Incidence and predictors of 2-year mortality following percutaneous left atrial appendage occlusion in the EWOLUTION trial.

AIMS: Sufficient survival time following left atrial appendage occlusion (LAAO) is essential for ensuring the efficacy and cost-effectiveness of this strategy for stroke prevention. Understanding prognostic factors for early mortality after LAAO could optimize patient selection. In the current study, we perform an in-depth analysis of 2-year mortality after LAAO, focusing particularly on potential predictors. METHODS AND RESULTS: The EWOLUTION registry is a real-world cohort comprising 1020 patients that underwent LAAO. Endpoint definitions were pre-specified, and death was categorized as cardiovascular, non-cardiovascular, or unknown origin. Mortality rates were calculated from Kaplan-Meier estimates. Baseline characteristics significantly associated with death in univariate Cox regression analysis were incorporated into the multivariate analysis. All multivariate predictors were included in a risk model. Two-year mortality rate was 16.4% [confidence interval (CI): 14.0-18.7%], with 50% of patients dying from a non-cardiovascular cause. Multivariate baseline predictors of 2-year mortality included age [hazard ratio (HR) 1.05, CI: 1.03-1.08, per year increase], heart failure (HR 1.73, CI: 1.24-2.41), vascular disease (HR 1.47, CI: 1.05-2.05), valvular disease (HR 1.63, CI: 1.15-2.33), abnormal liver function (HR 1.80, CI: 1.02-3.17), and abnormal renal function (HR 1.58, CI: 1.10-2.27). Mortality rate exhibited a gradual rise as the number of risk factors increased, reaching 46.1% in patients presenting with five or six risk factors. CONCLUSION: One in six patients died within 2 years after LAAO. We identified six independent predictors of mortality. When combined, this model showed a gradual increase in mortality rate with a growing number of risk factors, which may guide appropriate patient selection for LAAO. CLINICAL TRIAL REGISTRATION: The original EWOLUTION registry was registered at clinicaltrials.gov under identifier NCT01972282.

[Nausea and vomiting in pregnancy]. / Nausées et vomissements gravidiques.

NAUSEA AND VOMITING IN PREGNANCY. Nausea and vomiting during pregnancy are common symptoms experienced by pregnant women. In more severe cases, known as hyperemesis gravidarum, these symptoms can become a pathological condition that can lead to significant complications in both the short and long term. Short-term complications include hydro-electrolyte imbalances, pregnancy termination, and growth retardation. Long-term complications may include anxiety disorders, depression, and post-traumatic stress disorder. Mild cases can often be alleviated through lifestyle and dietary adjustments or non-pharmacological treatments like ginger, acupuncture, or acupressure. However, moderate to severe cases require specific psychological support, anti-emetic treatments, and sometimes hospitalization with intravenous treatment and parenteral rehydration. Managing these cases is complex and challenging because it does not guarantee the complete disappearance of symptoms, which can pose difficulties for caregivers.

NAUSÉES ET VOMISSEMENTS GRAVIDIQUES. Les nausées et vomissements de la grossesse sont un symptôme classique chez la femme enceinte. Le plus souvent sans gravité, les formes modérées à sévères, appelées hyperémèse gravidique, constituent une pathologie qui peut être invalidante, source de complications de la grossesse à court terme (troubles hydroélectrolytiques, arrêt de grossesse, retard de croissance) mais aussi à long terme (troubles anxiodépressifs, état de stress post-traumatique). Les formes minimes peuvent être atténuées par des règles hygiénodiététiques ou des traitements non médicamenteux (gingembre, acupuncture, acupression). Les formes modérées à sévères nécessitent un accompagnement psychologique spécifique, des traitements antiémétiques et, parfois, une hospitalisation avec traitement par voie intraveineuse et réhydratation parentérale. Leur prise en charge est complexe et difficile car elle ne permet pas toujours une disparition des symptômes, ce qui peut mettre en difficulté les soignants.

Ultrasound-guided versus fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions: the international, multicentre, randomised ULTRACOLOR Trial.

BACKGROUND: Transfemoral access is often used when large-bore guide catheters are required for percutaneous coronary intervention (PCI) of complex coronary lesions, especially when large-bore transradial access is contraindicated. Whether the risk of access site complications for these procedures may be reduced by ultrasound-guided puncture is unclear. AIMS: We aimed to show the superiority of ultrasound-guided femoral puncture compared to fluoroscopy-guided access in large-bore complex PCI with regard to access site-related Bleeding Academic Research Consortium 2, 3 or 5 bleeding and/or vascular complications requiring intervention during hospitalisation. METHODS: The ULTRACOLOR Trial is an international, multicentre, randomised controlled trial investigating whether ultrasound-guided large-bore femoral access reduces clinically relevant access site complications compared to fluoroscopy-guided large-bore femoral access in PCI of complex coronary lesions. RESULTS: A total of 544 patients undergoing complex PCI mandating large-bore (≥7 Fr) transfemoral access were randomised at 10 European centres (median age 71; 76% male). Of these patients, 68% required PCI of a chronic total occlusion. The primary endpoint was met in 18.9% of PCI with fluoroscopy-guided access and 15.7% of PCI with ultrasound-guided access (p=0.32). First-pass puncture success was 92% for ultrasound-guided access versus 85% for fluoroscopy-guided access (p=0.02). The median time in the catheterisation laboratory was 102 minutes versus 105 minutes (p=0.43), and the major adverse cardiovascular event rate at 1 month was 4.1% for fluoroscopy-guided access and 2.6% for ultrasound-guided access (p=0.32). CONCLUSIONS: As compared to fluoroscopy-guided access, the routine use of ultrasound-guided access for large-bore transfemoral complex PCI did not significantly reduce clinically relevant bleeding or vascular access site complications. A significantly higher first-pass puncture success rate was demonstrated for ultrasound-guided access. CLINICALTRIALS: gov identifier: NCT04837404.

Real-World 1-Year Results of Tricuspid Edge-to-Edge Repair From the bRIGHT Study.

BACKGROUND: Severe tricuspid regurgitation (TR) is known to be associated with poor quality of life and increased risk of death when left untreated. OBJECTIVES: We sought to report the 1-year clinical outcomes of subjects treated by tricuspid transcatheter edge-to-edge repair (TEER) with the TriClip system (Abbott Cardiovascular) in a contemporary real-world setting. METHODS: The bRIGHT (An Observational Real-World Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device) postapproval study is a prospective, single-arm, open-label, multicenter postmarket registry conducted at 26 sites in Europe, with central event adjudication and echocardiographic core-laboratory assessment. RESULTS: Enrolled subjects (n = 511) were elderly (79 ± 7 years) with significant comorbidities. A total of 88% had baseline massive or torrential TR, and 80% of subjects were in NYHA functional class III/IV. TR was reduced to moderate or less in 81% at 1 year. Significant improvements in NYHA functional class (21% to 75% I/II, P < 0.0001) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (19 ± 26-point improvement, P <0.0001) were observed at 1 year. One-year mortality was significantly lower in subjects who achieved moderate or lower TR at 30 days; however, there was no difference in mortality among subjects who achieved moderate, mild, or trace TR at 30 days. In addition to TR reduction at 30 days, baseline serum creatinine and baseline right ventricular tricuspid annular plane systolic excursion (RV TAPSE) were independently associated with mortality at 1 year (OR: 2.169; 95% CI: 1.494-3.147; P < 0.0001; OR: 0.636; 95% CI: 0.415-0.974; P = 0.0375). Mortality was not associated with baseline TR grade or with center volume. CONCLUSIONS: Tricuspid TEER using the TriClip system was safe and effective through 1 year for subjects with significant TR and advanced disease in a diverse real-world population. (An Observational Real-world Study Evaluating Severe Tricuspid Regurgitation Patients Treated With the Abbott TriClip Device [bRIGHT]; NCT04483089).

Safety and efficacy of the latest generation biodegradable polymer-coated ultrathin sirolimus-eluting stent in the treatment of coronary artery disease in a European all-comer population with or without high bleeding risk: The Cruz HBR Registry.

BACKGROUND: The latest generation ultrathin Supraflex Cruz (Sahajanand Medical Technologies Limited, Surat, India) sirolimus-eluting stent (SES) has shown early healing properties and represents an attractive percutaneous coronary intervention (PCI) device in a high bleeding risk (HBR) population. The aim of this Cruz HBR registry was to assess safety and efficacy of the Supraflex Cruz SES in a large cohort of all-comer patients, of whom about one third were patients at HBR. METHODS: Patients undergoing PCI were enrolled in this prospective, multi-centre, open label registry and stratified into non-HBR and HBR groups. The primary endpoint was a device-oriented composite endpoint (DOCE), a composite of cardiovascular death, myocardial infarction not clearly attributable to a non-target vessel and clinically driven target lesion revascularization within 12 months after PCI. The predefined aims were to show non-inferiority of the non-HBR group to the Supraflex arm of the TALENT Trial, and of the HBR group to polymer-free biolimus-coated stent arm of LEADERS FREE Trial. RESULTS: A total of 1203 patients were enrolled across 26 European centers, including a significant proportion (38.7%; N.=466) of HBR patients. A total of 1745 lesions were treated in 1203 patients and 2235 stents were implanted. The DOCE occurred within the total cohort in 5.8% of patients with a significant difference between HBR patients and non-HBR patients (8.1% vs. 4.4%; P<0.001). All-cause mortality at 12 months was significantly (P<0.0001) different among HBR (9.0%) and non-HBR patients (1.7%), respectively. At 12 months, the overall incidence of definite and probable stent thrombosis was 1.0%. Major bleeding occurred in 5.9% patients of the HBR group. These results met the non-inferiority criteria with respect to the TALENT trial for the non-HBR group (P<0.0001), and the LEADERS FREE trial for the HBR group (P<0.0001). CONCLUSIONS: The Cruz HBR registry confirms that PCI with the Supraflex Cruz SES is associated with a favorable clinical outcome in an all-comer population, including complex patients with HBR.

Bilirubin Exerts Protective Effects on Alveolar Type II Pneumocytes in an In Vitro Model of Oxidative Stress.

Newborn infants face a rapid surge of oxygen and a more protracted rise of unconjugated bilirubin after birth. Bilirubin has a strong antioxidant capacity by scavenging free radicals, but it also exerts direct toxicity. This study investigates whether cultured rat alveolar epithelial cells type II (AEC II) react differently to bilirubin under different oxygen concentrations. The toxic threshold concentration of bilirubin was narrowed down by means of a cell viability test. Subsequent analyses of bilirubin effects under 5% oxygen and 80% oxygen compared to 21% oxygen, as well as pretreatment with bilirubin after 4 h and 24 h of incubation, were performed to determine the induction of apoptosis and the gene expression of associated transcripts of cell death, proliferation, and redox-sensitive transcription factors. Oxidative stress led to an increased rate of cell death and induced transcripts of redox-sensitive signaling pathways. At a non-cytotoxic concentration of 400 nm, bilirubin attenuated oxidative stress-induced responses and possibly mediated cellular antioxidant defense by influencing Nrf2/Hif1α- and NFκB-mediated signaling pathways. In conclusion, the study demonstrates that rat AEC II cells are protected from oxidative stress-induced impairment by low-dose bilirubin.

Mitral Valve Transcatheter Edge-to-Edge Repair: 1-Year Outcomes From the MiCLASP Study.

BACKGROUND: Mitral transcatheter edge-to-edge repair (M-TEER) is a guideline-recommended treatment option for patients with severe symptomatic mitral regurgitation (MR). Outcomes with the PASCAL system in a post-market setting have not been established. OBJECTIVES: The authors report 30-day and 1-year outcomes from the MiCLASP (Transcatheter Repair of Mitral Regurgitation with Edwards PASCAL Transcatheter Valve Repair System) European post-market clinical follow-up study. METHODS: Patients with symptomatic, clinically significant MR were prospectively enrolled. The primary safety endpoint was clinical events committee-adjudicated 30-day composite major adverse event rate and the primary effectiveness endpoint was echocardiographic core laboratory-assessed MR severity at discharge compared with baseline. Clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. RESULTS: A total of 544 patients were enrolled (59% functional MR, 30% degenerative MR). The 30-day composite major adverse event rate was 6.8%. MR reduction was significant from baseline to discharge and sustained at 1 year with 98% of patients achieving MR ≤2+ and 82.6% MR ≤1+ (all P < 0.001 vs baseline). One-year Kaplan-Meier estimate for survival was 87.3%, and freedom from heart failure hospitalization was 84.3%. Significant functional and quality-of-life improvements were observed at 1 year, including 71.6% in NYHA functional class I/II, 14.4-point increase in Kansas City Cardiomyopathy Questionnaire score, and 24.2-m improvement in 6-minute walk distance (all P < 0.001 vs baseline). CONCLUSIONS: One-year outcomes of this large cohort from the MiCLASP study demonstrate continued safety and effectiveness of M-TEER with the PASCAL system in a post-market setting. Results demonstrate high survival and freedom from heart failure hospitalization, significant and sustained MR reduction, and improvements in symptoms, functional capacity, and quality of life.

Oxygen and HIF1α-dependent SDF1 expression in primary astrocytes.

In the naturally hypoxic in utero fetal environment of preterm infants, oxygen and oxygen-sensitive signaling pathways play an important role in brain development, with hypoxia-inducible factor-1α (HIF1α) being an important regulator. Early exposure to nonphysiological high oxygen concentrations by birth in room can induce HIF1α degradation and may affect neuronal and glial development. This involves the dysregulation of astroglial maturation and function, which in turn might contribute to oxygen-induced brain injury. In this study, we investigated the effects of early high oxygen exposure on astroglial maturation and, specifically, on astroglial stromal cell-derived factor 1 (SDF1) expression in vivo and in vitro. In our neonatal mouse model of hyperoxia preterm birth brain injury in vivo, high oxygen exposure affected astroglial development and cortical SDF1 expression. These results were further supported by reduced Sdf1 expression, impaired proliferation, decreased total cell number, and altered expression of astroglial markers in astrocytes in primary cultures grown under high oxygen conditions. Moreover, to mimic the naturally hypoxic in utero fetal environment, astroglial Sdf1 expression was increased after low oxygen exposure in vitro, which appears to be regulated by HIF1α activity. Additionally, the knockdown of Hif1α revealed HIF1α-dependent Sdf1 expression in vitro. Our results indicate HIF1α and oxygen-dependent chemokine expression in primary astrocytes and highlight the importance of oxygen conditions for brain development.

Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

The ethics of induction of labor at 39 weeks in low-risk nulliparas in research and clinical practice.

The "A Randomized Trial of Induction Versus Expectant Management" trial (ARRIVE trial) published in 2018 suggested that induction of labor can be considered a "reasonable option" for low-risk nulliparous women at ≥39 weeks of gestation. The study results led some professional societies to endorse the option for elective induction of labor at 39 weeks of gestation in low-risk nulliparas, and this has begun to change obstetrical practice. The ARRIVE trial provided valuable information supporting the benefits of induction of labor; however, the trial is insufficient to serve as the primary justification for widespread elective induction of labor at 39 weeks of gestation in low-risk nulliparas because of concerns about external validity. Thus, the French ARRIVE trial was designed to test the hypothesis in a different setting that elective induction of labor at 39 weeks of gestation in low-risk nulliparas leads to a lower cesarean delivery rate than expectant management. This ongoing trial has been criticized as "pseudoscientific" and telling "women where, when, and how to give birth." We reject these allegations and extensively examine the ethical framework that should govern clinical and research interventions, including elective induction of labor at 39 weeks of gestation in low-risk nulliparas. This study aimed to discuss the ethical issues that emerge from randomized trials of elective induction of labor at 39 weeks of gestation in low-risk nulliparas and the ethics of the clinical practice itself. The analysis of existing evidence shows the importance of further research on induction of labor at 39 weeks of gestation in low-risk women. Certain aspects of research ethics in this area, particularly the consent of pregnant women in a context where autonomy remains fragile, call for vigilance. In addition, we emphasize that childbirth is not only a medical object but also a social phenomenon that cannot be regarded only from the perspective of a health risk to be managed by clinical research. Further research on this issue is needed to allow pregnant women to make informed decisions, and the results should be integrated with social issues. The perspective of women is required in constructing, evaluating, and implementing medical interventions in childbirth, such as induction of labor at 39 weeks of gestation.

[Preeclampsia: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and recommendations were formulated as a (i) strong, (ii) weak or (iii) no recommendation. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Preeclampsia is defined by the association of gestational hypertension (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg) and proteinuria≥0.3g/24h or a Proteinuria/Creatininuria ratio≥30mg/mmol occurring after 20 weeks of gestation. Data from the literature do not show any benefit in terms of maternal or perinatal health from implementing a broader definition of preeclampsia. Of the 31 questions, there was agreement between the working group and the external reviewers on 31 (100%). In general population, physical activity during pregnancy should be encouraged to reduce the risk of preeclampsia (Strong recommendation, Quality of the evidence low) but an early screening based on algorithms (Weak recommendation, Quality of the evidence low) or aspirin administration (Weak recommendation, Quality of the evidence very low) is not recommended to reduce maternal and neonatal morbidity related to preeclampsia. In women with preexisting diabetes or hypertension or renal disease, or multiple pregnancy, the level of evidence is insufficient to determine whether aspirin administration during pregnancy is useful to reduce maternal and perinatal morbidity (No recommendation, Quality of the evidence low). In women with a history of vasculo-placental disease, low dose of aspirin (Strong recommendation, Quality of the evidence moderate) at a dosage of 100-160mg per day (Weak recommendation, Quality of the evidence low), ideally before 16 weeks of gestation and not after 20 weeks of gestation (Strong recommendation, Quality of the evidence low) until 36 weeks of gestation (Weak recommendation, Quality of the evidence very low) is recommended. In a high-risk population, additional administration of low molecular weight heparin is not recommended (Weak recommendation, Quality of the evidence moderate). In case of preeclampsia (Weak recommendation, Quality of the evidence low) or suspicion of preeclampsia (Weak recommendation, Quality of the evidence moderate, the assessment of PlGF concentration or sFLT-1/PlGF ratio is not routinely recommended) in the only goal to reduce maternal or perinatal morbidity. In women with non-severe preeclampsia antihypertensive agent should be administered orally when the systolic blood pressure is measured between 140 and 159mmHg or diastolic blood pressure is measured between 90 and 109mmHg (Weak recommendation, Quality of the evidence low). In women with non-severe preeclampsia, delivery between 34 and 36+6 weeks of gestation reduces severe maternal hypertension but increases the incidence of moderate prematurity. Taking into account the benefit/risk balance for the mother and the child, it is recommended not to systematically induce birth in women with non-severe preeclampsia between 34 and 36+6 weeks of gestation (Strong recommendation, Quality of evidence high). In women with non-severe preeclampsia diagnosed between 37+0 and 41 weeks of gestation, it is recommended to induce birth to reduce maternal morbidity (Strong recommendation, Low quality of evidence), and to perform a trial of labor in the absence of contraindication (Strong recommendation, Very low quality of evidence). In women with a history of preeclampsia, screening maternal thrombophilia is not recommended (Strong recommendation, Quality of the evidence moderate). Because women with a history of a preeclampsia have an increased lifelong risk of chronic hypertension and cardiovascular complications, they should be informed of the need for medical follow-up to monitor blood pressure and to manage other possible cardiovascular risk factors (Strong recommendation, Quality of the evidence moderate). CONCLUSION: The purpose of these recommendations was to reassess the definition of preeclampsia, and to determine the strategies to reduce maternal and perinatal morbidity related to preeclampsia, during pregnancy but also after childbirth. They aim to help health professionals in their daily clinical practice to inform or care for patients who have had or have preeclampsia. Synthetic information documents are also offered for professionals and patients.

Delivery of twins : lessons learnt from the national observational prospective comparative study JUMODA / L'accouchement des femmes enceintes de jumeaux : les enseignements de l'étude nationale observationnelle prospective comparative JUMODA.

OBJECTIVES: To summerize the results of the JUMODA study (JUmeaux MODe d'Accouchement) on the planned mode of delivery of twin pregnancy and the management of second twin delivery. METHODS: JUMODA was a national observational prospective comparative study that took place between february 2014 and march 2015 in 176 french maternity units performing more than 1500 deliveries per year. Its main objectives were the comparison of neonatal and maternal morbidity according to the planned mode of delivery and the determination of the managements of second twin delivery associated with the best neonatal outcomes. To control for potential confounding factors and indication biases, statistical analyses comprized multivariate logistic regressions and matching on propensity scores. RESULTS: The JUMODA study recruited 8823 women with twin delivery at or beyond 22 weeks of gestation. For twin pregnancies with a cephalic first twin at 32 weeks of gestation and beyond, severe neonatal morbidity was higher in the planned cesarean (150/2908 (5.2 %) than in the planned vaginal delivery group (199/8922 (2.2 %), aOR 1.56, 95 % CI 1.19-2.04). Increased neonatal morbidity in the planned cesarean delivery group was explained by higher severe morbidity in neonates born preterm (aOR 1.64, 95 % CI 1.13-2.39, for deliveries between 32+0 and 34+6 weeks of gestation, aOR 2.04, 95 % CI 1.22-3.41, for deliveries between 35+0 SA and 36+6 weeks of gestation) but not in neonates born at term (aOR 1.19, 95 % CI 0.58-2.44). In comparison with planned cesarean delivery, planned vaginal delivery was not associated with increased severe neonatal morbidity in case of breech presenting first twin after 32 weeks of gestation or with decreased survival witout severe neonatal morbidity in case of delivery before 32 weeks of gestation whatever the first twin presentation. In comparison with planned vaginal delivery, planned cesarean delivery was associated with increased severe maternal morbidity only in women aged 35 and higher. Delivery of non cephalic second twin was associated with similar severe neonatal morbidity rate than delivery of cephalic second twin. Finally, in case of cephalic second twin, internal version followed by total breech extraction was associated with less cesarean for the second twin but with higher severe neonatal morbidity in case of preterm birth in comparison with pushing efforts, ocytocin perfusion and artificial rupture of membranes. CONCLUSIONS: Planned vaginal delivery is the planned mode of delivery to encourage for the majority of pregnant women with twins, whatever first twin presentation and gestational age at delivery. No management of cephalic second twin appears better than an other, its choice will rest on obstetrician preferences.

Targeted therapy with a localised abluminal groove, low-dose sirolimus-eluting, biodegradable-polymer coronary stent - five-year results of the TARGET All Comers randomised clinical trial.

BACKGROUND: In the prospective, multicentre, randomised TARGET All Comers study, percutaneous coronary intervention (PCI) with the FIREHAWK biodegradable-polymer sirolimus-eluting stent (BP-SES) was non-inferior to the durable-polymer everolimus-eluting stent (DP-EES) for the primary endpoint of target lesion failure (TLF) at 12 months. AIMS: We aimed to report the final study outcomes at 5 years. METHODS: Patients referred for PCI were randomised to receive either a BP-SES or DP-EES in a 1:1 ratio in 10 European countries. Randomisation was stratified by centre and ST-elevation myocardial infarction (STEMI) presentation, and clinical follow-up extended to 5 years. The primary endpoint was TLF (composite of cardiac death, target vessel myocardial infarction [MI], or ischaemia-driven target lesion revascularisation). Secondary endpoints included patient-oriented composite events (POCE; composite of all-cause death, all MI, or any revascularisation and its components). RESULTS: From December 2015 to October 2016, 1,653 patients were randomly assigned to the BP-SES or DP-EES groups, of which 93.8% completed 5-year clinical follow-up or were deceased. At 5 years, TLF occurred in 17.1% of the BP-SES group and in 16.3% of the DP-EES group (p=0.68). POCE occurred in 34.0% of the BP-SES group and 32.7% of the DP-EES group (p=0.58). Revascularisation was the most common POCE, occurring in 19.3% of patients receiving BP-SES and 19.2% receiving DP-EES, of which less than one-third was ischaemia-driven target lesion-related. In the landmark analysis, there were no differences in the rates of TLF and POCE between groups from 1 to 5 years, and these results were consistent across all subgroups. CONCLUSIONS: In an all-comers population requiring stent implantation for myocardial ischaemia, the BP-SES was non-inferior to the DP-EES for the primary endpoint of TLF at 12 months, and results were sustained at 5 years, confirming the long-term safety and efficacy of the FIREHAWK BP-SES.

Bifurcation left main stenting with or without intracoronary imaging: Outcomes from the EBC MAIN trial.

BACKGROUND: The impact of intracoronary imaging on outcomes, after provisional versus dual-stenting for bifurcation left main (LM) lesions, is unknown. OBJECTIVES: We investigated the effect of intracoronary imaging in the EBC MAIN trial (European Bifurcation Club LM Coronary Stent study). METHODS: Four hundred and sixty-seven patients were randomized to dual-stenting or a stepwise provisional strategy. Four hundred and fifty-five patients were included. Intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was undertaken at the operator's discretion. The primary endpoint was death, myocardial infarction or target vessel revascularization at 1-year. RESULTS: Intracoronary imaging was undertaken in 179 patients (39%; IVUS = 151, OCT = 28). As a result of IVUS findings, operators reintervened in 42 procedures. The primary outcome did not differ with intracoronary imaging versus angiographic-guidance (17% vs. 16%; odds ratio [OR]: 0.92 (95% confidence interval [CI]: 0.51-1.63) p = 0.767), nor for reintervention based on IVUS versus none (14% vs. 16%; OR: 0.88 [95% CI: 0.32-2.43] p = 0.803), adjusted for syntax score, lesion calcification and ischemic symptoms. With angiographic-guidance, primary outcome events were more frequent with dual versus provisional stenting (21% vs. 10%; adjusted OR: 2.11 [95% CI: 1.04-4.30] p = 0.039). With intracoronary imaging, there were numerically fewer primary outcome events with dual versus provisional stenting (13% vs. 21%; adjusted OR: 0.56 [95% CI: 0.22-1.46] p = 0.220). CONCLUSIONS: In EBC MAIN, the primary outcome did not differ with intracoronary imaging versus none. However, in patients with angiographic-guidance, outcomes were worse with a dual-stent than provisional strategy When intracoronary imaging was used, there was a trend toward better outcomes with the dual-stent than provisional strategy.