RESUMO
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.
Assuntos
Envelhecimento , Pele , Humanos , Pessoa de Meia-Idade , Adulto , Adolescente , Adulto Jovem , Pele/metabolismo , Pele/química , Feminino , Masculino , Criança , Envelhecimento/patologia , Lactente , Pré-Escolar , Recém-Nascido , Envelhecimento da Pele , Idoso , Imuno-HistoquímicaRESUMO
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.
Assuntos
Cicatriz , Fibrose , Infarto do Miocárdio , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Animais , Camundongos , Humanos , Cicatriz/metabolismo , Cicatriz/patologia , Cicatriz/genética , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , Colágenos Fibrilares/metabolismo , Colágenos Fibrilares/genética , Feminino , Modelos Animais de Doenças , Colágeno/metabolismo , Pessoa de Meia-Idade , Camundongos Endogâmicos C57BLRESUMO
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.
Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Idoso , Função Ventricular Esquerda , Volume Sistólico , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Meios de Contraste , Estudos Prospectivos , Readmissão do Paciente , Gadolínio , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/complicações , PrognósticoRESUMO
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.
Assuntos
Células Endoteliais , Infarto do Miocárdio , Camundongos , Animais , Células Endoteliais/metabolismo , Neovascularização Fisiológica/genética , Infarto do Miocárdio/metabolismo , RNA/metabolismo , Análise de Sequência de RNARESUMO
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.
Assuntos
Cicatriz , Infarto do Miocárdio , Suínos , Animais , Cicatriz/patologia , Análise de Fourier , Reprodutibilidade dos Testes , Colágeno/análise , Infarto do Miocárdio/patologia , Hematoxilina , Amarelo de Eosina-(YS)RESUMO
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.
Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Angiografia Coronária/métodos , Vasodilatadores , Imagem de Perfusão do Miocárdio/métodos , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Valor Preditivo dos TestesRESUMO
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.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Meios de Contraste , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Volume Sistólico , Função Ventricular EsquerdaRESUMO
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.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Idoso , Idoso de 80 Anos ou mais , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Volume Sistólico , Prognóstico , Função Ventricular Esquerda , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Espectroscopia de Ressonância MagnéticaRESUMO
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.
Assuntos
Infarto do Miocárdio , Transcriptoma , Camundongos , Animais , Infarto do Miocárdio/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Perfilação da Expressão Gênica , RNA/metabolismo , Remodelação Ventricular/genética , Miocárdio/metabolismoRESUMO
The outbreak of severe acute respiratory syndrome coronavirus 2 that first emerged in Wuhan in December 2019 has resulted in the devastating pandemic of coronavirus disease 2019, creating an emerging need for knowledge sharing. Meanwhile, myocardial infarction is and will probably remain the foremost cause of death in the Western world throughout the coming decades. Severe deregulation of the immune system can unnecessarily expand the inflammatory response and participate in target and multiple organ failure, in infection but also in critical illness. Indeed, the course and fate of inflammatory cells observed in severe ST-elevation myocardial infarction (neutrophilia, monocytosis, and lymphopenia) almost perfectly mirror those recently reported in severe coronavirus disease 2019. A pleiotropic proinflammatory imbalance hampers adaptive immunity in favor of uncontrolled innate immunity and is associated with poorer structural and clinical outcomes. The goal of the present review is to gain greater insight into the cellular and molecular mechanisms underlying this canonical activation and downregulation of the two arms of the immune response in both entities, to better understand their pathophysiology and to open the door to innovative therapeutic options. Knowledge sharing can pave the way for therapies with the potential to significantly reduce mortality in both infectious and noninfectious scenarios.
Assuntos
COVID-19/imunologia , Sistema Imunitário/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , COVID-19/complicações , Humanos , Inflamação/etiologia , Inflamação/terapia , Infarto do Miocárdio/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/complicaçõesRESUMO
BACKGROUND: Following myocardial infarction (MI), we aimed to characterize morphometric and genetic changes in extracellular matrix (ECM) components from ischemia onset until late phases after coronary reperfusion in necrotic and salvaged myocardium. RESULTS: Swine were divided into one control (n = 5) and three MI groups: 90-min of ischemia without reperfusion, or followed by 1-week or 1-month reperfusion (n = 5 per group). In samples from the necrotic and salvaged areas, ECM components were morphometrically quantified and mRNA levels of factors involved in ECM remodeling were evaluated. After 90-min of ischemia, fibronectin, laminin, and elastic fibers content as well as upregulated mRNA expression of tissue inhibitors of metalloproteinases (TIMP)1, TIMP2, TIMP3 and connective tissue growth factor increased in the necrotic and salvaged myocardium. In both reperfused MI groups, collagen-I, collagen-III, elastic fibers, glycosaminoglycans, laminin, and fibronectin levels heightened in the necrotic but not the salvaged myocardium. Moreover, mRNA expression of TIMP1, TIMP2 and TIMP3, as well as metalloproteinase-2 and metalloproteinase-9 heightened in the necrotic but not in the salvaged myocardium. CONCLUSIONS: Matrix remodeling starts after ischemia onset in both necrotic and salvaged myocardium. Even if ECM composition from the salvaged myocardium was altered after severe ischemia, ECM makes a full recovery to normal composition after reperfusion. Therefore, rapid coronary reperfusion is essential not only to save cardiomyocytes but also to preserve matrix, thus avoiding impaired left ventricular remodeling.
Assuntos
Matriz Extracelular/patologia , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica , Animais , Colágeno/metabolismo , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Feminino , Modelos Animais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sus scrofa , Inibidores Teciduais de Metaloproteinases/metabolismo , Remodelação Ventricular/fisiologiaRESUMO
Purpose To characterize the incidence, outcomes, and predictors of left ventricular (LV) thrombus by using sequential cardiac magnetic resonance (MR) imaging after ST-segment-elevation myocardial infarction (STEMI). Materials and Methods Written informed consent was obtained from all patients, and the study protocol was approved by the committee on human research. In a cohort of 772 patients with STEMI, 392 (mean age, 58 years; range, 24-89 years) were retrospectively selected who were studied with cardiac MR imaging at 1 week and 6 months. Cardiac MR imaging guided the initiation and withdrawal of anticoagulants. Patients with LV thrombus at 6 months were restudied at 1 year. For predicting the occurrence of LV thrombus, a multiple regression model was applied. Results LV thrombus was detected in 27 of 392 patients (7%): 18 (5%) at 1 week and nine (2%) at 6 months. LV thrombus resolved in 22 of 25 patients (88%) restudied within the first year. During a mean follow-up of 181 weeks ± 168, patients with LV thrombus displayed a very low rate of stroke (0%), peripheral embolism (0%), and severe hemorrhage (n = 1, 3.7%). LV ejection fraction (LVEF) less than 50% (P < .001) and anterior infarction (P = .008) independently helped predict LV thrombus. The incidence of LV thrombus was as follows: (a) nonanterior infarction, LVEF 50% or greater (one of 135, 1%); (b) nonanterior infarction, LVEF less than 50% (one of 50, 2%); (c) anterior infarction, LVEF 50% or greater (two of 92, 2%); and (d) anterior infarction, LVEF less than 50% (23 of 115, 20%) (P < .001 for the trend). Conclusion Cardiac MR imaging contributes information for the diagnosis and therapy of LV thrombus after STEMI. Patients with simultaneous anterior infarction and LVEF less than 50% are at highest risk. © RSNA, 2017 Online supplemental material is available for this article.
Assuntos
Trombose Coronária/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Adulto , Idoso , Trombose Coronária/epidemiologia , Trombose Coronária/terapia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do TratamentoRESUMO
PURPOSE: To assess predictors of reverse remodeling by using cardiac magnetic resonance (MR) imaging soon after ST-segment-elevation myocardial infarction (STEMI). MATERIALS AND METHODS: Written informed consent was obtained from all patients, and the study protocol was approved by the institutional committee on human research, ensuring that it conformed to the ethical guidelines of the 1975 Declaration of Helsinki. Five hundred seven patients (mean age, 58 years; age range, 24-89 years) with a first STEMI were prospectively studied. Infarct size and microvascular obstruction (MVO) were quantified at late gadolinium-enhanced imaging. Reverse remodeling was defined as a decrease in left ventricular (LV) end-systolic volume index (LVESVI) of more than 10% from 1 week to 6 months after STEMI. For statistical analysis, a simple (from a clinical perspective) multiple regression model preanalyzing infarct size and MVO were applied via univariate receiver operating characteristic techniques. RESULTS: Patients with reverse remodeling (n = 211, 42%) had a lesser extent (percentage of LV mass) of 1-week infarct size (mean ± standard deviation: 18% ± 13 vs 23% ± 14) and MVO (median, 0% vs 0%; interquartile range, 0%-1% vs 0%-4%) than those without reverse remodeling (n = 296, 58%) (P < .001 in pairwise comparisons). The independent predictors of reverse remodeling were infarct size (odds ratio, 0.98; 95% confidence interval [CI]: 0.97, 0.99; P = .04) and MVO (odds ratio, 0.92; 95% CI: 0.86, 0.99; P = .03). Once infarct size and MVO were dichotomized by using univariate receiver operating characteristic techniques, the only independent predictor of reverse remodeling was the presence of simultaneous nonextensive infarct-size MVO (infarct size < 30% of LV mass and MVO < 2.5% of LV mass) (odds ratio, 3.2; 95% CI: 1.8, 5.7; P < .001). CONCLUSION: Assessment of infarct size and MVO with cardiac MR imaging soon after STEMI enables one to make a decision in the prediction of reverse remodeling.
Assuntos
Técnicas de Imagem de Sincronização Cardíaca/métodos , Imageamento por Ressonância Magnética/métodos , Infarto do Miocárdio/patologia , Remodelação Ventricular , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares , Valor Preditivo dos Testes , Estudos Prospectivos , Sistema de Registros , TransativadoresRESUMO
We aimed to characterize the organization of collagen within a fibrotic scar in swine and human samples from patients with chronic infarctions. Swine were subjected to occlusion of the left anterior descending artery followed by reperfusion 1 week (acute myocardial infarction group) or 1 month (chronic myocardial infarction group) after infarction. The organization of the collagen fibers (Fast Fourier Transform of samples after picrosirius staining; higher values indicate more disorganization) was studied in 100 swine and 95 human samples. No differences in collagen organization were found between the acute and chronic groups in the core area of the scar in the experimental model. In the chronic group, the endocardium [0.90 (0.84-0.94); median (interquartile range)], epicardium [0.84 (0.79-0.91)] and peripheral area [0.73 (0.63-0.83)] displayed a much more disorganized pattern than the core area of the fibrotic scar [0.56 (0.45-0.64)]. Similarly, in human samples, the collagen fibers were more disorganized in all of the outer areas than in the core of the fibrotic scar (P < 0.0001). Both in a highly controlled experimental model and in patient samples, collagen fibers exhibited an organized pattern in the core of the infarction, whereas the outer areas displayed a high level of inhomogeneity. This finding contributes pathophysiological information regarding the healing process and may lead to a clearer understanding of the genesis and invasive treatment of arrhythmias after acute myocardial infarction.
Assuntos
Cicatriz/patologia , Colágeno/análise , Vasos Coronários/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suínos , CicatrizaçãoRESUMO
PURPOSE: The aim of this study was to establish reference values for segmental myocardial strain measured by magnetic resonance (MR) cardiac tagging in order to characterize the regional function of the heart. MATERIAL AND METHODS: We characterized the left ventricular (LV) systolic deformation in 39 subjects (26 women and 13 men, age 58.8 ± 11.6 years) whose cardiological study had not revealed any significant abnormality. The deformation was measured from MR-tagged (Siemens 1.5T MR) images using an algorithm based on sine wave modeling. Circumferential and radial peak systolic strain values along with the torsion angle and circumferential-longitudinal (CL) shear were determined in 16 LV segments in order to settle the reference values for these parameters. RESULTS: Circumferential strain was highest at the anterior and lateral walls (-20.2 ± 4.0% and -21.8 ± 4.3%, respectively; P < 0.05) and was lowest at the base level (-17.2 ± 3.1% vs. -20.1 ± 3.1% "mid level," P < 0.05; -17.2 ± 3.1% vs. -20.3 ± 3.0% "apical level," P < 0.05). Radial strain highest values were from inferior and lateral walls (13.7 ± 7.4% and 12.8 ± 7.8%, respectively; P < 0.05) and it was lowest medially (9.4 ± 4.1% vs. 13.1 ± 4.1% "base level," P < 0.05; 9.4 ± 4.1% vs. 12.1 ± 4.4% "apical level," P < 0.05). Torsion angle (counterclockwise when viewed from the apex) increased with the distance from the base (7.9 ± 2.4° vs. 16.8 ± 4.4°, P < 0.05), and the highest and lowest values were found at lateral (medial lateral: 12.0 ± 4.4°, apical lateral: 25.1 ± 6.4°, P < 0.05) and septal wall (medial septal: 3.6 ± 2.1°, apical septal: 8.3 ± 5.3°, P < 0.05), respectively. These differences were found again in CL shear values, around the LV circumference. However, CL shear remained constant with increasing distance from the base (9.1 ± 2.6°, medium and 9.8 ± 2.4°, apex). CONCLUSION: In summary, this study provides reference values for the assessment of regional myocardial function by MR cardiac tagging. Comparison of patient deformation parameters with normal deformation patterns may permit early detection of regional systolic dysfunction.
Assuntos
Coração/fisiologia , Imageamento por Ressonância Magnética/métodos , Diástole/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Valores de Referência , Reprodutibilidade dos Testes , Função Ventricular/fisiologia , Função Ventricular Esquerda/fisiologiaRESUMO
The benefits of cardiac imaging are immense, and modern medicine requires the extensive and versatile use of a variety of cardiac imaging techniques. Cardiologists are responsible for a large part of the radiation exposures every person gets per year from all medical sources. Therefore, they have a particular responsibility to avoid unjustified and non-optimized use of radiation, but sometimes are imperfectly aware of the radiological dose of the examination they prescribe or practice. This position paper aims to summarize the current knowledge on radiation effective doses (and risks) related to cardiac imaging procedures. We have reviewed the literature on radiation doses, which can range from the equivalent of 1-60 milliSievert (mSv) around a reference dose average of 15 mSv (corresponding to 750 chest X-rays) for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multidetector coronary angiography, or a myocardial perfusion imaging scintigraphy. We provide a European perspective on the best way to play an active role in implementing into clinical practice the key principle of radiation protection that: 'each patient should get the right imaging exam, at the right time, with the right radiation dose'.
Assuntos
Técnicas de Imagem Cardíaca/efeitos adversos , Cardiopatias/diagnóstico por imagem , Doses de Radiação , Cardiologia , Criança , Feminino , Cardiopatias/terapia , Humanos , Consentimento Livre e Esclarecido , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/prevenção & controle , Gravidez , Complicações na Gravidez/etiologia , Diagnóstico Pré-Natal/efeitos adversos , Lesões por Radiação/etiologia , Proteção Radiológica/métodos , Proteção Radiológica/normas , Fatores de Risco , Tomografia Computadorizada por Raios X/efeitos adversos , Procedimentos DesnecessáriosRESUMO
BACKGROUND: In patients with ST-segment elevation myocardial infarction (STEMI) reperfused with primary coronary intervention (PCI), the dynamics of endothelial cell (EC) viability, apoptosis and necrosis and its relationship with the structural consequences on the left ventricle have not been addressed so far. DESIGN: In 20 STEMI patients, we incubated human umbilical vein endothelial cells (HUVECs) with serum drawn before reperfusion and subsequently afterwards (24, 96 h, 30 days). Viability, apoptosis and necrosis percentages were evaluated by flow cytometry. Values were compared with 12 age- and sex-matched control subjects with normal coronary arteries. Cardiac magnetic resonance (CMR) was performed during the first week after infarction. RESULTS: Serum from STEMI patients induced a progressive loss of EC viability, with a nadir of 67.7 ± 10.2% at 96 h (baseline: 75 ± 6% and controls: 80.2 ± 3.9%, P < 0.001 in both cases). This is due to an increase in apoptosis that peaked at 96 h after reperfusion (15.2 ± 7.1% vs. 11 ± 6 at baseline and 5.8 ± 1.6% in controls, P < 0.001 in both cases). However, no significant dynamic changes in EC necrosis were detected. Extensive myocardial oedema (> 30%, median of left ventricular mass) was the only CMR variable significantly associated with a higher percentage of EC apoptosis at 96 h (extensive vs. nonextensive oedema: 18.3 ± 6.8% vs. 12.1 ± 6.3%, P < 0.05). CONCLUSIONS: Dynamic changes in EC viability occur in the setting of STEMI patients reperfused with PCI, these changes peak late after reperfusion, they are mainly the result of an increase of apoptosis and are associated with the presence of extensive myocardial oedema.
Assuntos
Apoptose/fisiologia , Células Endoteliais/fisiologia , Infarto do Miocárdio/fisiopatologia , Soro/fisiologia , Idoso , Idoso de 80 Anos ou mais , Técnicas de Imagem Cardíaca , Estudos de Casos e Controles , Sobrevivência Celular/fisiologia , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/terapia , Necrose/fisiopatologia , Intervenção Coronária PercutâneaRESUMO
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.
Assuntos
Intervenção Coronária Percutânea , Traumatismo por Reperfusão , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Células Endoteliais , Imageamento por Ressonância Magnética/métodos , Necrose/etiologia , Traumatismo por Reperfusão/etiologia , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
Aims: Recently, novel post-processing tools have become available that measure intraventricular pressure gradients (IVPGs) on routinely obtained long-axis cine cardiac magnetic resonance (CMR) images. IVPGs provide a comprehensive overview of both systolic and diastolic left ventricular (LV) functions. Whether IVPGs are associated with clinical outcome after ST-elevation myocardial infarction (STEMI) is currently unknown. Here, we investigated the association between CMR-derived LV-IVPGs and major adverse cardiovascular events (MACE) in a large reperfused STEMI cohort with long-term outcome. Methods and results: In this prospectively enrolled multi-centre cohort study, 307 patients underwent CMR within 14 days after the first STEMI. LV-IVPGs (from apex-to-base) were estimated on the long-axis cine images. During a median follow-up of 9.7 (5.9-12.5) years, MACE (i.e. composite of cardiovascular death and de novo heart failure hospitalisation) occurred in 49 patients (16.0%). These patients had larger infarcts, more often microvascular injury, and impaired LV-IVPGs. In univariable Cox regression, overall LV-IVPG was significantly associated with MACE and remained significantly associated after adjustment for common clinical risk factors (hazard ratio (HR) 0.873, 95% confidence interval (CI) 0.794-0.961, P = 0.005) and myocardial injury parameters (HR 0.906, 95% CI 0.825-0.995, P = 0.038). However, adjusted for LV ejection fraction and LV global longitudinal strain (GLS), overall LV-IVPG does not provide additional prognostic information (HR 0.959, 95% CI 0.866-1.063, P = 0.426). Conclusion: Early after STEMI, CMR-derived LV-IVPGs are univariably associated with MACE and this association remains significant after adjustment for common clinical risk factors and measures of infarct severity. However, LV-IVPGs do not add prognostic value to LV ejection fraction and LV GLS.
RESUMO
Background/Objectives: Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods: One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results: Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91-0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26-2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02-1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19-2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84-0.95; p < 0.001). Conclusions: Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders.