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Objectives: to characterize the cost of caring for an outpatient in Canada with Alzheimer disease (AD) based on disease severity, and to describe how costs change with increases in disease severity.Method: community-dwelling patients with mild-to-moderate AD were enrolled in a 3-year, naturalistic, observational study. Assessments included cognition (Mini Mental Status Examination), global ratings (Global Deterioration Scale [GDS]), and daily function (Functional Autonomy Measurement System) as part of the Canadian Outcomes Study in Dementia. Direct (medical and nonmedical) and indirect costs were collected using resource use questionnaires. Costs at baseline were compared with costs at follow-up and correlated with disease severity.Results: total costs associated with treating AD were significantly higher with greater disease severity. The mean total cost to treat patients with very mild AD (GDS = 2) was $367 per month, compared with $4063 per month for patients with severe or very severe AD (GDS = 6). From baseline to follow-up, the greatest changes in cost were observed in the group of patients with the most severe AD as measured by all scales. The largest component of total cost was indirect costs at most severity levels, though medication costs contributed the most in patients with very mild AD. Significant independent contributors to cost were being female, having more impaired activities of daily living, and exhibiting more neuropsychiatric symptoms.Conclusions: costs for treating a patient with AD were strongly associated with disease severity, even though none of the patients were institutionalized. Delaying the progression of AD may reduce indirect costs and burden to caregivers. [ABSTRACT FROM AUTHOR]

Patients with at least one prior failed incisional glaucoma procedure showed a 33% reduction in IOP at 1-year follow-up. [ABSTRACT FROM AUTHOR]

This feature article delves into the realm of α-L-threose nucleic acid (TNA), an artificial nucleic acid analog characterized by a backbone comprising an unconventional four-carbon sugar, α-L-threose, with phosphodiester linkages connecting at the 2' and 3' vicinal positions of the sugar ring. Within this article, we encapsulate the potential, progress, current state of the art, and persisting challenges within TNA research. Kicking off with a historical overview of xeno nucleic acids (XNAs), the discussion transitions to the compelling attributes and structure-property relationships of TNAs as advanced tools when contrasted with natural nucleic acids. Noteworthy aspects such as their advantageous spatial arrangements of functional groups around the sugar ring, stable Watson-Crick base pairing, high binding affinity, biostability, biocompatibility, and in vivo bio-safety are highlighted. Moreover, the narrative unfolds the latest advancements in chemical and biological methodologies for TNA synthesis, spanning from monomer and oligomer synthesis to polymerization, alongside cutting-edge developments in enzyme engineering aimed at bolstering large-scale TNA synthesis for in vitro selection initiatives. The article sheds light on the evolution of TNA aptamers over time, expounding on the tools and selection techniques engineered to unearth superior binding aptamers and TNA catalysts. Furthermore, the article accentuates the recent applications of TNAs across diverse domains such as molecular detection, immunotherapy, gene therapy, synthetic biology, and molecular computing. In conclusion, we summarize the key aspects of recent TNA research, address persisting gaps and challenges, and provide crucial insights and future perspectives in the dynamic domain of TNA research.

Background: Mitral valve replacement in the setting of severe annular calcification (MAC) is associated with high morbidity and mortality. Direct surgical implantation of a transcatheter heart valve (THV) through a transatrial approach is a strategy to mitigate surgical risk. This study reports the perioperative and 1-year outcomes of mitral valve replacement using a THV in patients with severe circumferential MAC at 3 Canadian centers., Methods: Charts were reviewed between January 1, 2018 and September 30, 2023 to identify patients with severe circumferential MAC who had undergone direct implantation of a THV. Primary outcomes were 30-day mortality, debilitating stroke, and 1-year mortality. Secondary outcomes included left ventricular outflow tract obstruction, degree of paravalvular leak (PVL), transvalvular mean pressure gradient, and length of stay., Results: Twenty-two patients at the 3 centers underwent direct implantation of a THV. Nineteen patients were female, with mean age of 70.41 ± 9.33 years. A THV was successfully implanted in all patients. There were 2 deaths at 30 days. Four patients of noncardiac causes at 1 year, and 1 patient had a postoperative stroke. Seventeen (77%) patients had no PVL or trace PVL, 4 had mild PVL, and 1 patient had mild-moderate PVL. The mean transvalvular gradient was 4.42 ± 4.40 mm Hg. There were no cases of left ventricular outflow tract obstruction., Conclusions: Direct deployment of a THV in patients with severe MAC may be a reasonable option. Thirty-day and 1-year mortality rates of 9% and 18%, respectively, suggest that this approach should be reserved for high-risk patients who are not able to undergo conventional strategies., Competing Interests: Disclosures Michael W.A Chu reports financial support was provided by Edwards Lifesciences Corporation. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Randomized trials of transcatheter versus surgical aortic valve replacements have excluded bicuspid anatomy. We compared 3-year outcomes of transcatheter aortic valve replacement versus surgical aortic valve replacement in patients aged more than 65 years with bicuspid aortic stenosis., Methods: The Centers for Medicare and Medicaid data were used to identify 6450 patients undergoing isolated surgical aortic valve replacement (n = 3771) or transcatheter aortic valve replacement (n = 2679) for bicuspid aortic stenosis (2012-2019). Propensity score matching with 21 baseline characteristics including frailty created 797 pairs., Results: Unmatched patients undergoing transcatheter aortic valve replacement were older than patients undergoing surgical aortic valve replacement (78 vs 70 years), with more comorbidities and frailty (all P < .001). After matching, transcatheter aortic valve replacement was associated with a similar mortality risk compared with surgical aortic valve replacement within the first 6 months (hazard ratio [HR], 1.08, 95% CI, 0.67-1.69) but a higher mortality risk between 6 months and 3 years (HR, 2.16, 95% CI, 1.22-3.83). Additionally, transcatheter aortic valve replacement was associated with a lower risk of heart failure readmissions before 6 months (HR, 0.51, 95% CI, 0.31-0.87) but a higher risk between 6 months and 3 years (HR, 4.78, 95% CI, 2.21-10.36). The 3-year risks of aortic valve reintervention (HR, 1.03, 95% CI, 0.30-3.56) and stroke (HR, 1.21, 95% CI, 0.75-1.96) were similar., Conclusions: Among matched Medicare beneficiaries undergoing transcatheter aortic valve replacement or surgical aortic valve replacement for bicuspid aortic stenosis, 3-year mortality was higher after transcatheter aortic valve replacement. However, transcatheter aortic valve replacement was associated with a similar risk of mortality and a lower risk of heart failure readmissions during the first 6 months after the intervention. Randomized comparative data are needed to best inform treatment choice., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Combination therapy has been proven as an effective strategy for cancer treatment. To this end, we report herein a self-assembled nucleic acid-based complex for dual photodynamic and antisense therapy. It contains a nucleolin-targeting As1411-based G-quadruplex platform, a partially hybridized antisense oligonucleotide 4625, which can inhibit the antiapoptotic protein B cell lymphoma-xL inducing apoptotic cell death, and a zinc(II) phthalocyanine (ZnPc)-based photosensitizer held by noncovalent interactions. Through a series of in vitro experiments, we have demonstrated that this DNA complex can be internalized selectively to nucleolin-overexpressed MCF-7 and A549 cells through receptor-mediated endocytosis and is localized in the lysosomes. Upon light irradiation, the photosensitization of ZnPc triggers the formation of reactive oxygen species for cell killing and promotes the lysosomal escape of 4625 for antisense therapy. The combined therapeutic effect can eliminate the cancer cells effectively with a half maximal inhibitory concentration of ca. 0.5 μM., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The optimal revascularization strategy in patients with diabetes and multivessel disease in the setting of a non-ST-segment elevation myocardial infarction (NSTEMI) is unknown., Objectives: The purpose of this study was to compare all-cause mortality between coronary artery bypass grafting (CABG) and multivessel percutaneous coronary intervention (PCI) among patients with diabetes and NSTEMI., Methods: All patients with diabetes and multivessel disease admitted for NSTEMI in Ontario, Canada, between April 2009 and March 2020 were included. Those with previous CABG, PCI in the previous 90 days, or shock were excluded. The primary outcome was all-cause mortality. Propensity score matching was used to account for confounding. Patients who had a cardiac surgeon consultation and then received PCI were classified as being potentially ineligible for CABG., Results: The cohort included 4,649 CABG and 6,760 PCI patients (mean age: 67.8 ± 11.5 years; 70.4% males), resulting in 2,385 matched pairs. CABG was associated with reduced all-cause mortality compared to PCI over a median follow-up of 5.5 years (5-year estimates: 23.4% vs 26.5%; HR: 0.89; 95% CI: 0.80-0.98; P  = 0.021). However, no significant differences in mortality were observed between CABG and PCI patients without a surgical consultation (2,130 pairs; HR: 0.97; 95% CI: 0.86-1.08), while CABG was associated with reduced mortality when compared against PCI patients who had received a surgical consultation (388 pairs; HR: 0.72; 95% CI: 0.58-0.88; P  = 0.002)., Conclusions: While CABG was associated with reduced all-cause mortality compared to multivessel PCI in patients with diabetes and NSTEMI, CABG benefit was seen only against PCI patients potentially ineligible for CABG after receiving a preprocedure surgical consultation., Competing Interests: This study is funded in part by a Foundation Grant (FDN 154333) from the 10.13039/501100000024Canadian Institutes of Health Research (CIHR). This study was supported by ICES, which is funded by an annual grant from the Ontario 10.13039/100009647Ministry of Health (MOH) and the Ministry of Long-Term Care (MLTC). Dr Godoy receives the Frederick Banting and Charles Best Canada Graduate Scholarship (Doctoral Research Award) from the Canadian Institutes of Health Research. Dr Farkouh has received research grants from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/501100004191Novo Nordisk, and 10.13039/100004336Novartis; and serves as a consultant to Otitopic. Dr Shah is supported by the 10.13039/501100004191Novo Nordisk Research Chair in Equitable Care of Diabetes and Related Conditions from the University of Toronto. Dr Nicolau has received research grants from 10.13039/100002429Amgen, 10.13039/100004325AstraZeneca, 10.13039/100004326Bayer, 10.13039/100008322CSL Behring, 10.13039/501100022274Daiichi Sankyo, Dalcor, 10.13039/501100022336Esperion, 10.13039/100014554Janssen, 10.13039/100004336Novartis, 10.13039/501100004191Novo Nordisk, 10.13039/100004339Sanofi, Vifor; and a scholarship from the Brazilian National Council for Scientific and Technological Development (CNPq #303448/2021/0). Dr Fremes has received research support from AMGEN, Boston Scientific, Medtronics, the Canadian Institutes of Health Research and the National Institutes of Health. Dr Lawler has received unrelated royalties from McGraw-Hill Publishing; and is supported by the Fonds de Recherche du Quebec. Dr Wijeysundera is supported by a Canada Research Chair in Structural Heart Disease Policy and Outcomes. Dr Gaudino has received research grants from the 10.13039/100000002National Institutes of Health and the 10.13039/501100000024Canadian Institutes of Health Research. Dr Ko is supported by the Jack Tu Research Chair in Cardiovascular Outcomes Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Consensus guidelines recommend surgical aortic valve replacement (SAVR) over transcatheter aortic valve replacement (TAVR) in patients with severe aortic stenosis aged ≤65 years. This analysis evaluates clinical practice and outcomes of TAVR and SAVR in patients aged ≤60 years., Methods: We identified 2360 patients aged ≤60 years, including 523 TAVR (22.2%) and 1837 SAVR (77.8%) procedures, from 2013 through 2021 using the California Department of Health Care Access and Information database. The median follow-up time was 2.4 years (interquartile range, 1.1-4.5 years) after TAVR and 4.9 years (interquartile range, 2.8-6.9 years) after SAVR. The primary outcome was 5-year survival. Secondary outcomes included cumulative incidences of reoperation, endocarditis, stroke, and heart failure readmissions with death as a competing risk, compared using propensity score matching., Results: Between 2013 and 2021 TAVR rates in patients aged ≤60 years increased from 7.2% to 45.7% (annual increase of 4.7%, P < .001). Mortality at 30 days was similar for SAVR and TAVR (0.2% vs 0.4%, P = .20). In 358 propensity-matched pairs, TAVR was associated with an increased hazard of 5-year mortality (hazard ratio, 2.5; 95% CI, 1.1-3.7; P = .02). There was no significant difference in the cumulative incidences of reoperation (2.2% vs 3.8%, P = .25), stroke (1.1% vs 0.8%, P = .39), endocarditis (0.8% vs 0.4%, P = .38), and heart failure readmission (1.9% vs 1.2%, P = .10)., Conclusions: TAVR use approaches SAVR use in patients aged ≤60 years in California and is associated with significantly worse 5-year survival. This may indicate a need for randomized trials to inform best practice recommendations., Competing Interests: Disclosures Dr Joanna Chikwe serves as The Annals of Thoracic Surgery Editor-In-Chief. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Contemporary national outcomes of open and endovascular aortic repair for descending thoracic aortic aneurysms (DTAAs) and thoracoabdominal aortic aneurysms (TAAAs) are unclear. This study evaluated this issue by using The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD)., Methods: From July 1, 2017 to June 30, 2022, study investigators identified 3522 adults who underwent planned DTAA repair (open, 328; endovascular, 1895) or TAAA repair (open, 870; endovascular, 429), after excluding ascending aorta or aortic arch aneurysms (zone 0, 1, or 2), interventions with a proximal extent in zone 0 or zone 1, juxtarenal or infrarenal aortic interventions, hybrid procedures, aortic trauma, and aortic infection., Results: Most DTAA interventions (85.2%) were endovascular repairs, whereas most TAAA interventions were open repairs (66.9%). For DTAA interventions, the operative mortality, permanent stroke rate, and rate of spinal cord injury were 4.2%, 3.8%, and 2.4% for endovascular repairs and 9.2%, 8.5%, and 4.6% for open repairs, respectively (all P < .05). For TAAA interventions, the operative mortality, permanent stroke rate, and rate of spinal cord injury were 6.5%, 2.1%, and 3.0% for endovascular repairs and 11.7%, 6.0%, and 12.2% for open repairs, respectively (all P < .05). Increasing annual open TAAA repair volume was associated with lower odds of experiencing the composite of operative mortality, permanent stroke, or spinal cord injury., Conclusions: On the basis of STS ACSD data, endovascular repair was the predominant approach for treating DTAA, whereas most patients undergoing TAAA interventions had an open surgical repair. Outcome differences between open and endovascular approaches may be related to patient selection. Increasing center experience with open TAAA repair is associated with improved outcomes., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Coronary artery disease is a common cause of ischemic left ventricular systolic dysfunction (LVSD), for which the optimal revascularisation strategy remains unclear. We aimed to determine whether percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) results in greater survival advantage in patients with LVSD., Methods: Study-level (SLMA) and reconstructed individual patient data (rIPDMA) meta-analyses from Kaplan-Meier (KM) survival curves were performed. A systematic search of Medline, Embase, and Cochrane Library was conducted for observational and randomised studies published after 2010 that compared PCI and CABG in patients with left ventricular ejection fraction ≤ 40%. The primary outcome was all-cause mortality at longest follow-up. The secondary outcomes were myocardial infarction (MI), stroke, repeated revascularisation, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCE) at longest follow-up., Results: Fourteen studies (11 observational, 3 randomised, 13,063 patients) were eligible for the SLMA. Seven contained digitisable KM curves from which individual patient data could be reconstructed. Study-level analysis found PCI to be associated with increased all-cause mortality (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.18-1.69), MI (HR 2.10, 95% CI 1.62-2.72), repeated revascularisation (HR 2.39, 95% CI 1.37-4.17), and MACCE (HR 1.58, 95% CI 1.23-2.03), without significant differences in stroke (HR 0.86, 95% CI 0.39-1.92) or cardiovascular mortality (HR 1.42, 95% CI 0.78-2.59). In the rIPDMA, PCI resulted in increased all-cause mortality (HR 1.57, 95% CI 1.34-1.87) and repeated revascularisation (HR 3.63, 95% CI 3.12-4.21) but overall lower risk of stroke (HR 0.62, 95% CI 0.39-0.99) owing to fewer events during initial follow-up., Conclusions: In patients with ischemic LVSD, PCI was associated with higher risk of all-cause mortality and repeated revascularisation than CABG, but lower risk of short-term stroke. (PROSPERO: CRD42021291408)., (Copyright © 2024 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: Randomized controlled trials are the gold standard for evidence generation in medicine but are limited by their real-world generalizability, resource needs, shorter follow-up durations and inability to be conducted for all clinical questions. Decision analysis (DA) models may simulate trials and observational studies by using existing data and evidence- and expert-informed assumptions and extend analyses over longer time horizons, different study populations and specific scenarios, helping to translate population outcomes to patient-specific clinical and economic outcomes. Here, we present a scoping review and methodological primer on DA for cardiac surgery research., Methods: A scoping review was performed using the PubMed/MEDLINE, EMBASE and Web of Science databases for cardiac surgery DA studies published until December 2021. Articles were summarized descriptively to quantify trends and ascertain methodological consistency., Results: A total of 184 articles were identified, among which Markov models (N = 92, 50.0%) were the most commonly used models. The most common outcomes were costs (N = 107, 58.2%), quality-adjusted life-years (N = 96, 52.2%) and incremental cost-effectiveness ratios (N = 89, 48.4%). Most (N = 165, 89.7%) articles applied sensitivity analyses, most frequently in the form of deterministic sensitivity analyses (N = 128, 69.6%). Reporting of guidelines to inform the model development and/or reporting was present in 22.3% of articles., Conclusion: DA methods are increasing but remain limited and highly variable in cardiac surgery. A methodological primer is presented and may provide researchers with the foundation to start with or improve DA, as well as provide readers and reviewers with the fundamental concepts to review DA studies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Background: Screening programs for abdominal aortic aneurysm (AAA) are not available in Canada. We sought to determine the effectiveness and costutility of AAA screening in Ontario., Methods: We compared one-time ultrasonography-based AAA screening for people aged 65 years to no screening using a fully probabilistic Markov model with a lifetime horizon. We estimated life-years, quality-adjusted life-years (QALYs), AAA-related deaths, number needed to screen to prevent 1 AAA-related death and costs (in Canadian dollars) from the perspective of the Ontario Ministry of Health. We retrieved model inputs from literature, Statistics Canada, and the Ontario Case Costing Initiative., Results: Screening reduced AAA-related deaths by 84.9% among males and 81.0% among females. Compared with no screening, screening resulted in 0.04 (18.96 v. 18.92) additional life-years and 0.04 (14.95 v. 14.91) additional QALYs at an incremental cost of $80 per person among males. Among females, screening resulted in 0.02 (21.25 v. 21.23) additional life-years and 0.01 (16.20 v. 16.19) additional QALYs at an incremental cost of $11 per person. At a willingness-to-pay of $50 000 per year, screening was cost-effective in 84% (males) and 90% (females) of model iterations. Screening was increasingly cost-effective with higher AAA prevalence., Interpretation: Screening for AAA among people aged 65 years in Ontario was associated with fewer AAA-related deaths and favourable cost-effectiveness. To maximize QALY gains per dollar spent and AAA-related deaths prevented, AAA screening programs should be designed to ensure that populations with high prevalence of AAA participate., Competing Interests: Competing interests: Dominique Vervoort sits on the medical advisory board with the Global Alliance for Rheumatic and Congenital Hearts. Thomas Lindsay reports honoraria from Artivion and participation on an advisory board for Novartis. Varun Kapila is the provincial lead for vascular at Ontario Health. Charles de Mestral reports consulting fees from the Health Technology Assessment Unit, Ontario Health. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Objective: The role of surgical ventricular reconstruction (SVR) in patients with ischemic cardiomyopathy is controversial. Observational series and the Surgical Treatment of IsChemic Heart failure (STICH) trial reported contradictory results. SVR is highly dependent on operator experience. The aim of this study is to compare the long-term results of SVR between a high-volume SVR institution and the STICH trial using individual patient data., Methods: Patients undergoing SVR at San Donato Hospital (Milan) were compared with patients undergoing SVR in STICH (as-treated principle) by inverse probability treatment-weighted Cox regression. The primary outcome was all-cause mortality., Results: The San Donato cohort included 725 patients, whereas the STICH cohort included 501. Compared with the STICH-SVR cohort, San Donato patients were older (66.0, lower quartile, upper quartile [Q1, Q3: 58.0, 72.0] vs 61.9 [Q1, Q3: 55.1, 68.8], P < .001) and with lower left ventricular end-systolic volume index at baseline (LVESVI: 77.0 [Q1, Q3: 59.0, 97.0] vs 80.8 [Q1, Q3: 58.5, 106.8], P = .02). Propensity score weighting yielded 2 similar cohorts. At 4-year follow-up, mortality was significantly lower in the San Donato cohort compared with the STICH-SVR cohort (adjusted hazard ratio, 0.71; 95% confidence interval, 0.53-0.95; P = .001). Greater postoperative LVESVI was independently associated with mortality (hazard ratio, 1.02; 95% confidence interval, 1.01-1.03). At 4 to 6 months of follow-up, the mean reduction of LVESVI in the San Donato cohort was 39.6%, versus 10.7% in the STICH-SVR cohort (P < .001)., Conclusions: Patients with postinfarction LV remodeling undergoing SVR at a high-volume SVR institution had better long-term results than those reported in the STICH trial, suggesting that a new trial testing the SVR hypothesis may be warranted., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Senescent cells have become an important therapeutic target for many age-related dysfunctions and diseases. We report herein a novel nanophotosensitizing system that is responsive to the senescence-associated β-galactosidase (β-gal) for selective detection and elimination of these cells. It involves a dimeric zinc(II) phthalocyanine linked to a β-galactose unit via a self-immolative linker. This compound can self-assemble in aqueous media, forming stable nanoscale particles in which the phthalocyanine units are stacked and self-quenched for fluorescence emission and singlet oxygen production. Upon internalization into senescent HeLa cells, these nanoparticles interact with the overproduced senescence-associated β-gal inside the cells to trigger the disassembly process through enzymatic cleavage of the glycosidic bonds, followed by self-immolation to release the photoactive monomeric phthalocyanine units. These senescent cells can then be lit up with fluorescence and eliminated through the photodynamic action upon light irradiation with a half-maximal inhibitory concentration of 0.06 μM.

Background: Reducing the need for blood transfusion among patients undergoing cardiac surgery FLA reduce postoperative complications and mortality. Our study aimed to assess the effects of administering preoperative i.v. ferric carboxymaltose on postoperative red cell transfusion requirements in patients without anaemia undergoing on-pump cardiac surgery., Methods: This double-blind, randomised, placebo-controlled trial was conducted between October 2016 and November 2019, with a follow-up period of up to 6 weeks after surgery. Patients without anaemia who underwent on-pump cardiac surgery were included as participants and administered i.v. iron in the form of ferric carboxymaltose or placebo once, 24-72 h before surgery. The primary outcome was the number of red cell units transfused during the first four postoperative days, and the secondary outcome measures were blood haemoglobin concentrations at 4 days and 6 weeks after surgery., Results: The 200 patients included were randomly assigned to the ferric carboxymaltose (n=102) and placebo (n=98) groups. By postoperative Day 4, a significantly lower mean number of red cell units were transfused in the ferric carboxymaltose than in the placebo group, 0.3 (0.8) vs 1.6 (4.4), respectively; P=0.007. The mean haemoglobin concentrations on postoperative Day 4 were 9.7 (1) g dl -1 and 9.3 (1) g dl -1 , respectively (P=0.03). Corresponding values at 6 weeks after surgery were 12.6 (1.4) g dl -1 and 11.8 (1.5) g dl -1 , respectively (P=0.012)., Conclusions: In patients without anaemia undergoing on-pump cardiac surgery, treatment with a single dose of 1000 mg ferric carboxymaltose i.v. 1-3 days before surgery significantly reduced the need for red cell transfusions and increased the postoperative haemoglobin concentration., Clinical Trial Registration: NCT02939794., (Copyright © 2023 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Systemic administration of heparin is widely used in patients undergoing open elective abdominal aortic aneurysm (AAA) repair. However, no clear consensus exists in the use of intraoperative heparin during open ruptured AAA (rAAA) repair. In this study, we assessed the safety of intravenous heparin administration in patients undergoing open rAAA repair., Methods: A retrospective cohort study comparing patients who received and did not receive heparin during open rAAA repair in the Vascular Quality Initiative database between 2003 and 2020 was conducted. The primary outcomes were 30-day and 10-year mortality. The secondary outcomes included estimated blood loss, number of packed red blood cells transfused, early postoperative transfusions, and postsurgical complications. Propensity score matching was used to adjust for potentially confounding variables. The outcomes were compared between the 2 groups using relative risk for binary outcomes and paired t-test and the Wilcoxon rank-sum test for normally and non-normally distributed continuous variables, respectively. Survival was examined using Kaplan-Meier curves and compared using a Cox proportional hazards model., Results: A total of 2,410 patients who underwent open rAAA repair between 2003 and 2020 were studied. Of the 2,410 patients, 1,853 patients received intraoperative heparin and 557 did not. Propensity score matching on 25 variables yielded 519 pairs for the heparin to no heparin comparison. Thirty-day mortality was lower in the heparin group (risk ratio: 0.74; 95% confidence interval [CI]: 0.66-0.84) and in-hospital was also lower in the heparin group (risk ratio: 0.68; 95% CI: 0.60-0.77). Furthermore, estimated blood loss was 910 mL (95% CI: 230 mL to 1,590 mL) lower in the heparin group and the mean number of packed red blood cells transfused intraoperatively and postoperatively were 17 units lower in the heparin group (95% CI: 8-42). Ten-year survival was higher for patients who received heparin, and their rate of survival was approximately 40% higher than those who did not receive heparin (hazard ratio: 0.62; 95% CI, 0.53-0.72; P < 0.0001)., Conclusions: In patients who received systemic heparin administration at the time of open rAAA repair, there were significant short-term and long-term survival benefits within 30 days and at 10 years. Heparin administration may have afforded a mortality benefit or been a surrogate for healthier and less moribund patients at the time of the procedure., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: We sought to compare the long-term outcomes of multiarterial graft (MAG) coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) with second-generation drug-eluting stents (DES) to treat stable multivessel coronary artery disease., Methods: This study was a multicenter population-based retrospective analysis of all residents of Ontario, Canada, from January 1, 2011, to December 31, 2019. We identified 3600 cases of elective primary isolated CABG with MAG and 2187 cases of PCI with second-generation DES., Results: After the application of propensity score-weighting using overlap weights, MAG was associated with better survival over 5 years compared with DES (96.8% vs 94.5%; hazard ratio [HR], 0.56; 95% CI, 0.37-0.85). MAG was also associated with better secondary outcomes including a composite of death, myocardial infarction, and stroke (94.3% vs 88.5%; HR, 0.49; 95% CI, 0.36-0.65). The rate of death, stroke, myocardial infarction, and repeat revascularization (91.2% vs 70.7%; HR, 0.24; 95% CI, 0.20-0.30), and the individual end points of myocardial infarction (1.4% vs 6.9%; HR, 0.22; 95% CI, 0.13-0.35), and repeat revascularization (4.1% vs 24.2%; HR, 0.14; 95% CI, 0.10-0.18) were lower with MAG. PCI with second-generation DES was associated with a lower rate of stroke up to 5 years (0.6% vs 1.8%; HR, 3.97; 95% CI, 1.45-10.88)., Conclusions: CABG with MAG was associated with better survival and fewer major cardiac adverse events compared with second-generation DES and might be considered the treatment of choice for patients with stable multivessel coronary artery disease. Further randomized controlled trials are needed to confirm this hypothesis., (Copyright © 2021 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Cumulative costs of transcatheter aortic valve replacement (TAVR) differ in the referral, procedural and postprocedural phases depending on patient comorbidities, type of procedure, and procedural complications. Our goal was to determine the association between neighborhood measures of social deprivation and TAVR costs in each of the 3 phases., Methods: Demographics, patient comorbidities, procedural details, in-hospital complications, and costs for adults undergoing TAVR between 2017 and 2020 in Ontario, Canada were obtained from administrative databases and linked to social deprivation data using the Ontario Marginalization Index. The 3 dimensions of social deprivation assessed were (1) material deprivation, (2) residential instability, and (3) ethnic concentration. Hierarchical generalized linear models were used to determine the association between neighborhood social deprivation and cumulative TAVR costs, reported in 2018 Canadian dollars., Results: We identified a total of 7617 TAVR referrals with 3784 patients undergoing TAVR within our study period. Cumulative mean costs in the referral, procedural and postprocedural phases were $8116±$11 374, $32 790±$17 766, and $18 901±$32 490, respectively. After adjustment for clinical and demographic variables, higher factor scores in residential instability were associated with greater cumulative costs in the postprocedural phase, whereas higher factor scores in the other 2 dimensions of marginalization were not significantly associated with higher costs in any of the 3 phases., Conclusions: This analysis shows that residential instability is associated with higher cumulative costs in the postprocedural phase of TAVR. This lays the foundation for future studies to understand the mechanism of this finding and identify potential mitigation policies., Competing Interests: Disclosures None.

Objective: The reverse fragility index (RFI) describes the number of event conversions needed to convert a statistically nonsignificant dichotomous outcome to a significant one. The objective of the present study was to assess the RFI of vascular surgery randomized controlled trials (RCTs) comparing endovascular vs open surgery for the treatment of abdominal aortic aneurysms (AAAs), carotid artery stenosis (CAS), and peripheral artery disease (PAD)., Methods: MEDLINE and Embase were searched for RCTs that had investigated AAAs, CAS, or PAD with statistically nonsignificant binary primary outcomes. The primary outcome for the present study was the median RFI. Calculation of the RFI was performed by creating two-by-two contingency tables and subtracting events from the group with fewer events and adding nonevents to the same group until a two-tailed Fisher exact test had produced a statistically significant result (P ≤ .05)., Results: Of 4187 reports, 49 studies reporting 103 different primary end points were included. The overall median RFI was 7 (interquartile range [IQR], 5-13). The specific RFIs for AAA, CAS, and PAD were 10 (IQR, 6-15.5), 6 (IQR, 5-9.5), and 7 (IQR, 5.5-10), respectively. Of the 103 end points, 42 (47%) had had a loss to follow-up greater than the RFI, of which 10 were AAA trials (24%), 23 were CAS trials (55%), and 9 were PAD trials (21%). The Pearson correlation demonstrated a significant positive relationship between a study's RFI and the impact factor of its publishing journal (r = 0.38; 95% confidence interval [CI], 0.20-0.54; P < .01), length of follow-up (r = 0.43; 95% CI, 0.26-0.58; P < .01), and sample size (r = 0.28; 95% CI, 0.09-0.45; P < .01)., Conclusions: A small number of events (median, 7) was required to change the outcome of negative RCTs from statistically nonsignificant to significant, with 47% of the studies having missing data that could have reversed the finding of its primary outcome. Reporting of the RFI relative to the loss to follow-up could be of benefit in future trials and provide confidence regarding the robustness of the P value., (Copyright © 2022 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Randomized clinical trials (RCTs) have a key role in progressing biomedical research and guiding clinical decision making, but premature termination remains high (up to 30%), raising concerns regarding funding expenditure and resource allocation. This brief report sought to identify variables associated with RCTs' premature termination and completion., Competing Interests: Declaration of Competing Interest The authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Transcatheter aortic valve replacement (TAVR) has become the standard of care for a wide spectrum of patients with severe aortic stenosis. However, there are wide variations in access to TAVR among jurisdictions. It is unknown if such variation is associated with differences in postprocedural outcomes. Our objective was to determine whether differences in health care delivery in jurisdictions with high vs low access of care to TAVR translate to differences in postprocedural outcomes., Methods: In this observational, retrospective cohort study, we identified all Ontario and New York State residents greater than 18 years of age who received TAVR from January 1, 2012, to December 31, 2018. Our primary outcomes were post-TAVR 30 day in-hospital mortality and all-cause readmissions. Using indirect standardization, we calculated the observed vs expected outcomes for New York patients, had they been treated in Ontario., Results: Our cohort consisted of 16,814 TAVR patients at 36 hospitals in New York State and 5007 TAVR patients at 11 hospitals in Ontario. In Ontario, TAVR access rates increased from ∼18.2 TAVR per million in 2012 to 87.4 TAVR per million in 2018, whereas for New York State, the rates increased from 31.9 to 220.4 TAVR per million. For 30-day mortality, 3.1% of Ontario TAVR patients had an in-hospital death, compared with 2.5% of New York patients. With adjustment, this translated to an observed-expected ratio of 0.70 (95% confidence interval [CI], 0.54-0.92) for New York patients., Conclusions: Having greater access to TAVR may be associated with improved outcomes, potentially because of intervention earlier in the trajectory of the disease., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Aortic stenosis (AS) is a serious and complex condition, for which optimal management continues to evolve rapidly. An understanding of current clinical practice guidelines is critical to effective patient care and shared decision-making. This state of the art review of the 2021 European Society of Cardiology/European Association for Cardio-Thoracic Surgery Guidelines and 2020 American College of Cardiology/American Heart Association Guidelines compares their recommendations for AS based on the evidence to date. The European and American guidelines were generally congruent with the exception of three key distinctions. First, the European guidelines recommend intervening at a left ventricular ejection fraction of 55%, compared with 60% over serial imaging by the American guidelines for asymptomatic patients. Second, the European guidelines recommend a threshold of ≥65 years for surgical bioprosthesis, whereas the American guidelines employ multiple age categories, providing latitude for patient factors and preferences. Third, the guidelines endorse different age cut-offs for transcatheter vs. surgical aortic valve replacement, despite limited evidence. This review also discusses trends indicating a decreasing proportion of mechanical valve replacements. Finally, the review identifies gaps in the literature for areas including transcatheter aortic valve implantation in asymptomatic patients, the appropriateness of Ross procedures, concomitant coronary revascularization with aortic valve replacement, and bicuspid AS. To summarize, this state of the art review compares the latest European and American guidelines on the management of AS to highlight three areas of divergence: timing of intervention, valve selection, and surgical vs. transcatheter aortic valve replacement criteria., Competing Interests: Conflict of interest: G.B.-Z. has consulted for Cardionovum, Crannmedical, Innovheart, Guidotti, Meditrial, Opsens Medical, Replycare, Teleflex, and Terumo. D.Y.T. has consulted for Medtronics Inc (Canada) and Edwards Life Sciences (Canada). M.G. has received research grants from the Canadian Institute of Health Research and the National Institute of Health. S.F. has received grants from the the Canadian Institute of Health Research and is the site co-Principal Investigator for the Medtronic SURTAVI, Medtronic Low Risk, and Boston NeoAccurate IDE trials. The other authors have no conflicts to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To derive and validate models to predict the risk of a cardiac readmission within one year after specific cardiac surgeries using information that is commonly available from hospital electronic medical records., Methods: In this retrospective cohort study, we derived and externally validated clinical models to predict the likelihood of cardiac readmissions within one-year of isolated CABG, AVR, and combined CABG+AVR in Ontario, Canada, using multiple clinical registries and routinely collected administrative databases. For all adult patients who underwent these procedures, multiple Fine and Gray subdistribution hazard models were derived within a competing-risk framework using the cohort from April 2015 to March 2018 and validated in an independent cohort (April 2018 to March 2020)., Results: For the model that predicted post-CABG cardiac readmission, the c-statistic was 0.73 in the derivation cohort and 0.70 in the validation cohort at one-year. For the model that predicted post-AVR cardiac readmission, the c-statistic was 0.74 in the derivation and 0.73 in the validation cohort at one-year. For the model that predicted cardiac readmission following CABG+AVR, the c-statistic was 0.70 in the derivation and 0.66 in the validation cohort at one-year., Conclusions: Prediction of one-year cardiac readmission for isolated CABG, AVR, and combined CABG+AVR can be achieved parsimoniously using multidimensional data sources. Model discrimination was better than existing models derived from single and multicenter registries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier Inc.)

Background: Randomized trials have compared percutaneous coronary intervention and coronary artery bypass grafting (CABG) in patients with left main coronary artery disease undergoing nonemergent revascularization. However, there is a paucity of real-world contemporary observational studies comparing percutaneous coronary intervention (PCI) and CABG., Objectives: The purpose of this study was to compare the long-term clinical outcomes of CABG versus PCI in patients with left main coronary disease., Methods: Clinical and administrative databases for Ontario, Canada, were linked to obtain records of all patients with angiographic evidence of left main coronary artery disease (≥50% stenosis) treated with either isolated CABG or PCI from 2008 to 2020. Emergent, cardiogenic shock, and ST-segment elevation myocardial infarction patients were excluded. Baseline characteristics of patients were compared and 1:1 propensity score matching was performed. Late mortality and major adverse cardiac and cerebrovascular events were compared between the matched groups using a Cox proportional hazard model., Results: After exclusions, 1,299 and 21,287 patients underwent PCI and CABG, respectively. Prior to matching, PCI patients were older (age 75.2 vs 68.0 years) and more likely to be women (34.6% vs 20.1%), although they had less CAD burden. Propensity score matching on 25 baseline covariates yielded 1,128 well-matched pairs. There was no difference in early mortality between PCI and CABG (5.5% vs 3.9%; P = 0.075). Over 7-year follow-up, all-cause mortality (53.6% vs 35.2%; HR: 1.63; 95% CI: 1.42-1.87; P < 0.001) and major adverse cardiac and cerebrovascular events (66.8% vs 48.6%; HR: 1.77; 95% CI: 1.57-2.00) were significantly higher with PCI than CABG., Conclusions: CABG was the most common revascularization strategy in this real-world registry. Patients undergoing PCI were much older and of higher risk at baseline. After matching, there was no difference in early mortality but improved late survival and freedom from major adverse cardiac and cerebrovascular events with CABG., Competing Interests: Funding Support and Author Disclosures This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. This study also received funding from a Foundation grant from the Canadian Institutes of Health Research (grant FDN 148446) and the Ted Rogers Centre for Heart Research. The authors acknowledge that the clinical registry data used in this analysis are from participating hospitals through CorHealth Ontario, which serves as an advisory body to the Ontario Ministry of Health, is funded by the MOH, and is dedicated to improving the quality, efficiency, access, and equity in the delivery of the continuum of adult cardiac and stroke care in Ontario, Canada. Dr Lee has served as the Ted Rogers Chair in Heart Function Outcomes, University Health Network, University of Toronto. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Background Transcatheter aortic valve replacement (TAVR)/intervention has become the standard of care for treatment of severe aortic stenosis across the spectrum of risk. There are socioeconomic disparities in access to TAVR. The impact of these disparities on postprocedural outcomes remains unknown. Our objective was to examine the association between neighborhood-level social deprivation and post-TAVR mortality and hospital readmission. Methods and Results We conducted a population-based retrospective cohort study of all 4145 patients in Ontario, Canada, who received TAVR from April 1, 2017, to March 31, 2020. Our co-primary outcomes were 1-year postprocedure mortality and 1-year postprocedure readmission. Using Cox proportional hazards models for mortality and cause-specific competing risk hazard models for readmission, we evaluated the relationship between neighborhood-level measures of residential instability, material deprivation, and concentration of racial and ethnic groups with post-TAVR outcomes. After multivariable adjustment, we found a statistically significant relationship between residential instability and postprocedural 1-year mortality, ranging from a hazard ratio of 1.64 to a hazard ratio of 2.05. There was a significant association between the highest degree of residential instability and 1-year readmission (hazard ratio, 1.23 [95% CI, 1.01-1.49]). There was no association between material deprivation and concentration of racial and ethnic groups with post-TAVR outcomes. Conclusions Residential instability was associated with increased risk for post-TAVR mortality, and the highest quintile of residential instability was associated with increased post-TAVR readmission. To reduce health disparities and promote an equitable health care system, further research and policy interventions will be required to identify and support economically and socially minoritized patients undergoing TAVR.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low-dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real-world impact of this strategy on the COMPASS-eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population-based cohort of Ontario adults. We compared 5-year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS-eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very-low-dose rivaroxaban therapy would potentially impact ≈ $$ \approx $$ 2 in 5 patients with atherosclerotic disease in Ontario. Eligible individuals with ≥ $$ \ge $$ 2 comorbidities represent a high-risk subgroup that may derive the greatest benefit-to-risk ratio. Selection of patients with high-risk predisposing factors appears appropriate in routine practice.

Background: Transcatheter aortic valve replacement (TAVR) is approved for use across the entire spectrum of risk, including low-surgical-risk patients for severe aortic stenosis (AS). TAVR has been shown to be cost-effective compared with surgical aortic valve replacement (SAVR) in Canada. However, the affordability of implementing TAVR for low-risk AS patients from the hospital's payers' perspective is unknown., Methods: A budget impact analysis was conducted using a 1-year time horizon to quantify the total cost of health care resource utilisation to initially treat low-risk AS patients and manage subsequent adverse events. Differences in cost between TAVR and SAVR were calculated for 100 patients for various scenarios of TAVR uptake (10% to 70%) in low-risk AS patients. Event rates and associated costs were obtained from published literature and provincial datasets. Costs were reported in 2021 Canadian dollars. One-way sensitivity analysis on key TAVR input parameters was conducted., Results: Mean index hospitalisation costs of SAVR and TAVR per patient were $41,956 and $37,669, respectively. The average total costs of managing a low-risk AS patient in 1 year for TAVR and SAVR were $45,897 and $42,659, respectively. The incremental budget impacts of increasing TAVR uptake from 10% to 50% and 70% were 3% and 4.5%, respectively. One-way sensitivity analysis on key variables showed that the main contributors to the cost difference were the intensive care unit stay, permanent pacemaker rate, and hospital length of stay., Conclusions: The incremental annual cost of implementing TAVR in low-risk AS patients was small, making TAVR likely an affordable strategy., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)