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Objectives: Our objective was to report the baseline characteristics of participants in the Canadian HIV and Aging Cohort Study (CHACS) and present amendments to the initial protocol. Methods: CHACS is a multi‐centred prospective cohort study that was initially set from 2011 to 2016 and will now continue recruitment until 2024. Four additional years of follow‐up have been added, and additional outcomes and covariates will be prospectively collected. Frailty will be assessed using a modified version of the Fried's frailty phenotype. The four interrelated aspects of gender—gender roles, gender identity, gender relationships, and institutionalized gender—will be measured using the GENESIS‐PRAXY questionnaire. Diet will be assessed using a validated, web‐based, self‐administered food frequency questionnaire. Results: A total of 1049 participants (77% people living with HIV) were recruited between September 2011 and September 2019. Median age at baseline was 54 years (interquartile range 50–61). Most participants were male (84%) and white (83%). Compared with participants without HIV, those with HIV were more likely to be male; to report lower education levels and incomes; to be more sedentary; to use tobacco, recreational, and prescription drugs; to report a personal history of cardiovascular diseases; and to be frail. Conclusions: The new assessments added to the CHACS protocol will allow for an even more detailed portrait of the pathways leading to accentuated aging for people living with HIV. Participants in the CHACS cohort display important differences in socio‐economic and cardiovascular risk factors according to HIV serostatus. These imbalances must be taken into account for all further inferential analyses. [ABSTRACT FROM AUTHOR]

Rationale: Studies of excised lungs show that significant airway attrition in the "quiet" zone occurs early in chronic obstructive pulmonary disease (COPD).Objectives: To determine if the total number of airways quantified in vivo using computed tomography (CT) reflects early airway-related disease changes and is associated with lung function decline independent of emphysema in COPD.Methods: Participants in the multicenter, population-based, longitudinal CanCOLD (Canadian Chronic Obstructive Lung Disease) study underwent inspiratory/expiratory CT at visit 1; spirometry was performed at four visits over 6 years. Emphysema was quantified as the CT inspiratory low-attenuation areas below -950 Hounsfield units. CT total airway count (TAC) was measured as well as airway inner diameter and wall area using anatomically equivalent airways.Measurements and Main Results: Participants included never-smokers (n = 286), smokers with normal spirometry at risk for COPD (n = 298), Global Initiative for Chronic Obstructive Lung Disease (GOLD) I COPD (n = 361), and GOLD II COPD (n = 239). TAC was significantly reduced by 19% in both GOLD I and GOLD II compared with never-smokers (P < 0.0001) and by 17% in both GOLD I and GOLD II compared with at-risk participants (P < 0.0001) after adjusting for low-attenuation areas below -950 Hounsfield units. Further analysis revealed parent airways with missing daughter branches had reduced inner diameters (P < 0.0001) and thinner walls (P < 0.0001) compared with those without missing daughter branches. Among all CT measures, TAC had the greatest influence on FEV1 (P < 0.0001), FEV1/FVC (P < 0.0001), and bronchodilator responsiveness (P < 0.0001). TAC was independently associated with lung function decline (FEV1, P = 0.02; FEV1/FVC, P = 0.01).Conclusions: TAC may reflect the airway-related disease changes that accumulate in the "quiet" zone in early/mild COPD, indicating that TAC acquired with commercially available software across various CT platforms may be a biomarker to predict accelerated COPD progression. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to assess whether sex differences exist in plaque burden and plaque subtype as assessed by coronary computed tomography angiography (CCTA). Methods: The study cohort included 937 consecutive patients who underwent CCTA between 2008 and 2010. Stenosis was quantified using the Society of Cardiovascular Computed Tomography stenosis grading scale and a total stenosis score (TSS) was generated. Plaque morphology (PM) was reported as predominantly calcified (CP), noncalcified (NCP), or mixed (MP) plaque, and CP, NCP, and MP percentages were calculated. Results: On multivariate analysis, men were significantly more likely to have plaque (65.9% of men vs. 44.6% of women, p<0.001), at least one segment with ≥50% stenosis (22.7% of men vs. 10.3% of women, p<0.001) and higher TSS (mean score=2.81 for men vs. 1.58 for women, p<0.001). Sex was the strongest predictor in all models (odds ratio [OR]=2.55, 95% confidence interval [CI] 1.78-3.67, p<0.001 for any plaque; OR=2.48, 95% CI 1.48-4.16, p<0.01 for segments with ≥50% stenosis; β=1.46, 95% CI 0.69-2.22, p<0.001 for TSS). Among patients with coronary plaque present, no significant sex differences in PM were found. Conclusions: Sex was the strongest risk factor for the presence and extent of plaque. Significant sex differences in PM did not exist. [ABSTRACT FROM AUTHOR]

Background: Subclinical leaflet thrombosis, characterized by hypoattenuated leaflet thickening (HALT) and reduced leaflet motion observed on 4-dimensional computed tomography (CT), may represent a form of bioprosthetic valve dysfunction.Objectives: The U.S. Food and Drug Administration mandated CT studies to understand the natural history of this finding, differences between transcatheter and surgical valves, and its association with valve hemodynamics and clinical outcomes.Methods: The PARTNER 3 (The Safety and Effectiveness of the SAPIEN 3 Transcatheter Heart Valve in Low-Risk Patients With Aortic Stenosis) CT substudy randomized 435 patients with low-surgical-risk aortic stenosis to undergo transcatheter aortic valve replacement (n = 221) or surgery (n = 214). Serial 4-dimensional CTs were performed at 30 days and 1 year and were analyzed independently by a core laboratory.Results: The incidence of HALT increased from 10% at 30 days to 24% at 1 year. Spontaneous resolution of 30-day HALT occurred in 54% of patients at 1 year, whereas new HALT appeared in 21% of patients at 1 year. HALT was more frequent in transcatheter versus surgical valves at 30 days (13% vs. 5%; p = 0.03), but not at 1 year (28% vs. 20%; p = 0.19). The presence of HALT did not significantly affect aortic valve mean gradients at 30 days or 1 year. Patients with HALT at both 30 days and 1 year, compared with those with no HALT at 30 days and 1 year, had significantly increased aortic valve gradients at 1 year (17.8 ± 2.2 mm Hg vs. 12.7. ± 0.3 mm Hg; p = 0.04).Conclusions: Subclinical leaflet thrombosis was more frequent in transcatheter compared with surgical valves at 30 days, but not at 1 year. The impact of HALT on thromboembolic complications and structural valve degeneration needs further assessment. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) remains a leading cause of morbidity and mortality. In atherothrombotic MI (ST-elevation MI and type 1 non-ST-elevation MI), coronary artery occlusion leads to ischemia. Subsequent cardiomyocyte necrosis evolves over time as a wavefront within the territory at risk. The spectrum of ischemia and reperfusion injury is wide: it can be minimal in aborted MI or myocardial necrosis can be large and complicated by microvascular obstruction and reperfusion hemorrhage. Established risk scores and infarct classifications help with patient management but do not consider tissue injury characteristics. This document outlines the Canadian Cardiovascular Society classification of acute MI. It is an expert consensus formed on the basis of decades of data on atherothrombotic MI with reperfusion therapy. Four stages of progressively worsening myocardial tissue injury are identified: (1) aborted MI (no/minimal myocardial necrosis); (2) MI with significant cardiomyocyte necrosis, but without microvascular injury; (3) cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, "no-reflow"); and (4) cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. Clinical studies have shown worse remodeling and increase in adverse clinical outcomes with progressive injury. Notably, microvascular injury is of particular importance, with the most severe form (hemorrhagic MI) leading to infarct expansion and risk of mechanical complications. This classification has the potential to stratify risk in MI patients and lay the groundwork for development of new, injury stage-specific and tissue pathology-based therapies for MI., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient., Research Question: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines?, Study Design and Methods: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis., Results: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91)., Interpretation: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific., Competing Interests: Financial/Nonfinancial Disclosures None declared., (Crown Copyright © 2023. Published by Elsevier Inc. All rights reserved.)

Background Existing CT emphysema measurements quantify the extent or clustering of emphysema voxels in chronic obstructive pulmonary disease (COPD); however, these measurements do not quantify how those voxels are clustered. Purpose To develop a CT measurement to quantify the "compactness" of emphysema voxels, called the normalized join count (NJC), and to determine whether the NJC measurement differentiates COPD disease severity and correlates with lung function and visual emphysema scores. Materials and Methods In this secondary analysis of a prospective study, lung function and CT images were obtained from the Canadian Cohort Obstructive Lung Disease study visit 1 from 2009 to 2013. Participants were categorized as never-smokers, at risk, mild COPD, or moderate-severe COPD. Diffusion capacity for carbon monoxide/alveolar volume was measured. CT emphysema was scored visually by radiologists. CT measurements included the percentage low-attenuation area with attenuation less than -950 HU (%LAA -950insp ), low-attenuation cluster (LAC), and lowest 15th percentile point of the CT lung density histogram. NJC was developed to measure compactness of CT emphysema voxels. An analysis of variance determined differences between groups. Multivariable ridge regression determined association between CT measurements with lung function and radiologist scores. Results A total of 1294 participants (750 men; mean age, 67 years ± 10) were analyzed (277 never-smokers, 306 at risk, 427 mild COPD, and 284 moderate-severe COPD). NJC, %LAA -950insp , and LAC measurements were higher in moderate-severe COPD than in never-smokers and at-risk participants ( P < .05 for all comparisons), but only NJC was different between mild and ;moderate-severe COPD (mean, 1.98% ± 3.61 vs 1.44% ± 2.14; P < .05). In multivariable regression analysis, among all CT measurements NJC had the greatest relative contribution to diffusion capacity for carbon monoxide/alveolar volume ( P = .002) and visual emphysema score ( P < .001). Conclusion The relationship of normalized join count with severity of chronic obstructive pulmonary disease may indicate that the assessment of this disease is dependent on the number of low attenuating voxels or the size of clusters and the spatial arrangement of such voxels. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

Background People living with HIV (PLWH) have a higher risk of myocardial infarction. Coronary atherosclerotic plaque CT characterization helps to predict cardiovascular risk. Purpose To measure CT characteristics of coronary plaque in PLWH without known cardiovascular disease and healthy volunteers without HIV. Materials and Methods In this prospective study, noncontrast CT (all participants, n = 265) was used for coronary artery calcium (CAC) scoring in asymptomatic PLWH and healthy volunteers without HIV, without known cardiovascular disease, from 2012 to 2019. At coronary CT angiography ( n = 233), prevalence, frequency, and volume of calcified, mixed, and noncalcified plaque were measured. Poisson regressions were used with adjustment for cardiovascular risk factors. Results There were 181 PLWH (mean age, 56 years ± 7; 167 men) and 84 healthy volunteers (mean age, 57 years ± 8; 65 men) evaluated by using noncontrast CT. CT angiography was performed in 155 PLWH and 78 healthy volunteers. Median 10-year Framingham risk score was not different between PLWH and healthy volunteers (10% vs 9%, respectively; P = .45), as were CAC score (odds ratio [OR], 1.06; 95% CI: 0.58, 1.94; P = .85) and overall plaque prevalence (prevalence ratio, 1.07; 95% CI: 0.86, 1.32; P = .55) after adjustment for cardiovascular risk. Noncalcified plaque prevalence (prevalence ratio, 2.5; 95% CI: 1.07, 5.67; P = .03) and volume (OR, 2.8; 95% CI: 1.05, 7.40; P = .04) were higher in PLWH. Calcified plaque frequency was reduced in PLWH (OR, 0.6; 95% CI: 0.40, 0.91; P = .02). Treatment with protease inhibitors was associated with higher volume of overall (OR, 1.8; 95% CI: 1.09, 2.85; P = .02) and mixed plaque (OR, 1.6; 95% CI: 1.04, 2.45; P = .03). Conclusion Noncalcified coronary plaque burden at coronary CT angiography was two- to threefold higher in asymptomatic people living with HIV without known cardiovascular disease compared with healthy volunteers without HIV. © RSNA, 2021 Online supplemental material is available for this article . See also the editorial by Lai in this issue.

Magnetic resonance imaging (MRI) is often considered the gold-standard test for characterizing cardiac as well as noncardiac structure and function. However, many patients with cardiac implantable electronic devices (CIEDs) and/or severe renal dysfunction are unable to undergo this test because of safety concerns. In the past 10 years, newer-generation CIEDs and gadolinium-based contrast agents (GBCAs) as well as coordinated care between imaging and heart rhythm device teams have mitigated risk to patients and improved access to MRI at many hospitals. The purpose of this statement is to review published data on safety of MRI in patients with conditional and nonconditional CIEDs in addition to patient risks from older and newer GBCAs. This statement was developed through multidisciplinary collaboration of pan-Canadian experts after a relevant and independent literature search by the Canadian Agency for Drugs and Technologies in Health. All recommendations align with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Key recommendations include: (1) the development of standardized protocols for patients with a CIED undergoing MRI; (2) patients with MRI nonconditional pacemakers and pacemaker dependency should be programmed to asynchronous mode and those with MRI nonconditional transvenous defibrillators should have tachycardia therapies turned off during the scan; and (3) macrocyclic or newer linear GBCAs should be used in preference to older GBCAs because of their better safety profile in patients at higher risk of nephrogenic systemic fibrosis., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is underdiagnosed in the community. Thoracic CT scans are widely used for diagnostic and screening purposes for lung cancer. In this proof-of-concept study, we aimed to evaluate a software pipeline for the automated detection of COPD, based on deep learning and a dataset of low-dose CTs that were performed for early detection of lung cancer., Methods: We examined the use of deep residual networks, a type of artificial residual network, for the automated detection of COPD. Three versions of the residual networks were independently trained to perform COPD diagnosis using random subsets of CT scans collected from the PanCan study, which enrolled ex-smokers and current smokers at high risk of lung cancer, and evaluated the networks using three-fold cross-validation experiments. External validation was performed using 2153 CT scans acquired from a separate cohort of individuals with COPD in the ECLIPSE study. Spirometric data were used to define COPD, with stages defined according to the GOLD criteria., Findings: The best performing networks achieved an area under the receiver operating characteristic curve (AUC) of 0·889 (SD 0·017) in three-fold cross-validation experiments. When the same set of networks was applied to the ECLIPSE cohort without any modifications to the trained models, they achieved an AUC of 0·886 (0·017), a positive predictive value of 0·847 (0·056), and a negative predictive value of 0·755 (0·097), which is a greater performance than the best quantitative CT measure, the percentage of lung volumes of less than or equal to -950 Hounsfield units (AUC 0·742)., Interpretation: Our proposed approach could identify patients with COPD among ex-smokers and current smokers without a previous diagnosis of COPD, with clinically acceptable performance. The use of deep residual networks on chest CT scans could be an effective case-finding tool for COPD detection and diagnosis, particularly in ex-smokers and current smokers who are being screened for lung cancer., Funding: Data Science Institute, University of British Columbia; Canadian Institutes of Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To perform clinical and echocardiographic follow-up beyond 1 year in consecutive patients with severe bicuspid aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) with a current generation balloon-expandable valve., Background: Treatment of bicuspid aortic valve disease with TAVR remains controversial and late follow-up data is still scarce., Methods: We collected baseline characteristics, procedural data, 30-day and mid-term clinical follow-up findings from six centers in Europe and Canada from patients with bicuspid AS treated with TAVR using the SAPIEN 3 valve., Results: Seventy-nine patients underwent TAVR. Mean age was 76 ± 9 years; median STS risk score for mortality was 3.8% (interquartile range 2.3-5.5%). Median follow-up was 390 days (interquartile range 138-739 days). Device success was achieved in 95% of patients. Postimplantation mean aortic gradient decreased from 50.2 ± 16.2 to 8.8 ± 4.4 mmHg and no patient had more than mild aortic regurgitation. At last follow-up, there was persistent good valve performance. At 30 days and 1 year, the rates of all-cause mortality were 3.8 and 7.7%, stroke 1.2 and 1.2%, and the rate of new pacemakers 18 and 18%., Conclusions: Our data confirm that treating patients with stenotic bicuspid aortic valves is safe, effective, and has favorable valve performance over time., (© 2019 Wiley Periodicals, Inc.)

Objectives: To evaluate the long-term (≥2 years) outcomes following transcatheter tricuspid valve repair (TTVr) with the FORMA Transcatheter Tricuspid Valve Repair System (Edwards Lifesciences, Irvine, California)., Background: Scarce data exist on long-term outcomes following TTVr., Methods: This multicenter experience included patients with severe tricuspid regurgitation (TR) who underwent TTVr with the FORMA system at 4 centers under a compassionate clinical use program. Data were collected at baseline, 30 days, and 1 year, and yearly thereafter., Results: Nineteen patients (76 ± 9 years of age, 74% women, mean EuroSCORE II [European System for Cardiac Operative Risk Evaluation] 9.2 ± 5.6%) with functional TR were included. Procedural success was achieved in 17 (89%) patients and there were no cases of 30-day mortality. At a median follow-up of 32 (interquartile range: 24 to 36) months, 4 (24%) patients had died (3 from terminal heart failure, 1 from sepsis) and 3 (18%) patients required rehospitalization for heart failure. There was 1 device-related thrombosis and 1 pulmonary embolism, both in the setting of subtherapeutic oral anticoagulation. Less than severe TR was observed at echocardiography in 67% of patients at the 2- to 3-year follow-up. Among 15 successfully implanted patients with at least 24-month follow-up, significant improvements in New York Heart Association functional class (p < 0.001), 6-min walk test (+54 m; p = 0.016) and Kansas City Cardiomyopathy Questionnaire score (+16 points; p = 0.016) were observed, compared with baseline., Conclusions: TTVr using the FORMA system showed favorable long-term safety profile in high-surgical-risk patients, with sustained functional improvement and acceptable TR reduction up to 3 years., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Left atrial (LA) volume is a well-established cardiovascular prognosticator in patients with end-stage renal disease. Although dialysis intensification is associated with left ventricular mass regression, there are limited data regarding LA remodeling. Using cardiac magnetic resonance imaging (CMR), we examined changes in LA size and function relative to ventricular remodeling and cardiac biomarkers after dialysis intensification., Methods: In this prospective 2-centre cohort study, 37 patients receiving conventional hemodialysis (CHD, 4 h/session, 3×/week) were converted to in-centre nocturnal hemodialysis (INHD 7-8 h/session, 3×/week); 30 patients remained on CHD. CMR and biomarkers were performed at baseline and repeated at 52 weeks., Results: After 52 weeks, there were no significant changes in the LA volumes or LA ejection fraction (EF) within either the CHD or INHD group, and no significant differences between the two groups. Correlations existed between changes in LA and LV end-diastolic volume index (EDVi, Spearman's r = 0.69, p < 0.001), LA and LV end-systolic volume index (ESVi, r = 0.44, p = 0.001), LAEF and LVEF (r = 0.28, p = 0.04), LA and RV EDVi (r = 0.51, p < 0.001), LA and RV ESVi (r = 0.29, p = 0.039), and LA ESVi and LV mass index (r = 0.31, p = 0.02). At baseline, indexed LA volumes positively correlated with NT-proBNP, whereas LAEF negatively correlated with NT-proBNP and Troponin I. After 52 weeks, changes in biomarker levels did not correlate with changes in LA volume or EF., Conclusion: There was no significant change in LA size or systolic function after conversion to INHD. The significant correlations between LA and ventricular remodeling and cardiac biomarkers suggest common underlying pathophysiologic mechanisms., Trial Registration: ClinicalTrials.gov Identifier: NCT00718848.

Background: Severe mitral regurgitation (MR) conveys significant morbidity and mortality, and surgical repair or replacement may not be a desirable option., Objectives: The purpose of this study was to evaluate the feasibility of a percutaneous transseptal transcatheter mitral valve replacement (TMVR) system., Methods: This first-in-human study was conducted between August 2017 and August 2018. The system comprises a nitinol dock, which encircles the chordae tendineae, and a balloon-expandable transcatheter heart valve. The dock and transcatheter heart valve form an ensemble, with the native mitral valve leaflets secured in between, thereby abolishing MR. Key inclusion criteria were severe symptomatic MR and high surgical risk; exclusion criteria included left ventricular ejection fraction <30% or screening suggesting unfavorable anatomy. The primary endpoint was technical success as defined by Mitral Valve Academic Research Consortium (MVARC) criteria at completion of the index procedure. The secondary endpoint was freedom from mortality, stroke, and device dysfunction (MR grade >1, mitral gradient >6 mm Hg, left ventricular outflow tract gradient >20 mm Hg) at 30 days., Results: Ten patients with severe MR of various etiologies (4 degenerative, 4 functional, and 2 mixed) were treated. The device was successfully implanted and the primary endpoint was achieved in 9 of 10 patients (90%). By transesophageal echocardiography, total MR was reduced to ≤ trivial in all implanted patients, and mean transmitral gradient was 2.3 ± 1.4 mm Hg. A pericardial effusion occurred in 1 patient: pericardiocentesis was performed, and the device was not implanted. Median length of hospital stay was 1.5 days. At 30 days, there was no stroke, myocardial infarction, rehospitalization, left ventricular outflow tract obstruction, device migration, embolization, or conversion to mitral surgery. One patient had recurrent regurgitation due to a paravalvular leak, treated with a closure device. All other treated patients had ≤1+ MR. No patients died., Conclusions: Percutaneous transvenous transseptal TMVR is feasible and safe in patients with severe MR who are at high risk for mitral valve surgery. Further evaluation is warranted., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to prospectively determine the safety and efficacy of next-day discharge using the Vancouver 3M (Multidisciplinary, Multimodality, but Minimalist) Clinical Pathway., Background: Transfemoral transcatheter aortic valve replacement (TAVR) is an alternative to surgery in high- and intermediate-risk patients; however, hospital stays average at least 6 days in most trials. The Vancouver 3M Clinical Pathway is focused on next-day discharge, made possible by the use of objective screening criteria as well as streamlined peri- and post-procedural management guidelines., Methods: Patients were enrolled from 6 low-volume (<100 TAVR/year), 4 medium-volume, and 3 high-volume (>200 TAVR/year) centers in Canada and the United States. The primary outcomes were a composite of all-cause death or stroke by 30 days and the proportion of patients successfully discharged home the day following TAVR., Results: Of 1,400 screened patients, 411 were enrolled at 13 centers and received a SAPIEN XT (58.2%) or SAPIEN 3 (41.8%) valve (Edwards Lifesciences, Irvine, California). In centers enrolling exclusively in the study, 55% of screened patients were enrolled. The median age was 84 years (interquartile range: 78 to 87 years) with a median STS score of 4.9% (interquartile range: 3.3% to 6.8%). Next-day discharge home was achieved in 80.1% of patients, and within 48 h in 89.5%. The composite of all-cause mortality or stroke by 30 days occurred in 2.9% (95% confidence interval: 1.7% to 5.1%), with neither component of the primary outcome affected by hospital TAVR volume (p = 0.51). Secondary outcomes at 30 days included major vascular complication 2.4% (n = 10), readmission 9.2% (n = 36), cardiac readmission 5.7% (n = 22), new permanent pacemaker 5.7% (n = 23), and >mild paravalvular regurgitation 3.8% (n = 15)., Conclusions: Adherence to the Vancouver 3M Clinical Pathway at low-, medium-, and high-volume TAVR centers allows next-day discharge home with excellent safety and efficacy outcomes., (Copyright © 2019. Published by Elsevier Inc.)

Background: Pain, commonly localized to the trunk in individuals with COPD, may be due to osteoporosis-related vertebral deformity and chest wall hyper-expansion causing misalignment of joints between the ribs and vertebrae. The purpose of this study was to determine if thoracic vertebral deformity and arthropathy were independent contributors to trunk pain in COPD patients compared to people with a significant smoking history., Method: Participants completed the Brief Pain Inventory (BPI) on the same day as chest CT scans and spirometry. Current and ex-smokers were separated into COPD (n = 91) or non-COPD (n = 80) groups based on spirometry. Subsequently, CT images were assessed for thoracic vertebral deformity, bone attenuation values, and arthropathy of thoracic vertebral joints., Results: The trunk area was the most common pain location in both COPD and non-COPD groups. Thoracic vertebral deformity and costotransverse joint arthropathy were independent contributors to trunk pain in COPD patients (adjusted OR = 3.55 and 1.30, respectively) whereas alcohol consumption contributed to trunk pain in the non-COPD group (adjusted OR = 0.35 in occasional alcohol drinkers; 0.08 in non-alcohol drinkers). The spinal deformity index and the number of narrowed disc spaces were significantly positively related to the BPI intensity, interference, and total scores significantly in COPD patients., Conclusion: Trunk pain, at least in part, is caused by thoracic vertebral deformity, and costotransverse and intervertebral arthropathy in patients living with COPD. The results of this study provided the foundation for the management of pain, which requires further exploration., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Importance: Moderate/severe and even mild paravalvular regurgitation (PVR) are associated with increased mortality following transcatheter aortic valve replacement (TAVR) with first and second generations of transcatheter valves., Objective: To examine the incidence, evolution, and effect on 1-year outcomes of PVR following TAVR with a third-generation balloon-expandable transcatheter heart valve., Design, Setting, and Participants: Prespecified analysis of PVR in the Placement of Aortic Transcatheter Valves (PARTNER) II SAPIEN 3 trial, conducted between October 1, 2013, and September 3, 2014. Multicenter, nonrandomized registry of 1661 patients at intermediate or high surgical risk undergoing TAVR with the SAPIEN 3. Patients with severe, symptomatic aortic stenosis and high/intermediate surgical risk were enrolled in the registry at 51 sites in the United States and Canada., Interventions: Transcatheter aortic valve replacement with the SAPIEN 3 valve., Main Outcomes and Measures: Paravalvular regurgitation was assessed in a core laboratory at 30 days and 1 year according to a 5-class scheme: 0, none or trace; 1, mild; 2, mild to moderate; 3, moderate; 4, moderate to severe; and 5, severe. We assessed the effect of PVR on 1-year mortality and heart failure rehospitalization., Results: Among the 1661 included in the registry, 1592 received a SAPIEN 3 valve and had assessment of PVR. Of these patients, 55.7% had none-trace PVR, 32.6% had mild, 8.2% had mild to moderate, and 3.5% had at least moderate PVR at 30 days. At 1 year, 9.3% of patients had died and 14.2% had been rehospitalized. Only patients with at least moderate PVR had higher 1-year mortality (hazard ratio [HR], 2.40; 95% CI, 1.30-4.43; P = .005) and composite of mortality/rehospitalization (HR, 2.35; 95% CI, 1.52-3.62; P < .001). In a paired comparison including 1213 patients, 73% of the patients with at least moderate PVR at 30 days showed a reduction in PVR severity of at least 1 PVR class at 1 year., Conclusions and Relevance: In this series of patients undergoing TAVR with the SAPIEN 3 valve, at least moderate PVR was rare but associated with increased risk of death and heart failure rehospitalization at 1 year. Even the upper range of the mild class in the 3-class grading scheme (ie, mild to moderate in the 5-class scheme) had no significant effect on short-term mortality or rehospitalization. Most patients with at least moderate PVR at 30 days showed a decrease of PVR severity grade at 1 year., Trial Registration: clinicaltrials.gov Identifier: NCT01314313.

Background: Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use., Methods and Results: Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: R 2 =0.86±0.12; women: R 2 =0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; P <0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3-2.8] for 51-75th SIS% group and 3.4 [2.3-5.0] for >75th SIS% group; P <0.01 for both)., Conclusions: We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637., (© 2017 American Heart Association, Inc.)

Background: Thoracic computed tomography (CT) scans are widely performed in clinical practice, often leading to detection of airway or parenchymal abnormalities in asymptomatic or minimally symptomatic individuals. However, clinical relevance of CT abnormalities is uncertain in the general population., Methods: We evaluated data from 1361 participants aged ≥40 years from a Canadian prospective cohort comprising 408 healthy never-smokers, 502 healthy ever-smokers, and 451 individuals with spirometric evidence of chronic obstructive pulmonary disease (COPD) who had thoracic CT scans. CT images of subjects were visually scored for respiratory bronchiolitis(RB), emphysema(E), bronchial-wall thickening(BWT), expiratory air-trapping(AT), and bronchiectasis(B). Multivariable logistic regression models were used to assess associations of CT features with respiratory symptoms, dyspnea, health status as determined by COPD assessment test, and risk of clinically significant exacerbations during 12 months follow-up., Results: About 11% of life-time never-smokers demonstrated emphysema on CT scans. Prevalence increased to 30% among smokers with normal lung function and 36%, 50%, and 57% among individuals with mild, moderate or severe/very severe COPD, respectively. Presence of emphysema on CT was associated with chronic cough (OR,2.11; 95%CI,1.4-3.18); chronic phlegm production (OR,1.87; 95% CI,1.27-2.76); wheeze (OR,1.61; 95% CI,1.05-2.48); dyspnoea (OR,2.90; 95% CI,1.41-5.98); CAT score≥10(OR,2.17; 95%CI,1.42-3.30) and risk of ≥2 exacerbations over 12 months (OR,2.17; 95% CI, 1.42-3.0)., Conclusions: Burden of thoracic CT abnormalities is high among Canadians ≥40 years of age, including never-smokers and smokers with normal lung function. Detection of emphysema on CT scans is associated with pulmonary symptoms and increased risk of exacerbations, independent of smoking or lung function., Competing Interests: DDM, JCH, JMF, DOD, MK, CJH, RR, RC, SA, PL, and LZ have no conflict to declare. JL reports consultancy for CT scans vendors GE, Samsung, and Philips. DDS reports personal fees from Almirall, AstraZeneca, Amgen, and Novatis, and grants from AstraZeneca, outside the submitted work. FM reports grants and personal fees from GSK, Boehringer Ingelheim, and Novartis, and grants from Nycomed, and AstraZeneca during the conduct of the study. KRC reports grants from Novartis, Almirall, Boehringer Ingelheim, Forest, GSK, AstraZeneca, Amgen, Roche, CSL Behring, Grifols, Genentech, and Kamada, during the conduct of the study; and other from CIHR-GSK Research Chair in Respiratory Health Care Delivery, outside the submitted work. PH has received fees for delivering accredited CME and/or consultancy on advisory board for AstraZeneca, Boehringer Ingelheim, Bayer, CSL Behring, Grifols, GlaxoSmithKline, Merck, Novartis, Roche. Dr.Hernandez's institution has received funding for conducting research from Boehringer Ingelheim, Grifols, and CSL Behring. HOC reports personal fees from GSK, and Samsung, and grants from GSK, and Spiration Inc, outside the submitted work. JB and WCT report grants from the Canadian Institute of Heath Research (CIHR/Rx&D Collaborative Research Program Operating Grants- 93326) with industry partners Astra Zeneca Canada Ltd., Boehringer-Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Merck, Novartis Pharma Canada Inc., Nycomed Canada Inc., and Pfizer Canada Ltd., during the conduct of the study. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: This study sought to evaluate transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BAV) aortic stenosis (AS), with a particular emphasis on TAVR-directed bicuspid aortic valve imaging (BAVi) of morphological classification., Background: TAVR has been used to treat BAV-AS but with heterogeneous outcomes and uncertainty regarding the relevance of morphology., Methods: In 14 centers in the United States, Canada, Europe, and Asia, 130 BAV-AS patients underwent TAVR. Baseline cardiac computed tomography (CT) was analyzed by a dedicated Corelab. Outcomes were assessed in line with Valve Academic Research Consortium criteria., Results: Bicommissural BAV (vs. tricommissural) accounted for 68.9% of those treated in North America, 88.9% in Europe, and 95.5% in Asia (p = 0.003). For bicommissural bicuspids, non-raphe type (vs. raphe type) BAV accounted for 11.9% of those treated in North America, 9.4% in Europe, and 61.9% in Asia (p < 0.001). Overall rates of 30-day mortality (3.8%) and cerebrovascular events (3.2%) were favorable and similar among anatomical subsets. The rate of new permanent pacemaker insertion was high (26.2%) and similar between balloon-expandable (BE) and self-expanding (SE) designs (BE: 25.5% vs. SE: 26.9%; p = 0.83); there was a trend to greater permanent pacemaker insertion in BE TAVR in the presence of coronary cusp fusion BAV morphology. Paravalvular aortic regurgitation (PAR) ≥ moderate was 18.1% overall but lower at 11.5% in those with pre-procedural CT. In the absence of pre-procedural CT, there was an excess of PAR in BE TAVR that was not the case in those with a pre-procedural CT; SE TAVR required more post-dilation. Predictors of PAR included intercommissural distance for bicommissural bicuspids (odd ratio [OR]: 1.37; 95% confidence interval [CI]: 1.02 to 1.84; p = 0.036) and lack of a baseline CT for annular measurement (OR: 3.03; 95% CI: 1.20 to 7.69; p = 0.018)., Conclusions: In this multicenter study, TAVR achieved favorable outcomes in patients with pre-procedural CT, with the exception of high permanent pacemaker rates for all devices and shapes., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study evaluated the results of transcatheter aortic valve replacement (TAVR) in bicuspid aortic stenosis (AS) using a new-generation TAVR device., Background: A bicuspid AS is often considered a relative contraindication to TAVR. Although initial reports have demonstrated feasibility using early-generation devices, outcomes have not matched those seen with tricuspid AS. Paravalvular aortic regurgitation (AR) has been particularly problematic., Methods: We collected baseline characteristics, procedural data, and 30-day clinical follow-up findings from 8 centers in Europe and Canada that had performed TAVR in bicuspid AS using the SAPIEN 3 valve., Results: 51 patients underwent TAVR using the SAPIEN 3 valve. Patient mean age was 76.2 ± 9.3 years and the Society of Thoracic Surgeons predicted risk of mortality scores were 5.2 ± 3.7%. Bicuspid valve types were: type 0, 11.8%; type 1, 82.3%; and type 2, 1.9%. There were no cases of valve embolization or need for a second valve. Post-dilation was performed in 7.8%. The mean aortic gradient decreased from 49.4 ± 16.0 mm Hg to 11.2 ± 4.7 mm Hg. Post-implantation AR was none/trivial in 63% and mild in 37%. There were no cases of moderate or severe AR. At 30-day follow-up, there were 2 deaths (3.9%), 2 major vascular complications, and 12 patients (23.5%) required pacemaker implantation., Conclusions: TAVR in bicuspid AS using a new-generation device was feasible and effective with favorable valve performance and no cases of moderate or severe AR., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Awareness, diagnosis and treatment of COPD, compared to other major causes of death, remains far too low. This article describes the protocol objectives, design and the approaches taken in the Canadian Chronic Obstructive Lung Disease (CanCOLD) study, an epidemiological and integrated research. The CanCOLD study aims at better understanding heterogeneity of COPD presentation and disease progression. We hypothesize that individuals with unfavourable COPD "phenotypes" and subjects at-risk (ever smokers) with unhealthy lifestyle habits, environmental/work exposure, or co-morbidities will have increased risk of lung function decline independent of their cumulative exposure to cigarette smoke. The study is a prospective multi-center cohort study (9 sites in 6 provinces) built on the Canadian COPD prevalence study "COLD." The study plan is to include 1800 subjects at least 40 years old who were sampled from the general population and who were found to fall within 4 groups: 1) COPD moderate-severe (GOLD 2-4); 2) COPD mild (GOLD 1); 3) subjects at-risk (ever smoker); and, 4) subjects never-smoker free of airflow obstruction. Data collection is based on using strictly standardized methods involving questionnaires, pulmonary function and cardiorespiratory exercise tests, CT scans, and blood sampling. CanCOLD is a unique study that will address challenging and important research questions on COPD disease evolution and disease management and will help to define the natural history of COPD disease evolution in individuals at-risk for COPD and in those with COPD who have mild disease.

Objectives: This study sought to evaluate outcomes after implantation of a second transcatheter heart valve (THV-in-THV) for acute THV failure., Background: Aortic regurgitation after transcatheter aortic valve replacement (TAVR) may be valvular due to prosthetic leaflet dysfunction or paravalvular due to poor annular sealing., Methods: Patients undergoing aortic balloon-expandable TAVR at 3 centers were prospectively evaluated at baseline, intraprocedurally, at hospital discharge, and annually., Results: Of 760 patients undergoing TAVR, 21 (2.8%) received a THV-in-THV implant due to acute, severe regurgitation. Aortic regurgitation was paravalvular in 18 patients and transvalvular in the remaining 3 patients. THV-in-THV implantation was technically successful in 19 patients (90%) and unsuccessful in 2 patients (10%), who subsequently underwent open heart surgery. Mortality at 30 days and 1 year was 14.3% and 24%, respectively. After successful THV-in-THV, mean aortic valve gradient fell from 37 ± 12 mm Hg to 13 ± 5 mm Hg (p < 0.01); aortic valve area increased from 0.64 ± 0.14 cm(2) to 1.55 ± 0.27 cm(2) (p < 0.01); and paravalvular aortic regurgitation was none in 4 patients, mild in 13 patients, and moderate in 2 patients. At 1-year follow-up, 1 patient had moderate and the others had mild or no paravalvular leaks. The mean transvalvular gradient was 15 ± 4 mm Hg, which was higher than in patients undergoing conventional TAVR (11 ± 4 mm Hg, p = 0.02)., Conclusions: THV-in-THV implantation is feasible and results in satisfactory short- and mid-term outcomes., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)