Clinical profile and outcomes of primary percutaneous coronary intervention in young patients

AbstractBackgroundThe epidemiology of acute myocardial infarction with ST-segment elevation (STEMI) has been modified in recent years, focusing on young people. Our goal was compare the clinical profile, laboratory, angiographic, and 30-day clinical outcomes of patients ≤ 40 years with those > 40 years undergoing primary percutaneous coronary intervention (pPCI).MethodsProspective cohort study of consecutive patients undergoing pPCI between 2009 and 2011.ResultsA total of 1,055 patients were included, 3.3% of them ≤ 40 years. Young patients were more often black, smokers and with a family history of coronary artery disease, and less often hypertensive and dyslipidemic. In patients ≤ 40 years, leukocyte count and ultrasensitive troponin levels at admission were higher, and high density lipoprotein-cholesterol, lower. The left anterior descending artery as a culprit vessel and left ventricular ejection fraction did not differ between groups. Although the TIMI 3 flow pre-intervention was similar, young people showed higher prevalence of myocardial blush 3 pre-procedure. The door-to-balloon time was lower in younger patients (1.0 hour [0.8-1.4 hour] vs. 1.3 hour [0.9-1.7 hour]; p = 0.03). At 30 days, patients ≤ 40 years had a mortality of 0% vs. 8.8% for patients > 40 years (p = 0.07).ConclusionsPatients ≤ 40 years with STEMI and undergoing pPCI show differences in clinical, angiographic and procedural characteristics compared to those > 40 years. In this analysis, representative of the current medical practice, the 30-day mortality of these patients was very low

Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Anger and Coronary Artery Disease in Women Submitted to Coronary Angiography: A 48-Month Follow-Up

Abstract Background: Anger control was significantly lower in patients with coronary artery disease (CAD), regardless of traditionally known risk factors, occurrence of prior events or other anger aspects in a previous study of our research group. Objective: To assess the association between anger and CAD, its clinical course and predictors of low anger control in women submitted to coronary angiography. Methods: This is a cohort prospective study. Anger was assessed by use of Spielberger’s State-Trait Anger Expression Inventory (STAXI). Women were consecutively scheduled to undergo coronary angiography, considering CAD definition as ≥ 50% stenosis of one epicardial coronary artery. Results: During the study, 255 women were included, being divided into two groups according to their anger control average (26.99). Those with anger control below average were younger and had a family history of CAD. Patients were followed up for 48 months to verify the occurrence of major cardiovascular events. Conclusion: Women with CAD undergoing coronary angiography had lower anger control, which was associated with age and CAD family history. On clinical follow-up, event-free survival did not significantly differ between patients with anger control above or below average

Perfil clínico e resultados da intervenção coronária percutânea primária em pacientes jovens

ResumoIntroduçãoA epidemiologia do infarto agudo do miocárdio com supradesnivelamento do segmento ST (IAMCST) tem se modificado nos últimos anos, com incidência maior em jovens. Nosso objetivo foi comparar o perfil clínico, laboratorial e angiográfico, e os desfechos clínicos em 30 dias de pacientes ≤ 40 anos àqueles > 40 anos submetidos à intervenção coronária percutânea primária (ICPp).MétodosEstudo de coorte prospectivo com pacientes consecutivos submetidos à ICPp entre 2009 e 2011.ResultadosNo período, 1.055 pacientes foram incluídos, sendo identificados 3,3% com ≤ 40 anos. Pacientes jovens eram mais frequentemente negros, tabagistas e com história familiar de doença coronária, e menos frequentemente hipertensos e dislipidêmicos. Nos pacientes ≤ 40 anos, a dosagem de leucócitos e da troponina ultrassensível na admissão foi maior, e a lipoproteína de alta densidade‐colesterol, menor. A artéria descendente anterior como vaso culpado e a fração de ejeção do ventrículo esquerdo não foram diferentes entre os grupos. Apesar de o fluxo TIMI 3 pré ser similar, os jovens mostraram maior prevalência de blush miocárdico 3 pré‐procedimento. O tempo porta‐balão foi menor nos pacientes mais jovens (1,0 hora [0,8‐1,4 hora] vs. 1,3 hora [0,9‐1,7 hora]; p = 0,03). Em 30 dias, os pacientes ≤ 40 anos apresentaram mortalidade de 0% vs. 8,8% nos pacientes > 40 anos (p = 0,07).ConclusõesPacientes ≤ 40 anos com IAMCST e submetidos à ICPp apresentam diferenças nos perfis clínico, angiográfico e do procedimento quando comparados àqueles > 40 anos. Nesta análise, representativa da prática médica atual, a mortalidade em 30 dias desses pacientes foi muito baixa.AbstractBackgroundThe epidemiology of acute myocardial infarction with ST‐segment elevation (STEMI) has been modified in recent years, focusing on young people. Our goal was compare the clinical profile, laboratory, angiographic, and 30‐day clinical outcomes of patients ≤ 40 years with those > 40 years undergoing primary percutaneous coronary intervention (pPCI).MethodsProspective cohort study of consecutive patients undergoing pPCI between 2009 and 2011.ResultsA total of 1,055 patients were included, 3.3% of them ≤ 40 years. Young patients were more often black, smokers and with a family history of coronary artery disease, and less often hypertensive and dyslipidemic. In patients ≤ 40 years, leukocyte count and ultrasensitive troponin levels at admission were higher, and high density lipoprotein‐cholesterol, lower. The left anterior descending artery as a culprit vessel and left ventricular ejection fraction did not differ between groups. Although the TIMI 3 flow pre‐intervention was similar, young people showed higher prevalence of myocardial blush 3 pre‐procedure. The door‐to‐balloon time was lower in younger patients (1.0 hour [0.8‐1.4 hour] vs. 1.3 hour [0.9‐1.7 hour]; p = 0.03). At 30 days, patients ≤ 40 years had a mortality of 0% vs. 8.8% for patients > 40 years (p = 0.07).ConclusionsPatients ≤ 40 years with STEMI and undergoing pPCI show differences in clinical, angiographic and procedural characteristics compared to those > 40 years. In this analysis, representative of the current medical practice, the 30‐day mortality of these patients was very low

Diabetes Mellitus and Glucose as Predictors of Mortality in Primary Coronary Percutaneous Intervention

Background: Diabetes mellitus and admission blood glucose are important risk factors for mortality in ST segment elevation myocardial infarction patients, but their relative and individual role remains on debate. Objective: To analyze the influence of diabetes mellitus and admission blood glucose on the mortality of ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention. Methods: Prospective cohort study including every ST segment elevation myocardial infarction patient submitted to primary coronary percutaneous intervention in a tertiary cardiology center from December 2010 to May 2012. We collected clinical, angiographic and laboratory data during hospital stay, and performed a clinical follow-up 30 days after the ST segment elevation myocardial infarction. We adjusted the multivariate analysis of the studied risk factors using the variables from the GRACE score. Results: Among the 740 patients included, reported diabetes mellitus prevalence was 18%. On the univariate analysis, both diabetes mellitus and admission blood glucose were predictors of death in 30 days. However, after adjusting for potential confounders in the multivariate analysis, the diabetes mellitus relative risk was no longer significant (relative risk: 2.41, 95% confidence interval: 0.76 - 7.59; p-value: 0.13), whereas admission blood glucose remained and independent predictor of death in 30 days (relative risk: 1.05, 95% confidence interval: 1.02 - 1.09; p-value ≤ 0.01). Conclusion: In ST segment elevation myocardial infarction patients submitted to primary coronary percutaneous intervention, the admission blood glucose was a more accurate and robust independent predictor of death than the previous diagnosis of diabetes. This reinforces the important role of inflammation on the outcomes of this group of patients

Quantitative Signal Intensity in Fluid-Attenuated Inversion Recovery and Treatment Effect in the WAKE-UP Trial

International audienceBackground and Purpose— Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods— FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results— FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 ( P =0.169) and shift analysis ( P =0.086) but reached significance for mRS score of 0 to 2 ( P =0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions— In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset

Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial

Importance: The rationale for intravenous thrombolysis in patients with lacunar infarcts is debated, since it is hypothesized that the microvascular occlusion underlying lacunar infarcts might not be susceptible to pharmacological reperfusion treatment. Objective: To study the efficacy and safety of intravenous thrombolysis among patients with lacunar infarcts. Design, Setting, and Participants: This exploratory secondary post hoc analysis of the WAKE-UP trial included patients who were screened and enrolled between September 2012 and June 2017 (with final follow-up in September 2017). The WAKE-UP trial was a multicenter, double-blind, placebo-controlled randomized clinical trial to study the efficacy and safety of intravenous thrombolysis with alteplase in patients with an acute stroke of unknown onset time, guided by magnetic resonance imaging. All 503 patients randomized in the WAKE-UP trial were reviewed for lacunar infarcts. Diagnosis of lacunar infarcts was based on magnetic resonance imaging and made by consensus of 2 independent investigators blinded to clinical information. Main Outcomes and Measures: The primary efficacy variable was favorable outcome defined by a score of 0 to 1 on the modified Rankin Scale at 90 days after stroke, adjusted for age and severity of symptoms. Results: Of the 503 patients randomized in the WAKE-UP trial, 108 patients (including 74 men [68.5%]) had imaging-defined lacunar infarcts, whereas 395 patients (including 251 men [63.5%]) had nonlacunar infarcts. Patients with lacunar infarcts were younger than patients with nonlacunar infarcts (mean age [SD], 63 [12] years vs 66 [12] years; P = .003). Of patients with lacunar infarcts, 55 (50.9%) were assigned to treatment with alteplase and 53 (49.1%) to receive placebo. Treatment with alteplase was associated with higher odds of favorable outcome, with no heterogeneity of treatment outcome between lacunar and nonlacunar stroke subtypes. In patients with lacunar strokes, a favorable outcome was observed in 31 of 53 patients (59%) in the alteplase group compared with 24 of 52 patients (46%) in the placebo group (adjusted odds ratio [aOR], 1.67 [95% CI, 0.77-3.64]). There was 1 death and 1 symptomatic intracranial hemorrhage according to Safe Implementation of Thrombolysis in Stroke-Monitoring Study criteria in the alteplase group, while no death and no symptomatic intracranial hemorrhage occurred in the placebo group. The distribution of the modified Rankin Scale scores 90 days after stroke also showed a nonsignificant shift toward better outcomes in patients with lacunar infarcts treated with alteplase, with an adjusted common odds ratio of 1.94 (95% CI, 0.95-3.93). Conclusions and Relevance: While the WAKE-UP trial was not powered to demonstrate the efficacy of treatment in subgroups of patients, the results indicate that the association of intravenous alteplase with functional outcome does not differ in patients with imaging-defined lacunar infarcts compared with those experiencing other stroke subtypes.status: publishe

Morbidity and mortality after anaesthesia in early life: results of the European prospective multicentre observational study, neonate and children audit of anaesthesia practice in Europe (NECTARINE)

Background: Neonates and infants requiring anaesthesia are at risk of physiological instability and complications, but triggers for peri-anaesthetic interventions and associations with subsequent outcome are unknown. Methods: This prospective, observational study recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. The primary aim was to identify thresholds of pre-determined physiological variables that triggered a medical intervention. The secondary aims were to evaluate morbidities, mortality at 30 and 90 days, or both, and associations with critical events. Results: Infants (n=5609) born at mean (standard deviation [sd]) 36.2 (4.4) weeks postmenstrual age (35.7% preterm) underwent 6542 procedures within 63 (48) days of birth. Critical event(s) requiring intervention occurred in 35.2% of cases, mainly hypotension (>30% decrease in blood pressure) or reduced oxygenation (SpO2 <85%). Postmenstrual age influenced the incidence and thresholds for intervention. Risk of critical events was increased by prior neonatal medical conditions, congenital anomalies, or both (relative risk [RR]=1.16; 95% confidence interval [CI], 1.04-1.28) and in those requiring preoperative intensive support (RR=1.27; 95% CI, 1.15-1.41). Additional complications occurred in 16.3% of patients by 30 days, and overall 90-day mortality was 3.2% (95% CI, 2.7-3.7%). Co-occurrence of intraoperative hypotension, hypoxaemia, and anaemia was associated with increased risk of morbidity (RR=3.56; 95% CI, 1.64-7.71) and mortality (RR=19.80; 95% CI, 5.87-66.7). Conclusions: Variability in physiological thresholds that triggered an intervention, and the impact of poor tissue oxygenation on patient's outcome, highlight the need for more standardised perioperative management guidelines for neonates and infants

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE): a prospective European multicentre observational study

International audienceBackground: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences.Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airway management, and 30 and 90 day outcomes.Results: Tracheal intubation was planned in 4683 procedures. Difficult tracheal intubation, defined as two failed attempts of direct laryngoscopy, occurred in 266 children (271 procedures) with an incidence (95% confidence interval [CI]) of 5.8% (95% CI, 5.1-6.5). Bradycardia occurred in 8% of the cases with difficult intubation, whereas a significant decrease in oxygen saturation (SpO2<90% for 60 s) was reported in 40%. No associated risk factors could be identified among co-morbidities, surgical, or anaesthesia management. Using propensity scoring to adjust for confounders, difficult anaesthesia tracheal intubation did not lead to an increase in 30 and 90 day morbidity or mortality.Conclusions: The results of the present study demonstrate a high incidence of difficult tracheal intubation in children less than 60 weeks post-conceptual age commonly resulting in severe hypoxaemia. Reassuringly, the morbidity and mortality at 30 and 90 days was not increased by the occurrence of a difficult intubation event