflammatory infiltrate and polysaccharides as well as reduced number of microvessels and collagen content compared to those areas without microvascular hypoperfusion. These characteristics might underlie the development of adverse ventricular remodeling in MI patients with extensive MVO.

Impact of Persistent Microvascular Obstruction Late After STEMI on Adverse LV Remodeling: A CMR Study.

BACKGROUND: Little is known about the occurrence and implications of persistent microvascular obstruction (MVO) after reperfused ST-segment elevation myocardial infarction (STEMI). OBJECTIVES: The authors used cardiac magnetic resonance (CMR) to characterize the impact of persistent MVO on adverse left ventricular remodeling (ALVR). METHODS: A prospective registry of 471 STEMI patients underwent CMR 7 (IQR: 5-10) days and 198 (IQR: 167-231) days after infarction. MVO (≥1 segment) and ALVR (relative increase >15% at follow-up CMR) of left ventricular end-diastolic index (LVEDVI) and left ventricular end-systolic volume index (LVESVI) were determined. RESULTS: One-week MVO occurred in 209 patients (44%) and persisted in 30 (6%). The extent of MVO (P = 0.026) and intramyocardial hemorrhage (P = 0.001) at 1 week were independently associated with the magnitude of MVO at follow-up CMR. Compared with patients without MVO (n = 262, 56%) or with MVO only at 1 week (n = 179, 38%), those with persistent MVO at follow-up (n = 30, 6%) showed higher rates of ALVR-LVEDVI (22%, 27%, and 50%; P = 0.003) and ALVR-LVESVI (20%, 21%, and 53%; P < 0.001). After adjustment, persistent MVO at follow-up (≥1 segment) was independently associated with ΔLVEDVI (relative increase, %) (P < 0.001) and ΔLVESVI (P < 0.001). Compared with a 1:1 propensity score-matched population on CMR variables made up of 30 patients with MVO only at 1 week, patients with persistent MVO more frequently displayed ALVR-LVEDVI (12% vs 50%; P = 0.003) and ALVR-LVESVI (12% vs 53%; P = 0.001). CONCLUSIONS: MVO persists in a small percentage of patients in chronic phase after STEMI and exerts deleterious effects in terms of LV remodeling. These findings fuel the need for further research on microvascular injury repair.

MRI Investigation of the Differential Impact of Left Ventricular Ejection Fraction After Myocardial Infarction in Elderly vs. Nonelderly Patients to Predict Readmission for Heart Failure.

BACKGROUND: Patients with ST-segment elevation myocardial infarction (STEMI), especially elderly individuals, have an increased risk of readmission for acute heart failure (AHF). PURPOSE: To study the impact of left ventricular ejection fraction (LVEF) by MRI to predict AHF in elderly (>70 years) and nonelderly patients after STEMI. STUDY TYPE: Prospective. POPULATION: Multicenter registry of 759 reperfused STEMI patients (23.3% elderly). FIELD STRENGTH/SEQUENCE: 1.5-T. Balanced steady-state free precession (cine imaging) and segmented inversion recovery steady-state free precession (late gadolinium enhancement) sequences. ASSESSMENT: One-week MRI-derived LVEF (%) was quantified. Sequential MRI data were recorded in 579 patients. Patients were categorized according to their MRI-derived LVEF as preserved (p-LVEF, ≥50%), mildly reduced (mr-LVEF, 41%-49%), or reduced (r-LVEF, ≤40%). Median follow-up was 5 [2.33-7.54] years. STATISTICAL TESTS: Univariable (Student's t, Mann-Whitney U, chi-square, and Fisher's exact tests) and multivariable (Cox proportional hazard regression) comparisons and continuous-time multistate Markov model to analyze transitions between LVEF categories and to AHF. Hazard ratios (HR) with 95% confidence intervals (CIs) were computed. P < 0.05 was considered statistically significant. RESULTS: Over the follow-up period, 79 (10.4%) patients presented AHF. MRI-LVEF was the most robust predictor in nonelderly (HR 0.94 [0.91-0.98]) and elderly patients (HR 0.94 [0.91-0.97]). Elderly patients had an increased AHF risk across the LVEF spectrum. An excess of risk (compared to p-LVEF) was noted in patients with r-LVEF both in nonelderly (HR 11.25 [5.67-22.32]) and elderly patients (HR 7.55 [3.29-17.34]). However, the mr-LVEF category was associated with increased AHF risk only in elderly patients (HR 3.66 [1.54-8.68]). Less transitions to higher LVEF states (n = 19, 30.2% vs. n = 98, 53%) and more transitions to AHF state (n = 34, 53.9% vs. n = 45, 24.3%) were observed in elderly than nonelderly patients. DATA CONCLUSION: MRI-derived p-LVEF confers a favorable prognosis and r-LVEF identifies individuals at the highest risk of AHF in both elderly and nonelderly patients. Nevertheless, an excess of risk was also found in the mr-LVEF category in the elderly group. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 2.

Cardiac magnetic resonance outperforms echocardiography to predict subsequent implantable cardioverter defibrillator therapies in ST-segment elevation myocardial infarction patients.

Background: Implantable cardioverter defibrillators (ICD) are effective as a primary prevention measure of ventricular tachyarrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) and depressed left ventricular ejection fraction (LVEF). The implications of using cardiac magnetic resonance (CMR) instead of echocardiography (Echo) to assess LVEF prior to the indication of ICD in this setting are unknown. Materials and methods: We evaluated 52 STEMI patients (56.6 ± 11 years, 88.5% male) treated with ICD in primary prevention who underwent echocardiography and CMR prior to ICD implantation. ICD implantation was indicated based on the presence of heart failure and depressed LVEF (≤ 35%) by echocardiography, CMR, or both. Prediction of ICD therapies (ICD-T) during follow-up by echocardiography and CMR before ICD implantation was assessed. Results: Compared to echocardiography, LVEF was lower by cardiac CMR (30.2 ± 9% vs. 37.4 ± 7.6%, p < 0.001). LVEF ≤ 35% was detected in 24 patients (46.2%) by Echo and in 42 (80.7%) by CMR. During a mean follow-up of 6.1 ± 4.2 years, 10 patients received appropriate ICD-T (3.16 ICD-T per 100 person-years): 5 direct shocks to treat very fast ventricular tachycardia or ventricular fibrillation, 3 effective antitachycardia pacing (ATP) for treatment of ventricular tachycardia, and 2 ineffective ATP followed by shock to treat ventricular tachycardia. Echo-LVEF ≤ 35% correctly predicted ICD-T in 4/10 (40%) patients and CMR-LVEF ≤ 35% in 10/10 (100%) patients. CMR-LVEF improved on Echo-LVEF for predicting ICD-T (area under the curve: 0.76 vs. 0.48, p = 0.04). Conclusion: In STEMI patients treated with ICD, assessment of LVEF by CMR outperforms Echo-LVEF to predict the subsequent use of appropriate ICD therapies.

Risk of death associated with incident heart failure in patients with known or suspected chronic coronary syndrome.

AIMS: Traditional adverse events in chronic coronary syndrome (CCS) include atherothrombotic events but usually exclude heart failure (HF). Data are scarce about how new-onset HF modifies mortality risk. We aimed to determine the incidence of HF and compare its long-term mortality risk with myocardial infarction (MI) and stroke in patients with known or suspected CCS. METHODS: We prospectively evaluated 5811 consecutive HF-free patients submitted to vasodilator stress cardiac magnetic resonance (CMR) for known or suspected CCS. Ischaemic burden and left ventricular ejection fraction were assessed by CMR. HF included outpatient diagnosis or acute HF hospitalization. The mortality risk for the incident events and their cross-comparisons were evaluated using a Markov illness-death model with transition-specific survival models. RESULTS: The mean age was 55 ± 11 years, and 38.9% were female. At a median follow-up of 5.44 (IQR = 2.53-8.55) years, 591 deaths were registered (1.79 per 100 P-Y). The rates of new-onset HF were higher compared with MI and stroke [1.02, 0.62, and 0.51, respectively (P < 0.05)]. The adjusted association between new-onset HF, MI, and stroke, and subsequent mortality was time dependent. The risk increased almost linearly for HF and became significant by the third year. By Year 10, the mortality risk attributable to new-onset HF was more than 2.5-fold (HR: 2.68, 95% CI = 1.74-4.12). For MI, there was a significant increase in mortality risk up to the second year, followed by a monotonic decrease. For stroke, the mortality risk increased for the entire follow-up but became significant by the third year. A cross-comparison among incident endpoints HF outnumbers risk for those with MI by the sixth year (HRyear6.3 : 1.88, 95% CI = 1.03-3.43). There was no difference in mortality risk between incident HF and stroke. CONCLUSIONS: In patients with CCS, long-term rates of incident HF were higher than MI and stroke. Patients with new-onset HF showed a higher risk of long-term mortality.

Short-Course High-Intensity Statin Treatment during Admission for Myocardial Infarction and LDL-Cholesterol Reduction-Impact on Tailored Lipid-Lowering Therapy at Discharge.

We hypothesized that a short-course high-intensity statin treatment during admission for myocardial infarction (MI) could rapidly reduce LDL-C and thus impact the choice of lipid-lowering therapy (LLT) at discharge. Our cohort comprised 133 MI patients (62.71 ± 11.3 years, 82% male) treated with atorvastatin 80 mg o.d. during admission. Basal LDL-C levels before admission were analyzed. We compared lipid profile variables before and during admission, and LLT at discharge was registered. Achieved theoretical LDL-C levels were estimated using LDL-C during admission and basal LDL-C as references and compared to LDL-C on first blood sample 4-6 weeks after discharge. A significant reduction in cholesterol from basal levels was noted during admission, including total cholesterol, triglycerides, HDL-C, non-HDL-C, and LDL-C (-39.23 ± 34.89 mg/dL, p < 0.001). LDL-C levels were reduced by 30% in days 1-2 and 40-45% in subsequent days (R2 0.766, p < 0.001). Using LDL-C during admission as a reference, most patients (88.7%) would theoretically achieve an LDL-C < 55 mg/dL with discharge LLT. However, if basal LDL-C levels were considered as a reference, only a small proportion of patients (30.1%) would achieve this lipid target, aligned with the proportion of patients with LDL-C < 55 mg/dL 4-6 weeks after discharge (36.8%). We conclude that statin treatment during admission for MI can induce a significant reduction in LDL-C and LLT at discharge is usually prescribed using LDL-C during admission as the reference, which leads to insufficient LDL-C reduction after discharge. Basal LDL-C before admission should be considered as the reference value for tailored LLT prescription.

Residual ST-segment elevation to predict long-term clinical and CMR-derived outcomes in STEMI.

Residual ST-segment elevation after ST-segment elevation myocardial infarction (STEMI) has traditionally been considered a predictor of left ventricular (LV) dysfunction and ventricular aneurism. However, the implications in terms of long-term prognosis and cardiac magnetic resonance (CMR)-derived structural consequences are unclear. A total of 488 reperfused STEMI patients were prospectively included. The number of Q wave leads with residual ST-segment elevation > 1 mm (Q-STE) at pre-discharge ECG was assessed. LV ejection fraction (LVEF, %) and infarct size (IS, % of LV mass) were quantified in 319 patients at 6-month CMR. Major adverse cardiac events (MACE) were defined as all-cause death and/or re-admission for acute heart failure (HF), whichever occurred first. During a mean follow-up of 6.1 years, 92 MACE (18.9%), 39 deaths and 53 HF were recorded. After adjustment for baseline characteristics, Q-STE (per lead with > 1 mm) was independently associated with a higher risk of long-term MACE (HR 1.24 [1.07-1.44] per lead, p = 0.004), reduced (< 40%) LVEF (HR 1.36 [1.02-1.82] per lead, p = 0.04) and large (> 30% of LV mass) IS (HR 1.43 [1.11-1.85] per lead, p = 0.006) at 6-month CMR. Patients with Q-STE ≥ 2 leads (n = 172, 35.2%) displayed lower MACE-free survival, more depressed LVEF, and larger IS at 6-month CMR (p < 0.001 for all comparisons). Residual ST-segment elevation after STEMI represents a universally available tool that predicts worse long-term clinical and CMR-derived structural outcomes.

Meta-Analysis of Extracellular Matrix Dynamics after Myocardial Infarction Using RNA-Sequencing Transcriptomic Database.

Extracellular matrix (ECM) changes after myocardial infarction (MI) need precise regulation, and next-generation sequencing technologies provide omics data that can be used in this context. We performed a meta-analysis using RNA-sequencing transcriptomic datasets to identify genes involved in post-MI ECM turnover. Eight studies available in Gene Expression Omnibus were selected following the inclusion criteria. We compare RNA-sequencing data from 92 mice submitted to permanent coronary ligation or sham, identifying differentially expressed genes (p-value < 0.05 and Log2FoldChange ≥ 2). Functional enrichment analysis was performed based on Gene Ontology biological processes (BPs). BPs implicated in response to extracellular stimulus, regulation of ECM organization, and ECM disassembly were detected soon after ischemia onset. ECM disassembly occurred between days one to seven post-MI, compared with ECM assembly from day seven onwards. We identified altered mRNA expression of 19 matrix metalloproteinases and four tissue inhibitors of metalloproteinases at post-infarcted ECM remodeling and altered transcriptomic expression of 42 genes encoding 26 collagen subunits at the fibrotic stage. To our knowledge, this is the first meta-analysis using RNA-sequencing datasets to evaluate post-infarcted cardiac interstitium healing, revealing previously unknown mechanisms and molecules actively implicated in ECM remodeling post-MI, which warrant further validation.

Prognostic value of cardiac magnetic resonance early after ST-segment elevation myocardial infarction in older patients.

BACKGROUND: older patients with ST-segment elevation myocardial infarction (STEMI) represent a very high-risk population. Data on the prognostic value of cardiac magnetic resonance (CMR) in this scenario are scarce. METHODS: the registry comprised 247 STEMI patients over 70 years of age treated with percutaneous intervention and included in a multicenter registry. Baseline characteristics, echocardiographic parameters and CMR-derived left ventricular ejection fraction (LVEF, %), infarct size (% of left ventricular mass) and microvascular obstruction (MVO, number of segments) were prospectively collected. The additional prognostic power of CMR was assessed using adjusted C-statistic, net reclassification index (NRI) and integrated discrimination improvement index (IDI). RESULTS: during a 4.8-year mean follow-up, the number of first major adverse cardiac events (MACE) was 66 (26.7%): 27 all-cause deaths and 39 re-admissions for acute heart failure. Predictors of MACE were GRACE score (HR 1.03 [1.02-1.04], P < 0.001), CMR-LVEF (HR 0.97 [0.95-0.99] per percent increase, P = 0.006) and MVO (HR 1.24 [1.09-1.4] per segment, P = 0.001). Adding CMR data significantly improved MACE prediction compared to the model with baseline and echocardiographic characteristics (C-statistic 0.759 [0.694-0.824] vs. 0.685 [0.613-0.756], NRI = 0.6, IDI = 0.08, P < 0.001). The best cut-offs for independent variables were GRACE score > 155, LVEF < 40% and MVO ≥ 2 segments. A simple score (0, 1, 2, 3) based on the number of altered factors accurately predicted the MACE per 100 person-years: 0.78, 5.53, 11.51 and 78.79, respectively (P < 0.001). CONCLUSIONS: CMR data contribute valuable prognostic information in older patients submitted to undergo CMR soon after STEMI. The Older-STEMI-CMR score should be externally validated.

Fourier analysis of collagen bundle orientation in myocardial infarction scars.

Collagen bundle orientation (CBO) in myocardial infarct scars plays a major role in scar mechanics and complications after infarction. We aim to compare four histopathological methods for CBO measurement in myocardial scarring. Myocardial infarction was induced in 21 pigs by balloon coronary occlusion. Scar samples were obtained at 4 weeks, stained with Masson's trichrome, Picrosirius red, and Hematoxylin-Eosin (H&E), and photographed using light, polarized light microscopy, and confocal microscopy, respectively. Masson's trichrome images were also optimized to remove non-collagenous structures. Two observers measured CBO by means of a semi-automated, Fourier analysis protocol. Interrater reliability and comparability between techniques were studied by the intraclass correlation coefficient (ICC) and Bland-Altman (B&A) plots and limits of agreement. Fourier analysis showed an almost perfect interrater reliability for each technique (ICC ≥ 0.95, p < 0.001 in all cases). CBO showed more randomly oriented values in Masson's trichrome and worse comparability with other techniques (ICC vs. Picrosirius red: 0.79 [0.47-0.91], p = 0.001; vs. H&E-confocal: 0.70 [0.26-0.88], p = 0.005). However, optimized Masson's trichrome showed almost perfect agreement with Picrosirius red (ICC 0.84 [0.6-0.94], p < 0.001) and H&E-confocal (ICC 0.81 [0.54-0.92], p < 0.001), as well as these latter techniques between each other (ICC 0.84 [0.60-0.93], p < 0.001). In summary, a semi-automated, Fourier-based method can provide highly reproducible CBO measurements in four different histopathological techniques. Masson's trichrome tends to provide more randomly oriented CBO index values, probably due to non-specific visualization of non-collagenous structures. However, optimization of Masson's trichrome microphotographs to remove non-collagenous components provides an almost perfect comparability between this technique, Picrosirius red and H&E-confocal.

Sex Effect in the Decision to Perform Invasive Coronary Angiography in Patients With Chronic Coronary Syndrome After Undergoing Vasodilator Stress MRI.

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