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Showing 181–200 of 2058 publications.
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Chami, Jason; Moore, Benjamin M.; Nicholson, Calum; Cordina, Rachael Louise; Baker, David William; Celermajer, David S.Background: Brady- and tachyarrhythmias commonly complicate adult congenital heart disease (ACHD). Permanent pacemakers (PPMs) or implantable cardioverterdefibrillators (ICDs) are often utilised to prevent morbidity or mortality related to arrhythmia, but can also be associated with significant morbidity themselves. Methods: We analysed outcomes from patients in our comprehensive ACHD database who were seen at least twice since 2000 and once since 2018. Of 1953 ACHD patients, 134 had a PPM and 78 had an ICD (47 for primary and 31 for secondary prevention). Results: For PPM patients, 41% had a pacing percentage below 33%, 13% had 3366%, and 46% had above 66%. One fifth required PPM upgrade, most to cardiac resynchronisation therapy, the rest to ICD. There were 33 appropriate ICD shocks in 15 patients (19%) and 34 inappropriate shocks in 13 patients (17%) over a median follow up of 4.6 years (IQR 0.98.3 years). Anti-tachycardia pacing was delivered appropriately for 28% of patients and inappropriately for 9%. Apart from inappropriate therapy, one third of PPM and ICD patients had other device-related complications. Acute PPM complications included lead dysfunction requiring revision (2%), pneumothorax (2%), pleural effusion (2%) and pocket infection (2%). ICDs were also acutely complicated by lead dysfunction (4%) as well as pocket hematoma (3%). The most common long-term complication overall was lead dysfunction, affecting one sixth of both PPM and ICD patients. Finally, the rate of device insertion increased significantly with disease severity. Conclusions: Anti-arrhythmic devices can be lifesaving in ACHD patients, but inappropriate therapy and device-related complications are very common. 2023 The Authors
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Clode, Melanie; Tran, Derek L.; Majumdar, Avik; Ayer, Julian Ganesh J.; Ferrie, Suzie; Cordina, Rachael LouiseThe population of people living with a Fontan circulation are highly heterogenous, including both children and adults, who have complex health issues and comorbidities associated with their unique physiology throughout life. Research focused on nutritional considerations and interventions in the Fontan population is extremely limited beyond childhood. This review article discusses the current literature examining nutritional considerations in the setting of Fontan physiology and provides an overview of the available evidence to support nutritional management strategies and future research directions. Protein-losing enteropathy, growth deficits, bone mineral loss, and malabsorption are well-recognised nutritional concerns within this population, but increased adiposity, altered glucose metabolism, and skeletal muscle deficiency are also more recently identified issues. Emergencing evidence suggets that abnormal body composition is associated with poor circulatory function and health outcomes. Many nutrition-related issues, including the impact of congenital heart disease on nutritional status, factors contributing to altered body composition and comorbidities, as well as the role of the microbiome and metabolomics, remain poodly understood. The Author(s), 2024. Published by Cambridge University Press.
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Guan, Ivy A.; Liu, Joanna Shu Ting; Sawyer, Renata C.; Li, Xiang; Jiao, Wanting; Jiramongkol, Yannasittha; White, Mark D.; Hagimola, Lejla; Passam, Freda H.; Tran, Denise P.; Liu, Xiaoming; Schoenwaelder, Simone M.; Jackson, Shaun P.; Payne, Richard J.; Liu, XuyuA large variety of dietary phytochemicals has been shown to improve thrombosis and stroke outcomes in preclinical studies. Many of these compounds feature electrophilic functionalities that potentially undergo covalent addition to the sulfhydryl side chain of cysteine residues within proteins. However, the impact of such covalent modifications on the platelet activity and function remains unclear. This study explores the irreversible engagement of 23 electrophilic phytochemicals with platelets, unveiling the unique antiplatelet selectivity of sulforaphane (SFN). SFN impairs platelet responses to adenosine diphosphate (ADP) and a thromboxane A2 receptor agonist while not affecting thrombin and collagen-related peptide activation. It also substantially reduces platelet thrombus formation under arterial flow conditions. Using an alkyne-integrated probe, protein disulfide isomerase A6 (PDIA6) was identified as a rapid kinetic responder to SFN. Mechanistic profiling studies revealed SFNs nuanced modulation of PDIA6 activity and substrate specificity. In an electrolytic injury model of thrombosis, SFN enhanced the thrombolytic activity of recombinant tissue plasminogen activator (rtPA) without increasing blood loss. Our results serve as a catalyst for further investigations into the preventive and therapeutic mechanisms of dietary antiplatelets, aiming to enhance the clot-busting power of rtPA, currently the only approved therapeutic for stroke recanalization that has significant limitations. 2024 The Authors. Published by American Chemical Society
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Developmental heterogeneity of vascular cells: Insights into cellular plasticity in atherosclerosis?Lin, Alexander; Ramaswamy, Yogambha; Misra, Ashish K.Smooth muscle cells, endothelial cells and macrophages display remarkable heterogeneity within the healthy vasculature and under pathological conditions. During development, these cells arise from numerous embryological origins, which confound with different microenvironments to generate postnatal vascular cell diversity. In the atherosclerotic plaque milieu, all these cell types exhibit astonishing plasticity, generating a variety of plaque burdening or plaque stabilizing phenotypes. And yet how developmental origin influences intraplaque cell plasticity remains largely unexplored despite evidence suggesting this may be the case. Uncovering the diversity and plasticity of vascular cells is being revolutionized by unbiased single cell whole transcriptome analysis techniques that will likely continue to pave the way for therapeutic research. Cellular plasticity is only just emerging as a target for future therapeutics, and uncovering how intraplaque plasticity differs across vascular beds may provide key insights into why different plaques behave differently and may confer different risks of subsequent cardiovascular events. 2023 Elsevier Ltd
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Ha, Jeffrey T.; Freedman, S. Ben; Kelly, Dearbhla M.; Neuen, Brendon L.; Perkovic, Vlado; Jun, Min; Badve, Sunil V.Rationale & Objective: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKDestimated glomerular filtration rate (eGFR) and albuminuriaand incident AF. Study Design: Systematic review and meta-analysis of cohort studies and randomized controlled trials. Setting & Study Populations: Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis.Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria. Analytical Approach: Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models. Results: 38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR <60 vs ?60 mL/min/1.73 m2: RR, 1.43; 95% CI, 1.30-1.57; and eGFR <90 vs ?90 mL/min/1.73 m2: RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria categories. Limitations: Lack of patient-level data, interaction between eGFR and albuminuria could not be evaluated, possible ascertainment bias due to variation in the methods of AF detection. Conclusions: Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF. Plain-Language Summary: Irregular heartbeat, or atrial fibrillation (AF), is the commonest abnormal heart rhythm. AF occurs commonly in people with chronic kidney disease (CKD), and CKD is also common in people with AF. However, CKD in not widely recognized as a risk factor for new-onset or incident AF. In this research, we combined data on more than 28 million participants in 38 studies to determine whether CKD itself increases the chances of incident AF. We found that both commonly used markers of kidney disease (estimated glomerular filtration rate and albuminuria, ie, protein in the urine) were independently associated with a greater risk of incident AF. This finding suggests that CKD should be recognized as an independent risk factor for incident AF. 2023 National Kidney Foundation, Inc.
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Verrall, Charlotte E.; Tran, Derek L.; Kasparian, Nadine Angele; Williams, Tracey A.; Oxenham, Vincent; Ayer, Julian Ganesh J.; Celermajer, David S.; Cordina, Rachael LouiseAdults with complex congenital heart disease (CHD) are at risk for cognitive dysfunction. However, associations between cognitive dysfunction and psychosocial outcomes are poorly defined. Between June and November 2022, we prospectively recruited 39 adults with complex CHD who completed a computerized cognitive assessment (Cogstate) and validated psychosocial scales measuring psychological distress, health-related quality of life (HRQOL), and resilience. Participants had a mean age of 36.4 11.2years. Over half (62%) were women, most (79%) had complex biventricular CHD, and 21% had Fontan physiology. Prevalence of cognitive dysfunction was greatest in the domains of attention (29%), working memory (25%), and psychomotor speed (21%). Adjusting for age and sex, Pearson partial correlations between Cogstate z-scores and self-reported cognitive problems were small. Participants who lived in the most disadvantaged areas and those with a below-average annual household income had lower global cognitive z-scores (p = 0.02 and p = 0.03, respectively). Two-thirds (64%) reported elevated symptoms of depression, anxiety, and/or stress. Small correlations were observed between psychological distress and cognitive performance. Greater resilience was associated with lower psychological distress (r ? ?0.5, p < 0.001) and higher HRQOL (r = 0.33, p = 0.02). Our findings demonstrate that adults with complex CHD have a high risk of cognitive dysfunction, though may not recognize or report their cognitive challenges. Lower socioeconomic status may be an indicator for those at risk of poorer cognitive functioning. Psychological distress is common though may not be a strong correlate of performance-based cognitive functioning. Formal cognitive evaluation in this patient population is essential. Optimizing resilience may be a protective strategy to minimize psychological distress and bolster HRQOL. The Author(s) 2024.
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Ngwira, Memory M.; Gadama, Luis Aaron; Shanmugalingam, Renuka; Makris, Angela; Hennessy, AnnemarieObjectives: This study investigated perceptions of the challenges for patients and health care workers (HCW) in dealing with preeclampsia in Blantyre, Malawi. Methods: A descriptive cross-sectional formative study using semi-structured In-Depth Interviews (IDI) was conducted at Queen Elizabeth Central Hospital (QECH), Malawi. Data was analyzed using NVIVO software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. Patients were interviewed who recently had preeclampsia. Results: Stress, lack of information, physical symptoms, delay in receiving care were identified challenges to better care among patients as well as the impact of poor pregnancy outcomes. Late diagnosis, staff burn out, inadequate skills and lack of resources were expressed as challenge to provide better management by the interviewed HCWs. Conclusion: Our study showed that a diagnosis of preeclampsia is challenging to both patients and HCWs. These challenges need to be addressed carefully at all levels for optimal management of preeclampsia in Malawi, Africa and in order to improve outcomes. 2024 The Author(s)
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Lawer, Aggie; Schulz, Luke P.; Sawyer, Renata C.; Liu, XuyuPost-translational modifications (PTMs) are crucial mechanisms that underlie the intricacies of biological systems and disease mechanisms. This review focuses on the latest advancements in the design of heterobifunctional small molecules that hijack PTM machineries for target-specific modifications in living systems. A key innovation in this field is the development of proteolysis-targeting chimeras (PROTACs), which promote the ubiquitination of target proteins for proteasomal degradation. The past decade has seen several adaptations of the PROTAC concept to facilitate targeted (de)phosphorylation and acetylation. Protein fusion tags have been particularly vital in these proof-of-concept studies, aiding in the investigation of the functional roles of post-translationally modified proteins linked to diseases. This overview delves into protein-tagging strategies that enable the targeted modulation of ubiquitination, phosphorylation, and acetylation, emphasizing the synergies and challenges of integrating heterobifunctional molecules with protein tags in PTM research. Despite significant progress, many PTMs remain to be explored, and protein tag-assisted PTM-inducing chimeras will continue to play an important role in understanding the fundamental roles of protein PTMs and in exploring the therapeutic potential of manipulating protein modifications, particularly for targets not yet addressed by existing drugs. 2024 by the authors.
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Mant, Jonathan W.F.; Modi, Rakesh Narendra; Charlton, Peter H.; Dymond, Andrew; Massou, Efthalia; Brimicombe, James David; Freedman, Ben; Griffin, Simon J.; Hobbs, FD Richard; Lip, Gregory Y.H.; McManus, R. J.; Williams, Kate M.Aims: There are few data on the feasibility of population screening for paroxysmal atrial fibrillation (AF) using hand-held electrocardiogram (ECG) devices outside a specialist setting or in people over the age of 75. We investigated the feasibility of screening when conducted without face-to-face contact ('remote') or via in-person appointments in primary care and explored impact of age on screening outcomes. Methods and results: People aged ?65 years from 13 general practices in England participated in screening during 2019-20. This involved attending a practice nurse appointment (10 practices) or receiving an ECG device by post (three practices). Participants were asked to use a hand-held ECG for 1-4 weeks. Screening outcomes included uptake, quality of ECGs, AF detection rates, and uptake of anticoagulation if AF was detected. Screening was carried out by 2141 (87.5%) of people invited to practice nurse-led screening and by 288 (90.0%) invited to remote screening. At least 56 interpretable ECGs were provided by 98.0% of participants who participated for 3 weeks, with no significant differences by setting or age, except people aged 85 or over (91.1%). Overall, 2.6% (64/2429) screened participants had AF, with detection rising with age (9.2% in people aged 85 or over). A total of 53/64 (82.8%) people with AF commenced anticoagulation. Uptake of anticoagulation did not vary by age. Conclusion: Population screening for paroxysmal AF is feasible in general practice and without face-to-face contact for all ages over 64 years, including people aged 85 and over. 2024 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
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Hurst, Lauren; Kirwan, Morwenna; Christie, Vita; Cross, Cara; Baylis, Sam; White, Liam; Gwynne, Kylie G.Indigenous peoples globally experience a high burden of type 2 diabetes in comparison to non-Indigenous peoples. While community-based exercise interventions designed for type 2 diabetes (T2D) management have garnered success in non-Indigenous populations, they likely require adjustments to meet the needs of Indigenous people. This systematic review aims to determine if health outcomes in Indigenous peoples with T2D could be improved by community-based exercise programmes and the features of those programmes that best meet their needs. The CINAHL, Embase, Informit Indigenous Collection, Medline, PubMed, Scopus, SportDiscus, and Web of Science databases have been searched to identify peer-reviewed literature with original outcome data that report on the health effects of community-based exercise interventions for the management of T2D among Indigenous peoples. The Mixed Methods Appraisal Tool and Indigenous Community Engagement Tool were implemented to assess methodological quality. Three moderate-to-high-quality studies were selected for review, including participants of Polynesian or Native American Zuni Indian descent. Results indicated positive effects of group exercise on glycated haemoglobin (HbA1c), body mass index, body weight, total cholesterol, blood pressure, quality of life, and patient activation levels in high-adhering participants. This review concludes that community-based exercise interventions may improve health outcomes for Indigenous adults with T2D when conducted with strong community engagement. 2024 by the authors.
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Christie, Vita; Riley, Lynette; Green, Deb; Amin, Janaki; Skinner, John C.; Pyke, Christopher M.; Gwynne, Kylie G.In Australia, the incidence rate of breast cancer is lower in Indigenous* women than non-Indigenous women; however, the mortality rate is higher, with Indigenous women 1.2 times more likely to die from the disease. This paper provides practical and achievable solutions to improve health outcomes for Indigenous women with breast cancer in Australia. This research employed the ContextMechanismOutcome (CMO) framework to reveal potential mechanisms and contextual factors that influence breast cancer outcomes for Indigenous women, stratified into multiple levels, namely, micro (interpersonal), meso (systemic) and macro (policy) levels. The CMO framework allowed us to interpret evidence regarding Indigenous women and breast cancer and provides nine practical ways to improve health outcomes and survival rates. 2024 by the authors.
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Molloy, Cal D.; Long, Linda; Mordi, Ify R.; Bridges, Charlene; Sagar, Viral; Davies, Edward J.; Coats, Andrew J.S.; Dalal, Hasnain M.; Rees, Karen M.; Singh, Sally J.; Taylor, Rod S.Background: People with heart failure experience substantial disease burden that includes low exercise tolerance, poor health-related quality of life (HRQoL), increased risk of mortality and hospital admission, and high healthcare costs. The previous 2018 Cochrane review reported that exercise-based cardiac rehabilitation (ExCR) compared to no exercise control shows improvement in HRQoL and hospital admission amongst people with heart failure, as well as possible reduction in mortality over the longer term, and that these reductions appear to be consistent across patient and programme characteristics. Limitations noted by the authors of this previous Cochrane review include the following: (1) most trials were undertaken in patients with heart failure with reduced (< 45%) ejection fraction (HFrEF), and women, older people, and those with heart failure with preserved (? 45%) ejection fraction (HFpEF) were under-represented; and (2) most trials were undertaken in a hospital or centre-based setting. Objectives: To assess the effects of ExCR on mortality, hospital admission, and health-related quality of life of adults with heart failure. Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO and Web of Science without language restriction on 13 December 2021. We also checked the bibliographies of included studies, identified relevant systematic reviews, and two clinical trials registers. Selection criteria: We included randomised controlled trials (RCTs) that compared ExCR interventions (either exercise only or exercise as part of a comprehensive cardiac rehabilitation) with a follow-up of six months or longer versus a no-exercise control (e.g. usual medical care). The study population comprised adults (? 18 years) with heart failure - either HFrEF or HFpEF. Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were all-cause mortality, mortality due to heart failure, all-cause hospital admissions, heart failure-related hospital admissions, and HRQoL. Secondary outcomes were costs and cost-effectiveness. We used GRADE to assess the certainty of the evidence. Main results: We included 60 trials (8728 participants) with a median of six months' follow-up. For this latest update, we identified 16 new trials (2945 new participants), in addition to the previously identified 44 trials (5783 existing participants). Although the existing evidence base predominantly includes patients with HFrEF, with New York Heart Association (NYHA) classes II and III receiving centre-based ExCR programmes, a growing body of trials includes patients with HFpEF with ExCR undertaken in a home-based setting. All included trials employed a usual care comparator with a formal no-exercise intervention as well as a wide range of active comparators, such as education, psychological intervention, or medical management. The overall risk of bias in the included trials was low or unclear, and we mostly downgraded the certainty of evidence of outcomes upon GRADE assessment. There was no evidence of a difference in the short term (up to 12 months' follow-up) in the pooled risk of all-cause mortality when comparing ExCR versus usual care (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.71 to 1.21; absolute effects 5.0% versus 5.8%; 34 trials, 36 comparisons, 3941 participants; low-certainty evidence). Only a few trials reported information on whether participants died due to heart failure. Participation in ExCR versus usual care likely reduced the risk of all-cause hospital admissions (RR 0.69, 95% CI 0.56 to 0.86; absolute effects 15.9% versus 23.8%; 23 trials, 24 comparisons, 2283 participants; moderate-certainty evidence) and heart failure-related hospital admissions (RR 0.82, 95% CI 0.49 to 1.35; absolute effects 5.6% versus 6.4%; 10 trials; 10 comparisons, 911 participants; moderate-certainty evidence) in the short term. Participation in ExCR likely improved short-term HRQoL as measured by the Minnesota Living with Heart Failure (MLWHF) questionnaire (lower scores indicate better HRQoL and a difference of 5 points or more indicates clinical importance; mean difference (MD) ?7.39 points, 95% CI ?10.30 to ?4.77; 21 trials, 22 comparisons, 2699 participants; moderate-certainty evidence). When pooling HRQoL data measured by any questionnaire/scale, we found that ExCR may improve HRQoL in the short term, but the evidence is very uncertain (33 trials, 37 comparisons, 4769 participants; standardised mean difference (SMD) ?0.52, 95% CI ?0.70 to ?0.34; very-low certainty evidence). ExCR effects appeared to be consistent across different models of ExCR delivery: centre- versus home-based, exercise dose, exercise only versus comprehensive programmes, and aerobic training alone versus aerobic plus resistance programmes. Authors' conclusions: This updated Cochrane review provides additional randomised evidence (16 trials) to support the conclusions of the previous 2018 version of the review. Compared to no exercise control, whilst there was no evidence of a difference in all-cause mortality in people with heart failure, ExCR participation likely reduces the risk of all-cause hospital admissions and heart failure-related hospital admissions, and may result in important improvements in HRQoL. Importantly, this updated review provides additional evidence supporting the use of alternative modes of ExCR delivery, including home-based and digitally-supported programmes. Future ExCR trials need to focus on the recruitment of traditionally less represented heart failure patient groups including older patients, women, and those with HFpEF. 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
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Mayer, Kai R.H.; Ruhoff, Alexander M.; Chan, Nicholas Jun An; Waterhouse, Anna; O'Connor, Andrea J.; Scheibel, Thomas Rainer; Heath, Daniel E.Coronary artery stents are life-saving devices, and millions of these devices are implanted annually to treat coronary heart disease. The current gold standard in treatment is drug-eluting stents, which are coated with a biodegradable polymer layer that elutes antiproliferative drugs to prevent restenosis due to neointimal hyperplasia. Stenting is commonly paired with systemic antiplatelet therapy to prevent stent thrombosis. Despite their clinical success, current stents have significant limitations including inducing local inflammation that drives hyperplasia; a lack of hemocompatibility that promotes thrombosis, increasing need for antiplatelet therapy; and limited endothelialization, which is a critical step in the healing process. In this research, we designed a novel material for use as a next-generation coating for drug-eluting stents that addresses the limitations described above. Specifically, we developed a recombinant spider silk material that is functionalized with an REDV cell-adhesive ligand, a peptide motif that promotes specific adhesion of endothelial cells in the cardiovascular environment. We illustrated that this REDV-modified spider silk variant [eADF4(C16)-REDV] is an endothelial-cell-specific material that can promote the formation of a near-confluent endothelium. We additionally performed hemocompatibility assays using human whole blood and demonstrated that spider silk materials exhibit excellent hemocompatibility under both static and flow conditions. Furthermore, we showed that the material displayed slow enzyme-mediated degradation. Finally, we illustrated the ability to load and release the clinically relevant drug everolimus from recombinant spider silk coatings in a quantity and at a rate similar to that of commercial devices. These results support the use of REDV-functionalized recombinant spider silk as a coating for drug-eluting stents. 2024 American Chemical Society.
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Qadri, Sami F.; Wang, Xiaosuo; Tran, Collin; Fitzpatrick, Michael; Bonnitcha, Paul D.; Sullivan, David; Yki-Jvinen, Hannele; OSullivan, John F.We have recently determined dimethylguanidino valeric acid (DMGV) to be a novel biomarker of liver injury in non-alcoholic fatty liver disease (NAFLD) and an independent predictor of incident diabetes over a decade in advance. DMGV consists of two stereo-isomers, asymmetric dimethylguanidino valeric acid (ADGV) and symmetric dimethylguanidino valeric acid (SDGV). Here we report, for the first time, the upper limits of normal of both isomers in humans at the accepted 5.56% liver fat threshold for NAFLD, determined using in vivo magnetic resonance spectroscopy. We performed independent and blinded comparative analyses of ADGV and SDGV levels using two different liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods in (A) our laboratory, and (B) the New South Wales Chemical Pathology state laboratory, using unique columns, LC-MS/MS equipment, extraction protocols and normalisation approaches. Despite these differences, each laboratory reported consistent absolute concentrations across a range of liver fat percentages. We next determined the diagnostic performance of SDGV compared to ADGV in a cohort of 268 individuals with liver fat measurements. In derivation-validation analyses we determined rule-in/rule-out thresholds and the concentration of SDGV that provides optimal performance across sensitivity and specificity for the identification of NAFLD. In conclusion, we have herein determined for the first time the true human plasma reference range of both isoforms of an emerging novel biomarker of NAFLD, at the accepted upper normal threshold of liver fat. We have also identified that SDGV is the isoform with the best diagnostic performance and determined the optimal cut-point for its detection of NAFLD. 2023
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Lez-Ferndez, Teresa; Farmakis, Dimitrios T.; Ameri, Pietro; Asteggiano, Riccardo; de Azambuja, Evandro; Aznar, Marianne C.; Barac, A.; Bay-Gen, Antoni; Bax, Jeroen Joost J.; Bergler-Klein, Jutta; Boriani, Giuseppe; ?elutkiene, Jelena; Coats, Andrew J.S.; Cohen-Solal, Alain; Cdoba-Mascuno, Ra; Cosyns, Bernard; Filippatos, Gerasimos S.; Fox, Kevin F.; Gulati, Geeta; Inciardi, Riccardo M.; Lee, Geraldine Ann; Mamas, Mamas Andreas; Novo, Giuseppina Maria; Plummer, Chris John; Psyrri, A. K.; Rakisheva, Amina G.; Suter, Thomas Martin; Tini, Giacomo; Tocchetti, Carlo G.; Toutouzas, Konstantinos Pavlos; Wilhelm, Matthias; Metra, Marco; Lyon, Alexander Richard; Rosano, Giuseppe Massimo ClaudioCardio-oncology is a rapidly growing field of cardiovascular (CV) medicine that has resulted from the continuously increasing clinical demand for specialized CV evaluation, prevention and management of patients suffering or surviving from malignant diseases. Dealing with CV disease in patients with cancer requires special knowledge beyond that included in the general core curriculum for cardiology. Therefore, the European Society of Cardiology (ESC) has developed a special core curriculum for cardio-oncology, a consensus document that defines the level of experience and knowledge required for cardiologists in this particular field. It is structured into 8 chapters, including (i) principles of cancer biology and therapy; (ii) forms and definitions of cancer therapy-related cardiovascular toxicity (CTR-CVT); (iii) risk stratification, prevention and monitoring protocols for CTR-CVT; (iv) diagnosis and management of CV disease in patients with cancer; (v) long-term survivorship programmes and cardio-oncology rehabilitation; (vi) multidisciplinary team management of special populations; (vii) organization of cardio-oncology services; (viii) research in cardio-oncology. The core curriculum aims at promoting standardization and harmonization of training and evaluation in cardio-oncology, while it further provides the ground for an ESC certification programme designed to recognize the competencies of certified specialists. 2023 European Society of Cardiology.
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Lindow, Thomas; Manouras, Aristomenis; Lindqvist, Per; Manna, Daniel; Wieslander, Bjn; Kozor, Rebecca A.; Strange, G. A.; Playford, David A.; Ugander, MartinAims Grading of diastolic function can be useful, but indeterminate classifications are common. We aimed to invasively derive and validate a quantitative echocardiographic estimation of pulmonary artery wedge pressure (PAWP) and to compare its prognostic performance to diastolic dysfunction grading. Methods Echocardiographic measures were used to derive an estimated PAWP (ePAWP) using multivariable linear regression and results in patients undergoing right heart catheterization (RHC). Prognostic associations were analysed in the National Echocardiography Database of Australia (NEDA). In patients who had undergone both RHC and echocardiography within 2 h (n = 90), ePAWP was derived using left atrial volume index, mitral peak early velocity (E), and pulmonary vein systolic velocity (S). In a separate external validation cohort (n = 53, simultaneous echocardiography and RHC), ePAWP showed good agreement with invasive PAWP (mean standard deviation difference 0.5 5.0 mmHg) and good diagnostic accuracy for estimating PAWP >15 mmHg [area under the curve (95% confidence interval) 0.94 (0.881.00)]. Among patients in NEDA [n = 38,856, median (interquartile range) follow-up 4.8 (2.38.0) years, 2756 cardiovascular deaths], ePAWP was associated with cardiovascular death even after adjustment for age, sex, and diastolic dysfunction grading [hazard ratio (HR) 1.08 (1.071.09) per mmHg] and provided incremental prognostic information to diastolic dysfunction grading (improved C-statistic from 0.65 to 0.68, P < 0.001). Increased ePAWP was associated with worse prognosis across all grades of diastolic function [HR normal, 1.07 (1.061.09); indeterminate, 1.08 (1.071.09); abnormal, 1.08 (1.071.09), P < 0.001 for all]. Conclusion Echocardiographic ePAWP is an easily acquired continuous variable with good accuracy that associates with prognosis beyond diastolic dysfunction grading. The Author(s) 2023.
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Coats, Andrew J.S.[No abstract available]
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Ameri, Pietro; Mercurio, Valentina; Pollesello, Piero; Anker, Markus S.; Backs, Johannes; Bay-Gen, Antoni; Borlaug, Barry A.; Burkhoff, Daniel; Caravita, Sergio; Chan, Stephen Yu Wah; De Man, Frances S.; Giannakoulas, George A.; Gonzez, Arantxa; Guazzi, Marco; Hassoun, Paul M.; Hemnes, Anna Ryan; Maack, Christoph; Madden, Brendan Patrick; Melenovsky, Vojtech; Mler, Oliver Josef; Papp, Zolt; Pullamsetti, Soni Savai Avai; Rainer, Peter Paul; Redfield, Margaret M.; Rich, Stuart A.; Schiattarella, Gabriele Giacomo; Skaara, Hall; Stellos, Konstantinos; Tedford, Ryan Jm D.; Thum, Thomas; Vachiy, Jean Luc; van der Meer, Peter; van Linthout, Sophie A.; Pruszczyk, Piotr; Seferovic, Petar M.; Coats, Andrew J.S.; Metra, Marco; Rosano, Giuseppe Massimo Claudio; Rosenkranz, Stephan H.; Tocchetti, Carlo G.Pulmonary hypertension (PH) associated with left heart failure (LHF) (PH-LHF) is one of the most common causes of PH. It directly contributes to symptoms and reduced functional capacity and negatively affects right heart function, ultimately leading to a poor prognosis. There are no specific treatments for PH-LHF, despite the high number of drugs tested so far. This scientific document addresses the main knowledge gaps in PH-LHF with emphasis on pathophysiology and clinical trials. Key identified issues include better understanding of the role of pulmonary venous versus arteriolar remodelling, multidimensional phenotyping to recognize patient subgroups positioned to respond to different therapies, and conduct of rigorous pre-clinical studies combining small and large animal models. Advancements in these areas are expected to better inform the design of clinical trials and extend treatment options beyond those effective in pulmonary arterial hypertension. Enrichment strategies, endpoint assessments, and thorough haemodynamic studies, both at rest and during exercise, are proposed to play primary roles to optimize early-stage development of candidate therapies for PH-LHF. 2024 European Society of Cardiology.
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Singh, Jasneil; Gambhir, Tanya; Goh, Tiffany; van Vuuren, Isabelle; Gao, Lingzi; Wise, Steven G.; Waterhouse, AnnaAtherosclerotic plaques are commonly observed at low shear regions, in particular, the left main coronary artery (LMCA) bifurcation. Low shear regions at bifurcations promote endothelial dysfunction, a key factor initiating atherogenesis, however, mechanisms underlying this process are poorly understood. Dynamic in vitro models are critical to investigate endothelial dysfunction, but current static and vessels-on-chip systems typically lack physiologically complex geometries and local shear changes. Here, a bifurcating coronary artery-on-a-chip is developed, mimicking the human LMCA, displaying reduced shear near the bifurcation, verified using computational fluid dynamics simulations. Over 7 days of dynamic culture, human coronary artery endothelial cells aligned with the flow and expressed more Endothelial nitric oxide synthase (eNOS) and intercellular cell adheison molecule-1 (ICAM-1) at high shear regions (12.7dyncm?2) adjacent to, but not at the bifurcation (03dyncm?2). After tumor necrosis factor-alpha (TNF?) stimulation to induce endothelial dysfunction, spatially mapping cellular changes and shear gradients revealed cell alignment is disrupted over a larger area surrounding the bifurcation at a higher shear, and ICAM-1 expression is increased closer to the bifurcation at a lower shear. This coronary artery-on-a-chip establishes a system to spatially map endothelial cell behavior in response to differential shear and vessel geometry, enabling future studies into plaque initiation events, treatment targets, and drug screening. 2024 The Authors. Advanced Materials Technologies published by Wiley-VCH GmbH.
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Moonen, Avalon; Cao, Jacob Y.; Celermajer, David S.; Ng, Martin K.C.Background: Certain patients with functional mitral regurgitation survive longer with fewer heart failure hospitalizations after undergoing transcatheter edge-to-edge repair (TEER); however, clinical markers identifying who will benefit have not been established. The proportionality of mitral regurgitation (MR) severity compared to left ventricular size has been hypothesized to predict clinical outcome. Methods: We sought to combine existing studies to compare outcomes between proportionate MR and disproportionate MR in patients undergoing TEER. PubMed and Medline were searched from January 2018 until May 2023. Data was extracted and synthesized by 2 independent authors using random effects models with risk ratios (RRs) for binary outcomes. The primary outcome was a combined endpoint of all-cause mortality or heart failure hospitalization (ACM/HFH). Other outcomes of interest included ACM and residual >2+ MR after TEER. Results: Six trials with a total of 1594 patients (mean age 71 years, 66% male) were included, which assessed MR proportionality using either a ratio of estimated regurgitant orifice area to left ventricular end-diastolic volume (EROA:LVEDV) or regurgitant fraction. Seven hundred and five (mean age 70 years, 75% male) were classified as proportionate MR, and 889 (mean age 72 years, 60% male) had disproportionate MR. There was no significant association between MR proportionality (by EROA:LVEDV) and ACM (RR 0.79, 95% confidence interval [CI] 0.44-1.42). Proportionality did not significantly associate with ACM/HFH, though there were divergent effect signals when proportionality was measured by EROA:LVEDV (RR 0.80, 95% CI 0.45-1.44) or regurgitant fraction (RR 1.48, 95% CI 0.53-4.11). Disproportionate MR showed a greater association with residual MR > 2+ post-TEER that did not meet statistical significance (RR 1.86, 95% CI 0.77-4.49). Conclusions: In patients undergoing TEER for functional mitral regurgitation, MR proportionality was not significantly associated with ACM/HFH, all-cause mortality, or residual MR. 2024
