Maternal and Neonatal Exposure to Environmental Tobacco Smoke Targets Pro-Inflammatory Genes in Neonatal Arteries

Maternal mainstream tobacco smoking is known to have adverse outcomes on fetal respiratory function; however, no data is currently available on the effects of passive exposure to tobacco smoking and environmental tobacco smoke (ETS) on fetal systemic arterial structure and function. Eight pregnant rhesus macaque monkeys were studied at the California Regional Primate Research Center breeding colony. The estimated gestational age for each dam was established by sonography performed before gestational day 40. Two inhalation chambers were used, each with an air capacity of 3.5 m3, and each housed two dams. Aged and diluted sidestream smoke was used as a surrogate for ETS. Exposure to ETS (1 mg/m3) occurred for 6 h/day, 5 days/week, beginning on gestational day 100. All dams were allowed to give birth spontaneously and then ETS exposure continued 70–80 days postnatally with the chamber containing both the mother and infant. Carotid arteries from four control (C) and four ETS-treated newborns were analyzed for mRNA by gene macroarray and for protein by Western blotting. A total of 588 cardiovascular genes were studied. Four genes were upregulated by ETS compared to C, and nine genes were downregulated (≥2-fold change). Three genes were selected for further study. Following ETS exposure, neonatal carotid arteries of non-human primates manifested evidence of inflammation with increased gene and protein expression of LFA-1 and RANTES, proteins that are recognized to be important in vascular adhesion and inflammation, and downregulation of expression for the receptor for VEGF, which has a key role in angiogenesis. Prenatal and postnatal exposure to ETS increases expression of pro-inflammatory genes and may be responsible for early arterial vascular remodeling that is predisposing to a subsequent vascular disease

Complete Revascularization of Stable STEMI Patients Offers a Significant Benefit if Done During the Index PCI, but Not if It\u27s Done as a Staged Procedure

Background: Complete revascularization (CR) of hemodynamically stable STEMI improves outcomes when compared to culprit-only PCI. However, the optimal timing for CR (CR during index PCI [iCR] versus staged PCI [sCR]) is unknown. sCR is defined as revascularization of non-culprit lesions not done during the index procedure (mean 31.5±24.6 days after STEMI). Our goal was to determine whether iCR was the superior strategy when compared to sCR. Methods: A systematic review of Medline, Cochrane, and Embase was performed for RCTs reporting outcomes of stable STEMI patients who had undergone CR. Only RCTs with a clearly defined timing of CR, for the classification into iCR and sCR, and a follow-up of at least 12 months were included. Seven RCTs comprising 6647 patients (mean age:62.9±1.4 years, male sex:79.4%) met these criteria and were included. Results: After a mean follow-up of 25.1±9.4 months, iCR was associated with a significant reduction in cardiovascular mortality (risk ratio [RR] 0.48, 95% confidence interval [CI] 0.26-0.90, p=0.02, relative risk reduction [RRR] 52%) and non-fatal reinfarctions (RR 0.42, 95% CI 0.25-0.70, p=0.001, RRR: 58%). sCR showed a significant reduction in non-fatal reinfarctions only (RR 0.68, 95% CI 0.54-0.85, p=0.0008, RRR: 32%). There was no difference in the safety outcome of contrast-induced nephropathy between groups. Conclusion: iCR of stable STEMI patients is associated with a significant reduction in cardiovascular death and a trend towards reduction in all-cause mortality. These benefits are not seen in sCR. Both strategies are associated with a reduction in non-fatal reinfarctions

Procedural and Mid-Term Outcomes of Coronary Protection During Transcatheter Aortic Valve Replacement in Patients at Risk of Coronary Occlusion: Insight From a Single-Centre Retrospective Analysis

BACKGROUND: Detailed procedural analysis and long-term data is limited for coronary protection (CP) during transcatheter aortic valve replacement (TAVR) for patients with high anatomical risk for coronary occlusion (CO). We aim to assess the procedural and mid-term outcomes of CP during TAVR. METHODS: We retrospectively analyzed patients who underwent TAVR at Henry Ford Hospital, USA from January 2015 to August 2019 and identified those considered at risk of CO and underwent pre-emptive CP with or without subsequent chimney stenting (i.e. coronary stenting with intentional protrusion into the aorta). Procedural features, immediate and mid-term clinical outcomes were reviewed. RESULTS: Twenty-five out of 1166 (2.1%) patients underwent TAVR with CP, including 10 (40%) valve-in-valve procedures. Twenty-eight coronary arteries (Left: n = 11, Right: n = 11; Left + Right: n = 3) were protected. Eleven coronaries (39.3%) were electively chimney -stented due to angiographic evidence of coronary impingement (63.6%), tactile resistance while withdrawing stent (27.3%) and electrocardiogram change (9.1%). Twenty-four patients (24/25, 96%) had successful TAVR without CO. Procedure-related complications included stent-balloon entrapment (n = 1), stent entrapment (n = 1) and occlusive distal stent edge dissection (n = 1). After a mean follow-up of 19.1 months, there was 1 cardiac death but no target vessel re-intervention or myocardial infarction. CONCLUSIONS: Our study found that angiographic evidence of coronary impingement (63.6%) was the most common reason for stent deployment during TAVR with CP. The mid-term clinical outcome of CP with TAVR was favorable

INITIAL EXPERIENCE WITH LITHOTRIPSY FOR MITRAL BALLOON VALVULOPLASTY

Background: Mitral annular calcification (MAC) causes degeneration of the mitral valve function. Since these patients are poor surgical candidates, options are limited to percutaneous solutions. Use of balloon lithotripsy (BL) to augment mitral balloon valvuloplasty (MBV) is a novel technique for treatment of MAC-related mitral stenosis (MS). Methods: Single-center retrospective review of 35 consecutive MBV for MAC cases at Henry Ford from 3/2013 to 4/2021. Outcome variables are reported as median and interquartile ranges (IQR). Chi-squared and Wilcoxon-signed rank tests were used to compare categorical and continuous variables respectively using 95% confidence intervals for statistical significance. Procedural success was defined as a final mitral valve area ≥1.5 cm2 or ≥50% reduction in gradient. Results: Of 35 MBV cases done for MAC, 5 utilized lithotripsy balloons to augment valvuloplasty results (Table). Mean baseline gradients were similar and right ventricular systolic pressures trended higher for BL cases. Cases utilizing lithotripsy were longer and utilized more fluoroscopy time but the final invasive gradient trended lower (non-BL 7mmHg [4, 9] vs. BL 1 mmHg [0,5] p=0.113), therefore, higher rates of procedural success were seen (non-BL 47% vs. BL 80%, p=0.2). Survival analysis was hampered due to loss of follow-up in the BL group. Conclusion: BL appears to augment immediate valvuloplasty results. Further studies regarding the durable impact of balloon lithotripsy on MBV are warranted

SURVIVAL OF PATIENTS WITH RHEUMATIC AND NON-RHEUMATIC MITRAL VALVE STENOSIS AFTER VALVULOPLASTY

Background: Non-rheumatic (NR) mitral stenosis (MS) due to mitral annular calcification (MAC) presents in elderly patients and is difficult to treat due elevated surgical risk. In search for alternative treatments, mitral balloon valvuloplasty (MBV) has been performed in non-rheumatic mitral stenosis but no outcomes have been described in this cohort. Methods: Single center retrospective review of 85 consecutive MBV cases at Henry Ford from 3/2013 to 4/2021. Clinical and procedural outcome variables are reported as median and interquartile ranges (IQR). Kaplan-Meier method was used to estimate survival. Chi-squared and Wilcoxon-signed rank tests were used to compare categorical and continuous variables respectively using 95% confidence intervals for statistical significance. Results: Of 85 MBV cases, 50 and 35 were performed for rheumatic (R) and NR MS respectively. NR patients tended to be older and were more likely to have hypertension, diabetes, coronary artery disease, chronic kidney disease, aortic valve procedures. Rates of ≥moderate-severe mitral regurgitation (MR) (R 18% vs. NR 12% p=0.4) and procedure success (R 57% vs NR 42.9% p=0.2) were similar. Median follow up for the entire cohort was 0.5 yrs [0.1, 2.1]. Survival was significantly better for rheumatic cases (Figure). Conclusion: Survival of NR MS post-valvuloplasty is significantly attenuated as compared to those with R MS. Larger prospective studies are necessary in understanding optimal bridging therapies for patients with MAC

Epithelial GPR35 protects from Citrobacter rodentium infection by preserving goblet cells and mucosal barrier integrity.

Goblet cells secrete mucin to create a protective mucus layer against invasive bacterial infection and are therefore essential for maintaining intestinal health. However, the molecular pathways that regulate goblet cell function remain largely unknown. Although GPR35 is highly expressed in colonic epithelial cells, its importance in promoting the epithelial barrier is unclear. In this study, we show that epithelial Gpr35 plays a critical role in goblet cell function. In mice, cell-type-specific deletion of Gpr35 in epithelial cells but not in macrophages results in goblet cell depletion and dysbiosis, rendering these animals more susceptible to Citrobacter rodentium infection. Mechanistically, scRNA-seq analysis indicates that signaling of epithelial Gpr35 is essential to maintain normal pyroptosis levels in goblet cells. Our work shows that the epithelial presence of Gpr35 is a critical element for the function of goblet cell-mediated symbiosis between host and microbiota

Sex differences in treatment strategy for coronary artery aneurysms: Insights from the international Coronary Artery Aneurysm Registry

INTRODUCTION: Sex disparities exist in coronary artery disease (CAD) in terms of risk profile, clinical management and outcome. It is unclear if differences are also present in coronary aneurysms, a rare variant of CAD. METHODS: Patients were selected from the international Coronary Artery Aneurysm Registry (CAAR; ClinicalTrials.gov: NCT02563626), and differences between groups were analysed according to sex. The CAAR database is a prospective multicentre registry of 1565 patients with coronary aneurysms (336 females). Kaplan-Meier method was used for event-free survival analysis for death, major adverse cardiac events (MACE: composite endpoint of death, heart failure and acute coronary syndrome) and bleeding. RESULTS: Female patients were older, were more often hypertensive and less frequently smoker. They were treated conservatively more often compared to male patients and received significantly less frequently aspirin (92% vs 88%, p = 0.002) or dual antiplatelet therapy (DAPT) (67% vs 58%, p = 0.001) at discharge. Median DAPT duration was also shorter (3 vs 9 months, p = 0.001). Kaplan-Meier analysis revealed no sex differences in death, MACE or bleeding during a median follow-up duration of 37 months, although male patients did experience acute coronary syndrome (ACS) more often during follow-up (15% vs 10%, p = 0.015). CONCLUSIONS: These CAAR findings showed a comparable high-risk cardiovascular risk profile for both sexes. Female patients were treated conservatively more often and received DAPT less often at discharge, with a shorter DAPT duration. ACS was more prevalent among male patients; however, overall clinical outcome was not different between male and female patients during follow-up

Additive Value of Preprocedural Computed Tomography Planning Versus Stand-Alone Transesophageal Echocardiogram Guidance to Left Atrial Appendage Occlusion: Comparison of Real-World Practice

Background: Transesophageal echocardiogram is currently the standard preprocedural imaging for left atrial appendage occlusion. This study aimed to assess the additive value of preprocedural computed tomography (CT) planning versus stand-alone transesophageal echocardiogram imaging guidance to left atrial appendage occlusion. Methods and Results: We retrospectively reviewed 485 Watchman implantations at a single center to compare the outcomes of using additional CT preprocedural planning (n=328, 67.6%) versus stand-alone transesophageal echocardiogram guidance (n=157, 32.4%) for left atrial appendage occlusion. The primary end point was the rate of successful device implantation without major peri-device leak (\u3e5 mm). Secondary end points included major adverse events, total procedural time, delivery sheath and devices used, risk of major peri-device leak and device-related thrombus at follow-up imaging. A single/anterior-curve delivery sheath was used more commonly in those who underwent CT imaging (35.9% versus 18.8%; P\u3c0.001). Additional preprocedural CT planning was associated with a significantly higher successful device implantation rate (98.5% versus 94.9%; P=0.02), a shorter procedural time (median, 45.5 minutes versus 51.0 minutes; P=0.03) and a less frequent change of device size (5.6% versus 12.1%; P=0.01), particularly device upsize (4% versus 9.4%; P=0.02). However, there was no significant difference in the risk of major adverse events (2.1% versus 1.9%; P=0.87). Only 1 significant peri-device leak (0.2%) and 5 device-related thrombi were detected in follow-up (1.2%) with no intergroup difference. Conclusions: Additional preprocedural planning using CT in Watchman implantation was associated with a higher successful device implantation rate, a shorter total procedural time, and a less frequent change of device sizes

Coordinated optimization of visual cortical maps (II) Numerical studies

It is an attractive hypothesis that the spatial structure of visual cortical architecture can be explained by the coordinated optimization of multiple visual cortical maps representing orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we defined a class of analytically tractable coordinated optimization models and solved representative examples in which a spatially complex organization of the orientation preference map is induced by inter-map interactions. We found that attractor solutions near symmetry breaking threshold predict a highly ordered map layout and require a substantial OD bias for OP pinwheel stabilization. Here we examine in numerical simulations whether such models exhibit biologically more realistic spatially irregular solutions at a finite distance from threshold and when transients towards attractor states are considered. We also examine whether model behavior qualitatively changes when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. Our numerical results support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the spatially irregular architecture of the visual cortex. We discuss several alternative scenarios and additional factors that may improve the agreement between model solutions and biological observations.Comment: 55 pages, 11 figures. arXiv admin note: substantial text overlap with arXiv:1102.335