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Showing 81–100 of 2058 publications.
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Chioncel, O. Dragomir; Mebazaa, Alexandre; Farmakis, Dimitrios T.; Abdelhamid, Magdy A.; Lund, Lars H.; Harjola, Veli Pekka; Anker, Stefan D.; Filippatos, Gerasimos S.; Ben-Gal, Tuvia; Damman, Kevin; Skouri, Hadi N.; Antohi, Laura E.; Collins, Sean P.; Adamo, Marianna; MirAndreu, car; Hill, Loreena Michelle; Parissis, John T.; Moura, Brenda; Mller, Christian Immanuel; Jankowska, Ewa Anita; Lopatin, Yu M.; Dunlap, Mark E.; Volterrani, Maurizio; Fudim, Marat; Flammer, Andreas J.; Mullens, Wilfried; Pang, Peter S.; ?ica, Otilia Anca; Ponikowski, Piotr P.; Risti?, Arsen D.; Butler, Javed J.; Savarese, Gianluigi; Cicoira, Mariantonietta; Thum, Thomas; Bay-Gen, Antoni; Polyzogopoulou, Effie; Seferovi?, Petar M.; Yilmaz, Mehmet Birhan; Rosano, Giuseppe Massimo Claudio; Coats, Andrew J.S.; Metra, MarcoAcute heart failure (AHF) affects millions of people each year and vasodilators have been a central part of treatment for over 25 years. The haemodynamic effects of vasodilators vary considerably among individual agents. Some vasodilators, such as nitrates, primarily act on the venous system by redistributing the circulating blood volume away from the heart towards the venous capacitance system. Other vasodilators, such as nesiritide, lead to balanced vasodilatation in the arteries and veins, decreasing left ventricular afterload and preload. Considering mechanisms of action, intravenous vasodilators are thought to be effective in patients with AHF, particularly in those with acute pulmonary oedema, where increased cardiac filling pressures and elevated systemic blood pressures occur in the absence of, or with minimal systemic fluid accumulation. However, the 2021 European heart failure guidelines have downgraded the use of vasodilators due to two recent studies and several contemporary meta-analyses failing to show benefit in terms of survival. Thus, there remains no firm recommendation suggesting the use of vasodilator treatment over usual care. In addition, despite repeated efforts to develop new vasodilatory agents, no novel therapy has outperformed traditional AHF management. In parallel with the development of novel vasodilators, changing the design of clinical trials for AHF to consider phenotype diversity of AHF patients remains an unmet need. New randomized clinical trials should particularly focus on subgroups that may mechanistically derive benefit from vasodilators, which may entail moving enrolment of patients to clinical settings close to moment of decompensation, such as the emergency department. 2025 European Society of Cardiology.
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Wahab, Ali; Nadarajah, Ramesh; Larvin, Harriet; Farooq, Maryum; Raveendra, Keerthenan; Haris, Mohammad; Nadeem, Umbreen; Joseph, Tobin; Bhatty, Asad; Wilkinson, Chris G.; Khunti, Kamlesh K.; Vedanthan, Rajesh; Camm, Alan John; Svennberg, Emma; Lip, Gregory Y.H.; Freedman, Ben; Wu, Jianhua; Gale, Chris P.Background: Systematic screening individuals with non-invasive devices may improve diagnosis of atrial fibrillation (AF) and reduce adverse clinical events. We systematically reviewed the existing literature to determine the yield of new AF diagnosis associated with systematic AF screening, the relative increase in yield of new AF diagnosis with systematic screening compared to usual care, and the effect of systematic AF screening on clinical outcomes compared with usual care. Methods: The Medline, Embase, Web of Science and Cochrane Library databases were searched from inception through 1st February 2025 for prospective cohort studies or randomised clinical trials (RCTs) of systematic AF screening with the outcome of incidence of previously undiagnosed AF from screening. Incidence rates (IR) and relative risks were calculated and random effects meta-analysis performed to synthesise rates of AF in prospective cohort studies and RCTs, as well as outcomes in RCTs. Findings: From 3806 unique records we included 32 studies representing 735,542 participants from 8 RCTs and 24 prospective cohorts. The diagnosis rate for incident AF in prospective cohorts was 2.75% (95% CI 1.873.62), and the pooled relative risk in RCTs was 2.22 (95% CI 1.413.50). The use of age and NT-proBNP (IR 4.36%, 95% CI 3.775.08) or AF risk score classification (4.79%, 95% CI 3.626.29) led to higher new AF diagnosis yields than age alone (0.93%, 95% CI 0.282.99). Pooled data from RCTs did not demonstrate an effect of screening on death (RR 1.01, 95% CI 0.971.05), cardiovascular hospitalisation (1.00, 95% CI 0.971.03), stroke (0.95, 95% CI 0.871.04) or bleeding (1.08, 95% CI 0.911.29). Interpretation: Systematic screening for AF using non-invasive devices is associated with increased diagnosis of AF, but not reduced adverse clinical events. Screening studies of AF utilising alternative risk stratifications and outcome measures are required. Funding: British Heart Foundation (grant reference CC/22/250026) and National Institute for Health and Care Research. 2025 The Authors
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Koay, Yen Chin; McIntosh, Bailey; Ng, Yann Huey; Cao, Yang; Wang, Xiaosuo; Han, Yanchuang; Tomita, Saki; Bai, Angela Yu; Hunter, Benjamin; Misra, Ashish K.; Loughrey, Christopher M.; Bannon, Paul Gerard; Lal, Sean P.; Lusis, Aldons Jake; Kaye, David M.; Larance, Mark; OSullivan, John F.BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) has overtaken heart failure with reduced ejection fraction as the leading type of heart failure globally and is marked by high morbidity and mortality rates, yet with only a single approved pharmacotherapy: SGLT2i (sodium-glucose co-transporter 2 inhibitor). A prevailing theory for the mechanism underlying SGLT2i is nutrient deprivation signaling, of which ketogenesis is a hallmark. However, it is unclear whether the canonical ketogenic enzyme, HMGCS2 (3-hydroxy-3-methylglutaryl-coenzyme A synthase 2), plays any cardiac role in HFpEF pathogenesis or therapeutic response. METHODS: We used human myocardium, human HFpEF and heart failure with reduced ejection fraction transcardiac blood sampling, an established murine model of HFpEF, ex vivo Langendorff perfusion, stable isotope tracing in isolated cardiomyocytes, targeted metabolomics, proteomics, lipidomics, and a novel cardiomyocyte-specific conditional HMGCS2-deficient model that we generated. RESULTS: We demonstrate, for the first time, the intrinsic capacity of the human heart to produce ketones via HMGCS2. We found that increased acetylation of HMGCS2 led to a decrease in the enzymes specific activity. However, this was overcome by an increase in the steady-state levels of protein. Oxidized form of nicotinamide adenine dinucleotide repletion restored HMGCS2 function via deacetylation, increased fatty acid oxidation, and rescued cardiac function in HFpEF. Critically, using a conditional, cardiomyocyte-specific HMGCS2 knockdown murine model, we revealed that the oxidized form of nicotinamide adenine dinucleotide is unable to rescue HFpEF in the absence of cardiomyocyte HMGCS2. CONCLUSIONS: The canonical ketogenic enzyme, HMGCS2, mediates the therapeutic effects of the oxidized form of nicotinamide adenine dinucleotide repletion in HFpEF by restoring normal lipid metabolism and mitochondrial function. 2025 The Authors.
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Greene, Stephen J.; Bm, Michael; Bozkurt, Biykem; Butler, Javed J.; Cleland, John G.F.; Coats, Andrew J.S.; Desai, Nihar R.; Grobbee, Diederick E.; Kelepouris, Ellie; Pinto, Fausto J.; Rosano, Giuseppe Massimo Claudio; Morin, Isabelle Ouellet; Szecsy, Peter; Fabien, Solenn; Waechter, Sandra; Crespo-Leiro, Mar Generosa; Hsmann, Martin P.; Kempf, Tibor; Pfister, O.; Pouleur, Anne Catherine M.; Sauer, Andrew J.; Saxena, Manish; Schulz, Martin; Volterrani, Maurizio; Anker, Stefan D.; Kosiborod, Mikhail N.Background: Despite guideline recommendations, many patients with heart failure (HF) do not receive target dosages of renin-angiotensin-aldosterone system inhibitors (RAASis) in clinical practice due, in part, to concerns about hyperkalemia (HK). Methods and Results: This noninterventional, multinational, multicenter registry (NCT04864795; 111 sites in Europe and the USA) enrolled 2558 eligible adults with chronic HF (mostly with reduced ejection fraction [HFrEF]). Eligibility criteria included use of angiotensin-converting-enzyme inhibitor/angiotensin-II receptor blocker/angiotensin-receptor-neprilysin inhibitor, being a candidate for or treatment with a mineralocorticoid receptor antagonist, and increased risk of HK (eg, current serum potassium > 5.0 mmol/L), history of HK in the previous 24 months, or estimated glomerular filtration rate < 45 mL/min/1.73 m2). Information on RAASi and other guideline-recommended therapies was collected retrospectively and prospectively (? 6 months). Patients were followed according to local clinical practice, without study-specific visits or interventions. The main objectives were to characterize RAASi treatment patterns compared with guideline recommendations, describe RAASi modifications following episodes of HK, and describe RAASi treatment in patients treated with patiromer. Baseline characteristics for the first 1000 patients are presented. Conclusions: CARE-HK is a multinational prospective HF registry designed to report on the management and outcomes of patients with HF at high risk for HK in routine clinical practice. 2024 The Author(s)
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Vitale, Cristiana A.; Berthelot, Emmanuelle; Coats, Andrew J.S.; Hill, Loreena Michelle; Albert, Nancy M.; Tkaczyszyn, Micha?; Adamopoulos, Stamatis N.; Anderson, Lisa J.; Anker, Markus S.; Anker, Stefan D.; Bell, Derek; Ben-Gal, Tuvia; Bistola, Vasiliki; Bozkurt, Biykem; Brooks, Poppy; Camafort, Miguel; Carrero, Juan Jes; Chioncel, O. Dragomir; Choi, Dong?Ju; Chung, Wook-jin; Doehner, Wolfram; Fernandez-Berges, D. J.; Ferrari, Roberto; Fiuzat, Mona; Gomez Mesa, Juan Esteban; Gustafsson, Finn; Jankowska, Ewa Anita; Kang, Seokmin; Kinugawa, Koichiro; Khunti, Kamlesh K.; Hobbs, F. D.Richard; Lee, Christopher Sean; Lopatin, Yuri M.; Maddocks, Matthew; Maltese, Giuseppe; Marqu-Sul Elena; Matsue, Yuya; MirAndreu, car; Moura, Brenda; PIEPOLI, MASSIMO Francesco; Ponikowski, Piotr P.; Pulignano, Giovanni; Rakisheva, Amina G.; Ray, Robin; Sciacqua, Angela; Seferovic, Petar M.; Sentandreu-Ma, Trinidad; Sze, Shirley; Sinclair, Alan James; Strberg, Anna E.; Theou, Olga; Tsutsui, Hiroyuki; Uchmanowicz, Izabella; Vid, Maite Teresa; Volterrani, Maurizio; von Haehling, Stephan; Yoo, Byungsu Soo; Zhang, Jian; Zhang, Yuhui; Metra, Marco; Rosano, Giuseppe Massimo ClaudioAims: The Heart Failure Frailty Score (HFFS) is a novel, multidimensional tool to assess frailty in patients with heart failure (HF). It has been developed to overcome limitations of existing frailty assessment tools while being practical for clinical use. The HFFS reflects the concept of frailty as a multidimensional, dynamic and potentially reversible state, which increases vulnerability to stressors and risk of poor outcomes in patients with HF. Methods and results: The HFFS was developed through a Delphi consensus process involving 54 international experts. This approach involved iterative rounds of questionnaires and interviews, where a panel of experts provided their opinions on specific questions prepared by the Steering Committee. The experts were invited to vote and share their views anonymously, using a 5-point Likert scale over iterative rounds. An 80% threshold was set for agreement or disagreement for each statement. Twenty-two variables from four domains (clinical, functional, psycho-cognitive and social) have been selected for inclusion in the HFFS after the third round of the Delphi process. A shorter version (S-HFFS), including 10 variables, has also been developed for daily clinical use. Conclusions: The HFFS is a new multidimensional tool for the identification of frailty in patients with HF. It should also enables healthcare providers to identify potential red flags for frailty in order to develop personalized care plans. The next step will be to validate the new score in patients with HF. 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
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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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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.
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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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Atherton, John James; Sindone, Andrew Paul; Coats, Andrew J.S.[No abstract available]
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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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Ren, Jianfang; Abidin, Nurul Aisha Zainal; Sun, Allan; Gao, Rui; Chen, Yuxin; Nasser, Arian; Wang, Zihao; Zhao, Yunduo Charles; Dupuy, Alexander; Waterhouse, Anna; Su, Qian Peter; Vigolo, Daniele; Wu, Mike C.L.; Ju, Lining ArnoldComplex flow patterns play a critical role in arterial thrombosis, yet the specific contribution of vorticitythe rotational component of fluid flowremains poorly understood. An innovative microfluidic platform with systematically varied expansion angles (? = 30-150) in a double stenosis design is developed to isolate vorticity's effects under controlled conditions. The high expansion-ratio device with sharp-angled geometries successfully generates distinct vortical flow patterns, confirmed through computational and experimental flow visualizations. Real-time confocal microscopy revealed a strong positive correlation (r = 0.6698) between vorticity magnitude and thrombus size, with high-vorticity conditions producing thrombi up to four times larger than low-vorticity settings. Mechanistic investigations demonstrated enhanced von Willebrand Factor (vWF) accumulation and platelet integrin activation in vortical environments. Platelets in high-vorticity regions exhibited integrin ?<inf>IIb</inf>?<inf>3</inf> intermediate activation states with significantly enhanced calcium signaling, suggesting vorticity amplifies platelet mechanosensing pathways. Inhibition of the interaction between vWF and platelet glycoprotein Ib? (GPIb?) receptor abolished biomechanical platelet aggregation in vortical regions. These findings provide valuable insights into platelet thrombosis in complex flow environments with significant implications for optimizing medical devices to minimize thrombotic complications associated with vortex formation. 2025 The Author(s). Advanced Healthcare Materials published by Wiley-VCH GmbH.
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Frlich, Ann Kathrin; Porthun, Jan; Talha, Khawaja Muhammad; Lena, Alessia; Hadzibegovic, Sara; Wilkenshoff, Ursula M.; Sonntag, Frederike; Nikolski, Anja; Ramer, Luisa Valentina; Zeller, Tanja; Keller, Ulrich Bernd; Bullinger, Lars B.; Anker, Stefan D.; Haverkamp, Wilhelm L.; von Haehling, Stephan; Doehner, Wolfram; Rauch, Ursula; Skurk, Carsten; Cleland, John G.F.; Butler, Javed J.; Coats, Andrew J.S.; Landmesser, Ulf E.; Karakas, Mahir; Anker, Markus S.Background: Growth hormone (GH) resistance is characterized by high GH levels but low levels of insulin-like growth factor-I (IGF-I) and growth hormone binding protein (GHBP) and, for patients with chronic disease, is associated with the development of cachexia. Objectives: We investigated whether GH resistance is associated with changes in left ventricular (LV) mass (cardiac wasting) in patients with cancer. Methods: We measured plasma IGF-I, GH, and GHBP in 159 women and 148 men with cancer (83% stage III/IV). Patients were grouped by tertile of echocardiographic LVmass/height2 (women, < 50, 5061, > 61g/m2; men, < 60, 6074, > 74g/m2) and by presence of wasting syndrome with unintentional weight loss (BMI < 24kg/m2 and weight loss ? 5% in the prior 12months). Repeat echocardiograms were obtained usually within 36months for 85 patients. Results: Patients in the lowest LVmass/height2 tertile had higher plasma GH (median (IQR) for 1st, 2nd, and 3rd tertile women, 1.8 (0.94.2), 0.8 (0.22.2), 0.5 (0.31.6) ng/mL, p = 0.029; men, 2.1 (0.83.2), 0.6 (0.11.7), 0.7 (0.21.9) ng/mL, p = 0.003). Among women, lower LVmass was associated with higher plasma IGF-I (68 (48116), 72 (4895), 49 (3576) ng/mL, p = 0.007), whereas such association did not exist for men. Patients with lower LVmass had lower log IGF-I/GH ratio (women, 1.60 0.09, 2.02 0.09, 1.88 0.09, p = 0.004; men, 1.64 0.09, 2.14 0.11, 2.04 0.11, p = 0.002). GHBP was not associated with LVmass. Patients with wasting syndrome with unintentional weight loss had higher plasma GH and GHBP, lower log IGF-I/GH ratio, and similar IGF-I. Overall, GHBP correlated inversely with log IGF-I/GH ratio (women, r = ? 0.591, p < 0.001; men, r = ? 0.575, p < 0.001). Additionally, higher baseline IGF-I was associated with a decline in LVmass during follow-up (r = ? 0.318, p = 0.003). Conclusion: In advanced cancer, reduced LVmass is associated with increased plasma GH and reduced IGF-I/GH ratio, suggesting increasing GH resistance, especially for patients with wasting syndrome with unintentional weight loss. Higher baseline IGF-I was associatedwith a decrease in relative LVmass during follow-up. The Author(s) 2024.
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Han, Ting; Liu, Shangjing; Liu, Hao; Wang, Xin; Yang, Xiaojia; Chan, Shanan; Tumanov, Sergey; Cannon, Richard David; Yang, Yang; Ting-Li Han, Ting Li HanPolycystic ovary syndrome (PCOS) is the most prevalent endocrine disorder in women of childbearing age. Numerous studies have indicated a significantly elevated incidence of depression and anxiety in women affected by PCOS, often attributed to dysbiosis of gut microbiota resulting from poor sleep quality. However, the intricate relationship between sleep disorders, gut microbiota, and depression/anxiety in PCOS remains unclear. In this study, we aimed to elucidate the effects of sleep deprivation on the anxiety and depression of PCOS mice through an investigation of the gut-brain axis in order to understand the potential microbialhost interactions contributing to the occurrence of these psychological disorders. We found that sleep deprivation induced symptoms of depression and anxiety in PCOS mice and exacerbated PCOS-like pathology. Moreover, sleep deprivation altered the gut microbiota composition by suppressing beneficial bacteria such as Lactobacillus and Ruminococcus species. Additionally, sleep deprivation upregulated intestinal tryptophan-kynurenine metabolism, increased intestinal wall permeability, promoted systemic inflammation, and compromised blood-brain barrier integrity. Furthermore, the hippocampal metabolomic analysis indicated that sleep deprivation affected the metabolism of fatty acid and oxylipins, upregulated the tryptophan-kynurenine metabolic pathway, and exhibited a significant correlation with anxiety and depressive behaviors. Overall, this study suggests that sleep deprivation plays a pivotal role in the pathological mechanism of depression and anxiety in PCOS mice by modulating tryptophan and lipid metabolism through the gut-brain axis. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
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Chau, Josephine Yuk Yin; Hunter, John; Gwynn, Josephine Diana; Dharmayani, Ms Putu Novi Arfirsta; Henson, Connie; Ludlow, Briellyn; Skinner, John C.; Gwynne, Kylie G.; Rambaldini, BoeIssue Addressed: Citizen science, an approach to health promotion that involves public participation and collaboration, has been posited as a promising approach to reach diverse or marginalised populations. This scoping review aims to explore the involvement of Aboriginal and Torres Strait Islanders and other First Nations and Indigenous peoples internationally in citizen science in health-related studies. While current health promotion in Indigenous communities is already strongly embedded in participatory approaches, we sought to examine whether citizen science methodologies have been used in health promotion and see what it could add. Methods: We searched three databases for self-identified citizen science studies on health-related topics in the peer-reviewed literature using the term citizen science combined with search terms relevant to Aboriginal and Torres Strait Islanders and global Indigenous populations. We recorded data about project characteristics and the citizen science approach used and appraised the cultural engagement quality of studies included. Results: Eleven articles were included for full-text review. Included studies focused on a range of health-related topics, including environmental issues, physical health, food security, and youth mental health. Six studies (55%) adopted a co-created citizen science approach in which citizen scientists had input in key project phases and activities as collaborators and partners. The remaining studies took contributory (27%) or collaborative (9%) approaches, while no studies were citizen-led. The cultural engagement quality of included citizen science projects was positive overall, although there were areas for improvement, specifically having clear Indigenous research leadership and governance, and transparent agreements on rights to cultural and intellectual property arising from the research. Conclusion: Citizen science projects focusing on health-related issues among Indigenous peoples and communities are relatively few. The potential of this approach to enrich current community-based participatory or co-design approaches to health promotion among Indigenous communities remains to be determined. So What?: Future citizen science projects involving Indigenous people and communities should prioritise and support Indigenous-led citizen science approaches where communities initiate, lead, and govern research processes. Cultural engagement quality could be improved, particularly in relation to having Indigenous-led research governance, and rights of access to and protections of Indigenous intellectual and cultural property. 2025 The Author(s). Health Promotion Journal of Australia published by John Wiley & Sons Australia, Ltd on behalf of Australian Health Promotion Association.
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Madronio, Christine M.; Pathan, Shahab K.; Low, Gary Kim Kuan; Nundlall, Nishant; Williams, Kathryn Helen; Badorrek, Sally; Devadas, Michael; Gallaty, Lynette; Madan, Kedar; Loh, Han; Ahmad, Shiva; Negishi, Kazuaki; Pathan, Faraz K.Background: To improve management of cardiovascular-kidney-metabolic syndrome, a better understanding of the early effects of body size on the heart is crucial and remains under investigation, considering the increasing global prevalence of obesity. Most data available on cardiovascular haemodynamics come from echocardiography despite the known challenges in image acquisition in the context of overweight and obesity. Using cardiac magnetic resonance imaging, we aimed to further investigate the effect of body size on cardiac output (CO) and other early imaging biomarkers of cardiovascular disease. Method: Participants including healthy volunteers and individuals with obesity who were planning to undergo bariatric surgery were recruited from two completed studies. The participants underwent cardiac magnetic resonance imaging. Measures of cardiovascular haemodynamics and myocardial mechanics were collected, including CO, stroke volume, heart rate, chamber volumes, and myocardial strain. The relationship of these variables with body size were assessed. Results: A total of 57 participants were recruited (79% female; mean age, 41 years). A positive linear relationship was observed between CO vs body mass index (BMI) (p<0.01) and body surface area (BSA) (p<0.01). A similar trend was seen with stroke volume vs BSA (p<0.01) and BMI (p<0.01). Indexation to BSA rendered chamber volumes similar. We found significant differences in left and right atrial strain between the groups. Regression analysis demonstrated an association between left ventricular global longitudinal strain and right atrial strain with BSA and between left ventricular global longitudinal strain, right ventricular free wall strain, and right atrial strain with BMI. Conclusions: Obesity is associated with increased CO; this increase is a result of cardiac remodelling and consequent increase in stroke volume. Obesity is associated with an impairment of subclinical markers of cardiovascular disease measured using multichamber strain. 2025 The Authors
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Sindone, Andrew Paul; Abhayaratna, Walter P.; Chan, Alicia; Leung, Melissa; Hopper, Ingrid K.; Amerena, John V.; de Pasqulae, Carmine G.; Burdeniuk, Christine Mary; Coats, Andrew J.S.; Atherton, John JamesHeart failure (HF) affects approximately 2.1% of adult Australians and is associated with substantial morbidity and mortality. Approximately half of all patients with HF have HF with a preserved ejection fraction (HFpEF), which is increasing in incidence driven by an ageing population and an increasing prevalence of obesity and diabetes. Obesity drives HFpEF via multiple mechanisms, with a linear relationship between various anthropometric measures and the risk of developing HFpEF. Heightened diagnostic awareness is required to identify patients with obesity-associated HFpEF, given the availability of therapeutics that have been shown to improve quality of life and clinical outcomes, including sodium-glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists, and glucagon-like peptide-1 agonist-based therapies. This review provides an overview of our current understanding of the impact of obesity on the development of HFpEF and outlines an approach to diagnosis and new therapeutic options. 2025
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Xu, Xiaohan; Sun, Jing; Zhang, Jinlun; Yang, Zhou; Ou, ChunquanBackground The coronavirus disease 2019 (COVID-19) pandemic has imposed a substantial disease burden globally and has further exacerbated pre-existing health inequities. This study aimed to provide a comprehensive assessment of the burden and inequities associated with COVID-19 across diverse populations. Methods Using data from the Global Burden of Disease 2021, we systematically analyzed deaths, incidence, disability-adjusted life years (DALYs), and years of life lost (YLLs) of COVID-19 stratified by sex, age, and region. The temporal trends pre-and post-2019 (i.e., 19902019 and 20192021) were measured using average annual percent change (AAPC). Additionally, the cross-country absolute and relative sociodemographic index (SDI)-related health inequities were assessed using the slope index and concentration index, respectively. The SDI is a composite development indicator that incorporates income, educational attainment, and fertility conditions. Results Trends in the global burden of all-cause mortality and DALYs exhibited significant declines (AAPC < 0) from 1990 to 2019 but underwent a marked reversal trend (AAPC > 0) following the COVID-19 pandemic. In 2021, COVID-19 resulted in 2.28 billion incident cases and 7.89 million deaths globally, with an age-standardized DALYs rate of 2,501 per 100,000 population. While incidence rates were relatively evenly distributed across populations, mortality was disproportionately higher among males and older adults. Substantial health inequities in the burden of COVID-19 were evident across 204 countries and territories, with absolute widening inequities notably in 2021 (e.g., the slope index of inequity for DALYs rose from 2,713 in 2020 to 4,044 in 2021). Greater inequities are disproportionately concentrated among males, middle-aged and older individuals, and regions with lower SDI levels. Conclusions These findings highlight the substantial disease burden of COVID-19 and elucidate the multidimensional health inequities exacerbated by the pandemic, providing crucial evidence for targeted interventions to address inequities and strengthen resilience in future global health emergencies. 2025 Xu et al.
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Hersant, Jeanne; Kruger, Ruan; Bianchini, Elisabetta; Kigstein, Karsten; Sinha, Manish D.; Hidvi, Erzset Valia; Kodithuwakku, Vimarsha; Mill, JosGeraldo; Dz, Alejandro A.; Zocalo, Y.; Bia Santana, Daniel; Celermajer, David S.; Hanssen, Henner; Johansson, Madeleine; Pucci, Giacomo; Litwin, Mieczyslaw S.; Stone, Keeron J.; Pugh, Christopher J.A.; Stoner, Lee; Urbina, Elaine M.; Bruno, Rosa Maria; Nilsson, Peter M.; Climie, Rachel Emma D.Since the conceptualization of early vascular aging (EVA) in 2008, significant efforts have been made to develop and improve its assessment. Initially lead by the investigation of arterial stiffness through pulse wave velocity (PWV), several additional vascular aging biomarkers have gained prominence in recent years. Despite expanding literature addressing methodological concerns associated with these biomarkers in youth, a standardized approach for clinical evaluation of EVA remains elusive, leaving pertinent gaps in understanding the optimal methodology. This article, resulting from international consensus efforts from the Youth Vascular Consortium, aims to provide an updated overview of methods available to measure EVA in youth and to discuss challenges in translating these methods into clinical practice. 2025 Wolters Kluwer Health, Inc. All rights reserved.
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Dupuy, Alexander; Qi, Miao; Fenwick, Jemma C.L.; Yates, Daisie M.; Coleman, Paul R.; Gamble, Jennifer R.; Ju, Lining Arnold; Passam, Freda H.Mouse models, such as the intravital laser-induced model of thrombus formation, are commonly used for mechanistic and preclinical studies in thrombosis. However, their translational value is limited by species differences. Few in vitro models incorporate laser-induced vascular injury. Here, we developed an endothelialized microfluidic device, the Endo-chip, to model thrombus formation in response to laser injury. Citrated blood was treated with IXA4, an endoplasmic reticulum stress inducer, or with antithrombotic agents including antitissue factor antibody (5G9), antiplatelet drugs (abciximab, aspirin), and anticoagulants (argatroban, heparin). Fluorescently labeled antibodies (to platelets, fibrin, or von Willebrand factor [VWF]), annexin V or the calcium dye Cal520, were added to the blood. After recalcification at 10 mM, blood was perfused through the Endo-chip at a shear rate of 100 s1 or 800 s1. Endothelial injury was induced with a 355-nm laser pulse producing a focal 10-?m injury, and phosphatidylserine exposure on endothelial cells within ?1 cell diameter from the injury site. Annexin V-positive endothelial cells expressed tissue factor and released VWF, supporting localized platelet and fibrin deposition. The thrombus formed a teardrop morphology aligned with flow incorporating VWF with increasing shear. IXA4 enhanced platelet cytoplasmic calcium. Platelet accumulation was inhibited by abciximab but not aspirin, whereas coagulation inhibitors (5G9, argatroban, heparin) markedly reduced thrombus formation. These findings support that the Endo-chip laser-injury model incorporates key features of thrombus formation after endothelial injury, and provides a humanized, in vitro, alternative or auxiliary to mouse models for preclinical studies and antithrombotic drug development. 2025 The American Society of Hematology
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Sun, Wen; Freedman, Ben; Martinez, Carlos; Wallenhorst, Christopher; Chan, Christy K.Y.; Yan, Bryan Ping YenBackground Atrial fibrillation (AF) screening is recommended at age ?65 years, but the age threshold in Asians is uncertain because of higher ischemic stroke risk <65 years. Objectives This study evaluated AF screening yield in a Chinese population aged 55 to 64 years, comparing stroke risk of those with and without AF, and the effect of oral anticoagulants (OAC). Methods Patients aged 55 to 64 years attending Hong Kong outpatient clinics underwent opportunistic handheld electrocardiogram screening. Repeat screening was performed if >1 clinic visits. Crude incidence rate ratios of ischemic stroke were determined and compared between 3 cohorts: screen-detected AF; clinically diagnosed AF; and no AF. Ischemic stroke risk for all AF categories was compared with individuals without AF, using adjusted subdistribution HRs (aSHRs) accounting for death as a competing risk. Results Of 3,926 subjects screened, 338 (8.6%) had known AF, and 3,588 had no AF history. New AF yield was 0.8% (28/3,588). AF was clinically diagnosed during follow-up in 2.3% (n = 82) and during subsequent screening in 7 subjects. Of 35 subjects with screen-detected AF, 26 (74%) had ?1 non-age, non-sex risk factor for stroke, mean age 60.8 2.5 years, and mean CHA<inf>2</inf>DS<inf>2</inf>-VASc score 1.9 1.4. At a median follow-up of 5.0 years, 2 patients (6%) with screen-detected AF experienced ischemic stroke, both with ?1 non-age, non-sex risk factor. AF exposure without OAC treatment was associated with highest risk of ischemic stroke (aSHR: 3.4 [1.3-8.5]). OAC treatment had similar low ischemic stroke risk as no AF. Conclusions Although diagnostic yield of AF screening in Chinese patients aged 55 to 64 years is low, those with AF are at increased stroke risk and may warrant being on anticoagulation. 2025 The Authors.
