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Skin represents the main barrier against the external environment, but also plays a role in human relations, as one of the prime determinants of beauty, resulting in a high consumer demand for skincare-related pharmaceutical products. Given the importance of skin aging in both medical and social spheres, the present research aims to characterize microscopic changes in human skin composition due to intrinsic aging (as opposed to aging influenced by external factors) via histological analysis of a photoprotected body region. Samples from 25 autopsies were taken from the periumbilical area and classified into four age groups: group 1 (0-12 years), group 2 (13-25 years), group 3 (26-54 years), and group 4 (≥ 55 years). Different traditional histological (hematoxylin-eosin, Masson's trichrome, orcein, toluidine, Alcian blue, and Feulgen reaction) and immunohistochemical (CK20, CD1a, Ki67, and CD31) stains were performed. A total of 1879 images photographed with a Leica DM3000 optical microscope were morphometrically analyzed using Image ProPlus 7.0 for further statistical analysis with GraphPad 9.0. Our results showed a reduction in epidermis thickness, interdigitation and mitotic indexes, while melanocyte count was raised. Papillary but not reticular dermis showed increased thickness with aging. Specifically, in the papillary layer mast cells and glycosaminoglycans were expanded, whereas the reticular dermis displayed a diminution in glycosaminoglycans and elastic fibers. Moreover, total cellularity and vascularization of both dermises were diminished with aging. This morphometric analysis of photoprotected areas reveals that intrinsic aging significantly influences human skin composition. This study paves the way for further research into the molecular basis underpinning these alterations, and into potential antiaging strategies.
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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.
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Cicatriz , Fibrosis , Infarto del Miocardio , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Infarto del Miocardio/genética , Animales , Ratones , Humanos , Cicatriz/metabolismo , Cicatriz/patología , Cicatriz/genética , Masculino , Miocardio/metabolismo , Miocardio/patología , Colágenos Fibrilares/metabolismo , Colágenos Fibrilares/genética , Femenino , Modelos Animales de Enfermedad , Colágeno/metabolismo , Persona de Mediana Edad , Ratones Endogámicos C57BLRESUMEN
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.
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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.
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Intervención Coronaria Percutánea , Daño por Reperfusión , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico , Infarto del Miocardio con Elevación del ST/cirugía , Infarto del Miocardio con Elevación del ST/etiología , Células Endoteliales , Imagen por Resonancia Magnética/métodos , Necrosis/etiología , Daño por Reperfusión/etiología , Intervención Coronaria Percutánea/efectos adversos , Resultado del TratamientoRESUMEN
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.
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Células Endoteliales , Infarto del Miocardio , Ratones , Animales , Células Endoteliales/metabolismo , Neovascularización Fisiológica/genética , Infarto del Miocardio/metabolismo , ARN/metabolismo , Análisis de Secuencia de ARNRESUMEN
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.
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Infarto del Miocardio , Remodelación Ventricular , Humanos , Femenino , Porcinos , Animales , Matriz Extracelular , Colágeno , PolisacáridosRESUMEN
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.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/complicaciones , Valor Predictivo de las Pruebas , Imagen por Resonancia Magnética , Corazón , Intervención Coronaria Percutánea/efectos adversos , Microcirculación , Remodelación VentricularRESUMEN
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.
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A non-neglectable percentage of patients with non-ST elevation myocardial infarction (NSTEMI) show non-obstructive coronary arteries (MINOCA). Specific data in older patients are scarce. We aimed to identify the clinical predictors of MINOCA in older patients admitted for NSTEMI and to explore the long-term prognosis of MINOCA. This was a single-center, observational, consecutive cohort study of older (≥70 years) patients admitted for NSTEMI between 2010 and 2014 who underwent coronary angiography. Univariate and multivariate Cox regression were performed to analyze the association of variables with MINOCA and all-cause mortality and with major adverse cardiac events (MACE), defined as a combined endpoint of all-cause mortality and nonfatal myocardial infarction and a combined endpoint of cardiovascular mortality, nonfatal myocardial infarction, and unplanned revascularization. The registry included 324 patients (mean age 78.8 ± 5.4 years), of which 71 (21.9%) were diagnosed with MINOCA. Predictors of MINOCA were female sex, left bundle branch block, pacemaker rhythm, chest pain at rest, peak troponin level, previous MI, Killip ≥2, and ST segment depression. Regarding prognosis, patients with obstructive coronary arteries (stenosis ≥50%) and the subgroup of MINOCA patients with plaques <50% had a similar prognosis; while MINOCA patients with angiographically smooth coronary arteries had a reduced risk of MACE. We conclude that the following: (1) in elderly patients admitted for NSTEMI, certain universally available clinical, electrocardiographic, and analytical variables are associated with the diagnosis of MINOCA; (2) elderly patients with MINOCA have a better prognosis than those with obstructive coronary arteries; however, only those with angiographically smooth coronary arteries have a reduced risk of all-cause mortality and MACE.
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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.
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Insuficiencia Cardíaca , Infarto del Miocardio , Infarto del Miocardio con Elevación del ST , Humanos , Anciano , Función Ventricular Izquierda , Volumen Sistólico , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/complicaciones , Medios de Contraste , Estudios Prospectivos , Readmisión del Paciente , Gadolinio , Imagen por Resonancia Magnética/métodos , Infarto del Miocardio/complicaciones , PronósticoRESUMEN
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.
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Insuficiencia Cardíaca , Infarto del Miocardio , Accidente Cerebrovascular , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Volumen Sistólico , Factores de Riesgo , Función Ventricular Izquierda , Infarto del Miocardio/complicacionesRESUMEN
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.
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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.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Disfunción Ventricular Izquierda , Humanos , Corazón , Volumen Sistólico , Imagen por Resonancia Magnética , Función Ventricular Izquierda , Espectroscopía de Resonancia Magnética , Pronóstico , Intervención Coronaria Percutánea/efectos adversos , Imagen por Resonancia Cinemagnética , Valor Predictivo de las PruebasRESUMEN
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.
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Infarto del Miocardio , Transcriptoma , Ratones , Animales , Infarto del Miocardio/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , ARN/metabolismo , Remodelación Ventricular/genética , Miocardio/metabolismoRESUMEN
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.
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Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Anciano , Anciano de 80 o más Años , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/terapia , Infarto del Miocardio con Elevación del ST/etiología , Volumen Sistólico , Pronóstico , Función Ventricular Izquierda , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Espectroscopía de Resonancia MagnéticaRESUMEN
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.
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Cicatriz , Infarto del Miocardio , Porcinos , Animales , Cicatriz/patología , Análisis de Fourier , Reproducibilidad de los Resultados , Colágeno/análisis , Infarto del Miocardio/patología , Hematoxilina , Eosina Amarillenta-(YS)RESUMEN
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.
Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Angiografía Coronaria/métodos , Vasodilatadores , Imagen de Perfusión Miocárdica/métodos , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Valor Predictivo de las PruebasRESUMEN
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.
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Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Anciano , Humanos , Imagen por Resonancia Cinemagnética , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Pronóstico , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) is the most accurate imaging technique for left ventricular ejection fraction (LVEF) quantification, but as yet the prognostic value of LVEF assessment at any time after ST-segment elevation myocardial infarction (STEMI) for subsequent major adverse cardiac event (MACE) prediction is uncertain. PURPOSE: To explore the prognostic impact of MRI-derived LVEF at any time post-STEMI to predict subsequent MACE (cardiovascular death or re-admission for acute heart failure). STUDY TYPE: Prospective. POPULATION: One thousand thirteen STEMI patients were included in a multicenter registry. 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: Post-infarction MRI-derived LVEF (reduced [r]: <40%; mid-range [mr]: 40%-49%; preserved [p]: ≥50%) was sequentially quantified at 1 week and after >3 months of follow-up. STATISTICAL TESTS: Multi-state Markov model to determine the prognostic value of each LVEF state (r-, mr- or p-) at any time point assessed to predict subsequent MACE. A P-value <0.05 was considered to be statistically significant. RESULTS: During a 6.2-year median follow-up, 105 MACE (10%) were registered. Transitions toward improved LVEF predominated and only r-LVEF (at any time assessed) was significantly related to a higher incidence of subsequent MACE. The observed transitions from r-LVEF, mr-LVEF, and p-LVEF states to MACE were: 15.3%, 6%, and 6.7%, respectively. Regarding the adjusted transition intensity ratios, patients in r-LVEF state were 4.52-fold more likely than those in mr-LVEF state and 5.01-fold more likely than those in p-LVEF state to move to MACE state. Nevertheless, no significant differences were found in transitions from mr-LVEF and p-LVEF states to MACE state (P-value = 0.6). DATA CONCLUSION: LVEF is an important MRI index for simple and dynamic post-STEMI risk stratification. Detection of r-LVEF by MRI at any time during follow-up identifies a subset of patients at high risk of subsequent events. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.
Asunto(s)
Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Medios de Contraste , Gadolinio , Humanos , Imagen por Resonancia Magnética/métodos , Imagen por Resonancia Cinemagnética/métodos , Espectroscopía de Resonancia Magnética , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Sistema de Registros , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/etiología , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
PURPOSE: Vasodilator stress cardiac magnetic resonance (VS-CMR) has become crucial in the workup of patients with known or suspected chronic coronary syndrome (CCS). Whether traditional exercise ECG testing (ExECG) contributes prognostic information beyond VS-CMR is unclear. METHODS: We retrospectively included 288 patients with known or suspected CCS who had undergone ExECG and subsequent VS-CMR in our institution. Clinical, ExECG, and VS-CMR variables were recorded. We defined the serious adverse events (SAE) as a combined endpoint of acute coronary syndrome, admission for heart failure, or all-cause death. RESULTS: During a mean follow-up of 4.2 ± 2.15 yr, we registered 27 SAE (15 admissions for acute coronary syndrome, eight admissions for heart failure, and four all-cause deaths). Once adjusted for clinical, ExECG, and VS-CMR parameters associated with SAE, the only independent predictors were HRmax in ExECG (HR = 0.98: 95% CI, 0.96-0.99; P = .01) and more extensive stress-induced perfusion defects (PDs, number of segments) in VS-CMR (HR = 1.19: 95% CI, 1.07-1.34; P < .01). Adding HRmax significantly improved the predictive power of the multivariable model for SAE, including PDs (continuous reclassification improvement index: 0.47: 95% CI, 0.10-0.81; P < .05). The annualized SAE rate was 1% (if PD < 2 segments and HRmax > 130 bpm), 2% (if PD < 2 segments and HRmax ≤ 130 bpm), 3.2% (if PD ≥ 2 segments and HRmax > 130 bpm), and 6.3% (if PD ≥ 2 segments and HRmax ≤ 130 bpm), P < .01, for the trend. In patients on ß-blocker therapy, however, only PDs in VS-CMR, but not HRmax, predicted SAE. CONCLUSIONS: We conclude that ExECG contributes significantly to prognostic information beyond VS-CMR in patients with known or suspected CCS.