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Showing 101–120 of 2058 publications.
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Rim, Donggyu; Dawood, Tye; Fatouleh, Rania H.; McCarthy, Brendan; Sesa-Ashton, Gianni; Hennessy, Annemarie; Schlaich, Markus Peter; Henderson, Luke A.; Macefield, Vaughan G.Objective:Hypertension is characterized by elevations in sympathetic nerve activity that are consistently observed regardless of severity and treatment status. Structural changes in the brain occur with hypertension, including grey matter changes, which are associated with elevated blood pressure (BP). However, whether or not these changes are associated with increased sympathetic nerve activity in hypertensives has not been investigated. The present study aimed to determine the relationship between regional grey matter density, muscle sympathetic nerve activity (MSNA) and BP in people with hypertension, compared to normotensive participants.Methods:T1-weighted anatomical scans (3T MRI) were acquired from 35 hypertensive and 57 normotensive participants; MSNA was successfully obtained from the right peroneal nerve in 26 hypertensives and 55 normotensives. Voxel-based morphometry (VBM) analysis was conducted to determine regional grey matter density and the relationships between MSNA and BP in both groups.Results:An inverse relationship between MSNA and grey matter density was found in the left dorsolateral prefrontal cortex, right precentral gyrus, left superior parietal lobule, and right cuneus in hypertensives but not in normotensives. In addition, hypertensive participants showed a negative correlation between grey matter density and DBP in the right precentral gyrus and left postcentral gyrus, which was not observed in controls.Conclusion:We have shown an association between specific nuclei of the brain with elevated MSNA and BP in hypertension. These findings suggest a functional link between grey matter density in specific brain nuclei and MSNA and BP in patients with hypertension. 2025 Wolters Kluwer Health, Inc.
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Volterrani, Maurizio; Halasz, Geza; Adamopoulos, Stamatis N.; Agostoni, Piergiuseppe; Butler, Javed; Coats, Andrew J.S.; Cohen-Solal, Alain; Doehner, Wolfram; Filippatos, Gerasimos S.; Jankowska, Ewa Anita; Lam, Carolyn Su Ping; Lambrinou, Ekaterini; Lund, Lars H.; Rosano, Giuseppe Massimo Claudio; Metra, Marco; Paolillo, Stefania; Perrone-Filardi, Pasquale; Rakisheva, Amina G.; Savarese, Gianluigi; Seferovic, Petar M.; Tocchetti, Carlo G.; PIEPOLI, MASSIMO FrancescoFor most patients with chronic, progressive illnesses, maintaining good quality of life (QoL), with preserved functional capacity, is just as crucial as prolonging survival. Patients with heart failure (HF) experience much worse QoL and effort intolerance than both the general population and people with other chronic conditions, since they present a range of physical and psychological symptoms, including shortness of breath, chest discomfort, fatigue, fluid congestion, trouble with sleeping, and depression. These symptoms reduce patients' capacity for daily social and physical activity. Usual endpoints of large-scale trials in chronic HF have mostly been defined to evaluate treatments regarding hospitalizations and mortality, but more recently, patients' priorities and needs expressed with QoL are gaining more awareness and are being more extensively evaluated. This scientific statement aims at discussing the importance of QoL in HF, summarizing the most largely adopted questionnaires in HF care, and providing an overview on their application in trials and the potential for their transition to clinical practice. Finally, by discussing the reasons limiting their application in daily clinical routine and the strategies that may promote their implementation, this statement aims at fostering the systematic integration of the patient's standpoint in HF care. 2025 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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Ngwira, Memory M.; Makris, Angela; Shanmugalingam, Renuka; Mbotwa, John L.; Mayani, Josiah; Gadama, Luis Aaron; Hennessy, AnnemarieBACKGROUND: Preeclampsia remains one of the major causes of maternal and neonatal mortality and morbidity, and yet it is uncertain whether aspirin combined with calcium would reduce the burden of preeclampsia in Malawian women, as elsewhere. This study assessed the efficacy of early low-dose aspirin in preventing in women given calcium to prevent preeclampsia/eclampsia in Blantyre, Malawi. METHODS: This was a pragmatic, double-blind, cluster randomized controlled trial conducted in 4 urban health centers and Queen Elizabeth Central Hospital in Blantyre. A total of 306 women at high risk of preeclampsia were assigned to low-dose aspirin (150 mg/day) or placebo from 12 to 16 weeks until 34 weeks of gestation in clusters. All women were given calcium 1 g/day. The intention-to-treat analysis and adherence analysis were conducted with the primary end point of preeclampsia. RESULTS: A total of 39 women were lost to follow-up, and 1 withdrew consent. Data for 266 women were available for analysis. Overall, preeclampsia occurred in 15.8% (42/266) and eclampsia in 2.3% (6/266) of all women. There was no statistically significant difference in the rate of preeclampsia between the low-dose aspirin group 19.3% (26/135) and placebo group (12.2% 16/131; adjusted odds ratio, 1.16 [95% CI, 0.41-3.41]; P=0.781). No statistically significant difference was observed in the secondary maternal and neonatal outcomes. The overall adherence was 69%. CONCLUSIONS: In high-risk women treated with calcium, additional low-dose aspirin resulted in no difference in the rate of preeclampsia, cesarean section rates, or important neonatal outcomes in Malawi. 2025 Lippincott Williams and Wilkins. All rights reserved.
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Tocchetti, Carlo G.; Gonzez, Arantxa; Backs, Johannes; Pollesello, Piero; Rainer, Peter Paul; Schiattarella, Gabriele Giacomo; Bellin, Milena; Begley, Glenn; Bock-Marquette, Ildiko; Balligand, Jean Luc; Falc-Pires, In?s P.; Gorczynski, Rick; Hirsch, Emilio; Hulot, Jean Sebastien; Klebl, Bert Matthias; Lyon, Alexander Richard; Maack, Christoph; McKinsey, Timothy A.; Mler, Oliver Josef; Lunde, Ida Gjervold; Montgomery, Rusty L.; Vergaro, Giuseppe G.V.; Bay-Gen, Antoni; Thum, Thomas; van der Meer, Peter; van Laake, Linda Wilhelmina; Ruschitzka, Frank T.; Seferovi?, Petar M.; Coats, Andrew J.S.; Metra, Marco; Rosano, Giuseppe Massimo Claudio; van Linthout, Sophie A.; De Boer, Rudolf A.A rift has opened and is widening between basic research (bench) and clinical research and patients (bed) who need their new treatments, diagnostics and preventive strategies. This problem involving the translation of basic scientific findings into clinical applications and potential treatments or biomarkers for a condition like heart failure is widely recognized both in academia and industry. Despite the attempts that have been made by both sides to improve this situation, the high attrition rates of drug development and the problem with reproducibility and translatability of preclinical findings to human applications still persist. As a result, the return on investment of basic research has been limited in terms of clinical impact. In this scientific statement we describe and discuss various issues with relevance to this theme and try to dissect how to move our field towards the development of more effective heart failure drugs. We zoom in on facilitating the process of heart failure drug development, the unnecessary gaps (valley of death) between the critical steps in heart failure drug development, validation and de-validation of new concepts as early as possible (rigorous translation). We describe forums on how to stimulate cross-talk and interaction between clinician-scientists, basic heart failure researchers, biotech and industry, and how to enable them to speak the same language, and lessons learned from successes outside the heart failure field. 2025 European Society of Cardiology.
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Jeyaruban, Andrew Sujeevan; Bose, Bhadran; Lee, Vincent W.; Jardine, Meg J.; Mallawaarachchi, Amali C.; Ritchie, Angus Graham; Wong, Muh Geot; Makris, Angela; Badve, Sunil V.; Siriwardana, Amanda N.; Yong, Kenneth; Perkovic, Vlado; Kotwal, Sradha S.Background: The diverse and rare causes of glomerular disease, coupled with the absence of Australian registries and biobanks, pose significant research and treatment challenges. Aim: To establish a longitudinal glomerular disease data registry, a biorepository, and to enhance patient participation in clinical trials. Methods: This prospective, observational study includes incident and prevalent patients with biopsy-proven glomerular disease. Patients are offered participation in collection of clinical and demographic data from medical records with optional consent for (i) collection of blood samples for biobanking, (ii) participation in future clinical trials, (iii) data linkage and (iv) participation in a consumer engagement committee. Annual follow-up is conducted through medical records, with no study-specific visits. Blood samples for DNA-extraction and plasma are collected and stored in de-identified fashion for future analyses. Results: Recruitment commenced in December 2018 and ended in February 2025, with 230 patients enrolled and 114 bio samples collected. The median age of the participants was 49 years and 39% of participants were female. Immunoglobulin A nephropathy (38%) was the most common underlying disease followed by membranous nephropathy (17%). The median baseline estimated glomerular filtration (eGFR) was 64 mL/min/1.73m2 (IQR: 37.590) with median urine albumin creatinine ratio of 188.05 mg/mmol (IQR: 54.45398.83). Corticosteroids were the most common immunosuppressant (30.4%) used, followed by cyclophosphamide (8.7%) and rituximab (5.7%). Conclusion: The establishment of this registry provides opportunities to monitor patients with glomerular disease, identify eligible participants for trials and facilitate future genetic testing. 2025 Royal Australasian College of Physicians.
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Chen, Yiyao Catherine; Louis, Naveen Eugene Richard; Huang, Angela; Sun, Allan; Dupuy, Alexander; Moldovan, Laura; Pelaia, Tiana Maria; Ren, Jianfang; Cohen, Taylor Sitarik; Gilbert, Sarah C.; Tran, Huyen Anh M.; Peter, Karlheinz H.; McFadyen, James D.; Ju, Lining ArnoldRare thrombotic events associated with ChAdOx1 nCoV-19 (ChAdOx1) vaccination have raised concerns; however, the underlying mechanisms remain elusive. Here, we report a novel biophysical mechanism by which ChAdOx1 directly interacts with platelets under arterial shear conditions, potentially contributing to postvaccination arterial thrombosis. Using microfluidic post assays, we demonstrate that ChAdOx1 induces shear-dependent platelet aggregation, distinct from conventional von Willebrand factormediated adhesion. This interaction is mediated by platelet integrin ?<inf>IIb</inf>?<inf>3</inf> and requires biomechanical activation, explaining the absence of significant binding under static conditions. Molecular dynamics simulations and docking studies reveal preferential binding of ChAdOx1's penton arginine-glycine-aspartic acid (RGD) motif to the activated conformation of ?<inf>IIb</inf>?<inf>3</inf>. Inhibiting integrin ?<inf>IIb</inf>?<inf>3</inf> completely abolishes ChAdOx1-induced platelet aggregation, whereas blocking glycoprotein (GP) Ib has minimal effect, confirming a mechanism that bypasses the conventional GPIb-dependent platelet adhesion pathway. Mutagenesis of the RGD motif to AAA eliminates platelet binding, verifying the specificity of this interaction. These findings provide a potential explanation for the association between ChAdOx1 vaccination and arterial thrombotic events, distinct from vaccine-induced immune thrombotic thrombocytopenia. Our results highlight the importance of considering biomechanical factors in vaccine-related thrombotic complications and suggest that shear-dependent integrin activation may be another determinant in the pathogenesis of these rare adverse events. 2025 American Society of Hematology
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Volterrani, Maurizio; Halasz, Geza; Adamopoulos, Stamatis N.; Agostoni, Piergiuseppe; Butler, Javed J.; Coats, Andrew J.S.; Cohen-Solal, Alan; Doehner, Wolfram; Filippatos, Gerasimos S.; Jankowska, Ewa Anita; Lam, Carolyn Su Ping; Lambrinou, Ekaterini; Lund, Lars H.; Rosano, Giuseppe Massimo Claudio; Metra, Marco; Paolillo, Stefania; Perrone-Filardi, Pasquale; Rakisheva, Amina G.; Savarese, Gianluigi; Seferovi?, Petar M.; Tocchetti, Carlo G.; PIEPOLI, MASSIMO FrancescoFor most patients with chronic, progressive illnesses, maintaining good quality of life (QoL), with preserved functional capacity, is just as crucial as prolonging survival. Patients with heart failure (HF) experience much worse QoL and effort intolerance than both the general population and people with other chronic conditions, since they present a range of physical and psychological symptoms, including shortness of breath, chest discomfort, fatigue, fluid congestion, trouble with sleeping, and depression. These symptoms reduce patients' capacity for daily social and physical activity. Usual endpoints of large-scale trials in chronic HF have mostly been defined to evaluate treatments regarding hospitalizations and mortality, but more recently, patients' priorities and needs expressed with QoL are gaining more awareness and are being more extensively evaluated. This scientific statement aims at discussing the importance of QoL in HF, summarizing the most largely adopted questionnaires in HF care, and providing an overview on their application in trials and the potential for their transition to clinical practice. Finally, by discussing the reasons limiting their application in daily clinical routine and the strategies that may promote their implementation, this statement aims at fostering the systematic integration of the patient's standpoint in HF care. 2025 This article has been co-published with permission in the European Journal of Preventive Cardiology and European Journal of Heart Failure. All rights reserved. the European Society of Cardiology. The articles are identical except for minor stylistic and spelling differences in keeping with each journal's style. Either citation can be used when citing this article.
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Doudesis, Dimitrios; Lee, Kuanken; Anwar, Mohamed Subhan; Singer, Adam John; Hollander, Judd E.; Chenevier-Gobeaux, Camille; Claessens, Yann Erick; Wussler, Desiree Nadine; Weil, Dominic; Kozhuharov, Nikola Asenov; Strebel, Ivo; Sabti, Zaid; DeFilippi, Christopher R.; Seliger, Stephen L.; Mesquita, Evandro Tinoco; Wiemer, Jan C.; Mkel, Martin; Coste, Jo L.; Jourdain, Patrick; Kimiaki, Komukai; Yoshimura, Michihiro; Ibrahim, Irwani Bte; Ooi, Shirley Beng Suat; Kuan, Win Sen; Gegenhuber, Alfons; Mueller, Thomas; Hanon, Olivier; Vidal, Jean Sastien; Cameron, Peter A.; Lam, Louisa L.; Freedman, Ben; Chung, Tommy; Collins, Sean P.; Lindsell, Christopher John; Newby, David Ernest; Japp, Alan G.; Shah, Anoop S.V.; Villacorta, Humberto; Richards, Arthur Mark; McMurray, John JV; Mller, Christian Immanuel; Januzzi, James Louis; Mills, Nicholas Linton; Moe, Gordon W.; Fernando, Carlos; Gaggin, Hanna Kim; Bay-Gen, Antoni; van Kimmenade, Roland R.J.; Pinto, Yigal Martin; Rutten, Joost Henricus Wilhelmus; van den Meiracker, Anton H.; Gargani, Luna; Pugliese, Nicola Riccardo; Pemberton, C. J.; Neumaier, Michael; Behnes, Michael; Akin, Ibrahim; Bombelli, Michele G.; Grassi, Guido M.; Nazerian, Peiman; Albano, Giovanni; Bahrmann, PhilippAims B-type natriuretic peptide (BNP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) testing are guideline-recommended to aid in the diagnosis of acute heart failure. Nevertheless, the diagnostic performance of these biomarkers is uncertain. Methods and results We performed a systematic review and individual patient-level data meta-analysis to evaluate the diagnostic performance of BNP and MR-proANP. We subsequently developed and externally validated a decision-support tool called CoDE-HF that combines natriuretic peptide concentrations with clinical variables using machine learning to report the probability of acute heart failure. Fourteen studies from 12 countries provided individual patient-level data in 8493 patients for BNP and 3899 patients for MR-proANP, in whom, 48.3% (4105/8493) and 41.3% (1611/3899) had an adjudicated diagnosis of acute heart failure, respectively. The negative predictive value (NPV) of guideline-recommended thresholds for BNP (100?pg/mL) and MR-proANP (120?pmol/L) was 93.6% (95% confidence interval 88.4-96.6%) and 95.6% (92.2-97.6%), respectively, whilst the positive predictive value (PPV) was 68.8% (62.9-74.2%) and 64.8% (56.3-72.5%). Significant heterogeneity in the performance of these thresholds was observed across important subgroups. CoDE-HF was well calibrated with excellent discrimination in those without prior acute heart failure for both BNP and MR-proANP [area under the curve of 0.914 (0.906-0.921) and 0.929 (0.919-0.939), and Brier scores of 0.110 and 0.094, respectively]. CoDE-HF with BNP and MR-proANP identified 30% and 48% as low-probability [NPV of 98.5% (97.1-99.3%) and 98.5% (97.7-99.0%)], and 30% and 28% as high-probability [PPV of 78.6% (70.4-85.0%) and 75.1% (70.9-78.9%)], respectively, and performed consistently across subgroups. Conclusion The diagnostic performance of guideline-recommended BNP and MR-proANP thresholds for acute heart failure varied significantly across patient subgroups. A decision-support tool that combines natriuretic peptides and clinical variables was more accurate and supports more individualized diagnosis. 2025 The Author(s). Published by Oxford University Press on behalf of the European Society of Cardiology.
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Mondal, Amandeep Rashid; Misra, Ashish K.Atherosclerosis is a leading cause of cardiovascular morbidity and mortality worldwide, driven by complex interactions among various plaque cell types, including endothelial cells, macrophages, and smooth muscle cells. Traditional therapies targeting systemic risk factors such as cholesterol and blood pressure fail to directly address the underlying mechanisms governing plaque formation and progression. Recent advances in cell-specific therapies offer new avenues for targeting the cellular and molecular processes driving atherosclerosis. This Review explores innovative strategies including nanoparticles, viral vectors and CRISPR-Cas9 technology, which have the potential to modulate gene expression and behaviour within plaques cells to alleviate disease. By focusing on the specific roles of key cell types in atherosclerosis, these emerging therapies promise to provide more precise, effective, and personalised treatment options without inducing off-target effects. Moreover, insights gained from successful applications of these technologies in oncology are considered for potential repurposing in atherosclerosis-related disease. As these cell-specific approaches advance through preclinical and clinical development, they may significantly enhance our ability to treat atherosclerosis at its cellular roots, offering new hope for reducing the burden of cardiovascular disease. 2025
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Badal, Tanya; Nicholson, Calum; Ayer, Julian Ganesh J.; Cheung, Michael M.H.; Grigg, Leeanne Elizabeth; Celermajer, David S.; Strange, G. A.Background: Previous research has outlined significant gaps in the care of children and adults with Congenital Heart Disease (CHD). The Australian Study of the Burden and Outcomes of CHD will assess medical, psychological, social and economic issues affecting CHD patients and carers and provide a detailed account of CHD patients healthcare utilisation. Methods: A random sample of patients aged ?5 years, equally split between genders, CHD complexity (mild, moderate, severe) and rural and remote locations (2025%) was extracted from the National Australian CHD Registry (n = 68,214) from four large participating CHD centres (2 adult and 2 child). Patients and their carers were invited to participate in an in-person study visit for physical assessment and for a series of surveys questioning physical and mental health, neurodevelopment, and quality of life. Results: Of 6,726 contacted patients, 1,911 (28%) consented, with 99.5% of surveys completed online. 1,658 consented participants completed at least one study activity (87% response rate). Proxies/carers completed surveys for 11% of participants (primarily those under age 8 or with intellectual disability). All study activities were completed by 750 respondents (45%). Respondents were older (median age 24 [IQR 1241 years] vs 18 [IQR 1135 years], p = 0.005) and had a higher proportion of severe CHD (28%) compared to non-respondents (23%). No significant differences in disease complexity were observed between respondents and non-respondents. Conclusion: This multi-site study of over 1600 CHD patients aims to offer the first comprehensive profiling of the burdens and outcomes faced by Australia's growing CHD population. 2025 The Authors
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Anker, Stefan D.; Friede, Tim; Butler, Javed; Talha, Khawaja Muhammad; Placzek, Marius; Diek, Monika; Nosko, Anna; Stas, Adriane; Kluge, Stefan; Jarczak, Dominik; DeHeer, Geraldine; Rybczynski, Meike; Bay-Gen, Antoni; Bm, Michael; Coats, Andrew J.S.; Edelmann, Frank; Filippatos, Gerasimos S.; Hasenfuss, Gerd; Haverkamp, Wilhelm L.; Lain?ak, Mitja; Landmesser, Ulf E.; Macdougall, Iain C.; Merkely, Ba Peter; Pieske, Burkert Mathias; Pinto, Fausto J.; Rassaf, Tienush; Visser-Rogers, Jennifer K.; Rosano, Giuseppe Massimo Claudio; Volterrani, Maurizio; von Haehling, Stephan; Anker, Markus S.; Doehner, Wolfram; Ince, Hus?eyin Sefa; Koehler, Friedrich; Savarese, Gianluigi; Khan, Muhammad Shahzeb; Rauch, Ursula; Gori, Tommaso; Trenkwalder, Teresa; Akin, Ibrahim; Paitazoglou, Christina; Kobielusz-Gembala, Iwona; Kuthi, Luca Katalin; Frey, Norbert; Licka, M. B.; Kb, Stefan; Laugwitz, Karl Ludwig; Ponikowski, Piotr P.; Karakas, MahirImportance: Uncertainty remains about the efficacy of intravenous iron in patients with heart failure and iron deficiency. Objective: To assess the efficacy and safety of ferric carboxymaltose in patients with heart failure and iron deficiency. Design, Setting, and Participants: This multicenter, randomized clinical trial enrolled 1105 patients with heart failure (defined as having a left ventricular ejection fraction of ?45%) and iron deficiency (serum ferritin level <100 ng/mL; or if transferrin saturation was <20%, a serum ferritin level between 100 ng/mL and 299 ng/mL) at 70 clinic sites in 6 European countries from March 2017 to November 2023. The median follow-up was 16.6 months (IQR, 7.9-29.9 months). Intervention: Administration of ferric carboxymaltose (n = 558) initially given at an intravenous dose of up to 2000 mg that was followed by 500 mg every 4 months (unless stopping criteria were met) vs a saline placebo (n = 547). Main Outcomes and Measures: The primary end point events were (1) time to cardiovascular death or first heart failure hospitalization, (2) total heart failure hospitalizations, and (3) time to cardiovascular death or first heart failure hospitalization in patients with a transferrin saturation less than 20%. All end point events were measured through follow-up. The end points would be considered statistically significant if they fulfilled at least 1 of the following conditions: (1) P ?.05 for all 3 of the end point comparisons, (2) P ?.025 for 2 of the end point comparisons, or (3) P ?.0167 for any of the 3 end point comparisons (Hochberg procedure). Results: Of the 1105 participants (mean age, 70 years [SD, 12 years]; 33% were women), cardiovascular death or first heart failure hospitalization (first primary outcome) occurred in 141 in the ferric carboxymaltose group vs 166 in the placebo group (hazard ratio, 0.79 [95% CI, 0.63-0.99]; P =.04). The second primary outcome (total heart failure hospitalizations) occurred 264 times in the ferric carboxymaltose group vs 320 times in the placebo group (rate ratio, 0.80 [95% CI, 0.60-1.06]; P =.12). The third primary outcome (cardiovascular death or first heart failure hospitalization in patients with a transferrin saturation <20%) occurred in 103 patients in the ferric carboxymaltose group vs 128 patients in the placebo group (hazard ratio, 0.79 [95% CI, 0.61-1.02], P =.07). A similar amount of patients had at least 1 serious adverse event in the ferric carboxymaltose group (269; 48.2%) vs in the placebo group (273; 49.9%) (P =.61). Conclusions and Relevance: In patients with heart failure and iron deficiency, ferric carboxymaltose did not significantly reduce the time to first heart failure hospitalization or cardiovascular death in the overall cohort or in patients with a transferrin saturation less than 20%, or reduce the total number of heart failure hospitalizations vs placebo. 2025 American Medical Association. All rights reserved.
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Penders, Yolanda W.H.; Falsey, Ann Regina; Bhatt, Deepak L.; Bm, Michael; Coats, Andrew J.S.; Mason, Lauren M.K.; Mora, Laura; Saeedi, Pouya; Michaud, Jean Philippe; Kosfeld, Frithjof; Harrington, LaurianeCardiovascular diseases (CVD) are risk factors for severe respiratory syncytial virus (RSV) infection, which in turn increases the risk of cardiovascular complications. The burden of RSV disease among adults with CVD is not yet fully understood and evidence remains to be consolidated through a systematic approach. Covering the publication period from January 1, 2000 to November 28, 2023, this systematic literature review documented RSV disease burden among adults ?18 years with CVD including heart failure (HF), ischemic heart disease (IHD), and non-specified CVD. Relevant publications were retrieved from databases (PubMed, Embase) and gray literature (conference abstracts) to quantify the prevalence of CVD among RSV-infected adults, and RSV-related hospitalizations, complications, and mortality among adults with CVD. Sixty-two studies were selected for data extraction; most were conducted in the United States and among inpatients. The highest pooled estimates of CVD prevalence were observed among inpatients: 27.5 % (95 % confidence interval: 24.031.2) for HF, 22.9 % (17.729.0) for IHD, and 44.4 % (38.550.5) for non-specified CVD. Adults with CVD were at significantly higher risk of hospitalization following RSV infection compared to those without these comorbidities. Various general, respiratory, and cardiovascular complications attributable to RSV were documented among adults with CVD. RSV-related in-hospital case fatality rates of 7.814.8 % (HF), 13.720.0 % (IHD), and 2.912.5 % (non-specified CVD) were reported. This study shows that adults with CVD bear a significant burden of RSV infection, highlighting the need for effective RSV preventive measures and strategies (i.e., vaccination) targeting this high-risk population. 2025 GSK.
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Bass-Stringer, Sebastian; Donner, Daniel G.; May, Clive Newton; Matsumoto, Aya; Masterman, Emma I.; D'Elia, Aascha A.; Chen, Yi Ching; Kiriazis, Helen; Luo, Jieting; Chooi, Roger; Ming, Clara Liu Chung; Gregorevic, Paul; Thomas, Colleen J.; Bernardo, Bianca C.; Weeks, Kate L.; McMullen, Julie R.Heart failure (HF) remains a clinical challenge with cardiac dysfunction typically progressing even with treatment, and heart transplants only available to small numbers. We previously identified phosphoinositide 3-kinase (PI3K, p110?) as a master regulator of exercise-induced cardioprotection, and showed that gene therapy, incorporating a constitutively active form of PI3K (caPI3K) improved function of the failing mouse heart. However, this approach was not cardiac-specific and the gene therapy was challenging to manufacture. The aim of this study was to develop new PI3K-based gene therapies with more optimal properties for clinical translation. We generated and assessed adeno-associated viruses (AAV6) encoding various PI3K constructs, with different enhancers, promoters and transgene components in healthy adult male mice. The most promising AAV construct based on AAV expression, cardiac-specificity, and ease of manufacture contained a cardiac troponin T (cTnT) promoter together with a small region of the regulatory subunit of PI3K (iSH2), and an intron from the ?-globin gene which enhances transcription (IVS2). This AAV (1 1012, 2 1012 vg) was administered to mice with myocardial ischemia/reperfusion injury (I/R: 1 h ischemia with reperfusion; AAV delivered 24 h post-I/R). Direct cardiac injections of PI3K-based AAVs were also performed in healthy adult female sheep. I/R mouse hearts treated with the AAV6-cTnT-IVS2-iSH2 displayed increased phosphorylation of Akt, but no improvement in cardiac function or structure was observed. AAV6-cTnT-IVS2-iSH2 successfully transduced healthy sheep hearts which increased endogenous PI3K catalytic activity. Further testing/optimization of the AAV (time of delivery and/or duration) will be required to assess the therapeutic potential of this approach. 2025 The Authors
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Lloyd, Larissa K.; Ruban, Sasha O.; Badal, Tanya; Strange, G. A.; Celermajer, David S.; Bonner, CarissaBackground: The survival prospects of adults with congenital heart disease have improved considerably due to improved surgical interventions, resulting in a growing population. This study aims to explore the experiences of adults with congenital heart disease, to identify support needs. Methods: Participants were recruited from the National Australian Congenital Heart Disease Registry using purposive sampling to ensure diversity in terms of gender, rurality and disease complexity. Semi-structured interviews were conducted with adults with congenital heart disease. The interviews were recorded digitally and transcribed verbatim. Framework Analysis was used to ensure rigour in identifying themes. Results: 43 interviews were completed (23 males and 20 females; age 20 to 54 years). Three main themes and seven subthemes were identified to explain varying experiences of living with congenital heart disease: I. Lifestyle factors; (i) physical activity, (ii) weight management. II. Practical issues; (iii) employment, (iv) financial stress, (v) education. III. Psychosocial impact; (vi) mental health and resilience, and (vii) social engagement. Participants across a range of disease complexities reported more impact on their lives when they felt inadequately supported by their healthcare providers to address these challenges, such as insufficient education on exercise leading to difficulty performing clinically recommended physical activity. Conclusions: The lived experiences of adults living with congenital heart disease highlight specific areas needing support, which could inform future improvements in their whole of life care. This could include referral to allied health professionals, education across lifestyle and practical domains, and appropriate peer support networks. 2025 The Authors
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Wu, Mike C.L.; Italiano, Ethan; Jarvis-Child, Rocko; Alwis, Imala D.; Smythe, Rhyll E.; Albornoz, Eduardo A.; Noonan, Jonathan; Portelli, Marie; Baptista, Marissa; Maclean, Jessica A.A.; Noori, Pashtana; Yang, Jinglu; Lee, John D.; McFadyen, James D.; Sharland, Alexandra F.; Woodruff, Trent M.; Samson, Andre L.; Rapkiewicz, Amy V.; Barrett, Tessa J.; Pham, Alan; Schoenwaelder, Simone M.; Yuan, Yuping; Jackson, Shaun P.Microangiopathy is a major complication of SARS-CoV-2 infection and contributes to the acute and chronic complications of the disease1. Endotheliopathy and dysregulated blood coagulation are prominent in COVID-19 and are considered to be major causes of microvascular obstruction1,2. Here we demonstrate extensive endothelial cell (EC) death in the microvasculature of COVID-19 organs. Notably, EC death was not associated with fibrin formation or platelet deposition, but was linked to microvascular red blood cell (RBC) haemolysis. Importantly, this RBC microangiopathy was associated with ischaemiareperfusion injury, and was prominent in the microvasculature of humans with myocardial infarction, gut ischaemia, stroke, and septic and cardiogenic shock. Mechanistically, ischaemia induced MLKL-dependent EC necroptosis and complement-dependent RBC haemolysis. Deposition of haemolysed RBC membranes at sites of EC death resulted in the development of a previously unrecognized haemostatic mechanism preventing microvascular bleeding. Exaggeration of this haemolytic response promoted RBC aggregation and microvascular obstruction. Genetic deletion of Mlkl from ECs decreased RBC haemolysis, microvascular obstruction and reduced ischaemic organ injury. Our studies demonstrate the existence of a RBC haemostatic mechanism induced by dying ECs, functioning independently of platelets and fibrin. Therapeutic targeting of this haemolytic process may reduce microvascular obstruction in COVID-19, and other major human diseases associated with organ ischaemia. The Author(s), under exclusive licence to Springer Nature Limited 2025.
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Jiang, Fengtao; Zhang, Yingqi; Fang, Guocheng; Wang, Yao; Dupuy, Alexander; Jin, Jasmine; Shen, Yi; Lim, K. S.; Wang, Yinyan; Zhang, Y. Shrike; Cho, Ann-Na; Lu, Hongxu; Ju, Lining ArnoldCancer metastasis begins with intravasation, where cancer cells enter blood vessels through complex interactions with the endothelial barrier. Understanding this process remains challenging due to the lack of physiologically relevant models. Here, INVADE (Intravasation-on-Device), a biomimetic microfluidic platform, is presented, enabling high-throughput analysis of cancer cell intravasation under controlled conditions. This engineered platform integrates 23 parallel niche chambers with an endothelialized channel, providing both precise microenvironmental control and optical accessibility for real-time visualization. Using this platform, distinct intravasation mechanisms are uncovered: MCF-7 cells exhibit collective invasion, while MDA-MB-231 cells demonstrate an interactive mode with three functionally distinct subpopulations. A previously unknown epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) switch is We discovered during intravasation, where MDA-MB-231 cells initially increase Vimentin expression before undergoing a 2.3 fold decrease over 96 h alongside a 1.5 fold increase in epithelial cell adhesion molecule (EpCAM). Remarkably, endothelial cells directly suppress cancer cell mesenchymal properties, as evidenced by a 4.6 fold reduction in Vimentin expression compared to mono-cultures. Additionally, bilateral cancer-endothelial interactions are revealed, aggressive cancer cells induce significant intercellular adhesion molecule-1 (ICAM-1) upregulation in endothelium. The INVADE platform represents an engineering advancement for studying complex cellcell interactions with implications for understanding metastatic mechanisms. 2025 The Author(s). Advanced Materials published by Wiley-VCH GmbH.
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Playford, David A.; Stewart, S.; Watts, Andrew; Kezurer, Dean; Chan, Yih Kai; Strange, G. A.Background: Identification of left ventricular (LV) dysfunction following echocardiographic investigations remains problematic, particularly when the ejection fraction (EF) is preserved. Objectives: The authors examined the operational characteristics of artificial intelligence LV dysfunction (AI-LVD) identification from routinely obtained echocardiographic measurements. Methods: Following initial training in 126,136 (imputation cohort) and 254,735 (training cohort) cases from the National Echo Database of Australia, the AI-LVD was tested in 81,509 cases (last echo January 1, 2000-May 21, 2019) with no mitral valve intervention or pacemaker. This cohort comprised 41,796 men (51.3%) aged 62.3 17.1 years and 39,713 women aged 63.2 18.4 years, in whom 4,490 (5.5%), 3,734 (4.6%), and 59,297 (72.7%) had reduced, mildly reduced, and preserved EF, while 13,988 (17.2%) had no recorded EF and 39,940 (45.2%) had indeterminate filling pressures. Results: Overall, the AI-LVD generated a (sex-specific) output in decile distributions consistent with increasingly higher levels of LV dysfunction and mortalityactual 5-year mortality rising from 5.7% to 66.3% and 2.3% to 64.2% in men and women, respectively. The prognostic capacity of the AI-LVD persisted in preserved EF, when adjusting for age, year of echo, and missing echo parameterswith adjusted hazard for all-cause mortality during 1,541 (812-2,682) days follow-up 4.93-fold (95% CI: 4.35-5.59) and 7.11-fold (95% CI: 5.85-8.64) higher in the highest vs lowest decile group in men and women, respectively. Conclusions: A new AI-LVD algorithm using only echocardiographic measurements can reliably identify prognostically important LV dysfunction, including in preserved EF, even when key reporting parameters are missing. The AI-LVD can be used in real-time during routine echocardiography reporting. 2025 The Authors
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Atherton, John James; Sindone, Andrew Paul; Coats, Andrew J.S.[No abstract available]
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Dupuy, Alexander; Liu, Xiaoming; Kong, Yvonne X.; Qi, Miao; Perdomo, JosSail; Fenwick, Jemma C.L.; Tieng, Jessica; Johnston, Bede; Shi, Qiyu Sara; Larance, Mark; Zhang, Yingqi; Ju, Lining Arnold; Coleman, Paul R.; Gamble, Jennifer R.; Gardiner, Elizabeth E.; Poncz, Mortimer; Tran, Huyen Anh M.; Chen, Vivien Mun Yee; Passam, Freda H.Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but serious complication of the ChAdOx1 nCOV-19 vaccine. In Australia, the diagnosis of VITT required the detection of antibodies against platelet factor 4 (PF4) in plasma using a PF4/polyanion enzyme-linked immunosorbent assay (ELISA). Half of the patients who fulfilled the clinical criteria for VITT tested positive when using this ELISA and another third tested positive when using platelet activation assays, highlighting limitations in the assays used for VITT. Using a microfluidic device coated with endothelial cells, the Endo-chip, we measured the effects of serum and immunoglobulin G (IgG) from patients with clinical VITT on endothelial thromboinflammation. Our cohort comprised 40 patients (21 ELISA-positive and 19 ELISA-negative patients as measured by PF4/polyanion ELISA), 12 vaccinated patients with venous thromboembolism without VITT, and 17 individuals who received the ChAdOx1 vaccine without adverse events (vax controls). Treatment with VITT serum, plasma, or IgG increased endothelial tissue factor (TF) expression and activity. Perfusion of blood from healthy donors labelled with fluorescent antibodies against platelets, neutrophils, and fibrin through Endo-chips treated with VITT serum or IgG induced a twofold to threefold increase in platelet, neutrophil, and fibrin deposition. Thromboinflammation was enhanced with addition of PF4 and reduced with an inhibitory antibody against TF. We conclude that endothelial activation contributes to thromboinflammation in patients with clinical features of VITT. The Endo-chip offers a platform for the study of endothelial responses in immune thrombosis. 2025 American Society of Hematology.
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Huang, Yan Yan Shery; Ju, Lining ArnoldEngineering a biologically functional structure from living cells can solve global health challenges by supplying abundant artificial tissues and organs for drug screening, disease modeling, and transplantation (14). A vascular system is an essential component for the survival of thick tissues. This tree-like network delivers nutrients to cells, regulates blood pressure, and provides resilient blood flow through a hierarchical structure (5). Designing a micro- to millimeter-scale vascular architecture for a centimeter-scale artificial tissue requires extensive computational resources (6). Consequently, engineered vascular networks often have a simple lattice structure that is easy to fabricate but exhibits nonuniform pressure gradient and flow distribution. On page 1198 of this issue, Sexton et al. (7) report a computational approach that can design a complex vascular tree network at more than 230 times the speed of traditional methods. This enables the design of anatomically realistic vascular networks for organ-scale biofabrication. 2025 American Association for the Advancement of Science. All rights reserved.
