Capoulade R.,Massachusetts General Hospital |
Zeng X.,Massachusetts General Hospital |
Overbey J.R.,Mount Sinai School of Medicine |
Ailawadi G.,University of Virginia |
And 15 more authors.
Circulation | Year: 2016
Background: In ischemic mitral regurgitation (IMR), ring annuloplasty is associated with a significant rate of recurrent MR. Ring size is based on intertrigonal distance without consideration of left ventricular (LV) size. However, LV size is an important determinant of mitral valve (MV) leaflet tethering before and after repair. We aimed to determine whether LV-MV ring mismatch (mismatch of LV size relative to ring size) is associated with recurrent MR in patients with IMR after restrictive ring annuloplasty. Methods: Patients with moderate or severe IMR from the 2 Cardiothoracic Surgical Trials Network IMR trials who received MV repair were examined at 1 year after surgery. Baseline LV size was assessed by LV end-diastolic dimension and LV end-systolic dimension (LVESd). LV-MV ring mismatch was calculated as the ratio of LV to ring size (LV end-diastolic dimension/ring size and LVESd/ring size). Results: At 1 year after ring annuloplasty, 45 of 214 patients with MV repair (21%) had moderate or greater MR. In univariable logistic regression analysis, larger LVESd (P=0.02) and LVESd/ring size (P=0.007) were associated with recurrent MR. In multivariable models adjusted for age, sex, baseline LV ejection fraction, and severe IMR, only LVESd/ring size (odd ratio per 0.5 increase, 2.20; 95% confidence interval, 1.05-4.62; P=0.038) remained significantly associated with 1-year MR recurrence. Conclusions: LV-MV ring size mismatch is associated with increased risk of MR recurrence. This finding may be helpful in guiding choice of ring size to prevent recurrent MR in patients undergoing MV repair and in identifying patients who may benefit from MV repair with additional subvalvular intervention or MV replacement rather than repair alone. Clinical Trial Registration: URL:http://clinicaltrials.gov. Unique identifiers: NCT00806988 and NCT00807040. © 2016 American Heart Association, Inc.
Ritchie A.J.,University of British Columbia |
Ritchie A.J.,Royal Brisbane Hospital |
Sanghera C.,University of British Columbia |
Jacobs C.,Royal Brisbane Hospital |
And 19 more authors.
Journal of Thoracic Oncology | Year: 2016
Objectives: To implement a cost-effective low-dose computed tomography (LDCT) lung cancer screening program at the population level, accurate and efficient interpretation of a large volume of LDCT scans is needed. The objective of this study was to evaluate a workflow strategy to identify abnormal LDCT scans in which a technician assisted by computer vision (CV) software acts as a first reader with the aim to improve speed, consistency, and quality of scan interpretation. Methods: Without knowledge of the diagnosis, a technician reviewed 828 randomly batched scans (136 with lung cancers, 556 with benign nodules, and 136 without nodules) from the baseline Pan-Canadian Early Detection of Lung Cancer Study that had been annotated by the CV software CIRRUS Lung Screening (Diagnostic Image Analysis Group, Nijmegen, The Netherlands). The scans were classified as either normal (no nodules ≥1 mm or benign nodules) or abnormal (nodules or other abnormality). The results were compared with the diagnostic interpretation by Pan-Canadian Early Detection of Lung Cancer Study radiologists. Results: The overall sensitivity and specificity of the technician in identifying an abnormal scan were 97.8% (95% confidence interval: 96.4-98.8) and 98.0% (95% confidence interval: 89.5-99.7), respectively. Of the 112 prevalent nodules that were found to be malignant in follow-up, 92.9% were correctly identified by the technician plus CV compared with 84.8% by the study radiologists. The average time taken by the technician to review a scan after CV processing was 208 ± 120 seconds. Conclusions: Prescreening CV software and a technician as first reader is a promising strategy for improving the consistency and quality of screening interpretation of LDCT scans. © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
Guauque-Olarte S.,Institute University Of Cardiologie Et Of Pneumologie Of Quebecqc |
Messika-Zeitoun D.,Bichat Hospital |
Messika-Zeitoun D.,French Institute of Health and Medical Research |
Droit A.,Laval University |
And 16 more authors.
Circulation: Cardiovascular Genetics | Year: 2015
Background-Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. Methods and Results-A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. MRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5×10-6 in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcription factor 2), encoding an osteogenic transcription factor, demonstrated some association with AS (genome-wide association studies P=5.33×10-5). The mRNA expression levels of RUNX2 were upregulated in calcified valves and associated with eQTL-SNPs. CACNA1C encoding a subunit of a voltage-dependent calcium channel was upregulated in calcified valves. The eQTL-SNP with the most significant association with AS located in CACNA1C was associated with higher expression of the gene. Conclusions-This integrative genomic study confirmed the role of RUNX2 as a potential driver of AS and identified a new AS susceptibility gene, CACNA1C, belonging to the calcium signaling pathway. © 2015 American Heart Association, Inc.
Boivin J.,University Laval |
Beddar S.,University of Houston |
Guillemette M.,University Laval |
Guillemette M.,Institute University Of Cardiologie Et Of Pneumologie Of Quebecqc |
Beaulieu L.,University Laval
IFMBE Proceedings | Year: 2015
A plastic scintillation detector (PSD) has been developed and optimized to measure dose rate in real-time for low energy beams. The PSD is composed of a scintillating fiber coupled to a clear optical fiber transmitting the scintillator’s light to a photodetector. A spectrometer was used to characterize the scintillator’s spectrum under low and high energy exposures. Seven photodetectors were then evaluated to identify their operating range and potential applications. They comprise a photomultiplier tube (PMT), an avalanche photodiode, two passive diodes of which, and a set of three CCD cameras. The scintillator was exposed to low energy potential beams (120 kVp, 180 kVp, and 220 kVp) of an orthovoltage unit. The source-to-detector distance was varied to explore a broad dose rate range likely to be used in radiology and superficial treatment. Every detector could measure dose rate down to 10 mGy/s while keeping a relative standard deviation below 2%. The CCD cameras were the less sensitive devices, but they allow multiple fibers to be read simultaneously. Among the photodetectors, the PMT was found to be the most sensitive detector with a relative standard deviation of less than 1% at the lowest dose rate available. The PMT was then included in the PSD design for an in vivo study in interventional radiology where low dose rate sensitivity is essential. The PSD was located inside a plastic water phantom to measure skin and depth dose from 1 mm down to 24 cm. There was less than a 2% difference between the PSD measured dose rate and the ion chamber reading located at the same depth. These results indicate that a broad range of photodetectors can be used in the PSD design, but low dose rate measurements require very sensitive devices such as a PMT. © Springer International Publishing Switzerland 2015.
Boothroyd L.J.,Institute National dExcellence en Sante et en Services Sociaux |
Lambert L.J.,Institute National dExcellence en Sante et en Services Sociaux |
Segal E.,Sir Mortimer B Davis Jewish General Hospital |
Segal E.,Corporation dUrgences sante |
And 11 more authors.
American Journal of Cardiology | Year: 2014
In a systematic province-wide evaluation of care and outcomes of ST elevation myocardial infarction (STEMI), we sought to examine whether a previously documented association between ambulance use and outcome remains after control for clinical risk factors. All 82 acute care hospitals in Quebec (Canada) that treated at least 30 acute myocardial infarctions annually participated in a 6-month evaluation in 2008 to 2009. Medical record librarians abstracted hospital chart data for consecutive patients with a discharge diagnosis of myocardial infarction who presented with characteristic symptoms and met a priori study criteria for STEMI. Linkage to administrative databases provided outcome data (to 1 year) and co-morbidities. Of 1,956 patients, 1,222 (62.5%) arrived by ambulance. Compared with nonusers of an ambulance, users were older, more often women, and more likely to have co-morbidities, low systolic pressure, abnormal heart rate, and a higher Thrombolysis In Myocardial Infarction risk index at presentation. Ambulance users were less likely to receive fibrinolysis or to be sent for primary angioplasty (78.5% vs 83.2% for nonusers, p = 0.01), although if they did, treatment delays were shorter (p <0.001). The 1-year mortality rate was 18.7% versus 7.1% for nonusers (p <0.001). Greater mortality persisted after adjusting for presenting risk factors, co-morbidities, reperfusion treatment, and symptom duration (hazard ratio 1.56, 95% confidence interval 1.30 to 1.87). In conclusion, ambulance users with STEMI were older and sicker than nonusers. Mortality of users was substantially greater after adjustment for clinical risk factors, although they received faster reperfusion treatment overall. © 2014 Elsevier Inc. All rights reserved.
Rundell K.W.,The Commonwealth Medical College |
Anderson S.D.,Royal Prince Alfred Hospital |
Sue-Chu M.,Norwegian University of Science and Technology |
Bougault V.,University of Lille Nord de France |
Boulet L.-P.,Institute University Of Cardiologie Et Of Pneumologie Of Quebecqc
Comprehensive Physiology | Year: 2015
Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested. © 2015 American Physiological Society.
Amit G.,Hamilton Health Sciences |
Wang J.,Hamilton Health Sciences |
Connolly S.J.,Hamilton Health Sciences |
Glikson M.,Leviev Heart Center |
And 15 more authors.
Journal of Cardiovascular Electrophysiology | Year: 2016
ICD Lead Position and Outcome Introduction We aim to compare the acute and long-term success of defibrillation between non-apical and apical ICD lead position. Methods and Results The position of the ventricular lead was recorded by the implanting physician for 2,475 of 2,500 subjects in the Shockless IMPLant Evaluation (SIMPLE) trial, and subjects were grouped accordingly as non-apical or apical. The success of intra-operative defibrillation testing and of subsequent clinical shocks were compared. Propensity scoring was used to adjust for the impact of differences in baseline variables between these groups. There were 541 leads that were implanted at a non-apical position (21.9%). Patients implanted with a non-apical lead had a higher rate of secondary prevention indication. Non-apical location resulted in a lower mean R-wave amplitude (14.0 vs. 15.2, P < 0.001), lower mean pacing impedance (662 ohm vs. 728 ohm, P < 0.001), and higher mean pacing threshold (0.70 V vs. 0.66 V, P = 0.01). Single-coil leads and cardiac resynchronization devices were used more often in non-apical implants. The success of intra-operative defibrillation was similar between propensity score matched groups (89%). Over a mean follow-up of 3 years, there were no significant differences in the yearly rates of appropriate shock (5.5% vs. 5.4%, P = 0.98), failed appropriate first shock (0.9% vs. 1.0%, P = 0.66), or the composite of failed shock or arrhythmic death (2.8% vs. 2.3% P = 0.35) according to lead location. Conclusion We did not detect any reduction in the ICD efficacy at the time of implant or during follow-up in patients receiving a non-apical RV lead. © 2016 Wiley Periodicals, Inc.
Healey J.S.,McMaster University |
Hohnloser S.H.,Goethe University Frankfurt |
Glikson M.,Leviev Heart Center |
Neuzner J.,Klinikum Kassel |
And 17 more authors.
The Lancet | Year: 2015
Background Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. Methods In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. Findings Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). Interpretation Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. Funding Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office). © 2015 Elsevier Ltd.
Todd C.M.,McMaster University |
Salter B.M.,McMaster University |
Murphy D.M.,McMaster University |
Murphy D.M.,Cork University Hospital |
And 7 more authors.
Pulmonary Pharmacology and Therapeutics | Year: 2016
Background Neutrophils are effector cells recruited to airways in patients with asthma. Migration of neutrophils occurs predominantly through activation of the CXCR1 and CXCR2 receptors by CXC chemokines, including IL-8 and Gro-α. The dual CXCR1/CXCR2 antagonist SCH 527123 has been developed to target neutrophil migration to alleviate airway neutrophilia. This study investigated the effects of SCH 527123 on neutrophil levels within the bone marrow, peripheral blood and airways, and on isolated bone marrow and peripheral blood neutrophil migration from mild allergic asthmatics. Methods Thirteen subjects with mild allergic asthma completed a double blind, placebo-controlled, multi-center crossover study and were randomized to daily dosing of 30 mg SCH 527123 and placebo for 8 days. Subjects provided bone marrow, peripheral blood and sputum samples pre-dosing and on the last day of dosing. Neutrophil numbers were quantified in all samples and chemotaxis assays were performed on neutrophils purified from bone marrow and peripheral blood. Results Neutrophil numbers fell significantly in the peripheral blood and sputum following treatment with SCH 527123 compared to placebo treatment. No change in neutrophil numbers was observed in bone marrow. SCH 527123 reduced IL-8-induced migration of purified peripheral blood neutrophils (p < 0.05), but had limited effects on migration of neutrophils purified from bone marrow. Conclusions The results from this study demonstrate that oral administration of the dual CXCR1/CXCR2 antagonist SCH 527123 reduces neutrophil levels in the circulation and airways through inhibition of migration. There were no toxic effects of SCH 527123 on granulocytic progenitor cells in the bone marrow. © 2016