Impact of Elevated Gradients After Transcatheter Aortic Valve Implantation for Degenerated Surgical Aortic Valve Bioprostheses.

BACKGROUND: Elevated aortic valve gradients are common after transcatheter aortic valve implantation for degenerated surgical aortic valve replacement bioprostheses, but their clinical impact is uncertain. METHODS: A total of 12 122 patients who underwent transcatheter aortic valve implantation-in-surgical aortic valve replacement from November 2011 to December 2019 in the Society of Thoracic Surgery/American College of Cardiology Transvalvular Therapeutics Registry were included. The primary outcome was a composite of 1-year all-cause mortality, stroke, myocardial infarction, or valve reintervention. Secondary outcomes included 1-year all-cause mortality, readmission, and change from baseline 12-question self-administered Kansas City Cardiomyopathy Questionnaire-Overall Summary Score. Due to nonlinearity observed with restricted cubic splines analysis, a Cox regression analysis with aortic valve mean gradient modeled as a spline-continuous variable (with 20 mm Hg as a cutoff) was used to study the 1-year composite outcome and mortality. RESULTS: The composite outcome occurred most frequently in patients with aortic valve mean gradient ≥30 and <10 mm Hg, as compared with those with 10 to 20 and 20 to 30 mm Hg ranges (unadjusted rates, 13.9%, 12.1%, 7.5%, and 6.5%, respectively; P=0.002). When the mean aortic valve gradient was ≥20 mm Hg, higher gradients were associated with greater risk of the 1-year composite outcome (adjusted hazard ratio, 1.02 [1.02-1.03] per mm Hg; P<0.001) and 1-year mortality (adjusted hazard ratio, 1.02 [1.00-1.03] per mm Hg; P=0.007). Whereas when the mean aortic valve gradient was <20 mm Hg, higher gradients were not significantly associated with the composite outcome (adjusted hazard ratio, 0.99 [0.98-1.003] per mm Hg; P=0.12) but were associated with lower 1-year mortality (adjusted hazard ratio, 0.98 [0.97-0.99] per mm Hg; P=0.007). CONCLUSIONS: The relationship between postprocedural aortic valve mean gradient after transcatheter aortic valve implantation-in-surgical aortic valve replacement and clinical outcomes is complex and nonlinear, with relatively greater adverse events occurring at low and high gradient extremes. Further study of factors mediating the relationship between postprocedural gradients and clinical outcomes, including low-flow states, is necessary.

Intravascular Imaging-Guided Versus Coronary Angiography-Guided Complex PCI: A Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: Trials evaluating the role of intravascular imaging in percutaneous coronary intervention (PCI) for complex coronary artery disease have yielded mixed results. This study aimed to compare the outcomes of intravascular imaging specifically intravascular ultrasound (IVUS) with those from conventional coronary angiography in complex PCI. METHODS: Comprehensive electronic search of MEDLINE, EMBASE, and Cochrane databases was performed until March 2023 for randomized clinical trials (RCTs) comparing intravascular imaging with coronary angiography in patients undergoing complex PCI. Complex PCI was defined per each study, and included PCI for American College of Cardiology/American Heart Association (ACC/AHA) type B2/C lesions, unprotected left main coronary artery disease, or multivessel stenting. The primary study outcome was major adverse clinical events (MACE). RESULTS: The meta-analysis included 10 RCTs with a total of 6615 patients (3576 in the intravascular imaging group and 3039 in the coronary angiography group). The weighted mean-follow up was 28.9 months. Compared with coronary angiography, intravascular imaging reduced MACE (8% vs. 13.3%; relative risk [RR] 0.63; 95% confidence interval [CI] 0.54-0.73), cardiac death (RR 0.47; 95% CI 0.31-0.73), definite/probable stent thrombosis (RR 0.48; 95% CI 0.24-0.97), target vessel revascularization (RR 0.62; 95% CI 0.46-0.83), and target lesion revascularization (RR 0.61; 95% CI 0.47-0.79). There was no difference between both groups in all-cause death (RR 0.79; 95% CI 0.53-1.18) and myocardial infarction (RR 0.80; 95% CI 0.61-1.04). CONCLUSION: In patients undergoing complex PCI, intravascular imaging-specifically IVUS-reduced MACE by decreasing the incidence of cardiac death, stent thrombosis, and target vessel and target lesion revascularization.

Distributed Medical Education (DME) in psychiatry: perspectives on facilitators, obstacles, and factors affecting psychiatrists' willingness to engage in teaching activities.

BACKGROUND: Distributed Medical Education (DME), a decentralized model focused on smaller cities and communities, has been implemented worldwide to bridge the gap in psychiatric education. Faculty engagement in teaching activities such as clinical teaching, supervision, and examinations is a crucial aspect of DME sites. Implementing or expanding DME sites requires careful consideration to identify enablers that contribute to success and barriers that need to be addressed. This study aims to examine enablers, barriers, and factors influencing psychiatrists' willingness to start or continue participating in teaching activities within Dalhousie University's Faculty of Medicine DME sites in two provinces in Atlantic Canada. METHODOLOGY: This cross-sectional study was conducted as part of an environmental scan of Dalhousie Faculty of Medicine's DME programs in Nova Scotia (NS) and New Brunswick (NB), Canada. In February 2023, psychiatrists from seven administrative health zones in these provinces anonymously participated in an online survey. The survey, created with OPINIO, collected data on sociodemographic factors, practice-related characteristics, medical education, and barriers to teaching activities. Five key outcomes were assessed, which included psychiatrists' willingness to engage in (i) clinical training and supervision, (ii) lectures or skills-based teaching, (iii) skills-based examinations, (iv) training and supervision of Canadian-trained psychiatrists, and (v) training and supervision of internationally trained psychiatrists. The study employed various statistical analyses, including descriptive analysis, chi-square tests, and logistic regression, to identify potential predictors associated with each outcome variable. RESULTS: The study involved 60 psychiatrists, primarily male (69%), practicing in NS (53.3%), with international medical education (69%), mainly working in outpatient services (41%). Notably, 60.3% lacked formal medical education training, yet they did not perceive the lack of training as a significant barrier, but lack of protected time as the main one. Despite this, there was a strong willingness to engage in teaching activities, with an average positive response rate of 81.98%. The lack of protected time for teaching/training was a major barrier reported by study participants. Availability to take the Royal College of Physicians and Surgeons of Canada Competency by Design training was the main factor associated with psychiatrists' willingness to participate in the five teaching activities investigated in this study: willingness to participate in clinical training and supervision of psychiatry residents (p = .01); provision of lectures or skills-based teaching for psychiatry residents (p < .01); skills-based examinations of psychiatry residents (p < .001); training/supervision of Canadian-trained psychiatrists (p < .01); and training and supervision of internationally trained psychiatrists (p < .01). CONCLUSION: The study reveals a nuanced picture regarding psychiatrists' engagement in teaching activities at DME sites. Despite a significant association between interest in formal medical education training and willingness to participate in teaching activities, clinicians do not consider the lack of formal training as a barrier. Addressing this complexity requires thoughtful strategies, potentially involving resource allocation, policy modifications, and adjustments to incentive structures by relevant institutions.

Exploring Current Practices, Needs, and Barriers for Expanding Distributed Medical Education and Scholarship in Psychiatry: Protocol for an Environmental Scan Using a Formal Information Search Approach and Explanatory Design.

BACKGROUND: Distributed medical education (DME) offers manifold benefits, such as increased training capacity, enhanced clinical learning, and enhanced rural physician recruitment. Engaged faculty are pivotal to DME's success, necessitating efforts from the academic department to promote integration into scholarly and research activities. Environmental scanning has been used to gather, analyze, and apply information for strategic planning purposes. It helps organizations identify current practices, assess needs and barriers, and respond to emerging risks and opportunities. There are process models and conceptual frameworks developed for environmental scanning in the business and educational sectors. However, the literature lacks methodological direction on how to go about designing and implementing this strategy to guide research and practice in DME, especially in the psychiatry field. OBJECTIVE: This paper presents a protocol for an environmental scanning that aims to understand current practices and identify needs and barriers that must be addressed to facilitate the integration of psychiatrists from the Dalhousie University Faculty of Medicine's distributed education sites in Nova Scotia and New Brunswick into the Department of Psychiatry, contributing for the expansion of DME in both provinces and informing strategic planning and decision-making within the organization. METHODS: This protocol adopts an innovative approach combining a formal information search and an explanatory design that includes quantitative and qualitative data. About 120 psychiatrists from 8 administrative health zones of both provinces will be invited to complete an anonymous web-based survey with questions about demographics, participants' experience and interest in undergraduate, postgraduate, and continuing medical education, research and scholarly activities, quality improvement, and knowledge translation. Focus group sessions will be conducted with a purposive sample of psychiatrists to collect qualitative data on their perspectives on the expansion of DME. RESULTS: Results are expected within 6 months of data collection and will inform policy options for expanding Dalhousie University's psychiatry residency and fellowship programs using the infrastructure and human resources at distributed learning sites, leveraging opportunities regionally, especially in rural areas. CONCLUSIONS: This paper proposes a comprehensive environmental scan procedure adapted from existing approaches. It does this by collecting important characteristics that affect psychiatrists' desire to be involved with research and scholarly activities, which is crucial for the DME expansion. Furthermore, its concordance with the literature facilitates interpretation and comparison. The protocol's new method also fills DME information gaps, allowing one to identify insights and patterns that may shape psychiatric education. This environmental scan's results will answer essential questions about how training programs could involve therapists outside the academic core and make the most of training experiences in semiurban and rural areas. This could help other psychiatry and medical units outside tertiary care establish residency and fellowship programs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46835.

Contemporary Use of Coronary Physiology in Cardiology.

Coronary angiography has a limited ability to predict the functional significance of intermediate coronary lesions. Hence, physiological assessment of coronary lesions, via fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR), has been introduced to determine their functional significance. An accumulating body of evidence has consolidated the role of physiology-guided revascularization, particularly among patients with stable ischemic heart disease. The use of FFR or iFR to guide decision-making in patients with stable ischemic heart disease and intermediate coronary lesions received a class I recommendation from major societal guidelines. Nevertheless, the role of coronary physiology testing is less clear among certain patients' groups, including patients with serial coronary lesions, acute coronary syndromes, aortic stenosis, heart failure, as well as post-percutaneous coronary interventions. In this review, we aimed to discuss the utility and clinical evidence of coronary physiology (mainly FFR and iFR), with emphasis on those specific patient groups.

Outcomes among patients undergoing transcatheter aortic valve replacement with very low baseline gradients.

Background: While there is evidence that patients with low-flow, low-gradient aortic stenosis (AS) benefit from transcatheter aortic valve replacement (TAVR), data are lacking regarding outcomes of patients with a very low gradient (VLG). Methods: In this retrospective, single-center study of patients with severe AS who underwent TAVR, three groups were defined using baseline mean aortic valve gradient: VLG (≤25 mmHg), low gradient (LG, 26-39 mmHg), and high gradient (HG, ≥40 mmHg). The primary outcome was the composite of Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 of <45, decrease in KCCQ-12 of ≥10 compared with baseline, or death at 1 year. Results: One-thousand six patients were included: 571 HG, 353 LG, and 82 VLG. The median age was 82.1 years [interquartile range (IQR) 76.3-86.9]; VLG patients had more baseline comorbidities compared with the other groups. The primary outcome was highest at 1 year in the VLG group (VLG, 46.7%; LG, 29.9%; HG, 23.1%; p = 0.002), with no difference between groups after adjustment for baseline characteristics. At baseline, <30% of VLG patients had an excellent or good (50-100) KCCQ-12, whereas more than 75% and 50% had an excellent or good KCCQ-12 at 30-day and 1-year follow-up, respectively. Conclusion: Although patients with VLG undergoing TAVR have a higher rate of poor outcomes at 1 year compared with patients with LG and HG severe AS, this difference is largely attributable to baseline comorbidities. Patients with severe AS undergoing TAVR have significant improvement in health status outcomes regardless of resting mean gradient.

Augmenting Mental Health Support for Patients Accessing Different Degrees of Formal Psychiatric Care through a Supportive Text Messaging Program: Protocol for a Randomized Controlled Trial.

Patients feel more vulnerable when accessing community mental health programs for the first time or after being discharged from psychiatric inpatient units. Long wait times for follow-up appointments, shortage of mental health professionals, lack of service integration, and scarcity of tailored support can weaken their connection to the health care system. As a result, patients can present low adherence, dissatisfaction with treatment, and recurrent hospitalizations. Finding solutions to avoid unnecessary high-cost services and providing tailored and cost-effective mental health interventions may reduce the health system burden and augment patient support. We propose implementing an add-on, supportive text messaging service (Text4Support), developed using cognitive-behavioural therapy (CBT) principles to augment mental health support for patients attending to or being discharged from psychiatric care in Nova Scotia, Canada. This randomized controlled trial aims to investigate the effectiveness of Text4Support in improving mental health outcomes and overall mental well-being compared with usual care. We also will examine the intervention's impact on health services utilization and patient satisfaction. The results from this study will provide evidence on stepped and technology-based mental health care, which will contribute to generating new knowledge about mental health innovations in various clinical contexts, which is not only helpful for the local context but to other jurisdictions in Canada and abroad that are seeking to improve their health care.

Medicine 2032: The future of cardiovascular disease prevention with machine learning and digital health technology.

Machine learning (ML) refers to computational algorithms that iteratively improve their ability to recognize patterns in data. The digitization of our healthcare infrastructure is generating an abundance of data from electronic health records, imaging, wearables, and sensors that can be analyzed by ML algorithms to generate personalized risk assessments and promote guideline-directed medical management. ML's strength in generating insights from complex medical data to guide clinical decisions must be balanced with the potential to adversely affect patient privacy, safety, health equity, and clinical interpretability. This review provides a primer on key advances in ML for cardiovascular disease prevention and how they may impact clinical practice.

Fractional flow reserve versus angiography alone in guiding myocardial revascularisation: a systematic review and meta-analysis of randomised trials.

BACKGROUND: Randomised trials evaluating the efficacy and safety of fractional flow reserve (FFR)-guided versus angiography-guided revascularisation among patients with obstructive coronary artery disease (CAD) have yielded mixed results. AIMS: To examine the comparative efficacy and safety of FFR-guided versus angiography-guided revascularisation among patients with obstructive CAD. METHODS: An electronic search of MEDLINE, SCOPUS and Cochrane databases without language restrictions was performed through November 2021 for randomised controlled trials that evaluated the outcomes of FFR-guided versus angiography-guided revascularisation. The primary outcome was major adverse cardiac events (MACE). Data were pooled using a random-effects model. RESULTS: The final analysis included seven trials with 5094 patients. The weighted mean follow-up duration was 38 months. Compared with angiography guidance, FFR guidance was associated with fewer number of stents during revascularisation (standardised mean difference=-0.80; 95% CI -1.33 to -0.27), but no difference in total hospital cost. There was no difference between FFR-guided and angiography-guided revascularisation in long-term MACE (13.6% vs 13.9%; risk ratio (RR) 0.97, 95% CI 0.85 to 1.11). Meta-regression analyses did not reveal any evidence of effect modification for MACE with acute coronary syndrome (p=0.36), proportion of three-vessel disease (p=0.88) or left main disease (p=0.50). There were no differences between FFR-guided and angiography-guided revascularisation in the outcomes all-cause mortality (RR 1.16, 95% CI 0.80 to 1.68), cardiovascular mortality (RR 1.27, 95% CI 0.50 to 3.26), repeat revascularisation (RR 0.99, 95% CI 0.81 to 1.21), recurrent myocardial infarction (RR 0.92, 95% CI 0.74 to 1.14) or stent thrombosis (RR 0.61, 95% CI 0.31 to 1.21). CONCLUSION: Among patients with obstructive CAD, FFR-guided revascularisation did not reduce the risk of long-term adverse cardiac events or the individual outcomes. However, FFR-guided revascularisation was associated with fewer number of stents. PROSPERO REGISTRATION NUMBER: CRD42021291596.

Digital health intervention in patients with recent hospitalization for acute heart failure: A systematic review and meta-analysis of randomized trials.

AIM: To examine the efficacy of digital health interventions (DHI) versus standard of care among patients with prior heart failure (HF) hospitalization. METHODS: An electronic search of MEDLINE, Cochrane, OVID, CINHAL and ERIC, databases was performed through August 2021 for randomized clinical trials that evaluated the outcomes with DHI among patients with HF. Data were pooled using the random-effects model. The primary outcome was all-cause mortality. RESULTS: 10 randomized trials were included in our analysis, with a total of 7204 patients and a weighted follow up duration of 15.6 months. Compared with the reference group, patients in the DHI group had lower all-cause mortality (8.5% vs. 10.2%, risk ratio-RR 0.80; 95% confidence interval-CI 0.66 to 0.96; P = 0.02), as well as lower cardiovascular mortality (7.3% vs. 9.6%, RR 0.76; 95% CI 0.62 to 0.94; P = 0.01). There was no significant difference in HF-related hospitalizations (23.4% vs. 26.2%, RR 0.82; 95% CI 0.66 to 1.02; P = 0.07) and all-cause hospitalizations (48.3% vs. 49.9%, RR 0.89; 95% CI 0.77 to 1.03; P = 0.11) in the DHI versus reference groups. Patients in the DHI group had fewer days lost due to HF-related hospitalizations (mean difference-MD: -1.77; 95% CI -3.06,-0.48, p = 0.01; I2 = 51), but similar days lost to all-cause hospitalizations (MD: -0.76; 95% CI -3.07,-1.55, p = 0.52; I2 = 69) compared with patients in the reference group. CONCLUSION: Compared with usual care, DHI among patients with HF provided significant reduction of all-cause mortality and cardiovascular mortality and had fewer total days lost to HF hospitalizations. There were no differences in all-cause hospitalizations, and HF hospitalizations.

DOACs and Atherosclerotic Cardiovascular Disease Management: Can We Find the Right Balance Between Efficacy and Harm.

PURPOSE OF REVIEW: The balance between efficacy and harm remains a challenge in the adoption of non-vitamin K antagonist direct oral anticoagulants (DOACs) for secondary atherosclerotic disease prevention. We provide a comprehensive review of the evidence for and against the addition of DOACs to the current management of atherosclerotic cardiovascular disease, including stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and percutaneous coronary interventions (PCI). RECENT FINDINGS: The DOAC class exerts pleiotropic effects on atherosclerotic progression through coagulation and inflammatory pathways. In ACS, low-dose DOAC provides no added efficacy in the setting of dual antiplatelet therapy; however, full-dose DOAC increases bleeding. Efficacy-safety profile favor use of low-dose rivaroxaban in select stable CAD or PAD patients. Atrial fibrillation patients undergoing PCI resort to dual therapy with DOAC due to prohibitory bleeding with triple anti-thrombotic therapy. Evidence favors DOAC use in CAD and PAD; however, careful individual considerations must be undertaken.

FFR- Versus Angiography-Guided Revascularization for Nonculprit Stenosis in STEMI and Multivessel Disease: A Network Meta-Analysis.

OBJECTIVES: The aim of this study was to examine the efficacy and safety of fractional flow reserve (FFR)-guided versus angiography-guided approaches for nonculprit stenosis among patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel disease. BACKGROUND: The optimal strategy to guide revascularization of nonculprit stenosis among patients with STEMI and multivessel disease remains uncertain. METHODS: Electronic databases were searched for randomized trials evaluating the outcomes of culprit-only revascularization, angiography-guided complete revascularization (CR), or FFR-guided CR. A pairwise meta-analysis comparing CR versus culprit-only revascularization and a network meta-analysis comparing the different revascularization techniques were conducted. The primary outcome was major adverse cardiac events (MACE). RESULTS: The analysis included 11 trials with 8,195 patients. CR (ie, angiography-guided or FFR-guided CR) was associated with a lower incidence of MACE (odds ratio [OR]: 0.46; 95% CI: 0.35 to 0.59), cardiovascular mortality (OR: 0.63; 95% CI: 0.41 to 0.98), recurrent myocardial infarction (OR: 0.67; 95% CI: 0.48 to 0.95), and repeat ischemia-driven revascularization (OR: 0.26; 95% CI: 0.19 to 0.35). Network meta-analysis demonstrated that the incidence of MACE was lower with both angiography-guided CR (OR: 0.43; 95% CI: 0.31 to 0.58) and FFR-guided CR (OR: 0.52; 95% CI: 0.35 to 0.78) compared with a culprit-only approach, while there was no difference in risk for MACE between angiography-guided and FFR-guided CR (OR: 0.81; 95% CI: 0.51 to 1.29). CONCLUSIONS: Among patients with STEMI and multivessel disease, CR, with angiographic or FFR guidance for nonculprit stenosis, was associated with lower incidence of adverse events compared with culprit-only revascularization. FFR-guided CR was not superior to angiography-guided CR in reducing the incidence of adverse events. Future studies investigating other tools to risk-stratify nonculprit stenoses are encouraged.

Molecular genetics of surfactin and its effects on different sub-populations of Bacillus subtilis.

Surfactin is a biosurfactant produced by Bacillus subtilis. The srfA operon, Sfp gene, and two quorum sensing systems are required for its production. The master regulator spo0A also plays an indispensable role in proper surfactin synthesis. Upon production, surfactin itself acts as a signaling molecule and triggers the activation of Spo0A gene which in turn regulates cell differentiation. Interestingly, surfactin producing cells are immune to the action of surfactin but trigger other cells to differentiate into non-motile cells, matrix producing cells, cannibals, and spores. In case of competent cell differentiation, comS, which resides within the srfA operon, is co-expressed along with surfactin and plays a vital role in competent cell differentiation in response to quorum sensing signal. Surfactin inhibits the motility of certain cell subpopulations, although it helps the non-motile cells to swarm. Thus, surfactin plays significant roles in the differentiation of different subpopulations of specialized cell types of B. subtilis.

Cardiovascular and Obstetric Delivery Complications in Pregnant Women With Valvular Heart Disease.

Women with valvular heart disease may be more likely to have adverse obstetric and cardiovascular complications during pregnancy. Most current recommendations focus on stenotic lesions with less guidance regarding regurgitant lesions. We aimed to compare adverse events at delivery for women with various stenotic and regurgitant valvular diseases. We used the 2016 to 2018 National Inpatient Sample data to compare demographics, comorbidities, and obstetric and cardiovascular complications during delivery hospitalizations. After adjusting for clinical and socioeconomic factors, logistic regression was performed to investigate associations between valvular disease and outcomes. Among >11.2 million deliveries, 20,349 were in women with valvular disease. Women with valvular disease were older, had longer length of stays, and higher costs associated with delivery. They had higher prevalence of underlying cardiovascular comorbidities compared with women without valvular disease (hypertension: 5.1 vs 0.25%; pulmonary hypertension: 7.0 vs <0.1%). At delivery, they had higher adjusted odds of obstetric events including preeclampsia and/or eclampsia (aOR 1.9 [1.8 to 2.2]) and intrapartum/postpartum hemorrhage (aOR 1.4 [1.2 to 1.6]), and cardiovascular events including peripartum cardiomyopathy (aOR 65 [53 to 78]), pulmonary edema (aOR 17 [13 to 22]), acute ischemic heart disease (aOR 19 [12 to 30]) and arrhythmias (aOR 22 [19 to 27]). There were valve lesion-specific differences in the magnitude of risk but both stenotic and regurgitant lesions were associated with elevated risk of cardiovascular complications. In conclusion, pregnant women with stenotic and regurgitant valvular disease have a greater burden of cardiovascular comorbidities and increased odds of obstetric and cardiovascular events at delivery. These women may benefit from specialized care from a Cardio-Obstetrics team.

TAVI Beyond 3 Years: Durability and Predictors for Survival.

The use of transcatheter aortic valve implantation (TAVI) has greatly increased over the past 2 decades and now has overtaken surgical aortic valve replacement. We have limited data regarding the long-term durability of TAVI and the predictors of survival. Calcification, inflammation, fibrous tissue deposition, and mechanical stress are important in the structural deterioration of surgical bioprosthetic valves and likely contribute to TAVI durability. However, TAVI has several differences to surgical valve replacement such as valve preparation, valve to native anatomy interaction, and valve sizing which all likely contribute to durability and long-term survival. Most procedures have been performed on older patients and therefore long-term follow-up studies have noted mortality of approximately 50% at 5 years and 75% by 7 years. Current data are limited by the high mortality of patients who have received TAVI often as a result of age, frailty, and other competing comorbidities. TAVI as compared with surgical valve replacement is associated with several differences including higher conduction abnormalities (i.e., need for pacemakers) and paravalvular leak, both of which may affect long-term morbidity and mortality. In this review, we discuss the current status of our knowledge and identify areas that require further investigation.

Europe PMC in 2020.

Europe PMC (https://europepmc.org) is a database of research articles, including peer reviewed full text articles and abstracts, and preprints - all freely available for use via website, APIs and bulk download. This article outlines new developments since 2017 where work has focussed on three key areas: (i) Europe PMC has added to its core content to include life science preprint abstracts and a special collection of full text of COVID-19-related preprints. Europe PMC is unique as an aggregator of biomedical preprints alongside peer-reviewed articles, with over 180 000 preprints available to search. (ii) Europe PMC has significantly expanded its links to content related to the publications, such as links to Unpaywall, providing wider access to full text, preprint peer-review platforms, all major curated data resources in the life sciences, and experimental protocols. The redesigned Europe PMC website features the PubMed abstract and corresponding PMC full text merged into one article page; there is more evident and user-friendly navigation within articles and to related content, plus a figure browse feature. (iii) The expanded annotations platform offers ∼1.3 billion text mined biological terms and concepts sourced from 10 providers and over 40 global data resources.