Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes.

OBJECTIVES: The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND: Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS: The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS: Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.info:eu-repo/semantics/publishedVersio

Habitual physical activity levels in women attending the one stop infertility clinic: A prospective cross-sectional observational study.

Optimisation of lifestyle factors such as smoking and alcohol are encouraged to improve fecundability rates in the fertility setting. Currently, routine fertility consultations do not involve counselling or imparting advice regarding habitual physical activity (PA) and/or structured exercise, despite data showing that vigorous PA can be associated with delayed time to pregnancy. Therefore, this study aimed to determine habitual PA in a sample of women attending the one stop infertility (OSI) clinic. 250 women attending a large tertiary level NHS fertility unit prospectively anonymously completed a questionnaire over a period of 9 months. Participant's (mean age 34±5years, mean BMI 29±7kg/m2) habitual PA levels varied from vigorous exercise on ≥5 days/week (8%, n=17), to no moderate or high intensity activities across the whole week (66%, n=29). The majority of women reported no structured exercise (72%, n=179). No association was identified between any domain of PA and BMI, age, alcohol units, regular periods, or time spent trying to conceive (P > 0.05). Participant's habitual PA levels varied widely and no association between any domain of PA and background of the women was identified. No existing evidence and/or guidelines to explicitly inform women attempting to conceive regarding recommended PA levels are available, despite PA being a modifiable, affordable, and feasible lifestyle choice with the possible potential to improve fertility. A large-scale, clinical trial assessing effects of PA on fecundability is warranted to gain insights into the potential of this lifestyle factor to improve fertility outcomes and to explore the underlying biological mechanisms involved

Abnormally located SSEA1+/SOX9+ endometrial epithelial cells with a basalis-like phenotype in the eutopic functionalis layer may play a role in the pathogenesis of endometriosis

STUDY QUESTION:Is endometriosis associated with abnormally located endometrial basalis-like (SSEA1+/SOX9+) cells in the secretory phase functionalis and could they contribute to ectopic endometriotic lesion formation? SUMMARY ANSWER:Women with endometriosis had an abnormally higher number of basalis-like SSEA1+/SOX9+ epithelial cells present in the stratum functionalis and, since these cells formed 3D structures in vitro with phenotypic similarities to ectopic endometriotic lesions, they may generate ectopic lesions following retrograde menstruation. WHAT IS KNOWN ALREADY:Endometrial basalis cells with progenitor potential are postulated to play a role in the pathogenesis of endometriosis and SSEA1 and nuclear SOX9 (nSOX9) mark basalis epithelial cells that also have some adenogenic properties in vitro. Induction of ectopic endometriotic lesions in a baboon model of endometriosis produces characteristic changes in the eutopic endometrium. Retrograde menstruation of endometrial basalis cells is proposed to play a role in the pathogenesis of endometriosis. STUDY DESIGN, SIZE, DURATION:This prospective study included endometrial samples from 102 women with and without endometriosis undergoing gynaecological surgery and from six baboons before and after induction of endometriosis, with in vitro assays examining the differentiation potential of human basalis-like cells. PARTICIPANTS/MATERIALS, SETTING, METHODS:The study was conducted at a University Research Institute. SSEA1 and SOX9 expression levels were examined in human endometrial samples from women aged 18-55 years (by immunohistochemistry (IHC) and qPCR) and from baboons (IHC). The differential gene expression and differentiation potential was assessed in freshly isolated SSEA1+ endometrial epithelial cells from women with and without endometriosis (n = 8/group) in vitro. In silico analysis of selected published microarray datasets identified differential regulation of genes of interest for the mid-secretory phase endometrium of women with endometriosis relative to that of healthy women without endometriosis. MAIN RESULTS AND THE ROLE OF CHANCE:Women with endometriosis demonstrated higher number of basalis-like cells (SSEA1+, nSOX9+) in the functionalis layer of the eutopic endometrium compared with the healthy women without endometriosis in the secretory phase of the cycle (P < 0.05). Induction of endometriosis resulted in a similar increase in basalis-like epithelial cells in the eutopic baboon endometrium. The isolated SSEA1+ epithelial cells from the eutopic endometrium of women with endometriosis had higher expression of OCT4, NANOG, FUT4 mRNA (P = 0.05, P = 0.007, P = 0.018, respectively) and they differentiated into ectopic endometriotic gland-like structures in 3D culture, but not into mesodermal lineages (adipose or bone cells). LARGE SCALE DATA:N/A. LIMITATIONS, REASONS FOR CAUTION:Small sample size. Bioinformatics analysis and results depends on the quality of published microarray datasets and the stringency of patient selection criteria employed. Differentiation of SSEA-1+ cells was only examined for two mesodermal lineages (adipogenic and osteogenic). WIDER IMPLICATIONS OF THE FINDINGS:Since endometrial epithelial cells with SSEA1+/nSOX9+ basalis-like phenotype generate endometriotic gland-like structures in vitro, they may potentially be a therapeutic target for endometriosis. An in depth analysis of the function of basalis-like eutopic endometrial epithelial cells might provide insights into their potential deregulation in other disorders of the endometrium including heavy menstrual bleeding and endometrial cancer where their function may be aberrant. STUDY FUNDING/COMPETING INTEREST(S):We acknowledge the support by Wellbeing of Women project grant RG1073 (D.K.H., C.E.G.) and R01 HD083273 from the National Institutes of Health (A.T.F.). We also acknowledge the support of Liverpool Women's Hospital Foundation Trust (J.D.), Institute of Translational Medicine (L.D.S., H.A.L., A.J.V., D.K.H.), University of Liverpool, the National Health and Medical Research Council of Australia ID 1042298 (C.E.G.) and the Victorian Government Operational Infrastructure Support Fund. All authors declare no conflict of interest

Coronary flow reserve and cardiovascular outcomes: a systematic review and meta-analysis.

AIMS: This meta-analysis aims to quantify the association of reduced coronary flow with all-cause mortality and major adverse cardiovascular events (MACE) across a broad range of patient groups and pathologies. METHODS AND RESULTS: We systematically identified all studies between 1 January 2000 and 1 August 2020, where coronary flow was measured and clinical outcomes were reported. The endpoints were all-cause mortality and MACE. Estimates of effect were calculated from published hazard ratios (HRs) using a random-effects model. Seventy-nine studies with a total of 59 740 subjects were included. Abnormal coronary flow reserve (CFR) was associated with a higher incidence of all-cause mortality [HR: 3.78, 95% confidence interval (CI): 2.39-5.97] and a higher incidence of MACE (HR 3.42, 95% CI: 2.92-3.99). Each 0.1 unit reduction in CFR was associated with a proportional increase in mortality (per 0.1 CFR unit HR: 1.16, 95% CI: 1.04-1.29) and MACE (per 0.1 CFR unit HR: 1.08, 95% CI: 1.04-1.11). In patients with isolated coronary microvascular dysfunction, an abnormal CFR was associated with a higher incidence of mortality (HR: 5.44, 95% CI: 3.78-7.83) and MACE (HR: 3.56, 95% CI: 2.14-5.90). Abnormal CFR was also associated with a higher incidence of MACE in patients with acute coronary syndromes (HR: 3.76, 95% CI: 2.35-6.00), heart failure (HR: 6.38, 95% CI: 1.95-20.90), heart transplant (HR: 3.32, 95% CI: 2.34-4.71), and diabetes mellitus (HR: 7.47, 95% CI: 3.37-16.55). CONCLUSION: Reduced coronary flow is strongly associated with increased risk of all-cause mortality and MACE across a wide range of pathological processes. This finding supports recent recommendations that coronary flow should be measured more routinely in clinical practice, to target aggressive vascular risk modification for individuals at higher risk

Management of Acute Coronary Syndromes During the Coronavirus Disease 2019 Pandemic: Deviations from Guidelines and Pragmatic Considerations for Patients and Healthcare Workers

Coronavirus disease 2019 (COVID-19) is forcing cardiology departments to rapidly adapt existing clinical guidelines to a new reality and this is especially the case for acute coronary syndrome pathways. In this focused review, the authors discuss how COVID-19 is affecting acute cardiology care and propose pragmatic guideline modifications for the diagnosis and management of acute coronary syndrome patients, particularly around the appropriateness of invasive strategies as well as length of hospital stay. The authors also discuss the use of personal protective equipment for healthcare workers in cardiology. Based on shared global experiences and growing peer-reviewed literature, it is possible to put in place modified acute coronary syndrome treatment pathways to offer safe pragmatic decisions to patients and staff

Bioresorbable vascular scaffold radial expansion and conformation compared to a metallic platform: Insights from in vitro expansion in a coronary artery lesion model

Aims: This study aimed to compare the acute expansion behaviour of a polymer-based bioresorbable scaffold and a second-generation metallic DES platform in a realistic coronary artery lesion model. Experimental mechanical data with conventional methods have so far shown little difference between metallic stents and currently available polymer-based bioresorbable scaffolds (BRS). Nevertheless, differences in acute results have been observed in clinical studies comparing BRS directly with metallic DES platforms. Methods and results: We examined the expansion behaviour of the bioresorbable vascular scaffold (3.0 718 mm Absorb BVS; Abbott Vascular, Santa Clara, CA, USA) and a metallic DES (3.0 718 mm XIENCE Prime; Abbott Vascular) after expansion at 37\ub0C using identical coronary artery stenosis models (in total 12 experiments were performed). Device expansion was compared during balloon inflation and after deflation using microscopy to allow assessment of plaque recoil. Minimal lumen diameter (MLD) and minimal lumen area (MLA) and stent eccentricity were quantified from optical coherence tomography (OCT) imaging at nominal diameter and after post-dilation at 18 atm. The MLA in the models with BVS deployed was 4.92\ub10.17 mm2 while in the metallic DES it was 5.40\ub10.13 mm2 (p=0.02) at nominal pressure (NP), and 5.41\ub10.20 and 6.07\ub10.25 mm2 (p=0.02), respectively, after expansion at 18 atm. Stent eccentricity index at the MLA was 0.71\ub10.02 in BVS compared to 0.81\ub10.02 in the metal stent at NP (p=0.004), and 0.73\ub10.03 compared to 0.75\ub10.02 at 18 atm (p=0.39). Conclusions: Results obtained in this in vitro lesion model were comparable to the results in randomised clinical trials comparing BVS and XIENCE stents in vivo. Such models may be useful in future BRS developments to predict their acute response in vivo in eccentric lesions

Correction: Reusable snorkel masks adapted as particulate respirators

ntroduction During viral pandemics, filtering facepiece (FFP) masks together with eye protection form the essential components of personal protective equipment (PPE) for healthcare workers. There remain concerns regarding insufficient global supply and imperfect protection offered by currently available PPE strategies. A range of full-face snorkel masks were adapted to accept high grade medical respiratory filters using bespoke-designed 3D-printed connectors. We compared the protection offered by the snorkel to that of standard PPE using a placebo-controlled respirator filtering test as well as a fluorescent droplet deposition experiment. Out of the 56 subjects tested, 42 (75%) passed filtering testing with the snorkel mask compared to 31 (55%) with a FFP3 respirator mask (p = 0.003). Amongst the 43 subjects who were not excluded following a placebo control, 85% passed filtering testing with the snorkel versus to 68% with a FFP3 mask (p = 0.008). Following front and lateral spray of fluorescence liquid particles, the snorkel mask also provided superior protection against droplet deposition within the subject’s face, when compared to a standard PPE combination of FFP3 masks and eye protection (3.19x108 versus 6.81x108 fluorescence units, p<0.001). The 3D printable adaptors are available for free download online at https://www.ImperialHackspace.com/COVID-19-Snorkel-Respirator-Project/. Conclusion Full-face snorkel masks adapted as particulate respirators performed better than a standard PPE combination of FFP3 mask and eye protection against aerosol inhalation and droplet deposition. This adaptation is therefore a promising PPE solution for healthcare workers during highly contagious viral outbreaks

Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial

Background: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. Methods: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. Findings: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI −8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. Interpretation: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy

Impact of Percutaneous Revascularization on Exercise Hemodynamics in Patients With Stable Coronary Disease

Background: Recently, the therapeutic benefits of percutaneous coronary intervention (PCI) have been challenged in patients with stable coronary artery disease (SCD). Objectives: The authors examined the impact of PCI on exercise responses in the coronary circulation, the microcirculation, and systemic hemodynamics in patients with SCD. Methods: A total of 21 patients (mean age 60.3 ± 8.4 years) with SCD and single-vessel coronary stenosis underwent cardiac catheterization. Pre-PCI, patients exercised on a supine ergometer until rate-limiting angina or exhaustion. Simultaneous trans-stenotic coronary pressure-flow measurements were made throughout exercise. Post-PCI, this process was repeated. Physiological parameters, rate-limiting symptoms, and exercise performance were compared between pre-PCI and post-PCI exercise cycles. Results: PCI reduced ischemia as documented by fractional flow reserve value (pre-PCI 0.59 ± 0.18 to post-PCI 0.91 ± 0.07), instantaneous wave-free ratio value (pre-PCI 0.61 ± 0.27 to post-PCI 0.96 ± 0.05) and coronary flow reserve value (pre-PCI 1.7 ± 0.7 to post-PCI 3.1 ± 1.0; p < 0.001 for all). PCI increased peak-exercise average peak coronary flow velocity (p < 0.0001), coronary perfusion pressure (distal coronary pressure; p < 0.0001), systolic blood pressure (p = 0.01), accelerating wave energy (p < 0.001), and myocardial workload (rate-pressure product; p < 0.01). These changes observed immediately following PCI resulted from the abolition of stenosis resistance (p < 0.0001). PCI was also associated with an immediate improvement in exercise time (+67 s; 95% confidence interval: 31 to 102 s; p < 0.0001) and a reduction in rate-limiting angina symptoms (81% reduction in rate-limiting angina symptoms post-PCI; p < 0.001). Conclusions: In patients with SCD and severe single-vessel stenosis, objective physiological responses to exercise immediately normalize following PCI. This is seen in the coronary circulation, the microcirculation, and systemic hemodynamics

Sex Differences in Instantaneous Wave-Free Ratio or Fractional Flow Reserve–Guided Revascularization Strategy

Objectives: This study sought to evaluate sex differences in procedural characteristics and clinical outcomes of instantaneous wave-free ratio (iFR)– and fractional flow reserve (FFR)–guided revascularization strategies. Background: An iFR-guided strategy has shown a lower revascularization rate than an FFR-guided strategy, without differences in clinical outcomes. Methods: This is a post hoc analysis of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate stenosis to guide Revascularization) study, in which 601 women and 1,891 men were randomized to iFR- or FFR-guided strategy. The primary endpoint was 1-year major adverse cardiac events (MACE), a composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization. Results: Among the entire population, women had a lower number of functionally significant lesions per patient (0.31 ± 0.51 vs. 0.43 ± 0.59; p &lt; 0.001) and less frequently underwent revascularization than men (42.1% vs. 53.1%; p &lt; 0.001). There was no difference in mean iFR value according to sex (0.91 ± 0.09 vs. 0.91 ± 0.10; p = 0.442). However, the mean FFR value was lower in men than in women (0.83 ± 0.09 vs. 0.85 ± 0.10; p = 0.001). In men, an FFR-guided strategy was associated with a higher rate of revascularization than an iFR-guided strategy (57.1% vs. 49.3%; p = 0.001), but this difference was not observed in women (41.4% vs. 42.6%; p = 0.757). There was no difference in MACE rates between iFR- and FFR-guided strategies in both women (5.4% vs. 5.6%, adjusted hazard ratio: 1.10; 95% confidence interval: 0.50 to 2.43; p = 0.805) and men (6.6% vs. 7.0%, adjusted hazard ratio: 0.98; 95% confidence interval: 0.66 to 1.46; p = 0.919). Conclusions: An FFR-guided strategy was associated with a higher rate of revascularization than iFR-guided strategy in men, but not in women. However, iFR- and FFR-guided strategies showed comparable clinical outcomes, regardless of sex. (Functional Lesion Assessment of Intermediate Stenosis to guide Revascularization [DEFINE-FLAIR]; NCT02053038