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
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
Purkinje cells (PCs) are more resistant to ischemia than myocardial cells, and are suspected to participate in ventricular arrhythmias following myocardial infarction (MI). Histological studies ...afford little evidence on the behavior and adaptation of PCs in the different stages of MI, especially in the chronic stage, and no quantitative data have been reported to date beyond subjective qualitative depictions. The present study uses a porcine model to present the first quantitative analysis of the distal cardiac conduction system and the first reported change in the spatial distribution of PCs in three representative stages of MI: an acute model both with and without reperfusion; a subacute model one week after reperfusion; and a chronic model one month after reperfusion. Purkinje cells are able to survive after 90 minutes of ischemia and subsequent reperfusion to a greater extent than cardiomyocytes. A decrease is observed in the number of PCs, which suffer reversible subcellular alterations such as cytoplasm vacuolization, together with redistribution from the mesocardium-the main localization of PCs in the heart of ungulate species-towards the endocardium and perivascular epicardial areas. However, these changes mainly occur during the first week after ischemia and reperfusion, and are maintained in the chronic stages. This anatomical substrate can explain the effectiveness of endo-epicardial catheter ablation of monomorphic ventricular tachycardias in the chronic scar after infarction, and sets a basis for further electrophysiological and molecular studies, and future therapeutic strategies.
Cardiovascular diseases and oxidative stress are related to polycystic ovary syndrome (PCOS) and insulin resistance (IR). We have evaluated the relationship between myeloperoxidase (MPO) and ...leukocyte activation in PCOS patients according to homeostatic model assessment of IR (HOMA-IR), and have explored a possible correlation between these factors and endocrine and inflammatory parameters. This was a prospective controlled study conducted in an academic medical center. The study population consisted of 101 PCOS subjects and 105 control subjects. We divided PCOS subjects into PCOS non-IR (HOMA-IR<2.5) and PCOS IR (HOMA-IR>2.5). Metabolic and anthropometric parameters, total and mitochondrial reactive oxygen species (ROS) production, MPO levels, interactions between human umbilical vein endothelial cells and leukocytes, adhesion molecules (E-selectin, ICAM-1 and VCAM-1) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. Oxidative stress was observed in PCOS patients, in whom there was an increase in total and mitochondrial ROS production and MPO levels. Enhanced rolling flux and adhesion, and a decrease in polymorphonuclear cell rolling velocity were also detected in PCOS subjects. Increases in IL-6 and TNF-α and adhesion molecules (E-selectin, ICAM-1 and VCAM-1) were also observed, particularly in the PCOS IR group, providing evidence that inflammation and oxidative stress are related in PCOS patients. HOMA-IR was positively correlated with hsCRP (p<0.001, r = 0.304), ROS production (p<0.01, r = 0.593), leukocyte rolling flux (p<0.05, r = 0.446), E-selectin (p<0.01, r = 0.436) and IL-6 (p<0.001, r = 0.443). The results show an increase in the rate of ROS and MPO levels in PCOS patients in general, and particularly in those with IR. Inflammation in PCOS induces leukocyte-endothelium interactions and a simultaneous increase in IL-6, TNF-α, E-selectin, ICAM-1 and VCAM-1. These conditions are aggravated by the presence of IR.
Abstract 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.
Enhanced leukocyte recruitment is an inflammatory process that occurs during early phases of the vascular dysfunction that characterises atherosclerosis. We evaluated the impact of anti-TNF-α ...(adalimumab, infliximab and etanercept) and anti-IL-12/23 (ustekinumab) on interactions between human leukocytes and endothelial cells in a flow chamber that reproduced in vivo conditions. Clinical concentrations of anti-TNF-α were evaluated on the leukocyte recruitment induced by a variety of endothelial (TNF-α, interleukin-1β, lymphotoxin-α and angiotensin-II) and leukocyte (PAF, IL-12 and IL-23) stimuli related to inflammation and atherosclerosis. Treatment with anti-TNF-α, even before or after establishing the inflammatory situation induced by TNF-α, diminished leukocyte–endothelial cell interactions induced by this stimuli. Our results also implicated adhesion molecules (ICAM-1, VCAM-1 and E-selectin) in the actions of anti-TNF-α in terms of leukocyte adhesion to endothelium. However, anti-TNF-α drugs did not influence the actions of interleukin-1β, but prevented those of lymphotoxin-α and angiotensin-II. However, once established, inflammatory response elicited by the latter three stimuli could not be reversed. Pre-treatment with anti-TNF-α, also prevented leukocyte actions induced by IL-23 on PBMC rolling flux and rolling velocity and by IL-12 on PMN adhesion. Ustekinumab exhibited a more discreet profile, having no effect on leukocyte recruitment induced by any of the endothelial stimuli, while blocking the effects of IL-23 on leukocyte activation and those of IL-12 on PMN adhesion and PAF on PBMC rolling velocity. These findings endorse the idea that biological anti-inflammatory drugs, in particular anti-TNF-α, have the capacity to influence cardiovascular risk accompanying psoriasis and rheumatoid arthritis by ameliorating vascular inflammation.
•Uncontrolled immune response after STEMI correlates with deleterious cardiac events.•Genes involved in lymphocyte activation and regulation are altered following STEMI.•Overexpression of immune ...checkpoints correlates with reduced infarct size.•Exploring therapies aimed at these checkpoints would be very useful in the future.•Increased CD25 expression is associated with better cardiac structure and function.
Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest.
Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months. mRNA expression of genes implicated in lymphocyte activation (CD25 and CD69) and regulation programmed death (PD)-1 and cytotoxic T-lymphocyte antigen (CTLA)-4 were determined by qRT-PCR.
In comparison to controls, STEMI patients showed heightened mRNA expression of CD25 and lower PD-1 and CTLA-4 96 h after coronary reperfusion. Patients with extensive infarctions (>30% of left ventricular mass) at 1 week displayed a notable reduction in CD25, CD69, PD-1, and CTLA-4 expression (p < 0.05). However, CD25 was the only predictor of 1-week extensive infarct size in multivariate logistic regression analysis (odds ratio 0.019; 95% confidence interval 0.001–0.505; p = 0.018). Regarding long-term ventricular function, mRNA expression of CD25 under the mean value was associated with worse ventricular function and more adverse remodelling.
Following STEMI, heightened expression of genes expressed in regulatory T cells (CD25 and CD69) and immune checkpoints (PD-1 and CTLA-4) correlates with a better short- and long-term cardiac structure and function. Advancing understanding of the pathophysiology of lymphopenia and evaluating novel immunomodulatory therapies will help translate these results into future clinical trials.
Reliable noninvasive prognostic biomarkers for left ventricular (LV) remodeling in ST-segment elevation myocardial infarction (STEMI) are needed. This study aimed to evaluate a panel of circulating ...microRNAs (miRNAs) as biomarkers of LV remodeling using cardiovascular magnetic resonance (CMR). We prospectively evaluated patients with a first STEMI treated with primary percutaneous coronary intervention who underwent CMR imaging at 1 week and 6 months after STEMI (n = 70). miRNAs were measured using PCR-based technologies in plasma samples collected at admission. The associations between miRNAs and LV diastolic and systolic volumes, and ejection fraction at 6-months were estimated in adjusted models. Median age was 60 years, 71.4% were male. miR-1254 was significantly associated in univariate analyses. Patients in the highest tertile of miR-1254 exhibited lower values of LVEDVI and LVESVI and higher values of LVEF at 1 week. After comprehensive multivariate adjustment including clinical, CMR variables, hs-troponin-T and NT-proBNP, miRNA-1254 was associated with decreasing LVESVI (P = 0.006), and borderline negative associated with LVEDVI (P = 0.063) at 6-months. miR-1254 also exhibited a significant positive association with increasing LVEF during follow-up (P < 0.001). Plasma miRNA-1254 predicted changes in LV volumes and LVEF at 6 months after STEMI. The value of miR-1254 to inform tailored treatment selection and monitor ongoing efficacy deserves further investigation.
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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