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Background: Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission., Methods: The present study is a phase 3, randomised, double-blind, adaptive, placebo-controlled, multicentre trial. The study was done in Brazil, Canada, Greece, South Africa, Spain, and the USA, and was led by the Montreal Heart Institute. Patients with COVID-19 diagnosed by PCR testing or clinical criteria who were not being treated in hospital were eligible if they were at least 40 years old and had at least one high-risk characteristic. The randomisation list was computer-generated by an unmasked biostatistician, and masked randomisation was centralised and done electronically through an automated interactive web-response system. The allocation sequence was unstratified and used a 1:1 ratio with a blocking schema and block sizes of six. Patients were randomly assigned to receive orally administered colchicine (0·5 mg twice per day for 3 days and then once per day for 27 days thereafter) or matching placebo. The primary efficacy endpoint was the composite of death or hospital admission for COVID-19. Vital status at the end of the study was available for 97·9% of patients. The analyses were done according to the intention-to-treat principle. The COLCORONA trial is registered with ClinicalTrials.gov (NCT04322682) and is now closed to new participants., Findings: Trial enrolment began in March 23, 2020, and was completed in Dec 22, 2020. A total of 4488 patients (53·9% women; median age 54·0 years, IQR 47·0-61·0) were enrolled and 2235 patients were randomly assigned to colchicine and 2253 to placebo. The primary endpoint occurred in 104 (4·7%) of 2235 patients in the colchicine group and 131 (5·8%) of 2253 patients in the placebo group (odds ratio [OR] 0·79, 95·1% CI 0·61-1·03; p=0·081). Among the 4159 patients with PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4·6%) of 2075 patients in the colchicine group and 126 (6·0%) of 2084 patients in the placebo group (OR 0·75, 0·57-0·99; p=0·042). Serious adverse events were reported in 108 (4·9%) of 2195 patients in the colchicine group and 139 (6·3%) of 2217 patients in the placebo group (p=0·051); pneumonia occurred in 63 (2·9%) of 2195 patients in the colchicine group and 92 (4·1%) of 2217 patients in the placebo group (p=0·021). Diarrhoea was reported in 300 (13·7%) of 2195 patients in the colchicine group and 161 (7·3%) of 2217 patients in the placebo group (p<0·0001)., Interpretation: In community-treated patients including those without a mandatory diagnostic test, the effect of colchicine on COVID-19-related clinical events was not statistically significant. Among patients with PCR-confirmed COVID-19, colchicine led to a lower rate of the composite of death or hospital admission than placebo. Given the absence of orally administered therapies to prevent COVID-19 complications in community-treated patients and the benefit of colchicine in patients with PCR-proven COVID-19, this safe and inexpensive anti-inflammatory agent could be considered for use in those at risk of complications. Notwithstanding these considerations, replication in other studies of PCR-positive community-treated patients is recommended., Funding: The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The effect of direct laryngoscopy using a Macintosh blade (MAC) vs GlideScope™ videolaryngoscopy using a Spectrum LoPro blade (GVL) on nociceptive stimulation has not been quantitatively studied. This study used the new nociception level (NOL) index to compare the nociceptive response induced by GVL or MAC during laryngoscopy with or without intubation., Methods: Patients underwent two laryngoscopies at four-minute intervals (L1, L2), one with GVL and the other with MAC (first randomization). A third laryngoscopy (L3) followed by tracheal intubation was performed four minutes after L2 (GVL or MAC, second randomization). Nociception was quantitatively assessed by NOL and standard hemodynamic parameters (heart rate [HR] and mean arterial pressure). For the crossover design, blade comparisons accounted for sequence and blade type. A possible carryover effect between laryngoscopies was assessed., Results: In the 50 patients randomized, there was no carryover effect from one laryngoscopy to the next for all analyzed parameters. Nociception level index peak values were higher with MAC than GVL. Analysis of ΔNOL showed a lower nociceptive response with GVL for L1+L2 combined. Mean peak NOL values were significantly higher after L3+intubation than after L1+L2, for both GVL and MAC groups. Analysis of ΔHR values did not show a significant difference between GVL and MAC for any laryngoscopy., Conclusion: Laryngoscopy alone with GVL induces less nociception than with MAC. The NOL was more sensitive than HR at detecting nociceptive responses to MAC vs GVL. Additionally, and irrespective of which technique/blade was used, the combination of laryngoscopy + tracheal intubation produced a much greater nociceptive response than the laryngoscopy alone., Trial Registration: www.clinicaltrials.gov (NCT03277872); registered 29 August 2017.

We conducted a genome-wide association study of time to remission of COVID-19 symptoms in 1723 outpatients with at least one risk factor for disease severity from the COLCORONA clinical trial. We found a significant association at 5p13.3 (rs1173773; P = 4.94 × 10 -8 ) near the natriuretic peptide receptor 3 gene (NPR3). By day 15 of the study, 44%, 54% and 59% of participants with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. In 851 participants not treated with colchicine (placebo), there was a significant association at 9q33.1 (rs62575331; P = 2.95 × 10 -8 ) in interaction with colchicine (P = 1.19 × 10 -5 ) without impact on risk of hospitalisations, highlighting a possibly shared mechanistic pathway. By day 15 of the study, 46%, 62% and 64% of those with 0, 1, or 2 copies of the effect allele respectively, had symptom remission. The findings need to be replicated and could contribute to the biological understanding of COVID-19 symptom remission.

Background: Hypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment option for patients with hypertension; however, there is conflicting evidence about their effects on AF recurrence. Therefore, our objective was to assess the efficacy of perindopril, compared with placebo, to reduce AF recurrence in patients with hypertension and AF., Methods: In a multicenter, double-blind, placebo-controlled trial, patients with hypertension and symptomatic AF were randomly assigned (1:1) to perindopril or placebo based on a stratification factor of antiarrhythmic drug use. Patients with terminated AF were followed up from 30 days after randomization to 7 to 13 months. The primary endpoint was AF recurrence. Secondary endpoints included AF hospitalization, cardioversion, and blood pressure control. Recurrent events, AF burden, and safety endpoints were also investigated., Results: A total of 315 patients were randomly assigned, and 301 patients were included in the modified intent-to-treat analysis (155 vs 146 patients in the perindopril and placebo groups, respectively). The mean follow-up was 336 ± 70 days, and 91.1% of patients were compliant to the treatment medication throughout the study. After adjustment for baseline antiarrhythmic drugs, there was no statistically significant difference in the hazards of AF recurrence (hazard ratio, 1.22; 95% confidence interval, 0.92-1.61), with similar blood pressure. The incidence of secondary endpoints and adverse events also did not differ between treatment arms., Conclusions: Perindopril does not reduce recurrence or the number of AF episodes in patients with hypertension and AF., (© 2021 The Authors.)

Background: The randomized, placebo-controlled COLCOT (Colchicine Cardiovascular Outcomes Trial) has shown the benefits of colchicine 0.5 mg daily to lower the rate of ischemic cardiovascular events in patients with a recent myocardial infarction. Here, we conducted a post hoc pharmacogenomic study of COLCOT with the aim to identify genetic predictors of the efficacy and safety of treatment with colchicine., Methods: There were 1522 participants of European ancestry from the COLCOT trial available for the pharmacogenomic study of COLCOT trial. The pharmacogenomic study's primary cardiovascular end point was defined as for the main trial, as time to first occurrence of cardiovascular death, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization. The safety end point was time to the first report of gastrointestinal events. Patients' DNA was genotyped using the Illumina Global Screening array followed by imputation. We performed a genome-wide association study in colchicine-treated patients., Results: None of the genetic variants passed the genome-wide association study significance threshold for the primary cardiovascular end point conducted in 702 patients in the colchicine arm who were compliant to medication. The genome-wide association study for gastrointestinal events was conducted in all 767 patients in the colchicine arm and found 2 significant association signals, one with lead variant rs6916345 (hazard ratio, 1.89 [95% CI, 1.52-2.35], P =7.41×10 -9 ) in a locus which colocalizes with Crohn disease, and one with lead variant rs74795203 (hazard ratio, 2.51 [95% CI, 1.82-3.47]; P =2.70×10 -8 ), an intronic variant in gene SEPHS1 . The interaction terms between the genetic variants and treatment with colchicine versus placebo were significant., Conclusions: We found 2 genomic regions associated with gastrointestinal events in patients treated with colchicine. Those findings will benefit from replication to confirm that some patients may have genetic predispositions to lower tolerability of treatment with colchicine.

Aims: The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine., Methods and Results: In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4-7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32-0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53-1.75) or > Day 8 (HR = 0.82, 95% CI 0.61-1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05)., Conclusion: Patients benefit from early, in-hospital initiation of colchicine after MI., Trial Registration: COLCOT ClinicalTrials.gov number, NCT02551094., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Experimental and clinical evidence supports the role of inflammation in atherosclerosis and its complications. Colchicine is an orally administered, potent antiinflammatory medication that is indicated for the treatment of gout and pericarditis., Methods: We performed a randomized, double-blind trial involving patients recruited within 30 days after a myocardial infarction. The patients were randomly assigned to receive either low-dose colchicine (0.5 mg once daily) or placebo. The primary efficacy end point was a composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization. The components of the primary end point and safety were also assessed., Results: A total of 4745 patients were enrolled; 2366 patients were assigned to the colchicine group, and 2379 to the placebo group. Patients were followed for a median of 22.6 months. The primary end point occurred in 5.5% of the patients in the colchicine group, as compared with 7.1% of those in the placebo group (hazard ratio, 0.77; 95% confidence interval [CI], 0.61 to 0.96; P = 0.02). The hazard ratios were 0.84 (95% CI, 0.46 to 1.52) for death from cardiovascular causes, 0.83 (95% CI, 0.25 to 2.73) for resuscitated cardiac arrest, 0.91 (95% CI, 0.68 to 1.21) for myocardial infarction, 0.26 (95% CI, 0.10 to 0.70) for stroke, and 0.50 (95% CI, 0.31 to 0.81) for urgent hospitalization for angina leading to coronary revascularization. Diarrhea was reported in 9.7% of the patients in the colchicine group and in 8.9% of those in the placebo group (P = 0.35). Pneumonia was reported as a serious adverse event in 0.9% of the patients in the colchicine group and in 0.4% of those in the placebo group (P = 0.03)., Conclusions: Among patients with a recent myocardial infarction, colchicine at a dose of 0.5 mg daily led to a significantly lower risk of ischemic cardiovascular events than placebo. (Funded by the Government of Quebec and others; COLCOT ClinicalTrials.gov number, NCT02551094.)., (Copyright © 2019 Massachusetts Medical Society.)

Background: Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating., Methods: Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation (BRAIN-AF) is a prospective, multicentric, double-blind, randomized-controlled trial, recruiting patients with nonvalvular AF and a low risk of stroke. Patients with a high risk of bleeding will be excluded from the study. Participants will be randomized to receive either rivaroxaban (15 mg daily) or standard of care (placebo in patients without vascular disease or acetylsalicylic acid 100 mg daily in patients with vascular disease)., Results: The primary outcome is the composite of stroke, transient ischemic attack, and cognitive decline (defined by a decrease in the Montreal Cognitive Assessment score ≥ 3 at any follow-up visit after baseline). Approximately 3250 patients will be enrolled in approximately 130 clinical sites until 609 adjudicated primary outcome events have occurred., Conclusions: BRAIN-AF determines whether oral anticoagulation therapy with rivaroxaban compared with standard of care reduces the risk of stroke, transient ischemic attack, or cognitive decline in patients with nonvalvular AF and a low risk of stroke., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess sex- and gender-related factors associated with cardiac rehabilitation (CR) enrollment following acute coronary syndrome among systematically referred patients., Methods: This secondary analysis of a randomized controlled trial used an exploratory approach to examine the TRANSITion process for patients between the coronary care unit and CR (TRANSIT-UC). The present analysis examined the relationship between sex- and gender-related factors and CR enrollment in systematically referred women (n = 35) and men (n = 207). We performed χ and logistic regression analyses to identify statistically significant results. Using the Bonferroni method, a P value of .002 or less was considered a significant statistical result. A raw difference of 15% or more between enrolled and nonenrolled participants was considered a difference worthy of further investigation., Results: Men who were regularly engaged in physical activity prior to their hospitalization and who lived near the CR center showed a statistically higher CR enrollment rate. In women and men, a radial entry site for percutaneous coronary intervention resulted in a clinically significant difference in favor of CR enrollment. In women, 3 sex-related and 9 gender-related variables were associated with a difference of 15% or more between enrolled and nonenrolled participants., Conclusion: Factors related to CR enrollment in women and men are suggested. As women keep showing a lower rate of CR enrolment, the investigation of these factors in a larger sample of patients may hold valuable insights to improve CR enrolment.

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients., Methods and Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001)., Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Pharmacogenomic studies have shown that ADCY9 genotype determines the effects of the CETP (cholesteryl ester transfer protein) inhibitor dalcetrapib on cardiovascular events and atherosclerosis imaging. The underlying mechanisms responsible for the interactions between ADCY9 and CETP activity have not yet been determined., Methods: Adcy9-inactivated ( Adcy9 Gt/Gt ) and wild-type (WT) mice, that were or not transgenic for the CETP gene (CETPtg Adcy9 Gt/Gt and CETPtg Adcy9 WT ), were submitted to an atherogenic protocol (injection of an AAV8 [adeno-associated virus serotype 8] expressing a PCSK9 [proprotein convertase subtilisin/kexin type 9] gain-of-function variant and 0.75% cholesterol diet for 16 weeks). Atherosclerosis, vasorelaxation, telemetry, and adipose tissue magnetic resonance imaging were evaluated., Results: Adcy9 Gt/Gt mice had a 65% reduction in aortic atherosclerosis compared to WT ( P<0.01). CD68 (cluster of differentiation 68)-positive macrophage accumulation and proliferation in plaques were reduced in Adcy9 Gt/Gt mice compared to WT animals ( P<0.05 for both). Femoral artery endothelial-dependent vasorelaxation was improved in Adcy9 Gt/Gt mice (versus WT, P<0.01). Selective pharmacological blockade showed that the nitric oxide, cyclooxygenase, and endothelial-dependent hyperpolarization pathways were all responsible for the improvement of vasodilatation in Adcy9 Gt/Gt ( P<0.01 for all). Aortic endothelium from Adcy9 Gt/Gt mice allowed significantly less adhesion of splenocytes compared to WT ( P<0.05). Adcy9 Gt/Gt mice gained more weight than WT with the atherogenic diet; this was associated with an increase in whole body adipose tissue volume ( P<0.01 for both). Feed efficiency was increased in Adcy9 Gt/Gt compared to WT mice ( P<0.01), which was accompanied by prolonged cardiac RR interval ( P<0.05) and improved nocturnal heart rate variability ( P=0.0572). Adcy9 inactivation-induced effects on atherosclerosis, endothelial function, weight gain, adipose tissue volume, and feed efficiency were lost in CETPtg Adcy9 Gt/Gt mice ( P>0.05 versus CETPtg Adcy9 WT )., Conclusions: Adcy9 inactivation protects against atherosclerosis, but only in the absence of CETP activity. This atheroprotection may be explained by decreased macrophage accumulation and proliferation in the arterial wall, and improved endothelial function and autonomic tone.

Aim: To evaluate the impact of AGTR1 A1166C (rs5186) on the response to candesartan in patients with heart failure., Materials & Methods: Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40%., Results: Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1 A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p = 0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p = 0.022)., Conclusion: AGTR1 1166C carriers may experience a greater long-term compensatory renin-angiotensin-aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation. Clinicaltrials.gov : NCT00400582.

Aims: Patients suffering from out-of-hospital cardiac arrest (OHCA) are frequently transported to the closest hospital. Percutaneous coronary intervention (PCI) is often indicated following OHCA. This study's primary objective was to determine the association between being transported to a PCI-capable hospital and survival to discharge for patients with OHCA. The additional delay to hospital arrival which could offset a potential increase in survival associated with being transported to a PCI-capable center was also evaluated., Methods: This study used a registry of OHCA in Montreal, Canada. Adult patients transported to a hospital following a non-traumatic OHCA were included. Hospitals were dichotomized based on whether PCI was available on-site or not. The effect of hospital type on survival to discharge was assessed using a multivariable logistic regression. The added prehospital delay which could offset the increase in survival associated with being transported to a PCI-capable center was calculated using that regression., Results: A total of 4922 patients were included, of whom 2389 (48%) were transported to a PCI-capable hospital and 2533 (52%) to a non-PCI-capable hospital. There was an association between being transported to a PCI-capable center and survival to discharge (adjusted odds ratio = 1.60 [95% confidence interval 1.25-2.05], p < .001). Increasing the delay from call to hospital arrival by 14.0 min would offset the potential benefit of being transported to a PCI-capable center., Conclusions: It could be advantageous to redirect patients suffering from OHCA patients to PCI-capable centers if the resulting expected delay is of less than 14 min., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Vascular inflammation is increased in patients with psoriasis. This randomized, double-blind, multicenter study evaluated the effects of tumor necrosis factor-α antagonist adalimumab on vascular inflammation in patients with psoriasis. A total of 107 patients were randomized (1:1) to receive adalimumab for 52 weeks or placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography. There were no differences in the change from baseline in vessel wall target-to-background ratio (TBR) from the ascending aorta (primary endpoint) (adalimumab: TBR = 0.002, 95% confidence interval [CI] = -0.048 to 0.053; placebo: TBR = -0.002, 95% CI = -0.053 to 0.049; P = 0.916) and the carotids (adalimumab: TBR = 0.031, 95% CI = -0.005 to 0.066; placebo: TBR = 0.018, 95% CI = -0.019 to 0.055; P = 0.629) at week 16 between adalimumab and placebo. After 52 weeks of treatment with adalimumab there was no significant change from start of treatment in TBR from the ascending aorta (TBR = -0.006, 95% CI = -0.049 to 0.038; P = 0.796), but there was an increase in TBR in carotids (TBR = 0.027, 95% CI = 0.000 to 0.054; P = 0.046). This study showed no difference over 16 weeks in vascular inflammation in patients treated with a tumor necrosis factor-α antagonist or placebo and a modest increase in vascular inflammation in carotids after 52 weeks of treatment with adalimumab., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The management of paediatric asthma exacerbations is based on trials in children of all ages. Recent studies from 2009 raised the possibility that preschoolers (younger than 6 years) with viral-induced wheezing and children exposed to tobacco smoke might be at an increased risk of treatment failure. The study objective was to identify factors associated with management failure in children presenting to the emergency department with moderate or severe asthma exacerbations., Methods: We undertook a prospective, multicentre cohort study of children aged 1-17 years presenting to five emergency departments with moderate or severe asthma (defined as a Pediatric Respiratory Assessment Measure [PRAM] of 4 to 12). Children received oral corticosteroids and severity-specific inhaled bronchodilator therapy. The primary outcome was emergency department management failure (hospital admission, prolonged emergency department therapy [≥8 h], or relapse within 72 h of discharge from the emergency department with admission to hospital or prolonged emergency department stay). Viral cause was ascertained by PCR on nasopharyngeal specimens and environmental tobacco smoke exposure by salivary cotinine concentration. This study is registered at ClinicalTrials.gov (NCT02013076)., Findings: Between Feb 14, 2011, and Dec 20, 2013, we screened 1893 children and enrolled 1012 eligible children. Of those eligible children, 973 participants were included in the analysis. 165 (17%) of 965 children experienced management failure in the emergency department, which was significantly associated with viral detection (110 [19%] of 579 participants with virus detection vs 46 [13%] of 354 participants without viral detection, odds ratio [OR] 1·57; 95% CI 1·04-2·37), fever (24% vs 15%, 1·96; 1·32-2·92), baseline PRAM (OR 1·38 per 1-point increase; 1·22-1·56), oxygen saturation of less than 92% (50% vs 12%, 3·94; 1·97-7·89), and presence of symptoms between exacerbations (21% vs 16%, 1·73; 1·13-2·64). Age, salivary cotinine concentration, and oral corticosteroids dose were not significantly associated with management failure. Viral detection (67% vs 46%, p<0·0001) and fever (31% vs 16%, p<0·0001) occurred more frequently in preschoolers than in older children. Viral detection was also associated with reduced speed of recovery over the 10 days after discharge., Interpretation: In children presenting with moderate or severe asthma, viral detection, but not age, was associated with failure of symptom management, independently from exacerbation severity (ie, baseline PRAM and oxygen saturation), fever, and symptom chronicity (viral detection). Although it did not reach statistical significance, the association between treatment management failure and exposure to tobacco smoke warrants further investigation., Funding: Canadian Institutes of Health Research., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: The objective of this study was to evaluate the safety and efficacy of external beam radiation (EBR) in preventing restenosis after superficial femoral artery (SFA) stenting in comparison with a control group treated with SFA stenting only., Methods: In this Institutional Review Board-approved study, patients who provided written informed consent were randomly assigned to 0 Gy or 14 Gy of EBR to the stent site 24 hours after SFA stenting. The primary end point was the angiographic binary restenosis rate 2 years after stenting. Categorical and continuous end points were respectively analyzed using logistic regression models and Wilcoxon tests. End points expressed as time to event were analyzed using a log-rank test., Results: The study included 155 patients, 46 women and 109 men (mean age, 66 years; range, 45-85 years). In the 0 and 14 Gy groups, binary restenosis was present, respectively, in 44% (34/77) and 68% (52/76; P = .003) 2 years after stenting. Stent thrombosis occurred in 13% (10/78) of the 0 Gy group and in 33% (25/77) of the 14 Gy group (P = .003). Target lesion revascularization at 2 years was 26% (25/78) in the 0 Gy group and 30% (23/77) in the 14 Gy group (P = .56). There were no significant differences in total walking distances change from baseline to 2 years (46 ± 100 and 26 ± 79 m, respectively, in the 0 Gy and 14 Gy group; P = .25). There were no procedure-related deaths and no major amputations., Conclusions: A single 14 Gy dose of EBR to the SFA stenting site did not prevent in-stent restenosis., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Measurements of oxidative stress biomarkers in patients with heart failure (HF) have yielded controversial results. This study aimed at testing the hypothesis that circulating levels of the lipid peroxidation product 4-hydroxynonenal bound to thiol proteins (4HNE-P) are strongly associated with those of its potential precursors, namely n-6 polyunsaturated fatty acids (PUFA)., Methods and Results: Circulating levels of 4HNE-P were evaluated by gas chromatography-mass spectrometry in 71 control subjects and 61 ambulatory symptomatic HF patients along with various other clinically- and biochemically-relevant parameters, including other oxidative stress markers, and total levels of fatty acids from all classes, which reflect both free and bound to cholesterol, phospholipids and triglycerides. All HF patients had severe systolic functional impairment despite receiving optimal evidence-based therapies. Compared to controls, HF patients displayed markedly lower circulating levels of HDL- and LDL-cholesterol, which are major PUFA carriers, as well as of PUFA of the n-6 series, specifically linoleic acid (LA; P=0.001). Circulating 4HNE-P in HF patients was similar to controls, albeit multiple regression analysis revealed that LA was the only factor that was significantly associated with circulating 4HNE-P in the entire population (R (2)=0.086; P=0.02). In HF patients only, 4HNE-P was even more strongly associated with LA (P=0.003) and HDL-cholesterol (p<0.0002). Our results demonstrate that 4HNE-P levels, expressed relative to HDL-cholesterol, increase as HDL-cholesterol plasma levels decrease in the HF group only., Conclusion: Results from this study emphasize the importance of considering changes in lipids and lipoproteins in the interpretation of measurements of lipid peroxidation products. Further studies appear warranted to explore the possibility that HDL-cholesterol particles may be a carrier of 4HNE adducts.

Objective: The aim of this study was to evaluate the effect of a smoking cessation intervention provided after discharge from a specialized cardiac hospital., Design: A randomized pilot study (N = 40); after discharge, the experimental group (EG) received 6 phone calls from a nurse specialized in tobacco cessation counselling., Results: Patients in the EG showed improved scores on two aspects of illness representations (perceive their illness as chronic and reported less negative emotional representations). No significant difference in smoking cessation was observed at 6 months (p = 0.72)., Conclusion: The non-significant difference may be explained in part by the smoking characteristics within this sample exemplifying the more nicotine dependent "hard core" smokers who persist in their smoking habits despite the serious health consequences incurred by continued smoking. This population of smokers may require a more intensive, specialized intervention to achieve smoking cessation.

The authors assessed the effect of very long-term cardiac rehabilitation (over 1 year) on exercise tolerance and coronary heart disease risk factors in patients older than 80 years with coronary heart disease relative to an elderly cohort without coronary heart disease. Included in this retrospective analysis were patients older than 80 at the time of their last evaluation who had completed at least 1 year of a cardiac prevention and exercise training program. A total of 43 coronary heart disease patients and 15 age-matched healthy subjects were included in this study. Long-term cardiac rehabilitation in very elderly coronary heart disease patients was shown to be feasible and effective in improving functional capacity (+5.4% after 1 year; P< .05) and risk factor control, and slowing the decline in exercise tolerance that occurs with normal aging.

Background: Percutaneous coronary intervention induces an early inflammatory reaction. The intensity of such a reaction as measured by high-sensitivity C-reactive protein has been correlated with recurrent ischemic events, but its association with restenosis remains uncertain., Objectives: To characterize the type and duration of the postangioplasty inflammatory reaction and to identify new inflammatory markers correlating with restenosis., Methods: Fifty-three consecutive patients who underwent successful balloon angioplasty were studied. Levels of specific inflammatory markers were measured before intervention, and at one-month and six-month follow-up. Six-month clinical and angiographic follow-up was conducted in all patients, and quantitative coronary analysis was systematically performed., Results: Levels of soluble CD40 ligand (sCD40L) and matrix metalloproteinase-2 showed a rise and fall pattern over six months, with peak levels measured at one month (P < 0.0001), while levels of soluble vascular cell adhesion molecule-1 increased after angioplasty and remained elevated at six months (P = 0.07). Plasma levels of sCD40L at one month correlated with angiographic late loss (r = 0.48, P = 0.001) and were predictive of six-month restenosis (area under receiver operating characteristic curve 0.75 [95% CI 0.61 to 0.88])., Conclusions: The results imply that inflammation persists for at least one month following angioplasty and that future therapeutic interventions targeting inflammation to prevent restenosis should be active during this period. Furthermore, the ability of sCD40L levels to predict restenosis at six months may indicate the relevance of this pathway as a therapeutic target for restenosis prevention.

Background and Aim of the Study: Tricuspid regurgitation secondary to pulmonary hypertension due to left-sided heart valve lesions is common. Here, the results are reported of 25 years' experience with three surgical techniques; the De Vega semicircular annuloplasty, the Bex flexible linear reducer, and the Carpentier-Edwards prosthetic ring annuloplasty., Methods: Between 1976 and 2002, 463 patients underwent 478 tricuspid annuloplasty procedures to correct valve regurgitation during associated left-sided valve surgery. Patients were followed prospectively at the Montreal Heart Institute Valve Clinic., Results: A total of 107 patients (23%) underwent the De Vega semicircular annuloplasty, 267 (58%) the Bex flexible linear reducer, and 89 (19%) the Carpentier-Edwards prosthetic ring annuloplasty. Excluding 30-day mortality, the mean 5-, 10- and 15-year patient survival was 82+/-4%, 58+/-6% and 30+/-6% respectively after the De Vega semicircular annuloplasty, 76+/-3%, 54+/-4% and 36+/-6% respectively after the Bex flexible linear reducer, and the mean five-year patient survival was 88+/-4% after the Carpentier-Edwards prosthetic ring annuloplasty (p = 0.65, for comparison of the three survival curves). The mean freedom rate from tricuspid repair failure (clinical right heart failure, redo annuloplasty, tricuspid valve replacement at follow up) was 95+/-3%, 93+/-3% and 72+/-8% at 5, 10 and 15 years respectively after the De Vega semicircular annuloplasty, and 97+/-1%, 87+/-4% and 66+/-9% after the Bex flexible linear reducer. The mean freedom rate from repair failure was 94+/-3% at five years after the Carpentier-Edwards prosthetic ring annuloplasty (p = 0.18 for comparison of the three freedom from failure curves)., Conclusion: All three techniques of tricuspid valve repair resulted in a low rate of failure, and in good patient survival at long-term follow up.

Objective: The goal of our study was to compare Doppler sonography and renal scintigraphy as tools for predicting the therapeutic response in patients after undergoing renal angioplasty. SUBJECTS AND METHODS. Seventy-four hypertensive patients underwent clinical examination, Doppler sonography, and renal scintigraphy before and after receiving captopril in preparation for renal revascularization. The patients were evaluated for the status of hypertension 3 months after the procedure. The predictive values of the findings of clinical examination, Doppler sonography, renal scintigraphy, and angiography were assessed., Results: For prediction of a favorable therapeutic outcome, abnormal results from renal scintigraphy before and after captopril administration had a sensitivity of 58% and specificity of 57%. Findings of Doppler sonography had a sensitivity of 68% and specificity of 50% before captopril administration and a sensitivity of 81% and specificity of 32% after captopril administration. Significant predictors of a cure or reduction of hypertension after revascularization were low unilateral (p = 0.014) and bilateral resistive (p = 0.016) indexes on Doppler sonography before (p = 0.009) and after (p = 0.028) captopril administration. On multivariate analysis, the best predictors were a unilateral resistive index of less than 0.65 (odds ratio [OR] = 3.7) after captopril administration and a kidney longer than 93 mm (OR = 7.8). The two best combined criteria to predict the favorable therapeutic outcome were a bilateral resistive index of less than 0.75 before captopril administration combined with a unilateral resistive index of less than 0.70 after captopril administration (sensitivity, 76%; specificity, 58%) or a bilateral resistive index of less than 0.75 before captopril administration and a kidney measuring longer than 90 mm (sensitivity, 81%; specificity, 50%)., Conclusion: Measurements of kidney length and unilateral and bilateral resistive indexes before and after captopril administration were useful in predicting the outcome after renal angioplasty. Renal scintigraphy had no significant predictive value.